AIMTo evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH).METHODSTwelve patients with biopsy-proven NASH were randomized to sitagliptin (10...AIMTo evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH).METHODSTwelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy.RESULTSSitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 μg/mL vs 3.9 ± 2.7 μg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mm展开更多
Collagen is a major extracellular matrix protein.Given the potential anti-inflammatory and antioxidant profiles of these bioactive compounds,there has been increasing interest in using collagen derived peptides and pe...Collagen is a major extracellular matrix protein.Given the potential anti-inflammatory and antioxidant profiles of these bioactive compounds,there has been increasing interest in using collagen derived peptides and peptide-rich collagen hydrolysates for skin health,due to their immunomodulatory,antioxidant and proliferative effects on dermal fibroblasts.However,all hydrolysates are not equally effective in exerting the beneficial effects;hence,further research is needed to determine the factors that improve the therapeutic applicability of such preparations.We used different enzymatic conditions to generate a number of different collagen hydrolysates with distinct peptide profiles.We found that the use of two rather than one enzyme for hydrolysis generates a greater abundance of low molecular weight peptides with consequent improvement in bioactive properties.Testing these hydrolysates on human dermal fibroblasts showed distinct actions on inflammatory changes,oxidative stress,type I collagen synthesis and cellular proliferation.Our findings suggest that different enzymatic conditions affect the peptide profile of hydrolysates and differentially regulate their biological activities and potential protective responses on dermal fibroblasts.展开更多
Cardiac resident macrophages (CRMs) are the main population of cardiac immune cells. The role of these cells in regeneration, functional remodeling, and repair after cardiac injury is always the focus of research. How...Cardiac resident macrophages (CRMs) are the main population of cardiac immune cells. The role of these cells in regeneration, functional remodeling, and repair after cardiac injury is always the focus of research. However, in recent years, their dynamic changes and contributions in physiological states have a significant attention. CRMs have specific phenotypes and functions in different cardiac chambers or locations of the heart and at different stages. They further show specific differentiation and development processes. The present review will summarize the new progress about the spatiotemporal distribution, potential developmental regulation, and their roles in cardiac development and aging as well as the translational potential of CRMs on cardiac diseases. Of course, the research tools for CRMs, their respective advantages and disadvantages, and key issues on CRMs will further be discussed.展开更多
Low-and middle-income countries(LMICs)bear the greater share of the global mental health burden but are ill-equipped to deal with it because of severe resource constraints leading to a large treatment gap.The remote p...Low-and middle-income countries(LMICs)bear the greater share of the global mental health burden but are ill-equipped to deal with it because of severe resource constraints leading to a large treatment gap.The remote provision of mental health services by digital means can effectively augment conventional services in LMICs to reduce the treatment gap.Digital psychiatry in LMICs has always lagged behind high-income countries,but there have been encouraging developments in the last decade.There is increasing research on the efficacy of digital psychiatric interventions.However,the evidence is not adequate to conclude that digital psychiatric interventions are invariably effective in LMICs.A striking development has been the rise in mobile and smartphone ownership in LMICs,which has driven the increasing use of mobile technologies to deliver mental health services.An innovative use of mobile technologies has been to optimize task-shifting,which involves delivering mental healthcare services in community settings using non-specialist health professionals.Emerging evidence from LMICs shows that it is possible to use digital tools to train non-specialist workers effectively and ensure that the psychosocial interventions they deliver are efficacious.Despite these promising developments,many barriers such as service costs,underdeveloped infrastructure,lack of trained professionals,and significant disparities in access to digital services impede the progress of digital psychiatry in LMICs.To overcome these barriers,digital psychiatric services in LMICs should address contextual factors influencing the delivery of digital services,ensure collaboration between different stakeholders,and focus on reducing the digital divide.展开更多
Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies.The majority of patients with colon c...Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies.The majority of patients with colon cancer are diagnosed at an early stage(stages I to III),which provides an opportunity for cure.The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients,which is directed at the eradication of minimal residual disease to achieve a cure.Surgery alone is curative for the vast majority of colon cancer patients.Currently,surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement.Adjuvant chemotherapy is recommended for all patients with stage III colon cancer,while the benefit in stage II patients is not unequivocally established despite several large clinical trials.Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques,strategies to limit treatment-related toxicities,precise patient selection for adjuvant therapy,utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology.In this review,we will discuss the current standard treatment,evolving treatment paradigms,and the emerging biomarkers,that will likely help improve patient selection and personalization of therapy leading to superior outcomes.展开更多
The serine/threonine phosphatase （PP1） isoform PP1γ2, predominantly expressed in the testis, is a key enzyme in spermatozoa. High PP1γ2 catalytic activity holds motility in check in immature spermatozoa. Inhibitio...The serine/threonine phosphatase （PP1） isoform PP1γ2, predominantly expressed in the testis, is a key enzyme in spermatozoa. High PP1γ2 catalytic activity holds motility in check in immature spermatozoa. Inhibition of PP1γ2 causes motility initiation in immature spermatozoa and motility stimulation and changes in flagellar beat parameters in mature spermatozoa. The PP1γ2 isoform is present in all mammalian spermatozoa studied： mouse, rat, hamster, bovine, non-human primate and man. We have now identified at least four of its regulatory proteins that regulate distinct pools of PP1γ2 within spermatozoa. Our studies provide new insights into biochemical mechanisms underlying development and regulation of sperm motility. We hypothesize that changes in sperm PP1γ2 activity as a result of phosphorylation and reversible binding of the regulatory proteins to the catalytic subunit are critical in the development and regulation of motility and the ability of sperm to fertilize eggs. Targeted disruption of the Ppplcc gene, which encodes the PP1γ1 or PP1γ2 isoforms, causes male infertility in mice as a result of impaired spermiogenesis. Our observations suggest that, in addition to motility, the protein phosphatase PP1γ2 might play an isoform-specific function in the development of specialized flagellar structures of mammalian spermatozoa. （Asian J Androl 2007 July; 9： 445--452）展开更多
Objective Many studies have been conducted in order to evaluate the genotoxicity of chemicals and waste materials, which utilized in vivo test protocols. The use of animals for routine toxicity testing is now question...Objective Many studies have been conducted in order to evaluate the genotoxicity of chemicals and waste materials, which utilized in vivo test protocols. The use of animals for routine toxicity testing is now questioned by a growing segment of society. Methods Keeping the above fact in mind, we have conducted in the present study the genotoxicity evaluation of oily sludge samples generated from a petroleum refinery and petrochemical industry and ETP sludge from petroleum refinery using DNA damage, chromosomal aberration, p53 protein induction and apoptosis in short term in vitro mammalian Chinese Hamster Ovary cell cultures. Results It is evident from the results that the oily sludge compounds derived from petroleum refinery and petrochemical industry could cause DNA damage, chromosomal aberration, p53 protein accumulation and apoptotic cell death on exposure to oily sludge extracts in the presence of metabolic activation system (S-9 mix), however, ETP sludge extract could not cause significant genotoxicity in comparison to oily sludge extract and negative control. Conclusion The effect may be attributed to polycyclic aromatic hydrocarbons present in the samples as evidenced from GC-MS.展开更多
<abstract>Aim: To identify possible spermicidal agents through screening a number of edible medicinal plants with antimicrobial activity. Methods: Initial screening was made on the basis of ram cauda epididymal ...<abstract>Aim: To identify possible spermicidal agents through screening a number of edible medicinal plants with antimicrobial activity. Methods: Initial screening was made on the basis of ram cauda epididymal sperm immobilization immediately after addition of extracts. The most potent extract was selected and was evaluated on both ram and human spermatozoa. To unravel its mode of action several sperm functional tests were carried out, namely viability of cells, hypo-osmotic swelling test for membrane integrity and assays of membrane-bound enzyme 5'-nucleotidase and acrosomal marker enzyme acrosin. Results: The crude aqueous extract of the bulb of Allium sativum L. showed the most promising results by instant immobilization of the ram epididymal sperm at 0.25 g/mL and human ejaculated sperm at 0.5 g/mL. Sperm immobilizing effects were irreversible and the factor of the extract responsible for immobilization was thermostable up to 90 癈. On boiling at 100 癈 for 10 minutes, this activity was markedly reduced. Moreover, this extract was able to cause aggregation of ram sperms into small clusters after 30 minutes of incubation at 37 癈. However this property was not found in human spermatozoa. More than 50 % reduction in sperm viability and hypo-osmotic swelling occurred in treated sperm as compared with the controls, indicating the possibility of plasma membrane disintegration which was further supported by the significant reduction in the activity of membrane bound 5'-nucleotidase and acrosomal acrosin. Conclusion: The crude aqueous extract of A. sativum bulb possesses spermicidal activity in vitro.展开更多
Rapid-cycling bipolar disorder(RCBD)is a phase of bipolar disorder defined by the presence of≥4 mood episodes in a year.It is a common phenomenon characterized by greater severity,a predominance of depression,higher ...Rapid-cycling bipolar disorder(RCBD)is a phase of bipolar disorder defined by the presence of≥4 mood episodes in a year.It is a common phenomenon characterized by greater severity,a predominance of depression,higher levels of disability,and poorer overall outcomes.It is resistant to treatment by conventional pharmacotherapy.The existing literature underlines the scarcity of evidence and the gaps in knowledge about the optimal treatment strategies for RCBD.However,most reviews have considered only pharmacological treatment options for RCBD.Given the treatment-refractory nature of RCBD,nonpharmacological interventions could augment medications but have not been adequately examined.This review carried out an updated and comprehensive search for evidence regarding the role of nonpharmacological therapies as adjuncts to medications in RCBD.We identified 83 reviews and meta-analyses concerning the treatment of RCBD.Additionally,we found 42 reports on adjunctive nonpharmacological treatments in RCBD.Most of the evidence favoured concomitant electroconvulsive therapy as an acute and maintenance treatment.There was preliminary evidence to suggest that chronotherapeutic treatments can provide better outcomes when combined with medications.The research on adjunctive psychotherapy was particularly scarce but suggested that psychoeducation,cognitive behavioural therapy,family interventions,and supportive psychotherapy may be helpful.The overall quality of evidence was poor and suffered from several methodological shortcomings.There is a need for more methodologically sound research in this area,although clinicians can use the existing evidence to select and individualize nonpharmacological treatment options for better management of RCBD.Patient summaries are included to highlight some of the issues concerning the implementation of adjunctive nonpharmacological treatments.展开更多
Vibrio harveyi is a Gram-negative,rod-shaped,polar flagellate,facultatively anaerobic,halophilic,bioluminescent marine bacteria that belongs to the family of Vibrionaceae,class,Gammaproteobacteria.This pathogenic orga...Vibrio harveyi is a Gram-negative,rod-shaped,polar flagellate,facultatively anaerobic,halophilic,bioluminescent marine bacteria that belongs to the family of Vibrionaceae,class,Gammaproteobacteria.This pathogenic organism is responsible for various diseases of vertebrates and invertebrates in marine habitats,including shrimp aquaculture.Various symptoms like lesions,gastroenteritis,skin ulcers,eye lesions,and tail rot have been observed due to V.harveyi infection.The pathogenic-ity mechanism of V.harveyi involves endotoxin lipopolysaccharide,extracellular proteases,and bacteriophage interaction.Hemolysin genes encoded extracellular hemolysin-like phospholipase B toxin could inactivate fish species via the caspase inactivation pathway,ultimately leading to apoptosis.In addition,VBNC(viable but nonculturable)cells are another basis of vibriosis outbreaks in the shrimp aquaculture sector.The extensive amount of antibiotic use promotes the generation of multidrug-resistant strains.Therefore,as an alternative strategy to combat V.harveyi infection,bacteriophages are utilized as a biocontrol agent.However,there is a lack of research on the immobilization and development of encapsulation strategies of V.harveyi-infecting bacteriophages which need to be studied further.In conclusion,the pathogenicity of V.harveyi and its biocontrol by bacteriophages has been documented in this review.展开更多
All over the world women are the predominant providers of informal care for family members with chronic medical conditions or disabilities, including the elderly and adults with mental illnesses. It has been suggested...All over the world women are the predominant providers of informal care for family members with chronic medical conditions or disabilities, including the elderly and adults with mental illnesses. It has been suggested that there are several societal and cultural demands on women to adopt the role of a family-caregiver. Stress-coping theories propose that women are more likely to be exposed to caregiving stressors, and are likely to perceive, report and cope with these stressors differently from men. Many studies, which have examined gender differences among family-caregivers of people with mental illnesses, have concluded that women spend more time in providing care and carry out personal-care tasks more often than men. These studies have also found that women experience greater mental and physical strain, greater caregiver-burden, and higher levels of psychological distress while providing care. However, almost an equal number of studies have not found any differences between men and women on these aspects. This has led to the view that though there may be certain differences between male and female caregivers, most of these are small in magnitude and of doubtful clinical significance. Accordingly, caregivergender is thought to explain only a minor proportion of the variance in negative caregiving outcomes. A similar inconsistency characterizes the explanations provided for gender differences in caregiving such as role expectations, differences in stress, coping and social support, and response biases in reporting distress. Apart from the equivocal and inconsistent evidence, there are other problems in the literature on gender differences in caregiving. Most of the evidence has been derived from studies on caregivers of elderly people who either suffer from dementia or other physical conditions. Similar research on other mental illnesses such as schizophrenia or mood disorders is relatively scarce. With changing demographics and social norms men are increasingly assuming roles as caregivers. However, the experie展开更多
The history of the Qinghai-Tibetan Plateau and the Himalayas(QTPH)region makes it a‘living laboratory'for understanding how the Earth's abiotic evolution has shaped regional biotas.However,no studies to date ...The history of the Qinghai-Tibetan Plateau and the Himalayas(QTPH)region makes it a‘living laboratory'for understanding how the Earth's abiotic evolution has shaped regional biotas.However,no studies to date have attempted to investigate general macro-scale biogeographical patterns and biogeographical affinities of the QTPH terrestrial fauna in a global context.Based on the analyses of the global distributions of QTPH Aphidomorpha species,we examined generalized distribution patterns for them and investigated the biogeographical affinities between the QTPH and other regions.Track analysis and cluster analysis of the global distributions of 298 Aphidomorpha species in the QTPH identified seven generalized biogeographical tracks and eight general distribution patterns.Both approaches detected similarly generalized distribution patterns.Four marginal areas where the generalized tracks intersect,i.e.the eastern Himalayas,the western Himalayas,the Hengduan Mountains,and the northeastern QTPH,were identified as biogeographical nodes.The generalized distribution patterns indicate the biogeographical affinities between the QTPH and other regions and suggest the complex nature of the QTPH fauna.A spatial congruence between the nodes and diversity centres detected by previous studies indicates the four marginal areas have been key areas in fauna evolution as centres for faunal exchange as well as glacial refugia.Based on the biogeographical patterns,the geological history of the QTPH and the evolutionary history of Aphidomorpha,we propose an evolutionary scenario for the evolution of the QTPH aphid fauna in which faunal exchanges,vicariance due to the uplift of geographical barriers,environmental heterogeneity and Quarternary glaciations have shaped the diversity patterns and fauna in the QTPH.展开更多
BACKGROUND The existing literature indicates that psychotherapeutic treatment,especially exposure and response prevention(ERP)is efficacious in treating obsessivecompulsive disorder(OCD).The coronavirus disease 2019 p...BACKGROUND The existing literature indicates that psychotherapeutic treatment,especially exposure and response prevention(ERP)is efficacious in treating obsessivecompulsive disorder(OCD).The coronavirus disease 2019 pandemic adversely impacted many patients with OCD and disrupted their usual treatment.Moreover,the pandemic forced a global switch to telemental health(TMH)services to maintain the standards and continuity of care.Consequently,clinicians are increasingly using TMH-based psychotherapeutic treatments to treat OCD.However,several challenges have made it difficult for them to implement these treatments in the changed circumstances imposed by the pandemic.AIM To describe the formulation,implementation,feasibility,and usefulness of videoconferencing-based ERP(VC-ERP)treatment for OCD during the coronavirus disease 2019 pandemic.METHODS This prospective,observational study was conducted in the psychiatric unit of a multi-specialty hospital in north India over 12 mo(July 2020-June 2021).All patients with OCD were assessed using the home-based TMH services of the department.The VC-ERP protocol for OCD was the outcome of weekly Zoom meetings with a group of clinicians involved in administering the treatment.After a systematic evaluation of the available treatment options,an initial protocol for delivering VC-ERP was developed.Guidelines for clinicians and educational materials for patients and their families were prepared.The protocol was implemented among patients with OCD attending the TMH services,and their progress was monitored.The weekly meetings were used to upgrade the protocol to meet the needs of all stakeholders.Feasibility and efficacy outcomes were examined.RESULTS All patients were diagnosed with OCD as a primary or a comorbid condition according to the International Classification of Diseases,10th version criteria.Out of 115 patients who attended the services during the study period,37 were excluded from the final analysis.Of the remaining 78 patients,VC-ERP was initiated in 43 patients.Six pati展开更多
Study of seismo-ionospheric coupling mechanism demands the quiet geomagnetic condition to eliminate any kind of contamination in the lower atmospheric and ionospheric parameters. In this manuscript, we present the eff...Study of seismo-ionospheric coupling mechanism demands the quiet geomagnetic condition to eliminate any kind of contamination in the lower atmospheric and ionospheric parameters. In this manuscript, we present the effect of back to back two geomagnetic storms before a strong earthquake happened in Imphal, India on January 4, 2016 (M</span><span style="font-family:""> </span><span style="font-family:Verdana;">=</span><span style="font-family:""> </span><span style="font-family:Verdana;">6.7). We studied the lower ionospheric irregularities for </span><span style="font-family:Verdana;">the</span><span style="font-family:Verdana;"> duration of 31 days by computing the nighttime fluctuations in Very Low Frequency (VLF) radio signal received transmitter JJI (22.2 kHz) in Japan at Ionospheric and Earthquake Research Centre & Optical Observatory (IERCOO), Sitapur, India. We also studied the presence of Atmospheric Gravity Wave (AGW) in nighttime VLF signal in lower ionospheric heights and the same computed that from SABER/TIMED satellite. Two geomagnetic storms occurred on December 21, and 31, 2015. By the conventional analysis, we found that there is a significant decrease in nighttime trend and an increase in nighttime fluctuations around 15 days before the earthquake and just on the first storm and thus the pre-seismic effects on VLF signal gets contaminated due to the presence of storms. The wave-like structure in VLF fluctuations shows significant increase in intensity by using Fourier and Wavelet analysis before the earthquake. By analysis of SABER data, we found significant enhancement in AGW around 10 days before the earthquake. As the wavelike structures are coming from neutral acoustics reasons from pressure or temperature variations, this paper exhibits a significant example of contamination in ionospheric parameters due to geomagnetic storm where the acoustics parameters remain un-contaminated.展开更多
The present study area involves part of a deformed coalesced fan located along the Himalayan Frontal Thrust(HFT)on the east of river Tista near the India-Bhutan border.The area is marked by two spectacular E-W trendin...The present study area involves part of a deformed coalesced fan located along the Himalayan Frontal Thrust(HFT)on the east of river Tista near the India-Bhutan border.The area is marked by two spectacular E-W trending south-sloping scarps namely the Matiali(ca.60 m)and Chalsa(ca.90 m)Scarps and a north-sloping E-W trending Thaljhora(ca.80 m)Scarp.Our work comprises of a comparative study of geomorphology and geologic history in the adjacent interfluves of Jaldhaka-Gathia and Neora-Murti rivers to understand the tectonic history of the area.We mapped the Jaldhaka-Gathia river interfluve at a 1:25,000 scale and report a hitherto unidentified northerly sloping small scarp of ca.5 m height named the Nagrakata Scarp.This scarp was identified using satellite images,DEMs,and total station survey.We interpret that the two northsloping,E-W trending scarps(Thaljhora and Nagrakata Scarps)are manifestations of steep limbs of anticlines over blind south-dipping back thrusts.Together they form a wrinkle-ridge pair behind the north-dipping HFT,which is manifested by south-sloping Chalsa Scarp.We propose a plausible geomorphic model interpreting that deformation along the small fan in the Jaldhaka-Gathia interfluves is younger compared to fan deposition and deformation in the adjacent Mal-Murti interfluve.The most recent geomorphology of the Jaldhaka-Gathia interfluve is controlled by tectonism associated with the thrust below the Nagrakata Scarp where the youngest deformation episode is recorded to at around^6 ka and is likely related to motion on a splay off of the thrust beneath the Thaljhora Scarp.展开更多
The World Health Organization’s 11^(th)revision of the International Classification of Diseases(ICD-11)including the chapter on mental disorders has come into effect this year.This review focuses on the“Bipolar or R...The World Health Organization’s 11^(th)revision of the International Classification of Diseases(ICD-11)including the chapter on mental disorders has come into effect this year.This review focuses on the“Bipolar or Related Disorders”section of the ICD-11 draft.It describes the benchmarks for the new version,particularly the foremost principle of clinical utility.The alterations made to the diagnosis of bipolar disorder(BD)are evaluated on their scientific basis and clinical utility.The change in the diagnostic requirements for manic and hypomanic episodes has been much debated.Whether the current criteria have achieved an optimum balance between sensitivity and specificity is still not clear.The ICD-11 definition of depressive episodes is substantially different,but the lack of empirical support for the changes has meant that the reliability and utility of bipolar depression are relatively low.Unlike the Diagnostic and Statistical Manual of Mental Disorders,5th edition(DSM-5),the ICD-11 has retained the category of mixed episodes.Although the concept of mixed episodes in the ICD-11 is not perfect,it appears to be more inclusive than the DSM-5 approach.Additionally,there are some uncertainties about the guidelines for the subtypes of BD and cyclothymic disorder.The initial results on the reliability and clinical utility of BD are promising,but the newly created diagnostic categories also appear to have some limitations.Although further improvement and research are needed,the focus should now be on facing the challenges of implementation,dissemination,and education and training in the use of these guidelines.展开更多
About 40%-70%of the patients with treatment-resistant schizophrenia have a poor response to adequate treatment with clozapine.The impact of clozapineresistant schizophrenia(CRS)is even greater than that of treatment r...About 40%-70%of the patients with treatment-resistant schizophrenia have a poor response to adequate treatment with clozapine.The impact of clozapineresistant schizophrenia(CRS)is even greater than that of treatment resistance in terms of severe and persistent symptoms,relapses and hospitalizations,poorer quality of life,and healthcare costs.Such serious consequences often compel clinicians to try different augmentation strategies to enhance the inadequate clozapine response in CRS.Unfortunately,a large body of evidence has shown that antipsychotics,antidepressants,mood stabilizers,electroconvulsive therapy,and cognitive-behavioural therapy are mostly ineffective in augmenting clozapine response.When beneficial effects of augmentation have been found,they are usually small and of doubtful clinical significance or based on low-quality evidence.Therefore,newer treatment approaches that go beyond the evidence are needed.The options proposed include developing a clinical consensus about the augmentation strategies that are most likely to be effective and using them sequentially in patients with CRS.Secondly,newer approaches such as augmentation with long-acting antipsychotic injections or multi-component psychosocial interventions could be considered.Lastly,perhaps the most effective way to deal with CRS would be to optimize clozapine treatment,which might prevent clozapine resistance from developing.Personalized dosing,adequate treatment durations,management of side effects and non-adherence,collaboration with patients and caregivers,and addressing clinician barriers to clozapine use are the principal ways of ensuring optimal clozapine treatment.At present,these three options could the best way to manage CRS until research provides more firm directions about the effective options for augmenting clozapine response.展开更多
Telepsychiatry, i.e., the use of information and communication technologies to provide psychiatric services from a distance, has been around for more than half a century now. Research over this period has shown that v...Telepsychiatry, i.e., the use of information and communication technologies to provide psychiatric services from a distance, has been around for more than half a century now. Research over this period has shown that videoconferencing-based telepsychiatry is an enabling and empowering form of service delivery, which promotes equality of access, and high levels of satisfaction among patients. The range of services offered by videoconferencing-based telepsychiatry, potential users and points of delivery of such services are theoretically limitless. Telepsychiatry has both clinical utility and non-clinical uses such as administrative, learning and research applications. A large body of accumulated evidence indicates that videoconferencingbased telepsychiatric assessments are reliable, and clinical outcomes of telepsychiatric interventions are comparable to conventional treatment among diverse patient populations, ages and diagnostic groups, and on a wide range of measures. However, on many aspects of effectiveness, the evidence base is still relatively limited and often compromised by methodological problems. The lack of cost-effectiveness data in particular, is a major hindrance, raising doubts about the continued viability of telepsychiatric services. Added to this are the vagaries of technology, negative views among clinicians, poor uptake by providers, and several legal, ethical and administrative barriers. These hamper the widespread implementation of telepsychiatry and its integration with routine care. Though further advances in technology and research are expected to solve many of these problems, the way forward would be to promote telepsychiatry as an adjunct to conventional care, and to develop hybrid models, which incorporate both traditional and telepsychiatric forms of mental health-care.展开更多
Objective From the ancient period cow’urine has been used as a medicine. In Veda, cow’urine was compared to the nectar. In Susrut, several medicinal properties of cow’ urine have been mentioned and are known to ca...Objective From the ancient period cow’urine has been used as a medicine. In Veda, cow’urine was compared to the nectar. In Susrut, several medicinal properties of cow’ urine have been mentioned and are known to cause weight loss, reversal of certain cardiac and kidney problems, indigestion, stomach ache, edema, etc. However, the literature and scripture did not mention the antigenotoxic properties of cow’urine. Methods In the present investigation, the antigenotoxic/ antioxidant properties of cow’ urine distillate and redistillate were studied in vitro. The antioxidant status and volatile fatty acid levels were determined. Actinomycin-D (0.1ol/L) and hydrogen peroxide (150 mol/L) were used for inducing DNA strand break with 0.1% DMSO as negative control. Dose for the antigenotoxic effect of cow’ urine was chosen from the dose response study carried out earlier. Results Both actinomycin-D and H2O2 caused statistically significant DNA unwinding of 80% & 75% respectively (P<0.001) as revealed by fluorimetric analysis of DNA unwinding (FADU), and the damage could be protected with the redistilled cow urine distillate (1, 50 & 100 ) in simultaneous treatment with genotoxic chemicals. Conclusion The redistillate of cowurine was found to possess total antioxidant status of around 2.6 mmol, contributed mainly by volatile fatty acids (1500 mg/L) as revealed by the GC-MS studies. These fatty acids and other antioxidants might cause the observed protective effects.展开更多
基金the Physicians’Services Incorporated Foundation 10q2083(Joy TR and Beaton MD)Academic Medical Organization of Southwestern Ontario,No.F10-002(Beaton MD)+1 种基金partly funded through academic research funds from the Program of Experimental Medicine(Joy TR)Department of Medicine Academic Funds(Joy TR)from Western University,London,Ontario,Canada
文摘AIMTo evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH).METHODSTwelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy.RESULTSSitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 μg/mL vs 3.9 ± 2.7 μg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mm
基金This study was funded by grants from Alberta Livestock and Meat Agency(ALMA)and the Natural Sciences and Engineering Research Council(NSERC)of Canada to JW.The funders had no role in the study design,data collection and analysis,decision to publish or preparation of this manuscript。
文摘Collagen is a major extracellular matrix protein.Given the potential anti-inflammatory and antioxidant profiles of these bioactive compounds,there has been increasing interest in using collagen derived peptides and peptide-rich collagen hydrolysates for skin health,due to their immunomodulatory,antioxidant and proliferative effects on dermal fibroblasts.However,all hydrolysates are not equally effective in exerting the beneficial effects;hence,further research is needed to determine the factors that improve the therapeutic applicability of such preparations.We used different enzymatic conditions to generate a number of different collagen hydrolysates with distinct peptide profiles.We found that the use of two rather than one enzyme for hydrolysis generates a greater abundance of low molecular weight peptides with consequent improvement in bioactive properties.Testing these hydrolysates on human dermal fibroblasts showed distinct actions on inflammatory changes,oxidative stress,type I collagen synthesis and cellular proliferation.Our findings suggest that different enzymatic conditions affect the peptide profile of hydrolysates and differentially regulate their biological activities and potential protective responses on dermal fibroblasts.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.32370984 and 82101914)Six Talent Peaks Project in Jiangsu Province(2019-WSN-122,China)+2 种基金Projects of International Cooperation from Jiangsu Province(BX2019100,China)Key Funds from the Health Commission of Jiangsu Province(ZD2021009,China)the Social Development Foundation of Zhenjiang(SH2022060,China).
文摘Cardiac resident macrophages (CRMs) are the main population of cardiac immune cells. The role of these cells in regeneration, functional remodeling, and repair after cardiac injury is always the focus of research. However, in recent years, their dynamic changes and contributions in physiological states have a significant attention. CRMs have specific phenotypes and functions in different cardiac chambers or locations of the heart and at different stages. They further show specific differentiation and development processes. The present review will summarize the new progress about the spatiotemporal distribution, potential developmental regulation, and their roles in cardiac development and aging as well as the translational potential of CRMs on cardiac diseases. Of course, the research tools for CRMs, their respective advantages and disadvantages, and key issues on CRMs will further be discussed.
文摘Low-and middle-income countries(LMICs)bear the greater share of the global mental health burden but are ill-equipped to deal with it because of severe resource constraints leading to a large treatment gap.The remote provision of mental health services by digital means can effectively augment conventional services in LMICs to reduce the treatment gap.Digital psychiatry in LMICs has always lagged behind high-income countries,but there have been encouraging developments in the last decade.There is increasing research on the efficacy of digital psychiatric interventions.However,the evidence is not adequate to conclude that digital psychiatric interventions are invariably effective in LMICs.A striking development has been the rise in mobile and smartphone ownership in LMICs,which has driven the increasing use of mobile technologies to deliver mental health services.An innovative use of mobile technologies has been to optimize task-shifting,which involves delivering mental healthcare services in community settings using non-specialist health professionals.Emerging evidence from LMICs shows that it is possible to use digital tools to train non-specialist workers effectively and ensure that the psychosocial interventions they deliver are efficacious.Despite these promising developments,many barriers such as service costs,underdeveloped infrastructure,lack of trained professionals,and significant disparities in access to digital services impede the progress of digital psychiatry in LMICs.To overcome these barriers,digital psychiatric services in LMICs should address contextual factors influencing the delivery of digital services,ensure collaboration between different stakeholders,and focus on reducing the digital divide.
文摘Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies.The majority of patients with colon cancer are diagnosed at an early stage(stages I to III),which provides an opportunity for cure.The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients,which is directed at the eradication of minimal residual disease to achieve a cure.Surgery alone is curative for the vast majority of colon cancer patients.Currently,surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement.Adjuvant chemotherapy is recommended for all patients with stage III colon cancer,while the benefit in stage II patients is not unequivocally established despite several large clinical trials.Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques,strategies to limit treatment-related toxicities,precise patient selection for adjuvant therapy,utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology.In this review,we will discuss the current standard treatment,evolving treatment paradigms,and the emerging biomarkers,that will likely help improve patient selection and personalization of therapy leading to superior outcomes.
文摘The serine/threonine phosphatase （PP1） isoform PP1γ2, predominantly expressed in the testis, is a key enzyme in spermatozoa. High PP1γ2 catalytic activity holds motility in check in immature spermatozoa. Inhibition of PP1γ2 causes motility initiation in immature spermatozoa and motility stimulation and changes in flagellar beat parameters in mature spermatozoa. The PP1γ2 isoform is present in all mammalian spermatozoa studied： mouse, rat, hamster, bovine, non-human primate and man. We have now identified at least four of its regulatory proteins that regulate distinct pools of PP1γ2 within spermatozoa. Our studies provide new insights into biochemical mechanisms underlying development and regulation of sperm motility. We hypothesize that changes in sperm PP1γ2 activity as a result of phosphorylation and reversible binding of the regulatory proteins to the catalytic subunit are critical in the development and regulation of motility and the ability of sperm to fertilize eggs. Targeted disruption of the Ppplcc gene, which encodes the PP1γ1 or PP1γ2 isoforms, causes male infertility in mice as a result of impaired spermiogenesis. Our observations suggest that, in addition to motility, the protein phosphatase PP1γ2 might play an isoform-specific function in the development of specialized flagellar structures of mammalian spermatozoa. （Asian J Androl 2007 July; 9： 445--452）
文摘Objective Many studies have been conducted in order to evaluate the genotoxicity of chemicals and waste materials, which utilized in vivo test protocols. The use of animals for routine toxicity testing is now questioned by a growing segment of society. Methods Keeping the above fact in mind, we have conducted in the present study the genotoxicity evaluation of oily sludge samples generated from a petroleum refinery and petrochemical industry and ETP sludge from petroleum refinery using DNA damage, chromosomal aberration, p53 protein induction and apoptosis in short term in vitro mammalian Chinese Hamster Ovary cell cultures. Results It is evident from the results that the oily sludge compounds derived from petroleum refinery and petrochemical industry could cause DNA damage, chromosomal aberration, p53 protein accumulation and apoptotic cell death on exposure to oily sludge extracts in the presence of metabolic activation system (S-9 mix), however, ETP sludge extract could not cause significant genotoxicity in comparison to oily sludge extract and negative control. Conclusion The effect may be attributed to polycyclic aromatic hydrocarbons present in the samples as evidenced from GC-MS.
文摘<abstract>Aim: To identify possible spermicidal agents through screening a number of edible medicinal plants with antimicrobial activity. Methods: Initial screening was made on the basis of ram cauda epididymal sperm immobilization immediately after addition of extracts. The most potent extract was selected and was evaluated on both ram and human spermatozoa. To unravel its mode of action several sperm functional tests were carried out, namely viability of cells, hypo-osmotic swelling test for membrane integrity and assays of membrane-bound enzyme 5'-nucleotidase and acrosomal marker enzyme acrosin. Results: The crude aqueous extract of the bulb of Allium sativum L. showed the most promising results by instant immobilization of the ram epididymal sperm at 0.25 g/mL and human ejaculated sperm at 0.5 g/mL. Sperm immobilizing effects were irreversible and the factor of the extract responsible for immobilization was thermostable up to 90 癈. On boiling at 100 癈 for 10 minutes, this activity was markedly reduced. Moreover, this extract was able to cause aggregation of ram sperms into small clusters after 30 minutes of incubation at 37 癈. However this property was not found in human spermatozoa. More than 50 % reduction in sperm viability and hypo-osmotic swelling occurred in treated sperm as compared with the controls, indicating the possibility of plasma membrane disintegration which was further supported by the significant reduction in the activity of membrane bound 5'-nucleotidase and acrosomal acrosin. Conclusion: The crude aqueous extract of A. sativum bulb possesses spermicidal activity in vitro.
文摘Rapid-cycling bipolar disorder(RCBD)is a phase of bipolar disorder defined by the presence of≥4 mood episodes in a year.It is a common phenomenon characterized by greater severity,a predominance of depression,higher levels of disability,and poorer overall outcomes.It is resistant to treatment by conventional pharmacotherapy.The existing literature underlines the scarcity of evidence and the gaps in knowledge about the optimal treatment strategies for RCBD.However,most reviews have considered only pharmacological treatment options for RCBD.Given the treatment-refractory nature of RCBD,nonpharmacological interventions could augment medications but have not been adequately examined.This review carried out an updated and comprehensive search for evidence regarding the role of nonpharmacological therapies as adjuncts to medications in RCBD.We identified 83 reviews and meta-analyses concerning the treatment of RCBD.Additionally,we found 42 reports on adjunctive nonpharmacological treatments in RCBD.Most of the evidence favoured concomitant electroconvulsive therapy as an acute and maintenance treatment.There was preliminary evidence to suggest that chronotherapeutic treatments can provide better outcomes when combined with medications.The research on adjunctive psychotherapy was particularly scarce but suggested that psychoeducation,cognitive behavioural therapy,family interventions,and supportive psychotherapy may be helpful.The overall quality of evidence was poor and suffered from several methodological shortcomings.There is a need for more methodologically sound research in this area,although clinicians can use the existing evidence to select and individualize nonpharmacological treatment options for better management of RCBD.Patient summaries are included to highlight some of the issues concerning the implementation of adjunctive nonpharmacological treatments.
基金The authors are grateful to Science and Engineering Research Board(SERB),a statutory body of the Department of Science&Technology,Govt.of India(Sanction Order No.CRG/2019/001750 dated 14th January,2020)for financial assistance.
文摘Vibrio harveyi is a Gram-negative,rod-shaped,polar flagellate,facultatively anaerobic,halophilic,bioluminescent marine bacteria that belongs to the family of Vibrionaceae,class,Gammaproteobacteria.This pathogenic organism is responsible for various diseases of vertebrates and invertebrates in marine habitats,including shrimp aquaculture.Various symptoms like lesions,gastroenteritis,skin ulcers,eye lesions,and tail rot have been observed due to V.harveyi infection.The pathogenic-ity mechanism of V.harveyi involves endotoxin lipopolysaccharide,extracellular proteases,and bacteriophage interaction.Hemolysin genes encoded extracellular hemolysin-like phospholipase B toxin could inactivate fish species via the caspase inactivation pathway,ultimately leading to apoptosis.In addition,VBNC(viable but nonculturable)cells are another basis of vibriosis outbreaks in the shrimp aquaculture sector.The extensive amount of antibiotic use promotes the generation of multidrug-resistant strains.Therefore,as an alternative strategy to combat V.harveyi infection,bacteriophages are utilized as a biocontrol agent.However,there is a lack of research on the immobilization and development of encapsulation strategies of V.harveyi-infecting bacteriophages which need to be studied further.In conclusion,the pathogenicity of V.harveyi and its biocontrol by bacteriophages has been documented in this review.
文摘All over the world women are the predominant providers of informal care for family members with chronic medical conditions or disabilities, including the elderly and adults with mental illnesses. It has been suggested that there are several societal and cultural demands on women to adopt the role of a family-caregiver. Stress-coping theories propose that women are more likely to be exposed to caregiving stressors, and are likely to perceive, report and cope with these stressors differently from men. Many studies, which have examined gender differences among family-caregivers of people with mental illnesses, have concluded that women spend more time in providing care and carry out personal-care tasks more often than men. These studies have also found that women experience greater mental and physical strain, greater caregiver-burden, and higher levels of psychological distress while providing care. However, almost an equal number of studies have not found any differences between men and women on these aspects. This has led to the view that though there may be certain differences between male and female caregivers, most of these are small in magnitude and of doubtful clinical significance. Accordingly, caregivergender is thought to explain only a minor proportion of the variance in negative caregiving outcomes. A similar inconsistency characterizes the explanations provided for gender differences in caregiving such as role expectations, differences in stress, coping and social support, and response biases in reporting distress. Apart from the equivocal and inconsistent evidence, there are other problems in the literature on gender differences in caregiving. Most of the evidence has been derived from studies on caregivers of elderly people who either suffer from dementia or other physical conditions. Similar research on other mental illnesses such as schizophrenia or mood disorders is relatively scarce. With changing demographics and social norms men are increasingly assuming roles as caregivers. However, the experie
基金supported by the National Natural Sciences Foundation of China(Grant numbers:32270499,30900133)。
文摘The history of the Qinghai-Tibetan Plateau and the Himalayas(QTPH)region makes it a‘living laboratory'for understanding how the Earth's abiotic evolution has shaped regional biotas.However,no studies to date have attempted to investigate general macro-scale biogeographical patterns and biogeographical affinities of the QTPH terrestrial fauna in a global context.Based on the analyses of the global distributions of QTPH Aphidomorpha species,we examined generalized distribution patterns for them and investigated the biogeographical affinities between the QTPH and other regions.Track analysis and cluster analysis of the global distributions of 298 Aphidomorpha species in the QTPH identified seven generalized biogeographical tracks and eight general distribution patterns.Both approaches detected similarly generalized distribution patterns.Four marginal areas where the generalized tracks intersect,i.e.the eastern Himalayas,the western Himalayas,the Hengduan Mountains,and the northeastern QTPH,were identified as biogeographical nodes.The generalized distribution patterns indicate the biogeographical affinities between the QTPH and other regions and suggest the complex nature of the QTPH fauna.A spatial congruence between the nodes and diversity centres detected by previous studies indicates the four marginal areas have been key areas in fauna evolution as centres for faunal exchange as well as glacial refugia.Based on the biogeographical patterns,the geological history of the QTPH and the evolutionary history of Aphidomorpha,we propose an evolutionary scenario for the evolution of the QTPH aphid fauna in which faunal exchanges,vicariance due to the uplift of geographical barriers,environmental heterogeneity and Quarternary glaciations have shaped the diversity patterns and fauna in the QTPH.
文摘BACKGROUND The existing literature indicates that psychotherapeutic treatment,especially exposure and response prevention(ERP)is efficacious in treating obsessivecompulsive disorder(OCD).The coronavirus disease 2019 pandemic adversely impacted many patients with OCD and disrupted their usual treatment.Moreover,the pandemic forced a global switch to telemental health(TMH)services to maintain the standards and continuity of care.Consequently,clinicians are increasingly using TMH-based psychotherapeutic treatments to treat OCD.However,several challenges have made it difficult for them to implement these treatments in the changed circumstances imposed by the pandemic.AIM To describe the formulation,implementation,feasibility,and usefulness of videoconferencing-based ERP(VC-ERP)treatment for OCD during the coronavirus disease 2019 pandemic.METHODS This prospective,observational study was conducted in the psychiatric unit of a multi-specialty hospital in north India over 12 mo(July 2020-June 2021).All patients with OCD were assessed using the home-based TMH services of the department.The VC-ERP protocol for OCD was the outcome of weekly Zoom meetings with a group of clinicians involved in administering the treatment.After a systematic evaluation of the available treatment options,an initial protocol for delivering VC-ERP was developed.Guidelines for clinicians and educational materials for patients and their families were prepared.The protocol was implemented among patients with OCD attending the TMH services,and their progress was monitored.The weekly meetings were used to upgrade the protocol to meet the needs of all stakeholders.Feasibility and efficacy outcomes were examined.RESULTS All patients were diagnosed with OCD as a primary or a comorbid condition according to the International Classification of Diseases,10th version criteria.Out of 115 patients who attended the services during the study period,37 were excluded from the final analysis.Of the remaining 78 patients,VC-ERP was initiated in 43 patients.Six pati
文摘Study of seismo-ionospheric coupling mechanism demands the quiet geomagnetic condition to eliminate any kind of contamination in the lower atmospheric and ionospheric parameters. In this manuscript, we present the effect of back to back two geomagnetic storms before a strong earthquake happened in Imphal, India on January 4, 2016 (M</span><span style="font-family:""> </span><span style="font-family:Verdana;">=</span><span style="font-family:""> </span><span style="font-family:Verdana;">6.7). We studied the lower ionospheric irregularities for </span><span style="font-family:Verdana;">the</span><span style="font-family:Verdana;"> duration of 31 days by computing the nighttime fluctuations in Very Low Frequency (VLF) radio signal received transmitter JJI (22.2 kHz) in Japan at Ionospheric and Earthquake Research Centre & Optical Observatory (IERCOO), Sitapur, India. We also studied the presence of Atmospheric Gravity Wave (AGW) in nighttime VLF signal in lower ionospheric heights and the same computed that from SABER/TIMED satellite. Two geomagnetic storms occurred on December 21, and 31, 2015. By the conventional analysis, we found that there is a significant decrease in nighttime trend and an increase in nighttime fluctuations around 15 days before the earthquake and just on the first storm and thus the pre-seismic effects on VLF signal gets contaminated due to the presence of storms. The wave-like structure in VLF fluctuations shows significant increase in intensity by using Fourier and Wavelet analysis before the earthquake. By analysis of SABER data, we found significant enhancement in AGW around 10 days before the earthquake. As the wavelike structures are coming from neutral acoustics reasons from pressure or temperature variations, this paper exhibits a significant example of contamination in ionospheric parameters due to geomagnetic storm where the acoustics parameters remain un-contaminated.
基金the Fast Track Project for Young scientists granted to Chandreyee Chakraborty Goswami by the Department of Science and Technology, Government of India (Grant No. SR/FTP/ES-47/2013)
文摘The present study area involves part of a deformed coalesced fan located along the Himalayan Frontal Thrust(HFT)on the east of river Tista near the India-Bhutan border.The area is marked by two spectacular E-W trending south-sloping scarps namely the Matiali(ca.60 m)and Chalsa(ca.90 m)Scarps and a north-sloping E-W trending Thaljhora(ca.80 m)Scarp.Our work comprises of a comparative study of geomorphology and geologic history in the adjacent interfluves of Jaldhaka-Gathia and Neora-Murti rivers to understand the tectonic history of the area.We mapped the Jaldhaka-Gathia river interfluve at a 1:25,000 scale and report a hitherto unidentified northerly sloping small scarp of ca.5 m height named the Nagrakata Scarp.This scarp was identified using satellite images,DEMs,and total station survey.We interpret that the two northsloping,E-W trending scarps(Thaljhora and Nagrakata Scarps)are manifestations of steep limbs of anticlines over blind south-dipping back thrusts.Together they form a wrinkle-ridge pair behind the north-dipping HFT,which is manifested by south-sloping Chalsa Scarp.We propose a plausible geomorphic model interpreting that deformation along the small fan in the Jaldhaka-Gathia interfluves is younger compared to fan deposition and deformation in the adjacent Mal-Murti interfluve.The most recent geomorphology of the Jaldhaka-Gathia interfluve is controlled by tectonism associated with the thrust below the Nagrakata Scarp where the youngest deformation episode is recorded to at around^6 ka and is likely related to motion on a splay off of the thrust beneath the Thaljhora Scarp.
文摘The World Health Organization’s 11^(th)revision of the International Classification of Diseases(ICD-11)including the chapter on mental disorders has come into effect this year.This review focuses on the“Bipolar or Related Disorders”section of the ICD-11 draft.It describes the benchmarks for the new version,particularly the foremost principle of clinical utility.The alterations made to the diagnosis of bipolar disorder(BD)are evaluated on their scientific basis and clinical utility.The change in the diagnostic requirements for manic and hypomanic episodes has been much debated.Whether the current criteria have achieved an optimum balance between sensitivity and specificity is still not clear.The ICD-11 definition of depressive episodes is substantially different,but the lack of empirical support for the changes has meant that the reliability and utility of bipolar depression are relatively low.Unlike the Diagnostic and Statistical Manual of Mental Disorders,5th edition(DSM-5),the ICD-11 has retained the category of mixed episodes.Although the concept of mixed episodes in the ICD-11 is not perfect,it appears to be more inclusive than the DSM-5 approach.Additionally,there are some uncertainties about the guidelines for the subtypes of BD and cyclothymic disorder.The initial results on the reliability and clinical utility of BD are promising,but the newly created diagnostic categories also appear to have some limitations.Although further improvement and research are needed,the focus should now be on facing the challenges of implementation,dissemination,and education and training in the use of these guidelines.
文摘About 40%-70%of the patients with treatment-resistant schizophrenia have a poor response to adequate treatment with clozapine.The impact of clozapineresistant schizophrenia(CRS)is even greater than that of treatment resistance in terms of severe and persistent symptoms,relapses and hospitalizations,poorer quality of life,and healthcare costs.Such serious consequences often compel clinicians to try different augmentation strategies to enhance the inadequate clozapine response in CRS.Unfortunately,a large body of evidence has shown that antipsychotics,antidepressants,mood stabilizers,electroconvulsive therapy,and cognitive-behavioural therapy are mostly ineffective in augmenting clozapine response.When beneficial effects of augmentation have been found,they are usually small and of doubtful clinical significance or based on low-quality evidence.Therefore,newer treatment approaches that go beyond the evidence are needed.The options proposed include developing a clinical consensus about the augmentation strategies that are most likely to be effective and using them sequentially in patients with CRS.Secondly,newer approaches such as augmentation with long-acting antipsychotic injections or multi-component psychosocial interventions could be considered.Lastly,perhaps the most effective way to deal with CRS would be to optimize clozapine treatment,which might prevent clozapine resistance from developing.Personalized dosing,adequate treatment durations,management of side effects and non-adherence,collaboration with patients and caregivers,and addressing clinician barriers to clozapine use are the principal ways of ensuring optimal clozapine treatment.At present,these three options could the best way to manage CRS until research provides more firm directions about the effective options for augmenting clozapine response.
文摘Telepsychiatry, i.e., the use of information and communication technologies to provide psychiatric services from a distance, has been around for more than half a century now. Research over this period has shown that videoconferencing-based telepsychiatry is an enabling and empowering form of service delivery, which promotes equality of access, and high levels of satisfaction among patients. The range of services offered by videoconferencing-based telepsychiatry, potential users and points of delivery of such services are theoretically limitless. Telepsychiatry has both clinical utility and non-clinical uses such as administrative, learning and research applications. A large body of accumulated evidence indicates that videoconferencingbased telepsychiatric assessments are reliable, and clinical outcomes of telepsychiatric interventions are comparable to conventional treatment among diverse patient populations, ages and diagnostic groups, and on a wide range of measures. However, on many aspects of effectiveness, the evidence base is still relatively limited and often compromised by methodological problems. The lack of cost-effectiveness data in particular, is a major hindrance, raising doubts about the continued viability of telepsychiatric services. Added to this are the vagaries of technology, negative views among clinicians, poor uptake by providers, and several legal, ethical and administrative barriers. These hamper the widespread implementation of telepsychiatry and its integration with routine care. Though further advances in technology and research are expected to solve many of these problems, the way forward would be to promote telepsychiatry as an adjunct to conventional care, and to develop hybrid models, which incorporate both traditional and telepsychiatric forms of mental health-care.
文摘Objective From the ancient period cow’urine has been used as a medicine. In Veda, cow’urine was compared to the nectar. In Susrut, several medicinal properties of cow’ urine have been mentioned and are known to cause weight loss, reversal of certain cardiac and kidney problems, indigestion, stomach ache, edema, etc. However, the literature and scripture did not mention the antigenotoxic properties of cow’urine. Methods In the present investigation, the antigenotoxic/ antioxidant properties of cow’ urine distillate and redistillate were studied in vitro. The antioxidant status and volatile fatty acid levels were determined. Actinomycin-D (0.1ol/L) and hydrogen peroxide (150 mol/L) were used for inducing DNA strand break with 0.1% DMSO as negative control. Dose for the antigenotoxic effect of cow’ urine was chosen from the dose response study carried out earlier. Results Both actinomycin-D and H2O2 caused statistically significant DNA unwinding of 80% & 75% respectively (P<0.001) as revealed by fluorimetric analysis of DNA unwinding (FADU), and the damage could be protected with the redistilled cow urine distillate (1, 50 & 100 ) in simultaneous treatment with genotoxic chemicals. Conclusion The redistillate of cowurine was found to possess total antioxidant status of around 2.6 mmol, contributed mainly by volatile fatty acids (1500 mg/L) as revealed by the GC-MS studies. These fatty acids and other antioxidants might cause the observed protective effects.
