There are no standard guidelines to follow when a patient with chronic hepatitis B infection becomes pregnant or desires pregnancy. Topics to consider include which patients to treat, when to start treatment, what tre...There are no standard guidelines to follow when a patient with chronic hepatitis B infection becomes pregnant or desires pregnancy. Topics to consider include which patients to treat, when to start treatment, what treatment to use and when to stop treatment. Without any prophylaxis or antiviral therapy, a hepatitis B surface antigen and E antigen positive mother has up to a 90% likelihood of vertical transmission of hepatitis B virus(HBV) to child. Standard of care in the United States to prevent perinatal transmission consists of administration of hepatitis B immune globulin and HBV vaccination to the infant. The two strongest risk factors of mother to child transmission(MTCT) of HBV infection despite immunoprophylaxis are high maternal HBV viral load and high activity of viral replication. The goal is to prevent transmission of HBV at birth by decreasing viral load and/or decreasing activity of the virus. Although it is still somewhat controversial, most evidence shows that starting antivirals in the third trimester is effective in decreasing MTCT without affecting fetal development. There is a growing body of literature supporting the safety and efficacy of antiviral therapies to reduce MTCT of hepatitis B. There are no formal recommendations regarding which agent to choose. Tenofovir, lamivudine and telbivudine have all been proven efficacious in decreasing viral load at birth without known birth defects, but final decision of which antiviral medication to use will have to be determined by physician and patient. The antivirals may be discontinued immediately if patient is breastfeeding, or within first four weeks if infant is being formula fed.展开更多
Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus a...Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, S.aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.展开更多
AIM:To integrate results from different studies in examining the effectiveness of music in reducing the procedure time and the amount of sedation used during colonoscopic procedure. METHODS: An electronic search in va...AIM:To integrate results from different studies in examining the effectiveness of music in reducing the procedure time and the amount of sedation used during colonoscopic procedure. METHODS: An electronic search in various databases was performed to identify related articles. Study quality was evaluated by the Jadad’s scale. The random effect model was used to pool the effect from individual trials and the Cohen Q-statistic was used to determine heterogeneity. Egger’s regression was used to detect publication bias. RESULTS: Eight studies with 722 subjects were included in this meta-analysis. The combined mean difference for the time taken for the colonoscopy procedure between the music and control groups was -2.84 with 95% CI (-5.61 to -0.08), implying a short time for the music group. The combined mean difference for the use of sedation was -0.46 with 95%CI (-0.91 to -0.01), showing a significant reduction in the use of sedation in the music group. Heterogeneity was observed in both analyses but no publication bias was detected. CONCLUSION: Listening to music is effective in reducing procedure time and amount of sedation during colonoscopy and should be promoted.展开更多
Double fertilization in flowering plants occurs when the two sperm cells, carried by the pollen tube, are released in a synergid cell of the embryo sac and then fertilize the egg and the central cell. Proteins on the ...Double fertilization in flowering plants occurs when the two sperm cells, carried by the pollen tube, are released in a synergid cell of the embryo sac and then fertilize the egg and the central cell. Proteins on the surfaces of the sperm, egg, central, and synergid cells might be important for guidance and recognition/fusion of the gametes. Here, we present functional analyses ofArabidopsis GEX3, which encodes a plasma membrane-localized protein that has homologs in other plants. GEX3 is expressed in both the vegetative and sperm cells of the male gametophyte and in the egg cell of the female gametophyte. Transgenic lines in which GEX3 was down-regulated or overexpressed, using the Arabidopsis GEX2 promoter, had reduced seed set. Reciprocal crosses and imaging after pollination with a reporter line showed that, in both cases, the defect causing reduced seed set occurred in the female. In the antisense lines, micropylar pollen tube guidance failed, In the overexpression lines, fertilization of mutant ovules was mostly blocked because pollen tube guidance failed, although, occasionally, non-viable embryos were formed. We conclude that properly regulated expression of GEX3 in the egg cell of Arabidopsis is essential for pollen tube guidance.展开更多
Hematopoietic tumors are associated with diagnostic and therapeutic challenges and a poor prognosis. Furthermore, their pathophysiology in dogs is not well understood. Chronic lymphocytic leukemia has been rarely repo...Hematopoietic tumors are associated with diagnostic and therapeutic challenges and a poor prognosis. Furthermore, their pathophysiology in dogs is not well understood. Chronic lymphocytic leukemia has been rarely reported in golden retrievers, perhaps due to difficulties in diagnosis and care. An 8-year-old spayed female golden retriever was referred to our hospital with a 2-month history of fatigue, weakness, and selective appetite. The dog was diagnosed with chronic lymphocytic leukemia based on blood smear evaluation. Despite treatment, the dog deteriorated and the owners opted for euthanasia. Histopathological examination revealed atypical lymphocytes in the spleen, extramedullary hematopoiesis in the spleen and liver, bone marrow depletion, moderate neutrophilic myocarditis, and acute renal tubular necrosis. In an immunohistochemical panel, cells in the spleen and bone marrow were positive for anti-CD20, anti-CD45, anti-CD3, anti-IBA-1, anti-Ki67, anti-MUM-1, and anti-PAX-5. In conclusion, the leukemia diagnosis was confirmed through reactive histiocytosis, marked extramedullary hematopoiesis, and other clinical and laboratory findings. Herein, we report a case of chronic lymphocytic leukemia in a female dog with clinical, laboratory, and necroscopy findings.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liv...Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liver disease varies substantially among populations.It is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with MASLD.Nonalcoholic steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of MASLD.MASLD diagnosis is based on the presence of steatosis,noninvasive scores and altered liver tests.Noninvasive scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely available.Currently,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical practice.Unfortunately,there is no definite pharmacological treatment for the condition.Creating public health policies to treat patients with risk factors for MASLD prevention is essential.展开更多
The R-spondin family of proteins are Wnt agonists, and the complete embryonic disruption of Rspo2 results in skeletal developmental defects that recapitulate the phenotype observed with Lrp5/6 deficiency. Previous wor...The R-spondin family of proteins are Wnt agonists, and the complete embryonic disruption of Rspo2 results in skeletal developmental defects that recapitulate the phenotype observed with Lrp5/6 deficiency. Previous work has shown that R-spondin-2(Rspo2, RSPO2) is both highly expressed in Wnt-stimulated pre-osteoblasts and its overexpression induces osteoblast differentiation in the same cells, supporting its putative role as a positive autocrine regulator of osteoblastogenesis. However, the role of Rspo2 in regulating osteoblastogenesis and bone formation in postnatal bone has not been explored. Here we show that limb-bud progenitor cells from Rspo2 knockout mice undergo reduced mineralization during osteoblastogenesis in vitro and have a corresponding alteration in their osteogenic gene expression profile. We also generated the first Rspo2 conditional knockout(Rspo2 floxed) mouse and disrupted Rspo2 expression in osteoblast-lineage cells by crossing to the Osteocalcin-Cre mouse line(OcnCre + Rspo2 ^(f/f)). Ocn-Cre + Rspo2 f/fmale and female mice at 1, 3, and 6 months were examined. Ocn-Cre + Rspo2 f/fmice are decreased in overall body size compared to their control littermates and have decreased bone mass. Histomorphometric analysis of1-month-old mice revealed a similar number of osteoblasts and mineralizing surface per bone surface with a simultaneous decrease in mineral apposition and bone formation rates. Consistent with this observation, serum osteocalcin in 3-month-old Ocn-Cre +Rspo2 f/fwas reduced, and bone marrow-mesenchymal stem cells from Ocn-Cre + Rspo2 f/fmice undergo less mineralization in vitro.Finally, gene expression analysis and immunohistochemistry of mature bone shows reduced beta-catenin signaling in Ocn-Cre +Rspo2 f/f. Overall, RSPO2 reduces osteoblastogenesis and mineralization, leading to reduced bone mass.展开更多
Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Amon...Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major conditions contributing to these symptoms are pelvic and retroperitoneal surgery, diabetes, congenital spinal abnormalities, multiple sclerosis and spinal cord injury, Erectile dysfunction can be managed by an increasingly invasive range of treatments including medications, injection therapy and the surgical insertion of a penile implant. Retrograde ejaculation is managed by medications to reverse the condition in mild cases and in bladder harvest of semen after ejaculation in more severe cases. Anejaculation might also be managed by medication in mild cases while assisted ejaculatory techniques including penile vibratory stimulation and eiectroejaculation are used in more severe cases. If these measures fail, surgical sperm retrieval can be attempted. Ejaculation with penile vibratory stimulation can be done by some spinal cord injured men and their partners at home, followed by in-home insemination if circumstances and sperm quality are adequate. The other options always require assisted reproductive techniques including intrauterine insemination or in vitrofertilization with or without intracytoplasmic sperm injection. The method of choice depends largely on the number of motile sperm in the ejaculate.展开更多
AIM: To perform a systematic review and meta-analysis comparing operative vs non-operative treatment of displaced proximal humerus fractures in elderly patients.METHODS: A systematic literature search was performed us...AIM: To perform a systematic review and meta-analysis comparing operative vs non-operative treatment of displaced proximal humerus fractures in elderly patients.METHODS: A systematic literature search was performed using EMBASE and MEDLINE through the OVID interface,CINAHL,the Cochrane Central Register of Controlled Trials(CENTRAL),Proquest,Web of Science,SAE digital library,and Transportation Research Board's TRID database.Searches of conference proceedings were also conducted.All available randomized controlled trials comparing operative vs non-operative management of displaced three- and four-part proximal humerus fractures in elderly patients were included.The primary outcomes measures included physical function,pain,health related quality of life,mortality,and the re-operation rate.RESULTS: Six randomized controlled trials(n = 287) were included.There was no statistically significant difference in function(MD = 1.72,95%CI:-2.90-6.34,P = 0.47),as measured by the Constant score,between the operative and the non-operative treatment groups.There was no statistically significance difference insecondary outcomes of health related quality of life(standardized MD = 0.27,95%CI:-0.05-0.59,P = 0.09),and mortality(relative risk 1.29,95%CI: 0.50-3.35,P = 0.60).Operative treatment had a statistically significant higher re-operation rate(relative risk 4.09,95%CI: 1.50-11.15,P = 0.006),and statistically significant decreased pain(MD = 1.26,95%CI: 0.02-2.49,P = 0.05).CONCLUSION: There is moderate quality evidence to suggest that there is no difference in functional outcomes between the two treatments.Further high quality randomized controlled trials are required to determine if certain subgroup populations benefit from surgical management.展开更多
Student engagement in a clinical learning environment is a vital component in the curricula of pre-licensure nursing students, providing an opportunity to combine cognitive, psychomotor, and affective skills. This pap...Student engagement in a clinical learning environment is a vital component in the curricula of pre-licensure nursing students, providing an opportunity to combine cognitive, psychomotor, and affective skills. This paper is significant in Arab world as there is a lack of knowledge, attitude and practice of student involvement in the new clinical learning environment. The purpose of this review article is to describe the experiences and perspectives of the nurse educator in facilitating pre-licensure nursing students’ engagement in the new clinical learning environment. The review suggests that novice students prefer actual engagement in clinical learning facilitated through diversity experiences, shared learning opportunities, student-faculty interaction and active learning. They expressed continuous supervision, ongoing feedback, interpersonal relationship and personal support from nurse educators useful in the clinical practice. However, the value of this review lies in a better understanding of what constitutes quality clinical learning environment from the students’ perspective of engagement in evidence-based nursing, reflective practice, e-learning and simulated case scenarios facilitated by the nurse educators. This review is valuable in planning and implementing innovative clinical and educational experiences for improving the quality of the clinical teaching-learning environment.展开更多
Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolat...Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis;however,there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis.A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil,which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production.Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events.The patient was managed without a biliary stent.However,there was a return of symptoms,jaundice,increase in transaminases,and hyperbilirubinemia when the prednisone dose reached 11 mg per day.In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis,the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events,but it did not enable discontinuation of the steroids.Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.展开更多
Multiple sclerosis(MS)is characterized as an inflammatory demyelinating disease that affects the central nervous system(CNS),leading to sensory,motor and cognitive impairments.Ultimately,axonal denudation culminates i...Multiple sclerosis(MS)is characterized as an inflammatory demyelinating disease that affects the central nervous system(CNS),leading to sensory,motor and cognitive impairments.Ultimately,axonal denudation culminates in axonal lesions and neurodegeneration.Inflammatory demyelinating lesions in MS are associated with infiltration of immune cells combined with activation of the resident CNS inflammatory cells,astro-and microglia.展开更多
文摘There are no standard guidelines to follow when a patient with chronic hepatitis B infection becomes pregnant or desires pregnancy. Topics to consider include which patients to treat, when to start treatment, what treatment to use and when to stop treatment. Without any prophylaxis or antiviral therapy, a hepatitis B surface antigen and E antigen positive mother has up to a 90% likelihood of vertical transmission of hepatitis B virus(HBV) to child. Standard of care in the United States to prevent perinatal transmission consists of administration of hepatitis B immune globulin and HBV vaccination to the infant. The two strongest risk factors of mother to child transmission(MTCT) of HBV infection despite immunoprophylaxis are high maternal HBV viral load and high activity of viral replication. The goal is to prevent transmission of HBV at birth by decreasing viral load and/or decreasing activity of the virus. Although it is still somewhat controversial, most evidence shows that starting antivirals in the third trimester is effective in decreasing MTCT without affecting fetal development. There is a growing body of literature supporting the safety and efficacy of antiviral therapies to reduce MTCT of hepatitis B. There are no formal recommendations regarding which agent to choose. Tenofovir, lamivudine and telbivudine have all been proven efficacious in decreasing viral load at birth without known birth defects, but final decision of which antiviral medication to use will have to be determined by physician and patient. The antivirals may be discontinued immediately if patient is breastfeeding, or within first four weeks if infant is being formula fed.
基金supported by grants from AOTrauma, Clinical Priority Program (Davos, Switzerland)NIH NIAMS (P50 AR072000 and P30 AR069655)+9 种基金supported by grants from NIH NIAMS P30 AR069655 pilotAO Trauma Research Fellowship (Davos, Switzerland)supported by grants from the NIH (R01 AR43510 and R01 AG049994)supported by grants from the NIH (P30 AR061307 and T32 AR53459)the NIH (R21 AR074571 and R21 AR073321)supported by grants from the NIH (R21 AR073321, R21 AR500710 and P30 AR06965501 Pilot)supported by grants from the NIH (R21 AI119646)supported by grants from Amedica Incsupported by grants from Bristol-Myers, Astellas, and Asahi-Kaseisupported by the Goldstein Award from the Department of Orthopaedics, University of Rochester, Rochester, NY
文摘Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, S.aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.
文摘AIM:To integrate results from different studies in examining the effectiveness of music in reducing the procedure time and the amount of sedation used during colonoscopic procedure. METHODS: An electronic search in various databases was performed to identify related articles. Study quality was evaluated by the Jadad’s scale. The random effect model was used to pool the effect from individual trials and the Cohen Q-statistic was used to determine heterogeneity. Egger’s regression was used to detect publication bias. RESULTS: Eight studies with 722 subjects were included in this meta-analysis. The combined mean difference for the time taken for the colonoscopy procedure between the music and control groups was -2.84 with 95% CI (-5.61 to -0.08), implying a short time for the music group. The combined mean difference for the use of sedation was -0.46 with 95%CI (-0.91 to -0.01), showing a significant reduction in the use of sedation in the music group. Heterogeneity was observed in both analyses but no publication bias was detected. CONCLUSION: Listening to music is effective in reducing procedure time and amount of sedation during colonoscopy and should be promoted.
文摘Double fertilization in flowering plants occurs when the two sperm cells, carried by the pollen tube, are released in a synergid cell of the embryo sac and then fertilize the egg and the central cell. Proteins on the surfaces of the sperm, egg, central, and synergid cells might be important for guidance and recognition/fusion of the gametes. Here, we present functional analyses ofArabidopsis GEX3, which encodes a plasma membrane-localized protein that has homologs in other plants. GEX3 is expressed in both the vegetative and sperm cells of the male gametophyte and in the egg cell of the female gametophyte. Transgenic lines in which GEX3 was down-regulated or overexpressed, using the Arabidopsis GEX2 promoter, had reduced seed set. Reciprocal crosses and imaging after pollination with a reporter line showed that, in both cases, the defect causing reduced seed set occurred in the female. In the antisense lines, micropylar pollen tube guidance failed, In the overexpression lines, fertilization of mutant ovules was mostly blocked because pollen tube guidance failed, although, occasionally, non-viable embryos were formed. We conclude that properly regulated expression of GEX3 in the egg cell of Arabidopsis is essential for pollen tube guidance.
文摘Hematopoietic tumors are associated with diagnostic and therapeutic challenges and a poor prognosis. Furthermore, their pathophysiology in dogs is not well understood. Chronic lymphocytic leukemia has been rarely reported in golden retrievers, perhaps due to difficulties in diagnosis and care. An 8-year-old spayed female golden retriever was referred to our hospital with a 2-month history of fatigue, weakness, and selective appetite. The dog was diagnosed with chronic lymphocytic leukemia based on blood smear evaluation. Despite treatment, the dog deteriorated and the owners opted for euthanasia. Histopathological examination revealed atypical lymphocytes in the spleen, extramedullary hematopoiesis in the spleen and liver, bone marrow depletion, moderate neutrophilic myocarditis, and acute renal tubular necrosis. In an immunohistochemical panel, cells in the spleen and bone marrow were positive for anti-CD20, anti-CD45, anti-CD3, anti-IBA-1, anti-Ki67, anti-MUM-1, and anti-PAX-5. In conclusion, the leukemia diagnosis was confirmed through reactive histiocytosis, marked extramedullary hematopoiesis, and other clinical and laboratory findings. Herein, we report a case of chronic lymphocytic leukemia in a female dog with clinical, laboratory, and necroscopy findings.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liver disease varies substantially among populations.It is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with MASLD.Nonalcoholic steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of MASLD.MASLD diagnosis is based on the presence of steatosis,noninvasive scores and altered liver tests.Noninvasive scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely available.Currently,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical practice.Unfortunately,there is no definite pharmacological treatment for the condition.Creating public health policies to treat patients with risk factors for MASLD prevention is essential.
基金supported by the National Institutes of Health (NIH) National Institute of Arthritis and Musculoskeletal Diseases (NIAMS)funding of the University of Pennsylvania Center for Musculoskeletal Disorders (PCMD) (P30AR069619)the University of Michigan Integrative Musculoskeletal Health Core Center (P30AR069620)+1 种基金supported by NIH NIAMS R01AR066028supported by NIH NIAMS F31AR065858
文摘The R-spondin family of proteins are Wnt agonists, and the complete embryonic disruption of Rspo2 results in skeletal developmental defects that recapitulate the phenotype observed with Lrp5/6 deficiency. Previous work has shown that R-spondin-2(Rspo2, RSPO2) is both highly expressed in Wnt-stimulated pre-osteoblasts and its overexpression induces osteoblast differentiation in the same cells, supporting its putative role as a positive autocrine regulator of osteoblastogenesis. However, the role of Rspo2 in regulating osteoblastogenesis and bone formation in postnatal bone has not been explored. Here we show that limb-bud progenitor cells from Rspo2 knockout mice undergo reduced mineralization during osteoblastogenesis in vitro and have a corresponding alteration in their osteogenic gene expression profile. We also generated the first Rspo2 conditional knockout(Rspo2 floxed) mouse and disrupted Rspo2 expression in osteoblast-lineage cells by crossing to the Osteocalcin-Cre mouse line(OcnCre + Rspo2 ^(f/f)). Ocn-Cre + Rspo2 f/fmale and female mice at 1, 3, and 6 months were examined. Ocn-Cre + Rspo2 f/fmice are decreased in overall body size compared to their control littermates and have decreased bone mass. Histomorphometric analysis of1-month-old mice revealed a similar number of osteoblasts and mineralizing surface per bone surface with a simultaneous decrease in mineral apposition and bone formation rates. Consistent with this observation, serum osteocalcin in 3-month-old Ocn-Cre +Rspo2 f/fwas reduced, and bone marrow-mesenchymal stem cells from Ocn-Cre + Rspo2 f/fmice undergo less mineralization in vitro.Finally, gene expression analysis and immunohistochemistry of mature bone shows reduced beta-catenin signaling in Ocn-Cre +Rspo2 f/f. Overall, RSPO2 reduces osteoblastogenesis and mineralization, leading to reduced bone mass.
文摘Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major conditions contributing to these symptoms are pelvic and retroperitoneal surgery, diabetes, congenital spinal abnormalities, multiple sclerosis and spinal cord injury, Erectile dysfunction can be managed by an increasingly invasive range of treatments including medications, injection therapy and the surgical insertion of a penile implant. Retrograde ejaculation is managed by medications to reverse the condition in mild cases and in bladder harvest of semen after ejaculation in more severe cases. Anejaculation might also be managed by medication in mild cases while assisted ejaculatory techniques including penile vibratory stimulation and eiectroejaculation are used in more severe cases. If these measures fail, surgical sperm retrieval can be attempted. Ejaculation with penile vibratory stimulation can be done by some spinal cord injured men and their partners at home, followed by in-home insemination if circumstances and sperm quality are adequate. The other options always require assisted reproductive techniques including intrauterine insemination or in vitrofertilization with or without intracytoplasmic sperm injection. The method of choice depends largely on the number of motile sperm in the ejaculate.
基金Supported by In part by a Canada Research Chair to Dr.Bhandariin part by the Canadian Institutes of Health Research and Vancouver Coastal Health Research Institute to Dr.Slobogean
文摘AIM: To perform a systematic review and meta-analysis comparing operative vs non-operative treatment of displaced proximal humerus fractures in elderly patients.METHODS: A systematic literature search was performed using EMBASE and MEDLINE through the OVID interface,CINAHL,the Cochrane Central Register of Controlled Trials(CENTRAL),Proquest,Web of Science,SAE digital library,and Transportation Research Board's TRID database.Searches of conference proceedings were also conducted.All available randomized controlled trials comparing operative vs non-operative management of displaced three- and four-part proximal humerus fractures in elderly patients were included.The primary outcomes measures included physical function,pain,health related quality of life,mortality,and the re-operation rate.RESULTS: Six randomized controlled trials(n = 287) were included.There was no statistically significant difference in function(MD = 1.72,95%CI:-2.90-6.34,P = 0.47),as measured by the Constant score,between the operative and the non-operative treatment groups.There was no statistically significance difference insecondary outcomes of health related quality of life(standardized MD = 0.27,95%CI:-0.05-0.59,P = 0.09),and mortality(relative risk 1.29,95%CI: 0.50-3.35,P = 0.60).Operative treatment had a statistically significant higher re-operation rate(relative risk 4.09,95%CI: 1.50-11.15,P = 0.006),and statistically significant decreased pain(MD = 1.26,95%CI: 0.02-2.49,P = 0.05).CONCLUSION: There is moderate quality evidence to suggest that there is no difference in functional outcomes between the two treatments.Further high quality randomized controlled trials are required to determine if certain subgroup populations benefit from surgical management.
文摘Student engagement in a clinical learning environment is a vital component in the curricula of pre-licensure nursing students, providing an opportunity to combine cognitive, psychomotor, and affective skills. This paper is significant in Arab world as there is a lack of knowledge, attitude and practice of student involvement in the new clinical learning environment. The purpose of this review article is to describe the experiences and perspectives of the nurse educator in facilitating pre-licensure nursing students’ engagement in the new clinical learning environment. The review suggests that novice students prefer actual engagement in clinical learning facilitated through diversity experiences, shared learning opportunities, student-faculty interaction and active learning. They expressed continuous supervision, ongoing feedback, interpersonal relationship and personal support from nurse educators useful in the clinical practice. However, the value of this review lies in a better understanding of what constitutes quality clinical learning environment from the students’ perspective of engagement in evidence-based nursing, reflective practice, e-learning and simulated case scenarios facilitated by the nurse educators. This review is valuable in planning and implementing innovative clinical and educational experiences for improving the quality of the clinical teaching-learning environment.
基金Supported by Department of Medicine,Emory University
文摘Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis;however,there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis.A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil,which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production.Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events.The patient was managed without a biliary stent.However,there was a return of symptoms,jaundice,increase in transaminases,and hyperbilirubinemia when the prednisone dose reached 11 mg per day.In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis,the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events,but it did not enable discontinuation of the steroids.Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.
基金supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)(to FCAG and VGC),Fundação Carlos Chagas Filho de AmparoàPesquisa do Estado do Rio de Janeiro(FAPERJ)(to FCAG)Ministério da Saúde(MS-Decit)(to FCAG).
文摘Multiple sclerosis(MS)is characterized as an inflammatory demyelinating disease that affects the central nervous system(CNS),leading to sensory,motor and cognitive impairments.Ultimately,axonal denudation culminates in axonal lesions and neurodegeneration.Inflammatory demyelinating lesions in MS are associated with infiltration of immune cells combined with activation of the resident CNS inflammatory cells,astro-and microglia.
