Mutations in the WFS1 gene have been reported in Wolfram syndrome (WFS), a rare and autosomal recessive disorder defined <span style="font-family:Verdana;">by early onset of diabetes mellitus and progr...Mutations in the WFS1 gene have been reported in Wolfram syndrome (WFS), a rare and autosomal recessive disorder defined <span style="font-family:Verdana;">by early onset of diabetes mellitus and progressive optic and hearing impairment. Only few data are available concerning the association between clinical and molecular aspects of the WFS. We present a consanguineous family with a patient presenting an early onset of WFS and severe manifestations. Sequencing of </span><i><span style="font-family:Verdana;">WFS1</span></i><span style="font-family:Verdana;"> gene was performed for all the family members to search for responsible mutation and bioinformatics tools </span><span style="font-family:Verdana;">were </span><span style="font-family:;" "=""><span style="font-family:Verdana;">conducted to predict its effect on structure and function of the protein. We have detected a novel frameshift mutation in the proband at homozygous state and at the heterozygous state in the parents who have no WFS manifestations. In silico analysis predicted the pathogenicity of the mutation and could lead to a complete loss of its function. Thus, 3D modeling showed that the mutation abolishes the interaction of the CaM binding region to the N-terminal of WFS1 and then impairs the W</span><span style="font-family:Verdana;">FS1-CaM complex formation. Genotype-phenotype correlation study show</span><span style="font-family:Verdana;">s that the novel mutation predisposes to early onset of diabetes and severe symptoms observed in the proband. We also report the effect of the frameshift mutation on the CaM-WFS1 impaired binding, and we discuss its possible consequence in pancreatic </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-cells dysfunction and its role in the early onset of diabetes. In conclusion, the combination of impaired functions of WFS1 including unproper interaction of the CaM, Ca</span><sup><span style="font-family:Verdana;">2+</span></sup><span style="font-family:Verdana;"> uptake, mitochondrial dysfunction, and apoptosis under the ER stress could be involved in the severe phenotype and early onset of WFS of our patient.</span></span>展开更多
Diagnostic laboratories play a crucial role in surveillance and epidemic preparedness.However,gaps in adherence to biosecurity and biosafety protocols in managing,isolating,storing,and disposing of infec-tious pathoge...Diagnostic laboratories play a crucial role in surveillance and epidemic preparedness.However,gaps in adherence to biosecurity and biosafety protocols in managing,isolating,storing,and disposing of infec-tious pathogens in these facilities pose a serious risk to the laboratory,local populations,and the sur-rounding environment.In this study,we evaluated adherence to biosecurity and biosafety protocols in 96 public and private biomedical and veterinary laboratories in Benin to identify and address such gaps.We followed a cross-sectional study design.We used the Biosafety and Biosecurity in Laboratory Tool to assess biomedical laboratories and the Laboratory Mapping Tool to assess veterinary laboratories.Data were collected using KoBoCollect and analyzed with R software version 4.0.5.Descriptive analysis,the chi-squared test,and logistic regression were used to analyze the data.The findings revealed that most laboratories did not comply with established guidelines.Of all laboratories surveyed,42%presented a very high risk,38%a high risk,15%moderate risk,and 5%were low risk.Overall,80%of biomedical lab-oratories and 100%of veterinary laboratories were rated high risk.To improve effective biosecurity prac-tices in laboratories in Benin to an acceptable standard,it is essential to implement robust biosecurity and biosafety policies.Additionally,capacity-building sessions should be conducted for laboratory staff and managers to educate them on the latest biosecurity protocols.展开更多
Background Pituitary apoplexy(PA)is defined as the hemorrhage or the infraction of a pituitary adenoma.Aiming to determine the epidemiological,clinical,paraclinical characteristics as well as management and outcomes o...Background Pituitary apoplexy(PA)is defined as the hemorrhage or the infraction of a pituitary adenoma.Aiming to determine the epidemiological,clinical,paraclinical characteristics as well as management and outcomes of PA in our population,we conducted this cross-sectional study.Methods This cross-sectional study was conducted at the Department of Endocrinology of Hedi chaker university hospital,Sfax.Data was collected from medical charts of patients with pituitary apoplexy admitted in our department between 2000 and 2017.Results We included 44 patients with PA.Their mean age was 50±12.6 years.Among them,31.8%had a known pituitary adenoma,and it was in all cases a macroadenoma,predominantly a prolactin secreting tumor(42.8%).A triggering factor of PA was encountered in 31.8%of cases and it was mainly:head trauma,dopamine antagonists,and hypertension.The clinical presentation of PA encompassed headaches(84.1%),visual disturbances(75%),and neurological signs(40.9%).Gonadotropin deficiency was the most frequent form of hypopituitarism noted(59.1%),followed by corticotropin deficiency(52.3%),thyrotropin deficiency(47.7%),and somatotropin deficiency(2.3%).Hormonal assessment at PA onset,concluded that 23 had a secreting adenoma:18 prolactinomas,3 ACTH-secreting adenomas,and 2 GH-secreting adenomas.In the 21 remaining cases,the tumor was non-functioning(47.7%).Pituitary MRI was performed in 42 cases(95.5%),revealing infraction and or hemorrhage in the pituitary gland in 33 cases;a heterogenous signal or a fluid level within the adenoma,in nine cases.Urgent administration of intra venous hydrocortisone was required in 19 cases.Mannitol administration was mandatory in a patient who had severe intracranial hypertension.Surgical management of the PA was imperative in 24 patients(54.5%):15 suffered from severe visual impairment,4 had an intracranial hypertension,2 cases demonstrated an impaired consciousness,2 patients experienced a tumor enlargement and one case had a severe Cushing’s disease.Operative complications found were rhinorrhea attributable to cerebral spinal fluid leakage,insipidus diabetes associated with rhinorrhea,isolated insipidus diabetes,and hydrocephalus in one case each.Long-term follow-up concluded that headaches persisted in five cases,owing to the tenacity of a macroprolactinoma regardless of cabergoline treatment in one case,the recurrence of an adenoma in two cases and its persistence despite the medical and the surgical treatment in two patients.Concerning the visual acuity defects,only two patients had persistent diminished visual acuity at long-term follow-up.Among 25 patients,13 were diagnosed with definitive thyrotropin deficiency.Similarly,14 patients had persistent corticotropin deficiency(CD).Additionally,CD was de novo diagnosed in two patients.Otherwise,gonadotropin deficiency prevailed in all cases.Persistent prolactin deficiency was seen in two patients.Disappearance of the pituitary tumor was encountered in 11 out of 24 cases at long-term follow-up.Overall,surgery was associated with better outcome than conservative management.Pituitary apoplexy is a challenging condition due to its variable course,its diagnosis difficulty and management,as gaps remain to determine the best approach to treat this condition.Conclusions To conclude,pituitary apoplexy is a challenging condition due to its variable course,its diagnosis difficulty and management,as gaps remain to determine the best approach to treat this condition.Further studies are thus needed.展开更多
文摘Mutations in the WFS1 gene have been reported in Wolfram syndrome (WFS), a rare and autosomal recessive disorder defined <span style="font-family:Verdana;">by early onset of diabetes mellitus and progressive optic and hearing impairment. Only few data are available concerning the association between clinical and molecular aspects of the WFS. We present a consanguineous family with a patient presenting an early onset of WFS and severe manifestations. Sequencing of </span><i><span style="font-family:Verdana;">WFS1</span></i><span style="font-family:Verdana;"> gene was performed for all the family members to search for responsible mutation and bioinformatics tools </span><span style="font-family:Verdana;">were </span><span style="font-family:;" "=""><span style="font-family:Verdana;">conducted to predict its effect on structure and function of the protein. We have detected a novel frameshift mutation in the proband at homozygous state and at the heterozygous state in the parents who have no WFS manifestations. In silico analysis predicted the pathogenicity of the mutation and could lead to a complete loss of its function. Thus, 3D modeling showed that the mutation abolishes the interaction of the CaM binding region to the N-terminal of WFS1 and then impairs the W</span><span style="font-family:Verdana;">FS1-CaM complex formation. Genotype-phenotype correlation study show</span><span style="font-family:Verdana;">s that the novel mutation predisposes to early onset of diabetes and severe symptoms observed in the proband. We also report the effect of the frameshift mutation on the CaM-WFS1 impaired binding, and we discuss its possible consequence in pancreatic </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-cells dysfunction and its role in the early onset of diabetes. In conclusion, the combination of impaired functions of WFS1 including unproper interaction of the CaM, Ca</span><sup><span style="font-family:Verdana;">2+</span></sup><span style="font-family:Verdana;"> uptake, mitochondrial dysfunction, and apoptosis under the ER stress could be involved in the severe phenotype and early onset of WFS of our patient.</span></span>
基金supported by the Elizabeth R.Griffin Pro-gram through funding provided by the U.S.Department of State,Nonproliferation and Disarmament Fund(grant number SISNDF22GR0010)The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Diagnostic laboratories play a crucial role in surveillance and epidemic preparedness.However,gaps in adherence to biosecurity and biosafety protocols in managing,isolating,storing,and disposing of infec-tious pathogens in these facilities pose a serious risk to the laboratory,local populations,and the sur-rounding environment.In this study,we evaluated adherence to biosecurity and biosafety protocols in 96 public and private biomedical and veterinary laboratories in Benin to identify and address such gaps.We followed a cross-sectional study design.We used the Biosafety and Biosecurity in Laboratory Tool to assess biomedical laboratories and the Laboratory Mapping Tool to assess veterinary laboratories.Data were collected using KoBoCollect and analyzed with R software version 4.0.5.Descriptive analysis,the chi-squared test,and logistic regression were used to analyze the data.The findings revealed that most laboratories did not comply with established guidelines.Of all laboratories surveyed,42%presented a very high risk,38%a high risk,15%moderate risk,and 5%were low risk.Overall,80%of biomedical lab-oratories and 100%of veterinary laboratories were rated high risk.To improve effective biosecurity prac-tices in laboratories in Benin to an acceptable standard,it is essential to implement robust biosecurity and biosafety policies.Additionally,capacity-building sessions should be conducted for laboratory staff and managers to educate them on the latest biosecurity protocols.
文摘Background Pituitary apoplexy(PA)is defined as the hemorrhage or the infraction of a pituitary adenoma.Aiming to determine the epidemiological,clinical,paraclinical characteristics as well as management and outcomes of PA in our population,we conducted this cross-sectional study.Methods This cross-sectional study was conducted at the Department of Endocrinology of Hedi chaker university hospital,Sfax.Data was collected from medical charts of patients with pituitary apoplexy admitted in our department between 2000 and 2017.Results We included 44 patients with PA.Their mean age was 50±12.6 years.Among them,31.8%had a known pituitary adenoma,and it was in all cases a macroadenoma,predominantly a prolactin secreting tumor(42.8%).A triggering factor of PA was encountered in 31.8%of cases and it was mainly:head trauma,dopamine antagonists,and hypertension.The clinical presentation of PA encompassed headaches(84.1%),visual disturbances(75%),and neurological signs(40.9%).Gonadotropin deficiency was the most frequent form of hypopituitarism noted(59.1%),followed by corticotropin deficiency(52.3%),thyrotropin deficiency(47.7%),and somatotropin deficiency(2.3%).Hormonal assessment at PA onset,concluded that 23 had a secreting adenoma:18 prolactinomas,3 ACTH-secreting adenomas,and 2 GH-secreting adenomas.In the 21 remaining cases,the tumor was non-functioning(47.7%).Pituitary MRI was performed in 42 cases(95.5%),revealing infraction and or hemorrhage in the pituitary gland in 33 cases;a heterogenous signal or a fluid level within the adenoma,in nine cases.Urgent administration of intra venous hydrocortisone was required in 19 cases.Mannitol administration was mandatory in a patient who had severe intracranial hypertension.Surgical management of the PA was imperative in 24 patients(54.5%):15 suffered from severe visual impairment,4 had an intracranial hypertension,2 cases demonstrated an impaired consciousness,2 patients experienced a tumor enlargement and one case had a severe Cushing’s disease.Operative complications found were rhinorrhea attributable to cerebral spinal fluid leakage,insipidus diabetes associated with rhinorrhea,isolated insipidus diabetes,and hydrocephalus in one case each.Long-term follow-up concluded that headaches persisted in five cases,owing to the tenacity of a macroprolactinoma regardless of cabergoline treatment in one case,the recurrence of an adenoma in two cases and its persistence despite the medical and the surgical treatment in two patients.Concerning the visual acuity defects,only two patients had persistent diminished visual acuity at long-term follow-up.Among 25 patients,13 were diagnosed with definitive thyrotropin deficiency.Similarly,14 patients had persistent corticotropin deficiency(CD).Additionally,CD was de novo diagnosed in two patients.Otherwise,gonadotropin deficiency prevailed in all cases.Persistent prolactin deficiency was seen in two patients.Disappearance of the pituitary tumor was encountered in 11 out of 24 cases at long-term follow-up.Overall,surgery was associated with better outcome than conservative management.Pituitary apoplexy is a challenging condition due to its variable course,its diagnosis difficulty and management,as gaps remain to determine the best approach to treat this condition.Conclusions To conclude,pituitary apoplexy is a challenging condition due to its variable course,its diagnosis difficulty and management,as gaps remain to determine the best approach to treat this condition.Further studies are thus needed.
