A previous diagnosis of gestational diabetes(GDM)carries a lifetime risk of progression to type 2 diabetes of up to 60%.Identification of those women at higher risk of progression to diabetes allows the timely introdu...A previous diagnosis of gestational diabetes(GDM)carries a lifetime risk of progression to type 2 diabetes of up to 60%.Identification of those women at higher risk of progression to diabetes allows the timely introduction of measures to delay or prevent diabetes onset.However,there is a large degree of variability in the literature with regard to the proportion of women with a history of GDM who go on to develop diabetes.Heterogeneity between cohorts with regard to diagnostic criteria used,duration of follow-up,and the characteristics of the study population limit the ability to make meaningful comparisons across studies.As the new International Association for Diabetes in Pregnancy Study Group criteria are increasingly adopted worldwide,the prevalence of GDM is set to increase by two-to three-fold.Here,we review the literature to examine the evolution of diagnostic criteria for GDM,the implications of changing criteria on the proportion of women with previous GDM progressing to diabetes,and how the use of different diagnostic criteria may influence the development of appropriate follow-up strategies.展开更多
BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more ad...BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life.展开更多
Research indicates that high levels of sedentary behavior(sitting or lying with low energy expenditure) are adversely associated with health. A key factor in improving our understanding of the impact of sedentary beha...Research indicates that high levels of sedentary behavior(sitting or lying with low energy expenditure) are adversely associated with health. A key factor in improving our understanding of the impact of sedentary behavior(and patterns of sedentary time accumulation) on health is the use of objective measurement tools that collect date and time-stamped activity information. One such tool is the activP AL monitor. This thigh-worn device uses accelerometer-derived information about thigh position to determine the start and end of each period spent sitting/lying, standing, and stepping, as well as stepping speed, step counts, and postural transitions. The activP AL is increasingly being used within field-based research for its ability to measure sitting/lying via posture. We summarise key issues to consider when using the activP AL in physical activity and sedentary behavior field-based research with adult populations. It is intended that the findings and discussion points be informative for researchers who are currently using activP AL monitors or are intending to use them. Pre-data collection decisions, monitor preparation and distribution, data collection considerations, and manual and automated data processing possibilities are presented using examples from current literature and experiences from 2 research groups from the UK and Australia.展开更多
Coronavirus disease 2019(COVID-19)is a global pandemic where several comorbidities have been shown to have a significant effect on mortality.Patients with diabetes mellitus(DM)have a higher mortality rate than non-DM ...Coronavirus disease 2019(COVID-19)is a global pandemic where several comorbidities have been shown to have a significant effect on mortality.Patients with diabetes mellitus(DM)have a higher mortality rate than non-DM patients if they get COVID-19.Recent studies have indicated that patients with a history of diabetes can increase the risk of severe acute respiratory syndrome coronavirus 2 infection.Additionally,patients without any history of diabetes can acquire newonset DM when infected with COVID-19.Thus,there is a need to explore the bidirectional link between these two conditions,confirming the vicious loop between“DM/COVID-19”.This narrative review presents(1)the bidirectional association between the DM and COVID-19,(2)the manifestations of the DM/COVID-19 loop leading to cardiovascular disease,(3)an understanding of primary and secondary factors that influence mortality due to the DM/COVID-19 loop,(4)the role of vitamin-D in DM patients during COVID-19,and finally,(5)the monitoring tools for tracking atherosclerosis burden in DM patients during COVID-19 and“COVID-triggered DM”patients.We conclude that the bidirectional nature of DM/COVID-19 causes acceleration towards cardiovascular events.Due to this alarming condition,early monitoring of atherosclerotic burden is required in“Diabetes patients during COVID-19”or“new-onset Diabetes triggered by COVID-19 in Non-Diabetes patients”.展开更多
Cardiovascular disease(CVD) is an important cause of mortality and morbidity in India.Mortality statistics and morbidity surveys indicate substantial regional variations in CVD prevalence and mortality rates.Data from...Cardiovascular disease(CVD) is an important cause of mortality and morbidity in India.Mortality statistics and morbidity surveys indicate substantial regional variations in CVD prevalence and mortality rates.Data from the Registrar General of India reported greater ageadjusted cardiovascular mortality in southern and eastern states of the country.Coronary heart disease(CHD) mortality is greater in south India while stroke is more common in the eastern Indian states.CHD prevalence is higher in urban Indian populations while stroke mortality is similar in urban and rural regions.Case-control studies in India have identified that the common major risk factors account for more than 90% of incident myocardial infarctions and stroke.The case-control INTERHEART and INTERSTROKE studies reported that hypertension,lipid abnormalities,smoking,obesity,diabetes,sedentary lifestyle,low fruit and vegetable intake,and psychosocial stress are as important in India as in other populations of the world.Individual studies have reported that there are substantial regional variations in risk factors in India.At a macro-level these regional variations in risk factors explain some of the regional differences in CVD mortality.However,there is need to study the prevalence of multiple cardiovascular risk factors in different regions of India and to correlate them with variations in CVD mortality using a uniform protocol.There is also a need to determine the 'causes of the causes' or fundamental determinants of these risk factors.The India Heart Watch study has been designed to study socioeconomic,anthropometric and biochemical risk factors in urban populations in different regions of the country in order to identify regional differences.展开更多
We evaluated the efficacy and safety of as-needed tadalafil in a diverse clinical population (with varying patient demographics, disease severity, and comorbid medical conditions) of Asian men with erectile dysfunct...We evaluated the efficacy and safety of as-needed tadalafil in a diverse clinical population (with varying patient demographics, disease severity, and comorbid medical conditions) of Asian men with erectile dysfunction (ED). An integrated analysis of five double-blind, placebo-controlled trials (N = 1 046) was performed. Patients were randomly assigned to receive 10 mg tadalafil (N = 185), 20 mg tadalafil (N = 510), or placebo (N = 351). Efficacy assessments included the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) diary and Global Assessment Question (GAQ). Patients receiving 10 mg or 20 mg tadalafil showed significant improvement from baseline-to-end point on the Erectile Function domain of the International Index of Erectile Function (IIEF-EF) domain score in all clinical sub-populations analyzed, compared with patients receiving placebo (P 〈 0.001). The 10-mg and 20-mg tadalafil groups showed a mean success rate of 64.1% and 70.5% for sexual intercourse attempts (SEP3, successful intercourse), respectively, compared with 33.4% in the placebo group (P 〈 0.001), and 85.5% and 85.4% reported improved erections at end point GAQ, respectively, versus 43.5% in the placebo group (P 〈 0.001). Tadalafil was well tolerated across all groups studied. Headache and back pain were the most frequently reported adverse events. Overall, tadalafil was effective and well tolerated across a diverse clinical spectrum of Asian men with ED.展开更多
Bacterial resistance to antibiotics is an increasing threat to global healthcare systems.We therefore sought compounds with potential to reverse antibiotic resistance in a clinically relevant multi-drug resistant isol...Bacterial resistance to antibiotics is an increasing threat to global healthcare systems.We therefore sought compounds with potential to reverse antibiotic resistance in a clinically relevant multi-drug resistant isolate of Escherichia coli(NCTC 13400).200 natural compounds with a history of either safe oral use in man,or as a component of a traditional herb or medicine,were screened.Four compounds;ellagic acid,propyl gallate,cinchonidine and cepharanthine,lowered the minimum inhibi-tory concentrations(MICs)of tetracycline,chloramphenicol and tobramycin by up to fourfold,and when combined up to eightfold.These compounds had no impact on the MICs of ampicillin,erythromycin or trimethoprim.Mechanistic studies revealed that while cepharanthine potently suppressed efflux of the marker Nile red from bacterial cells,the other hit com-pounds slowed cellular accumulation of this marker,and/or slowed bacterial growth in the absence of antibiotic.Although cepharanthine showed some toxicity in a cultured HEK-293 mammalian cell-line model,the other hit compounds exhibited no toxicity at concentrations where they are active against E.coli NCTC 13400.The results suggest that phytochemicals with capacity to reverse antibiotic resistance may be more common in traditional medicines than previously appreciated,and may offer useful scaffolds for the development of antibiotic-sensitising drugs.展开更多
Neuropathy, or nerve injury, is a severe and common impediment of diabetes. Studies evaluate that 50% of people with diabetes will develop neuropathy. Diabetic nerve injury is impairment of a single solitary nerve (al...Neuropathy, or nerve injury, is a severe and common impediment of diabetes. Studies evaluate that 50% of people with diabetes will develop neuropathy. Diabetic nerve injury is impairment of a single solitary nerve (also named mononeuropathy). Com- monly 2 cranial nerves Viz., cranial nerve VII and cranial nerve VI are involved in facial nerve palsies. The former one is called Bell’s palsy and is acute Lower Motor Neuron facial nerve paralysis (>80%) causing an inability to control facial muscles on the affected side. The later one is sixth nerve palsy, (the abducens nerve), which is responsible for triggering contraction of the lateral rectus muscle to abduct (i.e., turn out) the eye resulting in double vision on the affected side. In recent times, we have found to our amazement, rapid restoration of normalcy within a few hours to a few days, of Cranial Nerve palsies in diabetic subjects at our centre. We are presenting a group of cases having Type2DM over different time periods from 6 to 20 years and those who suddenly suffered facial nerve palsy and they came to VHSDRC for treatment. They were started on the new modality called the Dynamic Acupuncture Mediated Meta-physical Energy Therapy (DAMM Therapy), to recover from the facial palsy. The DAMM therapy is a unique novel way of infusing and transferring healing energy from the therapist to the patient. Within 2 - 7 sittings of DAMM therapy patients showed 75% - 100% improvement in their clinical condition.展开更多
Type 1 diabetes is classically the true form of insulinopaenic diabetes usually occurring in young children below the age of 15 years and occasionally up to 20 years and characterised by very low/ negligible fasting C...Type 1 diabetes is classically the true form of insulinopaenic diabetes usually occurring in young children below the age of 15 years and occasionally up to 20 years and characterised by very low/ negligible fasting C-peptide in their blood due to extensive irreversible Beta cell damage. T1DM probably accounts for 5% to 10% of all diagnosed diabetes. The worldwide prevalence of T1DM is 0.1% to 0.3%, with 78,000 new cases every year, especially among young individuals (15. Type I diabetes is very much lower (20 times) in countries like Japan and India, than the western countries. The European Nicotinamide Diabetes Intervention Trial (ENDIT) is focused on the use of nicotinamide in the prevention of diabetes. In high doses (nicotinamide), it may cause a degree of sedation, a feeling of depression, and in very large dosages, liver toxicity. Because the vitamin cannot be marketed as a drug, the study is not getting a great deal of support from pharmaceutical companies. GAD antibodies (GADA) are a major diagnostic marker for Type 1 diabetes. Phase II clinical trials of a vaccine containing alum and recombinant GAD65, an auto antigen involved in type 1 diabetes, were promising, as of 2014 Phase III trial had failed. In our quest for improving the clinical condition & quality of life of type I DM & also to reduce the economic burden on them, we have embarked on a novel metaphysical energy therapy which we have been trying for the past 3 years at our research Centre. We have so far treated some 15 cases with this DAMM therapy. Among the 15 cases, 6 cases have shown significant improvement in fasting C-peptide levels. With the advent of this new modality of treatment (DAMM Therapy) the cost of treatment will be greatly reduced. This DAMM Therapy apparently has no side effects. This mode of treatment will open a new light in the world of Type I diabetes.展开更多
Sexual and reproductive health(SRH)services are crucial for women especially during disasters,to reduce maternal mortality and morbidity from miscarriages,unsafe abortions,and post-abortion complications.This study ex...Sexual and reproductive health(SRH)services are crucial for women especially during disasters,to reduce maternal mortality and morbidity from miscarriages,unsafe abortions,and post-abortion complications.This study explored the SRH interventions provided during disaster response.A systematic review was conducted to identify what menstrual regulation(MR),safe abortion(SA),and post-abortion care(PAC)approaches/interventions exist to promote resilience in the health system in disaster settings;what intervention components were most eff ective;and challenges and opportunities to meeting SRH rights.Five electronic databases were searched,resulting in 4194 records.Following the screening process,seven publications were included.The intervention-related information in each publication was assessed based on availability,accessibility,acceptability,and quality.Two SRH approaches/interventions were found.The eff ectiveness of intervention components could not be conducted due to the limited number of relevant studies.Challenges were found at facility and community levels,and opportunities included overcoming them,making MR,SA,and PAC integral to the mitigation phase,and policy change to overcome barriers related to unaff ordability and inaccessibility.Recommendations are provided to encourage research and policy towards improving neglected SRH in disaster settings to realize Sustainable Development Goal 3 and the Global Strategy and Sendai Framework's priority to promote disaster-resilient health systems.展开更多
Human induced pluripotent stem cell(hiPSC)-derived kidney organoids have prospective applications ranging from basic disease modelling to personalised medicine.However,there remains a necessity to refine the bio-physi...Human induced pluripotent stem cell(hiPSC)-derived kidney organoids have prospective applications ranging from basic disease modelling to personalised medicine.However,there remains a necessity to refine the bio-physical and biochemical parameters that govern kidney organoid formation.Differentiation within fully-controllable and physiologically relevant 3D growth environments will be critical to improving organoid reproducibility and maturation.Here,we matured hiPSC-derived kidney organoids within fully synthetic self-assembling peptide hydrogels(SAPHs)of variable stiffness(storage modulus,G′).The resulting organoids con-tained complex structures comparable to those differentiated within the animal-derived matrix,Matrigel.Single-cell RNA sequencing(scRNA-seq)was then used to compare organoids matured within SAPHs to those grown within Matrigel or at the air-liquid interface.A total of 13,179 cells were analysed,revealing 14 distinct clusters.Organoid compositional analysis revealed a larger proportion of nephron cell types within Transwell-derived organoids,while SAPH-derived organoids were enriched for stromal-associated cell populations.Notably,dif-ferentiation within a higher G’SAPH generated podocytes with more mature gene expression profiles.Addi-tionally,maturation within a 3D microenvironment significantly reduced the derivation of off-target cell types,which are a known limitation of current kidney organoid protocols.This work demonstrates the utility of syn-thetic peptide-based hydrogels with a defined stiffness,as a minimally complex microenvironment for the selected differentiation of kidney organoids.展开更多
文摘A previous diagnosis of gestational diabetes(GDM)carries a lifetime risk of progression to type 2 diabetes of up to 60%.Identification of those women at higher risk of progression to diabetes allows the timely introduction of measures to delay or prevent diabetes onset.However,there is a large degree of variability in the literature with regard to the proportion of women with a history of GDM who go on to develop diabetes.Heterogeneity between cohorts with regard to diagnostic criteria used,duration of follow-up,and the characteristics of the study population limit the ability to make meaningful comparisons across studies.As the new International Association for Diabetes in Pregnancy Study Group criteria are increasingly adopted worldwide,the prevalence of GDM is set to increase by two-to three-fold.Here,we review the literature to examine the evolution of diagnostic criteria for GDM,the implications of changing criteria on the proportion of women with previous GDM progressing to diabetes,and how the use of different diagnostic criteria may influence the development of appropriate follow-up strategies.
基金Supported by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (NIHR201165)by the NIHR Leicester Biomedical Research Centrethe NIHR Applied Research Collaboration East Midlands
文摘BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life.
基金supported by the National Institute for Health Researsch (NIHR) DietLifestyle & Physical Activity Biomedical Research Unit based at University Hospitals of Leicester and Loughborough University+5 种基金the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care-East Midlands (NIHR CLAHRC- EM)the Leicester Clinical Trials Unitsupported by a National Health and Medical Research Council (NHMRC) Centre for Research Excellence Grant on Sitting Time and Chronic Disease Prevention-Measurement, Mechanisms and Interventions (APP1057608)supported by a Heart Foundation Postdoctoral (PH 12B 7054)NHMRC Career Development (#1086029) Fellowshipsupported by an Australian Research Council Future Fellowship (FTE 100100918)
文摘Research indicates that high levels of sedentary behavior(sitting or lying with low energy expenditure) are adversely associated with health. A key factor in improving our understanding of the impact of sedentary behavior(and patterns of sedentary time accumulation) on health is the use of objective measurement tools that collect date and time-stamped activity information. One such tool is the activP AL monitor. This thigh-worn device uses accelerometer-derived information about thigh position to determine the start and end of each period spent sitting/lying, standing, and stepping, as well as stepping speed, step counts, and postural transitions. The activP AL is increasingly being used within field-based research for its ability to measure sitting/lying via posture. We summarise key issues to consider when using the activP AL in physical activity and sedentary behavior field-based research with adult populations. It is intended that the findings and discussion points be informative for researchers who are currently using activP AL monitors or are intending to use them. Pre-data collection decisions, monitor preparation and distribution, data collection considerations, and manual and automated data processing possibilities are presented using examples from current literature and experiences from 2 research groups from the UK and Australia.
文摘Coronavirus disease 2019(COVID-19)is a global pandemic where several comorbidities have been shown to have a significant effect on mortality.Patients with diabetes mellitus(DM)have a higher mortality rate than non-DM patients if they get COVID-19.Recent studies have indicated that patients with a history of diabetes can increase the risk of severe acute respiratory syndrome coronavirus 2 infection.Additionally,patients without any history of diabetes can acquire newonset DM when infected with COVID-19.Thus,there is a need to explore the bidirectional link between these two conditions,confirming the vicious loop between“DM/COVID-19”.This narrative review presents(1)the bidirectional association between the DM and COVID-19,(2)the manifestations of the DM/COVID-19 loop leading to cardiovascular disease,(3)an understanding of primary and secondary factors that influence mortality due to the DM/COVID-19 loop,(4)the role of vitamin-D in DM patients during COVID-19,and finally,(5)the monitoring tools for tracking atherosclerosis burden in DM patients during COVID-19 and“COVID-triggered DM”patients.We conclude that the bidirectional nature of DM/COVID-19 causes acceleration towards cardiovascular events.Due to this alarming condition,early monitoring of atherosclerotic burden is required in“Diabetes patients during COVID-19”or“new-onset Diabetes triggered by COVID-19 in Non-Diabetes patients”.
基金Supported by Ad hoc research grant from South Asian Society of Atherosclerosis and Thrombosis,Bangalore,India and Min-neapolis,United States
文摘Cardiovascular disease(CVD) is an important cause of mortality and morbidity in India.Mortality statistics and morbidity surveys indicate substantial regional variations in CVD prevalence and mortality rates.Data from the Registrar General of India reported greater ageadjusted cardiovascular mortality in southern and eastern states of the country.Coronary heart disease(CHD) mortality is greater in south India while stroke is more common in the eastern Indian states.CHD prevalence is higher in urban Indian populations while stroke mortality is similar in urban and rural regions.Case-control studies in India have identified that the common major risk factors account for more than 90% of incident myocardial infarctions and stroke.The case-control INTERHEART and INTERSTROKE studies reported that hypertension,lipid abnormalities,smoking,obesity,diabetes,sedentary lifestyle,low fruit and vegetable intake,and psychosocial stress are as important in India as in other populations of the world.Individual studies have reported that there are substantial regional variations in risk factors in India.At a macro-level these regional variations in risk factors explain some of the regional differences in CVD mortality.However,there is need to study the prevalence of multiple cardiovascular risk factors in different regions of India and to correlate them with variations in CVD mortality using a uniform protocol.There is also a need to determine the 'causes of the causes' or fundamental determinants of these risk factors.The India Heart Watch study has been designed to study socioeconomic,anthropometric and biochemical risk factors in urban populations in different regions of the country in order to identify regional differences.
文摘We evaluated the efficacy and safety of as-needed tadalafil in a diverse clinical population (with varying patient demographics, disease severity, and comorbid medical conditions) of Asian men with erectile dysfunction (ED). An integrated analysis of five double-blind, placebo-controlled trials (N = 1 046) was performed. Patients were randomly assigned to receive 10 mg tadalafil (N = 185), 20 mg tadalafil (N = 510), or placebo (N = 351). Efficacy assessments included the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) diary and Global Assessment Question (GAQ). Patients receiving 10 mg or 20 mg tadalafil showed significant improvement from baseline-to-end point on the Erectile Function domain of the International Index of Erectile Function (IIEF-EF) domain score in all clinical sub-populations analyzed, compared with patients receiving placebo (P 〈 0.001). The 10-mg and 20-mg tadalafil groups showed a mean success rate of 64.1% and 70.5% for sexual intercourse attempts (SEP3, successful intercourse), respectively, compared with 33.4% in the placebo group (P 〈 0.001), and 85.5% and 85.4% reported improved erections at end point GAQ, respectively, versus 43.5% in the placebo group (P 〈 0.001). Tadalafil was well tolerated across all groups studied. Headache and back pain were the most frequently reported adverse events. Overall, tadalafil was effective and well tolerated across a diverse clinical spectrum of Asian men with ED.
基金This work was supported by an Erasmus+Mobility Studentship(ref DK KOBENHA 57)awarded to DJ.The funder was not involved in the interpretation of results or writing of the article.
文摘Bacterial resistance to antibiotics is an increasing threat to global healthcare systems.We therefore sought compounds with potential to reverse antibiotic resistance in a clinically relevant multi-drug resistant isolate of Escherichia coli(NCTC 13400).200 natural compounds with a history of either safe oral use in man,or as a component of a traditional herb or medicine,were screened.Four compounds;ellagic acid,propyl gallate,cinchonidine and cepharanthine,lowered the minimum inhibi-tory concentrations(MICs)of tetracycline,chloramphenicol and tobramycin by up to fourfold,and when combined up to eightfold.These compounds had no impact on the MICs of ampicillin,erythromycin or trimethoprim.Mechanistic studies revealed that while cepharanthine potently suppressed efflux of the marker Nile red from bacterial cells,the other hit com-pounds slowed cellular accumulation of this marker,and/or slowed bacterial growth in the absence of antibiotic.Although cepharanthine showed some toxicity in a cultured HEK-293 mammalian cell-line model,the other hit compounds exhibited no toxicity at concentrations where they are active against E.coli NCTC 13400.The results suggest that phytochemicals with capacity to reverse antibiotic resistance may be more common in traditional medicines than previously appreciated,and may offer useful scaffolds for the development of antibiotic-sensitising drugs.
文摘Neuropathy, or nerve injury, is a severe and common impediment of diabetes. Studies evaluate that 50% of people with diabetes will develop neuropathy. Diabetic nerve injury is impairment of a single solitary nerve (also named mononeuropathy). Com- monly 2 cranial nerves Viz., cranial nerve VII and cranial nerve VI are involved in facial nerve palsies. The former one is called Bell’s palsy and is acute Lower Motor Neuron facial nerve paralysis (>80%) causing an inability to control facial muscles on the affected side. The later one is sixth nerve palsy, (the abducens nerve), which is responsible for triggering contraction of the lateral rectus muscle to abduct (i.e., turn out) the eye resulting in double vision on the affected side. In recent times, we have found to our amazement, rapid restoration of normalcy within a few hours to a few days, of Cranial Nerve palsies in diabetic subjects at our centre. We are presenting a group of cases having Type2DM over different time periods from 6 to 20 years and those who suddenly suffered facial nerve palsy and they came to VHSDRC for treatment. They were started on the new modality called the Dynamic Acupuncture Mediated Meta-physical Energy Therapy (DAMM Therapy), to recover from the facial palsy. The DAMM therapy is a unique novel way of infusing and transferring healing energy from the therapist to the patient. Within 2 - 7 sittings of DAMM therapy patients showed 75% - 100% improvement in their clinical condition.
文摘Type 1 diabetes is classically the true form of insulinopaenic diabetes usually occurring in young children below the age of 15 years and occasionally up to 20 years and characterised by very low/ negligible fasting C-peptide in their blood due to extensive irreversible Beta cell damage. T1DM probably accounts for 5% to 10% of all diagnosed diabetes. The worldwide prevalence of T1DM is 0.1% to 0.3%, with 78,000 new cases every year, especially among young individuals (15. Type I diabetes is very much lower (20 times) in countries like Japan and India, than the western countries. The European Nicotinamide Diabetes Intervention Trial (ENDIT) is focused on the use of nicotinamide in the prevention of diabetes. In high doses (nicotinamide), it may cause a degree of sedation, a feeling of depression, and in very large dosages, liver toxicity. Because the vitamin cannot be marketed as a drug, the study is not getting a great deal of support from pharmaceutical companies. GAD antibodies (GADA) are a major diagnostic marker for Type 1 diabetes. Phase II clinical trials of a vaccine containing alum and recombinant GAD65, an auto antigen involved in type 1 diabetes, were promising, as of 2014 Phase III trial had failed. In our quest for improving the clinical condition & quality of life of type I DM & also to reduce the economic burden on them, we have embarked on a novel metaphysical energy therapy which we have been trying for the past 3 years at our research Centre. We have so far treated some 15 cases with this DAMM therapy. Among the 15 cases, 6 cases have shown significant improvement in fasting C-peptide levels. With the advent of this new modality of treatment (DAMM Therapy) the cost of treatment will be greatly reduced. This DAMM Therapy apparently has no side effects. This mode of treatment will open a new light in the world of Type I diabetes.
文摘Sexual and reproductive health(SRH)services are crucial for women especially during disasters,to reduce maternal mortality and morbidity from miscarriages,unsafe abortions,and post-abortion complications.This study explored the SRH interventions provided during disaster response.A systematic review was conducted to identify what menstrual regulation(MR),safe abortion(SA),and post-abortion care(PAC)approaches/interventions exist to promote resilience in the health system in disaster settings;what intervention components were most eff ective;and challenges and opportunities to meeting SRH rights.Five electronic databases were searched,resulting in 4194 records.Following the screening process,seven publications were included.The intervention-related information in each publication was assessed based on availability,accessibility,acceptability,and quality.Two SRH approaches/interventions were found.The eff ectiveness of intervention components could not be conducted due to the limited number of relevant studies.Challenges were found at facility and community levels,and opportunities included overcoming them,making MR,SA,and PAC integral to the mitigation phase,and policy change to overcome barriers related to unaff ordability and inaccessibility.Recommendations are provided to encourage research and policy towards improving neglected SRH in disaster settings to realize Sustainable Development Goal 3 and the Global Strategy and Sendai Framework's priority to promote disaster-resilient health systems.
基金This publication has emanated from research conducted with the financial support of Science Foundation Ireland(SFI)co-funded under the European Regional Development Fund under Grant Number 13/RC/2073_P2+1 种基金The authors acknowledge support from Science Foundation Ireland(16/IA/4584)19/FFP/6833.J.K.W.would also like to acknowledge Royal Society of Chemistry grant(M19-6613).
文摘Human induced pluripotent stem cell(hiPSC)-derived kidney organoids have prospective applications ranging from basic disease modelling to personalised medicine.However,there remains a necessity to refine the bio-physical and biochemical parameters that govern kidney organoid formation.Differentiation within fully-controllable and physiologically relevant 3D growth environments will be critical to improving organoid reproducibility and maturation.Here,we matured hiPSC-derived kidney organoids within fully synthetic self-assembling peptide hydrogels(SAPHs)of variable stiffness(storage modulus,G′).The resulting organoids con-tained complex structures comparable to those differentiated within the animal-derived matrix,Matrigel.Single-cell RNA sequencing(scRNA-seq)was then used to compare organoids matured within SAPHs to those grown within Matrigel or at the air-liquid interface.A total of 13,179 cells were analysed,revealing 14 distinct clusters.Organoid compositional analysis revealed a larger proportion of nephron cell types within Transwell-derived organoids,while SAPH-derived organoids were enriched for stromal-associated cell populations.Notably,dif-ferentiation within a higher G’SAPH generated podocytes with more mature gene expression profiles.Addi-tionally,maturation within a 3D microenvironment significantly reduced the derivation of off-target cell types,which are a known limitation of current kidney organoid protocols.This work demonstrates the utility of syn-thetic peptide-based hydrogels with a defined stiffness,as a minimally complex microenvironment for the selected differentiation of kidney organoids.