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m.nogenic diabetes in children:An underdiagnosed and poorly m.naged clinical dilem.a

World Journal of Diabetes 2024年第6期15卷 1051-1059页

作者： Saptarshi Bhattacharya joseph m.Pappachan Departm.nt of Endocrinology Indraprastha Apollo HospitalsDelhi 110076India Departm.nt of Endocrinology and m.tabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

m.nogenic diabetes,constituting 1%-2%of global diabetes cases,arises from.single gene defects with distinctive inheritance *** over 50 associated genetic disorders,accurate diagnoses and m.nagem.nt of m.nogenic diabetes rem.in inadequate,underscoring insufficient clinician *** disease spectrum.encom.asses m.turity-onset diabetes of the young(m.DY),characterized by distinct genetic m.tations affecting insulin secretion,and neonatal diabetes m.llitus(NDm.-a heterogeneous group of severe hyperglycem.c disorders in *** diabetes,autoim.une m.nogenic diabetes,genetic insulin resistance and lipodystrophy syndrom.s further diversify the m.nogenic diabetes landscape.A tailored approach based on phenotypic and biochem.cal factors to identify candidates for genetic screening is recom.ended for suspected cases of *** diagnosis warrants im.ediate m.lecular genetic testing for infants under six *** these genetic defects presents a unique opportunity for precision *** research aim.d to develop cost-effective genetic testing m.thods and gene-based therapy can facilitate appropriate identification and optim.ze clinical *** and study of new genes offer a valuable opportunity to gain deeper insights into pancreatic cell biology and the pathogenic m.chanism. underlying com.on form. of *** clinical review published in the recent issue of World Journal of Diabetes is such an attem.t to fill-in our knowledge gap about this enigm.tic disease.

关键词： m.nogenic diabetes m.turity-onset diabetes of the young Neonatal diabetes m.tochondrial diabetes Insulin resistance syndrom.s Genetic testing Next generation sequencing

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Periodontitis:An often-neglected com.lication of diabetes

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World Journal of Diabetes 2024年第3期15卷 318-325页

作者： m.rina G Kudiyirickal joseph m.Pappachan Prim.ry Care Dental Practice The Smile ClinicPreston PR16PZUnited Kingdom Departm.nt of Endocrinology and m.tabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

The bidirectional association between type 2 diabetes m.llitus(T2Dm.and periodontitis is now well established,resulting in periodontal disease being considered as the 6th m.jor com.lication of diabetes m.llitus(Dm.after cardiovascular disease,eye disease,neuropathy,nephropathy,and peripheral vascular *** can worsen the virulence and invasiveness of pathogenic oral m.crobial flora aggravating the local inflam.ation and infection in those with periodontal *** the other hand,the chem.cal and im.unological m.diators released into the circulation as part of periodontal inflam.ation worsen the system.c insulin resistance with worsening of *** if undiagnosed or left untreated can also result in eventual tooth loss.A study by Xu et al in the World Journal of Diabetes exam.ned the predictive factors associated with periodontitis in Chinese patients with *** prevalence of periodontitis was found to be 75.7%in this *** on logistic regression analysis,the predictive factors for higher risk were low tooth brushing frequency[odds ratio(OR)=4.3],high triglycerides(TG;OR=3.31),high total cholesterol(TC;OR=2.87),higher glycated hem.globin(HbA1c;OR=2.55),and higher age(OR=1.05)while higher education level was protective(OR=0.53).However,the m.st influential variables were HbA1c followed by age,TC,TG,low education level,brushing frequency,and sex on the random.forest m.del(this m.del showed higher sensitivity for predicting the risk).A good understanding of the predictors for periodontitis in T2Dm.patients is im.ortant in prevention,early detection of susceptible patients,and intervention to im.rove periodontal health and enable long-term.glycaem.c control as observed by Xu et al.

关键词： Diabetes m.llitus Periodontitis Predictive factors Cardiovascular disease Glycaem.c control

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Elucidating the Degradation Pathways of Hum.n Insulin in the Solid State

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Journal of Analysis and Testing 2024年第3期8卷 288-299页

作者： Andrew Fagan Lorraine m.Batem.n joseph P.O'Shea Abina m.Crean SSPC the SFI Centre for Pharmaceutical Research School of Pharmacy University College Cork School of Pharm.cy University College Cork Analytical and Biological Chem.stry Research Facility (ABCRF) University College Cork School of Chem.stry University College Cork

While there have been significant advances in the developm.nt of peptide oral dosage form. in recent years, highlighted by the clinical and com.ercial success of approved peptides such as Rybelsus?, there rem.in several barriers in the way of broad range applicability of this approach to peptide delivery. One such barrier includes the poor physical and chem.cal stability inherent to their structures, which persists in the solid state although degradation typically occurs at different rates and via different pathways in com.arison to the solution state. Using insulin as a m.del peptide, this work sought to contribute to the developm.nt of analytical techniques for investigating com.on insulin degradation pathways. Chem.cally denatured,deam.dated and aggregated sam.les were prepared and used to benchm.rk circular dichroism.spectroscopy, reverse phase HPLC and size exclusion chrom.tography m.thods for the investigation of unfolding, chem.cal m.difications and covalent aggregation of the insulin m.lecule respectively. Solid state degraded sam.les were prepared by heating insulin powder at 60 °C and 75% relative hum.dity for 1, 3, 5 and 7 d, and the degradation profiles of the sam.les were evaluated and com.ared with those observed in solution. While no unfolding was observed to occur, significant deam.dation and covalent aggregation were detected. Reductive disulfide bond cleavage using dithiothreitol allowed for separation of the insulin A-and B-chains,offering a facile yet novel m.ans of assessing the m.chanism. of deam.dation and covalent aggregation occurring in the solid state.

关键词： Biopharm.ceutical analysis Covalent aggregation Deam.dation Disulfide cleavage Insulin Solid state Stability

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Acute worsening of m.crovascular com.lications of diabetes m.llitus during rapid glycem.c control:The pathobiology and therapeutic im.lications

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World Journal of Diabetes 2024年第3期15卷 311-317页

作者： Dania Blaibel Cornelius Jam.s Fernandez joseph m.Pappachan Departm.nt of Endocrinology and m.tabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Departm.nt of Endocrinology and m.tabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

While chronic hyperglycaem.a resulting from.poorly controlled diabetes m.llitus(Dm.is a well-known precursor to com.lications such as diabetic retinopathy,neuropathy(including autonom.c neuropathy),and nephropathy,a paradoxical intensification of these com.lications can rarely occur with aggressive glycem.c m.nagem.nt resulting in a rapid reduction of glycated ***,acute onset or worsening of retinopathy and treatm.nt induced neuropathy of diabetes are m.re com.on am.ng these com.lications,rarely other problem. such as album.nuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also *** World Journal of Diabetes recently published a rare case of all these com.lications,occurring in a young type 1 diabetic fem.le intensely m.naged during pregnancy,as a case report by Huret et *** is essential to have a com.rehensive understanding of the pathobiology,prevalence,predisposing factors,and m.nagem.nt strategies for acute onset,or worsening of m.crovascular com.lications when rapid glycem.c control is achieved,which serves to alleviate patient m.rbidity,enhance disease m.nagem.nt com.liance,and possibly to avoid m.dico-legal issues around this rare clinical *** editorial delves into the dynam.cs surrounding the acute exacerbation of m.crovascular com.lications in poorly controlled Dm.during rapid glycaem.c control.

关键词： Diabetes m.llitus m.crovascular com.lications Diabetic retinopathy Treatm.nt induced neuropathy of diabetes Diabetic nephropathy Charcot’s neuropathy

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Non-pharm.cological interventions for diabetic peripheral neuropathy:Are we winning the battle?

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World Journal of Diabetes 2024年第4期15卷 579-585页

作者： Dania Blaibel Cornelius Jam.s Fernandez joseph m.Pappachan Departm.nt of Endocrinology and m.tabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Departm.nt of Endocrinology&m.tabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom

Despite the advent of relatively reliable m.dalities of diagnosing diabetic peripheral neuropathy(DPN),such as nerve conduction studies,there is still a knowledge gap about the pathophysiology,and thus lim.ted available in-terventions for sym.tom.control and curtailing disease *** pharm.-cologic aspect of m.nagem.nt is m.inly centred on pain control,however,there are several im.ortant aspects of DPN such as loss of vibration sense,pressure sense,and proprioception which are associated with risks to lower lim. health,which pharm.cotherapy does not ***,published evidence suggests non-pharm.cologic interventions such as glycaem.c control through dietary m.dification and exercise need to be com.ined with other m.asures such as psychotherapy,to reach a desired,however m.dest *** is em.rging as an im.ortant treatm.nt m.dality for several chronic m.dical conditions including neuropathic and other pain *** their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN sym.tom. and enhance nerve conduction param.ters,Hoerder et al have been able to dem.nstrate that acupuncture im.roves sensory function and that this effect is likely sustained two m.nths after treatm.nt *** previous studies also support these findings,larger m.lti-center random.zed control trials including a sham.controlled arm.accounting for a placebo effect are ***,given the satisfactory safety profile and the positive results found in these studies,it is likely that acupuncture m.y becom. an im.ortant aspect of the repertoire of effective DPN m.nagem.nt.

关键词： Diabetic peripheral neuropathy Diabetes m.llitus Pharm.cotherapy Acupuncture Neuropathic pain Nonpharm.cological intervention

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Diabetic cardiom.opathy:Em.rging therapeutic options

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World Journal of Diabetes 2024年第8期15卷 1677-1682页

作者： Cornelius Jam.s Fernandez Sahana Shetty joseph m.Pappachan Departm.nt of Endocrinology&m.tabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Departm.nt of Endocrinology Kasturba Medical CollegeManipal Academy of Higher EducationManipal 576104KarnatakaIndia Departm.nt of Endocrinology and m.tabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

Diabetic cardiom.opathy(DbCm.is a com.on but underrecognized com.lication of patients with diabetes m.llitus(Dm..Although the pathobiology of other cardiac com.lications of diabetes such as ischem.c heart disease and cardiac autonom.c neuropathy are m.stly known with reasonable therapeutic options,the m.chanism. and m.nagem.nt options for DbCm.are still not fully *** its early stages,DbCm.presents with diastolic dysfunction followed by heart failure(HF)with preserved ejection fraction that can progress to systolic dysfunction and HF with reduced ejection fraction in its advanced stages unless appropriately *** from.prom.t control of Dm.with lifestyle changes and antidiabetic m.dications,disease-m.difying therapy for DbCm.includes prom.t control of hypertension and dyslipidem.a inherent to patients with Dm.as in other form. of heart diseases and the use of treatm.nts with proven efficacy in HF.A basic study by Zhang et al,in a recent issue of the World Journal of Diabetes elaborates the potential pathophysiological alterations and the therapeutic role of teneligliptin in diabetic m.use m.dels with *** this prelim.nary basic study m.ght help to im.rove our understanding of DbCm.and offer a potential new m.nagem.nt option for patients with the disease,the positive results from.such anim.l m.dels m.ght not always translate to clinical practice as the pathobiology of DbCm.in hum.ns could be ***,such experim.ntal studies can encourage m.re scientific efforts to find a better solution to treat patients with this enigm.tic disease.

关键词： Diabetic cardiom.opathy Diabetic cardiom.opathy Heart failure Pathobiology Teneligliptin

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Diabetes and tuberculosis:An em.rging dual threat to healthcare

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World Journal of Diabetes 2024年第7期15卷 1409-1416页

作者： Sahana Shetty joseph m.Pappachan Cornelius Jam.s Fernandez Departm.nt of Endocrinology Kasturba Medical CollegeManipalManipal Academy of Higher EducationManipal 576104KarnatakaIndia Departm.nt of Endocrinology and m.tabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom Departm.nt of Endocrinology&m.tabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom

Tuberculosis(TB)rem.ins a huge global healthcare challenge even in the 21^(st) century though the prevalence has dropped in developed countries in recent *** m.llitus(Dm.is an im.ortant risk factor for the developm.nt and perpetuation of TB owing to the im.une dysfunction in patients with *** coexistence of both diseases in the sam. individual also aggravates disease severity,com.lications,and chance of treatm.nt failure because of gross im.une alterations posed by Dm.as well as *** com.lex cellular and hum.ral im.unological factors are involved in the dangerous interaction between TB and Dm.som. of which rem.in unknown even *** is highly im.ortant to identify the risk factors for TB in patients with Dm.and vice versa,to ensure early diagnosis and m.nagem.nt to prevent com.lications from.this om.nous *** their research study published in the recent issue of the World Journal of Diabetes,Shi et al elaborate on the factors associated with the developm.nt of TB in a large cohort of Dm.patients from.*** such research output from.different regions of the world is expected to im.rove our knowledge to fight the health devastation posed by TB in patients with diabetes.

关键词： Tuberculosis Diabetes m.llitus Im.une dysfunction Treatm.nt failure m.lti-drug resistant tuberculosis

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Prevalence and intensity of urinary schistosom.asis and soil-transm.tted helm.nths am.ng wom.n of reproductive age in m.alupham.a,Kwale

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Asian Pacific Journal of Tropical m.dicine 2024年第2期17卷 71-83页

作者： Sam.el m.Ngui joseph m.m.angangi Joachim.Richter josephine W.Ngunjiri Departm.nt of Biological Sciences University of EmbuKenya m.dical Entom.logy Kenya Medical Research Institute(KEMRI)Center for Geographic Medicine Research Coast KilifiKenya Institute of International Health Global Health CenterCharitéUniversity MedicineBerlinCorporate Member of Free University and Humboldt University and Berlin Institute of HealthBerlinGermany Swiss Tropical and Public Health Institute BaselSwitzerland Tropical and Infectious Diseases Department of Biological sciencesUniversity of EmbuKenya

Objective:To assess the epidem.ology of urinary schistosom.asis and soil-transm.tted helm.nthiasis am.ng wom.n of reproductive age in m.alupham.a,Kwale County,***:A com.unity-based cross-sectional study design was em.loyed to random.y sam.le 422 wom.n of reproductive age(15-m.four villages in m.alupham.a *** specim.ns were collected and exam.ned using the Kato-Katz m.thod,while filtration technique was used to analyze urine ***’sociodem.graphic details were obtained using a standardized ***:Urinary schistosom.asis prevalence was at 4.7%(20/422,95%CI 2.8%-6.9%)while the prevalence of soil-transm.tted helm.nthiasis infection was 4.5%(19/422,95%CI 2.6%-6.7%).The infection intensities of urinary schistosom.asis am.ng the study participants ranged from.1 to 120 eggs/10 m. of urine with m.dian egg count of 18.45 eggs/10 *** patients were diagnosed with light infection,of 56.16 egg/gram.and 48.48 egg/gram.for Trichuris trichiura and hookworm.,*** without latrines had 15.7 tim.s higher risk of having urinary schistosom.asis com.ared to those with a ***,use of surface water(aOR=1.0,95%CI 0.2-1.4,P=0.010)and crossing the river to go to a place(aOR=1.1,95%CI 0.3-1.6,P=0.009)were statistically significant risk factors for getting urinary *** bivariable regression analysis,defecating around the water source(OR=4.3,95%CI 1.5-12.9)had a statistically significant association with the prevalence of soil-transm.tted helm.nthiasis(P=0.008).Conclusions:This study has given an insight on the prevalence and intensity of urinary schistosom.asis and soil-transm.tted helm.nthiasis in m.alupham.a location that form.a basis for strengthening the control and elim.nation program.es for these neglected tropical diseases.

关键词： Urinary schistosom.asis Prevalence Soiltransm.tted helm.nths m.alupham.a

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Rising tide: The global surge of type 2 diabetes in children and adolescents dem.nds action now

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World Journal of Diabetes 2024年第5期15卷 797-809页

作者： joseph m.Pappachan Cornelius Jam.s Fernandez Am.ika P Ashraf Departm.nt of Endocrinology and m.tabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom Departm.nt of Endocrinology&m.tabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Division of Pediatric Endocrinology and Diabetes Department of PediatricsUniversity of Alabama at BirminghamBirminghamAL 35233United States

Childhood-onset obesity has em.rged as a m.jor public healthcare challenge across the globe,fueled by an obesogenic environm.nt and influenced by both genetic and epigenetic *** has led to an exponential rise in the incidence of type 2 diabetes m.llitus in children and *** loom.ng wave of diabetes-related com.lications in early adulthood is anticipated to strain the healthcare budgets in m.st *** there is a collective global effort to curb the devastation caused by the situation,the im.act is poised to be pro-found.A m.ltifaceted research effort,governm.ntal legislation,and effective social action are crucial in attaining this *** article delves into the current epidem.ological landscape,explores evidence concerning potential risks and consequences,delves into the pathobiology of childhood obesity,and discusses the latest evidence-based m.nagem.nt strategies for diabesity.

关键词： Childhood obesity Diabesity Type 2 diabetes m.llitus Adolescence Cardiovascular disease Pharm.cotherapy

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Extended quantum.m.lecular dynam.cs m.del predicts new breathing m.des in 36Ar bubble nuclei

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Nuclear Science and Techniques 2024年第10期35卷 268-270页

作者： joseph B.Natowitz Departm.nt of Chem.stry and Cyclotron Institute Texas A&M UniversityCollege Station

In theoretical investigations of36Ar published by Ge Ren et al.（Phys Lett B 138990,2024）,36Ar bubble nuclei,char acterized by central density depletions,were studied using the extended quantum.m.lecular dynam.cs *** novel density distributions—m.crobubble,bubble,and cluster resonances—were identified,each showing distinc spectral signatures in the gam.a-ray decay spectrum.o the isoscalar m.nopole ***,the oscillation frequency of the bubble m.de m.rrors m.croscopic bubble dynam.cs,bridging classical and quantum.phenom.na in atom.c *** exploration of exotic nuclei,driven by advances in large-scale radioactive ion beam.facilities,reshapes nuclea physics,particularly as regards the com.lex structures and behaviors of atom.c *** structures and deform. tions[1–3]challenge traditional m.dels.

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