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Elucidating the Degradation Pathways of Human Insulin in the Solid State

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

作者： Andrew Fagan Lorraine m.Bateman joseph P.O’Shea Abina m.Crean SSPC the SFI Centre for Pharmaceutical ResearchSchool of PharmacyUniversity College CorkCork T12 YT20Ireland School of Pharmacy University College CorkCork T12 YT20Ireland Analytical and Biological Chemistry Research Facility(ABCRF) University College CorkCork T12 YN60Ireland School of Chemistry University College CorkCork T12 YN60Ireland

While there have been significant advances in the development of peptide oral dosage forms in recent years,highlighted by the clinical and commercial success of approved peptides such as Rybelsus®,there remain several barriers in the way of broad range applicability of this approach to peptide *** such barrier includes the poor physical and chemical stability inherent to their structures,which persists in the solid state although degradation typically occurs at different rates and via different pathways in comparison to the solution *** insulin as a model peptide,this work sought to contribute to the development of analytical techniques for investigating common insulin degradation *** denatured,deamidated and aggregated samples were prepared and used to benchmark circular dichroism spectroscopy,reverse phase HPLC and size exclusion chromatography methods for the investigation of unfolding,chemical modifications and covalent aggregation of the insulin molecule *** state degraded samples were prepared by heating insulin powder at 60°C and 75%relative humidity for 1,3,5 and 7 d,and the degradation profiles of the samples were evaluated and compared with those observed in *** no unfolding was observed to occur,significant deamidation and covalent aggregation were *** disulfide bond cleavage using dithiothreitol allowed for separation of the insulin A-and B-chains,offering a facile yet novel means of assessing the mechanisms of deamidation and covalent aggregation occurring in the solid state.

关键词： Insulin Stability Solid state Deamidation Covalent aggregation Disulfide cleavage Biopharmaceutical analysis

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Tattoos as a window to the psyche:How talking about skin art can inform psychiatric practice

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World Journal of Psychiatry 2017年第3期7卷 148-158页

作者： Hannah Roggenkamp Andrew Nicholls joseph m Pierre mental Illness Research Education and Clinical CenterVA Puget Sound Healthcare System VA Greater Los Angeles Healthcare System Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA

Tattooing the skin as a means of personal expression is a ritualized practice that has been around for centuries across many different ***,the symbolic meaning of tattoos has evolved over time and is highly individualized,from both the internal perspective of the wearer and the external perspective of an *** modern Western societies through the 1970 s,tattoos represented a cultural taboo,typically associated with those outside of the mainstream such as soldiers,incarcerated criminals,gang members,and others belonging to marginalized and counter-cultural *** paper aims to review the more recent epidemiology of tattoos in Western culture in order to establish that tattooing has become a mainstream *** then review psychological and psychiatric aspects of tattoos,with a goal of revising outmoded stigmas about tattooing and helping clinicians working with tattooed patients to facilitate an exploration of the personal meaning of skin art and *** suggest that as a kind of augmentation of the physical exam,looking at and talking to patients about their tattoos can provide a valuable window into the psyche,informing clinical practice.

关键词： Tattoos military psychiatry Deviance Skin art Psychopathology Psychology

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Climate Change in the Subtropical Jetstream during 1950–2009

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Advances in Atmospheric Sciences 2015年第1期32卷 140-148页

作者： B.ABISH P.V.joseph Ola.m.JOHANNESSEN Nansen Environmental Research Centre India Department of Atmospheric Sciences Cochin University of Science and Technology Nansen Environmental and Remote Sensing Center Nansen Scientific Society

A study of six decades（1950–2009） of reanalysis data reveals that the subtropical jetstream（STJ） of the Southern（Northern） Hemisphere between longitudes 0°E and 180°E has weakened（strengthened） during both the boreal winter（January,February） and summer（July, August） seasons. The temperature of the upper troposphere of the midlatitudes has a warming trend in the Southern Hemisphere and a cooling trend in the Northern Hemisphere. Correspondingly, the north–south temperature gradient in the upper troposphere has a decreasing trend in the Southern Hemisphere and an increasing trend in the Northern Hemisphere, which affects the strength of the STJ through the thermal wind relation. We devised a method of isotach analysis in intervals of 0.1 m s-1in vertical sections of hemispheric mean winds to study the climate change in the STJ core wind speed, and also core height and latitude. We found that the upper tropospheric cooling of the Asian mid-latitudes has a role in the strengthening of the STJ over Asia, while throughout the rest of the globe the upper troposphere has a warming trend that weakens the STJ. Available studies show that the mid-latitude cooling of the upper troposphere over Asia is caused by anthropogenic aerosols（particularly sulphate aerosols） and the warming over the rest of the global mid-latitude upper troposphere is due to increased greenhouse gases in the atmosphere.

关键词： subtropical jetstream upper troposphere greenhouse gases aerosols

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Anal intraepithelial neoplasia: A review of diagnosis and management

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World Journal of Gastrointestinal Oncology 2017年第2期9卷 50-61页

作者： joseph R Roberts Lacey L Siekas Andrew m Kaz Department of medicine Division of Gastroenterology University of Washington School of Medicine Gastroenterology Section VA Puget Sound Health Care System

Anal intraepithelial neoplasia(AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus(HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPVmediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.

关键词： Anal cancer Anal intraepithelial neoplasia Anal squamous cell carcinoma Human papillomavirus vaccine Human papillomavirus

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metabolic complications of hepatitis C virus infection

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World Journal of Gastroenterology 2021年第13期27卷 1267-1282页

作者： Rahul Chaudhari Sherouk Fouda Ashik Sainu joseph m Pappachan Department of medicine Pennsylvania Hospital of the University of PennsylvaniaPennsylvaniaPA 19104United States School of Health and Biomedical Sciences RMIT UniversityMelbourne VIC 3000Australia Department of Gastroenterology and Hepatology Aster Oman HospitalAl GhubraMuscat OM 133Oman Department of Endocrinology and metabolism 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

Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.

关键词： Chronic hepatitis C infection Insulin resistance metabolic syndrome Cardiovascular diseases Fatty liver Diabetes mellitus

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Comparative study of mechanical, corrosion and erosion-corrosion properties of cast hyper-duplex and super-duplex stainless steels

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International Journal of minerals,metallurgy and materials 2020年第7期27卷 954-961页

作者： P.Nithin Raj P.K.Navaneethkrishnan K.Sekar m.A.joseph Department of mechanical Engineering National Institute of TechnologyCalicutIndia

Duplex stainless steels(DSSs)used in subsea structures and desalination industries require high corrosion and erosion resistance as well as excellent mechanical *** newly introduced cast duplex grade ASTm A8907 A has a unique composition and is expected to have a much better resistance to corrosion and erosion compared with the super-duplex grades 5 A and 6 *** work is a comparative study of the mechanical properties,corrosion,and erosion-corrosion resistance of super-duplex grades 5 A and 6 A and the hyper-duplex grade 7 *** three DSSs exhibited equiaxial austenite islands in the ferrite matrix and balanced phase *** hardness of the grade 7 A was nearly 15%higher than those of the super-duplex grades,which is attributed to the effect of the higher contents of W and mn in 7 *** impact toughness of grade 7 A was found to be lower than those of the super-duplex grades due to the carbide precipitation resulting from the partial substitution of mo with *** oxide layer strengthening effect of rare earth elements and the higher pitting resistance equivalent number(PREN)of grade7 A resulted in higher corrosion *** harder and more passive grade 7 A showed a 35%lower material loss during erosion-corrosion.

关键词： hyper-duplex stainless steels erosion−corrosion electrochemical corrosion marine environment super-duplex stainless steels

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Biomechanics associated with tibial stress fracture in runners:A systematic review and meta-analysis

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Journal of Sport and Health Science 2023年第3期12卷 333-342页

作者： Clare E.milner Eric Foch joseph m.Gonzales Drew Petersen Department of Physical Therapy and Rehabilitation Sciences Drexel UniversityPhiladelphiaPA 19102USA Department of Health Sciences Central Washington UniversityEllensburgWA 98926USA

Background:Tibial stress fracture(TSF)is an overuse running injury with a long recovery *** many running studies refer to biomechanical risk factors for TSF,only a few have compared biomechanics in runners with TSF to *** aim of this systematic review and meta-analysis was to evaluate biomechanics in runners with TSF compared to ***:Electronic databases Pubmed,Web of Science,SPORTDiscus,Scopus,Cochrane,and CINAHL were *** of bias was assessed and meta-analysis conducted for variables reported in 3 or more ***:The search retrieved 359 unique records,but only the 14 that compared runners with TSF to controls were included in the *** studies were retrospective,2 were prospective,and most had a small sample size(5-30 per group).many variables were not significantly different between ***-analysis of peak impact,active,and braking ground reaction forces found no significant differences between *** studies found larger tibial peak anterior tensile stress,peak posterior compressive stress,peak axial acceleration,peak rearfoot eversion,and hip adduction in the TSF ***:meta-analysis indicated that discrete ground reaction force variables were not statistically significantly different in runners with TSF compared to *** individual included studies,many biomechanical variables were not statistically significantly different between ***,many were reported by only a single study,and sample sizes were *** encourage additional studies with larger sample sizes of runners with TSF and controls and adequate statistical power to confirm or refute these findings.

关键词： Bone stress injury Gait Kinematics Kinetics Tibial acceleration

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Hormone replacement therapy for menopausal mood swings and sleep quality:The current evidence

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World Journal of Psychiatry 2024年第10期14卷 1605-1610页

作者： Sanja Borozan Abul Bashar m Kamrul-Hasan joseph m Pappachan Department of Endocrinology Clinical Centre of MontenegroPodgorica 81000Montenegro Faculty of medicine University of MontenegroPodgorica 81000Montenegro Department of Endocrinology Mymensingh Medical College HospitalMymensingh 2200DhakaBangladesh Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Department of Endocrinology Kathmandu Medical CollegeManipal UniversityManipal 576104India

marked alterations in the normal female hormonal milieu in the perimenopausal period significantly affect women’s health,leading to decreased well-being,psychological distress,and impaired quality of *** menopausal symp-toms include hot flashes,sleep and mood changes,fatigue,weight gain,and urogenital *** often neglect mood swings and disrupted sleep,although those can significantly limit the productivity of women and impair their cognitive function and mental ***-based management should include a personalized,holistic approach to alleviate symptoms and careful consideration of the risks vs benefits of hormone replacement therapy(HRT),with due consideration of personal preferences.A research paper in the recent issue of the World Journal of Psychiatry by Liu et al investigated the role of HRT in altering mood changes and impaired sleep quality in menopausal women,which helps us to understand the benefits of this treatment approach.

关键词： menopausal symptoms mood changes Sleep quality Hormone replacement therapy Quality of life

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Generating a CRISPR knockout mouse through a strong premature termination codon:a cautionary tale

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The Journal of Biomedical Research 2021年第2期35卷 174-178,1-4页

作者： Qing Rex Lyu Peng Yao joseph m miano Aab Cardiovascular Research Institute University of Rochester School of Medicine & Dentistry Rochester NY 14642 USA. Vascular Biology Center Medical College of Georgia at Augusta University Augusta GA 30912 USA. Institute of Biomedicine and Health Chongqing Institute of Green and Intelligent Technology Chinese Academy of Sciences Chongqing 400714 China.

Dear Editor,Genetic inactivation or gene knockout(KO)has been a powerful method of elucidating gene function in *** traditional method of generating KO mice via targeting mouse embryonic stem cells through homologous ... 详细信息

关键词： knockout inactivation termination

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Non-pharmacological 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 James Fernandez joseph m Pappachan Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Department of Endocrinology&metabolism 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 modalities of diagnosing diabetic peripheral neuropathy(DPN),such as nerve conduction studies,there is still a knowledge gap about the pathophysiology,and thus limited available in-terventions for symptom control and curtailing disease *** pharma-cologic aspect of management is mainly centred on pain control,however,there are several important aspects of DPN such as loss of vibration sense,pressure sense,and proprioception which are associated with risks to lower limb health,which pharmacotherapy does not ***,published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy,to reach a desired,however modest *** is emerging as an important treatment modality for several chronic medical conditions including neuropathic and other pain *** their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN symptoms and enhance nerve conduction parameters,Hoerder et al have been able to demonstrate that acupuncture improves sensory function and that this effect is likely sustained two months after treatment *** previous studies also support these findings,larger multi-center randomized 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 may become an important aspect of the repertoire of effective DPN management.

关键词： Diabetic peripheral neuropathy Diabetes mellitus Pharmacotherapy Acupuncture Neuropathic pain Nonpharmacological intervention

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