Diabetic foot ulcer and its surgical management

Background: Almost 80% population of diabetic foot are from low to middle income countries like India, a country with second largest number of diabetic populations. Prevalence of diabetes mellitus in India is 9.3%. Lower extremity diseases, including peripheral neuropathy, peripheral arterial disease, and foot ulceration, is twice common in diabetic subjects. the most feared consequence of diabetic foot ulcer is limb amputation, which is seen 10 to 30 times more often in person with diabetes. The objective of this study concentrates on surgical management of diabetic foot ulcer.Methods: This is an observational prospective study of 100 cases for evaluation of diabetic foot ulcer and its surgical management at P.D.U. Hospital, Rajkot from January 2017 to November 2018.Results: The average age of presentation is 55.70 year. The male to female ratio was 1.27:1. Most of the patients are from lower middle class and upper lower class according to modified kuppuswamy socioeconomic classification. Most of the patients have duration of diabetes more than 5 years.  Most common microorganism grown from culture was Staphylococcus aureus. This study has higher rate of amputations of 74% due to late presentation and neglected disease due to peripheral neuropathy causes decreased pain sensation. There was no mortality in this study.Conclusions: Management of diabetic foot ulcer is by multimodal approach with conservative and surgical approaches. Preventive measures, early diagnosis and timely surgical intervention prevents limb amputations in diabetic foot ulcer

Magnetic glass in Shape Memory Alloy : Ni45Co5Mn38Sn12

The first order martensitic transition in the ferromagnetic shape memory alloy Ni45Co5Mn38Sn12 is also a magnetic transition and has a large field induced effect. While cooling in the presence of field this first order magnetic martensite transition is kinetically arrested. Depending on the cooling field, a fraction of the arrested ferromagnetic austenite phase persists down to the lowest temperature as a magnetic glassy state, similar to the one observed in various intermetallic alloys and in half doped manganites. A detailed investigation of this first order ferromagnetic austenite (FM-A) to low magnetization martensite (LM-M) state transition as a function of temperature and field has been carried out by magnetization measurements. Extensive cooling and heating in unequal field (CHUF) measurements and a novel field cooled protocol for isothermal MH measurements (FC-MH) are utilized to investigate the glass like arrested states and show a reverse martensite transition. Finally, we determine a field -temperature (HT) phase diagram of Ni45Co5Mn38Sn12 from various magnetization measurements which brings out the regions where thermodynamic and metastable states co-exist in the HT space clearly depicting this system as a 'Magnetic Glass'.Comment: Magnetic field tunes kinetic arrest and CHUF shows devitrification and melting of Magnetic glas

Existence of a Strong Correlation of Biomarkers and Mirna in Females With Metabolic Syndrome and Obesity in a Population of West Virginia

Objectives: Metabolic syndrome causes complications like cardiovascular disease and type 2 diabetes mellitus (T2DM). As metabolic syndrome develops, altered levels of cytokines and microRNAs (miRNA) are measurable in the circulation. We aimed to construct a panel detecting abnormal levels of cytokines and miRNAs in patients at risk for metabolic syndrome. Methods: Participants included 54 patients from a Family Medicine Clinic at Marshall University School of Medicine, in groups of: Control, Obese, and Metabolic Syndrome (MetS). Results: Serum levels of leptin, adiponectin, leptin: adiponectin ratio, IL-6, six miRNAs (320a, 197-3p, 23-3p, 221-3p, 27a-3p, and 130a-3p), were measured. Among the three groups, leptin, and leptin: adiponectin ratio, and IL-6 levels were highest in MetS, and levels in Obese were greater than Control (p\u3e0.05). Adiponectin levels were lower in Obese compared to Control, but lowest in MetS (p0.05). Conclusion: Our results support the clinical application of biomarkers in diagnosing early stage MetS, which will enable attenuation of disease progression before onset of irreversible complications. Since West Virginians are high-risk for developing MetS, our biomarker panel could reduce the disease burden on our population

Enabled Negatively Regulates Diaphanous-Driven Actin Dynamics In Vitro and In Vivo

Actin regulators facilitate cell migration by controlling cell protrusion architecture and dynamics. As the behavior of individual actin regulators becomes clear, we must address why cells require multiple regulators with similar functions and how they cooperate to create diverse protrusions. We characterized Diaphanous (Dia) and Enabled (Ena) as a model, using complementary approaches: cell culture, biophysical analysis, and Drosophila morphogenesis. We found that Dia and Ena have distinct biochemical properties that contribute to the different protrusion morphologies each induces. Dia is a more processive, faster elongator, paralleling the long, stable filopodia it induces in vivo, while Ena promotes filopodia with more dynamic changes in number, length, and lifetime. Acting together, Ena and Dia induce protrusions distinct from those induced by either alone, with Ena reducing Dia-driven protrusion length and number. Consistent with this, EnaEVH1 binds Dia directly and inhibits DiaFH1FH2-mediated nucleation in vitro. Finally, Ena rescues hemocyte migration defects caused by activated Dia

Phase 1 study of fianlimab, a human lymphocyte activation gene-3 (LAG-3) monoclonal antibody, plus cemiplimab in advanced melanoma

Background: Concurrent LAG-3 blockade may enhance efficacy of anti-program cell death-1 (PD-1) therapies such as cemiplimab. We present updated safety and clinical activity data from patients with advanced melanoma treated concurrently with cemiplimab and fianlimab (NCT03005782). Methods: Patients were included with unresectable or metastatic melanoma (excluding uveal melanoma) who were anti-PD-ligand (L) 1 treatment naive (expansion cohort [EC] 6) or anti-PD-(L)1 experienced within 3 months of screening (EC7). Patients received fianlimab 1600 mg + cemiplimab 350 mg intravenously every 3 weeks for 12 months (optional extra 12 months if clinically indicated). Tumours were measured every 6 weeks for 24 weeks, then every 9 weeks. In EC6 (n = 40) and EC7 (n = 15), respectively (data cutoff 9th February 2022), median age was 69.5 and 59.0 years, and median treatment duration was 37.1 and 9.0 weeks. Results: In EC6 and EC7, respectively, incidence of Grade ≥3 treatment-emergent adverse events (TEAEs) were 38% and 47%, incidence of serious TEAEs was 33% and 33%, and 18% and 13% of patients discontinued treatment due to a TEAE. Adrenal insufficiency rate was 13% and 7% in EC6 and EC7, respectively; no instances led to treatment discontinuation. Investigator-assessed objective response rate was63%(six complete responses; 19 partial responses) in EC6 and 13% (two partial responses) in EC7. Kaplan-Meier estimate of median progression-free survival was 14.2 (95% CI: 5.6-not estimated) months in EC6 and 1.4 (95% CI: 1.3-7.7) months in EC7. Median duration of response was not reached in EC6 or EC7. Conclusion: Fianlimab plus cemiplimab in advanced melanoma had a similar safety profile to anti-PD-1 monotherapies. Clinical activity in anti-PD-(L)1-naive patients appeared higher than previously reported for anti-PD-1monotherapy or anti-LAG-3 plus anti-PD-1. A Phase 3 trial (NCT05352672) investigating fianlimab plus cemiplimab in advanced melanoma is ongoing

Experimental and Theoretical Investigations of Fe-Doped Hexagonal MnNiGe

We report a comprehensive investigation of MnNi0.7Fe0.3Ge Heusler alloy to explore its magnetic, caloric, and electrical transport properties. The alloy undergoes a ferromagnetic transition across TC∼212 K and a weak-antiferromagnetic transition across Tt∼180 K followed by a spin-glass transition below Tf∼51.85 K. A second-order phase transition across TCwith mixed short and long-range magnetic interactions is confirmed through the critical exponent study and universal scaling of magnetic entropy and magnetoresistance. A weak first-order phase transition is evident across Ttfrom magnetization and specific heat data. The frequency dependent cusp in χAC(T) along with the absence of a clear magnetic transition in specific heat C(T) and resistivity ρ(T) establish the spin glass behavior below Tf. Mixed ferromagnetic and antiferromagnetic interactions with dominant ferromagnetic coupling, as revealed by density functional calculations, are experimentally evident from the large positive Weiss temperature, magnetic saturation, and negative magnetic-entropy and magnetoresistance. © 2022 American Chemical Society. All rights reserved.CSR-IC-256/2017-18/1337; Department of Physics, Harvard University; Council of Scientific and Industrial Research, India, CSIR: 09/926(0011)2K18, DST/INT/RFBR/IDIR/P-01/2016; Ministry of Education and Science of the Russian Federation, Minobrnauka: AAAA-A18-118020190098-5; Indian Institute of Technology Bombay, IITB; Russian Science Foundation, RSF: 22-42-02021; UGC-DAE Consortium for Scientific Research, University Grants Commission, UGC-DAE CSR; Industrial Research and Consultancy Centre, IRCCS.S.S., A.K.P., and K.G.S. thank IRCC and the Department of Physics, IIT Bombay, for X-ray diffraction and magnetization facilities. S.S.S. acknowledges UGC-DAE CSR, Indore, for financial support under the Collaborative Research Scheme (CSR-IC-256/2017-18/1337). V.G. acknowledges UGC-DAE CSR, Indore, for the support. A.K.M. thanks CSIR India, for SRF [File No.: 09/926(0011)2K18]. K.G.S. acknowledges financial support through Indo-Russian project: DST/INT/RFBR/IDIR/P-01/2016. The theoretical studies are supported by the Russian Science Foundation (Project No. 22-42-02021) for the electronic structure calculations and Ministry of Science and Higher Education of the Russian Federation for the exchange parameters calculations (theme "Electron" No. AAAA-A18-118020190098-5).S.S.S., A.K.P., and K.G.S. thank IRCC and the Department of Physics, IIT Bombay, for X-ray diffraction and magnetization facilities. S.S.S. acknowledges UGC-DAE CSR, Indore, for financial support under the Collaborative Research Scheme (CSR-IC-256/2017-18/1337). V.G. acknowledges UGC-DAE CSR, Indore, for the support. A.K.M. thanks CSIR, India, for SRF [File No.: 09/926(0011)2K18]. K.G.S. acknowledges financial support through Indo-Russian project: DST/INT/RFBR/IDIR/P-01/2016. The theoretical studies are supported by the Russian Science Foundation (Project No. 22-42-02021) for the electronic structure calculations and Ministry of Science and Higher Education of the Russian Federation for the exchange parameters calculations (theme “Electron” No. AAAA-A18-118020190098-5)

Identification of BRCA1 missense substitutions that confer partial functional activity: potential moderate risk variants?

Introduction: Many of the DNA sequence variants identified in the breast cancer susceptibility gene BRCA1 remain unclassified in terms of their potential pathogenicity. Both multifactorial likelihood analysis and functional approaches have been proposed as a means to elucidate likely clinical significance of such variants, but analysis of the comparative value of these methods for classifying all sequence variants has been limited. Methods: We have compared the results from multifactorial likelihood analysis with those from several functional analyses for the four BRCA1 sequence variants A1708E, G1738R, R1699Q, and A1708V. Results: Our results show that multifactorial likelihood analysis, which incorporates sequence conservation, co-inheritance, segregation, and tumour immunohistochemical analysis, may improve classification of variants. For A1708E, previously shown to be functionally compromised, analysis of oestrogen receptor, cytokeratin 5/6, and cytokeratin 14 tumour expression data significantly strengthened the prediction of pathogenicity, giving a posterior probability of pathogenicity of 99%. For G1738R, shown to be functionally defective in this study, immunohistochemistry analysis confirmed previous findings of inconsistent 'BRCA1-like' phenotypes for the two tumours studied, and the posterior probability for this variant was 96%. The posterior probabilities of R1699Q and A1708V were 54% and 69%, respectively, only moderately suggestive of increased risk. Interestingly, results from functional analyses suggest that both of these variants have only partial functional activity. R1699Q was defective in foci formation in response to DNA damage and displayed intermediate transcriptional transactivation activity but showed no evidence for centrosome amplification. In contrast, A1708V displayed an intermediate transcriptional transactivation activity and a normal foci formation response in response to DNA damage but induced centrosome amplification. Conclusion: These data highlight the need for a range of functional studies to be performed in order to identify variants with partially compromised function. The results also raise the possibility that A1708V and R1699Q may be associated with a low or moderate risk of cancer. While data pooling strategies may provide more information for multifactorial analysis to improve the interpretation of the clinical significance of these variants, it is likely that the development of current multifactorial likelihood approaches and the consideration of alternative statistical approaches will be needed to determine whether these individually rare variants do confer a low or moderate risk of breast cancer

Standardisation of rates using logistic regression: a comparison with the direct method

<p>Abstract</p> <p>Background</p> <p>Standardisation of rates in health services research is generally undertaken using the direct and indirect arithmetic methods. These methods can produce unreliable estimates when the calculations are based on small numbers. Regression based methods are available but are rarely applied in practice. This study demonstrates the advantages of using logistic regression to obtain smoothed standardised estimates of the prevalence of rare disease in the presence of covariates.</p> <p>Methods</p> <p>Step by step worked examples of the logistic and direct methods are presented utilising data from BETS, an observational study designed to estimate the prevalence of subclinical thyroid disease in the elderly. Rates calculated by the direct method were standardised by sex and age categories, whereas rates by the logistic method were standardised by sex and age as a continuous variable.</p> <p>Results</p> <p>The two methods produce estimates of similar magnitude when standardising by age and sex. The standard errors produced by the logistic method were lower than the conventional direct method.</p> <p>Conclusion</p> <p>Regression based standardisation is a practical alternative to the direct method. It produces more reliable estimates than the direct or indirect method when the calculations are based on small numbers. It has greater flexibility in factor selection and allows standardisation by both continuous and categorical variables. It therefore allows standardisation to be performed in situations where the direct method would give unreliable results.</p

Advances in small lasers

M.T.H was supported by an Australian Research council Future Fellowship research grant for this work. M.C.G. is grateful to the Scottish Funding Council (via SUPA) for financial support.Small lasers have dimensions or modes sizes close to or smaller than the wavelength of emitted light. In recent years there has been significant progress towards reducing the size and improving the characteristics of these devices. This work has been led primarily by the innovative use of new materials and cavity designs. This Review summarizes some of the latest developments, particularly in metallic and plasmonic lasers, improvements in small dielectric lasers, and the emerging area of small bio-compatible or bio-derived lasers. We examine the different approaches employed to reduce size and how they result in significant differences in the final device, particularly between metal- and dielectric-cavity lasers. We also present potential applications for the various forms of small lasers, and indicate where further developments are required.PostprintPeer reviewe

Are parents identifying positive aspects to parenting their child with an intellectual disability or are they just coping? A qualitative exploration

Although acknowledging the stress of raising their child with intellectual disabilities, parents also report that their child has brought about many positive changes in themselves and family. This study reports what parents perceive to be a positive aspect of parenting their child, as currently what constitutes a ‘positive’ is unclear. Seven key themes were identified; an increased sense of personal strength and confidence, changed priorities, greater appreciation of life, pleasure in the child’s accomplishments, increased faith/spirituality, more meaningful relationships and the positive effect that the child has on the wider community. Interpretive examination of the themes reveals that the positive aspects identified consist mostly of meaning-focused coping strategies. These enable parents to adapt successfully to the stressful experiences of raising their child and therefore could be amenable to meaning-focused therapeutic interventions for parents with newly diagnosed children or for those unable to identify any positive aspects of parenting their child