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The growing amount of evidence suggests the existence of a bidirectional relation between coronavirus disease 2019 (COVID-19) and type 2 diabetes mellitus (T2DM), as these two conditions exacerbate each other, causing a significant healthcare and socioeconomic burden. The alterations in innate and adaptive cellular immunity, adipose tissue, alveolar and endothelial dysfunction, hypercoagulation, the propensity to an increased viral load, and chronic diabetic complications are all associated with glucometabolic perturbations of T2DM patients that predispose them to severe forms of COVID-19 and mortality. Severe acute respiratory syndrome coronavirus 2 infection negatively impacts glucose homeostasis due to its effects on insulin sensitivity and β-cell function, further aggravating the preexisting glucometabolic perturbations in individuals with T2DM. Thus, the most effective ways are urgently needed for countering these glucometabolic disturbances occurring during acute COVID-19 illness in T2DM patients. The novel classes of antidiabetic medications (dipeptidyl peptidase 4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are considered candidate drugs for this purpose. This review article summarizes current knowledge regarding glucometabolic disturbances during acute COVID-19 illness in T2DM patients and the potential ways to tackle them using novel antidiabetic medications. Recent observational data suggest that preadmission use of GLP-1 RAs and SGLT-2is are associated with decreased patient mortality, while DPP-4is is associated with increased in-hospital mortality of T2DM patients with COVID-19. Although these results provide further evidence for the widespread use of these two classes of medications in this COVID-19 era, dedicated randomized controlled trials analyzing the effects of in-hospital use of novel antidiabetic agents in T2DM patients with COVID-19 are needed.

Introduction: Atherosclerosis can be considered a chronic inflammatory process that stands out as a dominant cause of cardiovascular disease (CVD). Since blood lipids are the leading risk factor for atherosclerosis development, lowering low-density lipoprotein cholesterol (LDL-C) and other apolipoprotein B-containing lipoproteins reduces the risk of future cardiovascular events. However, there has been significant progress in developing lipid-lowering drugs for aggressive management of dyslipidemia, the rates of CVD events remain unacceptably high, so there is great need to identify novel therapeutic pathways targeting the atherosclerosis process.Areas covered: We discussed the current guidelines on CVD prevention, the role of novel lipid-lowering drugs, as well as emerging drugs for atherosclerosis, emphasizing the current data on compounds targeting inflammatory and oxidant pathways.Expert Opinion: Although novel lipid-lowering drugs all showed their therapeutic efficacy in LDL-C lowering, data regarding their impact on cardiovascular outcomes is still inconclusive. On the other hand, some of the agents targeting inflammatory pathways, especially colchicine, showed promising results in terms of reducing CVD events. In contrast, those pointed at oxidant pathways failed to do so. Finally, exploring ways of targeting new therapeutic venues, such as adaptive immunity and clonal hematopoiesis, is a goal in the future.

A major issue is that the dissolution and assay methods are not discussed in any pharmacopeia, so the assay method was developed following the guidelines of the Food and Drug Administration. The analytical and dissolution methods were developed and validated in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use’s (ICH) guidelines. This study aims to discover the presence of counterfeit or substandard drugs in the market, to classify the most compliant brands, and to ascertain the appropriateness of interchangeability. Four different brands of rivaroxaban were selected in order to perform different quality control tests, which included the analytical, dissolution, and assay methods in accordance with the guidelines of the United States Pharmacopeia. The four chosen brands were tested and the results were found to be compliant with chemical parameters such as dissolution, content uniformity, and assay. Hence, it can be concluded that rivaroxaban 10 mg tablets, manufactured in Pakistan by leading pharmaceutical companies, are consistent in quality and can be easily interchangeable.

To estimate the prevalence and explore the predictors of vaccine uptake among older adults in India.We used data from the national Longitudinal Ageing Study in India, a national household survey conducted during 2017-2018. Based on interviewees' self-reports, we calculated population-weighted estimates of the uptake of influenza, pneumococcal, typhoid and hepatitis B vaccines among 64 714 Indian adults aged 45 years or older. We performed multivariable binary logistic regression analysis to examine the sociodemographic and health-related predictors of uptake of the vaccinations.The coverage of each of the studied vaccinations was less than 2%. The estimated percentages of respondents reporting ever being vaccinated were 1.5% (95% confidence interval, CI: 1.4-1.6) for influenza, 0.6% (95% CI: 0.6-0.7) for pneumococcal disease, 1.9% (95% CI: 1.8-2.0) for typhoid and 1.9% (95% CI: 1.8-2.0) for hepatitis B. Vaccine uptake was higher among respondents with cardiovascular disease, diabetes or lung disease than those without any of these conditions. Uptake of influenza vaccine was higher among those with lung disease, while hepatitis B vaccine uptake was higher among those with cardiovascular disease or diabetes. Male sex, urban residence, wealthier household, more years of schooling, existing medical conditions and sedentary behaviours were significant predictors of vaccine uptake.Targeted policies and programmes are needed for improving the low vaccination coverage among older adults in India, especially among those with chronic diseases. Further research could examine vaccine access, vaccine hesitancy, and vaccine-related information and communication channels to older adults and their health-care providers.Estimer la prévalence et explorer les facteurs prédictifs d’acceptation d’un vaccin chez les adultes plus âgés en Inde.Nous avons utilisé les données de l’Étude nationale longitudinale sur le vieillissement (Longitudinal Ageing Study) en Inde, enquête nationale auprès des ménages menée en 2017-2018. Sur la base des déclarations des personnes interrogées, nous avons calculé des estimations pondérées par la population de l’acceptation des vaccins contre la grippe, le pneumocoque, la typhoïde et l’hépatite B chez 64 714 adultes indiens âgés de 45 ans ou plus. Nous avons effectué une analyse de régression logistique binaire multivariable afin d’examiner les facteurs sociodémographiques et sanitaires liés à l’adoption des vaccins.La couverture de chacune des vaccinations étudiées était inférieure à 2%. Les pourcentages estimés de répondants déclarant avoir déjà été vaccinés étaient de 1,5% (intervalle de confiance (IC) à 95% : 1,4-1,6) pour la grippe, de 0,6% (IC à 95% : 0,6-0,7) pour les infections à pneumocoques, de 1,9% (IC à 95% : 1,8-2,0) pour la typhoïde et de 1,9% (IC à 95% : 1,8-2,0) pour l’hépatite B. Le recours au vaccin était plus élevé chez les personnes interrogées souffrant de maladies cardiovasculaires, de diabète ou de maladies pulmonaires que chez celles ne présentant aucune de ces affections. Le taux d’acceptation du vaccin contre la grippe était plus élevé chez les personnes souffrant de maladies pulmonaires, tandis que le taux d’acceptation du vaccin contre l’hépatite B était plus élevé chez les personnes souffrant de maladies cardiovasculaires ou de diabète. Le sexe masculin, l’habitat en zone urbaine, les revenus plus élevés du ménage, le nombre d’années d’études, les problèmes de santé existants et les comportements sédentaires étaient des facteurs prédictifs significatifs d’acceptation du vaccin.Des politiques et des programmes ciblés sont nécessaires pour améliorer la faible couverture vaccinale chez les personnes plus âgées en Inde, en particulier chez celles atteintes de maladies chroniques. D’autres recherches pourraient examiner l’accès aux vaccins, l’hésitation à se faire vacciner, ainsi que les canaux d’information et de communication liés aux vaccins pour les adultes plus âgés et leurs prestataires de soins de santé.Estimar la prevalencia y explorar los predictores de la aceptación de la vacuna entre los adultos mayores en la India.Se utilizaron datos del Estudio nacional de envejecimiento longitudinal en la India, una encuesta nacional de hogares realizada entre 2017 y 2018. A partir de los autoinformes de los entrevistados, se calcularon las estimaciones ponderadas a nivel poblacional de la aceptación de las vacunas antigripal, antineumocócica, antitifoidea y contra la hepatitis B entre 64 714 adultos indios de 45 años o más. Se realizó un análisis de regresión logística binaria multivariable para analizar los predictores sociodemográficos y sanitarios relacionados con la aceptación de las vacunas.La cobertura de cada una de las vacunas estudiadas fue inferior al 2 %. Los porcentajes estimados de los encuestados que declararon haberse vacunado alguna vez fueron del 1,5 % (intervalo de confianza del 95 %, IC: 1,4-1,6) para la gripe, el 0,6 % (IC del 95 %: 0,6-0,7) para las enfermedades neumocócicas, el 1,9 % (IC del 95 %: 1,8-2,0) para la fiebre tifoidea y el 1,9 % (IC del 95 %: 1,8-2,0) para la hepatitis B. La aceptación de la vacuna fue mayor entre los encuestados con enfermedades cardiovasculares, diabetes o enfermedades pulmonares que entre los que no padecían ninguna de estas enfermedades. La aceptación de la vacuna antigripal fue mayor entre los que padecían enfermedades pulmonares, mientras que la aceptación de la vacuna contra la hepatitis B fue mayor entre los que padecían enfermedades cardiovasculares o diabetes. El sexo masculino, la residencia en una ciudad, un hogar más rico, un mayor número de años de escolarización, las enfermedades existentes y los comportamientos sedentarios fueron predictores significativos de la aceptación de la vacuna.Se necesitan políticas y programas específicos para mejorar la escasa cobertura de vacunación entre los adultos mayores de la India, en especial entre los que padecen enfermedades crónicas. Otras investigaciones podrían analizar el acceso a las vacunas, las dudas al respecto y los canales de información y comunicación relacionados con la vacunación para los adultos mayores y sus proveedores de atención médica.لتقدير مدى الانتشار، واستكشاف عوامل التنبؤ بالحصول على اللقاح بين كبار السن في الهند.استخدمنا البيانات الواردة من دراسة الشيخوخة الطولية الوطنية في الهند، وهي مسح وطني للأسر تم إجراؤه خلال الفترة 2017 إلى 2018. بناءً على التقارير الذاتية للأشخاص الذين تمت مقابلتهم، قمنا بحساب التقديرات القائمة على السكان بخصوص الحصول على لقاحات الأنفلونزا، والمكورات الرئوية، والتيفوئيد والتهاب الكبد ب، بين 64714 بالغًا هنديًا تبلغ أعمارهم 45 عامًا أو أكبر. أجرينا تحليلًا للتحوّف اللوجستي الثنائي متعدد المتغيرات لفحص عوامل التنبؤ الاجتماعي السكاني والمتعلقة بالصحة والخاصة بالحصول على اللقاحات.كانت تغطية كل من التطعيمات التي خضعت للدراسة أقل من 2%. كانت النسب المئوية التقديرية للمستجيبين الذين أبلغوا عن تلقيحهم في أي وقت مضى 1.5% (بفاصل ثقة مقداره 95%: 1.4 إلى 1.6) للأنفلونزا، و0.6 (بفاصل ثقة مقداره 95%: 0.6 إلى 0.7) لمرض المكورات الرئوية، و1.9% (بفاصل ثقة مقداره 95%: 1.8 إلى 2.0) لمرض التيفوئيد، و1.9% (بفاصل ثقة مقداره 95%: 1.8 إلى 2.0) لالتهاب الكبد ب. كان الحصول على اللقاح أعلى بين المستجيبين المصابين بأمراض القلب والأوعية الدموية، أو السكري، أو أمراض الرئة من أولئك الذين لا يعانون من أي من هذه الأمراض. كان الحصول على لقاح الأنفلونزا أعلى بين المصابين بأمراض الرئة، بينما كان الحصول على لقاح التهاب الكبد ب أعلى بين المصابين بأمراض القلب والأوعية الدموية، أو مرض السكري. كان الذكور، والمقيمون في المدن، والأسرة الأكثر ثراءً، وسنوات التعليم الأكثر، والظروف الطبية الحالية، والسلوكيات المستقرة، من العوامل الهامة للتنبؤ بالحصول على اللقاح.هناك حاجة إلى سياسات وبرامج مستهدفة لتحسين تغطية التطعيم المنخفضة بين كبار السن في الهند، وخاصة بين من يعانون من أمراض مزمنة. يمكن لمزيد من الأبحاث التحقق من الحصول على اللقاح، والتردد في الحصول على اللقاح، والمعلومات المتعلقة باللقاح، وقنوات الاتصال لكبار السن، ومقدمي الرعاية الصحية.评估印度老年人疫苗接种覆盖率并探索预测因素。.我们采用了印度国家老龄化纵向研究的数据，该研究源自 2017-2018 开展的全国性家庭调查。根据受访者的自填报告，我们计算了 64,714 名 45 岁或以上的印度成年人中，接种流感疫苗、肺炎球菌疫苗、伤寒疫苗以及乙肝疫苗的人口权重估计值。我们采用多变量二元逻辑回归分析法来核验疫苗接种的社会人口和健康相关的预测因素。.所研究的每种疫苗接种覆盖率均低于 2%。报告曾经接种流感疫苗的受访者的百分比预计为 1.5%（95% 置信区间，CI：1.4–1.6），接种肺炎疫苗的为 0.6% (95% CI: 0.6-0.7)，接种伤寒疫苗的为 1.9% (95% CI: 1.8-2.0)，接种乙肝疫苗的为 1.9% (95% CI: 1.8–2.0)。患有心血管疾病、糖尿病或肺病的受访者的疫苗接种率高于没有任何这些疾病的受访者。患有肺病的受访者的流感疫苗接种率更高，患有心血管疾病或糖尿病的受访者的乙肝疫苗接种率更高。男性、城市居民、较富裕的家庭、受教育年限更长、现存医疗疾病和久坐行为是疫苗接种的重要预测因素。.需要有针对性的政策和计划来改善印度老年人（尤其是慢性病患者）疫苗接种覆盖率较低的情况。进一步的研究可以重点关注老年人及其医疗护理人员的疫苗获取、疫苗犹豫以及与疫苗相关的信息和沟通渠道情况。.Оценить распространенность и изучить предикторы охвата вакцинацией людей старшего возраста в Индии.Авторы использовали данные национального продольного исследования в области старения населения в Индии, национального обследования домохозяйств, проведенного в 2017–2018 гг. На основе самоотчетов интервьюируемых лиц авторы рассчитали средневзвешенные популяционные значения охвата вакцинацией против гриппа, пневмококка, брюшного тифа и гепатита B среди 64 714 взрослых индийцев в возрасте от 45 лет и старше. Авторы провели многомерный анализ бинарной логистической регрессии, чтобы изучить социально-демографические и связанные со здоровьем предикторы охвата вакцинацией.Охват каждой из изученных прививок составил менее 2%. Предполагаемый процент респондентов, сообщивших о любой своей вакцинации, составил 1,5% (95%-й ДИ: 1,4–1,6) для гриппа, 0,6% (95%-й ДИ: 0,6–0,7) для пневмококковой инфекции, 1,9% (95%-й ДИ: 1,8–2,0) для брюшного тифа и 1,9% (95%-й ДИ: 1,8–2,0) для гепатита B. Охват вакцинацией был выше среди респондентов с сердечно-сосудистыми заболеваниями, диабетом или заболеваниями легких, чем среди тех, у кого не было ни одного из этих состояний. Охват вакцинацией против гриппа был выше среди лиц с заболеваниями легких, а охват вакцинацией против гепатита В был выше среди лиц с сердечно-сосудистыми заболеваниями или диабетом. Важными предикторами охвата вакцинацией являлись мужской пол, проживание в городской местности, более обеспеченное домохозяйство, более долгий срок обучения, имеющиеся заболевания и малоподвижный образ жизни.Необходимы целенаправленная политика и программы для улучшения низкого охвата вакцинацией людей старшего возраста в Индии, особенно среди людей с хроническими заболеваниями. Дальнейшие исследования могли бы изучить доступ к вакцинам, нерешительность в отношении вакцин, а также каналы информации и связи, связанные с вакцинами, для людей старшего возраста и медицинских работников.

Background: Macular holes are a leading cause of visual impairment and blindness worldwide defined as a partial or full thickness anatomical defect in the fovea of the retina. Internal limiting membrane (ILM) peeling is a successful surgical procedure to repair the defect. However, it doesn’t have good efficacy with larger macular holes. Internal limiting membrane (ILM) flap is a novel technique and shows promising results. Objective This systematic review and meta-analysis aims to compare the effectiveness of these two techniques in treating any size and type of macular hole. Methods A comprehensive literature search was conducted in the PubMed, Medline, Cochrane Library and Web of Science databases to identify the relevant articles. The primary outcome measures were MH closure rate and postoperative visual acuity (VA). The statistical power was ensured by performing heterogeneity, publication bias, sensitivity analysis, and subgroup analysis. Pooled odds ratios (ORs), weighted mean difference (WMD), and 95% confidence intervals (CIs) were calculated. Results A total of 8 RCTs and 18 Retrospective studies were included in this meta-analysis, which involved 1052 eyes in the ILM flap group and 1050 eyes in the ILM peeling group. The overall MH closure rate came out to be in favor of ILM flap technique (OR=2.74, CI=1.62 TO 4.66; P = 0.0002). In overall analysis of postoperative VA, no significant difference was observed between the two surgical methods. However, it favored ILM flap technique on subgroup analysis based on study type and MH size specifically in the RCTS with macular hole size > 400μm (MD = -0.13, 95% CI = -0.16 to -0.09; P Conclusion ILM flap technique resulted in better anatomical outcomes as well as better visual outcomes specifically in larger macular holes and at all the follow-up months. Hence, it is recommended that the inverted internal limiting membrane (ILM) flap method should routinely be chosen as the preferred treatment for patients who have macular holes larger than 400 micrometers.

Purpose: Intraoperative stabilisation of bony fragments with maxillo-mandibular fixation (MMF) is an essential step in the surgical treatment of mandibular fractures that are treated with open reduction and internal fixation (ORIF). The MMF can be performed with or without wire-based methods, rigid or manual MMF, respectively. The aim of this study was to compare the use of manual versus rigid MMF, in terms of occlusal outcomes and infective complications. Materials and methods: This multi-centric prospective study involved 12 European maxillofacial centres and included adult patients (age ≥16 years) with mandibular fractures treated with ORIF. The following data were collected: age, gender, pre-trauma dental status (dentate or partially dentate), cause of injury, fracture site, associated facial fractures, surgical approach, modality of intraoperative MMF (manual or rigid), outcome (minor/major malocclusions and infective complications) and revision surgeries. The main outcome was malocclusion at 6 weeks after surgery. Results: Between May 1, 2021 and April 30, 2022, 319 patients-257 males and 62 females (median age, 28 years)-with mandibular fractures (185 single, 116 double and 18 triple fractures) were hospitalised and treated with ORIF. Intraoperative MMF was performed manually on 112 (35%) patients and with rigid MMF on 207 (65%) patients. The study variables did not differ significantly between the two groups, except for age. Minor occlusion disturbances were observed in 4 (3.6%) patients in the manual MMF group and in 10 (4.8%) patients in the rigid MMF group (p > .05). In the rigid MMF group, only one case of major malocclusion required a revision surgery. Infective complications involved 3.6% and 5.8% of patients in the manual and rigid MMF group, respectively (p > .05). Conclusion: Intraoperative MMF was performed manually in nearly one third of the patients, with wide variability among the centres and no difference observed in terms of number, site and displacement of fractures. No significant difference was found in terms of postoperative malocclusion among patients treated with manual or rigid MMF. This suggests that both techniques were equally effective in providing intraoperative MMF.

The receptor of Advanced Glycation Endproducts (RAGE) and Advanced Glycation Endproducts (AGE) have multiple functions in our body and their restraint are being observed in neurodegenerative and memory impairment disorders. The review of different pathways allows an understanding of the probable mechanism of neurodegeneration and memory impairment involving RAGE and AGE. Commonly we observe AGE accumulation in neural cells and tissues but the extent of accumulation increases with the presence of memory impairment disorder. The presence of AGEs can also be seen in morbid accumulation, pathological structures in the form of amyloid clots, and nervous fibrillary tangles in Alzheimer’s Disease (AD) and memory impairment disease.Many neuropathological and biochemical aspects of AD are explained by AGEs, including widespread protein crosslinking, glial activation of oxidative stress, and neuronal cell death. Oxidative stress is due to different reasons and glycation end products set in motion and form or define various actions which are normally due to AGE changes in a pathogenic cascade. By regulating the transit of ß-amyloid in and out of the brain or altering inflammatory pathways, AGE and it’s ensnare receptor such as soluble RAGE may function as blockage or shield AD development. RAGE activates the transcription-controlling factor Necrosis Factor (NF-κB) and increases the protraction of cytokines, like a higher number of Tumor Necrosis Factor (TNF-α) and Interleukin (IL-I) by inducing several signal transduction cascades. Furthermore, binding to RAGE can pro-activate reactive oxygen species (ROS), which is popularly known to cause neuronal death.

As the world enters its third year of the COVID-19 pandemic, individuals with diabetes have faced particular challenges from the virus. A deleterious bidirectional relationship exists between the two disorders, with heightened inflammatory, immunologic, and cellular mechanisms leading to a more severe illness and increased morbidity and mortality. Tight glucose control, though necessary, is hampered by physical restrictions and difficulty accessing health care. Novel glucose-lowering medications may provide unique benefits in this regard. It is imperative that multi-pronged efforts be prioritized in order to reduce adverse outcomes in patients with diabetes at risk for COVID-19.

This article addresses the problem of global stabilization of continuous-time linear systems subject to control constraints using a model-free approach. We propose a gain-scheduled low-gain feedback scheme that prevents saturation from occurring and achieves global stabilization. The framework of parameterized algebraic Riccati equations (AREs) is employed to design the low-gain feedback control laws. An adaptive dynamic programming (ADP) method is presented to find the solution of the parameterized ARE without requiring the knowledge of the system dynamics. In particular, we present an iterative ADP algorithm that searches for an appropriate value of the low-gain parameter and iteratively solves the parameterized ADP Bellman equation. We present both state feedback and output feedback algorithms. The closed-loop stability and the convergence of the algorithm to the nominal solution of the parameterized ARE are shown. The simulation results validate the effectiveness of the proposed scheme.

The goal of mandibular fracture treatment is to restore static and dynamic occlusal functions. Open reduction and internal fixation (ORIF) of these fractures can be associated with an intraoperative and/or postoperative maxillo-mandibular fixation (MMF). The aim of this study was to analyse the use of perioperative MMF and its effects on occlusal outcomes in the management of mandibular fractures.This multicentric prospective study included adult patients with mandibular fractures treated with ORIF. The following data were collected: age, gender, pre-trauma dental status (dentate, partially dentate), cause of injury, fracture site, associated facial fractures, surgical approach, type of ORIF (rigid, non-rigid or mixed), thickness and number of plates, modality of intraoperative MMF (arch bars, self-tapping and self-drilling screws [STSDSs], manual, other) and duration of postoperative MMF. The primary outcome was malocclusion at 6 weeks and 3 months. Statistical analyses were performed with Fisher's exact test or chi-square test, as appropriate.Between 1 May 2021 and 30 April 2022, 336 patients, 264 males and 72 females (median age, 28 years) with mandibular fractures (194 single, 124 double and 18 triple fractures) were hospitalized. Intraoperative MMF was performed in all patients. Osteosynthesis was rigid in 75% of single fractures, and rigid or mixed in 85% and 100% of double and triple fractures, respectively. Excluding patients who underwent manual reduction, postoperative MMF (median duration, 3 weeks) was performed in 140 (64%) patients, without differences by type or number of fractures (p0.05). No significant difference was found in the incidence of malocclusion in patients with postoperative MMF (5%, 95% confidence interval [CI], 2-10%) compared to those without (4%; 95% IC, 1-11%) (p0.05).Postoperative MMF was performed in more than half of the patients despite adequate fracture osteosynthesis, with wide variability among centers. No evidence of a reduction in the incidence of postoperative malocclusion in patients treated with postoperative MMF was found.