Search

This research examines the impact of the COVID-19 on cryptocurrencies' connectedness by employing two techniques: TVP-VAR-based connectedness and causality in the quantiles. First, the TVP-VAR-based connectedness unveils that cryptocurrencies act as a net receiver and transmitter of shocks, with Bitcoin, Ethereum are the highest transmitters among others. Moreover, the causality-in-quantile test shows that COVID-19 significantly causes spillover connectedness among cryptocurrencies, mainly at the quantiles ranging from 0.1 to 0.8, while an insignificant causal relationship is found in few cases. The study has implications for investors and policymakers., (© 2021 Elsevier Inc. All rights reserved.)

The aim of the proposed study is to develop a mucoadhesive buccal delivery system for the sustained delivery of metformin (MET) and sitagliptin (SIT) against diabetes mellitus (DM) with improved bioavailability. Polymeric blend of Carbopol ® 940 (CP), agarose (AG) or polyvinylpyrrolidone K30 (PVP) as mucoadhesive agents in formulations (R1-R15) were compressed via the direct compression technique. Tablets were characterized for solid state studies, physicochemical and in vivo mucoadhesion studies in healthy volunteers. Outcomes did not reveal any unusual peak or interaction between the drugs and polymers in the physical mixture through Fourier Transform Infrared Spectroscopy (FTIR) and DSC analysis. The mucoadhesive blend of CP and PVP was superior compared to other blends. The formulation R4 revealed exorbitant loading of drugs with complete drug release for 6 h with ex vivo mucoadhesive strength and time of 26.99 g and 8.1 h, respectively. It was further scrutinized to evaluate it as an optimized formulation where it was found to be stable for up to 6 months. The formulation R4 depicted Korsmeyer-Peppas model and first-order mode of release correspondingly for SIT and MET. Moreover, it showed hemocompatibility, biocompatibility and stability with non-significant changes in the dissolution profile. Overall, the CP blend with PVP was found appropriate to yield the desired release coupled with the optimized mucoadhesive properties of the buccal tablets, ensuring sufficient pharmaceutical stability.

Background: The COVID-19 pandemic during lockdown has highlighted the importance of identifying individuals most at risk of infection with SARS-CoV-2, underscoring the need to assess factors contributing to susceptibility to disease. With the rapidly evolving nature of the pandemic and its new variants, there is an inadequate understanding on whether there are certain factors such as a specific symptom or collection of symptoms that combined with life-style behaviors may be useful to predict susceptibility. The study aims to explore such factors from pre-vaccination data to guide public health response to potential new waves., Methods: An anonymous electronic survey was distributed through social media during the lockdown period in the United States from April to June 2020. Respondents were questioned regarding COVID testing, presenting symptoms, demographic information, comorbidities, and confirmation of COVID-19 test results. Stepwise logistic regression was used to identify predictors for COVID-19 perceived susceptibility. Selected classifiers were assessed for prediction performance using area under receiver operating characteristic (AUROC) curve analysis., Results: A total of 130 participants deemed as susceptible because they self-reported their perception of having COVID-19 (but without the evidence of positive test) were compared with 130 individuals with documented negative test results. Participants had a mean age of 45 years, and 165 (63%) were female. Final multivariable model showed significant associations with perceived susceptibility for the following variables: fever (OR:33.5; 95%CI: 3.9,85.9), body ache (OR:3.0; 95%CI:1.1,6.4), contact history (OR:2.7; 95%CI:1.1,6.4), age> 50 (OR:2.7; 95%CI:1.1, 6.6) and smoking (OR:3.3; 95%CI: 1.2,9.1) after adjusting for other symptoms and presence of comorbid conditions. The AUROC ranged from poor to fair (0.65-0.76) for cluster of symptoms but improved to a good model (AUROC = 0.803) after inclusion of sociodemographic and lifestyle behaviors e.g., age and smoking tobacco., Conclusions: Fever and body aches suggest association with perceived COVID-19 susceptibility in the presence of demographic and lifestyle behaviors. Using other constitutional and respiratory symptoms with fever and body aches, the parsimonious classifier correctly predicts 80.3% of COVID-19 perceived susceptibility. A larger cohort of respondents will be needed to study and refine classifier performance in future lockdowns and with expected surge of new variants of COVID-19 pandemic., Competing Interests: Competing interests None declared., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The aim of the projected study was to design and develop a novel strategy for evaluating the mucoadhesive potential of polymeric tablets of dexamethasone (DXM) for local delivery against wounds. Therefore, formulations (Q1-Q7) were synthesized via direct compression method by varying the concentrations of polymers, i.e., ethyl cellulose (EC) and agar extract (AG). Moreover, the mucoadhesive polymeric tablets were characterized via physicochemical, in vitro, ex vivo and in vivo experiments. However, physicochemical characteristics such as FTIR showed no interaction with different polymeric combination. Surface pH of all formulations was normal to slightly alkaline. Highest hydration of up to 6.22% and swelling index was comprehended with maximum concentration of AG (50% of total tablet weight). Whereas, ex vivo and in vivo residence time and mucoadhesion were attributed to the increased concentrations of polymers. Moreover, Q7, (optimized formulation), containing 10% of EC and 40% of AG, exhibited maximum release of DXM (100%) over 8 h, along with sufficient mucoadhesive strength up to 11.73 g, following first-order kinetics having r 2 value of 0.9778. Hemostatic effects and epithelialization for triggering and promoting wound healing were highly pronounced in cases of Q7. Furthermore, in vivo residence time was 7.84 h followed by salivary drug concentration (4.2 µg/mL). However, mucoadhesive buccal tablets showed stability for 6 months, thus following the standardization (ICH-Iva) stability zone. In summary, DXM mucoadhesive tablets seem to be an ideal candidate for eradication of wound infections via local targeted delivery.

Purpose: To evaluate the Canon CP-TX1 camera as a screening tool for ARFs in a pediatric population and estimate the prevalence of ARFs., Methods: In a pediatric outpatient space, largely in the immunization clinic, after obtaining parental consent, we encouraged children to be photographed from a distance of 5 feet in a dim room by using a CP-TX1 camera with the red-eye reduction feature off. Based on the captured red reflex, children were labeled as normal (symmetrical red reflexes in the two eyes, with no visible crescents); all others were considered as abnormal or positive for ARFs. All photographed children were assessed by an optometrist/refractionist for VA by age-appropriate methods. Data were entered into a 2 × 2 contingency table on statpages.org, and diagnostic indices were calculated with 95%CI., Results: With a sample of 262 children, we obtained a sensitivity of 0.82, a specificity of 0.98, a positive predictive value of 0.92, a negative predictive value of 0.94, a positive likelihood ratio of 41.06, a negative likelihood ratio of 0.17, and a prevalence of 0.24 for ARFs., Conclusion: CP-TX1 performed well as a screening tool to identify ARFs in children. Placing such a camera in an immunization clinic offers a chance to identify children with ARFs at a time when amblyopia is eminently reversible., Competing Interests: None

With the development of remote cardiac healthcare, wearable devices for electrocardiogram (ECG) monitoring are stringent requirements to cope with this rapid growth of demands. Due to the advantages of no-contact ECG measuring methods in safety, convenience, and comfortableness, it is more suitable for wearable long-term ECG monitoring than the conventional Ag/AgCl electrodes. The capacitance coupling printed circuit board (PCB) electrode with ultra-high input impedance proposed in this paper can realize non-contact ECG measurement through a multi-layer insulating medium. Then, an eight-channel ECG signal processing circuit is also designed and fabricated. In addition, the following important performance properties of the non-contact ECG measuring system, such as the input impedance, the phase-frequency characteristic, the amplitude-frequency characteristic, the coupling coefficient, and the input short-circuit input noise, were all experimentally measured. The synchronous comparison between the Ag/AgCl electrode and the PCB electrode was also conducted to verify the accuracy of the non-contact measuring method. Finally, the influence of the lead positions, coupling medium parameters, and the body motion states was also experimentally studied. The results demonstrate that the proposed non-contact ECG measuring method based on capacitance coupling PCB electrodes can effectively collect the main components of ECG signals and cardiac rhythm in various situations.

Waste recycling significantly contributes to reducing carbon emissions and other greenhouse gases, leading to enhanced environmental performance and safeguards natural resources. Therefore, this study examines municipal solid waste recycling and energy efficiency's impact on the environmental performance and economic well-being of the USA. Some studies have emphasized the usefulness of MSW and its indicators, but most of them are survey-based and illustrate the scientific process of disposing of waste. Hence, the study intends to analyze the connection among considered variables using the recently developed and advanced estimation procedure of nonparametric causality in quantile approach by analyzing the quarterly dataset for 1990(Q1) till 2018(Q4). Through this technique, we have examined the causal relationships in different quantiles. The causality-in-quantile outcome indicates the acceptance of the null hypothesis in different quantiles, especially at low and high tail quantiles, while at some quantiles, the null hypothesis rejection is highlighted. This study suggests valuable implications for future studies, government, environmentalists, and policymakers., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In nature, plant-insect interactions occur in complex settings involving multiple trophic levels, often with multiple species at each level. 1 Herbivore attack of a host plant typically dramatically alters the plant's odor emission in terms of concentration and composition. 2 , 3 Therefore, a well-adapted herbivore should be able to predict whether a plant is still suitable as a host by judging these changes in the emitted bouquet. Although studies have demonstrated that oviposition preferences of successive insects were affected by previous infestations, 4 , 5 the underlying molecular and olfactory mechanisms remain unknown. Here, we report that tobacco hawkmoths (Manduca sexta) preferentially oviposit on Jimson weed (Datura wrightii) that is already infested by a specialist, the three-lined potato beetle (Lema daturaphila). Interestingly, the moths' offspring do not benefit directly, as larvae develop more slowly when feeding together with Lema beetles. However, one of M. sexta's main enemies, the parasitoid wasp Cotesia congregata, prefers the headspace of M. sexta-infested plants to that of plants infested by both herbivores. Hence, we conclude that female M. sexta ignore the interspecific competition with beetles and oviposit deliberately on beetle-infested plants to provide their offspring with an enemy-reduced space, thus providing a trade-off that generates a net benefit to the survival and fitness of the subsequent generation. We identify that α-copaene, emitted by beetle-infested Datura, plays a role in this preference. By performing heterologous expression and single-sensillum recordings, we show that odorant receptor (Or35) is involved in α-copaene detection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction Mask ventilation is one of the key components in the management of airway during general anaesthesia, particularly when laryngoscopy is challenging. Adequate mask ventilation provides anaesthesiologists a safe time in case of unanticipated or anticipated difficult airway situations. The aim of this study was to determine the incidence of difficult bag-mask ventilation and intubation in patients having three or more predictors for difficult mask ventilation (DMV) in adult patients scheduled for elective surgery under anaesthesia. Methods A total of 294 patients requiring endotracheal intubation for elective surgical procedure having three or more risk factors were evaluated for the presence of difficulty in bag-mask ventilation and intubation by the anaesthesiologist. Chi-square test or Fisher's exact test and a multivariable stepwise logistic regression model were performed to identify predictors of DMV. Crude and adjusted odds ratio with 95% confidence interval were reported. Results In this study, the average age of the patients was 53.59±13.32 years with a 2:1 male-to-female ratio. DMV and difficult intubation (DI) were observed in 31.6% and 3% of patients, respectively. Multivariate analysis identified history of snoring, BMI (>35 kg/m 2 ), presence of beard and Mallampati III or IV as independent predictors for DMV. Patients with multiple factors (≥3 factors) had a threefold (OR=2.57) increased risk of difficulty in mask ventilation and a nearly fivefold (OR=4.63) increased risk of difficulty with intubation. Conclusion  In our study, the incidence of DMV was observed in 93 (31.6%) patients and DI was found in 9 (3%) patients. A simple DMV risk score may help to predict DMV better, potentially improving safety during difficult airway management, decreasing morbidity and mortality associated with it., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Khan et al.)

Background and Aims: Cholangiocarcinoma is a relatively rare malignancy with high mortality. In the U.S., incidence rates of cholangiocarcinoma have increased, particularly affecting younger age groups and Hispanic and Asian individuals. We investigated the incidence of cholangiocarcinoma in a largely under-represented, minority population., Methods: We performed a retrospective cohort study from 2005 to 2017 among adults in a county-funded healthcare system in Harris County, Texas. Incidence rate ratios were computed to compare age-standardized rates using U.S. standard population between 2 time periods: 2005-2011 and 2012-2017., Results: We identified 139 cholangiocarcinoma cases (64% intrahepatic, 36% extrahepatic). The median age at diagnosis was 57 years; 62% were Hispanic, and 56% were born outside the U.S. The incidence rate increased from 1.2 to 2.4 per 100,000 person-years (rate ratio 2.1 [95% confidence interval {CI}: 1.5, 3.0]). Hispanic individuals and those aged 40-69 years had the highest rate of incidence increase (respectively, rate ratio: 2.5 [95% CI: 1.6, 4.0] and rate ratio: 2.0 [95% CI: 1.2, 3.0]) between time periods. In 2012-2017, the risk of cholangiocarcinoma among patients with diabetes was 1.4 times relative to those without (relative risk: 1.4; 95% CI: 1.1, 1.5) and 1.2 times among those who were overweight/obese relative to those who were not (relative risk: 1.2; 95% CI: 1.1, 1.6)., Conclusion: Incidence of cholangiocarcinoma doubled during the 12-year study period, with Hispanic and middle-aged individuals disproportionately affected. Individuals with diabetes mellitus and those who were overweight or obese had a high risk of being diagnosed with cholangiocarcinoma in the later time period. Further studies should focus on preventing and improving earlier diagnosis of cholangiocarcinoma among Hispanics., (© 2022 The Authors.)

Background & Objective: Peganum harmala has been traditionally used to manage rheumatoid arthritis (RA) and other inflammatory conditions. However, its use against RA has not been scientifically evaluated. The current study was designed to assess the anti-arthritic and anti-inflammatory activities of the methanolic extract of P. harmala leaves by in vitro and in vivo methods., Methods: The in vitro assays were carried out to determine the effect of plant extract on inhibition of egg albumin denaturation and human red blood cell membrane (HRBC) stabilization. Moreover, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity was performed to determine the antioxidant potential. In vivo anti-arthritic activity was performed by determining the curative effect against Complete Freund's adjuvant (0.1 ml). The plant extract was administered to rats orally at 200, 400 and 600 mg/kg/day for 21 days., Results: The values of IC50 of plant extract in protein denaturation, stabilization of HRBC and DPPH assays were 77.54 mg/ml, 23.90 mg/ml and 58.09 μg/ml, respectively. Moreover, the plant extract significantly attenuated the poly-arthritis and weight loss, anemia and paw edema. The plant extract restored the level of C-reactive protein, rheumatoid factor, alanine transaminase, aspartate transaminase and alkaline phosphatase in poly-arthritic rats. Moreover, the plant extract restored the immune organs' weight in treated rats. Treatment with P. harmala also significantly subdued the oxidative stress by reinstating superoxide dismutase, reduced glutathione, catalase and malondialdehyde in poly-arthritic rats. The plant extract notably restored the prostaglandin-E2 and tumor necrosis factor (TNF)-α in the serum of poly-arthritic rats., Conclusion: It was concluded that P. harmala extract had potential antioxidant, anti-inflammatory and antiarthritic activities, which primarily might be attributed to alkaloids, flavonoids and phenols., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The impact of the COVID-19 pandemic upon care of malignant melanoma (MM) remains as yet poorly understood. We undertook a UK-wide national survey, in conjunction with a patient support group (Melanoma UK), to explore patient perceptions of the impact of the pandemic upon treatment and outpatient care of their MM. Our findings suggest that following the onset of COVID-19, a significant minority of treatments and appointments have been delayed, there has been a shift from face-to-face to virtual outpatient consultations and there may be a rise in psychological comorbidities in patients with MM. We would urge clinicians to consider mental health interventions as part of a holistic care package., (© 2021 British Association of Dermatologists.)

Introduction: Liquid Semisolid Matrix (LSSM) technology involves the filling of drugmixed gel in hard gelatin capsules for different applications., Methods: In continuation of our previous work on LSSM technology, 10% (w/w) of practically insoluble model drug, mefenamic acid was incorporated in gels of different poloxamers with 8% (w/w) SiO 2 ., Results: Gels exhibited plasticity or pseudoplasticity along thixotropy at 2 and 24 h enabling their easy filling into hard gelatin capsules without content seepage. Mefenamic acid gels prepared with L64 and L92 maintained their apparent viscosities for the study period of one month. Around 100% mefenamic acid was released within 90 min from L64- and in 150 min from L92-SiO 2 gels, both with first-order kinetics. In 12 month long-term stability studies, only mefenamic acid-L64- SiO gel at 30°C/65% RH indicated dispersion stability with similar rheology and release pattern to that at 2, 24 and 30 days. No chemical drug-polymer interactions were found in FTIR., Conclusion: The release of practically insoluble mefenamic acid could be enhanced from gel formulated with L64 and SiO 2 ., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Phytoestrogens are non-steroidal estrogen analogues and are found primarily in soy products. They have received increasing attention as dietary supplements for estrogen deficiency and as modulators of endogenous estrogen functions, including cognition and emotion. In addition to modifying the levels of circulating sex hormones, phytoestrogens also exert direct effects on estrogen and androgen receptors in the brain and thus effectively modulate the neural circuit functions. Objective: The aim of this study was to investigate the long-term effects of low phytoestrogen intake (∼6 weeks) on the hippocampal plasticity and hippocampus-dependent memory formation in the adult C57BL/6 male mice. Methods and Results: In comparison to mice on a diet with normal phytoestrogen content, mice on low phytoestrogen diet showed a significant reduction in the phosphorylation of NR2B subunit, a molecular correlate of plasticity in the Schaffer collateral-CA1 synapse. We observed a profound decrease in long-term potentiation (LTP) in the ventral hippocampus, whereas no effect on plasticity was evident in its dorsal portion. Furthermore, we demonstrated that acute perfusion of slices with an estrogen analogue equol, an isoflovane metabolized from daidzein produced by the bacterial flora in the gut, was able to rescue the observed LTP deficit. Examining potential behavioral correlates of the plasticity attenuation, we found that mice on phytoestrogen-free diet display decreased contextual fear memory at remote but not at recent time points after training. Conclusions: Our data suggests that nutritional phytoestrogens have profound effects on the plasticity in the ventral hippocampus and ventral hippocampus-dependent memory.

Purpose of the Review: Endovascular thrombectomy (EVT) for large vessel occlusion strokes (LVOS) presents several treatment challenges. We provide a summary of existing tools for patient selection (pre-EVT tools) and for prognostication of long-term outcomes following reperfusion therapy (post-EVT tools)., Recent Findings: Recently published randomized trials demonstrated superiority of EVT over medical therapy alone for LVOS. Uniform patient selection paradigms based on demographic, clinical, and radiographic variables are not completely standardized, leading to variability in patient selection for EVT for LVOS. Post-EVT, an accurate assessment of long-term prognosis is critical in the decision-making process., Summary: Prognostic scores can serve as useful adjuncts to facilitate clinical decision-making during early management of patients with ischemic stroke, particularly those with LVOS. The acute management of LVOS comprises rapid clinical assessment, triage, and cerebrovascular imaging, followed by evaluation for candidacy for thrombolysis and EVT. Pre-EVT prognostic tools that accurately predict the likelihood of benefit from EVT may guide reliable, efficient, and cost-effective patient selection. Following EVT, severe stroke deficits and subacute poststroke complications that portend a poor prognosis may warrant invasive therapies. Clinical decisions regarding these treatment options involve careful discussions between providers and patient families, and are also based on prognosis provided by the treating clinician. Reliable post-EVT prognostic tools can facilitate this by providing accurate and objective prognostic information. Several prognostic tools have been developed and validated in the literature, some of which may be applicable in the pre-EVT and post-EVT settings, although clinical utility and application varies. Validation in contemporary datasets as well as implementation and impact studies are needed before these scales can be used to guide clinical decisions for individual patients., (© 2021 American Academy of Neurology.)

Aim: To assess safety and effectiveness of gliclazide MR 60 mg in people with controlled or suboptimal controlled T2DM treated with breakable gliclazide MR 60 mg formulation., Method: This study data has been extracted from an international, observational study conducted in nine Asian and Middle Eastern countries. Total 220 patients with T2DM were recruited from Pakistan. The primary endpoint was the proportion of patients reporting at least 1 symptomatic HE, whereas secondary endpoints were changes in glycosylated haemoglobin (HbA 1c ) %, fasting plasma glucose (FPG) mg/dL, and body weight (kg) and proportion of patients reporting any HE (confirmed or severe), between inclusion visit (V0) and end of the study visit (V1)., Results: During Ramadan, 3.6% (n = 8/220) patients had experienced at least one symptomatic HEs. A significant (p-value < 0.001) reduction was observed in HbA 1c : (mean [SD]) (-0.4 [0.9] %), and body weight (-0.7 [4.8] kg). Thirteen adverse events (AEs) unrelated to gliclazide MR were reported during the study pre-Ramadan and post-Ramadan periods., Conclusion: This study shows safety and effectiveness profile of gliclazide MR 60 mg by emphasizing on the low risk of HEs, effective glycaemic control and body weight reduction in T2DM patients, who are inclined to fasting during Ramadan., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Gingivitis is a condition that needs sustained concentration of antibiotic locally over extended period of time. The current study aimed to formulate and evaluate the sustained and localized release of metronidazole (MTZ) as mucoadhesive buccal tablet containing hydroxypropylmethyl cellulose (HPMC), Carbopol 940® (CP), carboxymethylcellulose (CMC) and ethyl cellulose (EC) as mucoadhesive polymers. Tablets were directly compressed with proportions of polymeric blends (F1-F16). The results indicated that weight variation (249±2.10mg) and friability (0.21%) were within USP compendial limits. Maximum mucoadhesive strength and time were depicted by F1 and F14 which were 28.47g and 12hr respectively. Formulations, except F4, were within physiological pH limit. Maximum swellability index (261.9%) was exhibited by F16, at 8 hr, containing highest concentration of CP, HPMC and additional CMC. For in vitro release, the pre-set 8 hr complete release were shown by formulations, F15 and F16 which were 100% and 97%, respectively. Genetic algorithm was applied on the attributes to optimize polymeric response in accordance with desirability. The software predicted composition (F17) was tested which revealed that physical characteristics were in accordance with the compendial standards. The release kinetics, evaluated through DDsolver⌖, suggested that release of MTZ followed non-Fickian diffusion type in Korsmeyer-Peppas model. Therefore, MTZ, if delivered as mucoadhesive buccal formulation (F17) containing amounts (mg) of CP (16.4), HPMC (78.7), CMC (8.3) and EC (10.5) will simulate satisfactory release i.e. 96% at 8 hr in simulated buccal fluid.

Diabetes is a pandemic which is becoming endemic to society. Primary care physicians should be able to offer basic diabetes prevention and care services, to ensure timely detection and management of the condition. This expert opinion shares suggestions to help primary care physicians introduce and integrate diabetes care in their routine practice. It identifies and focuses on four pillars: improving oneself, strengthening the health care team, empowering the person living with diabetes, and sensitizing the public at large.

All over the world, humankind and nature are paying off economic development's opportunity cost through accelerated environmental degradation. Renewable energy is the best option to control and minimize environmental degradation for sustainable development. This study's primary motive is to examine the nonlinear relationship between renewable energy consumption, natural resource rent, and ecological footprint in the context of the world's top 15 renewable energy consumption economies to achieve sustainable development. Panel time-series data from 1996 to 2018 is focused on concluding the study. Panel Smooth Transition Model is used to explore the nonlinear relationship and transition between the low and high regimes because of the nonlinear behavior. The study's results suggest a negative association between renewable energy consumption and ecological footprint and a positive relationship between natural resource rent and ecological footprint in both low and high regimes in the case of these 15 economies. It is highly recommended that the nations must shift their energy consumption policies towards renewable energy sources by investing in renewable energy technology and research for a more sustainable development., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study sought to identify individual-level determinants of COVID-19 vaccine hesitancy based on the Health Belief Model (HBM) and Theory of Planned Behavior (TPB). An online population-based survey was distributed in English and Spanish. Data were derived from 1208 U.S. adults (52% female; 38.7% minorities), 43.5% of whom reported vaccine hesitancy. Multivariable analysis revealed that unemployed individuals were more likely (OR = 1.78, 95% CI: 1.16-2.73, p = 0.009) and married (OR = 0.57, 95% CI: 0.39-0.81, p = 0.002) and higher income individuals (OR = 0.52, 95% CI 0.32-0.84, p = 0.008) were less likely to be hesitant. Individuals with greater perceived susceptibility to COVID-19 (OR = 0.82, 95% CI: 0.71-0.94, p = 0.006), who perceived vaccination as being convenient (OR = 0.86, 95% CI: 0.74-1.00, p = 0.047), and who afforded greater importance to cues to action from government (OR = 0.84, 95% CI: 0.74-0.95, p = 0.005), public health (OR = 0.70, 95% CI: 0.59-0.82, p < 0.001), and healthcare experts (OR = 0.59, 95% CI: 0.50-0.69, p < 0.001) were also less likely to be hesitant. Findings suggest that HBM and TPB constructs may be useful in informing strategies to improve COVID-19 vaccine uptake. Specifically, framing appeals based on perceptions of COVID-19 susceptibility, making vaccination convenient, and rebuilding trust through unified cues to action may help to overcome vaccine hesitancy.

Background: There is limited data on Pakistani dental students perceived competence in managing orofacial pain (OFP). This study aims to evaluate dental students self-perceived competence regarding the management of orofacial pain., Methods: This cross-sectional study was conducted in Karachi at randomly selected two public and four private dental schools. This survey was conducted online from November 2020 to December 2020 in six dental schools. A questionnaire link was sent to the 475 students. A chi-square test and independent-sample t-test were conducted to assess the frequency distribution and compare mean scores of knowledge, diagnosis, and management parameters., Results: Of the 475 students, 280 students filled the online survey leaving a response rate of 59%. A significant number of fourth-year students, 65 (51%, p = 0.005), feels knowledgeable regarding neuropathic pain compared to third-year students. The majority of the fourth-year students, 100 (78%, p = 0.010), feel comfortable managing intraoral pain. Almost all the students reported thinking that they need more knowledge related to five types of OFP. The fourth-year students had high mean scores related to knowledge, comfort in diagnosing and managing OFP categories., Conclusion: This study found that dental students perceived competence regarding orofacial pain management varies in relation to specific categories, being lowest for psychogenic pain., (© 2021. The Author(s).)

In a developing country like India, both availability and affordability of medical care are obstacles, leading to delay in seeking timely treatment. To reduce the cost incurred to the patients for strabismus surgery, we used half of a 6-0 polyglactin suture for performing common muscle weakening and strengthening procedures: a fixed and hang back recessions with plication and resection. We cut the 45-cm-long double-armed 6-0 polyglactin sutures in two halves, and with a modified approach, used one-half in each of two patients planned for monocular two horizontal muscles surgeries: fixed recession-plication and hang back recession-resection. By devising an intuitive manner of threading a single armed 22.5 cm suture we successfully carried out horizontal extraocular muscle surgeries on each of two patients of exotropia. We believe in the long run, this will reduce the cost to individual patients and sponsoring groups, and suggest that strabismus surgeons consider adopting this option., Competing Interests: None

Objectives: Current knowledge and research on diabetes and Ramadan form the basis for evidence-based clinical practice. In this context, we aimed to explore physicians' perceptions of current knowledge gaps about research fasting (RF), barriers to, and foreseeable directions for advancement of the field., Methods: We conducted an online survey of a convenience sample of 260 physicians from 27 countries. The survey questionnaire addressed three main domains: perceived current knowledge gaps and unmet needs in research about RF and diabetes, barriers to the conduct of research, and future directions for furthering the evidence in this field., Results: Majority of respondents (65.7%) were senior physicians in adult endocrinology/diabetes (45.9%) working at tertiary centers (65.2%). The majority (67.3%) reported seeing an average of 20+ patients with diabetes weekly and felt "very or fairly confident" in managing diabetes during RF (67.7%). The knowledge gaps identified were the management of high-risk patients with diabetes (54.1%), such as renal impairment (59.8%), and pregnancy (61.5%). The main barriers to research were lack of adequate funding to academic centers (75.7%) and lack of interest of institutions in the subject (64.6%). Future efforts should be directed at the conduct of large epidemiological studies (49.5%) or double-blinded, placebo-controlled clinical trials (48.6%) to address the former gaps. Research findings should be widely disseminated via hands-on workshops (recommended by 70.3% of respondents) or international conferences (61.2%)., Conclusions: There is a wide agreement regarding the knowledge gaps in the management of diabetes during RF. Future efforts should focus on addressing these critical deficiencies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To examine the benefit of telehealth over current delivery options in oncology practices without genetic counselors., Methods: Participants meeting cancer genetic testing guidelines were recruited to this multi-center, randomized trial comparing uptake of genetic services with remote services (telephone or videoconference) to usual care in six predominantly community practices without genetic counselors. The primary outcome was the composite uptake of genetic counseling or testing. Secondary outcomes compare telephone versus videoconference services., Results: 147 participants enrolled and 119 were randomized. Eighty percent of participants in the telehealth arm had genetic services as compared to 16% in the usual care arm (OR 30.52, p < 0.001). Five genetic mutation carriers (6.7%) were identified in the telehealth arm, compared to none in the usual care arm. In secondary analyses, factors associated with uptake were lower anxiety (6.77 vs. 8.07, p = 0.04) and lower depression (3.38 vs. 5.06, p = 0.04) among those who had genetic services. There were no significant differences in change in cognitive or affective outcomes immediately post-counseling and at 6 and 12 months between telephone and videoconference arms., Conclusion: Telehealth increases uptake of genetic counseling and testing at oncology practices without genetic counselors and could significantly improve identification of genetic carriers and cancer prevention outcomes., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The present work was aimed at investigating hydroethanolic leaf extracts of Cassia fistula for their antioxidant and pancreatic lipase (PL) enzyme inhibitory properties. The most active extract was selected to profile the phytoconstituents by UHPLC-QTOF-MS/MS technique. Among the tested extracts, the 80% hydroethanolic extract exhibited the maximum levels of total phenolic and flavonoid contents (TPC and TFC) with a contribution of 201.3 ± 2.6 mg of gallic acid equivalent per gram of extract (GAE/g extract), and 116.3 ± 2.4 mg of rutin equivalent per gram of extract (RE/g extract), respectively. The same extract also showed promising 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and PL inhibitory activity with an IC 50 (half maximal inhibitory concentration) of 30.5 ± 2.8 µg/mL and 17.31 ± 1.18 μg/mL, respectively. The phytochemical profiling of 80% hydroethanolic extract confirmed the presence of 23 metabolites of immense medicinal significance. Docking studies were conducted to investigate the potential interactions of compounds identified in the study. The docking study-based binding energy data and the interaction scheme both revealed the possible role of the identified compounds towards PL inhibitor. Moreover, energies of frontier molecular orbitals (FMOs), ionization potentials (IP), electron affinities (EA) and molecular electrostatic potentials (MEP) were also explored. The findings of the current work suggest that C. fistula is a promising natural source of antioxidant and antiobesity agents, which may be exploited to add pharmacological functionalities to food.

Background and Purpose: Virus mitigation strategies such as adhering to stay-at-home orders, practicing social distancing, and engaging in personal protective behaviors are central to slowing the spread of COVID-19. This population-based cohort study sought to identify sociodemographic characteristics and Health Belief Model factors that are associated with nonadherence to COVID-19 mitigation strategies with the goal of informing public health messaging campaigns., Methods: An online population-based survey was distributed via social media over an 8-week period from April 13, 2020, to June 8, 2020., Results: Data were derived from 2,222 adults (57% female; 40% racial/ethnic minorities). Univariate analyses revealed that men, younger aged (18-30 years) and unmarried adults, and noncollege educated individuals had lower levels of perceived threat, control, and knowledge about COVID-19 (p ≤ .001). Multivariable linear regression models further revealed that male gender was significantly associated with reporting lower levels of adherence to COVID-19 mitigation strategies (p < .001), and that higher levels of perceived threat, perceived control, and knowledge about how to keep oneself and others safe from COVID-19 were significantly associated with reporting higher levels of adherence to COVID-19 mitigation strategies (p < .01)., Conclusions: Findings suggest that public health appeals that target men, emphasize individual risk, and provide clear, consistent guidance on what individuals can do to decrease their risk for COVID-19 may be effective in motivating increased mitigation adherence., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Adrenocortical carcinoma (ACC) is a rare and highly aggressive tumor with a poor prognosis. The literature on prognosis from low-income or low-middle-income countries is limited and scarce. This study aimed to determine the clinical and histopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and the factors affecting ACC's prognosis. This was a retrospective study of patients that presented with ACC to the Shaukat Khanum Memorial Cancer & Research Center, Lahore, Pakistan, between January 2011 and May 2018. Information regarding demographics and clinical and histopathological variables were extracted and analyzed. Of the 25 subjects, 16 (64%) were female. The median age of the sample was 35 years (range; 21 - 72 years). Statistically significant associations were found between RFS and functional status of the tumor (p = 0.014), cortisol overproduction (p = 0.02), androgen excess (testosterone [p = 0.03] and dehydroepiandrosterone sulfate [DHEA SO4] [p = 0.004]), Ki-67 score (p = 0.03), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.01), and composite variable of disease (p = 0.004). The OS was found to have statistical associations with cortisol hypersecretion (p = 0.02), DHEA SO4 excess (p = 0.01), Modified Weis Score (p < 0.001), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.003), and composite variable of disease (p = 0.001). Linear regression (forward-type) analysis suggested that the functional status of the tumor and the disease recurrence index statistically predicted the variance in RFS and OS, respectively. Multiple clinical and histopathological variables appear to affect the prognosis of ACC. However, based on multivariable analysis, it appears that the functional status of the tumor and the composite variable of disease recurrence are predictors of RFS and OS, respectively., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Sohail et al.)

The Tamarix dioica ( T. dioica ) is widely used medicinal plant to cure many chronic ailments. T. dioica is being used to manage diabetes mellitus in traditional medicinal system; however, very little scientific evidence is available on this plant in this context. The current study involves the fractionation of crude methanolic extract of T. dioica using n -hexane, ethyl acetate, chloroform, and n -butanol. The screening for antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was carried out. The in vitro antidiabetic potential was assessed by measuring α-glucosidase inhibition. Total phenolic and flavonoid contents were also determined for each fraction. The metabolites were identified using highly sensitive and emerging 1 H-NMR technique. The results revealed the ethyl acetate fraction as the most potent with DPPH scavenging activity of 84.44 ± 0.21% and α-glucosidase inhibition with IC 50 value of 122.81 ± 2.05 µg/mL. The total phenolic and flavonoid content values of 205.45 ± 1.36 mg gallic acid equivalent per gram dried extract and 156.85 ± 1.33 mg quercetin equivalent per gram dried extract were obtained for ethyl acetate fraction. The bucketing of 1 H-NMR spectra identified 22 metabolites including some pharmacologically important like tamarixetin, tamaridone, quercetin, rutin, apigenin, catechin, kaempferol, myricetin and isorhamnetin. Leucine, lysine, glutamic acid, aspartic acid, serine, and tyrosine were the major amino acids identified in ethyl acetate fraction. The molecular docking analysis provided significant information on the binding affinity among secondary metabolites and α-glucosidase. These metabolites were most probably responsible for the antioxidant activity and α-glucosidase inhibitory potential of ethyl acetate fraction. The study ascertained the ethnomedicinal use of T. dioica to manage diabetes mellitus and may be a helpful lead towards naturopathic mode for anti-hyperglycemia.

Introduction: To analyse the safety and effectiveness of gliclazide modified release (MR) in adults with type 2 diabetes mellitus participating in Ramadan from three geographically and culturally different regions of the world included in the DIA-RAMADAN study., Methods: DIA-RAMADAN was a real-world, observational, international, non-comparative study. The global study population was divided into three regional subgroups, with data gathered at inclusion 6-8 weeks prior to Ramadan (V0), during Ramadan (4.5 weeks) and 4-6 weeks after Ramadan (V1). Primary endpoint was the proportion of patients reporting ≥ 1 symptomatic hypoglycaemic events (HE), which were collected using a patient diary along with other adverse events., Results: Patient numbers from the three regions were n = 564 (46.5%; Indian sub-continent), n = 354 (29.1%; Middle East) and n = 296 (24.4%; South-East Asia). Patient baseline characteristics, demographics, fasting habits and antidiabetic treatments varied between regions. There were similar proportions of symptomatic HE between regions, with no severe HE. Significant weight reductions were observed in all regions following Ramadan, along with reductions in HbA 1c and fasting plasma glucose., Conclusion: These real-world study data indicate that gliclazide MR is safe and effective for management of type 2 diabetes during Ramadan in all three regions studied as part of DIA-RAMADAN., Trial Registration: Clinicaltrials.gov identifier NCT04132934. INFOGRAPHIC.

Environmental degradation has severely affected the natural cycle of ecosystem. It's high time now and humans should execute strategies effectively to protect the further degradation. Initially, we need to understand the ways that might affect the environment. Thus, existing research is designed to explore the nonlinear association between financial development (FD) and carbon dioxide emissions (CO2) in the context of low-income countries by employing the yearly data of 1990-2016. The panel smooth transition regression model (PSTR) is applied, and the result confirmed that the nexus between the two variables are nonlinear. Moreover, it also shows that at a low regime, FD increases the CO2 emissions but as the economy of low-income states progress to the high regime, the association between the two variables becomes negative and significant. The study also confirms that FD can reduce CO2 emissions once it reaches a certain threshold point. Based on these findings, new insights are provided for the policymakers, and several policies are suggested to improve the environmental quality in low-income countries.

Objective: To compare the accuracy of three diagnostic tests in predicting difficult laryngoscopy using Cormack and Lehane grade as the gold standard., Methods: The cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from August 2014 to August 2015, and comprised patients who required endotracheal intubation for elective surgical procedures. The primary investigator used ratio of height to thyromental distance, upper lip bite test and the modified Mallampati test for assessing the airway correlated with laryngoscopic view based on Cormack and Lehane grading. Data was analysed using SPSS 19., Results: Of the 383 patients, 59(15.4%) were classified as difficult cases of laryngoscopy. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ratio of height to thyromental distance were 84.7%, 90.1%, 60.9%, 97%, 89.3%; and those the corresponding values for the upper lip bite test were 83.1%, 89.2%, 58.3%, 96.7% and 88.3%. The values for the modified Mallampati test were 30.5%, 84.3%, 26.1%, 86.9% and 79.9% respectively. The area under receiver-operating characteristic curve for the first two tests was significantly more than for the modified Mallampati test (p<0.01)., Conclusions: RHTMD and ULBT both are acceptable alternatives for prediction of difficult laryngoscopy as a simple, single bed-side test.

The study was aimed to improve the aqueous solubility of atorvastatin (AT) and ameliorate permeability of metformin (MT) in a combination formulation, improving their oral bioavailability. Several AT-MT loaded polyvinylpyrrolidone (PVP) and hyaluronic acid (HA) based nanoparticles were prepared through electrospraying method (ES-NPs), and tested for physicochemical, in vitro, and in vivo parameters. Among the trialed formulations, a sample consisting of AT, MT, PVP, and HA at the weight ratio of 1/6.25/3.75/15 furnished the most satisfying solubility and release rate results. It enhanced approximately 10.3-fold and 3.6-fold solubility of AT as compared with AT powder and marketed product (Lipilow) in phosphate buffer pH = 6.8, respectively. Whereas, permeation of MT was 1.60-fold and 1.47-fold improved as compared with MT powder and marketed product (Glucophage), respectively. As compared with Lipilow, AUC (0-∞) and C max of AT with ES-NPs in rats were improved to 3.6-fold and 3.2-fold, respectively. Similarly, as compared with Glucophage, AUC (0-∞) and C max of MT were improved to 2.3-fold and 1.8-fold, respectively. Thus, ES-NPs significantly enhanced the solubility of AT (a BCS class II drug) and permeability of MT (a BCS class III drug) and might be a promising drug delivery system for co-delivery of these drugs., (Copyright © 2021. Published by Elsevier B.V.)

Background: Unrelieved postoperative pain afflicts millions each year in low and middle income countries (LMIC). Despite substantial advances in the study of pain, this area remains neglected. Current systematic review was designed to ascertain the types of clinical trials conducted in LMIC on postoperative pain management modalities over the last decade., Methods: A comprehensive search was performed in June 2019 on PubMed, Cochrane Library, CINAHL Plus, and Web of Science databases to identify relevant trials on the management of postoperative pain in LMIC. Out of 1450 RCTs, 108 studies were reviewed for quality evidence using structured form of critical appraisal skill program. Total of 51 clinical trials were included after applying inclusion/exclusion criteria., Results: Results are charted according to the type of surgery. Eleven trials on laparoscopic cholecystectomy used multimodal analgesia including some form of regional analgesia. Different analgesic modalities were studied in 4 trials on thoracotomy, but none used multimodal approach. In 11 trials on laparotomy, multimodal analgesia was employed along with the studied modalities. In 2 trials on hysterectomy, preemptive pregabalin or gabapentin were used for reduction in rescue analgesia. In 13 trials on breast surgical procedures and 10 on orthopaedic surgery, multimodal analgesia was used with some form of regional analgesia., Conclusion: We found that over the past 10 years, clinical trials for postoperative pain modalities have evolved in LMIC according to the current postoperative pain management guidelines i.e. multi-modal approach with some form of regional analgesia. The current review shows that clinical trials were conducted using multimodal analgesia including but not limited to some form of regional analgesia for postoperative pain in LMIC however this research snapshot (of only three countries) may not exactly reflect the clinical practices in all 47 countries. Post Operative Pain Management Modalities Employed in Clinical Trials for Adult Patients in LMIC; A Systematic Review.

Extensive pesticides use is negatively disturbing the environment and humans. Pesticide bioremediation with eco-friendly techniques bears prime importance. This study evaluates the bioremediation of chlorpyrifos in soil using indigenous Bacillus cereus Ct3, isolated from cotton growing soils. Strains were identified through ribotyping (16s rRNA) by Macrogen (Macrogen Inc. Geumchen-gu, South Korea). Bacillus cereus Ct3 was resistant up to 125 mg L -1 of chlorpyrifos and successfully degraded 88% of chlorpyfifos in 8 days at pH 8. Bacillus cereus Ct3 tolerated about 30-40 °C of temperature, this is a good sign for in situ bioremediation. Green compost, farmyard manure and rice husk were tested, where ANOVA (P < 0.05) and Plackett-Burman design, results indicated that the farm yard manure has significant impact on degradation. It reduced the lag phase and brought maximum degradation up to 88%. Inoculum size is a statistically significant (P < 0.05) factor and below 10 6 (CFU g -1 ) show lag phase of 4-6 days. Michaelis-Menten model results were as follows; R 2  = 0.9919, V max  = 18.8, K s  = 121.4 and V max /K s  = 0.1546. GC-MS study revealed that chlorpyrifos first converted into diethylthiophosphoric acid and 3,5,6-trichloro-2-pyridinol (TCP). Later, TCP ring was broken and it was completely mineralized without any toxic byproduct. Plackett-Burman design was employed to investigate the effect of five factors. The correlation coefficient (R 2 ) between experimental and predicted value is 0.94. Central composite design (CBD) was employed with design matrix of thirty one predicted and experimental values of chlorpyrifos degradation, having "lack of fit P value" of "0.00". The regression coefficient obtained was R 2  = 0.93 which indicate that the experimental vales and the predicted values are closely fitted. The most significant factors highlighted in CBD/ANOVA and surface response plots were chlorpyrifor concentration and inoculum size. Bacillus cereus Ct3 effectively degraded chlorpyrifos and can successfully be used for bioremediation of chlorpyrifos contaminated soils.

The current investigation examines causal relation between PPP investment in energy sector and CO2 emissions in selected developing countries by using non-parametric causality in quantiles and linear granger causality techniques. Range of the data is from January 1998 to December 2016. Although results obtained by linear granger causality test does not report any causal relation between PPP investment in energy and CO2 emissions, but findings from non-parametric test show that non-linear relationship exhibit between variables. The non-parametric outcomes indicate that PPP investment in non-renewable energy in the selected countries contribute to carbon emissions and thus degrade environment. And therefore, the need is to divert PPP investment to renewable energy where it is more effective. This investigation provides valuable information to policy-makers in developing countries to think out of box and address pressing environmental issues.

Background: One of the leading long-term complications of type 2 diabetes mellitus (T2DM) includes renal dysfunction and urinary tract infections (UTI) which are considered to be prevalent in uncontrolled diabetes. Moreover, physiological factors like age, gender, duration of diabetes, other diabetic complications like neuropathy, autonomic neuropathy and glycosuria are also considered as predisposing factors for increased prevalence of UTI in diabetes which can be symptomatic or asymptomatic., Methods: This was a cross-sectional, multi-centre study including diabetic patients from 12 clinical sites spread across major cities of Pakistan. The inclusion criteria were adult Pakistani population of age between 18 to 75 years both genders and suffering from T2DM irrespective of duration. A detailed clinical history of the past 3 months was recorded and, biochemical investigations of blood samples were conducted. Urine culture analysis performed identified the type of pathogen present and was done only for asymptomatic patients., Results: A total of 745 type 2 diabetic patients were initially screened, out of 545 patients considered for final analysis 501 (91.92%) were negative and the rest 44 (8.08%) had positive urine culture. Female gender had a significantly higher proportion of positive urine culture (77.27%, p-value< 0.001). Body mass index and mean age had insignificant distribution among the two groups of positive and negative urine culture, with age 40-59 years having higher proportion (70.45%) in the positive group. Escherichia coli was detected in most of the positive samples (52.3%). All bacterial samples were found resistant to Ciprofloxacin., Conclusion: Diabetic Pakistani muslim female patients are identified to be at high risk of suffering from asymptomatic UTI and age more than 40 years is an important risk factor. Escherichia coli was the most common causative organism among people living in this geographical area.

This study examined individual-level determinants of self-reported changes in healthy (diet and physical activity) and addictive (alcohol use, smoking, and vaping) lifestyle behaviors during the initial COVID-19 lockdown period in the USA. A national online survey was administered between May and June 2020 that targeted a representative U.S. sample and yielded data from 1276 respondents, including 58% male and 50% racial/ethnic minorities. We used univariate and multivariable linear regression models to examine the associations of sociodemographic, mental health, and behavioral determinants with self-reported changes in lifestyle behaviors. Some study participants reported increases in healthy lifestyle behaviors since the pandemic (i.e., 36% increased healthy eating behaviors, and 33% increased physical activity). However, they also reported increases in addictive lifestyle behaviors including alcohol use (40%), tobacco use (41%), and vaping (46%). With regard to individual-level determinants, individuals who reported adhering to social distancing guidelines were also more likely to report increases in healthy lifestyle behaviors (β = 0.12, 95% CI 0.04 to 0.21). Conversely, women (β = -0.37, 95% CI -0.62 to -0.12), and unemployed individuals (β = -0.33, 95% CI -0.64 to -0.02) were less likely to report increases in healthy lifestyle behaviors. In addition, individuals reporting anxiety were more likely to report increases in addictive behaviors (β = 0.26, 95% CI 0.09 to 0.43). Taken together, these findings suggest that women and unemployed individuals may benefit from interventions targeting diet and physical activity, and that individuals reporting anxiety may benefit from interventions targeting smoking and alcohol cessation to address lifestyle changes during the pandemic.

Bovine tuberculosis (bTB) is a widespread zoonotic infection targeting the livestock sector, especially in developing countries, and posing a risk to humans and animal populations. Its recent prevalence in river buffaloes has been estimated as higher as 33.7%. In emergent countries like Pakistan, there is likeliness of human-livestock interfaces extensively and lacking of effective preventive measures that illustrate the risk of spreading the infection at a remarkable rate. The river buffalo ( Bubalus bubalis ) is an upkeep host of Mycobacterium bovis and is responsible for disease transmission among buffaloes and other livestock species. In this study, potential molecular biomarkers in the Interferon-gamma gene (IFNg) were identified after genomic screening of river buffaloes. Unique genomic loci in river buffalo proved the novelty of the genomic structure of this phenomenal animal but also highlighted its significance in natural immunity against the Mycobacterium . A total of eight single nucleotide polymorphisms were identified in the coding region of IFNg. The SNPs in the exonic region were all transitions, i.e., the conversion of purines to purines. These SNPs were analyzed for Hardy Weinberg Equilibrium, chi 2 test, gene diversity, and protein structural conformation. Pathway analysis in tuberculosis revealed that IFNg inhibits the antigen-presenting cells (APC) through JAK and STAT pathways. Network analysis of IFNg proteins in both species showed strong associations among the immunity-related proteins (interleukins, tissue necrosis factors) and receptors of interferons. The identified polymorphic sites might be novel-potentiated markers for the selection of animals with superior immune response against bTB and can be exploited as promising genomic sites for breeding the resistant animal herds to combat Mycobacterium infection in a long run., Competing Interests: There is no conflict of interest in any part of this manuscript., (Copyright © 2021 Maryam Javed et al.)

Background: Cycas circinalis leaves are used to treat diabetes mellitus in local medicinal systems without any scientifically proved information on their medicinal potential and phytochemicals. In this study, the total phenolic contents, total flavonoid contents, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and inhibitory effects on α-glucosidase and α-amylase were determined for optimized hydroethanolic leaf extracts. Secondary metabolites were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS). In vivo studies on diabetic albino mice were also carried out to evaluate the impact of the most active extract on their blood glucose levels., Results: The 60% ethanolic extract showed the highest extract yield (209.70 ± 0.20 g kg -1 ) and total phenolic (154.24 ± 3.28 mg gallic acid equivalent) and flavonoid (78.52 ± 1.65 mg rutin equivalent per gram dried extract) contents and exhibited the maximum DPPH scavenging activity (IC 50 = 59.68 ± 2.82 μg mL -1 ). The IC 50 values for inhibition of α-glucosidase (58.42 ± 2.22 μg mL -1 ) and α-amylase (74.11 ± 1.70 μg mL -1 ) were also significant for the 60% ethanolic extract. The untargeted UHPLC-QTOF-MS/MS-based metabolite profiling confirmed the presence of iridoid glucoside, gibberellin A4, O-β-d-glucosyl-4-hydroxy-cinnamate, 3-methoxy-2-phyenyl-4H-furo[2,3-h]chromen-4-one, kaempferol, withaferin A, amentoflavone, quercitin-3-O-(6″-malonyl glucoside), ellagic acid, and gallic acid. Plant extract at a dose of 500 mg kg -1 body weight reduced the blood glucose level by a considerable extent and also improved the lipid profile of diabetic mice after a 28-day trial., Conclusion: The findings revealed the medicinal potential of C. circinalis leaves to treat diabetes mellitus and provided the nutraceutical leads for functional food development. © 2020 Society of Chemical Industry., (© 2020 Society of Chemical Industry.)

Background: To evaluate the incidence and modifiable risk factors of delirium in surgical intensive care unit (SICU) of tertiary care hospital in a low-income and middle-income country., Methods: We conducted a single cohort observational study in patients over 18 years of age who were admitted to the SICU for >24 hours in Aga Khan University Hospital from January to December 2016. Patients who had pre-existing cognitive dysfunction were excluded. Intensive Care Delirium Screening Checklist was used to assess delirium. Incidence of delirium was computed, and univariate and multivariable analyses were performed to observe the relationship between outcome and associated factors., Results: The average patient age was 43.29±17.38 and body mass index was 26.25±3.57 kg/m 2 . Delirium was observed in 19 of 87 patients with an incidence rate of 21.8%. Multivariable analysis showed chronic obstructive pulmonary disease, pain score >4 and hypernatremia were strong predictors of delirium. Midazolam (adjusted OR (aOR)=7.37; 95% CI 2.04 to 26.61) and propofol exposure (aOR=7.02; 95% CI 1.92 to 25.76) were the strongest independent predictors of delirium while analgesic exposures were not statistically significant to predict delirium in multivariable analysis., Conclusion: Delirium is a significant risk factor of poor outcome in SICU. There was an independent association between pain, sedation, COPD, hypernatremia and fever in developing delirium., Level of Evidence: IV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The study intends to explore the following objectives: initially, to examine the non-linear connection between globalization, renewable energy consumption, and environmental degradation. Secondly, to evaluate the role of globalization in increasing or decreasing the carbon emission at the threshold level for different income countries. Panel smooth transition regression (PSTR) is an econometric technique that has been applied for estimation utilizing the data from 1995 to 2017. Results signify that the globalization and environmental degradation have non-linear connection and depends on different regimes. Moreover, on the basis of estimation, it is considered that the effect beyond the threshold level can be damaging, whereas less than the threshold level globalization is positively related to carbon emission. Hence, the inverted U-shaped relation denotes that at a specific level, the rise in globalization reduces carbon emission, but later, a specific level globalization accumulates carbon emission. Carbon emission has non-linear and regime-dependent relation to economic development and renewable energy consumption. The study provides recommendations that can assist policymakers.

Introduction: Less invasive and quicker surgeries have become common. We compared two conjunctival incisional approaches in strabismus, namely Follow standard paralimbal approach for (SPLA) and single-snip paralimbal (SSPLA)., Materials and Methods: Forty-four patients with horizontal strabismus qualifying for uniocular recession-resection surgeries were randomized to SPLA and SSPLA. SSPLA involved a single v-shaped incision, with the apex of the V near the limbus, and the limbs facing away: by pinching up the conjunctiva with a forceps and delivering the single snip with a spring scissors. We compared the postoperative grades of redness, congestion, chemosis, foreign body sensation, and drop intolerance at day 1, 2 weeks, and 6-8 weeks; scar visibility, as yes or no, at 6-8 weeks; success rates, considered to be within 10 prism diopters of orthophoria, at 6-8 weeks; and operation duration in minutes., Statistical Analysis: Statistical analysis was done using Mann-Whitney U -test, for inflammatory grades, Chi-square for proportions, and t -test for parametric measures. Statistical significance was set at P < 0.05., Results: On postoperative day 1, congestion ( P = 0.02), foreign-body sensation ( P = 0.04), and total inflammatory score ( P = 0.003) were statistically significantly favoring the SSPLA group. While at 2 weeks, only congestion ( P = 0.02) was found to be significantly less in the SSPLA group. There were no significant differences in the proportions of scar visibility (5/22 in the SPLA vs. 3/22 in the SSPLA) and success rate: 20/22 vs. 18/22. The SSPLA was quicker on an average by 6 min ( P < 0.001, 95% confidence interval: 3.2-8.7)., Conclusion: Compared to the SPLA, the SSPLA is quicker and results in lesser inflammation in the immediate postoperative period., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Oman Ophthalmic Society.)

BACKGROUND Apixaban is one of the newer direct oral anticoagulants (DOACs) being used to manage venous thrombosis. Skin toxicities are recognized adverse effects of the new DOACs, but are rare and usually associated with vasculitis. This report is of a 78-year-old man admitted to the hospital with pulmonary thromboembolism, who developed severe and extensive skin necrosis of both forearms 7 days after treatment with apixaban. CASE REPORT A 78-year-old man was admitted for pulmonary embolism and congestive heart failure exacerbation. He was started on therapeutic enoxaparin and diuresis. Later on, enoxaparin was substituted with apixaban. Seven days after starting apixaban, he suddenly developed skin changes that developed into skin necrosis on both forearms and the abdominal wall. A skin biopsy was not performed due to the high risk of bleeding. Skin necrosis was diagnosed based on clinical findings. A review of clinical data and the patient's medication profile did not reveal any other possible etiology or culprit medication. Clinical presentation and lab values were not consistent with infections or autoimmune etiologies. Apixaban was discontinued as it was perceived to be the likely cause of skin necrosis. The skin changes gradually improved within 1 week with supportive wound care, and the patient did not require a skin graft. The patient was discharged safely with subcutaneous low-molecular-weight heparin therapy. CONCLUSIONS This report shows that skin toxicity can be associated with apixaban and that with the increasing use of these newer DOACs, clinicians should be aware of these potential adverse effects.

Background: In Pakistan, drug promotion practices, ethical or unethical, have rarely been in the spotlight. We aimed to assess the perception and barriers of medical representatives (MRs) and doctors (MDs) regarding ethical promotion of pharmaceuticals in Pakistan., Methods: A cross sectional survey was conducted in seven major cities of Pakistan for 6-months period. Self-administered questionnaire was used for data collection. Logistic regression and five-point Likert scale scoring was used to estimate the perceptions and barriers., Results: Compared to national companies (NCs), the medical representatives (MRs) of multinational companies (MNCs) strongly believed that their companies follow World Health Organization (WHO) (OR; 5.31, p = 0.0005), International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) (OR; 6.45, p = 0.0005) and national codes of ethics (OR; 5.84, p = 0.0005). MNCs trained their MRs (OR; 6.68, p = 0.0005), provide accurate and valid scientific data (OR; 4.01, p = 0.007) with adequate system of accountability and controls on product samples (OR; 1.96, p = 0.047), while, NCs sponsor social or entertainment activities, seminars and conferences, and all sort of facilitation in form of gifts of their choice and clinic renovation for medical doctors (MDs). MDs perceptions were similar to MRs mentioned above, yet strongly agreed that companies offer cash payments or equivalents to MDs. The MRs of NCs/MNCs and MDs agreed/strongly agreed that no external accountability, profiteering, pressure on sale targets, job insecurity, condoning unethical promotion by high-ups' and business promotion by junior MDs were the predominant barriers., Conclusion: In conclusion, MRs of MNCs and MDs believed that MNCs follow certain codes of ethics in the promotion of pharmaceuticals, while NCs tend to be more profit oriented and even condone unethical promotion. All stakeholders, MRs, MDs and companies, might pose certain barriers, intentionally or unintentionally, in ethical promotion.

Purpose: Assessing visual acuity (VA) is the cornerstone of an ophthalmic workup and needs VA charts in a four or six meters space. The objective of this study was to compare the performance of distant VA (DVA) on one meter mini-logMAR (MLM) with a standard six meter logMAR (SLM) chart., Methods: We developed a MLM chart to be used at 1 m with +1.0 D spectacles, by reducing the SLM chart designed for 6 meters, to 1/6 th its size, using AutoCAD version 2014. On an initial cohort, we obtained DVA on the two charts by optometrist trainees, masked to the outcomes on the different tests. We performed regression and checked agreement between the two measurements. Subsequently, on a new cohort, we validated the performance of the MLM., Results: Of the 56 initial subjects, mean DVA with SLM was 0.44 ± 0.13 and with MLM was 0.45 ± 0.13; mean difference of -0.01 ± 0.02, 95%CI: 0.007 to 0.018; P < 0.0001 on paired t-test. There was a significant correlation: r = 0.99; r 2 = 0.98, P < 0.0001. On an average, DVA with MLM was less than a letter worse than with SLM. The regression formula obtained: SLM DVA = -0.1312 + 1.0014 x (MLM DVA). The validation study revealed no significant difference (P = 0.29) between the predicted standard DVA calculated by the regression formula and the actual standard., Conclusion: We suggest that we can deduce distance logMAR VA from a mini-logMAR chart as devised and used by us. This will take less space, be portable and allow congenial interaction with patients., Competing Interests: None

The study aims to analyze two objectives: first is to explore the non-linear relationship between tourism development, economic growth, urbanization, and environmental degradation, and also to analyze the threshold level of the contribution of tourism development on environmental degradation in top tourist arrival destinations. We applied the newly proposed econometric method panel smooth transition regression (PSTR) framework with two regimes on yearly panel data from 1995 to 2017. Findings suggest that the relationship between tourism development and environmental degradation is non-linear and regime dependent. Furthermore, the findings indicated that the relationship above the threshold level is negative and significant, while below the threshold, tourism development is positive and significant effect on environmental degradation. Tourism development and environmental degradation also exhibit the inverted U-shape relationship meaning that at a particular point, increase in tourism development increases in environmental degradation but after a particular point, increase in tourism development decreases the environmental degradation. The economic growth and urbanization also portray a non-linear and regime-dependent relationship with environmental degradation. The study assists policies and empirical information.

Introduction: Although social distancing may help contain the spread of COVID-19, the social isolation and loneliness it causes can heighten stress, contribute to unhealthy lifestyle behaviours and have deleterious effects on social relationships. This ongoing longitudinal cohort study aims to (1) characterise the psychological, social and health behavioural impacts of the COVID-19 pandemic over a 12-month period in the USA; (2) determine whether these impacts differ for certain subgroups based on sociodemographics and other individual-level factors; and (3) explore whether there are modifiable factors (eg, coping, social support) that moderate the effects of the pandemic over time., Methods and Analysis: Adults (aged ≥18 years) who were fluent in either English or Spanish were recruited via social media and invited to complete an online survey during the 8-week period from 13 April to 8 June 2020 (baseline). Follow-up surveys will be conducted 6 and 12 months after baseline. Data transformations, non-parametric tests or other alternative methods will be used when appropriate. Descriptive statistics and cross-sectional analyses will be performed. Longitudinal associations will be analysed using multilevel modelling with time-variant and time-invariant predictors of change in trajectory over the study period., Ethics and Dissemination: Research ethics approval was received from the Baylor College of Medicine Institutional Review Board (H-47505). Overall, this study will provide timely information that can be used to inform public health messaging strategies and guide development of assessment tools and interventions to support vulnerable individuals dealing with the long-term impacts of the COVID-19 pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Diabetes mellitus affects over 463 million individuals worldwide. Religious activities such as the Hajj pilgrimage have a major impact on patients with diabetes mellitus, including increasing the risk of hyperglycaemia and hypoglycaemia. This increased risk is due to dietary changes and intense physical activity during pilgrimage while being on antidiabetic medications. Approximately 20% of the pilgrims with underlying illnesses who visit Mecca are diabetic, and complications, such as diabetic ketoacidosis, nonketotic hyperosmolar state, and fatigue/unconsciousness due to hypoglycaemia, have been observed among these patients. Diabetic patients are also at a high risk for foot complications and infections. To avoid any aggravation of the diabetes, a complete biochemical evaluation of the patient must be conducted before Hajj, and the patients must be provided contextualized educational guidance to avert these potential health challenges. This counselling should include the importance of carrying with them at all time their relevant medical history, summaries of the current treatment regimen and emergency snacks. In addition, to reduce the risk of hypoglycaemia, the dosage of insulin should be reduced in selected patients by 20% and that of sulfonylurea should be reduced as needed. Basal insulin and glucagon-like peptide 1 receptor agonists are associated with fewer complications and can be preferentially prescribed. Those patients with type 1 diabetes can continue with the use of insulin pump with suitable education prior to Hajj. For the prevention of foot problems, the use of padded socks and well-fitting shoes is recommended along with an insistence on not walking barefoot. After Hajj, the patient must be followed up, and necessary investigations must be made along with readjustment of insulin dosage in those patients for whom it was reduced. Until the pandemic situation abates, all diabetic patients should avoid making the Hajj journey.