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The central theme of this enterprise is to find common features, if any, displayed by genetically different antimony (Sb)-resistant viscerotropic Leishmania parasites to impart Sb resistance. In a limited number of clinical isolates (n = 3), we studied the breadth of variation in the following dimensions: (a) intracellular thiol content, (b) cell surface expression of glycan having N-acetyl-D-galactosaminyl residue as the terminal sugar, and (c) gene expression of thiol-synthesizing enzymes (CBS, MST, gamma-GCS, ODC, and TR), antimony-reducing enzymes (TDR and ACR2), and antimonial transporter genes (AQP1, MRPA, and PRP1). One of the isolates, T5, that was genotypically characterized as Leishmania tropica, caused Indian Kala-azar and was phenotypically Sb resistant (T5-LT-SSG-R), while the other two were Leishmania donovani, out of which one isolate, AG83, is antimony sensitive (AG83-LD-SSG-S) and the other isolate, T8, is Sb resistant (T8-LD-SSG-R). Our study showed that the Sb-resistant parasites, regardless of their genotype, showed significantly higher intracellular thiol compared with Sb-sensitive AG83-LD-SSG-S. Seemingly, T5-LT-SSG-R showed about 1.9-fold higher thiol content compared with T8-LD-SSG-R which essentially mirrored cell surface N-acetyl-D-galactosaminyl expression. Except TR, the expression of the remaining thiol-synthesizing genes was significantly higher in T8-LD-SSG-R and T5-LT-SSG-R than the sensitive one, and between the Sb-resistant parasites, the latter showed a significantly higher expression. Furthermore, the genes for Sb-reducing enzymes increased significantly in resistant parasites regardless of genotype compared with the sensitive one, and between two resistant parasites, there was hardly any difference in expression. Out of three antimony transporters, AQP1 was decreased with the concurrent increase in MRPA and PRP1 in resistant isolates when compared with the sensitive counterpart. Interestingly, no difference in expression of the above-mentioned transporters was noted between two Sb-resistant isolates. The enduring image that resonated from our study is that the genetically diverse Sb-resistant parasites showed enhanced thiol-synthesizing and antimony transporter gene expression than the sensitive counterpart to confer a resistant phenotype.

Advances in applied machine learning techniques for neuroimaging have encouraged scientists to implement models to diagnose brain disorders such as Alzheimer’s disease at early stages. Predicting the exact stage of Alzheimer’s disease is challenging; however, complex deep learning techniques can precisely manage this. While successful, these complex architectures are difficult to interrogate and computationally expensive. Therefore, using novel, simpler architectures with more efficient pattern extraction capabilities, such as transformers, is of interest to neuroscientists. This study introduced an optimized vision transformer architecture to predict the group membership by separating healthy adults, mild cognitive impairment, and Alzheimer’s brains within the same age group (>75 years) using resting-state functional (rs-fMRI) and structural magnetic resonance imaging (sMRI) data aggressively preprocessed by our pipeline. Our optimized architecture, known as OViTAD is currently the sole vision transformer-based end-to-end pipeline and outperformed the existing transformer models and most state-of-the-art solutions. Our model achieved F1-scores of 97%±0.0 and 99.55%±0.39 from the testing sets for the rs-fMRI and sMRI modalities in the triple-class prediction experiments. Furthermore, our model reached these performances using 30% fewer parameters than a vanilla transformer. Furthermore, the model was robust and repeatable, producing similar estimates across three runs with random data splits (we reported the averaged evaluation metrics). Finally, to challenge the model, we observed how it handled increasing noise levels by inserting varying numbers of healthy brains into the two dementia groups. Our findings suggest that optimized vision transformers are a promising and exciting new approach for neuroimaging applications, especially for Alzheimer’s disease prediction.

Purpose: Increasing cytokines is one of the body responses to exercise. The effect of inflammation on chronic fatigue syndrome is obvious but its effect on exercise induced fatigue and recovery is unknown. Therefore, this study was performed in order to investigate the effects of 4-weeks of fish oil supplementation on peripheral fatigue induced by incremental exhausting exercise.Methods: For this purpose, 20 healthy men were selected and assigned in fish oil (FO) and corn oil (CO) groups and consumed six gr/day of supplements. Before and after supplementation, peak to peak M-wave amplitudes and maximal voluntary contraction (MVC) of their tibialis anterior muscle were evaluated before, immediately after exercise and also, after 20-min recovery.Results: The results of two-way analysis of the differences of M-wave results didn’t show significant differences between groups while significant differences observed in MVC of participants in response to supplementation and after exercise and recovery (P < 0.05). In addition, we observed lower perceived exertion after exercise and supplementation only in FO group (P < 0.05).Conclusion: These results showed that FO can improve muscular performance but this improvement is not due to the improvement in neuromuscular propagation (M-wave), while it can be as a cause of reduce in central fatigue or muscle contractile properties. However, complete understanding of the exact role of inflammation and FO on neuromuscular function still need more investigations.

Aditya Verma,1,2 Tommaso Bacci,3,4 David Sarraf,5 K Bailey Freund,3,4 SriniVas R Sadda1,2 1Doheny Eye Institute, Los Angeles, CA, USA; 2Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 3Vitreous Retina Macula Consultants of New York, New York, NY, USA; 4Department of Ophthalmology, New York University Grossman School of Medicine, New York, NY, USA; 5Stein Eye Institute, David Geffen School of Medicine at University of California, Los Angeles, CA, 90095, USACorrespondence: SriniVas R Sadda Email SSadda@doheny.orgAbstract: This review article summarizes the patho-anatomy of the vortex veins, the major drainage channels for the choroid, and describes the various pathways of diseases associated with vortex vein abnormalities. This report also details the technical advancements to image the vortex veins, such as ultra-widefield indocyanine green angiography, which are critical to elucidate the importance of the vortices in various retino-choroidal disorders. Future applications of these advanced imaging systems to better understand the role of the vortex veins in health and disease are also discussed.Keywords: choroid, optical coherence tomography angiography, pachychoroid disease, ultra-widefield imaging, vortex veins

Introduction The present study was conducted to investigate the efficacy of inclusion peppermint, thyme, cinnamon essential oils and also probiotic supplement (Protexin, Probiotics International Ltd., south Petherton, UK) when added to whole milk on performance, some blood parameters, skeletal growth, and nutrient digestibility of Holstein dairy calves.Material and Methods A total of 25 Holstein dairy calves (10 females and 15 males; 1–10 days) with 42 ± 8 kg of average birth weight were used in a completely randomized design in which calves were randomly assigned to one of five different dietary treatments including 1) control diet without inclusion of any milk essential oil supplementation, 2, 3 and 4) control diet + 40 ml (20 ml in the morning and 20 ml in evening meals) per day of peppermint, thyme, cinnamon essential oils, respectively and 5) control diet + 0.5 g per day probiotic Protexin. Calves were individually housed and bedded with straw that was replaced every day. Feed and water were available ad libitum throughout the experiment. Calves were fed colostrum for 3 days and then fed with 10% of their birth weight until 80 days of age. The rations were iso-energetic. Ruminal fluid samples were collected by esophagus tube after morning feeding at the end of study. Starter intake was recorded individually and daily. The amount of feed consumed daily was calculated throughout the experiment from the difference between the feed poured and the remaining feed. Edible samples from calves were kept in the freezer (-20 °C) for approximate analysis experiments. Performance was analyzed in repeated measures of the mixed model (PROC MIXED) including initial BW as a covariate (covariate structure: compound symmetry) with treatment, week and their interaction as fixed components and animal as random effect. Structural growth data were evaluated by GLM. Gender was considered a block but was not significant and drop from the model. A mixed-effects regression analysis, which included calf and period as random effects and treatment and time relative to weaning (before or after) as fixed effects, was then performed. Analytical model was Yij = µ + Ti + Aij + β (BWij - x) + eij, where Yij was each observation, μ was the overall mean, Ti was the fixed effect of treatment i, Aij was the random effect of calve j in treatment i, β (BWij - x) was using initial BW as a covariate and eij was residual error. Treatments means were statistically compared by the test of Duncan.Results and Discussion The results showed that starter intake was not affected by the experimental treatments (p> 0.05). However, calves consuming cinnamon essential oil and probiotic Protexin had higher daily weight gain than other essential oils and control group (p 0.05). Ruminal pH value was lower in calves were fed milk supplemented with different essential oils and Protexin than those fed control treatment (p 0.05). The concentration of triglyceride in calves fed cinnamon essential oil was higher than that of other essential oils as well as probiotic Protexin (p 0.05). However, body length and hip heights were higher in the calves fed cinnamon essential oil than the control group. The apparent digestibility of dry matter and organic matter in calves consumed cinnamon essential oil tended to increase than the control group (p=0.06 and p=0.07, respectively). The digestibility of crude protein and neutral detergent fiber was not affected by the type of essential oil and Protexin supplementation in Holstein dairy calves.Conclusion Overall, essential oils especially cinnamon and probiotic Protexin may improve growth and performance by increasing daily gain and feed efficiency of Holstein dairy calves.

Abstract Objective The purpose of this clinical trial was to examine the effect of omega-3 fatty acids (W-3 FAs), nanocurcumin and their combination on serum levels and gene expression of VCAM in patients with episodic migraine. Results In this study, 80 patients were randomly divided in to 4 groups to receive for 2 months. Both serum levels and gene expression of VCAM showed remarkable decreases after single W-3 and after combined W-3 and nanocurcumin interventions. However, a borderline significant change and no remarkable change were observed after single nanocurcumin supplementation and in control group, respectively. While a significant difference between study groups in VCAM concentrations existed, there was no meaningful difference in VCAM gene expression among groups. It appears that the W-3 and combined W-3 and nanocurcumin can relieve VCAM serum level and its gene expression in patients with episodic migraine. Moreover, the combination of W-3 with nanocurcumin might cause more significant declines in VCAM level in the serum of migraine patients than when W-3 is administered alone. Trial Registration: This study was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: NCT02532023.

PurposeMigraine, particularly with aura, has been associated with ocular and systemic ischemic complications, but there are limited data on the ocular vasculature in migraine. We used optical coherence tomography angiography (OCTA) to assess perfusion of the macula and optic nerve in migraine patients, with (MA) and without (MO) aura, compared to healthy controls (HC).MethodsWe recruited 15 MA (mean age 42 years), 12 MO (mean age 46 years), and 22 HC (mean age 39 years) participants from neurology and neuro-ophthalmology clinics. Participants underwent optical coherence tomography and 3 × 3 mm OCTA of the macula and optic nerve. Foveal avascular zone area was automatically measured using AngioVue software, and vessel density was calculated as blood vessel length divided by scan area (mm-1) after skeletonization of OCTA images.ResultsOn macular OCTA, MA participants had an enlarged foveal avascular zone area when compared with HC (0.300 ± 0.019 vs. 0.220 ± 0.066 mm2, P = 0.006). In addition, superficial foveal vessel density was decreased in MA participants when compared with MO participants (7.8 ± 0.31 vs. 9.3 ± 0.44, P = 0.04) and HC (7.8 ± 0.31 vs. 9.4 ± 0.21 mm-1, P = 0.002). On optic nerve OCTA, the MA participants had reduced superior peripapillary vessel density when compared with the MO participants (12.0 ± 0.45 vs. 14.0 ± 0.38 mm-1, P = 0.031) and HC (12.0 ± 0.45 vs. 14.1 ± 0.53 mm-1, P = 0.035). There were no significant differences between the MO and HC groups.ConclusionsMigraine with, but not without, aura was associated with foveal and peripapillary vascular decrements, which may possibly mediate increased risk of ocular and systemic vascular complications in these patients. OCTA could potentially be useful as a biomarker for migraine with aura.

Background: Drug utilization study plays an important role in promotion of rational use of medicines. Pain a multidimensional experience, personalized to each patient. Appropriate use of analgesics in postoperative pain can alleviate the suffering of the patients and also has significant social and economic benefits. Objective was to find out the pattern of analgesic utilization in hospitalized patients in the surgical ward. Methods: A prospective observational study was conducted among the hospitalized patients in the surgery ward for two months using a self-designed proforma. The case record form of the patients were reviewed and the relevant data were collected. Descriptive statistics like mean, frequency, percentage and standard deviation were calculated. Average number of analgesics per patient, percentage of drugs prescribed by generic name, percentage of encounters with an injection prescribed and percentage of drugs prescribed from the National List of Essential Medicines (NLEM) were also calculated using Statistical Package for Social Science version 22.0. Results: Out 160 patients, (56.25%) were females. Mean age (±SD) of the patient was 43.32 ± 16.3 years. Cholelithiasis (53.13%) was the most common diagnosis followed by inguinal hernia (12, 7.5%). Average number of analgesics per patient was 2.4. Sixty six (41.25%) patients were prescribed two types of analgesics. Ketorolac (39.32%) was the most common prescribed analgesic drug followed by Etoricoxib (36.46%). About 61.72% of the analgesics were prescribed in the injection form and 7.29% analgesics were from the NLEM.

Antigen processing and antigen-specific CD8 T cell activation form part and parcel of cell-mediated immunity to infections. Yet, several lacunae remain in our understanding of how antigen processing and CD8 T cell response are coordinated. In this study, using mouse bone marrow-derived dendritic cells (BMDC) as antigen-presenting cells and Ovalbumin (OVA)/DQ-Ovalbumin (DQ-OVA) as model antigen we demonstrated that Wnt5A signaling in BMDC supports antigen processing/presentation and concomitant CD8 T cell activation through regulation of actin and proteasome dynamics. Recombinant Wnt5A conditioning of BMDC and associated actin assembly facilitated DQ-OVA processing, which was inhibited by the proteasome inhibitor MG132. Moreover, Wnt5A depletion led to a significant reduction in OVA processing and presentation. Impaired DQ-OVA processing in Wnt5A depleted BMDC correlated with altered dynamics of both actin and the proteasome regulator PA28α-PA28β, and reduced association of DQ-OVA with actin and proteasome subunits. Inhibited OVA processing/presentation in the Wnt5A depleted BMDC also resulted in subdued activation of OVA-sensitized CD8 T cells in co-culture with the BMDC. In concurrence with these findings, we demonstrated reduced OVA processing and impaired CD8 T cell response to OVA immunization in Wnt5A heterozygous mice lacking a copy of the Wnt5A gene in comparison to the wild-type cohorts. Taken together, our results reveal a crucial requirement of Wnt5A signaling in antigen processing/presentation and CD8 T cell activation, thus unveiling a vital regulatory node of cell-mediated immunity, unidentified thus far.

Abstract Infection of an injectable soft tissue filler may involve fascial spaces and appears similar to an odontogenic abscess. This case report addresses a 32‐year‐old female patient with facial swelling who was referred to the department of endodontics for the treatment of a suspected odontogenic infection.

Honey is a natural sweet substance produced by Apis sp. from floral nectar or other plant parts which are gathered, modified and stored in the honeycombs by honeybees. The current research was aimed to analyze the quality parameters of locally available honey. Honey samples of Apis laboriosa and Apis mellifera were collected during spring of 2019 & 2021 and autumn 2021 from the Bagmati province, Nepal. Samples were analyzed their physicochemical and phytochemical properties. The result shows that, the pH was ranged between [4.467 0.0306 - 5.05 0.02], rheological studies showed Newtonian flow and pseudo-plastic type of Non-Newtonian flow, specific optical rotation was ranged between [(+) 5.75 0.4684 - (-) 12.71 0.234], specific gravity was ranged between [1.35 0.00017 - 1.409 0.00022], moisture content was ranged between [19.2% - 25%]. Secondary Metabolite screening showed the honey samples possesses flavonoids, saponins, glycosides, tannins, amino acids, protein and reducing sugar. Total phenolic content was ranged between [1.0427 - 6.86288] gm GAE/Kg honey while total flavonoid content ranged between [0.016755 - 0.353132] gm QE/Kg Honey. IC50 obtained from DPPH assay ranged between [649.6465 - 9867.1617] ppm. Properties and qualities of honey are affected by seasonal factors and various floral sources. The samples were in positive correlation between flavanoid content, phenolic content and their respective anti-oxidant potency.

High-risk human papillomaviruses (HPV) can be present and cooperate with Epstein–Barr virus (EBV) to promote the onset and/or progression of various cancers including cervical, breast, head and neck as well as colorectal. In this investigation, we explored the co-prevalence of high-risk HPV and EBV in 74 breast cancer tissues from Qatari women using polymerase chain reaction. We found that high-risk HPV and EBV are present in 48/74 (65%) and 36/74 (49%) of the cases, respectively. While we noted that the presence of HPV presence is associated with triple-negative breast cancer (TNBC) (p = .008), however, the presence of EBV did not correlate with any breast cancer subgroup. Moreover, our data revealed that high-risk HPV and EBV are co-present in 35/74 (47%) of the samples and their co-presence is significantly associated with tumor grade (p = .04) and tumor stage (p = .04). These data indicate that HPV and EBV are commonly co-present in breast cancer and their association could be linked with a more aggressive tumor phenotype. Thus, further investigations are essential to understand the underlying mechanisms of HPV and EBV cooperation in breast carcinogenesis.

Abstract This study suggests that tampon‐based coronal pulpotomy using a calcium silicate–based biomaterial can be a reliable approach for the treatment of vital primary molars with irreversible pulpitis.

College admissions leaders increasingly desire to incorporate non-cognitive factors like grit into admissions decisions. Consequently, we examined the validity of the short grit scale (Grit-S) using data collected on undergraduates attending 38 colleges. Using confirmatory factor analysis (CFA), we found that Grit-S does not possess adequate model fit; however, a modified version of the scale does possess this property. Using multi-group CFA, we also found that Grit-S is relatively invariant across multiple demographic groups. Next, we examined the concurrent validity of grit with students' engagement, perceived gains, time spent studying, and grades. These results confirmed previous research that most of the predictive power of grit is contained in its perseverance of effort, not consistency of interest, dimension.

Purpose: To describe remarkable choroidal thickness fluctuations corresponding to episodes of recurrent anterior uveitis with subretinal fluid development when exceeding a choroidal thickness threshold. Methods: A patient with pachychoroid pigment epitheliopathy and unilateral acute anterior uveitis of the left eye was evaluated over a period of 3 years with multimodal retinal imaging including optical coherence tomography. Longitudinal changes in subfoveal choroidal thickness (CT) were measured and correlated with episodes of recurrent inflammation. Results: Over the course of five recurrent episodes of inflammation in the left eye treated with oral antiviral and topical steroid therapy, subfoveal CT increased as much as 200 mm or more. By contrast, subfoveal CT in the fellow quiescent right eye was within normal limits and minimally changed throughout the follow-up. Increased CT occurred with each episode of anterior uveitis and decreased by 200 mm or more during periods of quiescence in the affected left eye. Subretinal fluid and macular edema developed with a maximum CT of 486 mm and spontaneously resolved when CT decreased after treatment. Conclusion: In eyes with pachychoroid disease, anterior segment inflammation may lead to marked increases in subfoveal CT and the development of subretinal fluid at a threshold thickness value. [ABSTRACT FROM AUTHOR]

• To review on development of magnesium and its alloys. • To investigate multiple biomedical applications of magnesium-based materials including orthopedic implants, cardiovascular implants, biodegradable surgical wires, staplers, and their anti-tumor activity. • To explore magnesium alloys functional properties such as biocompatibility, density, mechanical properties, corrosion resistance in biomedical environment, ductility, nontoxicity, host tissue response, and various anti-microbial strategies. • To peruse different surface modification and advanced manufacturing technologies of magnesium and its alloy to improve biomedical properties. • To survey magnesium and its alloy for biomedical applications and future direction. Magnesium (Mg) and its alloys have recently gained increasing attention in the biomedical field as promising biodegradable materials with harmless degradation products. Magnesium-based alloys have a wide range of biomedical applications because of their outstanding biocompatibility and unique mechanical properties. Widespread use of Mg-based biomedical devices eliminates the need for post-healing biomaterial removal surgery and minimizes the negative consequences of the implantation of permanent biomaterials, including stress shielding and undesired metal ion release in the body. This paper provides a literature review on the properties and manufacturing methods of Mg-based alloys for biomedical applications, including orthopedic implants, cardiovascular applications, surgical wires and staplers, and antitumor activities. Each application of Mg-based biomaterials is investigated from a biological perspective, including matching functional properties, biocompatibility, host tissue responses, and anti-microbial strategies, along with potential additive manufacturing technologies for these applications. Finally, an outlook is presented to provide recommendations for Mg-based biomaterials in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Primary dysmenorrhea is the commonest gynecological problem in females of childbearing age. The severity of dysmenorrhea catalyzed females to use home remedies or self-medication to relieve pain. Aims and Objectives: The study aimed to find out the severity of primary dysmenorrhea and self-management practices in medical and dental students. Materials and Methods: Female students who had painful menstrual cycles were included. A self-responding semi-structured questionnaire was used to collect information related to demographic, menstrual characteristics and self-management practices. The severity of primary dysmenorrhea was estimated by using the Verbal Multidimensional Scoring System (VMSS). Descriptive statistics were used to present the study findings using SPSS version 11.5. Results: Out of 143 students, mild severity of primary dysmenorrhea was more common 85 (59.4%), followed by moderate 44 (30.8%) and severe 14 (9.8%) dysmenorrhea. Over two-thirds 124 (86.7%) of respondents used home remedies alone or in combination with analgesic drugs 87 (60.8%). Mefenamic acid 44 (50.6%) was the most common self-medicated drug. Among the respondents who practiced self-medication, the majority had used drugs once a day 68 (78.2%), and more than half of them 57 (65.5%) took medication for one day, and 59 (67.8%) had insufficient knowledge about drug dose. Conclusion: Most of the respondents experienced the mild severity of primary dysmenorrhea. Home remedies were the most commonly used methods of self-management. The majority of the respondents did not receive medical consultation, but they were preferred self-medication. Encouragement for medical consultation along with the implementation of educational awareness programs to control morbidity associated with primary dysmenorrhea is recommended.

Background and Aim: Obesity is a clinical condition that affects the growth-related hormonal system, especially in adolescents. High-Intensity Intermittent Training (HIIT) might reduce such destructive effects. Methods & Materials: In this quasi-experimental research, among adolescent boys [age: 13-18 years, height: 154±8 cm, Body Mass Index (BMI): 27.05±1.4 kg/m²], 30 volunteer subjects were selected. The study participants were divided into 3 groups of short-term and long-term periodic exercises as well as controls. The short-term exercise group performed 9 bouts of 30 seconds with 150-second breaks between sessions; the long-term exercise group performed 4 bouts of 150 seconds with 240-second breaks between sessions 3 times a week for 8 weeks. Body composition and blood samples were obtained 48 hours before and after conducting the training protocol to measure the desired parameters. The changes of each index were analyzed by repeated-measures Analysis of Variance (ANOVA) at the significant level of P0.05). Conclusion: Short- and long-term HIIT have the potential to improve the growth hormone status and body composition of overweight adolescents.

Este artigo procura “ligar os pontos” da trajetória de Maria Luiza Lacerda no teatro de bonecos, entre memórias e documentos, de 1965 a 1989. A partir de entrevista e depoimentos da própria bonequeira e de algumas mulheres da família, o artigo procura homenageá-la por sua contribuição para o teatro de bonecos no Brasil. Da criação do grupo pioneiro de teatro de bonecos para festas infantis do Rio de Janeiro, Fura Bolo, ao grupo Revisãode experimentação em Teatro de Animação, Maria Luiza esteve presente e atuante no início da ABTB, experimentou linguagens e recursos inéditos e conviveu e criou com grandes nomes do teatro de bonecos no Brasil.

Optimizing the water resources operation, especially in the agricultural sector, which has the largest share in the water resources operation, is extremely important. Therefore, in this research, while introducing Whale, Gray Wolf and Crow Search Optimization Algorithms, their performance in the optimum operation of Golestan single-reservoir system Dam was evaluated with the aim of providing water demand for the downstream lands based on reliability, Reversibility, and vulnerability indices. In this optimization problem, the objective function was defined as the minimization of the total deficiency during the operation period. Meanwhile, the constraints of continuity equation, overflow, storage and reservoir release volume were applied to the objective function of the problem. Then, the results were compared with the absolute optimal value based on the nonlinear programming method obtained from GAMS software; finally, a multi-criteria decision-making model was developed to rank the optimization algorithms in terms of performance. The absolute optimal response obtained by the GAMS software based on the nonlinear programming method was 19.41. The results showed that the Gray Wolf algorithm performed better than the other algorithms in optimizing the objective function, so that the average responses in Gray Wolf, Crow Search and Whale algorithms were 92, 84 and 67% of the absolute optimal response, respectively. Furthermore, the Gray Wolf optimization algorithm performs better than the Whale and Crow Search algorithms in all parameters. In addition, the coefficient of variation of the responses obtained by the Gray Wolf algorithm is 2 and 1.43 times smaller than that in the Whale and Crow Search Algorithms, respectively. Finally, the results of the multi-criteria decision-making model showed that the gray wolf algorithm had the first rank, as compared to the other two algorithms studied in solving the problem of the optimal operation of the Golestan dam reservoir.

Introduction: Various diagnostic procedures are available to reach a diagnosis in case of oral lesions/conditions. Biopsy is one of the important tools for confirmatory diagnosis. Therefore, the dentist should have adequate awareness regarding oral biopsy procedures. Objectives: The objective of the study was to determine the awareness of oral biopsy procedure among dentists in Haryana. Materials and Methods: It was a cross-sectional study conducted among dentists in Haryana, India, using a 16-item close-ended questionnaire. Google Forms was prepared via docs.google.com/forms, and the link was sent to the participants via social media platforms such as WhatsApp and Viber. The filled questionnaires were extracted from Google Forms and exported to Microsoft Excel 2016. Descriptive statistics such as frequency and percentage were calculated to present the data using the Statistical Package for the Social Sciences software, version 21. Results: Out of 68, only 35.3% and 50% of the dental surgeons were aware that the removal of tissue by laser or electrosurgery can introduce artifacts or tissue distortion and punch biopsy generally produces few artifacts within the biopsied sample, respectively. Among the respondents, 35.3% and 11.8% responded that formaldehyde and normal saline also can be used for fixation of the biopsy sample. Conclusion: Awareness of oral biopsy technique was not up to date among majority of the dentists. Eminent steps should be taken to increase the awareness of biopsy procedure among them.

This report constitutes a first-in-man description of pressure–volume analysis in all 4 cardiac chambers before and after transcatheter aortic valve replacement. Pressure–volume analysis demonstrated that the hemodynamic consequences of valve replacement are chamber-specific and influenced by all aspects of the procedure (i.e., rapid ventricular pacing), not just valve deployment. (Level of Difficulty: Advanced.)

Abstract SHP2 is a ubiquitous tyrosine phosphatase involved in regulating both tumor and immune cell signaling. In this study, we discovered a novel immune modulatory function of SHP2. Targeting this protein with allosteric SHP2 inhibitors promoted anti-tumor immunity, including enhancing T cell cytotoxic function and immune-mediated tumor regression. Knockout of SHP2 using CRISPR/Cas9 gene editing showed that targeting SHP2 in cancer cells contributes to this immune response. Inhibition of SHP2 activity augmented tumor intrinsic IFNγ signaling resulting in enhanced chemoattractant cytokine release and cytotoxic T cell recruitment, as well as increased expression of MHC Class I and PD-L1 on the cancer cell surface. Furthermore, SHP2 inhibition diminished the differentiation and inhibitory function of immune suppressive myeloid cells in the tumor microenvironment. SHP2 inhibition enhanced responses to anti-PD-1 blockade in syngeneic mouse models. Overall, our study reveals novel functions of SHP2 in tumor immunity and proposes that targeting SHP2 is a promising strategy for cancer immunotherapy.

Purpose: To describe a case of peripheral retinal neovascularization and its possible etiological connection to comorbid obstructive sleep apnea. Observations: In this case report we describe a diabetic patient with obstructive sleep apnea who presented with bilateral peripheral retinal neovascularization but in the absence of any other evidence of diabetic retinopathy. Aside from confirmed nocturnal hypoxia and reasonably controlled diabetes mellitus, etiological investigation was otherwise unrevealing. Conclusions and Importance: In the absence of typical findings for diabetic retinopathy, nocturnal hypoxia due to obstructive sleep apnea may be a contributing factor in the development of peripheral retinal neovascularization. There may be a role for more vigilant OSA screening in patients with peripheral retinal neovascularization as treatment with positive airway pressure devices may reduce the retinal hypoxic burden.

Purpose: To describe a case of persistent placoid maculopathy (PPM) complicated by macular neovascularization (MNV) that developed in areas of prior choroidal ischemia as illustrated with sequential optical coherence tomography angiography. Observations: A 65-year-old man presented with unilateral decreased vision and creamy plaque-like macular lesions in both eyes (OU) upon fundus examination. Optical coherence tomography angiography (OCTA) demonstrated inner choroidal ischemia, corresponding to the placoid lesions, that persisted for several months consistent with a diagnosis of PPM. The patient was treated with immunosuppressive therapy, but the areas of inner choroidal ischemia gave rise to the development of MNV in each eye warranting serial antiVEGF therapy. Conclusions and Importance: OCTA is a useful tool for the diagnosis and follow up of PPM patients and can demonstrate areas of persistent inner choroidal ischemia that can drive the development of choroidal neovascularization.

Introduction: Human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and mouse mammary tumor virus-like virus (MMTV-like virus) can be present and contribute to breast cancer development and progression. However, the role of these oncoviruses and their crosstalk in breast cancer is still unclear. Methods: We explored the co-presence of high-risk HPVs, EBV, and MMTV-like virus in 74 breast cancer samples from Qatar using PCR. Results: We found the presence of HPV and EBV in 65% and 49% of our cancer samples cohort; 47% of the samples are positive for both oncoviruses. The MMTV-like virus alone was detected in 15% of the samples with no significant association with clinicopathological features. The three oncoviruses were co-present in 14% of the cases; No significant association was noted between the co-presence of these viruses and the clinicopathological features. Conclusion: Despite the presence of the oncoviruses, additional studies are necessary to understand their interactions in human breast carcinogenesis.

In this research, after introducing the Whale, Cuckoo search and fruit fly Multi-Objective Optimization Algorithms, their performance individually and compared to each other was evaluated to optimize the Golestan Dam reservoir operation policies with an approach to reduce downstream water demand shortages and flood storage volume management based on reliability, resilience, vulnerability and sustainability criteria. The results showed that the proposed algorithms act differently in optimizing the objective functions. So that the whale multi-objective optimization algorithm leads to better values of objective functions. Regarding to the optimization time, although, there are no significant differences between the cuckoo search and whale algorithms, both perform far better than the fruit fly algorithm and achieve much more convergence over time. When comparing the whale algorithm, as the most efficient algorithm, with the fruit fly algorithm, as the most inefficient algorithm, the model reliability and resilience indices increased by 44% and 52%, respectively, and its vulnerability decreased by 23%, indicating a better performance compared to the other algorithms. Therefore, Whale multi-objective optimization algorithm performs better and converges better than the other algorithms, and cuckoo search and fruit fly multi-objective algorithms ranked second and third.

Background: Limited energy intake with physical activity is effective to reduce health problems associated with obesity. It has been shown that PYY3-36 level increased after intense exercise. This study investigated effect of exercise therapy on appetite suppression and weight loss among obese and/or overweight women. Methods: There was a quasi-experimental with a pretest-posttest design, two groups (control-exercise) study. Study population was overweight or obese women with 20-34 years old and body mass index 27-34 kg/m2. 13 women were randomly assigned in 2 groups (exercise group with 8 weeks of aerobic exercise training (n=7) and control group (n=6)). Weight, waist circumference, hip circumference, lipid profile, cortisol and PYY3-36 were measured at baseline and end of the study. Results: In baseline of study, there was no significant difference across the groups in factors mean (P>0.05).In control group, after 8 weeks, there was no significant difference in variables.(P>0.05) However, In exercise group significant decrease was observed in BMI, WHR, PYY3-36, TG, CHOLESTROL(TC) and LDL, compared to control group (P

This work is dedicated to figuring out robust epoxy/magnetite/boron carbide (EP/Mag/B4C) composite for radiation attenuation at multiple applications related to nuclear installations, as well as restoration mortar for cracking developed in concrete biological shields. The mechanical properties (flexural, compressive, and impact strengths) and the physical properties (water absorption, porosity, and dry bulk density), each, have been performed to label the composite integrity for practical application. In practice, attenuation properties have been performed by using a collimated beam emitted from spontaneous fission 252Cf (100 μg) neutron source and neutron gamma spectrometer with stilbene scintillator. The pulse shape discrimination technique which would come of the zero cross over method was used to measure the fast neutron and gamma-ray spectra. Thermal neutron fluxes have been measured by using the thermal neutron detection system and the BF-3 detector. The attenuation parameters: precisely, macroscopic effective removal cross-sections ΣR (cm-1), macroscopic cross-sections Σ (cm-1), and total attenuation coefficients μ (cm-1) of fast and thermal neutrons and total gamma-rays respectively were evaluated using the attenuation relations. Also, the MCNP5 code and MERCSF-N program have been used to compute the parameters theoretically. When applicable, measured and calculated results were compared, and it tells us a comprehensive agreement.

Background and purpose — The COVID-19 pandemic has been recognised as an unprecedented global health crisis. This study assesses the impact on a large acute paediatric hospital service in London, evaluating the trends in the acute paediatric orthopaedic trauma referral caseload and operative casemix before (2019) and during (2020) COVID-19 lockdown. Patients and methods — A longitudinal retrospective observational prevalence study of both acute paediatric orthopaedic trauma referrals and operative caseload was performed for the first 6 “golden weeks” of lockdown. These data were compared with the same period in 2019. Statistical analyses included median (± median absolute deviation), risk and odds ratios as well as Fisher’s exact test to calculate the statistical significance, set at p ≤ 0.05. Results — Acute paediatric trauma referrals in 2020 were reduced by two-thirds compared with 2019 (n = 302 vs. 97) with a halving risk (RR 0.55) and odds ratios (OR 0.43) of sporting-related mechanism of injuries (p = 0.002). There was a greater use of outpatient telemedicine in the COVID-19 period with more Virtual Fracture Clinic use (OR 97, RR 84, p < 0.001), and fewer patients being seen for consultation and followed up face to face (OR 0.55, RR 0.05, p < 0.001). Interpretation — The impact of the COVID-19 pandemic has led to a decline in the number of acute paediatric trauma referrals, admissions, and operations during the COVID period. There has also been a significant change in the patient pathway with more being reviewed via the means of telemedicine to reduce the risk of COVID-19 transmission and exposure. More work is required to observe for similar trends nationwide and globally as the pandemic has permanently affected the entire healthcare infrastructure.

In this study, a solvothermal method at the temperature of 180 °C for 4 h was used for the synthesis of hydroxyapatite-reduced graphene oxide (HA-rGO) nanopowders by employing the nitrogen gas injection. To synthesize the powders, a solvent containing dimethylformamide, anhydrous ethanol, diethylene glycol, and water was used (1:1:1:2, respectively). Calcium nitrate tetrahydrate and diammonium hydrogenphosphate were used as calcium and phosphate precursors, respectively. The synthesized powders were consolidated by a high-frequency induction heat sintering method. The powders and sintered samples were then evaluated using X-ray diffraction, Raman spectroscopy, high-resolution transmission electron microscopy, Vickers indentation technique, and biocompatibility assay. The findings of this study showed that the final powders synthesized by the solvothermal method had calcium to phosphate ratio of about 1.67. The high frequency induction heat sintering method was suitable for consolidating these powders and exhibited a higher relative density than other methods. The mechanical properties of the nanocomposite were higher than those of pure HA. In biological experiments the difference of HA effect in comparison with the nanocomposite was not significant and both were biocompatible.

The application of optimization tools and techniques to operate the reservoir on a Multi-objective basis under the circumstances of climate change is unavoidable. The present study utilizes the Multi-Objective Farmland Fertility Optimization (MOFFA) algorithm to derive optimum rules on the operation of the Golestan Dam in Golestan province under circumstances of climate change. The two targets of reducing vulnerability as well as maximizing reliability under baseline conditions (from April 2006 to October 2018) and climate change conditions (from April 2021 to October 2033) have been formulated for such guidelines. Results revealed that under climate change circumstances, the river flow decreased by 0.17 percent of the baseline period, although the temperature was increased by 20% as well as the rainfall decreased by 21.1%. However, the extent of vulnerability variations in baseline and climate change was 16-45% and 10-43%, respectively. The range of reliability variations in baseline and climate change circumstances was 47-90% and 27-93%. The vulnerability has also been measured at 29 percent and 27 percent for baseline and climate change, respectively, with 75 percent reliability. The increase in release rates for climate change in comparison with baseline circumstances and higher modification of release rates from the reservoir to demand and stronger dam efficiency in changing circumstances showed the comparison of releases and the water shortage requirements for each of Pareto points.

The importance of the proper implementation of the Groundwater Revival Plan (GRP) as one of the key approvals of the Supreme Water Council has been doubled due to the escalation of the groundwater crisis in most of Iran's aquifers. Therefore, the implementation of GRP principles is the only way to overcome the crisis and the related challenges. In this study, the management crisis of Iran's groundwater resources is re-evaluated from the perspective of the administrative, social, and legal system with the GRP challenging approach. Then, the best -worst fuzzy multi - criteria decision model in Lingo9 software is developed by collecting the opinions of 23 GRP experts, based on three general criteria of change in administrative structure (C1), policy structure (C2) and modification of GRP legal structure (C3), which includes 18 sub-criteria. The results showed that timely and appropriate allocation of financial resources (S22), creating incentive packages for farmers to improve the cultivation pattern (S23) and creating serious efforts at all levels of management in the field of implementation, continuity, and removal of obstacles (S21) respectively with weights. 0.2247, 0.1098, and 0.0946 - with more than 40% of the total importance - occupy the first to third ranks.

Objectives: This is an open-label randomized control trial with a parallel assignment with single masking comparing patients undergoing coronary angiography via dorsal radial and classical radial access. Methods: Study done at three tertiary cardiac care centers for two years. A total of 970 patients were finally recruited for the study. Patients were randomly selected for dorsal radial artery access Group A (485 patients) and classical radial artery access Group B (485 patients) without any bias for age & sex. Results: On comparative assessment both techniques are found to be equal in terms of procedural success rate. While dorsal access was superior in terms of fewer incidences of forearm radial artery occlusion, radial artery spasm, less post-procedure persistence of pain, and hand clumsiness. In comparison to this, the number of puncture attempts and time to achieve post-procedure hemostasis is less in classical radial access. Conclusion: So both techniques have pros and coins and it is the discretion of interventionists to adopt which technique.

Background and purpose — The COVID-19 pandemic has been recognized as an unprecedented global health crisis. This is the first observational study to evaluate its impact on the orthopedic workload in a London level 1 trauma center (i.e., a major trauma center [MTC]) before (2019) and during (2020) the “golden month” post-COVID-19 lockdown. Patients and methods — We performed a longitudinal observational prevalence study of both acute orthopedic trauma referrals, operative and anesthetic casemix for the first “golden” month from March 17, 2020. We compared the data with the same period in 2019. Statistical analyses included median (median absolute deviation), risk and odds ratios, as well as Fisher’s exact test to calculate the statistical significance, set at p ≤ 0.05. Results — Acute trauma referrals in the post-COVID period were almost halved compared with 2019, with similar distribution between pediatric and adult patients, requiring a significant 19% more admissions (RR 1.3, OR 2.6, p = 0.003). Hip fractures and polytrauma cases accounted for an additional 11% of the modal number of injuries in 2020, but with 19% reduction in isolated limb injuries that were modal in 2019. Total operative cases fell by a third during the COVID-19 outbreak. There was a decrease of 14% (RR 0.85, OR 0.20, p = 0.006) in aerosol-generating anesthetic techniques used. Interpretation — The impact of the COVID-19 pandemic has led to a decline in the number of acute trauma referrals, admissions (but increased risk and odds ratio), operations, and aerosolizing anesthetic procedures since implementing social distancing and lockdown measures during the “golden month.”

Financial reports are the only source of internal information where provided by the board of directors to investors. The qualitative features of the provided information, which have a significant role in the optimal allocation of resources, largely depend on the readability of the information. With respect to this fact that the readability and quickly getting the message from a report is one of the essential qualitative features of presenting information, the current study aims to investigate the effect of this qualitative feature on the reaction of investors and increase in quality of companies’ voluntary disclosure. The readability of the board's report is measured using Fog model while the investors' reaction is measured trough the cumulative abnormal return and trading volume. The statistical population of the research includes: Companies listed on Tehran Stock Exchange during 1392-1396, which out of them 159 companies were selected to study using the systematic exclusion sampling method. To test the hypotheses, multivariate regression, panel data and Eviews software have been used. The results indicate a significant relationship between the reaction of investors and readability of the board's report, however, the relationship between the readability of the board's report and the reaction of investors to major economic-political news was not approved. Due to the ability of the current research to inform investors from the manner of providing information by the manager and the readability of the reports, the results of the research are applicable.

In this study, the performance of the algorithms of whale, Differential evolutionary, crow search, and Gray Wolf optimization were evaluated to operate the Golestan Dam reservoir with the objective function of meeting downstream water needs. Also, after defining the objective function and its constraints, the convergence degree of the algorithms was compared with each other and with the absolute optimal values obtained from GAMS nonlinear programming method (19.41). These values together with each algorithm optimization results were ranked using six multi-criteria decision-making methods of TOPSIS, VICOR, Linmap, Codas, ELECTRE and Simple Additive Weighting after obtaining the performance evaluation criteria of each algorithm (Reliability, reversibility, and vulnerability). Finally, integration methods (Mean, Borda, and Copland techniques) were used to evaluate the performance of decision models. The results showed that the mean responses of the gray wolf, the whale, differential evolutionary, and crow search algorithms were 1.08, 1.49, 1.29 and 1.19 times the absolute optimal response and the answers’ coefficient of variation obtained by Gray Wolf algorithm was 113.2, and 1.43 times smaller than the whale, differential evolutionary, and crow search algorithms, respectively. Moreover, all integration techniques indicated the superiority of the gray wolf algorithm. Then, the Crow search, Differential evolutionary, and whale algorithms were ranked second to fourth, respectively. On the other hand, the use of these methods in solving the problem of Golestan Dam reservoir optimization was considered appropriate due to the similarity of the results obtained from the integration techniques with the results of TOPSIS, VICOR and Linmap methods.

The Mediterranean flour moth, Ephestia kuehniella Zeller, 1879 (Lep.: Pyralidae) is a polyphagous pest that its eggs and larvae are used to rear some important biological control agents. In this study, the effect of three photoperiods including complete darkness, complete lightness and 14:10 (L:D) on life table parameters of E. kuehniella investigated, using diet containing a mixture of wheat flour (68%), wheat bran (29%) and 3% yeast was tested at temperature 25 ± 1°C and 65±5% RH. The results show that the intrinsic rate of increase (rm), finite rate of population increase (λ), the net reproductive rate (R0) and the mean generation time (T) in full darkness were 0.10 day-1, 1.116 day-1, 157.06 offspring and 45.98 days, respectively. Also, these mentioned parameters for full lightness and 14:10 (L:D) were 0.083 day-1, 1.087 day-1, 64.72 offspring ,49.73 days and 0.11 day-1, 1.117 day-1, 141.26 offspring, 44.59 days, respectively. The values of the intrinsic rate of increase (rm), finite rate of population increase (λ), the net reproductive rate (R0) and the mean generation time (T) in the photoperiod of 14:10 (L:D) were significantly shorter than those of other treatments. The results indicated that changing in photoperiod has noticable effect on life table parameters of Mediterranean flour moth and should be considered for mass rearing of this moth.