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Background COVID-19 is a pacing pandemic that affected health systems, economy, and social life in the whole world. Currently, there is no treatment for it, but the world is in a race that yielded, in a relatively short time than usual, several approved, promising vaccines in the middle of a storm of debates because of the speed of their production and approval. Objective This study assessed the willingness of Middle Eastern Arab publics to receive COVID-19 vaccines and investigated the factors behind any reluctance to receive them. Methods A self-administered questionnaire was distributed through social media applications in four Arab countries (Jordan, Saudi Arabia, Lebanon, and Iraq). Participants’ demographics, medical history, their experience with COVID-19, and their willingness to receive the available vaccines were obtained and analyzed. Results A total of 2,925 completed forms were included. Only 25% of the participants were willing to receive a vaccine while 33% were hesitant. Iraqis were the most willing to receive it while Jordanians were the least (35% and 17% of each country, respectively). Interestingly, 60% of the acceptors were ready to pay for the vaccine if not covered by governments. It was also found that American vaccines were preffered by 50% of the acceptors. However, 30% of acceptors were unsure of which vaccine is the best and 11% stated that any vaccine is good. Social media were the major source of information about COVID-19 and its vaccines. Finally, predictors of acceptance of the vaccines included living in Saudi Arabia and Iraq, being unmarried, having monthly income > $1,000, holding a medical degree, having high fear from COVID-19, feeling of being at risk of getting infected with COVID-19, and previous reception of influenza vaccine, whereas predictors of refusal included female sex and previous infection with COVID-19. Conclusion Middle Eastern Arabs are less likely to accept receiving the COVID-19 vaccines compared with non-Arabs. Health authorities in these countries are advised to intensify their awareness-raising activities about the vaccines while ensuring fair distribution of them.

Long noncoding RNAs (lncRNAs) have been recently recognized as key players of gene expression in cerebral pathogenesis. Thus, their potential use in stroke diagnosis, prognosis, and therapy is actively pursued. Due to the complexity of the disease, identifying stroke-specific lncRNAs remains a challenge. This study investigated the expression of lncRNAs HIF1A-AS2 and LINK-A, and their target gene hypoxia-inducible factor-1 (HIF-1) in Egyptian stroke patients. It also aimed to determine the molecular mechanism implicated in the disease. A total of 75 stroke patients were divided into three clinical subgroups, besides 25 healthy controls of age-matched and sex-matched. Remarkable upregulation of lncRNA HIF1A-AS2 and HIF1-α along with a downregulation of lncRNA LINK-A was noticed in all stroke groups relative to controls. Serum levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated-Akt (p-Akt), vascular endothelial growth factor (VEGF), and angiopoietin-1 (ANG1) as well as their receptors, malondialdehyde (MDA), and total antioxidant capacity (TAC) were significantly increased, whereas brain-derived neurotrophic factor (BDNF) levels were significantly decreased particularly in hemorrhagic stroke versus ischemic groups. Eventually, these findings support the role of lncRNAs HIF1A-AS2 and LINK-A as well as HIF1-α in activation of angiogenesis, neovascularization, and better prognosis of stroke, especially the hemorrhagic type.

Purpose The development and production of novel vaccine to prevent COVID-19 is an international imperative to human lives. For that purpose, clinical trials have to be carried out as per international ethical standards. The current study was undertaken to examine the willingness to participate in COVID-19 vaccine clinical trials and to determine factors that might affect their decision to participate. Patients and Methods A cross-sectional survey study was carried out among the public in Jordan. During the study period, a convenience sample of adults (aged 18 years or above) were asked to participate via an online self-administered survey that was designed to evaluate the willingness to participate in COVID-19 vaccine clinical trials and to determine factors affecting their decision to participate. Results Results showed that, among participants (n=1,287), 36.1% reported to be willing to participate in clinical trials of the vaccine. Additionally, a lower percentage (18.1%) were willing to allow their children to participate. Motivators that encourage participation were the desire to return to normal life (73.2%), followed by the desire to help in finding a treatment for COVID-19 infection (68.1%). Barriers towards the participation were not wanting to be challenged by the virus (54.7%), fear (40.7%), lack of time (40.4%), and mistrust in pharmaceutical companies (38.9%). Finally, results showed that higher educational level was associated with lower willingness to participate (P=0.001), whereas having a previous participation in clinical studies is associated with a significantly higher willingness to participate in COVID-19 vaccine clinical trials (P

Background Pediatric pharmaceutical care is a new concept in the pharmacy profession. In Jordan, the knowledge of pediatric pharmaceutical care is limited, which may have negative consequences on pediatric pharmaceutical care and treatment efficacy and safety. Objectives The main objective of the present study is to assess parental needs for pediatric pharmaceutical care services and explore their current experiences of pharmaceutical services provided to their children. Setting Parental Facebook Groups in Jordan. Methods A descriptive, cross-sectional survey was designed and distributed online via Social Media networks, mainly Facebook. The validated survey contained 4 main sections addressing different themes related to pediatric pharmaceutical care services including: (1) parental perception of pediatric pharmaceutical care services. (2) Parental needs, wants, and expectations from the pharmacist when providing care to their children. (3) Parental awareness about pediatric pharmaceutical care, and parental satisfaction with current pediatric pharmaceutical care. Respondents who agreed to complete the survey signed and electronic informed consent form to access it. Main outcome measure The main outcomes measure was parental need for pediatric pharmaceutical care services. Results A total of 1104 respondents took part in the study. Of those 71% were female and 44% were 31-40 years old. The majority of respondents (78%) were not familiar with the pediatric pharmaceutical care term. The calculated overall mean perception score was 63.4%. The majority of respondents (89%) reported to need pediatric pharmaceutical care and the mean need score was 71.7%. Only 10.5% agreed/strongly agreed that their children were offered good pediatric pharmaceutical care services and respondents has a total mean satisfaction score of 65.7%. Conclusion The majority of the respondents reported that they need pharmaceutical care services for their children. Pharmacists in Jordan have to develop their role to incorporate pediatric pharmaceutical care services in their practice.

Background Tuberculosis remains a major health problem in the less developed nations and is now a major health problem in developed countries, owing to the emergence of human immunodeficiency virus (HIV) infection and (AIDS). However, despite the availability of effective chemotherapy, patient noncompliance with regimens is the most common reason for therapeutic failures. The aim of this study is to describe the cytological features of drug defaulters on lymph node fine-needle aspiration cytology (FNAC). Objective Due to the common problem of drug defaulters in developing countries like India, we had carried out a study to see the cytological features of drug defaulters on FNAC of the lymph node. Method Three hundred fifty tuberculosis cases, diagnosed based on Mantoux (Mx) test, acid-fast bacilli and/or culture, were followed up for drug compliance by cervical lymph node FNAC. Result Forty cases were found to be drug defaulters on detailed and meticulous follow-up. These patients were found to have splintered epithelioid cell granuloma with some viable epithelioid cells enmeshed in fibrous tissue elements. Other findings were degenerating epithelioid cells with or without surrounding eosinophilic infiltration and leaching of the degenerating lymphoid and epithelioid cells. Conclusion Lymph node FNAC can be used to identify tubercular drug defaulters, which may be time consuming and/or expensive by culture or other ancillary means.

One of the most lethal malignancies worldwide is colorectal cancer (CRC). Alterations in various signalling pathways, including PI3K-mTOR and NF-κB, have been reported in CRC with subsequent dysregulation of proliferation, apoptosis, angiogenesis and, questionably, autophagy processes. BEZ-235 (dactolisib) is a dual PI3K-mTOR inhibitor with potent anti-tumour activity. However, the observed toxicity of BEZ-235 necessitated the termination of its clinical trials. Hence, we aimed to evaluate the potential long-lasting anti-carcinogenic effects of adding diosmin (DIO, a natural NF-κB inhibitor) to BEZ-235 in HCT-116 CRC cells. The median inhibitory concentrations (IC50s) of BEZ-235 and/or DIO were evaluated in the HCT-116 CRC cell line. Caspase-3 activity was assessed colorimetrically, and p-Akt, NF-κB, CD1, VEGF and LC3B levels were assessed by ELISA. Additionally, LC3-II and P62 gene expression were assessed using qRT-PCR. The observed CIs (combination indices) and DRIs (dose reduction indices) confirmed the synergistic effect of DIO and BEZ-235. Co-administration of both drugs either in combination-1 (1 μM for BEZ-235, 250 μM for DIO) or in combination-2 (0.51 μM for BEZ-235 + 101.99 μM for DIO) inhibited the PI3K/Akt/mTOR/NF-κB axis, leading to the induction of apoptosis (via active caspase-3), and the inhibition of proliferation marker (CD1), angiogenesis marker (VEGF), autophagy protein (LC3B) and altered effects on LC3-IIandP62 gene expression. Our results reveal the synergistic chemotherapeutic effects of DIO combined with BEZ-235 in the HCT-116 CRC cell line and encourage future preclinical and clinical studies of this combination with reduced BEZ-235 concentrations to avoid its reported toxicity.

Objective In Jordan, research ethics have been subject to increasingly formal regulations and structuring. Recently the Ministry of Higher Education and Research Published the National Research Code of Ethics. However, little is known about the awareness of pharmacology researchers of this code and the extent of its applicability to their research. Methods Purposeful sampling through institutions’ websites was used to identify staff members with excellent profiles from 20 Faculties of Pharmacy in Jordan. After obtaining the required approvals, in-depth interviews were conducted, recorded, transcribed, and analyzed using NVivo 11 Software. The interviews followed a previously prepared and validated interview guide that covered various aspects of education, research, and training. Key findings Eighteen members of staff agreed to take part in the study. Qualitative analysis revealed three main themes each concerning respondents’ awareness of the National Code of Research Ethics in Jordan. The emerging themes were: the lack of awareness regarding the code of ethics, the need for clear guidelines for pharmacology research in Jordan, and the need for further workshops and training courses for pharmacology researchers. Conclusion This study highlights a lack of awareness regarding the presence of the National Research Ethics Code among pharmacology researchers in Jordan. This might have negative implications on medical research. It was thought that the code of ethics should be incorporated in postgraduate pharmacy education, training courses for pharmacy researchers, and workshops for pharmacy academic staff., Awareness, National Research Ethics Code, Qualitative Study, Pharmacology, Pharmacy Researchers

Papillary lesions of the breast include a broad spectrum of entities, many of which pose a diagnostic challenge for the pathologist. Papillary Carcinoma is a rare malignancy of the breast accounting for 0.5- 2% of all breast carcinomas. It occurs more frequently in post-menopausal women over the age of 60. The most common presentation is a painless, mobile mass with bloody nipple discharge. Mammography typically shows a large circumscribed mass with an irregular or nodular contour.We present a case of a 42-year-old-woman with a painless lump in the right breast for 11 months, diagnosed as encapsulated papillary carcinoma of breast with in-situ component. Keywords: Breast, Encapsulated papillary carcinoma, Histopathology.

The manner in which white adipose tissue (WAT) expands and remodels directly impacts the risk of developing metabolic syndrome in obesity. Preferential accumulation of visceral WAT is associated with increased risk for insulin resistance, whereas subcutaneous WAT expansion is protective. Moreover, pathologic WAT remodeling, typically characterized by adipocyte hypertrophy, chronic inflammation, and fibrosis, is associated with insulin resistance. Healthy WAT expansion, observed in the “metabolically healthy” obese, is generally associated with the presence of smaller and more numerous adipocytes, along with lower degrees of inflammation and fibrosis. Here, we highlight recent human and rodent studies that support the notion that the ability to recruit new fat cells through adipogenesis is a critical determinant of healthy adipose tissue distribution and remodeling in obesity. Furthermore, we discuss recent advances in our understanding of the identity of tissue-resident progenitor populations in WAT made possible through single-cell RNA sequencing analysis. A better understanding of adipose stem cell biology and adipogenesis may lead to novel strategies to uncouple obesity from metabolic disease.

Activated beige adipocytes have therapeutic potential due to their ability to improve glucose and lipid homeostasis. To date, the origin of beige adipocytes remains enigmatic. Whether beige cells arise through de novo differentiation from resident precursors or through reprogramming of mature white adipocytes has been a topic of intense discussion. Here, we offer our perspective on the natural origin of beige adipocytes in mice. In particular, we revisit recent lineage-tracing studies that shed light on this issue and offer new insight into how environmental housing temperatures early in life influence the mode of beige adipocyte biogenesis upon cold exposure later in life. We suggest a unified model in which beige adipocytes (UCP1+ multilocular cells) in rodents initially arise predominantly from progenitors (i.e., de novo beige adipogenesis) upon the first exposure to cold temperatures and then interconvert between “dormant beige” and “active beige” phenotypes (i.e., beige cell activation) upon subsequent changes in environmental temperature. Importantly, we highlight experimental considerations needed to visualize de novo adipogenesis versus beige cell activation in mice. A precise understanding of the cellular origins of beige adipocytes emanating in response to physiological and pharmacological stimuli may better inform therapeutic strategies to recruit beige adipocytes in vivo.

Pregabalin is an anticonvulsant that has an abuse potential. The aim of this study was to investigate abuse/misuse of pregabalin in Jordan from the perspective of community pharmacists. A cross-sectional survey using a structured questionnaire was delivered to a sample of community pharmacies. Self-reported method was used to fill the surveys. A total of 151/205 questionnaires were completed (response rate = 74.1%). A total of 132 respondents (87.4%) reported cases of pregabalin abuse in their pharmacies. Less than half of the respondents (n = 69; 45.7%) indicated that pregabalin requests were, in most of the cases, not accompanied by prescriptions. More than half of the sample (55.8%) noticed an increased pattern of pregabalin abuse/misuse during the last six months. The study underscored the need for regulatory efforts and pharmacovigilance to manage pregabalin abuse, along with a pharmacist and patient education at a community pharmacy level.

Aims of the study This study aims to determine females' views, experiences and attitudes regarding the caesarean section (CS) and to explore the factors that increase the prevalence of CS in Jordan. Design This is a cross-sectional study using a questionnaire that was distributed electronically through social media websites. Study participants included 1005 females with a history of at least one CS. Awareness, experiences about CS, complications and reasons for performing CS were investigated. Settings The participants were recruited from all Jordan cities by social media and emails. Findings Most of the respondents stated that the source of their knowledge about CS was from the internet (36.2%) followed by family and friends (31.6%). The majority of respondents were satisfied with their CS experience (72.8%). More than half of the participants (56.9%) reported that CS carries no risk for infants. About 53% of respondents stated that the most common reason leading women to choose to give birth via CS is the fear of labour pain. However, the majority of the respondents disagree with performing CS under maternal request (59.2%). Conclusions and implications This study indicated that Jordanian females do not have reliable sources of information about CS. This leads to lower awareness of CS and its complications, and, as expected, CS is more likely to be performed by privately insured women.

Background Investigating temperament has been a multi-subject exercise that attempts to determine the contribution of temperament to additional measurable phenomena like behavior. The existing research not only evaluates temperament as a variable with the ability to influence additional characteristics but has included interventions that can result in adapted outcomes. Develop an Arabic translation of the Infant Characteristics Questionnaire (ICQ). Purpose Examine the psychometric properties of the translation and establish modified criteria for evaluating the questionnaire. Methods Cross sectional design was used. Translation of the ICQ was achieved through translation/back translation. The population that used the ICQ translation on convenience sample of 40 Arabic-speaking women with children between the ages of 3–12‐months old; this same group also completed a demographic survey. Results The internal consistency of the translated instrument was almost equivalent to or higher than the reported from the United States (US) review. The alpha coefficients calculated from subscales varied between .47 and .87. Conclusion This research study described the translation of the ICQ into the Arabic language for use in the research and clinical setting. The ICQ is a useful tool for evaluating infant difficulty by describing and summarizing parents’ ratings., Highlights • In nursing for infants, the parent-child, is very significant and is often understood as bilateral, correlative and interdependent. • Infant temperament is described as regularities in responding to different situations, and reflect a infant's behavioral characteristics. • The information gathered from infant-temperament questionnaires can help health care professionals inform parents of interventions for improving infant temperament.

The Center for Disease Control and Prevention and the World Health Organization issued a practical approach and Global Action Plan to control the threatening emerging antibacterial resistance. One of the main basis of this plan is the Antimicrobial Stewardship Program (ASPs). This study aimed to evaluate community pharmacists’ awareness and perception towards antimicrobial resistance and ASPs in Jordan. Thus, a qualitative study was conducted through in-depth interviews with twenty community pharmacists. Convienience sampling was used in the study. Qualitative analysis of the data yielded four themes and eleven sub-themes. All the respondents showed good understanding about the causes of antimicrobial resistance. The most important causes reported by them was the non-restricted prescription of antimicrobials. Most of the pharmacists believed that they are competent to provide ASPs, however, they believed that there are several barriers against the implementation of ASPs in community pharmacies in Jordan. Barriers demonstrated by the pharmacists, including organizational obstacles, resources obstacles, and personal obstacles. As a conclusion, this study revealed several barriers against the implementation of ASPs in community pharmacies in Jordan. Incorporating ASPs in the community pharmacy settings requires proper pharmacist training, several academic disciplines team efforts, and good pharmacy practice of antimicrobial guidelines.

BACKGROUND: Community pharmacists play a pivotal role in healthcare worldwide Their role became more critical during the COVID-19 pandemic This study aims to investigate the community pharmacists' preparedness and responses to the COVID-19 pandemic, and how efficiently they were prepared to contain and prevent the spread of infection METHODS: An online questionnaire was distributed to community pharmacists in Saudi Arabia, Lebanon, and Jordan through social media platforms A scoring system was developed to measure their level of adherence to the preventive measures of the global infection RESULTS: The total included responses were 800 Around 44% of the pharmacists reported spending less than 15 minutes/day reading about COVID-19 updates Although more than half of them were reviewing official sites, 73% of them were also retrieving information through non-official channels Additionally, almost 35% of them were directly contacting customers without physical barriers, 81% reported encountering infected customers, and 12% wore the same facial masks for more than a day Moreover, 58% of the pharmacies reported the absence of door signs requesting infected customers to declare the infection, 43% of the pharmacies were not limiting the number of simultaneous customers, and 70% were not measuring customers' temperatures prior to entry Collectively, the mean total score of applied protective measures was 10 12 ± 2 77 (out of 17) CONCLUSION: The level of preparedness of the community pharmacies in these three Middle Eastern countries was not adequate for facing the COVID-19 pandemic Health authorities in these countries should closely monitor their adherence to the protective guidelines

BACKGROUND: COVID-19 is a pandemic disease with a significant threat to public health. Public knowledge and perceptions significance in tackling pandemics have been evidenced in the previous research. This study aimed to explore public perceptions about pharmacists' educational and prescribing role, and the medication delivery service provided during COVID-19 outbreak. METHOD: A cross-sectional study was conducted among the general population of Jordan using a convenient sampling technique for ten days (15-25 May 2020). Data was collected from 578 participants who agreed to fill the questionnaire, which was distributed online. The questionnaire items were piloted using face validity and reliability. RESULT: Participants showed a positive perception about the impact of pharmacists and pharmacy services provided during COVID-19 outbreak. More than half of the participants (61.1%) believed that pharmacists could prescribe over the counter medications, and only 15.7% believed that pharmacists could prescribe both over the counter and prescribed medications. Linear regression was performed to assess the factors that affect the participants' perception of pharmacists' prescribing and educational role and delivering medication during COVID-19. Females have lower perception scores towards medication delivery services compared to males (P-value= 0.008). However, male participants, those aged less than 50 years, those with postgraduate degrees, and those from non-medical profession showed a significantly higher perception score towards the impact of pharmacists and pharmacy services provided during COVID-19 outbreak compared to others (P-value

AIMS OF THE STUDY The purpose of this study was to assess pharmacists' knowledge and attitude towards early detection of colorectal cancer (CRC) in Jordan and to explore potential predictor variables of such knowledge and attitude. METHODS USED TO CONDUCT THE STUDY An electronic, self-reported questionnaire was used to collect data about demographics, knowledge and attitude regarding early detection of CRC. Both content and face validity were tested in a panel of experts. The participants' responses were analysed using descriptive statistics and multiple linear regressions. RESULTS OF THE STUDY The 352 pharmacists (78% females, 94% Jordanian) had a median age of 28 years and graduated mostly (83%) from public universities. Surprisingly, 90% were not able to identify carcinoembryonic antigen (CEA) as a non-accurate diagnostic method and almost one-third did not identify the correct screening tests. On a scale of 5, the majority of participants (59%) had moderate knowledge scores (3 or 4) in case scenarios. The median knowledge Percent of Maximum Possible (POMP) score was 67% and higher scores were associated with more years since graduation, pharmacists with MSc degree and higher, working in urban areas, studying oncology course and received oncology training (P

Adiponectin is essential for the regulation of tissue substrate utilization and systemic insulin sensitivity. Clinical studies have suggested a positive association of circulating adiponectin with healthspan and lifespan. However, the direct effects of adiponectin on promoting healthspan and lifespan remain unexplored. Here, we are using an adiponectin null mouse and a transgenic adiponectin overexpression model. We directly assessed the effects of circulating adiponectin on the aging process and found that adiponectin null mice display exacerbated age-related glucose and lipid metabolism disorders. Moreover, adiponectin null mice have a significantly shortened lifespan on both chow and high-fat diet. In contrast, a transgenic mouse model with elevated circulating adiponectin levels has a dramatically improved systemic insulin sensitivity, reduced age-related tissue inflammation and fibrosis, and a prolonged healthspan and median lifespan. These results support a role of adiponectin as an essential regulator for healthspan and lifespan.

Current guidelines emphasize the use of 100% oxygen during cardiopulmonary resuscitation after cardiac arrest. When patients are ventilated for variable periods after return of spontaneous circulation (ROSC), hyperoxia causes increased morbidity and mortality by overproduction of reactive oxygen species. Various patient, volunteer, and animal studies have shown the harmful effects of hyperoxia. This mini-review article aims to expand the potential clinical spectrum of hyperoxia on individual organ systems leading to organ dysfunction. A framework to achieve and maintain normoxia after ROSC is proposed. Despite the harmful considerations of hyperoxia in critically ill patients, additional safety studies including dose-effect, level and onset of the reactive oxygen species effect, and safe hyperoxia applicability period after ROSC, need to be performed in various animal and human models to further elucidate the role of oxygen therapy after cardiac arrest.

OBJECTIVES: The present study aimed to exploring community pharmacists' willingness and readiness to test for COVID-19 in Jordan. METHODS: Purposeful sampling was used to identify a list of 30 community pharmacies, which were approached to participate in the study. Twenty interviews were needed to reach data saturation. In-depth interviews were conducted, recorded, transcribed, and analysed using NVivo 11 Software. Interviews followed a previously prepared and validated 10-item interview guide. The interview guide discussed pharmacists' willingness and readiness to test for COVID-19. RESULTS: Twenty community pharmacists were interviewed for the purpose of the present study. Interviews took place during April 2020 and the mean interview duration was 23.30 minutes. Respondents had a mean age of 36.4 years and a mean experience of 8.8 years. The majority were female (70%) and 50% held a BSc in Pharmacy. Regarding respondents' willingness to test for COVID-19 emerging themes were helping other healthcare professional, willingness to contribute to official efforts in fighting COVID-19, acting as an accessible testing cite, willingness to carry out home testing. Regarding respondents' readiness to test for COVID-19 emerging themes were Pharmacists lack basic testing skills, pharmacies are not ready to preform tests and the need for training and certifying. CONCLUSION: Jordanian pharmacists are willing to test patients for COVID-19 in community pharmacies, however, they thought they are not ready enough to undergo such tests and needed extra training and better safety precautions.

Rapid and accurate diagnosis of bovine respiratory disease (BRD) presents a substantial challenge to the North American cattle industry. Here we utilize recombinase polymerase amplification (RPA), a fast and sensitive isothermal DNA-based technology for the detection of four BRD pathogens (Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Mycoplasma bovis), genes coding antimicrobial resistance (AMR) and integrative conjugative elements (ICE) which can harbor AMR genes. Eleven RPA assays were designed and validated including: a) one conventional species-specific multiplex assay targeting the 4 BRD pathogens, b) two species-specific real-time multiplex RPA assays targeting M. haemolytica/M. bovis and P. multocida/H. somni, respectively with a novel competitive internal amplification control, c) seven conventional assays targeting AMR genes (tetH, tetR, msrE, mphE, sul2, floR, erm42), and d) one real-time assay targeting ICE. Each real-time RPA assay was tested on 100 deep nasopharyngeal swabs (DNPS) collected from feedlot cattle previously assessed for targets using either culture methods and/or polymerase chain reaction (PCR) verification (TC-PCR). The developed RPA assays enabled sensitive and accurate identification of BRD agents and AMR/ICE genes directly from DNPS, in a shorter period than TC-PCR, showing considerable promise as a tool for point-of-care identification of BRD pathogens and antimicrobial resistance genes.

Background The 2019 Coronavirus infection (COVID-19) caused by a novel strain of coronavirus was detected in China in December 2019, and declared a public health emergency of international concern on January 30, 2020. Community pharmacists have an important role in supporting the local health emergency preparedness and response arrangements. Objectives To investigate pharmacists and pharmacy students’ awareness and source of their information regard the management of the coronavirus pandemic, and their perspective of their role during this emergent situation. Methods This descriptive cross-sectional online survey study was conducted in Jordan during the COVID-19 outbreak (from 15 to 30 March 2020). A validated online questionnaire addressing participants' current awareness about epidemics/pandemics and COVID-19, source of information and their perspectives of their role. Data were analyzed using statistical package for social science (SPSS). Results Participants (n = 726) had a mean age of 26.9 (8.0) years with 71.9% females. Pharmacy students made 35.3% of the sample while the rest were pharmacists. Only 54.3% of participants believed that they got enough education about epidemics/pandemics, and 94.6% of them follow on the latest coronavirus updates on treatments, and that is mainly from the media (59.5%) followed by the World Health Organization reports (58.7%) and then the published researches (57%). Awareness score (out of 20) of pharmacists (n = 470) was significantly higher (p

The adipose tissue stroma is a rich source of molecularly distinct stem and progenitor cell populations with diverse functions in metabolic regulation, adipogenesis, and inflammation. The ontology of these populations and the mechanisms that govern their behaviors in response to stimuli, such as overfeeding, however, are unclear. Here, we show that the developmental fates and functional properties of adipose platelet-derived growth factor receptor beta (PDGFRβ)+ progenitor subpopulations are tightly regulated by mitochondrial metabolism. Reducing the mitochondrial β-oxidative capacity of PDGFRβ+ cells via inducible expression of MitoNEET drives a pro-inflammatory phenotype in adipose progenitors and alters lineage commitment. Furthermore, disrupting mitochondrial function in PDGFRβ+ cells rapidly induces alterations in immune cell composition in lean mice and impacts expansion of adipose tissue in diet-induced obesity. The adverse effects on adipose tissue remodeling can be reversed by restoring mitochondrial activity in progenitors, suggesting therapeutic potential for targeting energy metabolism in these cells.

Objective The objective of the present study was to explore the barriers and supporting factors for adherence among HIV patients and to explore their needs for pharmaceutical care services. Methods This study utilizes in-depth interviews with HIV patients. Out of 50 patients approached, a total of 30 patients agreed to participate in the study. The researchers used a predesigned topic guide. The interview guide included two parts; the first one focused on the assessment of HIV patients' adherence to their treatment. The second part focused on patients' need for pharmaceutical care services. Results Three main themes emerged from the interviews. Those included patient-related factors, medication-related factors and Healthcare professional related factors. This study found that a number of barriers that decreased adherence in HIV patients included stigmatisation, fear from disclosure, dosage form of the drug, adverse events and poor cooperation from healthcare professionals. On the other side supporting factors included family and friends support, electronic mobile reminders, feeling responsible to raising children, religious beliefs and feeling improvement while using therapy. Furthermore, the study illustrated that HIV patients need to have a specialist pharmacist in their healthcare team who delivers specialised pharmaceutical care services which may increase patients' adherence. Conclusions The current study reveals a margin for medication adherence improvement in HIV patients. Patients in this study demonstrated the need for a pharmaceutical care. Future disease management and clinical pharmacy services programs should address the current study findings in order to improve the health service for HIV patients.

Background: There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort. Methods: SPI2 was a randomised, double-blind, parallel-group, placebo-controlled trial done at 90 academic and community multiple sclerosis clinics across 13 countries. Patients were aged 18-65 years, had a diagnosis of primary or secondary progressive multiple sclerosis fulfilling the revised International Panel criteria and Lublin criteria, a Kurtzke pyramidal functional subscore of at least 2 (defined as minimal disability), an expanded disability status scale (EDSS) score of 3·5-6·5, a timed 25-foot walk (TW25) of less than 40 s, evidence of clinical disability progression, and no relapses in the 2 years before enrolment. Concomitant disease-modifying therapies were allowed. Patients were randomly assigned (1:1) by an independent statistician using an interactive web response system, with stratification by study site and disease history, to receive MD1003 (oral biotin 100 mg three times daily) or placebo. Participants, investigators, and assessors were masked to treatment assignment. The primary endpoint was a composite of the proportion of participants with confirmed improvement in EDSS or TW25 at month 12, confirmed at month 15, versus baseline. The primary endpoint was assessed in the intention-to-treat analysis set, after all participants completed the month 15 visit. Safety analyses included all participants who received at least one dose of MD1003. This trial is registered with ClinicalTrials.gov (NCT02936037) and the EudraCT database (2016-000700-29). Findings: From Feb 22, 2017, to June 8, 2018, 642 participants were randomly assigned MD1003 (n=326) or placebo (n=316). The double-blind, placebo-controlled phase of the study ended when the primary endpoint for the last-entered participant was assessed on Nov 15, 2019. The mean time in the placebo-controlled phase was 20·1 months (SD 5·3; range 15-27). For the primary outcome, 39 (12%) of 326 patients in the MD1003 group compared with 29 (9%) of 316 in the placebo group improved at month 12, with confirmation at month 15 (odds ratio 1·35 [95% CI 0·81-2·26]). Treatment-emergent adverse events occurred in 277 (84%) of 331 participants in the MD1003 group and in 264 (85%) of 311 in the placebo group. 87 (26%) of 331 participants in the MD1003 group and 82 (26%) of 311 participants in the placebo group had at least one serious treatment-emergent adverse event. One (

Objectives: This study aimed to describe the effect of using an innovative teaching strategy using a video tutorial on enhancing students’ knowledge about medication reconciliation, and skills in identifying medication discrepancies. Methods: This is a one group pre-post interventional study that was conducted at the School of Pharmacy at Applied Science Private University. Sixty pharmacy students were invited to attend an educational sessions that involve watching a 6-minutes video tutorial. The first two levels of the Kirkpatrick’s Model were used to evaluate the effectiveness of this training tool. Level 1 (Reaction) was assessed using a satisfaction questionnaire, while level 2 (Learning) was assessed using two criteria: 1) student acquired knowledge about medication reconciliation using a questionnaire and a knowledge score out of 13 was calculated for each student, and 2) student acquired skills in identifying medication discrepancies using a virtual case scenario. If the student was able to identify any of the four impeded discrepancies he/she rewarded 1 point for each identified discrepancy, but if they identified any incorrect discrepancy they scored a negative point. Results: Among the 60 students who registered to participate in the study, 49 attended the educational training (response rate 81.6%). The majority of them (n=44, 89.8%) were satisfied with the training process. Before the video tutorial, students showed an overall low knowledge score [4.08/13.0, SD 1.81], and low ability to identify discrepancies [0.72 identified discrepancies out of 4.0, SD 1.1]. Following the video tutorial, the overall knowledge score was improved (p

Although ADP-ribosylation of histones by PARP-1 has been linked to genotoxic stress responses, its role in physiological processes and gene expression has remained elusive. We found that NAD+-dependent ADP-ribosylation of histone H2B-Glu35 by small nucleolar RNA (snoRNA)-activated PARP-1 inhibits AMP kinase-mediated phosphorylation of adjacent H2B-Ser36, which is required for the proadipogenic gene expression program. The activity of PARP-1 on H2B requires NMNAT-1, a nuclear NAD+ synthase, which directs PARP-1 catalytic activity to Glu and Asp residues. ADP-ribosylation of Glu35 and the subsequent reduction of H2B-Ser36 phosphorylation inhibits the differentiation of adipocyte precursors in cultured cells. Parp1 knockout in preadipocytes in a mouse lineage-tracing genetic model increases adipogenesis, leading to obesity. Collectively, our results demonstrate a functional interplay between H2B-Glu35 ADP-ribosylation and H2B-Ser36 phosphorylation that controls adipogenesis.

Background Fat grafting has been used extensively in plastic surgery in the past two decades. Here, the authors report the retrospective comparison of patients who underwent fractionated fat injection to blend the lid-cheek junction with those who had regular fat injection. Methods After obtaining institutional review board approval, a retrospective review of patients who underwent lower blepharoplasty with fractionated fat injection for blending the lid-cheek junction from January of 2014 through October of 2015 was performed. The results were compared to those of lower blepharoplasty patients who did not have fractionated fat injected before January of 2014. Twelve prospectively selected patients underwent histopathologic and gene expression comparisons. Results A comparison of complications between the two groups revealed no significant differences. Furthermore, there was no significant difference between the two groups for sequelae of fractionated fat injection and regular fat injection. The gene expression analysis of the fractionated and regular fat did not show any difference between undifferentiated and differentiated cells. In addition, Oil Red O staining of the fractionated and regular fat after differentiation showed that cells from both fat groups differentiated equally well. Conclusions Fractionated fat injection appears to be a safe addition in blending the lid-cheek junction in the five-step lower blepharoplasty. There is no fat nodule formation with injection of fractionated fat injection compared with injection of regular fat performed superficially in the tear trough area. Contrary to what has previously been shown, the presence of viable cells in fractionated fat was noted. Clinical question/level of evidence Therapeutic, III.

Objective The spliced transcription factor Xbp1 (Xbp1s), a transducer of the unfolded protein response (UPR), regulates lipolysis. Lipolysis is stimulated by fasting when uridine synthesis is also activated in adipocytes. Methods Here we have examined the regulatory role Xbp1s in stimulation of uridine biosynthesis in adipocytes and triglyceride mobilization using inducible mouse models. Results Xbp1s is a key molecule involved in adipocyte uridine biosynthesis and release by activation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD), the rate-limiting enzyme for UMP biosynthesis. Adipocyte Xbp1s overexpression drives energy mobilization and protects mice from obesity through activation of the pyrimidine biosynthesis pathway. Conclusion These observations reveal that Xbp1s is a potent stimulator of uridine production in adipocytes, enhancing lipolysis and invoking a potential anti-obesity strategy through the induction of a futile biosynthetic cycle., Highlights • ER stress is a key mechanism of obesity-related metabolic disorders. • Xbp1s, a key transducer of ER stress response, stimulates uridine biosynthesis. • Uridine synthesized in adipocytes is critical for plasma uridine supply. • Stimulation of uridine synthesis in adipocyte by Xbp1s promotes weight loss.

Pathologic expansion of white adipose tissue (WAT) in obesity is characterized by adipocyte hypertrophy, inflammation, and fibrosis; however, factors triggering this maladaptive remodeling are largely unknown. Here, we test the hypothesis that the potential to recruit new adipocytes from Pdgfrβ+ preadipocytes determines visceral WAT health in obesity. We manipulate levels of Pparg, the master regulator of adipogenesis, in Pdgfrβ+ precursors of adult mice. Increasing the adipogenic capacity of Pdgfrβ+ precursors through Pparg overexpression results in healthy visceral WAT expansion in obesity and adiponectin-dependent improvements in glucose homeostasis. Loss of mural cell Pparg triggers pathologic visceral WAT expansion upon high-fat diet feeding. Moreover, the ability of the TZD class of anti-diabetic drugs to promote healthy visceral WAT remodeling is dependent on mural cell Pparg. These data highlight the protective effects of de novo visceral adipocyte differentiation in these settings, and suggest Pdgfrβ+ adipocyte precursors as targets for therapeutic intervention in diabetes.

The compensatory proliferation of insulin-producing β cells is critical to maintaining glucose homeostasis at the early stage of type 2 diabetes. Failure of β cells to proliferate results in hyperglycemia and insulin dependence in patients. To understand the effect of the interplay between β cell compensation and lipid metabolism upon obesity and peripheral insulin resistance, we eliminated LDL receptor–related protein 1 (LRP1), a pleiotropic mediator of cholesterol, insulin, energy metabolism, and other cellular processes, in β cells. Upon high-fat diet exposure, LRP1 ablation significantly impaired insulin secretion and proliferation of β cells. The diminished insulin signaling was partly contributed to by the hypersensitivity to glucose-induced, Ca2+-dependent activation of Erk and the mTORC1 effector p85 S6K1. Surprisingly, in LRP1-deficient islets, lipotoxic sphingolipids were mitigated by improved lipid metabolism, mediated at least in part by the master transcriptional regulator PPARγ2. Acute overexpression of PPARγ2 in β cells impaired insulin signaling and insulin secretion. Elimination of Apbb2, a functional regulator of LRP1 cytoplasmic domain, also impaired β cell function in a similar fashion. In summary, our results uncover the double-edged effects of intracellular lipid metabolism on β cell function and viability in obesity and type 2 diabetes and highlight LRP1 as an essential regulator of these processes.

Disease severity of sickle cell anemia is highly variable, and it is commonly accepted that fetal hemoglobin (HbF) levels play a major role as an ameliorating factor. Investigation of genetic variants have identified several genes to be the principal influencers of HbF regulation. Here, we further elucidated the association of rs4527238 and rs35685045 of ANTXR1 genes in the context of HbF level variance in sickle cell anemia patients of the Arab-Indian haplotype. Samples from 630 sickle cell anemia patients were analyzed for the mutations at 2 specific locations of the ANTXR1 gene by TaqMan®-based real-time PCR. The CC genotype (p = 0.018) of rs4527238 and the TT genotype (p = 0.048) of rs35685045 of ANTXR1 were found to be significantly associated with low HbF expression. The frequency of the CC genotype of rs4527238 was observed to be high in the low HbF patient group compared to the high HbF group (p = 0.009). Likewise, the frequency of the TT genotype of rs35685045 was also high among the low HbF group (p = 0.017). The ANTXR1 genetic mutations and the association with HbF expression in the Arab-Indian haplotype sickle cell patients revealed that the ANTXR1 gene may be a major HbF modulator leading to potential therapeutic options that should be further explored.

AIM/HYPOTHESIS: Adiponectin (APN), a circulating hormone secreted by mature adipocytes, has been extensively studied because it has beneficial metabolic effects. While many studies have focused on the congenital loss of APN and its effects on systemic body glucose and lipid metabolism, little is known about the effects triggered by acute loss of APN in the adult mouse. We anticipated that genetically induced acute depletion of APN in adult mice would have a more profound effect on systemic metabolic health than congenital deletion of Adipoq, the gene encoding APN, with its associated potential for adaptive responses that may mask the phenotypes. METHODS: Mice carrying loxP-flanked regions of Adipoq were generated and bred to the Adipoq (APN) promoter-driven reverse tetracycline-controlled transactivator (rtTA) (APN-rtTA) gene and a tet-responsive Cre line (TRE-Cre) to achieve acute depletion of APN. Upon acute removal of APN in adult mice, systemic glucose and lipid homeostasis were assessed under basal and insulinopenic conditions. RESULTS: The acute depletion of APN results in more severe systemic insulin resistance and hyperlipidaemia than in mice with congenital loss of APN. Furthermore, the acute depletion of APN in adult mice results in a much more dramatic reduction in survival rate, with 50% of inducible knockouts dying in the first 5 days under insulinopenic conditions compared with 0% of congenital Adipoq knockout mice under similar conditions. CONCLUSIONS/INTERPRETATION: Acute systemic removal of APN results in a much more negative metabolic phenotype compared with congenital knockout of Adipoq. Specifically, our data demonstrate that acute depletion of APN is especially detrimental to lipid homeostasis, both under basal and insulinopenic conditions. This suggests that compensatory mechanisms exist in congenital knockout mice that offset some of the metabolic actions covered by APN.

Transcripts of key enzymes in the Leloir pathway of galactose metabolism in mouse livers are significantly increased after chronic high-fat/high-sucrose feeding. UDP-galactose-4-epimerase (GALE) is the last enzyme in this pathway that converts UDP-galactose to UDP-glucose and was previously identified as a downstream target of the endoplasmic reticulum (ER) stress effector spliced X-box binding protein 1, suggesting an interesting cross talk between galactose and glucose metabolism in the context of hepatic ER stress and whole-body metabolic fitness. However, its specific role in glucose metabolism is not established. Using an inducible and tissue-specific mouse model, we report that hepatic overexpression of Gale increases gluconeogenesis from pyruvate and impairs glucose tolerance. Conversely, genetic reduction of Gale in liver improves glucose tolerance. Transcriptional profiling identifies trefoil factor 3 (Tff3) as one of the downstream targets of GALE. Restoration of Tff3 expression corrects glucose intolerance in Gale-overexpressing mice. These studies reveal a new link between hepatic GALE activity and whole-body glucose homeostasis via regulation of hepatic Tff3 expression.

The ability to maintain and expand the pool of adipocytes in adults is integral to the regulation of energy balance, tissue/stem cell homeostasis, and disease pathogenesis. For decades, our knowledge of adipocyte precursors has relied on cellular models. The identity of native adipocyte precursors has remained unclear. Recent studies have identified distinct adipocyte precursor populations that are physiologically regulated and contribute to the development, maintenance, and expansion of adipocyte pools in mice. With new tools available, the properties of adipocyte precursors can now be defined, and the regulation and function of adipose plasticity in development and physiology can be explored.

Summary Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification of proteins mediated by PARP family members, such as PARP-1. Although PARylation has been studied extensively, few examples of definitive biological roles for site-specific PARylation have been reported. Here we show that C/EBPβ, a key pro-adipogenic transcription factor, is PARylated by PARP-1 on three amino acids in a conserved regulatory domain. PARylation at these sites inhibits C/EBPβ's DNA binding and transcriptional activities and attenuates adipogenesis in various genetic and cell-based models. Interestingly, PARP-1 catalytic activity drops precipitously during the first 48 hr of differentiation, corresponding to a release of C/EBPβ from PARylation-mediated inhibition. This promotes the binding of C/EBPβ at enhancers controlling the expression of adipogenic target genes and continued differentiation. Depletion or chemical inhibition of PARP-1, or mutation of the PARylation sites on C/EBPβ, enhances these early adipogenic events. Collectively, our results provide a clear example of how site-specific PARylation drives biological outcomes.

Dermal adipose tissue (also known as dermal white adipose tissue and herein referred to as dWAT) has been the focus of much discussion in recent years. However, dWAT remains poorly characterized. The fate of the mature dermal adipocytes and the origin of the rapidly reappearing dermal adipocytes at different stages remain unclear. Here, we isolated dermal adipocytes and characterized dermal fat at the cellular and molecular level. Together with dWAT's dynamic responses to external stimuli, we established that dermal adipocytes are a distinct class of white adipocytes with high plasticity. By combining pulse-chase lineage tracing and single-cell RNA sequencing, we observed that mature dermal adipocytes undergo dedifferentiation and redifferentiation under physiological and pathophysiological conditions. Upon various challenges, the dedifferentiated cells proliferate and redifferentiate into adipocytes. In addition, manipulation of dWAT highlighted an important role for mature dermal adipocytes for hair cycling and wound healing. Altogether, these observations unravel a surprising plasticity of dermal adipocytes and provide an explanation for the dynamic changes in dWAT mass that occur under physiological and pathophysiological conditions, and highlight the important contributions of dWAT toward maintaining skin homeostasis.

As a result of the pressing environmental and technological conditions dominant today, new frontiers for architectural production are emerging. Fueled by accelerated change and increased connectivity, these trajectories operate across multiple scales and domains. The evolving relationship between place, technology, and occupancy formulates a complex active structure that tends to have fluctuating levels of activity and impact. These conditions are giving way to hybridized settings where the interdependence of digital and analog is altering the very politics of place and identity. In response to the prevalence of amalgamated settings, the paradigm of “Dynamic Landscapes, Emerging Territories” is presented. Dynamic Landscapes have definitions and presence in multiple locations simultaneously, requiring new methods of documentation and assessment in order to conceive appropriate design responses. The paper uses the Syrian Refugee Crisis as a case study for deciphering the implications inherent in displacement in the context of dynamic landscapes. Furthermore, it presents an opportunity to think of new architectural trajectories rooted and driven by the animation of such sites. Inherently dynamic, forced displacement presents rich emerging territories where design carries significant impact and facilitates a tangible reassessment of a refugee’s narrative. Supported by robust information networks and active feedback loops, displaced landscapes as such can learn from their residents and inform their imminent futures specifically, as well as our collective human occupancy at large. Within constantly changing milieus, architecture’s premises and processes are being challenged to respond to fluctuating contexts and provide for transient occupancies. While some may see this as a loss of spatial agency when it comes to design, these conditions present an opportunity to think of new architectural trajectories that are rooted and driven by the dynamism of multilayered landscapes and new approaches towards practice.

Adipose precursor cells (APCs) exhibits regional variation in response to obesity, for unclear reasons. Here, we reveal that HIFα-induced PDGFRβ signaling within murine white adipose tissue (WAT) PDGFRβ+ cells drives inhibitory serine 112 (S112) phosphorylation of PPARγ, the master regulator of adipogenesis. Levels of PPARγ S112 phosphorylation in WAT PDGFRb+ cells are depot-dependent, with levels of PPARγ phosphorylation in PDGFRβ+ cells inversely correlating with their capacity for adipogenesis upon high fat diet feeding. HIFα suppression in PDGFRβ+ progenitors promotes subcutaneous and intra-abdominal adipogenesis, healthy WAT remodeling, and improved metabolic health in obesity. These metabolic benefits are mimicked by treatment of obese mice with the PDGFR antagonist, Imatinib, which promotes adipocyte hyperplasia and glucose tolerance in a progenitor cell PPARγ-dependent manner. Our studies unveil a mechanism underlying depot-specific responses of APCs to high-fat feeding, and highlight the potential for APCs to be targeted pharmacologically to improve metabolic health in obesity.

Objective Zfp423 is a multi zinc-finger transcription factor expressed in preadipocytes and mature adipocytes in vivo. Our recent work has revealed a critical role for Zfp423 in maintaining the fate of white adipocytes in adult mice through suppression of the beige cell thermogenic gene program; loss of Zfp423 in mature adipocytes of adult mice results in a white-to-beige phenotypic switch. However, the exact requirements of Zfp423 in the fetal stages of early adipose development in vivo have not been clarified. Method Here, we utilize two models that confer adipose-specific Zfp423 inactivation during fetal adipose development (Adiponectin-Cre; Zfp423loxP/loxP and Adiponectin-rtTA; TRE-Cre; Zfp423loxP/loxP). We assess the impact of fetal adipose Zfp423 deletion on the initial formation of adipose tissue and evaluate the metabolic consequences of challenging these animals with high-fat diet feeding. Results Deletion of Zfp423 during fetal adipose development results in a different phenotype than is observed when deleting Zfp423 in adipocytes of adult mice. Inactivation of Zfp423 during fetal adipose development results in arrested differentiation, specifically of inguinal white adipocytes, rather than a white-to-beige phenotypic switch that occurs when Zfp423 is inactivated in adult mice. This is likely explained by the observation that adiponectin driven Cre expression is active at an earlier stage of the adipocyte life cycle during fetal subcutaneous adipose development than in adult mice. Upon high-fat diet feeding, obese adipose Zfp423-deficient animals undergo a pathological adipose tissue expansion, associated with ectopic lipid deposition and systemic insulin resistance. Conclusions Our results reveal that Zfp423 is essential for the terminal differentiation of subcutaneous white adipocytes during fetal adipose tissue development. Moreover, our data highlight the striking adverse effects of pathological subcutaneous adipose tissue remodeling on visceral adipose function and systemic nutrient homeostasis in obesity. Importantly, these data reveal the distinct phenotypes that can occur when adiponectin driven transgenes are activated in fetal vs. adult adipose tissue., Highlights • Fetal adipose deletion of Zfp423 disrupts terminal differentiation of white adipocytes. • Inguinal WAT of Zfp423-deficient mice undergoes a pathological expansion in obesity. • Pathological expansion of subcutaneous adipose triggers systemic insulin resistance.

Endometrial cancer is the most common gynecologic malignancy in the United States. According to 2014 cancer statistics an estimated 52,630 cases of endometrial cancer and 8,590 of deaths cases are diagnosed in 2014.The classically diagnosis of endometrial cancer is abnormal vaginal bleeding. Most patients with this type of cancer have source of excess estrogen, high body mass index (BMI) as overweight or obese and often with other components of metabolic syndrome like hypertension.The aim of this study is investigate the role of hormonal balance and BMI in women patients with endometrial cancer. Fifty six endometrial cancer women patients mean aged (58.055 ± 10.561 years) not submitted to therapy in this study, and (n=30) healthy women volunteers mean aged (39.731 ± 13.504 years) as control group. The results in this study revealed a highly significant increased (P

"Beige" adipocytes reside in white adipose tissue (WAT) and dissipate energy as heat. Several studies have shown that cold temperature can activate pro-opiomelanocortin-expressing (POMC) neurons and increase sympathetic neuronal tone to regulate WAT beiging. WAT, however, is traditionally known to be sparsely innervated. Details regarding the neuronal innervation and, more importantly, the propagation of the signal within the population of "beige" adipocytes are sparse. Here, we demonstrate that beige adipocytes display an increased cell-to-cell coupling via connexin 43 (Cx43) gap junction channels. Blocking of Cx43 channels by 18α-glycyrrhetinic acid decreases POMC-activation-induced adipose tissue beiging. Adipocyte-specific deletion of Cx43 reduces WAT beiging to a level similar to that observed in denervated fat pads. In contrast, overexpression of Cx43 is sufficient to promote beiging even with mild cold stimuli. These data reveal the importance of cell-to-cell communication, effective in cold-induced WAT beiging, for the propagation of limited neuronal inputs in adipose tissue.

Objectives: We sought to study the expression of epithelial-to-mesenchymal transition markers E-cadherin and vimentin in precancerous lesions of the oral cavity and oropharynx and to use the specific pattern of expression to predict invasiveness. Methods: This cross-sectional study looked at 87 cases of oral and oropharyngeal lesions obtained between December 2012 and November 2014 in the Department of Pathology, Jawaharlal Nehru Medical College, Aligarh Muslim University, India. Fifty-three biopsies from the buccal mucosa, tongue, and pharynx and 34 resected oral specimens were evaluated for premalignant and malignant lesions using hematoxylin and eosin and immunohistochemical stains. Immunohistochemical expression of epithelial marker E-cadherin and mesenchymal marker vimentin was evaluated wherever possible. Slides were examined for staining pattern (cytoplasmic or membrane), proportion, and intensity of staining of tumor cells. Patients follow-up and therapy related changes were also studied. Results: There were 64 premalignant and 23 malignant cases in our study with 65 (74.7%) cases seen in males and 22 (25.3%) cases seen in females. The majority of malignant cases, (n = 15; 64.2%) were seen in the fifth and sixth decades of life while most of the premalignant lesions (n = 36; 56.4%) were seen in the fourth and fifth decade. Amongst the 64 premalignant oral lesions, leukoplakia comprised of 14 cases (21.9%), of which three cases had associated mild to moderate dysplasia. The majority of premalignant lesions showed strong E-cadherin expression and decreased expression of vimentin with negative and weak expression in both dysplasias and carcinoma in situ (p = 0.013). E-cadherin expression was significantly reduced in invasive carcinomas compared to dysplasias and carcinoma in situ and the difference in immunoreactivity was statistically significant (p < 0.050). Vimentin expression increased as the tumor progressed from dysplasias to carcinoma in situ to invasive carcinomas (p < 0.050). Conclusions: Invasiveness of cancer can be analyzed using E-cadherin and vimentin immunohistochemical stains, which can help in predicting tumor behavior. These biomolecules can also be used as biomarkers for further research on the microinvasion of oral cancers for early diagnosis.

Background A point‐of‐care rapid test (POCRT) may help early and targeted use of antiviral drugs for the management of influenza A infection. Objective (i) To determine whether antiviral treatment based on a POCRT for influenza A is cost‐effective and, (ii) to determine the thresholds of key test parameters (sensitivity, specificity and cost) at which a POCRT based‐strategy appears to be cost effective. Methods An hybrid « susceptible, infected, recovered (SIR) » compartmental transmission and Markov decision analytic model was used to simulate the cost‐effectiveness of antiviral treatment based on a POCRT for influenza A in the social perspective. Data input parameters used were retrieved from peer‐review published studies and government databases. The outcome considered was the incremental cost per life‐year saved for one seasonal influenza season. Results In the base‐case analysis, the antiviral treatment based on POCRT saves 2 lives/100 000 person‐years and costs $7600 less than the empirical antiviral treatment based on clinical judgment alone, which demonstrates that the POCRT‐based strategy is dominant. In one and two way‐sensitivity analyses, results were sensitive to the POCRT accuracy and cost, to the vaccination coverage as well as to the prevalence of influenza A. In probabilistic sensitivity analyses, the POCRT strategy is cost‐effective in 66% of cases, for a commonly accepted threshold of $50 000 per life‐year saved. Conclusion The influenza antiviral treatment based on POCRT could be cost‐effective in specific conditions of performance, price and disease prevalence.

Oncocytoma is a rare benign tumor of the salivary glands usually seen in elderly patients in the sixth to eighth decade. Microscopically, the hallmark of this lesion is the presence of oncocytes that comprise the entire tumor. These are large polygonal cells which have abundant eosinophilic granular cytoplasm, and from central to eccentric round nucleus. Several reactive as well as neoplastic lesions of salivary glands often have concurrent oncocytic changes. On fine-needle aspiration cytology, all of them have overlapping morphological features, thus making the diagnosis difficult by cytology alone. We report a case of oncocytoma of the right parotid gland in a 32-year-old Indian male. Although the tumor was initially suspected on cytology, confirmation was possible only after histopathological examination. The main purpose of this case report is to discuss the cytological differential diagnosis of oncocytic lesions of salivary glands and simultaneously emphasize the importance of histopathology for arriving at conclusive diagnosis in such cases.

Increasing non‐shivering thermogenesis (NST), which expends calories as heat rather than storing them as fat, is championed as an effective way to combat obesity and metabolic disease. Innate mechanisms constraining the capacity for NST present a fundamental limitation to this approach, yet are not well understood. Here, we provide evidence that Regulator of Calcineurin 1 (RCAN1), a feedback inhibitor of the calcium‐activated protein phosphatase calcineurin (CN), acts to suppress two distinctly different mechanisms of non‐shivering thermogenesis (NST): one involving the activation of UCP1 expression in white adipose tissue, the other mediated by sarcolipin (SLN) in skeletal muscle. UCP1 generates heat at the expense of reducing ATP production, whereas SLN increases ATP consumption to generate heat. Gene expression profiles demonstrate a high correlation between Rcan1 expression and metabolic syndrome. On an evolutionary timescale, in the context of limited food resources, systemic suppression of prolonged NST by RCAN1 might have been beneficial; however, in the face of caloric abundance, RCAN1‐mediated suppression of these adaptive avenues of energy expenditure may now contribute to the growing epidemic of obesity.

The precursor cells for metabolically beneficial beige adipocytes can alternatively become fibrogenic and contribute to adipose fibrosis. This adipogenic versus fibrogenic fate decision is poorly understood. Cold exposure or β3-adrenergic agonist treatment of mice decreased the fibrogenic profile of precursor cells and stimulated beige adipocyte differentiation. This fibrogenic-to-adipogenic transition was impaired in aged animals, correlating with reduced adipocyte expression of the transcription factor PRDM16. Genetic loss of Prdm16 mimicked the effect of aging in promoting fibrosis, whereas increasing PRDM16 in aged mice reduced fibrosis and restored beige adipogenesis. PRDM16-expressing adipose cells secreted the metabolite β-hydroxybutyrate (BHB), which blocked precursor fibrogenesis and enhanced beige adipogenesis. BHB catabolism in precursor cells, mediated by BDH1, was required for beige fat differentiation in vivo. Finally, dietary BHB supplementation in aged animals reduced adipose fibrosis and restored beige fat formation. Together, our results demonstrate that adipocytes secrete a metabolite signal that controls beige fat remodeling.

White adipose tissue (WAT) remodeling is dictated by coordinated interactions between adipocytes and resident stromal-vascular cells; however, the functional heterogeneity of adipose stromal cells has remained unresolved. We combined single-cell RNA-sequencing and FACS to identify and isolate functionally distinct subpopulations of PDGFRβ+ stromal cells within visceral WAT of adult mice. LY6C- CD9- PDGFRβ+ cells represent highly adipogenic visceral adipocyte precursor cells (‘APCs’), whereas LY6C+ PDGFRβ+ cells represent fibro-inflammatory progenitors (‘FIPs’). FIPs lack adipogenic capacity, display pro-fibrogenic/pro-inflammatory phenotypes, and can exert an anti-adipogenic effect on APCs. The pro-inflammatory phenotype of PDGFRβ+ cells is regulated, at least in part, by NR4A nuclear receptors. These data highlight the functional heterogeneity of visceral WAT perivascular cells, and provide insight into potential cell-cell interactions impacting adipogenesis and inflammation. These improved strategies to isolate FIPs and APCs from visceral WAT will facilitate the study of physiological WAT remodeling and mechanisms leading to metabolic dysfunction. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter)., eLife digest Fat tissue, also known as white adipose tissue, specializes in storing excess calories. Much of this storage happens under the skin, but fat tissue can also build up inside the abdomen and surround organs, where it is known as ‘visceral’ fat. When visceral fat tissue is unhealthy, it may help diseases such as diabetes and heart disease to develop. Unhealthy fat tissue contains enlarged fat cells, which may die from overwork. The stress this places on the surrounding tissue activates the immune system, causing inflammation and the build-up of collagen fibers around the cells (a condition known as fibrosis). Not all people develop this type of unhealthy fat tissue, but we do not yet understand why. In many tissues, blood vessels serve as a home for several types of adult stem cells that help to rejuvenate the tissue following damage. To identify these cells, Hepler et al. analyzed the genes used by more than 3,000 cells living around the blood vessels in the visceral fat of adult mice. Recent work had already revealed that stem cells called adipocyte precursor cells live in this region. Hepler et al. now reveal the presence of a second group of cells, termed fibro-inflammatory progenitor cells (or FIPs for short). To investigate the roles of each cell type in more detail, Hepler et al. developed a new technique to isolate the adipocyte precursor cells from other cell types. When grown in the right conditions in petri dishes, the adipocyte precursor cells were able to form new fat cells. They could also make new fat cells when transplanted into mice that lacked fat tissue. By contrast, the FIPs can suppress the activity of adipocyte precursor cells and activate immune cells. They may also help fibrosis to develop. It is not yet clear whether FIPs are present in human fat tissue. But, if they are, understanding them in greater detail may suggest new ways to treat diabetes and heart disease in obese people.