Cost-effectiveness analysis of once-weekly semaglutide vs. once-daily liraglutide administered subcutaneously in patients with overweight and obesity: a decision analysis.

OBJECTIVE: Obesity presents an enduring and multifaceted dilemma that impacts individuals, society, economies, and healthcare systems alike. Glucagon-like peptide-1 (GLP-1) receptor agonists, including liraglutide and semaglutide, have received FDA approval for obesity treatment. This study aims to present a cost-effectiveness analysis to compare the cost and clinical outcomes of semaglutide vs. liraglutide on weight loss in people with overweight and obesity. MATERIALS AND METHODS: A cost-effectiveness analysis was conducted to compare the cost and the clinical outcomes of adding weekly 2.4 mg SC semaglutide vs. daily 3.0 mg SC liraglutide or placebo to physical activity and diet control in overweight and obese patients. A clinical outcome of achieving ≥15% weight loss was chosen. A simple decision analysis model from a third-payer perspective was applied. Drug costs were based on the retail price of the USA market. One-way sensitivity analyses were performed. RESULTS: Results showed that 2.4 mg weekly semaglutide, when added to physical activity and diet control, was the most cost-effective choice in terms of ≥15% weight loss (ICER: $ 7,056/patient/68 weeks). The model was robust against the 50% increase in the unit cost of semaglutide and the 50% decrease in the unit cost of liraglutide, as well as the changes in probabilities by the corresponding 95% confidence intervals across the model. CONCLUSIONS: This cost-effectiveness analysis suggests that employing once-weekly 2.4 mg semaglutide emerges as a remarkably cost-effective option when contrasted with once-daily 3.0 mg liraglutide in patients with overweight and obesity when added to physical activity and diet control.

The role of the 5' sensing function of ribonuclease E in cyanobacteria.

RNA degradation is critical for synchronising gene expression with changing conditions in prokaryotic and eukaryotic organisms. In bacteria, the preference of the central ribonucleases RNase E, RNase J and RNase Y for 5'-monophosphorylated RNAs is considered important for RNA degradation. For RNase E, the underlying mechanism is termed 5' sensing, contrasting to the alternative 'direct entry' mode, which is independent of monophosphorylated 5' ends. Cyanobacteria, such as Synechocystis sp. PCC 6803 (Synechocystis), encode RNase E and RNase J homologues. Here, we constructed a Synechocystis strain lacking the 5' sensing function of RNase E and mapped on a transcriptome-wide level 283 5'-sensing-dependent cleavage sites. These included so far unknown targets such as mRNAs encoding proteins related to energy metabolism and carbon fixation. The 5' sensing function of cyanobacterial RNase E is important for the maturation of rRNA and several tRNAs, including tRNAGluUUC. This tRNA activates glutamate for tetrapyrrole biosynthesis in plant chloroplasts and in most prokaryotes. Furthermore, we found that increased RNase activities lead to a higher copy number of the major Synechocystis plasmids pSYSA and pSYSM. These results provide a first step towards understanding the importance of the different target mechanisms of RNase E outside Escherichia coli.

A cross-sectional analysis of the association between diabetes self-care practices and blood glucose regulation among Egyptian diabetic patients.

OBJECTIVE: Diabetes Mellitus (DM) is a main public health issue worldwide, with Egypt among the world's top countries with diabetic patients. Data on the degree of self-care behaviors of Egyptian diabetic patients is not fully reported. Therefore, the study aimed to assess the adequacy of diabetes self-management (DSM) habits among diabetic patients in Egypt and to identify associated socio-demographic factors that could negatively impact the patients' glycemic state, using a structured questionnaire. SUBJECTS AND METHODS: This study was a cross-sectional observational study. The diabetes self-management questionnaire (DSMQ) was used to assess diabetes self-care activities, which is a 16-item questionnaire. The statistical analysis was conducted on SPSS software, and the data were significant with a p-value <0.05. RESULTS: A total of 2,164 participants were included. The majority of the patients (83.8%) had type 2 DM. The mean glycated hemoglobin (HbA1c) of the study group was 8.44±1.99. Significant differences were found between different glycemic control groups both in terms of the DSMQ sum scores and the subscale scores, with the exception of physical activity. Moreover, there was a significant weak inverse correlation between the total DSMQ sum score and HbA1c ≥9.0% (ρ=-0.116, p<0.01). The overall internal consistency (Cronbach's alpha) was acceptable (0.756). CONCLUSIONS: The study indicated that patients with controlled blood glucose had significantly higher 'glucose management', and 'total DSMQ sum' scores compared to uncontrolled diabetic patients. All significant correlations between assessed parameters and DSMQ were weak.

The correlation of EMT and p53 immunohistochemical markers with cisplatin resistance in muscle invasive bladder cancer patients: A single-centred study.

INTRODUCTION: Although epithelial-mesenchymal transition (EMT) and p53 have been established to play a pivotal role in the aggressiveness of muscle-invasive bladder cancer (MIBC), its pathological correlation to cisplatin treatment in the Malaysian patient cohort is lacking. This study aimed to evaluate the association of EMT markers, e-cadherin, vimentin and actin, as well as tumour suppressor gene, p53, in cisplatin-receiving MIBC patients. MATERIALS AND METHODS: Formalin-fixed paraffinembedded (FFPE) blocks of muscle-invasive bladder cancer patients receiving cisplatin-based chemotherapy between January 2010 to December 2020 were traced. Immunohistochemistry staining was performed on traced blocks using antibodies to e-cadherin, vimentin and actin, and p53. RESULTS: p53 and e-cadherin were stained positive in most cases (p=0.515 and 0.242 respectively), although e-cadherin showed stronger positive expression in pre-cisplatin receiving MIBC cases. All the cases stained negative for actin and vimentin except for faint staining observed in one pre-cisplatin case. CONCLUSION: Although this study does not show a significant correlation between EMT markers and p53 with cisplatin-responsiveness in MIBC patients, the results serve as preliminary findings on the heterogeneous outcomes of molecular staining in the Malaysian MIBC patient cohort.

Delivery of costimulatory blockade to lymph nodes promotes transplant acceptance in mice.

The lymph node (LN) is the primary site of alloimmunity activation and regulation during transplantation. Here, we investigated how fibroblastic reticular cells (FRCs) facilitate the tolerance induced by anti-CD40L in a murine model of heart transplantation. We found that both the absence of LNs and FRC depletion abrogated the effect of anti-CD40L in prolonging murine heart allograft survival. Depletion of FRCs impaired homing of T cells across the high endothelial venules (HEVs) and promoted formation of alloreactive T cells in the LNs in heart-transplanted mice treated with anti-CD40L. Single-cell RNA sequencing of the LNs showed that anti-CD40L promotes a Madcam1+ FRC subset. FRCs also promoted the formation of regulatory T cells (Tregs) in vitro. Nanoparticles (NPs) containing anti-CD40L were selectively delivered to the LNs by coating them with MECA-79, which binds to peripheral node addressin (PNAd) glycoproteins expressed exclusively by HEVs. Treatment with these MECA-79-anti-CD40L-NPs markedly delayed the onset of heart allograft rejection and increased the presence of Tregs. Finally, combined MECA-79-anti-CD40L-NPs and rapamycin treatment resulted in markedly longer allograft survival than soluble anti-CD40L and rapamycin. These data demonstrate that FRCs are critical to facilitating costimulatory blockade. LN-targeted nanodelivery of anti-CD40L could effectively promote heart allograft acceptance.

Transcriptome-wide in vivo mapping of cleavage sites for the compact cyanobacterial ribonuclease E reveals insights into its function and substrate recognition.

Ribonucleases are crucial enzymes in RNA metabolism and post-transcriptional regulatory processes in bacteria. Cyanobacteria encode the two essential ribonucleases RNase E and RNase J. Cyanobacterial RNase E is shorter than homologues in other groups of bacteria and lacks both the chloroplast-specific N-terminal extension as well as the C-terminal domain typical for RNase E of enterobacteria. In order to investigate the function of RNase E in the model cyanobacterium Synechocystis sp. PCC 6803, we engineered a temperature-sensitive RNase E mutant by introducing two site-specific mutations, I65F and the spontaneously occurred V94A. This enabled us to perform RNA-seq after the transient inactivation of RNase E by a temperature shift (TIER-seq) and to map 1472 RNase-E-dependent cleavage sites. We inferred a dominating cleavage signature consisting of an adenine at the -3 and a uridine at the +2 position within a single-stranded segment of the RNA. The data identified mRNAs likely regulated jointly by RNase E and an sRNA and potential 3' end-derived sRNAs. Our findings substantiate the pivotal role of RNase E in post-transcriptional regulation and suggest the redundant or concerted action of RNase E and RNase J in cyanobacteria.

The effects of zinc oxide nanoparticles on the physical, mechanical and antimicrobial properties of chicken skin gelatin/tapioca starch composite films in food packaging.

The aim of this study was to characterize chicken skin gelatin/tapioca starch composite films with varying concentrations (0-5%) of zinc oxide nanoparticles using the casting technique. The incorporation of 5% zinc oxide nanoparticles increased the water vapor permeation (1.52-1.93 × 10-7 gmm/cm2hPa) and melting temperature of the films. The tensile strength (22.96-50.43 MPa) was increased, while elongation at break decreased with increasing concentrations of zinc oxide nanoparticles. The structures of the films were also investigated via Fourier transform infrared spectroscopy. The inhibitory zones for both the gram-positive (Staphylococcus aureus) (16-20 mm) and gram-negative (Escherichia coli) (15-20 mm) bacteria were larger in the film with 5% zinc oxide. Overall, chicken skin gelatin-tapioca starch composite films with 3% zinc oxide nanoparticles were found to have the optimal formulation, demonstrating good physical, mechanical and antibacterial properties. Gelatin-based composite films with nanoparticle incorporation show strong potential for use in biodegradable food packaging materials.

Unique situation of Gaza Strip dealing with COVID-19 crisis.

Infected COVID19 cases continue to increase, having already reached 21 million globally, attracting scientists around the world to trying to find a possible vaccine. Unlike many places around the world, movement restrictions and difficulties in travelling in and out due to a 13-year-old blockade with no possibility for tourists to travel in, has benefited Gaza in terms of being self-isolated and less likely to have many travellers or foreigners carrying the virus and infecting the population. First cases were discovered on 22 March 2020, and by 05 July 2020, there were still only 72 cases confirmed, 60 of whom were successfully treated, 11 active cases, and only 1 death. Constructively, this study follows a direct observation approach with in-depth disk review for data collected locally from official sources (Governmental bodies, UN agencies, and INGOs); concrete context analysis is then made and used toward predicting the potential risk scenarios associated with COVID19 supported by the application of a simple risk matrix for each scenario within a limited time frame covering the period from 22 March to 05 July 2020. Three different risk scenarios associated with COVID19 risks were studied and analysed towards understanding exceptional circumstances surrounding Gaza along with potential mitigation measures executed and suggested.

Positive effects of high salinity can buffer the negative effects of experimental warming on functional traits of the seagrass Halophila ovalis.

Coastal ecosystems, and especially estuaries, are subject to environmental fluctuations that can be amplified by anthropogenic changes. Under a future scenario of global warming, temperature and salinity are likely to be altered and the persistence of macrophyte-dominated ecosystems can be compromised, particularly native or local seagrass communities. This study examined the response of the local seagrass Halophila ovalis to the joint effect of a short-term salinity increase and a transient temperature stress, through two mesocosm experiments. Warming caused a decline in Fv/Fm, TNC content in leaves and plant growth, and increased dark respiration, revealing clear detrimental symptoms of heat stress on plant metabolism and performance. Salinity increase in isolation favoured ramet survival. However, in combination with warming, salinity had a positive effect on Gross Pmax. This suggests that increased salinities might dampen the negative effects of high temperatures, buffering, to some extent, the impact of global warming in temperate estuaries.

Development of A Disaster Kit Based on A Cultural Context for Flood Disaster Relief and Preparedness

@#Introduction: Flood disaster is a natural disaster that has unexpectedly occurred again. Community cooperation in terms of managing flood and focusing on families’ needs has become more systematic. It is important for a household to be prepared in any disaster. One of the preparations that should be done is the stockpiling of emergency supplies or flood supply kits during evacuation. This study aimed to develop a specific disaster kit for households for evacuation during a flood disaster based on cultural context. Methods: Data were collected from 75 key informants from every level of households that really have a great experience during the flood disaster that helping family packing for a living needs before evacuation. The development of the disaster kit based on cultural needs and all their views, needs, experiences, challenges, frustration and happiness was obtained from the interview sessions. Results: There are five themes that emerged from this research related to developing a disaster kit. The themes are community preparedness in dealing with flood disaster, hygiene issues during the flood, inadequate food supply, how the community responds to insufficient water supply, and coping method with illness. After being finalized, there are seven kits: a general supplies kit, documentation kit, emergency food and water supply kit, prayer kit, hygiene kit, basic first aid kit, and baby kit. Conclusion: The development disaster kit was created to help the communities to be more aware and prepared before disaster strikes.

Ceruminous gland adenocarcinoma in a domestic Persian-mix cat (Felis catus).

A nine years old Persian-mix female cat has been suffering from recurrent bilateral ceruminous gland adenocarcinoma for many years. Masses were first noticed and resected five years ago, but reoccurred later on two more occasions. The animal has usually experienced distressful ear canal problems in association with these masses. The tumor cellular morphology was reviewed, described and discussed. This article is the first in documenting ceruminous gland adenocarcinoma in a Persian-mix cat in Libya.

Fracture risk prediction in post-menopausal women with osteopenia and osteoporosis: preliminary findings

Objective: The study aims to identify the risk of obtaining a fracture among post-menopausal women with osteopenia and osteoporosis. Method: This work was a cross-sectional study involving a purposive sample of 87 post-menopausal women who attended the orthopedic and menopause clinics of Hospital Tengku Ampuan Afzan, Kuantan. The data were entered into the WHO fracture risk assessment tool (FRAX®) to predict major fracture and risk for hip fracture in 10 years' time. Results: The mean age of the respondents was 61.6 years (SD=7.9). Among the respondents, 50.6% had osteopenia and nearly half (48.3%) had osteoporosis. The mean number of menopausal years of the respondents was 11.9 (SD=8.5), ranging between 1 and 44 years. The FRAX findings indicated 9.7% major osteoporotic fracture probability and 3.5% hip fracture probability, which were denoted as high risk. A Pearson correlation coefficient was computed to assess the relationship between menopausal years and the FRAX major osteoporotic fracture probability. A significant positive correlation was found between the two, but the correlation was weak (r=0.581, n=87, p < 0.001). Conclusions: The present findings indicate that menopausal years have a positive correlation with the risk of obtaining a fracture

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What could be the reasons of late diagnosis of breast cancer in Tunisia?

INTRODUCTION: Breast cancer is often diagnosed at a late stage in Tunisia with long delay in time to consultation and to diagnosis. The aim of the study was to identify explanatory factors to delayed diagnosis. METHODS: A case control analytical was performed from January 2013 to December 2014 in the department of Medical Oncology in FarhatHachedUniveristy Hospital.Patients with the diagnosis of ductal breast carcinoma were included in the study.Characteristics of a first group of 200 women with locally advanced or metastatic breast cancer (G1)were compared to a second group of 200 patients with early stage (G2). RESULTS: Median delay in consultation and mean tumor size were significantly more important in group G1 (p<0,001).A low level of schooling, a rural origin, poor socio-economic conditions and no encouragement by the patient relatives do not allow an early diagnosis.Misinterpretation of clinical breast signs was the only explanatory factor related to the system. In multivariate study, a low level of schooling(adjusted OR=2.72; CI 95% [1,65-4,49]), no encouragement by the patient's relatives(adjusted OR=7.86; CI 95% [4,24-14,57])and more than three dependants(adjusted OR=2.49; CI 95% [1,58-3,93]) were the independent factors that could explain the delay in diagnosis. CONCLUSION: Our study confirm the inverse relationship between socio-economic and scholar level and disease stage. Health education campaigns particularly among women with a low schooling level and of rural origin could reduce time for consultation. Promoting continuing medical education could avoid diagnostic errors.

Prenatal stress alters diazepam withdrawal syndrome and 5HT1A receptor expression in the raphe nuclei of adult rats.

Early-life events have long-term effects on brain structures and cause behavioral alterations that persist into adulthood. The present experiments were designed to investigate the effects of prenatal stress on diazepam-induced withdrawal syndrome and serotonin-1A (5HT1A) receptor expression in the raphe nuclei of adult offspring. The results of the present study reveal that maternal exposure to chronic footshock stress increased the anxiety-like behavior in the prenatally stressed (PS) animals withdrawn from chronic diazepam (2.5mg/kg/day i.p for 1week). Moreover, prenatal stress induced a down-regulation of 5HT1A mRNA in the raphe nuclei of adult offspring. To our knowledge, this study is the first to demonstrate that maternal exposure to chronic footshock stress enhances diazepam withdrawal symptoms and alters 5HT1A receptor gene expression in the raphe nuclei of adult offspring. Thus, more studies are needed to clarify the mechanisms underlying the decrease of 5HT1A receptors expression in the raphe nuclei of PS rats.

Prenatal stress induces vulnerability to nicotine addiction and alters D2 receptors' expression in the nucleus accumbens in adult rats.

Prenatal stress (PS) can induce several long-lasting behavioral and molecular abnormalities in rats. It can also be considered as a risk factor for many psychiatric diseases like schizophrenia, depression or PTSD and predispose to addiction. In this study, we investigated the effect of prenatal stress on the reinforcing properties of nicotine in the CPP paradigm. Then, we examined the mRNA expression of the D2 dopaminergic receptors using the quantitative real-time PCR technique in the nucleus accumbens (NAcc). We found that prenatally stressed rats exhibited a greater place preference for the nicotine-paired compartment than the control rats. Moreover, we observed an overexpression of the DRD2 gene in adult offspring stressed in utero and a downregulation in the PS NIC group (PS rats treated with nicotine) compared with their control counterparts (C NIC). These data suggest that maternal stress can permanently alter the offspring's addictive behavior and D2 receptors' expression.

Effect of prenatal stress on memory, nicotine withdrawal and 5HT1A expression in raphe nuclei of adult rats.

Maternal distress has often been associated with cognitive deficiencies and drug abuse in rats. This study examined these behavioral effects in offspring of mothers stressed during gestation. To this end, pregnant dams were subjected to daily electric foot shocks during the last 10 days of pregnancy. We measured litter parameters and body weights of the descendants after weaning (21 days) and at adulthood (80 days). Afterwards, prenatally stressed and control rats' performances in the novel object recognition test were compared in order to evaluate their memory while others underwent the Water consumption test to assess the nicotine withdrawal intensity after perinatal manipulations. Meanwhile, another set of rats were sacrificed and 5HT1A receptors' mRNA expression was measured in the raphe nuclei by quantitative Real Time PCR. We noticed no significant influence of maternal stress on litter size and body weight right after weaning. However, control rats were heavier than the stressed rats in adulthood. The results also showed a significant decrease in the recognition score in rats stressed in utero compared to the controls. Moreover, a heightened anxiety symptom was observed in the prenatally stressed offspring following nicotine withdrawal. Additionally, the Real Time PCR method revealed that prenatal stress induced a significant decrease in 5HT1A receptors' levels in the raphe nuclei. Nicotine had a similar effect on these receptors' expression in both nicotine-treated control and prenatally stressed groups. Taken together, these findings suggest that the cognitive functions and drug dependence can be triggered by early adverse events in rats.

Long-term effects of prenatal stress and diazepam on D2 receptor expression in the nucleus accumbens of adult rats.

Early life stress during the gestational period alters specific neuronal circuits leading to behavioral alterations later in life. In the present study, we assessed the effects of prenatal stress and repeated benzodiazepine administration on dopamine receptor 2 expression in the nucleus accumbens of adult offspring. Our results show elevated Drd2 expression levels in the nucleus accumbens (NAcc) of prenatally stressed rats compared to control subjects, while repeated diazepam administration in adulthood down-regulated Drd2 expression and prevented the effect of prenatal stress. These observations suggest that prenatal stress may induce permanent alterations in the corticolimbic pathway implicated in drug-seeking behavior.

Effects of prenatal stress on anxiety-like behavior and nociceptive response in rats.

We assess the anxiety-like behavior in the open field and elevated plus maze tests and measure the nociceptive response in the tail flick test following prenatal stress exposure in adult male and female Wistar rats. In both behavioral anxiety tests, prenatal stress increased the anxiety-like behavior in male PS rats, but not in females suggesting a strong sex-dependent anxiogenic effect. The tail flick results showed a hypersensitivity to pain in male and female PS rats with a subtle gender difference. These findings suggest that prenatal stress is an important risk factor for multiple mental disorders.

Prenatal stress alters sensitivity to benzodiazepines in adult rats.

In rats, prenatal stress (PS) induces persistent changes in the brain that eventually can be translated in altered behavior leading to a greater consumption of psychostimulants in the offspring during adulthood. Though many studies have been carried on the effects of PS on stimulant drug responsiveness, little is known about susceptibility to benzodiazepines dependence in this animal model. We hereby examined the long-lasting impact of PS exposure during the last 10 days of pregnancy on the vulnerability to benzodiazepine addiction in adult rats. In addition, we also investigated the link between PS and the sensitivity to anxiolytics. Our results reveal that PS offspring exhibited a significantly greater preference to the diazepam-paired side than control offspring in the conditioned place preference. Importantly, we found that PS enhanced the anxiolytic effects of diazepam in the elevated plus maze paradigm. This work demonstrates that PS increased the abuse potential of benzodiazepines and the sensitivity to anxiolytic drugs in offspring of stressed mothers. Thus, investigating the interactions among addiction and PS may contribute to a better understanding how early life events modify neural circuitry and thereby behavior.

Assessing and Exploring the Competency of Prehospital Emergency Medical Service Personnel in Klang Valley, Malaysia: a Mixed Method Approach

The notion of competency in pre-hospital emergency medical service (EMS) personnel is mainly focused on the professional proficiency that he/she has to provide intervention outside of hospital setting. Consequently, the effectiveness of pre-hospital EMS performance very much depends upon the capability of the personnel at the scene and as well during transport to the definitive care center. The aim of this study is to appraise and explore the competency of pre-hospital care staff and provide strategies for improvement. Methods: A mixed method approach combining the qualitative and quantitative study design. Of 134 staffs only 111(82.84%) returned the questionnaire. Nine semi-structured interviews and two focus group discussions were performed. The main informants were nurses/assistant medical officers, nurse/assistant medical officer administrators, and emergency physicians. Results: From the quantitative finding on the competency of staff handling pre-hospital EMS, all had the essential knowledge and skills. However, most of them reported not having good knowledge and skills for invasive procedures (31%-61%), include giving medications (61%-66%). The qualitative information provided insight about the issues and strategies for the personnel in regards to competency. All the relevant qualitative data were merged into 5 categories relating issues and 5 categories to strategies that could affect the competency of the personnel. Conclusion: Pre-hospital EMS systems need to consider that the competency of pre-hospital EMS personnel has to come along with the responsible attitude of the staff itself, the support of medical direction, clear protocol for guiding them whenever needed, and continuous professional-development courses require them to maintain their professional proficiency.