Modification of χ_{c1}(3872) and ψ(2S) Production in pPb Collisions at sqrt[s_{NN}]=8.16 TeV.

The LHCb Collaboration measures production of the exotic hadron χ_{c1}(3872) in proton-nucleus collisions for the first time. Comparison with the charmonium state ψ(2S) suggests that the exotic χ_{c1}(3872) experiences different dynamics in the nuclear medium than conventional hadrons, and comparison with data from proton-proton collisions indicates that the presence of the nucleus may modify χ_{c1}(3872) production rates. This is the first measurement of the nuclear modification factor of an exotic hadron.

Analysis of Methylome of Different Forms of Basal Cell Hyperplasia and Squamous Cell Metaplasia of Bronchial Epithelium.

Squamous cell lung cancer (SCLC) occurs as a result of dysregenerative changes in the bronchial epithelium: basal cell hyperplasia (BCH), squamous cell metaplasia (SM), and dysplasia. We previously suggested that combinations of precancerous changes detected in the small bronchi of patients with SCLC may reflect various "scenarios" of the precancerous process: isolated BCH→stopping at the stage of hyperplasia, BCH+SM→progression of hyperplasia into metaplasia, SM+dysplasia→progression of metaplasia into dysplasia. In this study, DNA methylome of various forms of precancerous changes in the bronchial epithelium of SCLC patients was analyzed using the genome-wide bisulfite sequencing. In BCH combined with SM, in contrast to isolated BCH, differentially methylated regions were identified in genes of the pathogenetically significant MET signaling pathway (RNMT, HPN). Differentially methylated regions affecting genes involved in inflammation regulation (IL-23, IL-23R, IL12B, IL12RB1, and FIS1) were detected in SM combined with dysplasia in comparison with SM combined with BCH. The revealed changes in DNA methylation may underlie various "scenarios" of the precancerous process in the bronchial epithelium.

Nandrolone decanoate impairs gastrointestinal motility and duodenal morphometry in moderately exercised rats.

The misuse of anabolic androgenic steroid associated or not with physical workouts disrupts gastrointestinal (GI) function homeostasis. Our goal was to investigate the effects of nandrolone decanoate (ND) and moderate swimming on the GI transit of solid meals, GI motor contractility, and intestinal histology in rats. Male Wistar rats were allocated to four groups that received intramuscular injections of ND (5.0 mg/kg) or vehicle (60.0 µL) and were submitted or not to swimming sessions (60 min, 5% body weight overload) for 4 weeks. Gastric emptying, intestinal transit, in vitro GI contractility, intestinal morphometry, and duodenal mucosal mast cells were evaluated in all experimental groups. ND treatment accelerated gastric emptying, slowed small intestine transit time, enhanced gastric carbachol-mediated reactivity, decreased crypt depth and villus height, reduced mucosal thickness, and increased the circular and longitudinal muscle layer thickness of the duodenum in sedentary rats. Moderate exercise accelerated intestinal transit time and reduced submucosa thickness. In vehicle-treated animals, a strong negative correlation was found between intestinal transit and mucosal mast cells, which was reversed by ND treatment. Combining ND treatment and swimming accelerated gastric emptying, increased duodenal cholinergic reactivity, inhibited the sodium nitroprusside relaxing response, increased the number of duodenal mast cells, decreased villus height, and increased the thickness of all muscle layers. ND changed the morphological and functional properties of the GI tract over time, with intense dysmotility, especially in sedentary animals, but moderate exercise seemed to have played a compensatory role in these harmful effects in the gut.

Clarifying terminology and definitions in education services for mental health users: A disambiguation study.

In the wake of the mental health crisis in children and adolescents, the coordination of education and mental health services has become a global priority. However, differing terminologies and classifications across sectors, hinder effective comparison. The classification in education focuses mainly on outputs like qualifications or throughputs like teaching programs. This proof-of-concept study tested the applicability of a standard classification of health services, the Description and Evaluation of Services and DirectoriEs (DESDE), to evaluate education services for mental health users in the context of Spain and The Netherlands. It was conducted alongside the PECUNIA project, that sought to develop methods for the assessment of mental health costs and outcomes in different sectors. The study followed an ontoterminology approach involving: 1) identification of services from a predefined list of 46 resource-use items, 2) disambiguation of identified services with the DESDE, and classifying them as accurate, ambiguous, vague or confuse; and 3) external validation by an expert panel. The analysis was conducted at the level of type of resource, target population and care provision. From the initial list, only ten of the resources could be categorized as services using DESDE, and not activities, interventions or professionals. Only four of them (8,65%) were accurate across all disambiguation categories. Experts were unaware of terminology problems in classification of service provision in the education sector. Classifications and glossaries can clarify service naming, description and costing allowing comparative effectiveness analysis and facilitating cross-sectoral planning. This should be grounded in common methodologies, tools, and units of analysis.

Estimation of methane greenhouse gas emissions from livestock in Egypt during 1989 to 2021.

This study investigates methane emissions from the livestock sector, representing by enteric fermentation and manure management, in Egypt from 1989 to 2021, focusing on spatial and temporal variations at the governorate level. Utilizing IPCC guidelines and emission factors, methane emissions were estimated for dairy and non-dairy cattle, buffalo, sheep and goat, poultry, and other livestock categories. Results reveal fluctuating emission patterns over the study period, with notable declines in certain governorates such as Kafr El-Sheikh and Red Sea, attributed to reductions in livestock populations. However, increasing trends were observed overall, driven by population growth in other regions. Hotspots of methane emissions were identified in delta governorates like Behera and Sharkia, as well as agriculturally rich regions including Menia and Suhag. While livestock populations varied between regions, factors such as water availability, climatic conditions, and farming practices influenced distribution. Notably, cluster analysis did not reveal regional clustering among governorates, suggesting emissions changes were not dependent on specific geographic or climatic boundaries. Manure management accounted for only 5-6% of total emissions, with emissions at their lowest in the last three years due to population declines. Despite the highest livestock populations being sheep and goats, emissions from enteric fermentation and manure management were highest from buffalo and cattle. This study underscores the importance of accurate data collection and adherence to IPCC recommendations for estimating GHG emissions, enabling the development of targeted mitigation strategies to address climate change challenges in the livestock sector.

Cyclic quantum teleportation of two-qubit entangled states by using six-qubit cluster state and six-qubit entangled state.

Cyclic quantum teleportation schemes requires at least the existence of three collaborators acting all as senders and receivers of quantum information, each one of them has an information to be transmitted to the next neighbour in a circular manner. Here, new cyclic quantum teleportation scheme is proposed for perfectly transmitting cyclically three arbitrary unknown two-qubit states ( α , ß and γ ) among the three collaborators. In this scheme, Alice can send to Bob the quantum information contained in her two-qubit state α and receive from Charlie the quantum information contained in the two-qubit state in his possession γ and similarly, Bob can transmit to Charlie the quantum information contained in his two-qubit state ß through a quantum channel of twelve-qubit state consisting of a six-qubit cluster state and a six-qubit entangled state by sequentially and cyclically performing Bell state measurements. Subsequently, each one of the three participants can afterwards retrieve his own desired two-qubit state using classical channel and by performing appropriate unitary Pauli operators and we have shown that our proposed scheme performs efficiently.

Lower hair cortisol concentration in adolescent and young adult patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Q-Fever Fatigue Syndrome compared to controls.

BACKGROUND: In patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), momentary cortisol concentrations in blood, urine, and saliva are lower compared to healthy controls. Long-term cortisol concentration can be assessed through hair, but it is unclear whether these concentrations are also lower. Additionally, it is unknown if lower cortisol extends to other patients suffering from persistent fatigue and how hair cortisol concentration (HCC) relates to fatigue levels. Therefore, this study examines HCC in fatigued patients with ME/CFS, Q fever Fatigue Syndrome (QFS), Post-COVID-19 condition (PCC), and Juvenile Idiopathic Arthritis (JIA). METHODS: Adolescent and young adult patients with ME/CFS (n=12), QFS (n=20), PCC (n=8), JIA (n=19), and controls (n=57) were included. Patients participated in a randomized cross-over trial (RCT) targeting fatigue through lifestyle and dietary self-management strategies. HCC was measured pre-post RCT in patients and once in controls, quantified using a LC-MS/MS-based method. Fatigue severity was measured with the Checklist Individual Strength-8. HCC was compared between groups with ANOVAs. Relations between HCC, fatigue severity, and other variables were investigated using linear regression analyses. RESULTS: The ME/CFS (p=.009) and QFS (p=.047) groups had lower HCC compared to controls. Overall, HCC was negatively associated with the presence of symptoms related to chronic fatigue syndromes (e.g., sleeping issues, often feeling tired, trouble thinking clearly; ß=-0.018, p=.035), except in the QFS group (ß=.063, p<.001). Baseline HCC did not predict fatigue improvement during the RCT (p=.449), and HCC increased during the trial (Mdif=.076, p=.021) regardless of clinically relevant fatigue improvement (p=.658). CONCLUSION: Lower cortisol concentration can also be observed in the long-term. Lower HCC is not limited to ME/CFS, as it was also observed in QFS. The role of cortisol may differ between these diagnoses and appears to be unrelated to fatigue levels.

Identification of heparin-binding amino acid residues in antibody HS4C3 with the potential to design antibodies against heparan sulfate domains.

Heparan sulfate (HS) is a linear polysaccharide with high structural and functional diversity. Detection and localization of HS in tissues can be performed using single chain variable fragment (scFv) antibodies. Although several anti-HS antibodies recognizing different sulfation motifs have been identified, little is known about their interaction with HS. In this study the interaction between the scFv antibody HS4C3 and heparin was investigated. Heparin-binding lysine and arginine residues were identified using a protect and label methodology. Site-directed mutagenesis was applied to further identify critical heparin-binding lysine/arginine residues using immunohistochemical and biochemical assays. In addition, computational docking of a heparin tetrasaccharide towards a 3-D homology model of HS4C3 was applied to identify potential heparin-binding sites. Of the 12 lysine and 15 arginine residues within the HS4C3 antibody, 6 and 9, respectively, were identified as heparin-binding. Most of these residues are located within one of the complementarity determining regions (CDR) or in their proximity. All basic amino acid residues in the CDR3 region of the heavy chain were involved in binding. Computational docking showed a heparin tetrasaccharide close to these regions. Mutagenesis of heparin-binding residues reduced or altered reactivity towards HS and heparin. Identification of heparin-binding arginine and lysine residues in HS4C3 allows for better understanding of the interaction with HS and creates a framework to rationally design antibodies targeting specific HS motifs.

Menstrual pain self-medication relates to poor mental health outcomes from Al-Zaatri refugees' camp.

Dysmenorrhea, the most common gynecological pain syndrome reported in women, is understudied in refugee communities. In addition, the association between dysmenorrhea self-medication and mental health symptoms in this population is poorly understood. We aimed to examine whether the use of dysmenorrhea analgesic self-medications and other clinical factors are associated with post-traumatic stress disorder (PTSD), depression, anxiety and insomnia severity in female war refugees residing in Zaatari Camp. This study followed a cross-sectional design and was performed on a cohort of women with predefined inclusion criteria. The severity of PTSD, depression, anxiety and insomnia were assessed using Davidson Trauma Scale, the Patient Health Questionnaire-9, the General Anxiety Disorder-7, and the Arabic version of the Insomnia Severity Index, respectively. Data were analysed from 386 participants. Using OTC paracetamol was significantly associated with higher PTSD severity (B=4.16, t= 2.43, p=0.01), and severe depression (OR=1.88, 95% CI= 1.07-3.28, p=0.03), while OTC non-steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with severe insomnia (OR=1.62, 95% CI= 1.05-2.49, p= 0.02). In conclusion, self-medication with analgesics was correlated with poor mental health; close medical and psychiatric follow-up are required to supervise pain self-medication and implement non-pharmacological strategies to manage dysmenorrhea in this fragile community.

La dysménorrhée, le syndrome douloureux gynécologique le plus fréquemment signalé chez les femmes, est peu étudiée dans les communautés de réfugiés. De plus, l'association entre l'automédication de la dysménorrhée et les symptômes de santé mentale dans cette population est mal comprise. Nous avions pour objectif d'examiner si l'utilisation d'automédicaments analgésiques contre la dysménorrhée et d'autres facteurs cliniques sont associés au trouble de stress post-traumatique (SSPT), à la dépression, à l'anxiété et à la gravité de l'insomnie chez les réfugiées de guerre résidant dans le camp de Zaatari. Cette étude a suivi une conception transversale et a été réalisée sur une cohorte de femmes avec des critères d'inclusion prédéfinis. La gravité du SSPT, de la dépression, de l'anxiété et de l'insomnie a été évaluée à l'aide de l'échelle de traumatisme de Davidson, du questionnaire sur la santé du patient-9, du trouble d'anxiété général-7 et de la version arabe de l'indice de gravité de l'insomnie, respectivement. Les données ont été analysées auprès de 386 participants. L'utilisation de paracétamol en vente libre était significativement associée à une gravité plus élevée du SSPT (B = 4,16, t = 2,43, p = 0,01) et à une dépression sévère (OR = 1,88, IC à 95 % = 1,07-3,28, p = 0,03), tandis que les médicaments non stéroïdiens en vente libre les anti-inflammatoires (AINS) étaient associés de manière significative à l'insomnie sévère (OR = 1,62, IC à 95 % = 1,05-2,49, p = 0,02). En conclusion, l'automédication avec des analgésiques était corrélée à une mauvaise santé mentale ; un suivi médical et psychiatrique étroit est nécessaire pour encadrer l'automédication de la douleur et mettre en œuvre des stratégies non pharmacologiques pour prendre en charge la dysménorrhée dans cette communauté fragile.

Structure-Activity Relationship Studies of Aryl Sulfoxides as Reversible Monoacylglycerol Lipase Inhibitors.

Monoacylglycerol lipase (MAGL) is the key enzyme for the hydrolysis of endocannabinoid 2-arachidonoylglycerol (2-AG). The central role of MAGL in the metabolism of 2-AG makes it an attractive therapeutic target for a variety of disorders, including inflammation-induced tissue injury, pain, multiple sclerosis, and cancer. Previously, we reported LEI-515, an aryl sulfoxide, as a peripherally restricted, covalent reversible MAGL inhibitor that reduced neuropathic pain and inflammation in preclinical models. Here, we describe the structure-activity relationship (SAR) of aryl sulfoxides as MAGL inhibitors that led to the identification of LEI-515. Optimization of the potency of high-throughput screening (HTS) hit 1 yielded compound ±43. However, ±43 was not metabolically stable due to its ester moiety. Replacing the ester group with α-CF2 ketone led to the identification of compound ±73 (LEI-515) as a metabolically stable MAGL inhibitor with subnanomolar potency. LEI-515 is a promising compound to harness the therapeutic potential of MAGL inhibition.

Computer modeling of the peculiarities in the interaction of IL-1 with its receptors in schizophrenia.

One of the primary theories regarding the development of schizophrenia revolves around genetics, indicating the involvement of hereditary factors in various processes, including inflammation. Research has demonstrated that inflammatory reactions occurring in microglia can impact the progression of the disease. It has also been established that genetically determined changes in IL-1 can contribute to schizophrenia, thereby confirming the role of the IL-1 gene cluster in disease susceptibility. The aim of this study is a computer-based assessment of the structural interactions of IL-1 proteins with their receptors in schizophrenia. The study utilized the DisGeNET database, enabling the assessment of the reliability of identified IL-1 polymorphisms. Polymorphisms were also sought using NCBI PubMed. The NCBI Protein service was employed to search for and analyze the position of the identified polymorphisms on the chromosome. Structures for modeling were extracted from the Protein Data Bank database. Protein modeling was conducted using the SWISS-MODEL server, and protein interaction modeling was performed using PRISM. Notably, this study represents the first prediction of the interactions of IL-1α, IL-1ß, and IL- 1RA proteins, taking into account the presence of single-nucleotide polymorphisms associated with schizophrenia in the sequence of the corresponding genes. The results indicate that the presence of SNP rs315952 in the IL-1RA protein gene, associated with schizophrenia, may lead to a weakening of the IL-1RA binding to receptors, potentially triggering the initiation of the IL-1 signaling pathway by disrupting or weakening the IL-1RA binding to receptors and facilitating the binding of IL-1 to them. Such alterations could potentially lead to a change in the immune response. The data obtained contribute theoretically to the development of ideas about the molecular mechanisms through which hereditary factors in schizophrenia influence the interactions of proteins of the IL-1 family, which play an important role in the processes of the immune system.

A critical review of MXene-based composites in the adsorptive and photocatalysis of hexavalent chromium removal from industrial wastewater.

The growing concern of water pollution is a critical issue stemming from industrialization and urbanization. One of the specific concerns within this broader problem is the toxicity associated with chromium (Cr), especially in its Cr (VI) form. Transition metal carbides/nitrides (MXenes) are attractive materials for the treatment of water due to their unique properties such as layered structure, high surface area, conductivity, flexibility, scalable manufacture, and surface functions. Adsorption and photocatalysis reactions are the two promising methods for the removal of Cr (VI) by using MXenes. Still, most of the previous reviews were limited to the single application area. Hence, this review covers recent developments in MXene-based composites, highlighting their dual role as both adsorbents and photocatalysts in the removal of Cr (VI). MXene-based composites are found to be effective in both adsorption and photodegradation of Cr (VI). Most MXene-based composites have demonstrated exceptional removal efficiency for Cr (VI), achieving impressive adsorption capacities ranging from 100 to 1500 mg/g and degradation percentages between 80% and 100% in a relatively short period. The active functional groups present on the surface of MXene have a viable impact on the adsorption and photodegradation performance. The mechanism of Cr (VI) removal is explained, with MXenes playing a key role in electrostatic attraction for adsorption and as co-catalysts in photocatalysis. However, MXene-based composites have limitations such as instability, competition with co-existing ions, and regeneration challenges. Further research is needed to address these limitations. Additionally, MXene-based composites hold promise for addressing water contamination, heavy metal removal, hydrogen production, energy storage, gas sensing, and biomedical applications.

True uterus didelphys in she-camel: a case report and review of literature.

Background: Uterus didelphys is a rare congenital anomaly of the female reproductive tract characterized by a divided uterine cervix and body. It occurs due to abnormal development of the paramesonephric (Müllerian) duct. Different forms of uterus didelphys have been reported in several animal species, including bovine, equine, ewe, goat, swine, and bitch. However, there is no previous report that has documented a completely divided female genital tract in she-camel. Moreover, there is a lack of literature regarding this anomaly in animals. Therefore, the present study reports, for the first time, a rare case of a completely divided female genital tract in a she-camel. In addition, the existing relevant literature on uterus didelphys in different animal species is reviewed. Case presentation: A female reproductive tract of she-camel, approximately 10 years old, with a history of previous successful pregnancy, was brought to the anatomy department following the slaughtering of the animal. Initial examination revealed a normal reproductive tract consisting of two ovaries, two fallopian tubes, a uterus, and a vagina. A closer examination revealed a completely divided vagina, with an external os opened into each part of the vagina, as well as a divided uterine body and cervix. Intrauterine infusion of saline through one external os confirmed complete separation of uterine body and cervix. Conclusion: To the authors' knowledge, this is the first reported case of a completely divided female genital tract in a she-camel. This review summarizes the previous reports about uterus didelphys in farm animals.

Comparative immune profiling of pancreatic ductal adenocarcinoma progression among South African patients.

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer characterized by an immunosuppressive microenvironment. Patients from specific ethnicities and population groups have poorer prognoses than others. Therefore, a better understanding of the immune landscape in such groups is necessary for disease elucidation, predicting patient outcomes and therapeutic targeting. This study investigated the expression of circulating key immune cell markers in South African PDAC patients of African ancestry. METHODS: Blood samples were obtained from a total of 6 healthy volunteers (HC), 6 Chronic Pancreatitis (CP) and 34 PDAC patients consisting of 22 resectable (RPC), 8 locally advanced (LAPC) and 4 metastatic (MPC). Real-time Quantitative Polymerase Chain reactions (RT-qPCR), Metabolomics, Enzyme-Linked Immunosorbent Assay (ELISA), Reactive Oxygen Species (ROS), and Immunophenotyping assays were conducted. Statistical analysis was conducted in R (v 4.3.2). Additional analysis of single-cell RNA data from 20 patients (16 PDAC and 4 controls) was conducted to interrogate the distribution of T-cell and Natural Killer cell populations. RESULTS: Granulocyte and neutrophil levels were significantly elevated while lymphocytes decreased with PDAC severity. The total percentages of CD3 T-cell subpopulations (helper and double negative T-cells) decreased when compared to HC. Although both NK (p = 0.014) and NKT (p < 0.001) cell levels increased as the disease progressed, their subsets: NK CD56dimCD16- (p = 0.024) and NKTs CD56+ (p = 0.008) cell levels reduced significantly. Of note is the negative association of NK CD56dimCD16- (p < 0.001) cell levels with survival time. The gene expression analyses showed no statistically significant correlation when comparing the PDAC groups with the controls. The inflammatory status of PDAC was assessed by ROS levels of serum which were elevated in CP (p = 0.025), (RPC (p = 0.003) and LAPC (p = 0.008)) while no significant change was observed in MPC, compared to the HC group. ROS was shown to be positively correlated with GlycA (R = 0.45, p = 0.0096). Single-cell analyses showed a significant difference in the ratio of NKT cells per total cell counts in LAPC (p < 0.001) and MPC (p < 0.001) groups compared with HC, confirming observations in our sample group. CONCLUSION: The expression of these immune cell markers observed in this pilot study provides insight into their potential roles in tumour progression in the patient group and suggests their potential utility in the development of immunotherapeutic strategies.

Risk of acute coronary syndrome and relationship with the use of khat and tobacco products in the Jazan region, Saudi Arabia: A prospective case-control study.

INTRODUCTION: Previous studies have identified several risk factors for acute coronary syndrome (ACS). This study was intended to examine the potential risk of ACS associated with khat and tobacco use. METHODS: A case-control study of 344 people (172 cases and 172 controls) was conducted at Prince Mohammed Bin Nasser Hospital in Jazan, Saudi Arabia, from April to September 2019. The cases and controls were matched for age (±5 years) and gender. Data were analyzed using descriptive, inferential, and modeling analyses. We utilized the adjusted odds ratio (AOR) to express the results. RESULTS: The prevalence of ever khat chewing among all study participants was 29.1%, significantly higher for the cases with ACS than for the control group (43.6% vs 14.5%, p<0.001). Cigarette smokers accounted for 33.4% of the study participants, and 22.1% were ACS cases, which is a significantly higher percentage than the control group. The prevalence of smokeless tobacco was 20.3% among ACS cases and 14.5% among controls, with no statistically significant differences (p>0.05). In the final model, tobacco use was more likely to be reported among cases with myocardial infarction (MI) (AOR=4.58; 95% CI: 1.01-4.73, p<0.05) as was khat chewing (AOR=3.4; 95% CI: 1.55-7.46, p<0.05), after controlling for other traditional risk factors. CONCLUSIONS: Khat chewing was reported more by those who reported ACS. ACS cases were more likely to be frequent khat users with chewing sessions of five or more days per week. Regular tobacco use was also reported in those who reported ACS, and this increases with the amount of tobacco used. Implementing early intervention strategies can help mitigate the impact of khat chewing and smoking on the development of ACS.

Reconstruction of Z-pinch emission spectra in the wavelength range of less than 10 Å using a crystal X-ray spectrograph.

This work is devoted to the reconstruction of Z-pinch plasma emission spectra in the wavelength range of less than 10 Å recorded by using a crystal x-ray spectrograph at the Angara 5-1 mega-ampere facility. The spectrograph JA-1 used in experiments has a cylindrical mica crystal with dimensions of 50 × 40 mm2 and radius of curvature of 100 mm. Registration of spectra is performed on the photographic film UF-4 with dimensions of 30 × 10 mm2. To reconstruct the spectra, the previously developed method based on iterative approximation of a true spectrum shape while minimizing a residual between experimental and calculated spectrograms is used. The calculated spectrogram was obtained taking into account the instrumental function of the spectrograph. To define the instrumental function a virtual Monte-Carlo model in the Geant4 toolkit has been developed. This model takes into account the interaction of radiation with the mica crystal using dynamical theory of diffraction. A true spectrum of Z-pinch plasma radiation is reconstructed for a 16 mm high load made of two nested cylindrical wire liners. External liner with a diameter of 12 mm has 40 Al wires with a diameter of 18 µm. The internal liner with a diameter of 5 mm has 4 W wires with a diameter of 6 µm. The W wires have a sputtered layer of Re that is 0.5 µm thick.

SARS-CoV-2 clearance in term of Cycle Threshold (Ct) during first two waves of COVID-19 in Pakistan: a phenomenon of delayed viral clearance post-corticosteroid treatment.

SARS-CoV-2 is recently emerged virus, which caused millions of deaths, all over the world. To tackle COVID-19 pandemic, there is an utmost need for in-depth analysis of viral replication. We aimed to examine viral load in SARS-CoV-2 patients during first two waves of COVID-19 in Pakistan. 225,615 suspected subjects from 75 different regions of Pakistan were selected in the study. SARS-CoV-2 RNAs were detected via real time PCR. During first wave (period of June-July, 2020) of COVID-19 the prevalence of SARS-CoV-2 was 20.38%. However, during second wave (period of November-December, 2020) of COVID-19, the rate of prevalence was 9.41%. During first wave of COVID-19 96.31% of participants remained PCR positive for 14 to 21 days, 3.39% of subjects showed positive results for 22 to 35 days, while delayed Ct values were observed among 0.26% of participants for 36 to 49 days. However, during second wave of COVID-19 89.31% of the subjects exhibited symptoms and showed real-time PCR positive results for 14 to 21 days, 9.42% showed positive results for 22 to 35 days, while significantly delayed Ct value results were observed among 1.026% of participants for 36 to 63 days (3.95 times higher than first wave). In contrast to first wave of COVID-19, the factors that were different in second wave were neither viral (different strains) nor host (same population). But treatment factors changed significantly. As during second wave besides azithromycin, corticosteroid dexamethasone consumption was increased consequently causing delayed Ct value negativity. This suggests that corticosteroid treatment might be linked with delayed Ct value or viral clearance. This study is crucial for re-considering effective therapeutic options against COVID-19.

Feasibility, safety, and efficacy of dietary or lifestyle interventions for hypothalamic obesity: A systematic review.

BACKGROUND & AIMS: A dysfunctional hypothalamus may result in decreased feelings of satiety (hyperphagia), decreased energy expenditure, and increased fat storage as a consequence of hyperinsulinemia. Hypothalamic dysfunction may thus lead to morbid obesity and can be encountered in childhood as a consequence of congenital, genetic, or acquired disorders. There is currently no effective treatment for hypothalamic obesity (HO). However, comparable to alimentary obesity, dietary and lifestyle interventions may be considered the cornerstones of obesity treatment. We questioned the effect of dietary or lifestyle interventions for HO and systematically searched the literature for evidence on feasibility, safety, or efficacy of dietary or lifestyle interventions for childhood hypothalamic overweight or obesity. METHODS: A systematic search was conducted in MEDLINE (including Cochrane Library), EMBASE, and CINAHL (May 2023). Studies assessing feasibility, safety, or efficacy of any dietary or lifestyle intervention in children with hypothalamic overweight or obesity, were included. Animal studies, studies on non-diet interventions, and studies with no full text available were excluded. Because the number of studies to be included was low, the search was repeated for adults with hypothalamic overweight or obesity. Risk of bias was assessed with an adapted Cochrane Risk of Bias Tool. Level of evidence was assessed using the GRADE system. Descriptive data were described, as pooled-data analysis was not possible due to heterogeneity of included studies. RESULTS: In total, twelve studies were included, with a total number of 118 patients (age 1-19 years) of whom one with craniopharyngioma, one with ROHHAD-NET syndrome, 50 with monogenic obesity, and 66 with Prader-Willi syndrome (PWS). Four studies reported a dietary intervention as feasible. However, parents did experience difficulties with children still stealing food, and especially lowering carbohydrates was considered to be challenging. Seven studies reported on efficacy of a dietary intervention: a well-balanced restrictive caloric diet (30% fat, 45% carbohydrates, and 25% protein) and various hypocaloric diets (8-10 kcal/cm/day) were considered effective in terms of weight stabilization or decrease. No negative effect on linear growth was reported. Four studies reported on specific lifestyle interventions, of which three also included a dietary intervention. Combined dietary and lifestyle intervention resulted in decreased BMI, although BMI returned to baseline values on long-term. One additional study was identified in adults after brain trauma and showed a significant reduction in BMI in one out of eight patients after a combined dietary and lifestyle intervention. CONCLUSIONS: Hypocaloric diet or restrictive macronutrient diet with lower percentage of carbohydrates seems feasible and effective for childhood HO, although most of the studies had a high risk of bias, small cohorts without control groups, and were conducted in children with PWS only, compromising the generalizability. Lifestyle interventions only resulted in BMI decrease in short-term, indicating that additional guidance is needed to sustain its effect in the long-term. Literature on feasibility and efficacy of a dietary or lifestyle intervention for hypothalamic overweight or obesity is scarce, especially in children with acquired HO (following treatment for a suprasellar tumor). There is need for prospective (controlled) studies to determine which dietary and lifestyle intervention are most helpful for this specific patient group.