Search

Introduction: Opioid use disorder (OUD) is a major public health crisis worldwide. Patients with OUD inevitably experience withdrawal symptoms when they attempt to taper down on their current opioid use, abstain completely from opioids, or attempt to transition to certain medications for opioid use disorder. Acute opioid withdrawal can be debilitating and include a range of symptoms such as anxiety, pain, insomnia, and gastrointestinal symptoms. Whereas acute opioid withdrawal only lasts for 1-2 weeks, protracted withdrawal symptoms can persist for months after the cessation of opioids. Insufficient management of opioid withdrawal often leads to devastating results including treatment failure, relapse, and overdose. Thus, there is a critical need for cost-effective, nonopioid medications, with minimal side effects to help in the medical management of opioid withdrawal syndrome. We discuss the potential consideration of cannabidiol (CBD), a nonintoxicating component of the cannabis plant, as an adjunctive treatment in managing the opioid withdrawal syndrome. Materials and Methods: A review of the literature was performed using keywords related to CBD and opioid withdrawal syndrome in PubMed and Google Scholar. A total of 144 abstracts were identified, and 41 articles were selected where CBD had been evaluated in clinical studies relevant to opioid withdrawal. Results: CBD has been reported to have several therapeutic properties including anxiolytic, antidepressant, anti-inflammatory, anti-emetic, analgesic, as well as reduction of cue-induced craving for opioids, all of which are highly relevant to opioid withdrawal syndrome. In addition, CBD has been shown in several clinical trials to be a well-tolerated with no significant adverse effects, even when co-administered with a potent opioid agonist. Conclusions: Growing evidence suggests that CBD could potentially be added to the standard opioid detoxification regimen to mitigate acute or protracted opioid withdrawal-related symptoms. However, most existing findings are either based on preclinical studies and/or small clinical trials. Well-designed, prospective, randomized-controlled studies evaluating the effect of CBD on managing opioid withdrawal symptoms are warranted.

A 76-year-old man was admitted to the hospital with acute onset of involuntary movements of the left side of his body. His neurological examination revealed he was oriented only to himself, and aforementioned movements of his left arm and leg. CT head demonstrated old infarcts in his right aspect of his pons and basal ganglia. Cerebrospinal fluid analysis was unremarkable. He initially had a normal blood glucose with an elevated anion gap and elevated creatine kinase. Brain MRI showed a small lacunar-type ischaemic infarct within the anteromedial aspect of the right cerebral peduncle, which localised to his haemiballism. To prevent worsening rhabdomyolysis associated with his haemiballism, the primary team initiated both tetrabenazine and diazepam. His movements improved after 1 week of medication therapy. This report discusses a thorough workup for this movement disorder and when to intervene for this distressing condition.

Background Cannabis remains one of the most widely abused drugs during pregnancy. In utero exposure to its principal psychoactive component, Δ9-tetrahydrocannabinol (THC), can result in long-term neuropsychiatric risk for the progeny. The current study investigated epigenetic signatures underlying these enduring consequences. Methods Rat dams were exposed daily to THC (0.15mg/kg) during pregnancy and adult male offspring were examined for reward and depressive-like behavioral endophenotypes. Using unbiased sequencing approaches, we explored transcriptional and epigenetic profiles in the nucleus accumbens (NAc), a brain area central to reward and emotional processing. An in vitro CRISPRa model coupled with RNA-sequencing was also applied to study specific consequences of epigenetic dysregulation and altered molecular signatures were compared to human major depressive disorder (MDD) transcriptome datasets. Results Prenatal THC-exposure induced increased motivation for food, heightened learned helplessness and anhedonia, and altered stress sensitivity. We identified a robust increase specific to males in the expression of Histone-Lysine N-Methyltransferase 2A (Kmt2a) that targets lysine 4 on histone H3 (H3K4me) in cellular chromatin. Normalizing Kmt2a in the NAc restored the motivational phenotype of prenatally THC-exposed animals. Comparison of RNA and H3K4me3 sequencing datasets from the NAc of rat offspring with the in vitro model of Kmt2a upregulation revealed overlapping, significant disturbances in pathways that mediate synaptic plasticity. Similar epigenetic alterations were detected in human MDD. Conclusions These studies provide direct evidence for the persistent effects of prenatal cannabis exposure on transcriptional and epigenetic deviations in the NAc via Kmt2a dysregulation and associated psychiatric vulnerability.

Background: Tuberculosis (TB) is one of the top ten causes of death worldwide, while Chagas disease (CD) is the parasitic disease that kills the largest number of people in the Americas. TB is the leading cause of death for patients with AIDS; it kills 1.5 million people and causes 10 million new cases every year. The lack of newly developed chemotherapeutic agents and insufficient access to health care services for a diagnosis increase the incidence of multidrug-resistant TB (MDRTB) cases. Although CD was identified in 1909, the chronic stages of the disease still lack adequate treatment. Objective: The purpose of this work was to design and synthesize two new series of 2-nitroimidazole 5a-e and imidazooxazoles 6a-e with 1H-1,2,3-triazolil nucleus and evaluate their activities against Tc and Mycobacterium tuberculosis (Mtb). Methods: Two series of five compounds were synthesized in a 3 or 4-step route in moderated yields, and their structures were confirmed by NMR spectral data analyses. The in vitro antitrypanosomal evaluation of products was carried out in an intracellular model using L929 cell line infected with trypomastigotes and amastigote forms of Tc of β-galactosidase-transfected Tulahuen strain. Their antimycobacterial activity was evaluated against Mtb strain H37Rv. Results: In general, 2-nitroimidazolic derivatives proved to be more potent in regard to antitrypanocidal and antimycobacterial activity. The non-cytotoxic 2-nitroimidazole derivative 5b was the most promising with a half maximum inhibitory concentration of 3.2 μM against Tc and a minimum inhibitory concentration of 65.3 μM against Mtb. Conclusion: Our study reinforced the importance of 2-nitroimidazole and 1H-1,2,3-triazole nuclei in antimicrobial activity. In addition, derivative 5b proved to be the most promising, presenting important activity against Tc and Mtb and could be used as a starting point for the development of new agents against these diseases.

Background Mycoplasma pneumoniae (MP) infection is associated with extrapulmonary complications such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Objective We evaluated the differences in epidemiology, clinical characteristics, and disease outcomes between drug-induced and Mycoplasma-related SJS/TEN. Methods All patients with SJS/TEN admitted to our center between 2003 and 2016 inclusive were treated under a standardized protocol. Comparative analysis was made between patients who tested positive for MP versus a control group with negative MP serology in the presence of high-notoriety drugs defined by an algorithm for assessment of drug causality in epidermal necrolysis >5. Results Of 180 cases of SJS/TEN patients treated in our institution, 6 had positive MP serologies and were compared to a control group of 71 cases of drug-induced SJS/TEN with an algorithm for assessment of drug causality in epidermal necrolysis score of >5. There were no significant differences in baseline characteristics, disease classification, body surface area involved, and extent of mucosal involvement. We found significant differences in mortality rates between the Mycoplasma and control groups on discharge (0% vs 22.5%, P Limitations Retrospective design, small sample size. Conclusion Although recent studies have shown that MP-induced SJS/TEN is morphologically different and deserves a separate classification system, this would need to be borne out in larger prospective studies.

OBJECTIVE Miscommunication and poor coordination among surgical teams are known causes of preventable medical harms and operating room inefficiencies and inhibit surgical training. Technology may help overcome these challenges. This study used the personal experience of one of the authors as a former Air Force F-15 pilot to design a combat aviation pre- and postoperative communication workflow in the neurosurgery department and tested its effect on safety, efficiency, and education. The authors hypothesized that the adoption of this workflow through a tailored technological platform will increase compliance and improve the chances of sustainability. METHODS Data were prospectively collected from neurosurgery cases before (January–May 2020) and after (June–October 2020) implementation of this workflow. Briefing and debriefing were executed using a custom mobile platform and were defined as nonmandatory for all participants. All faculty and residents who operated at NYU Langone Medical Center (Tisch campus) during the intervention period were enrolled on the platform. Primary outcomes were morbidity and mortality per the department’s criteria, and intraoperative last-minute requests as reported by operating room staff in a double-blinded fashion. Secondary outcomes were user responses on the subjective questionnaires. RESULTS Data were collected from 637 and 893 cases during the preintervention and intervention periods, respectively. The average briefing rates for residents and surgeons were 71% and 81%, respectively, and the average debriefing rates for residents and surgeons were 67% and 88%. There was no significant difference in preoperative risk score between the preintervention and intervention patient populations (p = 0.24). The rate of intraoperative last-minute requests significantly decreased from 16.6% (35/211) to 10.5% (35/334, p = 0.048). There was no significant change in morbidity and mortality between the preintervention and intervention periods. On subjective questionnaires there was a statistically significant improvement in safety, efficiency, and educational aspects of the cases during the intervention period. CONCLUSIONS Implementation of aviation-like structured team communication practices in the neurosurgery department through a technological platform improved education and communication between surgical teams and led to a reduction in last-minute surgical requests that could impact costs.

A WHO global strategy launched in November 2020 sets out an ambitious pathway towards the worldwide elimination of cervical cancer as a public health problem within the next 100 years. Achieving this goal will require investment in innovative approaches. This review aims to describe integrated approaches that combine human papillomavirus (HPV) vaccination and cervical cancer screening in low- and middle-income countries (LMIC), and their efficacy in increasing uptake of services. A systematic review was conducted analyzing relevant papers from Embase, Medline, CINAHL and CAB Global Health databases, as well as grey literature. Narrative synthesis was performed on the included studies. Meta-analysis was not appropriate due to the heterogeneity and nature of included studies. From 5,278 titles screened, 11 uncontrolled intervention studies from four countries (from Africa and east Asia) were included, all from the past 12 years. Four distinct typologies of integration emerged that either increased awareness of HPV and/or cervical cancer screening, and/or coupled the delivery of HPV vaccination and cervical cancer screening programs. The synthesis of findings suggests that existing HPV vaccination programs can be a useful pathway for educating mothers and other female caregivers about cervical cancer screening; through in person conversations with care providers (preferred) or take-home communications products. Integrated service delivery through outreach and mobile clinics may overcome geographic and economic barriers to access for both HPV vaccination and cervical cancer screening, however these require significant program and system resources. One study promoted HPV vaccination as part of integrated service delivery, but there were no other examples found that examined use of cervical cancer screening platforms to promote or educate on HPV vaccination. This review has demonstrated gaps in published literature on attempts to integrate HPV vaccination and cervical cancer screening. The most promising practices to date seem to relate to integrated health communications for cervical cancer prevention. Future research should further explore the opportunities for integrated health communications to support the efforts towards the new global cervical cancer elimination agenda, and costs and feasibility of integrated service delivery for underserved populations.

BACKGROUND: Both the incidence of diabetes mellitus and consumption of sugar-sweetened beverages are high in the Hispanic/Latino population in the United States. The associations between consumption of sugar-sweetened beverages, artificially sweetened beverages, and 100% fruit juice with prediabetes and glucose metabolism markers in the diverse Hispanic/Latino population in the United States are unknown. OBJECTIVES: The objective of this study was to examine the cross-sectional associations between consumption of sugar-sweetened beverages, artificially sweetened beverages, and 100% fruit juice with prediabetes and glucose metabolism markers such as fasting glucose and insulin, 2-h oral-glucose-tolerance test, HOMA-IR, HOMA index for β-cell function (HOMA-B), and glycated hemoglobin (HbA1c) among US Hispanic/Latino adults. METHODS: Using baseline data from the Hispanic Community Health Study/Study of Latinos (2008–2011), beverage consumption was ascertained using two 24-h dietary recalls and a food propensity questionnaire. Diabetes/prediabetes status was defined by self-report, antihyperglycemic medication use, and American Diabetes Association laboratory criteria. Among 9965 individuals without diabetes (5194 normoglycemia, 4771 prediabetes) aged 18–74 y, the associations of beverage consumption with prediabetes and glucose metabolism markers were analyzed using logistic and linear regressions, respectively, accounting for complex survey design. RESULTS: Compared with individuals who consumed 2 servings/d (>480 mL/d) had 1.3 times greater odds of having prediabetes (95% CI: 1.06, 1.61) and higher glucose metabolism markers including fasting glucose, fasting insulin, HOMA-IR, and HbA1c. Consumption of artificially sweetened beverages showed an inverse association with β-cell function (HOMA-B). Intake of 100% fruit juice was not significantly associated with prediabetes nor with glucose metabolism markers. CONCLUSIONS: Among US Hispanic/Latino adults, higher sugar-sweetened beverage consumption was associated with increased odds of prediabetes and higher glucose metabolism markers. Public health initiatives to decrease sugar-sweetened beverage consumption could potentially reduce the burden of diabetes among Hispanics/Latinos in the United States.

Rationale Infants born prematurely have impaired capacity to deal with oxidative stress shortly after birth. Objectives We hypothesize that the relative impact of exposure to air pollution on lung function is higher in preterm than in term infants. Methods In the prospective BILD-birth-cohort of 254 preterm and 517 term infants, we investigated associations of particulate matter (PM10) and nitrogen dioxide with lung function at 44 weeks postconceptional age and exhaled markers of inflammation and oxidative stress response (fraction of exhaled nitric oxide (FeNO)) in an explorative hypothesis-driven study design. Multilevel mixed-effects models were used and adjusted for known confounders. Measurements and Main Results Significant associations of PM10 during the second trimester of pregnancy with lung function and FeNO were found in term and preterm infants. Importantly, we observed stronger positive associations in preterm infants (born 32 - 36 weeks), with an increase of [184.9 (79.1, 290.7) mL/min] minute ventilation per 10 ��g/m3 increase in PM10 than in term infants [75.3 (19.7, 130.8) mL/min] (pprematurity �� PM10 interaction = 0.04, after multiple comparison adjustment padj = 0.09). Associations of PM10 and FeNO differed between moderate to late preterm [3.4 (-0.1, 6.8) ppb] and term [-0.3 (-1.5, 0.9) ppb] infants, the interaction with prematurity was significant (pprematurity �� PM10 interaction = 0.006, padj = 0.036). Conclusion Preterm infants showed significant higher susceptibility even to low-to-moderate prenatal air pollution exposure than term infants, leading to increased impairment of postnatal lung function. FeNO results further elucidate differences in inflammatory/oxidative stress response comparing preterms to terms.

CASE DESCRIPTION A 12-year-old 32-kg neutered female crossbreed dog was treated for a large lumbosacral skin defect. CLINICAL FINDINGS The dog had sustained multiple, penetrating dog bite wounds to the lumbosacral and gluteal regions 5 days earlier. The referring veterinarian had initiated treatment with amoxicillin–clavulanic acid, which was continued at a dosage of 8.75 mg/kg, SC, every 24 hours at the referral hospital. Examination of the skin defect revealed a large subcutaneous abscess in the dorsal lumbosacral region with draining perimeter tracts at the wound margin. The partial-thickness wound measured 24 × 35 cm and had multifocal regions of necrosis extending caudally from the dorsal aspect of the T11 vertebra to the tail base. The skin defect was bounded by discolored and necrotic skin edges. TREATMENT AND OUTCOME The dog underwent extensive soft tissue wound reconstruction. A single, large, meshed full-thickness free skin graft was harvested from the left dorsolateral aspect of the thorax and grafted to the dorsal lumbosacral region, thereby enabling successful closure of the wound defect. Primary healing of the wound eventually occurred, without postoperative complications. CLINICAL RELEVANCE Use of a large, meshed full-thickness free skin graft led to a satisfactory outcome for this dog but required challenging postoperative management. Application of single, large, meshed full-thickness free skin grafts may be an option to manage large skin deficits in the lumbosacral area in dogs.

BACKGROUND Impaired paternal genome expression may cause poor embryonic development after in vitro fertilization (IVF). OBJECTIVE To evaluate the expression of male infertility on embryo morphokinetics using a time-lapse incubator and its impact on IVF cycles. MATERIALS AND METHODS This retrospective cohort study followed patients from January 2017 to August 2019. Patients were divided according to the cause of infertility to male factor (study group) and unexplained infertility (control group) and further subdivided according to the severity of male infertility. RESULTS A cohort of 462 patients who underwent IVF cycles, with a total of 3,252 embryos was evaluated. Intracytoplasmic sperm injection (ICSI) was conducted more often in the study group compared to the control group (94% vs. 47%, p

Introduction Basidiobolomycosis is a rare fungal disease, lately appearing in the gastrointestinal system of pediatric patients. Their clinical presentation resembles that of lymphoma or granulomatous inflammations. This non-specific presentation makes Gastrointestinal Basidiobolomycosis (GIB) a diagnostic challenge. Methods We are reporting the largest series of pediatric GIB, from Saudi Arabia. 12 patients were diagnosed between January 2012 and December 2019, between the ages of 16 months and 8 years. Results The most common symptoms were fever and abdominal pain. Further examination revealed an abdominal mass. Biopsy of the mass was the mainstay of diagnosis, with histological findings of typical filamentous fungal hyphae and zygospores, surrounded by eosinophils. Conclusion Role of surgery was limited to establishing the diagnosis and dealing with complications. Antifungal medication was the cornerstone of treatment in all our patients. Three of our patients were exceptional with complications such as entero-cutaneal fistula, entero-enteric fistula and short bowel syndrome. These complications have not been previously reported. We have discussed the challenges related to their management. The diagnosis of GIB in pediatric patients with abdominal mass, needs a high index of suspicion. We believe outcome depends on the severity of disease, involvement of surrounding tissues and presence of complications at the time of diagnosis.

Despite recent advances in the diagnosis and treatment of breast cancer (BC), it remains a global health issue affecting millions of women annually. Poor prognosis in BC patients is often linked to drug resistance as well as the lack of effective therapeutic options for metastatic and triple-negative BC. In response to these unmet needs, extensive research efforts have been devoted to exploring the anti-BC potentials of natural products owing to their multi-target mechanisms of action and good safety profiles. Various medicinal plant extracts/essential oils and natural bioactive compounds have demonstrated anti-cancer activities in preclinical BC models. Despite the promising preclinical results, however, the clinical translation of natural products has often been hindered by their poor stability, aqueous solubility and bioavailability. There have been attempts to overcome these limitations, particularly via the use of nano-based drug delivery systems (NDDSs). This review highlights the tumour targeting mechanisms of NDDSs, the advantages and disadvantages of the major classes of NDDSs and their current clinical status in BC treatment. Besides, it also discusses the proposed anti-BC mechanisms and nanoformulations of nine medicinal plants’ extracts/essential oils and nine natural bioactive compounds; selected via the screening of various scientific databases, including PubMed, Scopus and Google Scholar, based on the following keywords: “Natural Product AND Nanoparticle AND Breast Cancer”. Overall, these nanoformulations exhibit improved anti-cancer efficacy against preclinical BC models, with some demonstrating biocompatibility with normal cell lines and mouse models. Further clinical studies are, however, warranted to ascertain their efficacy and biocompatibility in humans., Graphical Abstract

Background/Purpose Epidermolysis bullosa (EB) is a rare disease of skin and mucosa which may causes surgical complications. We review these in a large patient cohort from Saudi Arabia. Methods A retrospective study was conducted at 21 centers between 2003 and 2020. Demographic data and information on EB type [Simplex (EBA), Dystrophic (DEB) and Junctional (JEB)]. The dataset included clinical features, operations, surgical complications, and treatment. Results There were 152 (63 male) children with EB [EBS n = 93 (61.2%); DEB n = 30 (19.7%); JEB n = 25 (16.4%), and Kindler syndrome n = 4, (2.6%)]. Children with JEB and DEB tended to have a higher frequency of skin and musculoskeletal system complications (skin cancer, pseudosyndactyly and recurrent skin infection). Esophageal strictures were mostly seen in DEB (n = 19, 63%) and to a lesser extent in EBS (n = 20, 21%) and JEB (n = 4, 16%). Pyloric atresia was uncommon (n = 4) and limited to those with JEB. Percutaneous gastrostomy for feeding support was used in all types. Ankyloglossia was common but often recurred (76%) after division. Circumcision was usually safe and complication-free in male children except in those with severe JEB. Phimosis was reported in 10% of uncircumcised patients. Conclusions Our series showed that surgeons play a key role in the management of some complications associated with EB. It is also important to be aware of the particular sub-type as this can predict the natural history and likely response to treatment. Level of Evidence 2

INTRODUÇÃO: A afibrinogenemia congênita, também conhecida como síndrome do fibrinogênio circulante indetectável, é um distúrbio autossômico recessivo extremamente raro, estimado em um a cada um milhão de habitantes. É uma alteração advinda de uma anormalidade em indivíduos homozigotos ou heterozigotos que apresentam mutações relacionadas ao gene que codifica a cadeia ? do fibrinogênio sendo estas alterações mais comuns em casos de consanguinidade e principalmente relacionadas ao gene FGA. As manifestações clínicas dessa condição se relacionam a ausência do fibrinogênio com hemorragias variáveis, podendo cursar até com óbito. O diagnóstico se dá através de uma exaustiva investigação laboratorial e o manejo advém da reposição do fibrinogênio ausente. OBJETIVOS: Relatar o caso de uma paciente com afibrinogenemia congênita que chegou ao atendimento emergencial com dor abdominal associada a vômitos. RESULTADOS: Paciente do sexo feminino, 6 anos, com diagnóstico prévio de afibrinogenemia congênita desde o primeiro mês de vida. Foi internada, durante 8 dias, devido a uma dor abdominal em região periumbilical. Nessa ocasião, fazia uso de concentrado de fibrinogênio (haemocomplettan®), uma vez na semana, sem melhora dos níveis laboratoriais de fibrinogênio, os quais persistiram extremamente baixos. A angiotomografia computadorizada de abdômen demonstrou ascite de moderado grau e hemoperitônio (fotografia 2), assim como, lesão esplênica com sangramento ativo (fotografia 1), responsável pela anemia evidenciada em exames laboratoriais. A conduta médica constituiu-se em jejum, repouso, solicitação de crioprecipitado, concentrados de hemácias, uso de haemocomplettan® em dias alternados e prescrição de ceftriaxona (rocefin®) juntamente com metronidazol, além da possibilidade de indicação de laparotomia exploratória. A paciente respondeu bem ao tratamento conservador, com resolução da anemia, melhora da dor abdominal, elevação do fibrinogênio e desaparecimento do líquido livre observado em ultrassonografia diária. Desse modo, não houve necessidade de intervenção cirúrgica e a paciente foi liberada após 8 dias de internação. DISCUSSÃO: Clinicamente, eventos traumáticos e invasivos, como cirurgias predispõem ao sangramento nesses pacientes. No presente relato de caso, se o tratamento conservador não fosse suficiente, a execução da laparotomia exploratória seria necessária, acrescentando riscos à vida do paciente. Sendo assim, enfatiza-se a importância de um tratamento apropriado com reposição de fibrinogênio, crioprecipitado e plasma fresco congelado para evitar cirurgias desnecessárias. Apesar de poder ocorrer hemorragias potencialmente fatais, como na ruptura esplênica, os pacientes com essa doença possuem prognóstico favorável quando tratados adequadamente. Também há uma susceptibilidade dos indivíduos com afibrinogenemia ter ruptura esplênica sem a ocorrência de um trauma, sendo ainda esse caso pouco compreendido nas literaturas. CONCLUSÃO: A sintomatologia clínica da afibrinogenemia é variável e caracteriza-se, principalmente, por hemorragias espontâneas ou pós traumáticas de intensidade leve a grave. Em geral, os pacientes portadores dessa doença possuem um prognóstico favorável com o diagnóstico precoce e tratamento adequado, como visto na paciente deste relato de caso. Por fim, por ser uma doença crônica e sem cura, é imprescindível a orientação dos cuidadores sobre a doença e atividades traumáticas que podem ocasionar sangramentos e, consequentemente, desencadear quadros potencialmente graves.

Background: Nutritional rickets has emerged as a public health problem in Bangladesh during the past two decades, with up to 8% of children being clinically affected in some areas. Insufficiency of vitamin D and dietary calcium is thought to be the underlying cause. Vitamin D administered with or without calcium is commonly regarded as the mainstay of treatment. Calcium alone or in combination with vitamin D has also been used in the treatment of nutritional rickets. So this study was done to assess the effects of vitamin D, calcium or combination of vitamin D and calcium for the treatment of nutritional rickets in Bangladeshi children. Methods: This open labeled randomized comparative study was done in the Department of Paediatrics, Sylhet MAG Osmani Medical College Hospital from July 1, 2010 to June 30, 2012 A total 48 rickets patient was enrolled in this study. After selection of cases patients were divided in to three groups by lottery method. Group A received single i/m dose of vitamin D 4,00,000 IU (2,00,000 IU in each buttock), Group B received calcium (750 mg per day) for 6 weeks and Group C received both calcium (750 mg per day) for 6 weeks and single i/m dose of vitamin D 4,00,000 IU (2,00,000 IU in each buttock). Response was evaluated by serum alkaline phosphatase level and using 10-point radiographic score developed by Thacher and colleagues at baseline, 6 weeks, and 12 weeks. Results: Mean age of the study participants was 35.83 months. Male to female ratio was 2:1. The radiographic score was significantly improved in first and second follow up (p

Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes (T2DM). Ferulic acid is known for attenuating the insulin resistance and reducing the blood glucose in T2DM rats. In this work, we designed and synthesized a library of new ferulic acid amides (FAA), which could be considered as ring opening derivatives of the antidiabetic PPARγ agonists Thiazolidinediones (TZDs). However, since these compounds displayed weak PPAR transactivation capacity, we employed a proteomics approach to unravel their molecular target(s) and identified the peroxiredoxin 1 (PRDX1) as a direct binding target of FAAs. Interestingly, PRDX1, a protein with antioxidant and chaperone activity, has been implied in the development of T2DM by inducing hepatic insulin resistance. SPR, mass spectrometry-based studies, docking experiments and in vitro inhibition assay confirmed that compounds VIe and VIf bound PRDX1 and induced a dose-dependent inhibition. Furthermore, VIe and VIf significantly improved hyperglycemia and hyperlipidemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats as confirmed by histopathological examinations. These results provide guidance for developing the current FAAs as new potential antidiabetic agents.

Availability of accelerometer data has made it possible to objectively and continuously monitor sedentary behavior. Various summaries of the extensive accelerometer data have been used to understand the relationship between sedentary behavior and health. However, the widely used summary measures on sedentary bouts, average bout length or its derivatives, fail to reveal patterns of accumulated sedentary behavior over time. Studies have suggested that prolonged uninterrupted sedentary behavior can be an important metric that is related to health states. Yet existing measures to capture the prolonged sedentary patterns either rely on parametric assumptions on the underlying distribution of sedentary bout length or have to categorize sedentary bout length into somewhat arbitrary categories. Gini index was also used; however, it only measures the variability in bout lengths but not the actual length. To overcome these limitations, we proposed a non-parametric weighted survival function to characterize uninterrupted sedentary behavior over time in a continuous fashion and used the area under the survival curve as a new summary measure to quantify sedentary behavior. We showed that this measure is a weighted average of bout length and contains the information on both the mean and variability of bout lengths. We demonstrated in the simulation studies that the proposed measure could better identify prolonged uninterrupted sedentary behavior and predict health outcomes. We applied this new measure and existing sedentary measures to data from the Hispanic Community Health Study/Study of Latinos to examine the association between sedentary behavior and overweight/obesity.

Background: In the 21st century, the prevalence pattern of hypertension in different developing countries differs from developed countries. Persistent hypertension is one of the risk factors and is the leading cause of heart disease, chronic kidney disease (CKD) & cerebrovascular disease. Even mild to moderate essential hypertension usually causes significant renal function impairment only after several years. Objectives: To assess the serum uric acid level in hypertensive patients and compare the findings with those found in normotensive people. Materials & Methods: This case-control study was done at the Department of Biochemistry, Mymensingh Medical College, Mymensingh during the period of January 2010 to December 2010. A total of 143 subjects of both sexes were selected for the purpose. Out of them, 73 were the case and 70 were the control. The subjects were classified into the following groups; Group I includes 73 were essential hypertensive subjects. Group II includes 70 were healthy adults. All statistical parameters analysis were done by SPSS 12.0 version; P-value

Ventricular enlargement is one long-term consequence of a traumatic brain injury, and a risk factor for memory disorders and epilepsy. One underlying mechanisms of the chronic ventricular enlargement is disturbed cerebrospinal-fluid secretion or absorption by choroid plexus. We set out to characterize the different aspects of ventricular enlargement in lateral fluid percussion injury (FPI) rat model by magnetic resonance imaging (MRI) and discovered choroid plexus injury in rats that later developed hydrocephalus. We followed the brain pathology progression for 6 months and studied how the ventricular growth was associated with the choroid plexus injury, cortical lesion expansion, hemorrhagic load or blood perfusion deficits. We correlated MRI findings with the seizure susceptibility in pentylenetetrazol challenge and memory function in Morris water-maze. Choroid plexus injury was validated by ferric iron (Prussian blue) and cytoarchitecture (Nissl) stainings. We discovered choroid plexus injury that accumulates iron in 90% of FPI rats by MRI. The amount of the choroid plexus iron remained unaltered 1-, 3- and 6-month post-injury. During this time, the ventricles kept on growing bilaterally. Ventricular growth did not depend on the cortical lesion severity or the cortical hemorrhagic load suggesting a separate pathology. Instead, the results indicate choroidal injury as one driver of the post-traumatic hydrocephalus, since the higher the choroid plexus iron load the larger were the ventricles at 6 months. The ventricle size or the choroid plexus iron load did not associate with seizure susceptibility. Cortical hypoperfusion and memory deficits were worse in rats with greater ventricular growth. Supplementary Information The online version contains supplementary material available at 10.1007/s00429-021-02395-5.

Objective The primary objective was to describe the incidence of post-partum hemorrhage at cesarean delivery before and after implementation of a new high dose oxytocin protocol at Chris Hani Baragwanath Academic Hospital. Methods This was a cross sectional retrospective record review 3 months before and 3 months after the implementation of a high dose oxytocin protocol. The study included all women that underwent cesarean delivery between 1 November 2016 and 30 April 2017 with a gestation of >24 weeks. Results A total of 4604 Cesarean deliveries were performed during the study period, 2162 before the implementation of the new protocol and 2442 after. The incidence of post-partum hemorrhage was 4.8% (n = 91) in the Before group and 3.9% (n = 89) in the After group (P = 0.17). There was a 17.9% change in incidence of postpartum hemorrhage between the groups (P = 0.17). There was no significant difference in uterine atony between the Before and After groups (21.8% and 30.1%, P = 0.30). Conclusion There was no difference in the incidence of postpartum hemorrhage at cesarean delivery after the implementation of a high dose oxytocin protocol.

Background and objectives Anemia is a prevalent complication endured by patients with chronic renal disease. Renal anemia also leads to the development of cardio-vascular complications. Epoetin alpha and beta are recombinant human erythropoietin prioritized for managing anemia in hemodialysis patients. The current study aimed to compare the therapeutic efficacy of both erythropoietin alpha and erythropoietin beta in treating renal anemia. Materials and methods This prospective observational study was conducted in a Renal Dialysis Centre at a tertiary care Hospital of Karachi, Pakistan for a period of 3 months. The two erythropoietin products used were human recombinant erythropoietin alpha (Tropin®) and erythropoietin beta (Recormon®). Both groups were age-matched, BMI, eGFR, gender, and comorbidities like diabetes and hypertension were indifferent. The comparative analysis was performed after the completion of 3 months. Results A total of 94 participants were included in the analysis, 54 in group A and 40 in group B. Mean albumin, urea, creatinine, ferritin, iron, and transferrin saturation at inclusion were statistically insignificant, TIBC was higher in group A (p = 0.005) and CRP levels were slightly higher in group B (p = 0.050). There was significant improvement in Hb level (p = 0.025), PCV (p = 0.001), and RBC count (p = 0.007) in group B. While in group A, there was significantly increased MCV (p = 0.005) and MCHC (p = 0.002). In intention to treat analysis, 22.2% of subjects in group A and 40.0% in group B reached desired Hb levels of ≥11 g/l after 3 months. Conclusion In our assessment of hemodialysis patients, erythropoietin beta was found more effective than erythropoietin alpha.

Highlights • Higher radiation doses to the brain may negatively affect quality of life. • Higher radiation doses to the brain may negatively affect patient-reported cognition. • Patients with fatigue had received higher dose to certain areas in the brain., Aim This study aimed to explore associations between radiation dose and patient-reported outcomes in patients with a primary non-glioblastoma brain tumour treated with radiation therapy (RT), with a focus on health-related quality-of-life (HRQoL) and self-reported cognitive function. Methods In this cross-sectional study, 78 patients who had received RT for a non-glioblastoma primary brain tumour, underwent neuropsychological testing and completed questionnaires on HRQoL, cognitive function, fatigue, depression, anxiety and perceived stress. The study explores the association between HRQoL scores, self-reported cognitive function and radiation doses to total brain, brainstem, hippocampus, thalamus, temporal lobes and frontal lobes. In addition, we examined correlations between neuropsychological test scores and self-reported cognitive function. Results The median time between RT and testing was 4.6 years (range 1–9 years). Patients who had received high mean radiation doses to the total brain had low HRQoL scores (Cohen’s d = 0.50, p = 0.04), brainstem (d = 0.65, p = 0.01) and hippocampus (d = 0.66, p = 0.01). High mean doses to the total brain were also associated with low scores on self-reported cognitive functioning (Cohen’s d = 0.64, p = 0.02), brainstem (d = 0.55, p = 0.03), hippocampus (d = 0.76, p

Introduction Preterm neonates have under-developed immune-regulatory system; consequently, there is a risk for developing chronic inflammation. Necrotizing enterocolitis (NEC) is an acute devastating neonatal intestinal inflammatory disorder. Due to the obscure multifactorial etiology, early diagnosis and effective treatment of NEC are limited. Consequently, effective strategies in the prevention of NEC, including nutritional approaches, are critically needed. The current study was conducted to assess the potential immunomodulatory effect of Docosahexaenoic Acid (DHA) supplementation in preterm neonates at neonatal intensive care unit (NICU) and subsequently its effect on preventing or reducing NEC incidence. Methods This was a prospective randomized controlled study. A total of 67 neonates, with gestational age equal or less than 32 weeks at birth and weight less than or equal 1500 g, were randomly assigned to either DHA group or the control group. Modified Bell’s staging criteria for NEC was used as an objective tool for diagnosis and staging of NEC. Levels of Interleukin 1 beta (IL-1β) were measured at baseline and after 10 days. Mortality and NICU length of stay (LOS) were also monitored. Results Thirty neonates of each group completed the study. A statistically significant difference was observed between the two groups regarding diagnosis and staging of NEC (p = 0.0001). There was also a statistically significant difference between DHA group 22(73.3), 95% CI [55.9, 86.5] and the control group 8 (26.7), 95% CI [13.5, 44.1] in the percentage change in IL-1β levels (p = 0.0001). A statistically significant association was found between IL and 1 β change and NEC diagnosis (p = 0.001). NICU LOS was significantly lower among DHA group 21.63 ± 6.67 compared to the control group 25.07 ± 4.67 (p = 0.025). Mortality n (%) among the control group 4 (11.8) was higher than DHA group 3 (9.1), however, no significant difference was detected (p = 1.0). Conclusion Findings of this study suggest that enteral DHA supplementation can reduce NEC incidence in preterm neonates through its immunoregulatory effect that modulates production of regulatory cytokines. Trial registration: Registered at clinical trials.gov (NCT03700957), 6 October 2018.

The risk of acute respiratory tract infections is particularly pronounced in patients deficient in 25-hydroxyvitamin D (25(OH)D). With respect to COVID-19, there are conflicting evidence on the association of 25(OH)D levels with disease severity. We undertook this study to evaluate the 25(OH)D status in COVID-19 patients admitted in Karachi, Pakistan, and associated vitamin D deficiency with primary outcomes of mortality, length of stay, intubation, and frequency of COVID-19 symptoms. A total of 91 patients were evaluated for 25(OH)D status during their COVID-19 disease course. 25-hydroxyvitamin D levels were classified as deficient (< 10 ng/mL), insufficient (10–30 ng/mL), or sufficient (> 30 ng/mL). The study population comprised 68.1% males (N = 62). The mean age was 52.6 ± 15.7 years. Vitamin D deficiency was significantly associated with intensive care unit (ICU) admission (RR: 3.20; P = 0.048), invasive ventilation (RR: 2.78; P = 0.043), persistent pulmonary infiltrates (RR: 7.58; P < 0.001), and death (RR: 2.98; P < 0.001) on univariate Cox regression. On multivariate Cox regression, only death (RR: 2.13; P = 0.046) and persistent pulmonary infiltrates (RR: 6.78; P = 0.009) remained significant after adjustment for confounding factors. On Kaplan Meier curves, vitamin D deficient patients had persistent pulmonary infiltrates and a greater probability of requiring mechanical ventilation than patients with 25(OH)D ≥ 10 ng/mL. Mechanical ventilation had to be initiated early in the deficient group during the 30-day hospital stay (Chi-square: 4.565, P = 0.033). Patients with 25(OH)D ≥ 10 ng/mL also demonstrated a higher probability of survival than those with 25(OH)D concentrations < 10 ng/mL. 25-hydroxyvitamin D deficient population had longer hospital stays and worse outcomes.

Objectives The mRNA coronavirus disease 2019 (COVID-19) vaccines have shown high effectiveness in the prevention of symptomatic COVID-19, hospitalization, severe disease and death. Nevertheless, a minority of vaccinated individuals might become infected and experience significant morbidity. Characteristics of vaccine breakthrough infections have not been studied. We sought to portray the population of Israeli patients, who were hospitalized with COVID-19 despite full vaccination. Methods A retrospective multicentre cohort study of 17 hospitals included patients fully vaccinated with Pfizer/BioNTech's BNT162b2 vaccine who developed COVID-19 more than 7 days after the second vaccine dose and required hospitalization. The risk for poor outcome, defined as a composite of mechanical ventilation or death, was assessed. Results A total of 152 patients were included, accounting for half of hospitalized fully vaccinated patients in Israel. Poor outcome was noted in 38 patients and mortality rate reached 22% (34/152). Notably, the cohort was characterized by a high rate of co-morbidities predisposing to severe COVID-19, including hypertension (108; 71%), diabetes (73; 48%), congestive heart failure (41; 27%), chronic kidney and lung diseases (37; 24% each), dementia (29; 19%) and cancer (36; 24%), and only six (4%) had no co-morbidities. Sixty (40%) of the patients were immunocompromised. Higher viral load was associated with a significant risk for poor outcome. Risk also appeared higher in patients receiving anti-CD20 treatment and in patients with low titres of anti-Spike IgG, but these differences did not reach statistical significance. Conclusions We found that severe COVID-19 infection, associated with a high mortality rate, might develop in a minority of fully vaccinated individuals with multiple co-morbidities. Our patients had a higher rate of co-morbidities and immunosuppression compared with previously reported non-vaccinated hospitalized individuals with COVID-19. Further characterization of this vulnerable population may help to develop guidance to augment their protection, either by continued social distancing, or by additional active or passive vaccinations.

γδ T cells are nonclassical T lymphocytes representing the major T-cell population at epithelial barriers. In the gingiva, γδ T cells are enriched in epithelial regions adjacent to the biofilm and are considered to regulate local immunity to maintain host-biofilm homeostatic interactions. This delicate balance is often disrupted resulting in the development of periodontitis. Previous studies in mice lacking γδ T cells from birth ( Tcrd-/-mice) examined the impact of these cells on ligature-induced periodontitis. Data obtained from those studies proposed either a protective effect or no impact to γδ T cells in this setting. Here, we addressed the role of γδ T cells in periodontitis using the recently developed Tcrd-GDL mice, enabling temporal ablation of γδ T cells. Specifically, the impact of γδ T cells during periodontitis was examined in 2 modalities: the ligature model and the oral infection model in which the pathogen Porphyromonas gingivalis was administrated via successive oral gavages. Ablation of γδ T cells during ligature-induced periodontitis had no impact on innate immune cell recruitment to the ligated gingiva. In addition, the number of osteoclasts and subsequent alveolar bone loss were unaffected. However, γδ T cells play a pathologic role during P. gingivalis infection, and their absence prevented alveolar bone loss. Further analysis revealed that γδ T cells were responsible for the recruitment of neutrophils and monocytes to the gingiva following the exposure to P. gingivalis. γδ T-cell ablation also downregulated osteoclastogenesis and dysregulated long-term immune responses in the gingiva. Collectively, this study demonstrates that whereas γδ T cells are dispensable to periodontitis induced by the ligature model, they play a deleterious role in the oral infection model by facilitating pathogen-induced bone-destructive immune responses. On a broader aspect, this study highlights the complex immunopathologic mechanisms involved in periodontal bone loss.

ObjectiveEvaluate the impact of the COVID-19 pandemic on access to contraception and pregnancy intentions.DesignNationwide prospective cohort study.SettingUnited Kingdom.ParticipantsWomen in the UK who were pregnant between 24 May and 31 December 2020.Main outcome measuresAccess to contraception and level of pregnancy intentions, using the London Measure of Unplanned Pregnancy (LMUP) in women whose last menstrual period was before or after 1 April 2020. While the official date of the first UK lockdown was 23 March, we used 1 April to ensure that those in the post-lockdown group would have faced restrictions in the month that they conceived.ResultsA total of 9784 women enrolled in the cohort: 4114 (42.0%) conceived pre-lockdown and 5670 (58.0%) conceived post-lockdown. The proportion of women reporting difficulties accessing contraception was higher in those who conceived after lockdown (n=366, 6.5% vs n=25, 0.6%, pConclusionsAccess to contraception in the UK has become harder during the COVID-19 pandemic and the proportion of unplanned pregnancies has almost doubled.

Objective:To find causes of maternal deaths and to calculate maternal mortality ratio at tertiary care hospital Karachi. Study Design and setting:An observational study was conducted from1st January 2019 to 31stDecember 2020 at theDepartment of Obstetrics & Gynecology Unit 1, JPMC Karachi. Methodology:Patients were selected according to inclusion criteria after ethical approval through non probability consecutivesampling technique. Details of patients were obtained from filesand record registers. Their demographic feature like age,parity, gestational age, booking status and presence or absence of medical disorders, their status of delivery and direct andindirect reasons of maternal deaths were noted and their frequency and percentages were calculated. Brought dead patientsand those who died accidently were excluded from the study. Results:During the period of two years the total numbers of deaths certified in the department were 90. Total number ofchild birth and live births were 19084 and 17892 respectively. The maternal mortality ratio was estimated as 503.01 per100,000 live births. Most of the patients 74(82.3%) were un booked. Direct Causes were about 67(74.5%). Haemorrhagewas found to be most common reason of maternal deaths in about21(23.3%). Eclampsia among18(20%) deaths. Anemia, cardiac disease, hepatic failure were the indirect causes of maternal deaths responsible for 23 (25.5%) of maternal deaths. Conclusion:Maternal Death rate is persistently elevated in JPMC, being tertiary care hospital mostly due to serious and referred complicated cases. Haemorrhage and eclampsia are still major killers of mothers as before.

Introduction: Osteoporosis is often under diagnosed, under treated and imposed a considerable economic burden on the health system. About two fifth of the post-menopausal women of Bangladesh are affected. Early diagnosis is necessary to halt the disease process. Serum osteocalcin, neutrophil-lymphocyte ratio (NLR) increases and bone mineral density (BMD) decreases in osteoporosis. There is no specific diagnostic test for osteoporosis except BMD. It is costly, has radiation hazard and not available in all laboratories in our country. On the other hand, serum osteocalcin and NLR are easily available and a promising marker which can be done as routine blood test for the diagnosis of osteoporosis. Objective: The objective of the study was to evaluate the association of serum osteocalcin and NLR with BMD for the diagnosis of osteoporosis. Materials and methods: This cross-sectional study was conducted in the Department of Laboratory Medicine and the Department of Orthopedic Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU) and Dhaka Medical College Hospital (DMCH) from March, 2020 to February, 2021. A total 50 diagnosed patient of osteoporosis, who fulfil the inclusion and exclusion criteria were selected as study population. They were grouped as normal, osteopenia and osteoporosis according to T-score of BMD report. Serum osteocalcin and NLR evaluated from routine blood test. Statistical analysis was done by statistical package for social science (SPSS) software windows version 22. Results: Negative Pearson’s correlation was found between serum osteocalcin with T-score of BMD (r=-0.812, p=0.002) and between NLR with T-score of BMD (r=-0.826, p=0.001). In receiver operating characteristic (ROC) curve analysis, cut off value of serum osteocalcin was 18.65 ng/mL having sensitivity 67.0% and specificity 70.0% with a cut off value of NLR was 4.54 with sensitivity 72.0% and specificity 75.0%. Conclusion: Serum osteocalcin and NLR has significant negative correlation with T-score of BMD. Because of high sensitivity and specificity, serum osteocalcin and NLR may be used to diagnosis of osteoporosis

Over a span of 1 year, with millions infected, COVID-19 has spread to every part of the world and now poses a health threat to each and every one of us. The outbreak has consequently resulted in multiple health problems such as stress, anxiety, depressive symptoms, insomnia, panic, and denial globally. Several factors have contributed to this rising number of psychiatric consults all over the world. The primary objective of this study was to investigate the impact of COVID-19 pandemic on the mental health of Pakistani population during the second wave of the pandemic in this region. We conducted an online web-based cross-sectional survey comprising 500 participants. The questionnaire assessed the demographic information, attitude, and knowledge concerning COVID-19 outbreak in addition to generalized anxiety disorder (GAD) utilizing the GAD-7 scale and depressive symptoms using the Center for Epidemiology Scale for Depression (CES-D) scale. The response rate of the study was 90.9%. The results of the survey indicated a prevalence of 25.4% of GAD, and 18.8% of depressive symptoms. Furthermore, nearly 34.8% of participants feared contracting COVID-19, 62.8% obtained constant critical updates regarding COVID-19, while 17.6% did not understand the knowledge regarding COVID-19. In the multivariate regression models, GAD was significantly associated with gender, age, and checking constantly of critical updates regarding COVID-19. Similarly, participants under 30 years had a higher risk of developing depressive symptoms than those above (> 30 years). Lastly, participants with no formal education were also found to be more prone to developing depression. We identified a potential threat to mental health during the pandemic.

Objective: to evaluate the efficacy of non-invasive procedures through biomimetic mineralization of a fluoride gel, bioactive glass materials with and without fluoride and self-organizing biomimetic peptides in the treatment of dentinal hypersensitivity due to early non-carious cervical lesions. Materials and methods: Twenty-eight patients with self-reported history of dentin hypersensitivity were evaluated sequentially for evidence of erosion, abrasion or gingival recession at facial cervical region. Patients were randomly distributed into four treatment groups of seven patients each according to the type of the treatment (group I: Elmex Gele'e, group II: BioMin™ F, group III: BioMin™ C group IV: CurodontTM D’senz). The teeth were subjected to five follow up periods (baseline, after 3,6,9 and 12 weeks) and assessed in response to evaporative air-blast stimulus utilizing Schiff Sensitivity and Visual Analogue Scales. Electrical test was performed utilizing electrical pulp tester. The extent of tubule occlusion was examined under scanning electron microscope using negative replica of randomly selected patients. Results: All the tested groups showed different degrees of relieving dentinal hypersensitivity symptoms. The difference between the studied groups was statistically significant. Under SEM, group II, III and IV showed complete tubule occlusion. However, group I showed partial tubule occlusion. Conclusions: Elmex® gelee, BioMin™ F, BioMin™ C and Curodont™ D’senz were effective to manage dentin hypersensitivity related to early non-carious cervical lesions based on the biomimetic mineralization concept that has focused on permanent management of dentin hypersensitivity. Keywords: Fluoride, Bioactive glass, self-organizing biomimetic peptides, non-carious cervical lesions, dentin hypersensitivity.

During the coronavirus disease 2019 (COVID-19) pandemic, there has been considerable discussion regarding the use of biologics in patients with inflammatory skin conditions, such as psoriasis, hidradenitis suppurativa, and atopic dermatitis. This article discusses clinical trial data, real-world evidence, and guidelines and recommendations for biologics that inhibit tumor necrosis factor, interleukin (IL)-12/23, IL-17, IL-23, and IL-4/13 during the COVID-19 pandemic. Across these inflammatory skin conditions, existing data generally suggest that biologics do not seem to increase the risk of COVID-19 infection or worsen COVID-19 outcomes. The impact of biologics on COVID-19 is an area of active exploration.

The current study investigated 304 children from a longitudinal project (the Stress in Pregnancy (SIP) Study) who were exposed and unexposed to Superstorm Sandy (“Sandy”) in utero. They were prospectively followed from 2 to 6 years of age and their clinical and adaptive behaviors were assessed annually. Using a hierarchical linear model, the study found that in utero Sandy exposure was associated with greater clinical (anxiety, depression, and somatization) and lower adaptive behaviors (social skills and functional communication) at age 2 years. However, the trajectories were notably different between the two groups. Anxiety increased more rapidly among the exposed than unexposed group at ages 2–4, and depression increased only among the exposed. In contrast, social skills and functional communication were lower in exposed compared to unexposed children at age 2, but quickly increased and exceeded the capacities of unexposed children by age 3. The findings confirm that prenatal Sandy exposure is not only associated with an increase in anxiety, depression, and somatization in offspring, but also with greater adaptive skills as the children got older. Our study demonstrates that while children who have experienced stress in utero demonstrate elevated suboptimal clinical behaviors related to affective disorders, they nevertheless have the potential to learn adaptive skills.

Background Cardiometabolic diseases are prevalent in aging Americans. Although some studies have implicated greater intake of dairy products, it is not clear how dairy intake is related to biomarkers of cardiometabolic health. Objective Our aim was to test the hypothesis that associations of dairy foods with biomarkers of lipid metabolism, insulin-like growth factor signaling, and chronic inflammation may provide clues to understanding how dairy can influence cardiometabolic health. Design This was a cross-sectional study in the Women's Health Initiative using baseline food frequency questionnaire data to calculate dairy intake. Participants/setting Participants were 35,352 postmenopausal women aged 50 to 79 years at 40 clinical centers in the United States. Main outcome measures Baseline (1993-1998) concentrations of 20 circulating biomarkers were measured. Statistical analyses Multivariable-adjusted linear regression was used to estimate percent difference in biomarker concentrations per serving of total dairy and individual foods (milk, cheese, yogurt, butter, and low-fat varieties). Results Lower triglyceride concentrations were associated with greater intake of total dairy (–0.8% [95% CI –1.2% to –0.3%]), mainly driven by full-fat varieties. Individual dairy foods had specific associations with circulating lipid components. For example, greater total milk intake was associated with lower concentrations of total cholesterol (–0.4% [95% CI –0.7% to –0.2%]) and high-density lipoprotein cholesterol (–0.5% [95% CI –0.9% to –0.1%]), whereas greater butter intake was associated with higher total cholesterol (0.6% [95% CI 0.2% to 1.0%]) and high-density lipoprotein cholesterol (1.6% [95% CI 1.1% to 2.0%]) concentrations. In contrast, higher total yogurt intake was associated with lower total cholesterol (–1.1% [95% CI –2.0% to –0.2%]) and higher high-density lipoprotein cholesterol (1.8% [95% CI 0.5% to 3.1%]). Greater total dairy intake (regardless of fat content), total cheese, full-fat cheese, and yogurt were consistently associated with lower concentrations of glucose, insulin, and C-reactive protein. However, milk and butter were not associated with these biomarkers. Conclusions Higher dairy intake, except butter, was associated with a favorable profile of lipids, insulin response, and inflammatory biomarkers, regardless of fat content. Yet, specific dairy foods might influence these markers uniquely. Findings do not support a putative role of dairy in cardiometabolic diseases observed in some previous studies.

Objective Assisted reproductive technology (ART) treatments are commonly used to aid conception in subfertile couples. This study aimed to evaluate the risks of adverse maternal and offspring outcomes in singleton pregnancy conceived with different ART treatments and techniques. Evidence Review We searched MEDLINE, Embase, CENTRAL, and HTA until December 2020 for all systematic reviews evaluating adverse outcomes in pregnancies conceived with various ART techniques, autologous or donor gametes, and embryo development stages. We assessed review quality using the AMSTAR 2 tool risk ratio (RR) or odds ratio (OR) with 95% confidence intervals (CIs) from the top quality reviews for each of the outcomes of interest across the identified ART treatments and population subgroups. Results We included 24 systematic reviews, which mostly reported on observational studies. Compared with spontaneous conception, ART pregnancies had a higher risk of placenta previa (RR, 3.71; 95% CI, 2.67–5.16), antepartum hemorrhage (RR, 2.11; 95% CI, 1.86–2.38), preterm birth (PTB) (RR, 1.71; 95% CI, 1.59–1.83), very preterm birth (RR, 2.12; 95% CI, 1.73–2.59), small for gestational age (SGA) (RR, 1.35; 95% CI, 1.20–1.52), low birth weight (LBW) (RR, 1.61; 95% CI, 1.49–1.75), and very low birth weight (VLBW) (RR, 2.12; 95% CI, 1.84–2.43). Frozen vs. fresh embryo transfer was associated with a lower risk of PTB (RR, 0.90; 95% CI, 0.84–0.97), SGA (RR, 0.61; 95% CI, 0.56–0.67), LBW (RR, 0.72; 95% CI, 0.67–0.77), and VLBW (RR, 0.76; 95% CI, 0.69–0.82). Embryo transfer at blastocyst vs. cleavage showed a higher risk of PTB (RR, 1.10; 95% CI, 1.01–1.20) and large for gestational age (RR, 1.12; 95% CI, 1.03–1.21) with a lower risk of SGA (RR, 0.84; 95% CI, 0.76–0.92). Using donor vs. autologous oocytes increased the odds of PTB (OR, 1.57; 95% CI, 1.33–1.86), LBW (OR, 1.94; 95% CI, 1.10–3.41), and VLBW (OR, 1.37; 95% CI, 1.22–1.54) as well as maternal complications, including postpartum hemorrhage (OR, 1.96; 95% CI, 1.20–3.20), gestational diabetes (OR, 1.27; 95% CI, 1.03–1.56), hypertensive disorders of pregnancy (OR, 2.63; 95% CI, 2.17–3.18), and cesarean section (OR, 2.28; 95% CI, 2.14–2.42). Conclusions Assisted reproductive technology treatments are associated with increased risks of adverse maternal and offspring outcomes, especially with donor oocytes. The characteristics of ART treatment should be incorporated into prenatal care planning to mitigate those risks. PROSPERO Registration CRD42020182612, registered March 9, 2020.

Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins’ putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care., Graphical Abstract Graphical Abstract

Cancer is one of the fatal diseases that cause many deaths around the world. Lung cancer has the highest incidence and mortality rates among cancer-related death worldwide. Lung cancer is a common malignant tumor that poses a severe threat to human life due to its high prevalence and mortality. There are no early screening biomarkers for lung cancer. Patients with lung cancer are often diagnosed in the middle and advanced stages of the disease that show unfavorable clinical outcomes. Chemotherapy, radiation therapy, and surgical removal are commonly used to cure lung cancer. Chemotherapy is among the most common techniques for treating lung cancer. Due to the incredibly low delivery potency and non-specificity of anti-cancer medications, systematic chemotherapy is limited in clinical effectiveness and has significant toxic side effects. Despite continued medical advances, lung cancer nevertheless needs successful treatment. Nanotechnology has recently emerged as a potential approach to lung cancer management and care. Present therapies have been transformed by nanotechnology, which focuses on reducing toxicity and enhancing the bioavailability of anticancer medications in tumor cells. However, nanotechnology would have to tackle many challenges to gain traction in lung cancer treatment. This article reviews the latest literature on the use of nano-drug delivery mechanisms in lung cancer treatment. This research aims to propose new ideas for developing nanocarriers for lung cancer drug delivery.

When a Jehovah’s Witness patient is traumatically injured, the lack of uniform professional consensus guidelines and the cultural knowledge deficit of many clinicians adds an additional layer of legal and ethical complexity to the inherent difficulty of managing a critically ill patient. We present here the case of an incapacitated Jehovah's Witness patient with severe traumatic hemorrhagic shock. We go on to discuss the historical and contemporary case law on proxy refusal of blood transfusion for the incapacitated adult, as well as the ethics of self-determination and the application of the principle of proportionate reason in the management of the critically injured Jehovah's Witness patient.

The aim of this study was to association between dynapenic abdominal obesity (DAO) and pulmonary function in community-dwelling older adults. Most of the pulmonary function variables were associated with abdominal obesity, dynapenia, and DAO conditions. In the adjusted model, there was an association of reduced FVC, FEV1, and PEF values only with dynapenia. No studies have previously analyzed the association between DAO and pulmonary function in older adults. Further longitudinal studies may provide additional information and confirm these findings. No studies have previously analyzed the association between dynapenic abdominal obesity (DAO) and pulmonary function in older adults. The aim of this study was to analyze whether there is an association between pulmonary function and abdominal obesity, dynapenia, and DAO in community-dwelling older adults. A cross-sectional study was conducted with community-dwelling older adults (n = 383) of Macapa, Amapa, Brazil. Pulmonary function variables were evaluated with spirometry; and DAO was evaluated with the combination of dynapenia and abdominal obesity. Cutoff points for handgrip strength, 26 kg force for men and 16 kg force for women, were used to detect dynapenia; and cutoff points of abdominal circumference of > 102 cm for men and > 88 cm for women were used to identify abdominal obesity. Most of the studied pulmonary function variables (obtained values and obtained versus predicted values) were associated with abdominal obesity, dynapenia, and DAO. However, in the adjusted model, there was an association of FVC (β = − 0.163; p

The link between diabetes and cognitive dysfunction has been reported in many recent articles. There is currently no disease-modifying treatment available for cognitive impairment. Boswellia serrata (B. serrata) is used traditionally to treat chronic inflammatory diseases such as type 2 diabetes (T2D), insulin resistance (IR), and Alzheimer's disease (AD). This review aims to highlight current research on the potential use of boswellic acids (BAs)/B. serrata extract in T2D and AD. We reviewed the published information through June 2021. Studies have been collected through a search on online electronic databases (Academic libraries as PubMed, Scopus, Web of Science, and Egyptian Knowledge Bank). Accumulating evidence in preclinical and small human clinical studies has indicated that BAs/B. serrata extract has potential therapeutic effect in T2D and AD. According to most of the authors, the potential therapeutic effects of BAs/B. serrata extract in T2D and AD can be attributed to immunomodulatory, anti-inflammatory, antioxidant activity, and elimination of the senescent cells. BAs/B. serrata extract may act by inhibiting the IκB kinase/nuclear transcription factor-κB (IKK/NF-κB) signaling pathway and increasing the formation of selective anti-inflammatory LOX-isoform modulators. In conclusion, BAs/B. serrata extract may have positive therapeutic effects in prevention and therapy of T2D and AD. However, more randomized controlled trials with effective, large populations are needed to show a definitive conclusion about therapeutic efficacy of BAs/B. serrata extract in T2D and AD.

Background Forcibly Displaced Myanmar Nationals (FDMNs) fled into Cox’s Bazar, Bangladesh due to internal conflict. Considering the public health situation, a surveillance network was established to identify the enteric pathogens and early detection of cholera epidemics. The purpose of this manuscript is to report the clinical, epidemiological determinants of cholera and other enteric pathogens among hospitalized diarrheal patients from FDMNs and host community. Methods A total of 11 sentinel surveillance sites were established around the camps in Ukhia and Teknaf Upazila, Cox’s Bazar. Rapid diagnostic testing was conducted for immediate detection of cholera cases. Stool samples were transferred to the Infectious Diseases Division, International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) laboratory for culture. Results A total of 8134 participants with diarrhea were enrolled from 2017 to 2019: 4881 were FDMNs and 3253 were from the Bangladeshi host community. Among the FDMNs, the proportion of Vibrio cholerae was 0.7%, the proportion of enterotoxigenic Escherichia coli (ETEC) was 4.9%, and the proportion of Shigella was 1.5%. The distributions from host community were 1.2% V cholerae, 1.8% ETEC, and 1.1% Shigella. Similar risk factors have been identified for the diarrheal pathogens for both communities. Conclusions This surveillance helped to monitor the situation of diarrheal diseases including cholera in refugee camps as well as in the neighboring host community. These findings lead policymakers to take immediate preventive measures.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma that carries a favourable prognosis. However, a small subset unfortunately shows transformation to least differentiated anaplastic carcinoma (AC) having a highly aggressive behavior. This process usually occurs within thyroid but is rare in metastatic cervical lymph node or soft tissue neck and exceedingly rare at distant sites. We report a unique case of a 75 years female who presented with anaplastic carcinoma in metastatic neck deposit with occult papillary thyroid carcinoma. To the best of our knowledge, this is the first case in the world literature having anaplastic transformation (AT) in the metastatic neck deposit, right at the presentation with a totally unnoticed PTC clinically. We present this case to emphasize that the transformation process can occur even when the differentiated malignancy in thyroid is small, insignificant or hidden and that metastasis solely can be the presenting feature which can be misleading clinically and even histopathologically. As AC is very aggressive, there is need for early and precise diagnosis & prompt therapeutic intervention. Keywords: Anaplastic carcinoma, Transformation, Papillary thyroid carcinoma, Dedifferentiation, Immunohistochemistry

Introduction: Piriformis syndrome is an uncommon disease resulting from the piriformis muscle’s compression of the sciatic nerve. Pain and numbness in the buttocks and down the leg are the most common symptoms. This study analyzes the laparoscopic surgical treatment of piriformis syndrome. Methods: We report three cases of piriformis syndrome diagnosed in our hospital. The first case was a 40 years old woman with a 7-year history of intermittent low back pain and sciatica on her right side. Hyperesthesia and cutaneous allodynia were observed in the right sciatic nerve dermatome. The second case was a 30 years old woman with a 2-year history of sciatica on her left side. The third case was a 30 years old woman with a 2-year history of sciatica on her right side. All the patients underwent laparoscopic decompression surgery, which was performed to release the sciatic nerve or sacral nerve roots. Results: The patients were reexamined at the postoperative 3rd and 6th months. Their visual analog scale (VAS) scores were found to be decreased from 10/10, 9/10, and 7/10 to 0/10, 1/10, and 0/10, respectively. Conclusion: Due to the very few cases in the literature, pelvic piriformis syndrome is an exclusively clinical diagnosis. If the sciatica is refractory to conservative treatments, laparoscopic exploration and decompression surgery of the pelvic nerves and piriformis muscle could be an option.

BACKGROUND: Cytokines are inflammatory mediators that regulate multiple processes potentially implicated in inflammation and autoimmunity. AIM: This study aimed to investigate the levels of circulating interleukin (IL)-35, IL-36, and IL-35/IL-36 ratio in Juvenile Idiopathic Arthritis (JIA) patients. METHODS: Fifty-one patients categorized based on the International League of Associations for Rheumatology classification criteria were enrolled, along with 46 healthy controls. Disease activity assessment was conducted according to the Juvenile Arthritis Disease Activity Score (JADAS-27) system. Serum cytokine levels were determined using the sandwich enzyme-linked immunosorbent assay. RESULTS: Compared to controls, the serum levels of IL-36 were significantly higher among JIA children (p = 0.002), and serum IL-35 levels and the IL-35/IL-36 ratio were significantly lower in the patients (p = 0.002, p < 0.001, respectively). Furthermore, the IL-35/IL-36 serum ratio, but not the absolute IL levels, correlated positively with the JADAS-27, giving a good indication of the disease outcome. Further, the IL-35/IL-36 serum ratio showed higher sensitivity and specificity compared to the absolute cytokine levels. CONCLUSION: A significant change in the circulating IL-35 and IL-36 levels and an imbalance in the IL35/IL36 ratio occur in JIA. This study is a novel attempt to explore the role of IL-35 and IL-36 in JIA; further studies are required to support our results. The IL-35/Il-36 ratio is a promising immunological marker to predict, diagnose, and monitor JIA.

Acinar cell carcinoma (ACC) is a very rare tumor of the exocrine pancreas, representing less than 1% of all pancreatic malignancies. The majority of data regarding ACC are limited to small case series.This is a retrospective study conducted at a large healthcare system from 1996 to 2019. Patients with pathologically confirmed ACC were included, and demographic data, tumor characteristics, and treatment outcomes were abstracted by chart review. Survival curves were obtained by using the Kaplan-Meier method and compared using the log-rank test.Sixty-six patients with ACC were identified. The median patient age at diagnosis was 64, and 42% presented with metastatic disease. The majority presented with abdominal pain or pancreatitis (69%), and laboratory parameters did not correlate with tumor size, metastatic disease, or survival. Several somatic abnormalities were noted in tumors (BRCA2, TP53, and mismatch-repair genes). In patients with localized disease that underwent resection, the median time to develop metastatic lesions was 13 months. The median overall survival (OS) was 24.7 months from diagnosis, with a survival difference based on metastatic disease at diagnosis (median 15 vs 38 mos). Surgery was associated with improved survival in non-metastatic cases (p = 0.006) but not metastatic cases (p = 0.22), and chemotherapy showed OS benefit in metastatic disease (p 0.01). Patients with metastatic ACC treated after 2010 utilized more platinum-based agents, and there was a OS benefit to FOLFOX or FOLFIRINOX chemotherapy compared to gemcitabine or capecitabine-based regimens (p = 0.006).Pancreatic ACC patients often present with advanced disease. Surgery was associated with survival benefit among patients presenting with localized disease. The use of FOLFOX or FOLFIRINOX chemotherapy regimens was associated with improved OS in metastatic patients. These data add to our knowledge in this rare malignancy, and improves understanding about the genomic underpinnings, prognosis and treatment for acinar cancers.

BACKGROUND/OBJECTIVES Acne is a common skin condition that may be treated by both dermatologists and pediatricians. However, the treatments provided by dermatologists and pediatricians may differ. We aimed to describe acne therapy prescribing patterns of dermatologists and pediatricians. METHODS We performed a population-based, cross-sectional analysis using data from the National Ambulatory Medical Care Survey from 2006 to 2016 for pediatric patients (age ≤ 18 years). RESULTS There were approximately 30.5 million (weighted) outpatient acne visits between 2006 and 2016 for pediatric patients; 52% of visits were conducted by dermatologists, 29% by pediatricians, and 19% by other providers. Compared to pediatricians, dermatologists saw older patients (mean age 15.5 ± 0.12 vs 13.5 ± 0.35; P

Background: Overweight and obesity are defined as abnormal or excessive fat accumulation that may impair health. Body mass index (BMI) is a simple index of weight-for-height that is commonly used to classify overweight and obesity in adults. It is defined as a person's weight in kilograms divided by the square of his height in meters (kg/m2). Aim of Study: Our study was conducted to assess serum zinc level before and after low carbohydrate diet program over 40 days. Patients and Methods: The study included 30 overweight and obese students with age range from (20-26 years) 22 females and 8 males selected randomly from Faculty of medicine Ain Shams University during 2019-2020 after ex-clusion of students with body mass index below 25kg/m2 and students with constipation, fatigue, diarrhea, heartburn, gas, nausea, vomiting, appetite changes or headache. Results: Serum zinc levels in overweight and obese students were low, most of participants have zinc deficiency which improved with the decrease of BMI after low carbohy-drate diet program this ensures that serum zinc levels affected by body weight and body mass index. Our single arm open label clinical trial showed that serum zinc level improved with decrease in body mass index among overweight and obese medical students after applying low carbohydrate diet program over the same period of time. Conclusion: Taken together the benefits of carbohydrate restriction in overweight/obese patients and the altered serum zinc levels in these patients, it was tempting to further serum zinc levels before and after low carbohydrate diet in overweight and obese youth, where to our knowledge, this is the first clinical study targeting this subject in Egypt.