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Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects a variety of animal species. Susceptibility to SARS-CoV-2 is primarily determined by the utilization of the viral receptor, ACE2. SARS-CoV-2 can utilize a broad range of animal ACE2 isoforms in vitro, including the ACE2 from various camelid species. However, experimental infection of these animals does not lead to productive infection or seroconversion. In this study, we investigate the susceptibility of camelids to SARS-CoV-2 using novel well-differentiated camelid nasal organoids. We show that camelid nasal organoids are highly susceptible to Middle East respiratory syndrome coronavirus (MERS-CoV) infection, but not to infection with different SARS-CoV-2 variants (614G, BA.1 or EG.5.1.1). All viruses efficiently infected human airway organoids. Immunohistochemistry analysis revealed the absence of ACE2 on camelid nasal organoids and dromedary camel upper respiratory tract. In contrast, DPP4 was expressed in both camelid nasal organoids and the camel upper respiratory tract, which correlates with MERS-CoV infection. This study indicates that the camelid upper respiratory tract lacks expression of ACE2, which is associated with resistance to SARS-CoV-2 infection.

Abstract Background Propofol has been the gold standard for anesthesia induction and maintenance due to its rapid onset and favorable pharmacokinetic properties. However, the search for alternative agents with improved safety and efficacy has led to the emergence of ciprofol (HSK3486), a structural analog of propofol. This systematic review and meta-analysis aim to comprehensively assess the safety and efficacy of ciprofol compared to propofol for anesthesia induction and maintenance in adult patients undergoing surgical procedures. Methods This study included only double-arm RCTs in which participants were aged eighteen or older undergoing surgery. For the statistical analysis of the extracted data, we employed RevMan 5.4.1. Results Ciprofol demonstrated a promising trend of higher anesthesiologists’ satisfaction during the induction phase (MD 0.14, 95%, CI − 0.28 to 0.56, p = 0.51), whereas Propofol was favored during maintenance. Propofol also exhibited advantages with a shorter time to successful anesthesia induction (MD 0.08 min, 95% CI 0.00 to 0.15, p = 0.04), and quicker attainment of full alertness (MD 0.11 min, 95% CI − 1.29 to 1.52, p = 0.87), suggesting its efficiency in clinical practice. Importantly, there were no significant disparities in the success rate of anesthesia. Conclusion Both ciprofol and propofol demonstrate comparable efficacy and safety for anesthesia induction and maintenance in adult patients undergoing surgery. While propofol provides a faster onset of induction, ciprofol exhibits advantages in terms of pain management. Clinicians should consider these findings when selecting anesthetic agents, and tailoring choices to individual patient needs and clinical scenarios.

Abstract Background Diarrhoeal diseases are common among children in low- and middle-income countries and are major causes of morbidity and mortality. Cryptosporidium and Giardia are considered to be the main parasitic causes of diarrhoea in children. The aim of the present study was to determine the prevalence and associated factors of Cryptosporidium and Giardia infection in children under five years of age presenting at two health centres (Ndirande and Limbe) in Blantyre, Malawi. Methods This cross-sectional study was performed from February to July 2019 and included 972 children under 5 years of age with diarrhoea. Stool samples were immediately tested after collection at enrolment with a rapid diagnostic test for Cryptosporidium and Giardia infection. Descriptive statistics were used to assess the prevalence of these protozoan parasitic infections, and differences in the basic demographic and anthroponotic variables (between children with diarrhoea and parasite infection, being either Cryptosporidium and Giardia or both versus children with diarrhoea but no RDT confirmed parasite infection) were assessed. Their association with Cryptosporidium and Giardia infection was analysed using simple logistic regressions. Results Of the children recruited, 88 (9.1%) tested positive for Cryptosporidium and 184 (18.9%) for Giardia. Children with only a Giardia infection or a coinfection (of both parasites) were significantly older (mean age 24–26 months) compared to children with only a Cryptosporidium infection (mean age 13 months) or no parasitic infection (mean age 14 months). No significant differences were found with respect to gender, body temperature, stunting or wasting between the different groups of children with moderate to severe diarrhoea. Children attending the Ndirande health centre had almost two times higher odds of testing positive for both infections than those attending Limbe health centre. Conclusion Cryptosporidium and Giardia infections are highly prevalent in children

Background: Infertility is a common problem globally affecting a large proportion of world population. Laparoscopy provides meaningful information regarding different factors that may cause infertility. Objective: To determine the frequency of causes of primary infertility in women by diagnostic laparoscopy. Study Design: Cross sectional study design Setting: Study was performed at the Department of Obstetrics and Gynecology, Jinnah Postgraduate Medical Centre, Karachi Duration: September 2011 to February 2012 Subjects and Methods: 86 patients with primary infertility were included in the study and underwent laparoscopy for deter – mining causes of infertility. Data was analyzed on SPSS, frequencies and percentages were determined for qualitative variables while mean and standard deviation was determined for quantitative variable. Results: Eighty six females were included in the study with mean age of 28.6 + 5.2 years and mean duration of infertility was 4.9 + 1.9 years. Findings on laparoscopy were analyzed and 51.2% of females were found with tubal blockage, while other findings were; hydrosalpinx in 25.6%, PCOs in 22.1%, Ovarian abnormalities in 38.4%, Pelvic adhesions in 38.4% and uterine congenital anomalies in 3.5%. Conclusion: Tubal diseases found to be one of the major factor causing primary infertility and diagnostic laparoscopy will play a valuable role in early and prompt diagnosis and management of causes leading primary infertility. Key Words: Primary Infertility, Diagnostic Laparoscopy, Tubal Blockage, PCOs, Pelvic Adhesions, Hydrosalpinx.

Objective: To compare the frequency of various types of responses in both genders undergoing tilt table test with unexplained syncope. Study Design: A comparative cross-sectional study. Place and Duration of Study: Department of EP studies, Armed Forces Institute of Cardiology and National Institute of Heart Diseases, Rawalpindi, from Aug 2017 to Jan 2018. Material and Methods: Patients were recruited through non-probability consecutive sampling. Patients of all age groups of both genders who had syncope as per operational definition were included in our study. Patients who were excluded from the study were, newly diagnosed or previously established history of arrhythmias, coronary artery disease, cardiomyopathies and structural heart disease e.g. HOCM, aortic stenosis, mitral stenosis. Patients who had history of epilepsy on medical record and history of anemia on medical record were also excluded from the study. Base line demographic information of patients (age, gender, duration of complain) and types of responses were recorded on especially designed proforma. Results: Total 294 patients were recruited for the study. Mean age of the patients was 46.7 ± 8.1 years, with minimum age 12 years and maximum age 85 years. Male patients were found to be 244 (82.4%) while female patients were 50 (16.9%). Mean duration of complaints was 1.5 ± 1.7 months. Our study showed that the most common type of response in male and females were mixed type (88.1%) and (84%) respectively, with the p-value of 0.022. while, cardioinhibitory type response was (2.8%) but found in male gender only. Next most common type was vasodepressor type response common in females than males with 6% and 2.4% respectively. Subsequently, less frequent type of response was showed with classic type of orthrostatic hypotension (2%) while type Initial orthrostatic hypotension was not recoreded in the study. Females were more frequent than males in Progressive orthrostatic hypotension with (5%) and (0.4%) in males. POTS response was not present in either gender. Conclusion: As our study showed, among type of responses, mixed type of response has a significantly high positive rate being more common in male gender, while vasodepressive type and progressive orthostatic hypotension type being more common in female gender. Tilt-table testing plays a major role during the evaluation of syncope patients, helps to differentiate syncope subtypes and could be useful in guiding treatment. however, the need for using another protocol with a similar diagnostic accuracy in gender specificity is necessary.

Madam, lung cancer is one of the commonly diagnosed causes of cancer mortality and morbidity worldwide, accounting for approximately 1.76 million deaths annually.1 In the past overall survival in patients with non-small cell lung cancer (NSCLC) remained uncertain. Many treatment regimens were under trial2 until, a breakthrough study incorporating neoadjuvant nivolumab with chemotherapy showed tremendous success in phase 3 CheckMate 816 trail3. Moreover, the FDA has recently approved this therapy for early-stage NSCLC.4 Nivolumab is an anti–programmed death 1 (PD-1) human antibody, which restores antitumor T cells activity. Whereas platinum-doublet chemotherapy improves antitumor immunity.3 In this trail, approximately 350 patients were randomly assigned in an equal ratio to receive nivolumab (360 mg) plus chemotherapy or chemotherapy alone for consecutive 3 weeks for three cycles before surgery. Two primary end points were established, event-free survival and complete pathological response. Median event-free survival was 31.6 months with nivolumab plus chemotherapy compared to 20.8 months with chemotherapy alone (hazard ratio for disease progression, recurrence, or death, 0.63; P=0.005). The pathological complete response was 24.0% in the nivolumab plus chemotherapy group and 2.2% in chemotherapy alone group (odds ratio, 13.94; P

Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Here the authors generate mutant clonal intestinal organoids for 19 host genes previously implicated in coronavirus biology and identify the cell surface protease TMPRSS2 as a potential therapeutic target.

Objective: To determine the diagnostic accuracy of Tzanakis and Alvarado score for the diagnosis of acute appendicitis taking histopathology as the gold standard. Materials and Methods: It was a Cross-sectional validation study The study was carried out at the emergency department of RMC allied hospital Rawalpindi. The study was completed in eighteen months from 1st May 2016 till 30th Nov 2017. After approval from the ethical committee total of 420 patients fulfilling inclusion criteria from the emergency department of District head Quarter hospital, Rawalpindi was taken. Informed consent was taken from patients or their attendants, and their demographic information like name, age, sex, and address was obtained. Alvarado score and Tzanakis score were calculated (as per operational definition) at the time of admission of the patients. After surgery, the specimen appendix was sent for histopathology in the hospital lab. The diagnosis of the acute appendix was based on a positive histological report which was verified by a pathologist. All the data was entered by a researcher who will collect the data by himself. Results: The mean age of patients in this study was 20.15±7.13 years with 218 (51.9%) males and 202 (48.1%) females. The mean Alvardo score was recorded as 7.22±1.58 with the mean Tzanakis score being 9.64±3.13. The histopathology for diagnosing appendicitis showed positive for 367 (87.4%) patients and negative for 53 (12.6%) patients. The sensitivity of Alvarado score for diagnosing appendicitis, keeping histopathology as the gold standard was 86.92%, specificity was 92.45%, Positive Predictive Value was 98.76%, and Negative Predictive Value was 50.52% and overall diagnostic accuracy was 87.62%. The sensitivity of the Tzanakis score for diagnosing appendicitis, keeping histopathology as the gold standard was 88.83%, specificity was 88.6%, Positive Predictive Value was 98.19%, Negative Predictive Value was 53.41% and overall diagnostic accuracy was 88.81%. Conclusion: The sensitivity of the Tzanakis score was high when compared to the Alvarado score. And specificity was high in the Alvarado score when compared to the Tzanakis score. Moreover, the overall diagnostic accuracy of the Tzanakis score was high when compared to the Alvarado score. SoTzanakis score can be utilized to predict appendix and in the future, we can avoid negative appendectomies.

Background: The exercise stress test (EST) is a non-invasive investigation to diagnose coronary artery disease. This research aimed to determine the relationship between erectile dysfunction (ED), cardiovascular risk factors, and coronary artery disease (CAD) in men referred for EST. Methods: A prospective cohort study enrolling 303 patients from August 2020 through September 2021. All patients filled out the international Index of Erectile Function (IIEF-5) questionnaire. . They underwent an exercise stress test (EST). A two-tailed independent sample t-test, chi-square tests, and binary logistic regression were used for statistical analysis. Results: EST was positive in 110 (36.3%) patients, negative in 154 (50.8%), and inconclusive in 39 (12.8%) patients. ED was present in 225 (74.3%) patients and absent in 78 (25.8%) patients. 278 (91.7%) had one or more cardiovascular risk factors. This study reported a significant relationship between diabetes mellitus (DM), hypertension (HTN), and the results of EST and ED. Compared to patients without ED, patients with ED had a positive EST result. Definite CAD was diagnosed in 21% of patients with ED compared to 1.3% in patients without ED. For a one-unit increase in age, the odds of ED increased by about 5%. Similarly, a negative EST is compared to a positive EST. Negative EST reduced the likelihood of ED by 82%. Conclusions: This research found a statistically significant connection between CAD, certain cardiovascular risk factors, and ED using the EST and IIEF-5 questionnaires. This research is significant because it may alter the way cardiovascular risk stratification is done.

Tuberculosis (TB)-associated uveitis is a common cause of infectious uveitis in the developing world. Diagnosis of TB uveitis remains a challenge. The role of interferon gamma release assays (IGRAs) is uncertain. Herein we summarise the available literature on the utility of IGRAs in the diagnosis and management of TB uveitis. We searched PubMed database from 1 August 2010 to 31 July 2020 using the following keywords alone and in combination: ‘interferon-gamma release assay’, ‘QuantiFERON’, ‘T-SPOT.TB’, ‘TB uveitis’, ‘serpiginous like choroiditis’, ‘tuberculoma’, ‘TB vasculitis’, ‘TB panuveitis’ and ‘ocular tuberculosis’. Data from 58 relevant studies were collated. The review is focused on currently marketed versions of IGRA tests: QuantiFERON-TB Gold In-Tube assay, QuantiFERON-TB Gold Plus assay (QFT-Plus) and T-SPOT.TB. We found limited evidence regarding the diagnostic utility of IGRA in patients with uveitis. No study was identified evaluating the newer QFT test—the QFT-Plus—in patients with uveitis. Similarly, there is lack of data directly comparing QFT-Plus with T-SPOT.TB specifically for the diagnosis of TB uveitis.

Virus propagation methods generally use transformed cell lines to grow viruses from clinical specimens, which may force viruses to rapidly adapt to cell culture conditions, a process facilitated by high viral mutation rates. Upon propagation in VeroE6 cells, SARS-CoV-2 may mutate or delete the multibasic cleavage site (MBCS) in the spike protein. Previously, we showed that the MBCS facilitates serine protease-mediated entry into human airway cells (Mykytyn et al., 2021). Here, we report that propagating SARS-CoV-2 on the human airway cell line Calu-3 – that expresses serine proteases – prevents cell culture adaptations in the MBCS and directly adjacent to the MBCS (S686G). Similar results were obtained using a human airway organoid-based culture system for SARS-CoV-2 propagation. Thus, in-depth knowledge on the biology of a virus can be used to establish methods to prevent cell culture adaptation.

Coronavirus entry is mediated by the spike protein that binds the receptor and mediates fusion after cleavage by host proteases. The proteases that mediate entry differ between cell lines, and it is currently unclear which proteases are relevant in vivo. A remarkable feature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is the presence of a multibasic cleavage site (MBCS), which is absent in the SARS-CoV spike. Here, we report that the SARS-CoV-2 spike MBCS increases infectivity on human airway organoids (hAOs). Compared with SARS-CoV, SARS-CoV-2 entered faster into Calu-3 cells and, more frequently, formed syncytia in hAOs. Moreover, the MBCS increased entry speed and plasma membrane serine protease usage relative to cathepsin-mediated endosomal entry. Blocking serine proteases, but not cathepsins, effectively inhibited SARS-CoV-2 entry and replication in hAOs. Our findings demonstrate that SARS-CoV-2 enters relevant airway cells using serine proteases, and suggest that the MBCS is an adaptation to this viral entry strategy.

Objective: To study the short-term and long-term outcomes of left main angioplasty at AFIC-NIHD. Study Design: Descriptive cross-sectional study. Place and Duration of Study: Armed Forces Institute of Cardiology/National Institute of Heart Disease (AFIC/NIHD) in 2018. Methodology: All cases of left main angioplasty done in 2018 were included in the study. The patients were followed up in clinic or on telephone and mortality (in-hospital, 30 days) outcomes and survival duration were recorded. Kaplan Meier curves were generated to show the survival difference between those who underwent primary or elective LMPCI and survival difference between patients based on extent of coronary artery disease. Results: A total of 73 patients underwent elective or primary left main angioplasty. The extent of coronary artery disease was: single vessel coronary artery disease (26%), double vessel coronary artery disease (37%), and three vessel coronary artery disease (37%). Thirteen patients (17.8%) had primary left main angioplasty, and 60 patients (82.2%) had elective left main angioplasty. Intravascular ultrasound was performed in only 3 patients. The mean duration of follow up was 395 days. A total of 6 (8.2%) patients died. Three patients died in-hospital, another 2 within the first 30 days, and the remaining beyond 30 days. Two of the dead patients had double vessel coronary artery disease, and 4 had three vessel coronary artery disease. The survival difference between the primary vs elective groups was insignificant (Log Rank (Mantel-Cox) (p=0.27). The survival difference between the 3 groups with different extent of coronary artery disease was insignificant (p=0.15). Conclusion: Left main PCI is a safe procedure with acceptable outcomes. Patients with more severe coronary artery disease tend to fare worse.

The title compound, C14H14N2O3, crystallized with three crystallographically independent molecules (A, B and C) in the asymmetric unit. The three molecules each have an E conformation about the C=N bond but differ in the orientation of the phenyl and pyran rings. The dihedral angles between the phenyl and pyran ring planes are 14.30 (1), 28.38 (1) and 25.58 (1)° in molecules A, B and C, respectively. There is an intramolecular O—H...N hydrogen bond in each molecule with an S(6) ring motif. In the crystal, molecules are linked by N—H...O and C—H...O hydrogen bonds, forming layers parallel to (001), enclosing R22(8) and R33(21) ring motifs. The layers are linked via C—H...π interactions, forming bilayers, which are joined by a further C—H...π interaction, forming a three-dimensional structure.

This case report describes a patient with Swyer-James-MacLeod Syndrome (SJMS) in an adult female diagnosed on the basis of findings on X-ray chest, high resolution CT (HRCT) of chest. This rare syndrome is considered to be an acquired disease due to repeated pneumonias in early childhood. [ABSTRACT FROM AUTHOR]

Objectives: To explore adult stakeholders' perspectives on what supports or undermines the mental health of sexual and gender minoritised adolescents (SGMA) in everyday life in order to better understand how to foster supportive psychosocial environments for SGMA., Design: Descriptive qualitative study design, using framework analysis., Methods: Semi-structured interviews were conducted remotely with 16 UK-based adult stakeholders which included parents of SGMA, health and social care professionals, community-based professionals, and professionals who commission services related to adolescent health and well-being., Results: Nine themes were identified that represented barriers and enablers of fostering psychosocial environments that are supportive of SGMA mental health. Example barrier themes include SGMA 'facing chronic and acute safety threats and stress', 'psychological responses to social connection losses and navigating alienation', 'digital exposure and online risk and vulnerability' and 'conflicting messages, resulting divisions and adult distancing'. Example enablers include 'exploring, owning, and changing (personal) identities', 'advocating alongside adolescents whilst containing oneself as the adult in the situation' and 'personally fostering adolescents' psychological safety and inclusion'., Conclusions: Adult stakeholders report that SGMA are often exposed to environments hostile to key aspects of their identity which then by extension undermines their mental health. These experiences can threaten their sense of safety and evolving identity. Practitioners in particular should be aware of the stressors relating to SGMA identity and minoritisation experiences in order to develop the psychological safety and sense of inclusion needed for SGMA to trust in the relationship and the support offered., (© 2024 The Author(s). Psychology and Psychotherapy: Theory, Research and Practice published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Background: Sexual and gender minority youth are at greater risk of compromised mental health than their heterosexual and cisgender peers. This is considered to be due to an increased burden of stigma, discrimination, or bullying resulting in a heightened experience of daily stress. Given the increasing digital accessibility and a strong preference for web-based support among sexual and gender minority youth, digital interventions are a key means to provide support to maintain their well-being., Objective: This paper aims to explicate the co-design processes and underpinning logic of Oneself, a bespoke web-based intervention for sexual and gender minority youth., Methods: This study followed a 6-stage process set out by Hagen et al (identify, define, position, concept, create, and use), incorporating a systematic scoping review of existing evidence, focus groups with 4 stakeholder groups (ie, sexual and gender minority youth, professionals who directly support them, parents, and UK public health service commissioners), a series of co-design workshops and web-based consultations with sexual and gender minority youth, the appointment of a digital development company, and young adult sexual and gender minority contributors to create content grounded in authentic experiences., Results: Oneself features a welcome and home page, including a free accessible to all animation explaining the importance of using appropriate pronouns and the opportunity to create a user account and log-in to access further free content. Creating an account provides an opportunity (for the user and the research team) to record engagement, assess users' well-being, and track progress through the available content. There are three sections of content in Oneself focused on the priority topics identified through co-design: (1) coming out and doing so safely; (2) managing school, including homophobic, biphobic, or transphobic bullying or similar; and (3) dealing with parents and families, especially unsupportive family members, including parents or caregivers. Oneself's content focuses on identifying these as topic areas and providing potential resources to assist sexual and gender minority youth in coping with these areas. For instance, Oneself drew on therapeutic concepts such as cognitive reframing, stress reduction, and problem-solving techniques. There is also a section containing relaxation exercises, a section with links to other recommended support and resources, and a downloads section with more detailed techniques and strategies for improving well-being., Conclusions: This study contributes to research by opening up the black box of intervention development. It shows how Oneself is underpinned by a logic that can support future development and evaluation and includes diverse co-designers. More interactive techniques to support well-being would be beneficial for further development. Additional content specific to a wider range of intersecting identities (such as care-experienced Asian sexual and gender minority youth from a minority faith background) would also be beneficial in future Oneself developments., International Registered Report Identifier (irrid): RR2-10.2196/31036., (©Katherine Brown, Mathijs F G Lucassen, Alicia Núñez-García, Katharine A Rimes, Louise M Wallace, Rajvinder Samra. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.05.2024.)