Diagnostic Reliability of Paediatric Appendicitis Score & Ultrasound Scan in Children with Suspected Acute Appendicitis

Objective:  To evaluate the efficacy of Paediatric Appendicitis Score and ultrasound scan in the paediatric population. This study evaluates the best predictive measure for diagnosing acute appendicitis.Methodology: We conducted a prospective observational study on 120 children (02-13 years) in the department of Neonatal and Paediatric Surgery at The Children’s Hospital PIMS, Islamabad, with suspected appendicitis. Each patient was evaluated based on their Paediatric Appendicitis Score and ultrasound findings. We performed open appendectomy under general anaesthesia in patients with Paediatric Appendicitis Score ≥06 or who presented with severe tenderness on cough, TLC more than 10,000/mm3, or positive ultrasound findings.Results: In our study, the sensitivity and specificity of the Paediatric Appendicitis Score were 92.6% and 72.0%, respectively. Its sensitivity and specificity were 84.09% and 85.71%, respectively, with cutoff ≥6 combined with ultrasound findings. The combined sensitivity and specificity of Paediatric Appendicitis Score <6 and ultrasound were 85.71% and 94.44%, respectively.Conclusion: Paediatric Appendicitis Score is a useful diagnostic tool for suspected appendicitis in pediatric population. Its efficacy is significantly increased when combined with ultrasound. Combined application of the Paediatric Appendicitis Score with ultrasonography helps to rule out negative appendectomies and reduces complications associated with delayed diagnosis

Geology, Petrographical Features and Ore Mineralization of Volcanic Hosted Iron Ore Deposit in the Mashki Chah Area Chagai District, Balochistan, Pakistan

The Mashki Chah iron ore deposits are located in the western Chagai magmatic belt and hosted withinandesitic rock units in the Late Cretaceous Sinjrani Volcanic Group. Geometry, morphology, and structure of iron orehave massive, thin to thick-bedded and veins type of iron. The major ore type including magnetite as primarymineralization of iron ore and hematite, siderite, goethite, and limonite are secondary mineralization of iron ore.Petrographically, the iron ore is hosted within the basic to the intermediate type of units (Basaltic Andesite, Andesite,and Dacite) within the Late Cretaceous Sinjrani Volcanic Group. Major constituents of basaltic andesitic units arecomposed of clinopyroxene and amphibole with minor constituents of quartz. Andesitic units consist of plagioclase,hornblende, k-feldspar, quartz and biotite. The dacitic unit is comprised of quartz, albite, k-feldspar, biotite, andmuscovite. SEM-EDX and BSE analysis of ore mineralization of iron ore to identify the mineral crystal structure,texture, and elemental composition of iron ore. BSE images indicate the crystal morphology of magnetite and hematitehave well-developed cubic and octahedron crystal shapes with a coarse grain texture. Elemental composition isidentified by the EDX graph that is indicated the high peaks of Fe and O elements associated with the high peak rockforming minerals elements Si and O with sub-peaks of Al, Na, K, and Ca and as well as have sub-peaks of ore-formingmineral elements are include a Cu, Ag, Ti, and Sn. The total iron reserve in the deposit area is approximately about 45to 50 million tons and an average percentage of magnetite is 86.16% and hematite is about 69.40 %. These ore deposithas significant value for economic purpose and as well as economically the Mashki Chah iron ore deposit is viable foriron ore mining

Oral thearubigins do not protect against acetaminopheninduced hepatotoxicity in mice

Purpose: To investigate the potential protective effect of oral repeated doses of thearubigins against acetaminophen-induced hepatotoxicity in mice.Methods: Mice were randomly divided into six groups (n=8) and administered the following: Control group (saline), acetaminophen group (saline), N-acetylcysteine group (500 mg/kg/day), and thearubigins groups (60, 70, 100 mg/kg/day). The drugs were given orally by gavage for seven days. On day 7, 1 h after the last dose of treatment, the mice (except control group) were given a single dose of acetaminophen (n-acetyl-p-aminophenol, APAP) orally by gavage (350 mg/kg) and then sacrificed 4 h post-APAP intake. Blood was collected for biochemical measurements and their liver were subjected to biochemical and histopathological assessment.Results: The acetaminophen group showed significant increases (p < 0.001) in serum alanine aminotransferase level, hepatic cytochrome P2E1 level, and serum and hepatic malondialdehyde levels. Moreover it showed significant decrease (p < 0.001) in serum and hepatic glutathione levels. Morphologically, the liver sections showed cellular necrosis, vacuolization, and degeneration around the centrilobular veins. Pretreatment with N-acetylcysteine reversed all acetaminophen-induced changes (p < 0.001 for all biomarkers except for hepatic MDA (p = 0.014) while pretreatment with thearubigins failed to reverse any of them.Conclusion: Oral repeated doses of thearubigins failed to protect against acetaminophen-induced hepatotoxicity in mice and didn't affect hepatic cytochrome P2E1 level.Keywords: Acetaminophen, Hepatotoxicity, Thearubigins, N-acetylcysteine, Cellular necrosis, Vacuolization, Hepatic cytochrome P2E

Therapeutic effects of co-inhaled roflumilast or formoterol and fluticasone on asthma-induced ultrastructural changes in murine airways

Purpose: To investigate the therapeutic effects of "inhaled" roflumilast and formoterol separately or combined with fluticasone on the ultrastructural airway changes in ovalbumin-induced asthmatic mice.Methods: The asthmatic mice were divided randomly into seven groups (n = 8): positive control, vehicle, and five treated groups. The following treatments were given by inhalation (15 min once/day) for seven days: roflumilast (500 μg/kg), formoterol (50 μg/kg), fluticasone (1000 μg/kg), roflumilast + fluticasone (500 + 1000 μg/kg), and formoterol + fluticasone (50 + 1000 μg/kg). Ultrathin lung sections (50 - 70 nm thick) were examined by transmission electron microscopy.Results: The asthmatic mice showed marked degenerative changes in bronchiolar epithelial cells. The alveolar septal walls were thickened with cellular changes and capillary congestion. The basement membranes showed marked thickening and the airway lumens contained abundant mucinous secretions. These ovalbumin-induced ultrastructural airway changes were markedly-reversed in the roflumilast + fluticasone group, moderately-reversed in the roflumilast, fluticasone, and formoterol + fluticasone groups, but were not affected in the formoterol group.Conclusion: Co-inhalation of roflumilast + fluticasone significantly improved the ultrastructural airway changes than co-inhalation of formoterol + fluticasone in ovalbumin-asthmatic mice due to its antiinflammatory and antifibrotic effects.Keywords: Asthma, Fluticasone Propionate, Formoterol, Roflumilast, Ovalbumin, Remodeling, Bronchiolar epitheliu

Case report: A novel de novo loss of function variant in the DNA-binding domain of TBX2 causes severe osteochondrodysplasia

Background: T-box family members are transcription factors characterized by highly conserved residues corresponding to the DNA-binding domain known as the T-box. TBX2 has been implicated in several developmental processes, such as coordinating cell fate, patterning, and morphogenesis of a wide range of tissues and organs, including lungs, limbs, heart, kidneys, craniofacial structures, and mammary glands.Methods: In the present study, we have clinically and genetically characterized a proband showing a severe form of chondrodysplasia with developmental delay. Whole-exome sequencing (WES), Sanger sequencing, and 3D protein modeling were performed in the present investigation.Results: Whole-exome sequencing revealed a novel nonsense variant (c.529A>T; p.Lys177*; NM_005994.4) in TBX2. 3D-TBX2 protein modeling revealed a substantial reduction of the mutated protein, which might lead to a loss of function (LOF) or nonsense-mediated decay (NMD).Conclusion: This study has not only expanded the mutation spectrum in the gene TBX2 but also facilitated the diagnosis and genetic counseling of related features in affected families

Regulation of Coronary Blood Flow

The heart is uniquely responsible for providing its own blood supply through the coronary circulation. Regulation of coronary blood flow is quite complex and, after over 100 years of dedicated research, is understood to be dictated through multiple mechanisms that include extravascular compressive forces (tissue pressure), coronary perfusion pressure, myogenic, local metabolic, endothelial as well as neural and hormonal influences. While each of these determinants can have profound influence over myocardial perfusion, largely through effects on end-effector ion channels, these mechanisms collectively modulate coronary vascular resistance and act to ensure that the myocardial requirements for oxygen and substrates are adequately provided by the coronary circulation. The purpose of this series of Comprehensive Physiology is to highlight current knowledge regarding the physiologic regulation of coronary blood flow, with emphasis on functional anatomy and the interplay between the physical and biological determinants of myocardial oxygen delivery. © 2017 American Physiological Society. Compr Physiol 7:321-382, 2017

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030