Phytochemical investigation of extract of amorphophallus campanulatus tubers

Pharmacognostic evaluation of Amorphophallus campanulatus tubers for alkaloids, saponins, coumarins, tannin, steroids, flavones, quinones, proteins phenols, carbohydrates. It was concluded that the extract of tuber contain important constitutents for pharmacological acitivity Keywords: Phytochemical Screening, Amorphophallus campanulatus, tuber

FLUORIDE INDUCED NEPHROTOXICITY: APOPTOSIS, ULTRASTRUCTURAL CHANGES AND RENAL TUBULAR INJURY IN EXPERIMENTAL ANIMALS

Fluorosis is endemic in many countries across the globe. Most of the Indian states are endemic for fluorosis. Fluoride is known to cause many types of health complications and affects skeletal & soft tissues. The kidneys are one of the highly exposed organs for all the ingested toxins including fluoride. Therefore fluoride exposed subjects are highly vulnerable to fluoride induced nephrotoxicity. In recent years it has been demonstrated that the prevalence of renal impairment is remarkably high in different fluorosis endemic areas. Higher prevalence of CKD observed in central dry zone of Sri Lanka, a fluorosis endemic region. The prevalence of renal tubular dysfunctions is significantly high in residents of El Quel, which is also an endemic fluorosis area in Southern Algeria. On the basis of previous research reports it may be concluded that fluoride induces renal impairments and renal tubular injuries, cellular and sub-cellular ultrastructural changes. But all the research reports available are confined to animal models only. The data available on fluoride associated renal impairment in human is scant and limited to case reports and epidemiological studies. Due to the variation in types of animal models used in the studies, variations in quantity of fluoride administered and variations in route of fluoride administration, the generated insight cannot be translated to clinic. Therefore there is need to adopt a direct holistic approach to evaluate the adverse effects of fluoride on kidney structure and function in human subjects.

QUALITY OF LIFE AFTER BURN INJURY; A DEVELOPING COUNTRY PERSPECTIVE

Introduction: Millions of people experience severe form of burn that is often life threatening and requires extensive medical care and rehabilitation. The debilitating effect of burn is not confined to physical health only; rather it has a profound impact on a person’s functional, social and psychological health. This study was designed to assess the quality of life among individuals with burn injuries from different areas of Khyber Pakhtunkhwa, Pakistan. Material & Methods: This was a cross sectional study conducted on burn survivors. The data was collected from patients who were visiting outpatient department of ‘Burn and Plastic Surgery Center Hayatabad Peshawar’. This center is the first and the only center specialized in dealing burn casualties. After applying inclusion criteria (both gender, age ≥18, %TBSA ≤40%, type of burn, duration and out-patient only) and exclusion criteria (not participating, %TBSA >40%, in-patient, not fulfilling inclusion criteria), a total 109 patients were recruited in the study using non-probability convenience sampling technique. Informed consent was taken from all the participants. Burn-Specific-Health-Scale (BSHS) was used to assess the impact of burn on quality of life (QOL). SPSS version 22 was used for data analysis. Results: The mean age of the participants was 26.58 ± 11.37 years. The male to female ratio was 70:39. Independent t-test was used to identify the difference among different domains of BSHS. The study revealed that 67 to 69% of patients were extremely affected in work domain. On a scale of severity from 0= extremely affected to 4= not affected at all; Males were affected more in simple abilities like dressing / bathing as compared to females (p=0.03). Lack of sexual desire was reported in married people (p= 0.01). Percentage of total burn surface area (TBSA), duration and type of burn had significant effect on QOL. Conclusion: This study concluded that burn has severely limited individuals working capacity encompassing both house chores and occupation. It has also adversely affected individual’s sensitivity to environmental temperature, self-care, sexuality and body image

Soil Quality Variation under Different Land Use Types in Haramosh Valley, Gilgit, Pakistan

Soil quality is a fundamental component of environmental quality and impact of land use is also a keydetrimental factor in today’s rapid urbanization era. The study aims to evaluate the effects of different land-use type on selected soil quality indicators. Sixty soil samples were collected from various land use types, i.e, pasture, forest and agriculture from a depth of 0-15cm. Analysis of variance (ANOVA) showed that the land use type significantly affected the soil’s physical and chemical properties. The moisture content was significantly higher (p<0.001) in the pasture (41.7%) than the forest (26.2%) and lowest in agricultural land (14.4%). The soil pH was significantly higher or slightly alkaline for agriculture (7.8), while for pasture (6.5) and forest (6.1), it was found to be slightly acidic. Electric conductivity (EC) and bulk density (BD) did not vary significantly with land use type, but the EC followed the decreasing order: forest (203.7μS/cm) < pasture (235μS/cm) < agriculture (328.7μS/cm). The soil organic matter (SOM) and soil organic carbon (SOC) significantly (p<0.05) differed with land use type and found in the order: forest (3.0%, 1.3 %) > pasture land (2.9%, 1.2%) > arable land (2.5%, 1.1%). NO3-N, available P and exchangeable K did not vary significantly across land use types. However, mean values were higher for agriculture (10.2mg/kg, 4.5mg/kg, 66mg/kg) than forest (10mg/kg,3.5mg/kg, 60mg/kg) and pasture (9.8mg/kg, 4.3, 60.2mg/kg). Alpine soils are good ecological indicators because of vulnerability to environmental change, therefore, regular monitoring of soil properties along with carbon stocks is essential to maintain soil health, enhance agricultural productivity and sustain agroecosystems

Divergent age patterns of under-5 mortality in south Asia and sub-Saharan Africa: a modelling study.

BACKGROUND: Understanding the age pattern of under-5 mortality is essential for identifying the most vulnerable ages and underlying causes of death, and for assessing why the decline in child mortality is slower in some countries and subnational areas than others. The aim of this study is to detect age patterns of under-5 mortality that are specific to low-income and middle-income countries (LMICs). METHODS: In this modelling study, we used data from 277 Demographic and Health Surveys (DHSs), 58 Health and Demographic Surveillance Systems (HDSSs), two cohort studies, and two sample-registration systems. From these sources, we collected child date of birth and date of death (or age at death) from LMICs between 1966 and 2020. We computed 22 deaths rates from each survey with the following age breakdowns: 0, 7, 14, 21, and 28 days; 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, and 21 months; and 2, 3, 4, and 5 years. We assessed how probabilities of dying estimated for the 22 age groups deviated from predictions generated by a vital registration model that reflects the historical mortality of 25 high-income countries. FINDINGS: We calculated mortality rates of 81 LMICs between 1966 and 2020. In contrast with the other regions of the world, we found that under-5 mortality in south Asia and sub-Saharan Africa was characterised by increased mortality at both ends of the age range (ie, younger than 28 days and older than 6 months) at a given level of mortality. Observed mortality in these regions was up to 2 times higher than predicted by the vital registration model for the younger-than-28 days age bracket, and up to 10 times higher than predicted for the older-than-6 months age bracket. This age pattern of under-5 mortality is significant in 17 countries in south Asia and sub-Saharan Africa. Excess mortality in children older than 6 months without excess mortality in children younger than 28 days was found in 38 countries. In south Asia, results were consistent across data sources. In sub-Saharan Africa, excess mortality in children younger than 28 days was found mostly in DHSs; the majority of HDSSs did not show this excess mortality. We have attributed this difference in data sources mainly to omissions of early deaths in HDSSs. INTERPRETATION: In countries with age patterns of under-5 mortality that diverge from predictions, evidence-based public health interventions should focus on the causes of excess of mortality; notably, the effect of fetal growth restriction and infectious diseases. The age pattern of under-5 mortality will be instrumental in assessing progress towards the decline of under-5 mortality and the Sustainable Development Goals. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health

High Y-chromosomal differentiation among ethnic groups of Dir and Swat districts, Pakistan

The ethnic groups that inhabit the mountainous Dir and Swat districts of northern Pakistan are marked by high levels of cultural and phenotypic diversity. To obtain knowledge of the extent of genetic diversity in this region, we investigated Y‐chromosomal diversity in five population samples representing the three main ethnic groups residing within these districts, including Gujars, Pashtuns and Kohistanis. A total of 27 Y‐chromosomal short tandem repeats (Y‐STRs) and 331 Y‐chromosomal single nucleotide polymorphisms (Y‐SNPs) were investigated. In the Y‐STRs, we observed very high and significant levels of genetic differentiation in nine of the 10 pairwise between‐group comparisons (RST 0.179–0.746), and the differences were mirrored in the Y‐SNP haplogroup frequency distribution. No genetic differences were found between the two Pashtun subethnic groups Tarklanis and Yusafzais (RST = 0.000). Utmankhels, also considered Pashtuns culturally, were not closely related to any of the other population samples (RST 0.451–0.746). Thus, our findings provide examples of both associations and dissociations between cultural and genetic legacies. When analyzed within a larger continental‐scale context, these five ethnic groups fall mostly outside the previously characterized Y‐chromosomal gene pools of the Indo‐Pakistani subcontinent. Male founder effects, coupled with culturally and topographically based constraints upon marriage and movement, are likely responsible for the high degree of genetic structure in this region

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency

Background &amp; Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p &lt;0.001). Without siEHC, NLS in the BSEP1/3 group was similar to that in BSEP3/3, but considerably lower than in BSEP1/1 (at age 10 years: 38%, 30%, and 71%, respectively; p = 0.003). After siEHC, BSEP1/3 and BSEP3/3 were associated with similarly low NLS, while NLS was much higher in BSEP1/1 (10 years after siEHC, 27%, 14%, and 92%, respectively; p &lt;0.001). Conclusions: Individuals with BSEP deficiency with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as those with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment. Impact and implications: This manuscript defines the clinical features and prognosis of individuals with BSEP deficiency involving the combination of one relatively mild and one very severe BSEP deficiency mutation. Until now, it had always been assumed that the mild mutation would be enough to ensure a relatively good prognosis. However, our manuscript shows that the prognosis of these patients is just as poor as that of patients with two severe mutations. They do not respond to biliary diversion surgery and will likely not respond to the new IBAT (ileal bile acid transporter) inhibitors, which have recently been approved for use in BSEP deficiency.</p

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. Homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC), in contrast to patients with two predicted protein truncating mutations (PPTM). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n=31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n=30), and with two PPTMs (BSEP3/3; n=77). We compared presentation, native liver survival (NLS), and effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (P<0.001). Without siEHC in their follow-up, NLS of BSEP1/3 was similar to BSEP3/3 patients, but considerably lower than BSEP1/1 patients (at age 10 years: 38%, 30%, and 71%, resp; P=0.003). After siEHC, BSEP1/3 and BSEP3/3 patients had similarly low NLS, while this was much higher in BSEP1/1 patients (10 years after siEHC, 27%, 14%, and 92%, resp.; P<0.001). Conclusions: BSEP deficiency patients with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as patients with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research