Pathobiome driven gut inflammation in Pakistani children with environmental enteric dysfunction

Environmental Enteric Dysfunction (EED) is an acquired small intestinal inflammatory condition underlying high rates of stunting in children \u3c5 years of age in low- and middle-income countries. Children with EED are known to have repeated exposures to enteropathogens and environmental toxins that leads to malabsorptive syndrome. We aimed to characterize association of linear growth faltering with enteropathogen burden and subsequent changes in EED biomarkers. In a longitudinal birth cohort (n = 272), monthly anthropometric measurements (Length for Age Z score- LAZ) of asymptomatic children were obtained up to 18 months. Biological samples were collected at 6 and 9 months for the assessment of biomarkers. A customized TaqMan array card was used to target 40 enteropathogens in fecal samples. Linear regression was applied to study the effect of specific enteropathogen infection on change in linear growth (ΔLAZ). Presence of any pathogen in fecal sample correlated with serum flagellin IgA (6 mo, r = 0.19, p = 0.002), fecal Reg 1b (6 mo, r = 0.16, p = 0.01; 9mo, r = 0.16, p = 0.008) and serum Reg 1b (6 mo, r = 0.26, p\u3c0.0001; 9 mo, r = 0.15, p = 0.008). At 6 months, presence of Campylobacter [β (SE) 7751.2 (2608.5), p = 0.003] and ETEC LT [β (SE) 7089.2 (3015.04), p = 0.019] was associated with increase in MPO. Giardia was associated with increase in Reg1b [β (SE) 72.189 (26.394), p = 0.006] and antiflic IgA[β (SE) 0.054 (0.021), p = 0.0091]. Multiple enteropathogen infections in early life negatively correlated with ΔLAZ, and simultaneous changes in gut inflammatory and permeability markers. A combination vaccine targeting enteropathogens in early life could help in the prevention of future stuntin

Gut integrity and duodenal enteropathogen burden in undernourished children with environmental enteric dysfunction

Environmental enteric dysfunction (EED) is a subclinical condition of intestinal inflammation, barrier dysfunction and malabsorption associated with growth faltering in children living in poverty. This study explores association of altered duodenal permeability (lactulose, rhamnose and their ratio) with higher burden of enteropathogen in the duodenal aspirate, altered histopathological findings and higher morbidity (diarrhea) that is collectively associated with linear growth faltering in children living in EED endemic setting. In a longitudinal birth cohort, 51 controls (WHZ \u3e 0, HAZ \u3e -1.0) and 63 cases (WHZ\u3c -2.0, refractory to nutritional intervention) were recruited. Anthropometry and morbidity were recorded on monthly bases up to 24 months of age. Dual sugar assay of urine collected after oral administration of lactulose and rhamnose was assessed in 96 children from both the groups. Duodenal histopathology (n = 63) and enteropathogen analysis of aspirate via Taqman array card (n = 60) was assessed in only cases. Giardia was the most frequent pathogen and was associated with raised L:R ratio (p = 0.068). Gastric microscopy was more sensitive than duodenal aspirate in H. pylori detection. Microscopically confirmed H. pylori negatively correlated with HAZ at 24 months (r = -0.313, p = 0.013). Regarding histopathological parameters, goblet cell reduction significantly correlated with decline in dual sugar excretion (p\u3c 0.05). Between cases and controls, there were no significant differences in the median (25th, 75th percentile) of urinary concentrations (μg/ml) of lactulose [27.0 (11.50, 59.50) for cases vs. 38.0 (12.0, 61.0) for controls], rhamnose [66.0 (28.0, 178.0) vs. 86.5 (29.5, 190.5)] and L:R ratio [0.47 (0.24, 0.90) vs. 0.51 (0.31, 0.71)] respectively. In multivariable regression model, 31% of variability in HAZ at 24 months of age among cases and controls was explained by final model including dual sugars. In conclusion, enteropathogen burden is associated with altered histopathological features and intestinal permeability. In cases and controls living in settings of endemic enteropathy, intestinal permeability test may predict linear growth. However, for adoption as a screening tool for EED, further validation is required due to its complex intestinal pathophysiology

Current practice of histopathology in Pakistan: difficulties, challenges, and solutions

Histopathology is the gold standard for diagnosis of cancers as well as many non- neoplastic diseases. Pakistan is a country of more than 220 million people and the fifth most populated country of the world. Unfortunately, it has a weak healthcare system in general and poor pathology services in particular. Till date, only 338 histopathologists have passed their fellowship examination in Pakistan; this has led to a very alarming situation considering the marked increase in the prevalence of cancer cases and other diseases which need histopathological interpretation. There are only 18 big histopathological labs in the country, the majority of which are located in major cities which further delays the diagnosis of patients who live in rural areas. Immediate steps are required for better histopathology services in the country. Adoption of digital tools may bridge the gaps of histopathology-practice and ensure consistency across the country

Dawn of artificial intelligence -Enable digital Pathology in Pakistan-A paradigm shift

Pathology particularly histopathology is considered to be a busy and challenging field. It is considered as gold standard for the diagnosis and management of patient particularly in cases of tumor. It has been more than twenty years since the introduction of whole slide imaging (WSI) in the developed part of the world. Various whole slide image (WSI) devices and use of artificial intelligence (AI) based softwares have transformed the field of Pathology1. Digital pathology is a novel technology and currently being implemented in most of the developed part of the world.2 Once the patient’s data becomes digital, it is easily stored, reproducible on a single click and quality remains same. This data can be used to make disease models, disease trends and predict the outcome of a particular disease through data mining which will open new horizons of precise medicine. The use of WSI with computational pathology and data storage devices have revolutionized the working in histopathology. The world witnessed an exponential rise in its adoption particularly after Covid-19 pandemic1. However, in the developing world either it is not being implemented or its use is still sub-optimal. By realizing the potential of digital and computational pathology along with the use of artificial intelligence software, we can bring a drastic change in the field of personalized medicine in the developing part of the world 3. Numerous validation studies have been published indicating that WSI is a reliable tool for routine diagnosis in surgical pathology 4 Continuous..

Current practice of histopathology in Pakistan: Difficulties, challenges, and solutions

Histopathology is the gold standard for diagnosis of cancers as well as many non 14 neoplastic diseases. Pakistan is a country of more than 220 million people and the fifth most populated country of the world. Unfortunately, it has a weak healthcare system in general and poor pathology services in particular. Till date, only 338 histopathologists have passed their fellowship examination in Pakistan; this has led to a very alarming situation considering the marked increase in the prevalence of cancer cases and other diseases which need histopathological interpretation. There are only 18 big histopathological labs in the country, the majority of which are located in major cities which further delays the diagnosis of patients who live in rural areas. Immediate steps are required for better histopathology services in the country. Adoption of digital tools may bridge the gaps of histopathology-practice and ensure consistency across the country

The role of microbiome in preterm labor: Recent advances and future challenges

Background: Our current understanding of preterm labor is limited in the context of dysbiosis of microbiome. Human microbiome is comprised of trillions of microorganisms, residing on and within our bodies that are associated with the vital function of organs and systems. Few studies have highlighted the role of maternal gut microbiome dysbiosis as a contributing factor for metabolic syndrome and may be associated with risk of preterm labor. A clear understanding of dysbiosis in placenta or vagina with early ripening of cervix for initiation of preterm labor is not fully elucidated.Aim: Our aim is to contextualize the alteration in microbial community structure in maternal and fetal organs in association with risk of preterm labor.Methods: In this review, we summarized the studies published from 2000 to 2016 in the field of microbiome in association with preterm labor.Findings & Discussion: Evidence suggest that placental microbiome has promising correlation with preterm labor, while findings are equivocal for maternal gut and vaginal microbiome in inducing preterm labor. Similar alteration in fetal intestinal microbiome of meconium is supposed to evoke an inflammatory response that may lead to preterm labor.Conclusion: To understand the relationship of microbiome and preterm labor, both maternal and fetal microbiome should be studied in parallel to determine the causality. Dysregulation of immune response due to disturbance in normal or commensal flora might be an underlying cause of preterm labor

A suggested way forward for adoption of AI-Enabled digital pathology in low resource organizations in the developing world

Abstract Low- and middle-income countries (LMICs) represent a big source of data not only for endemic diseases but also for neoplasms. Data is the fuel which drives the modern era. Data when stored in digital form can be used for constructing disease models, analyzing disease trends and predicting disease outcomes in various demographic regions of the world. Most labs in developing countries don’t have resources such as whole slide scanners or digital microscopes. Owing to severe financial constraints and lack of resources, they don’t have the capability to handle large amounts of data. Due to these issues, precious data cannot be saved and utilized properly. However, digital techniques can be adopted even in low resource settings with significant financial constraints. In this review article, we suggest some of the options available to pathologists in developing countries which can enable them to start their digital journey and move forward despite resource-poor health system

A clinico-mycological spectrum of superficial mycoses of scalp in pediatric population: A clinico-mycological spectrum of superficial mycoses of scalp

Objective: A clinico-mycological study was conducted to assess the profile of dermatophytes and non-dermatophytes in patients with superficial mycoses of scalp. Methods:  This Descriptive cross sectional study was conducted at Department of Microbiology, Basic Medical Sciences Institute, in collaboration with Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi. The study was carried out from May 2019 to September 2019. A total of 114 children were enrolled in the study having a clinical diagnosis of superficial mycoses of scalp. The hair specimens and scales from the scalp were collected. The specimens were processed for wet mounts (KOH and CFW staining) and mycological culture.  . Results: The most common clinical presentation was found to be dermatophytoses (28%). Non-dermatophytoses was seen in 16.1% cases, while 55.2% cases were culture negative. The most common isolated dermatophyte was Trichophyton violaceum (35.4%), while among non-dermatophyte molds, Aspergillus spp accounted for 45% of cases. Conclusion: The unambiguous diagnosis of scalp mycoses can be made by mycological culture and conventional techniques like KOH mounts and CFW staining. Keywords: Calcoflour white stain, Dermatophytes, KOH mount, Tinea capiti

Catalytic activity of palladium doped activated carbon from waste coffee on some environmental pollutants

The presence of nitro compounds and such commercial dyes as Congo red, methylene blue, methyl orange and methyl red in water/wastewater causes environmental issues. The treatment of such industrial contaminants, new efficient hybrid catalysts are designed by Research groups all around the world. For this aim, a large of catalyst systems were designed and their water treatment capacities were investigated. As a part of Green Chemistry approach, food wastes could be used for production of porous carbon materials. In this work, a palladium/activated carbon hybrid catalyst (AC–Pd) was prepared and characterized by XRD, SEM/EDS and TEM. It was found from TEM analysis that the average particle size of AC–Pd hybrid was about 54 nm. The reduction capacity of AC–Pd for nitroarenes and organic dyes was investigated by UV–Vis. spectroscopy in aqueous media. According to catalytic tests results, AC–Pd nanocatalyst could be used in reduction of both nitro compounds and organic dyes

Mesoporous chromium oxide doped palladium catalysis for cyanation reaction of some aryl halides

A Pd/Cr2O3 hybrid catalyst for cyanation reaction of some aryl halides was synthesized and characterized by XRD, SEM/EDS and TEM. The porous structure of the catalyst was also investigated by BET analysis. All XRD characteristic lines were obtained for Cr2O3 and Pd/Cr2O3 hybrid in good agreement with the reference XRD data. It was found that average particle size of Pd/Cr2O3 composite was about 22 nm. The catalytic efficiency of the Pd/Cr2O3–catalyzed cyanation reaction was evaluated for some m- and p-substituted aryl halides. The influence of solvent, reaction time, and base on the activity of the Pd/Cr2O3 catalyst was investigated, and the optimal reaction conditions were systematically obtained. Catalytic investigations showed that Pd/Cr2O3 hybrid can exhibit very good catalytic performance for cyanation reaction of aryl halides with a high yield of around 90%, and retained its catalytic activity throughout successive 5 cycles. Comparative TEM images of Pd/Cr2O3 hybrid catalyst, as-synthesized and after 5th cycle, showed that nano-sized structure of Pd/Cr2O3 catalyst was protected without significant change