AimsType 2 Diabetes (T2DM) has been linked to ferroptosis. This study aimed to assess expression levels of genes linked with iron metabolism in peripheral blood mononuclear cells (PBMCs) from T2DM patients and to investigate the association of these expression levels with anthropometric and clinical parameters. MethodsGene expression of iron metabolism genes (Ferritin Light Chain, FTL; Ferritin Heavy Chain, FTH1; Transferrin Receptor, TFRC; Divalent Metal Transporter 1, SLC11A2; Ferroportin, SLC40A1) in archival PBMCs was assessed using quantitative real-time PCR assays. Correlations of gene expression with anthropometric/biochemical patient data were evaluated. ResultsThe study included 36 (18 male/18 female) T2DM patients and 45 (28 male/17 female) normoglycemic (NGT) subjects with a mean age of 38.1 ± 6.8 years and 47.6 ± 8.6 years respectively. Relative expression of FTL was significantly lower in T2DM females compared to that in NGT females (P = 0.027). Relative expression of SLC40A1 was significantly lower in the T2DM group (P = 0.043) and in the T2DM females (P = 0.021). Relative expression of SLC11A2 was negatively correlated with systolic blood pressure in T2DM male patients. Relative expression of SLC40A1 was negatively associated with serum phosphorous and positively associated with serum thyroid stimulating hormone in male T2DM patients. ConclusionsOur findings indicate a reduction in the expression of FTL in perimenopausal T2DM females. Also, in male T2DM patients and NGT subjects, biochemical markers are significantly correlated with the expression of FTL, FTH1, SLC11A2, and SLC40A1 in PBMCs.

Introduction Patients undergoing hematopoietic stem cell transplant (HSCT) are at high risk of life-threatening bacterial infections. Although the prevalence and pattern of resistance varies amongst centres and countries, there is a growing global problem of resistance to antibiotics. The increased use of broad-spectrum antibiotics and injudicious antibiotic policies have contributed to the selection of multidrug resistant(MDR) pathogens. Translocation of organisms which normally colonize the gut into the bloodstream during the febrile neutropenia has long been postulated as a pathogenic factor for life-threatening gram-negative infections. We routinely do stool surveillance culture of all patients admitted for autologous and allogenic stem cell transplant to guide us on empirical antibiotic usage. This analysis was conducted to evaluate the incidence of carbapenem resistant organisms (CROs) and their molecular pattern of resistance in stool surveillance cultures. Methods This is a single centre retrospective analysis of patients who underwent autologous and allogenic stem cell transplant for haematological malignancies from December 2021 to January 2023. In all patients stool surveillance cultures were sent at baseline during admission and then weekly thereafter till discharge . A blood Biofire syndromic multiplex PCR was performed in a fraction of stool isolates to identify the gene responsible for carbapenem resistance. Biofire syndromic multiplex PCR was performed only once for one patient on the first stool culture that grew a CRO. Biofire is a multiplex PCR that identifies Gram negative organisms including Acinetobacter Baumanni, Bacteroides Fragilis, Enterobacter cloacae, E. coli, Klebsiella, Proteus, Salmonella, Serratia, H. influenza, Neisseria meningitides, Pseudomonas aeruginosa, Stenotrophomonas maltophilia; it also identifies the gene responsible for resistance. The Carbapenem resistant genes included in the Biofire syndromic multiplex PCR were IMP Carbapenemase, KPC Carbapenamase, OXA-48, NDM, VIM, CTXM. Results Seventy-one patients underwent HSCT from December 2021 to January 2023. These included 39 allogenic and 32 autologous stem cell transplants. The median age of the cohort was 33 years (range 3-63 years) with 48 males and 23 females. The diagnoses were AML(n=8), ALL(n=14), CML(n=14), HL(n=10), Multiple Myeloma(n=19), Myelofibrosis(n=1), Non-Hodgkin Lymphoma (n=5). A total of 430 stool surveillance cultures from 71 patients were analysed. Of 430, 90 (20.9%) stool samples in 30 (42%) patients grew carbapenem resistant organism. Of these 90 CROs, twenty-three stool culture isolates belonging to 23 different patients were analysed for genotypic resistance. These 23 CROs included Escherichia coli 12 (52%) and Klebsiella pneumonia 11 (48%). On phenotypic sensitivity testing, the CROs were sensitive to Ceftriaxone-Sulbactam-EDTA (23/23, 100%), Ceftazidime-Avibactam (2/15, 13%), Colistin (23/23, 100%), Aztreonam (3/23, 13%), Tigecycline (17/23, 74%), Minocycline (9/23, 39%) and Aminoglycosides (11/23, 48%) shown in Figure 1a Resistance gene panel in these 23 stool isolates revealed NDM alone in 7 (31%), CTX-M along with NDM in 9 (39%), CTX-M along with OXA 48 like in 2(9%), CTX-M, OXA 48 along with NDM in 4 (17%) and NDM with OXA 48 in 1 (4%) (Figure 1b). Of the remaining 67 stools in which Biofire was not performed, Escherichia coli grew in 31 (46%) and Klebsiella pneumonia grew in 35 (52%) and Pseudomonas Aeruginosa in 1 (2%). On drug sensitivity testing, these CROs were sensitive to Ceftriaxone-Sulbactam-EDTA (65/67, 97%), Ceftazidime-Avibactam (4/15, 26%), Colistin (65/67, 97%), Aztreonam (7/65, 11%), Tigecycline (39/57, 68%), Minocycline (24 /62, 39%) and Aminoglycosides (33/67, 49%). Conclusion: About 40% of our patients were colonized with CROs at some point during their transplant. Molecular patterns identified NDM alone or in combination with other resistance genes in more than 90% of stools where molecular testing was performed. The antibiotics to which these MDR organisms were most susceptible included Ceftriaxone-sulbactam-EDTA, Colistin and tigecycline. Our study suggests that NDM is the most common resistance gene responsible for carbapenem resistance in our patients. Thus, antibiotics or antibiotic combinations that target NDM should be considered early in patients with MDR sepsis.

Introduction For multiple myeloma (MM), Cyclophosphamide (Cy) based chemo-mobilization offers advantage in term of higher stem cell yield and can overcome adverse impact of prior lenalidomide therapy on stem cell harvest. However, considering need for hospital stay and risk of febrile neutropenia, steady state mobilization with G-CSF and pre-emptive plerixafor (PEF) is becoming increasingly popular. Until few years back, cost of PEF was prohibitive thereby limiting its use and prompting a search for alternative cheaper drugs. Mouse models have shown that Proteasome Inhibitors aid in hematopoietic stem-cell (HSC) mobilization by down-regulating very-late antigen-4 (VLA-4) on bone marrow stromal cells which interacts with vascular cell adhesion molecule (VCAM-1) on HSC. We previously reported that bortezomib (Bort) in combination with Cy-G-CSF showed a trend towards higher CD34 yield and reduced need for apheresis sessions, without additional toxicity. There is limited data comparing mobilization regimens, especially from low-middle income countries where HSC collection may not be done after 4-6 cycles of first-line therapy. We hereby report our 15-year experience of various mobilization regimens for MM. Methods All patients with MM who underwent HSC mobilization from September 2007 - December 2022 were included in this analysis. Various mobilization regimens [Group 1 - G-CSF + Bort (August 2018 - December 2022); Group 2 - G-CSF + plerixafor (August 2018 - December 2022); Group 3 - Bort-Cy-GCSF (April 2016 - July 2018); Group 4 - Cy + G-CSF (September 2007 - March 2016)] were used as per respective time-periods (Table 1). Our aim was to collect CD34 cell dose of 5million/kg to suffice for 2 transplants. G-CSF (5 mcg/kg subcutaneously BD) was given on days 1-5 (Groups 1 and 2). Bort (1.3mg/m 2 iv / sc) (Group 1) or PEF (Group 2) were given on day 4 twelve hours prior to planned apheresis on day 5. Apheresis was done on day 5, and additionally on day 6, if first harvest was inadequate for 2 transplants. In group 3, Bort (1.3mg/m 2 iv) was given on days-1,4,8,11, with Cy (1gm/m 2 iv) on days 8 and 9, followed by G-CSF from day 11 onwards. Cy (1gm/m 2 iv) was given on day 1 and 2 (Group 4), followed by G-CSF from day 4 onwards. Stem cell harvest was done in groups 3 and 4 once peripheral blood CD34 (PB CD34) was >20/µL. In groups 3 and 4, if PB CD34 was <20/µL for 2 subsequent days, PEF was used according to physician's discretion, if available. Similarly in Group 1, if PB CD34 was between 10-20/µl on day 4, PEF was used according to physician's discretion. PEF was used in any group after the first harvest if the cell dose was deemed inadequate, at physician's discretion. Primary objective was to determine proportion of patients with CD34 + dose ≥5x10 6/kg in first apheresis in various groups. Secondary objectives were to determine total median CD34 + dose (x10 6/kg) collected, median CD34 + (x10 6/kg) in first apheresis, and frequency of mobilization failure. Mobilization failure was defined as total collected CD34 + dose of <2x10 6/kg or abandoned harvest attempt anticipating a poor collection.Analysis was done as per planned regimen (intention to treat analysis). Results Total 205 patients were analyzed. Median age was 48 years (27-65 years) and 143 (70%) were males (Table 1). Median day of first collection in groups 3 and 4 was day10 from the first dose of cyclophosphamide. Percentage of patients who collected ≥5x10 6 CD34 + cells/kg in first apheresis were 26%, 53%, 69% and 63%, respectively in Groups 1-4 (p=0.0001) (Table 1). CD34+ cell-dose in first apheresis and total dose collected are shown in Table 1. In comparison to groups 1 and 2, both chemo-mobilization groups (group 3 and 4) had a significantly higher total cell dose (Figure 1). In comparison to group 1, both Cy chemo-mobilization groups had a significantly higher cell dose in first harvest, but there was no significant difference between group 2 and group 4 (p=0.23) (Figure 1). PEF was required additionally in 47%, 22%, and 7% of patients in groups 1, 3 and 4 respectively (P<0.00001). Amongst transplanted patients, there was no difference in neutrophil or platelet engraftment and the frequency of engraftment syndrome in various groups. Conclusion Cy-based chemo-mobilization regimens have advantage of higher total stem cell yield, while they are equivalent to G-CSF + Plerixafor for harvest in single apheresis. Addition of Bortezomib to Cyclophosphamide may help to increase stem cell yield.

The deuterium dose-to-mother (DTM) method measures the human milk intake of breastfed children. Recently, the use of this method has been expanded to classify babies objectively as exclusively breast fed (EBF) or not (non-EBF) based on quantification of non-milk oral water intake (NMOI). However, the calculation of NMOI estimates involves atmospheric temperature and humidity. To evaluate the effects of atmospheric temperature and humidity on NMOI calculation and the classification of exclusive breastfeeding. The effect of indoor temperature and relative humidity on NMOI and the estimated prevalence of non-EBF were examined in two existing data sets of DTM in children by varying temperature in the range of 15 to 35°C and relative humidity in the range of 20 to 80% representing the maximum span of indoor conditions expected. Population-level estimates of NMOI distributions were derived using the rstan package for R v2.21.2. The NMOI decreased at a rate of -1.15 g/day per °C increase and at a rate of -1.01 g/day per percent increase in relative humidity; this was due to variations in non-oral water intake from the atmosphere, a component of the calculation of NMOI, which is dependent on temperature and humidity. For the various locations considered, the mean calculated NMOI varied between 24.6 and 53.3 g/day using the same input data. In the mixed-fed sample of babies, the prevalence of non-EBF based on the earlier defined NMOI cut-off of 86.6 g/day was reduced by 19% when relative humidity was increased by 60%. Atmospheric conditions are essential factors in the computation of NMOI, used in the objective classification of babies as exclusively breast fed or not, and should be considered when the DTM method is used to classify exclusive breastfeeding.

BackgroundDuplex kidneys represent an embryologic maldevelopment at time of renogenesis resulting in a spectrum of bifurcation anomalies of the reno-ureteric system. Though most are antenatally detected, recurrent urinary tract infections (UTIs), abdominal mass due to obstruction and incontinence are other common manifestations. Upper moiety ureter is usually obstructed and the lower moiety is refluxing. Management is guided by the percentage function of each of the moieties. A non-functioning system warrants a heminephrectomy. We report a toddler with right flank mass and a provisional diagnosis of right duplex system following investigations but met with a cryptic cause at surgery thereby altering the management.Case presentationA 2 ½ years girl with progressively increasing right abdominal mass for 6 weeks was found to have 12 × 10 cm right non-tender flank mass. Ultrasonography, contrast tomography and nuclear scans showed a right duplex system with obstructed, poorly functioning lower moiety. A lower moiety heminephrectomy was planned but at surgery, a densely adherent cystic structure displacing the right kidney superiorly was noted. On decompressing, the ureter was found to enter the cyst with discontinuation for a length of 6cms before being traced distally to its entry into the bladder. Retrograde pyelogram confirmed mid-ureteral transection and cystic urinoma. The cyst was excised and the ureter reconstructed with an appendicular interposition graft. Child recovered uneventfully and at 8 months follow up is well with good drainage across the conduit.ConclusionThe case highlights a rare presentation of mid-ureteral transection with urinoma masquerading as a duplex system and its satisfactory management.

Children with linear growth faltering refractory to nutritional management show evidence of environmental enteropathy, which may compromise nutrient availability. Protein could be particularly affected, due to the possibility of sub-optimal digestibility and/or increase in requirement for immune response. This increase in protein requirement along with poor intake could potentially lead to increased breakdown of body protein sources and in turn a depleted protein state. The present review focuses on protein status in children at risk of linear growth faltering and environmental enteropathy. One pig study is also presented. There is consistent evidence of low circulating essential and conditionally essential amino acids, in children. One study showed no difference in protein synthesis/breakdown, and fat free mass (FFM) in children at risk of linear growth faltering and environmental enteropathy. Weanling pigs exposed to nutrient deprivation showed a decrease in plasma albumin, with a slower rate of weight and length accretion, and a lower FFM. These findings emphasize the need for improving intake of high-quality protein in children living in regions with a high prevalence of environmental enteropathy, with careful studies of the effect on growth rate and protein status.

Colorectal cancer is one of the most diagnosed and the third deadliest diseases worldwide. Despite early detection and screening have increased the survival rate, colorectal cancer still takes hundreds of thousands of lives each year globally. Near 50% of current chemotherapeutic drugs are indirect or direct descendants of compounds isolated from medicinal plants, which indicates plants are great potential sources of novel therapeutics. In this research, we studied the Oliveria decumbens Vent. which holds numerous secondary metabolites with pharmacological activities. However, no study on anticancer activity of this kind has been reported. The Oliveria decumbens Vent. is a rare, wild, and endemic Persian medicinal plant which is traditionally used in cases of gastrointestinal diseases and infections in Persian Traditional Medicine. Nevertheless, this is to be studied scientifically for the very first time. Consequently, this research is aimed to evaluate the anticancer effect of the flower Oliveria decumbens Vent. ethanolic extract against HT-29 colorectal cancer cell line using 6 techniques including cytotoxicity, cell viability by MTT assay, DPPH, gene expression assay, wound-healing assay (scratch-test) along with a DNA damage test. The ethanolic extract showed an Ic50 of 14.39 μg/ml. The results from real-time PCR demonstrated that the ethanolic extract from Oliveria decumbens effectively promoted apoptosis by increasing the expression of the pro-apoptotic gene, bax, and slightly decreasing the anti-apoptotic gene, bcl2. Additionally, the Scratch test indicated its potential in inhibiting metastasis, while DNA fragmentation confirmed its ability to induce DNA damage. Considering these findings, the Oliveria decumbens ethanolic extract holds promise as a prospective anticancer and chemotherapeutic agent, warranting further investigation in future studies.

The nephrology and critical care communities have seen an increase in studies exploring acute kidney injury (AKI) epidemiology in children. As a result, we now know that AKI is highly prevalent in critically ill neonates, children, and young adults. Furthermore, children who develop AKI experience greater morbidity and higher mortality. Yet knowledge gaps still exist that suggest a more comprehensive understanding of AKI will form the foundation for future efforts designed to improve outcomes. In particular, the areas of community acquired AKI, AKI in non-critically ill children, and cohorts from low-middle income countries have not been well studied. Longer-term functional outcomes and patient-centric metrics including social determinants of health, quality of life, and healthcare utilization should be the foci of the next phase of scholarship. Current definitions identify AKI-based upon evidence of dysfunction which serves as a proxy for injury; biomarkers capable of identifying injury as it occurs are likely to more accurately define populations with AKI. Despite the strength of the association, the causal and mechanistic relationships between AKI and poorer outcomes remain inadequately examined. A more robust understanding of the relationship represents a potential to identify therapeutic targets. Once established, a more comprehensive understanding of AKI epidemiology in children will allow investigation of preventive, therapeutic, and quality improvement interventions more effectively.

BackgroundClinical and biochemical vitamin B12 (B12) deficiency is lower than anticipated in vegetarians. Extraileal absorption, such as from the colon, as well as reduced daily excretion, may be adaptive mechanisms to maintain B12 homeostasis with marginal intakes. ObjectiveTo measure the absorption of B12 from the small and large intestine, and its daily rate of excretion from the body, using a [13C]-cyanocobalamin tracer. MethodsOral B12 bioavailability was measured over 12 h after administration of [13C]-cyanocobalamin tracer (2.5 μg) in normal participants. The colonic B12 bioavailability was evaluated by direct instillation of [13C]-cyanocobalamin (5 μg) into the ascending colon. Bioavailability was calculated from 2-compartmental modeling of the tracer appearance in plasma. The excretion rate of B12 was measured from [13C]-cyanocobalamin elimination from the body over 4 wk after oral dosing (5 μg). ResultsThe oral B12 bioavailability (n = 11) was 63% ± 10% measured over 12 h. A late absorption peak, accounting for 12% of the absorption, was observed after an average lag time of 8.7 h from dosing. The colonic B12 bioavailability (n = 10) was 7% ± 5% over 4 h. The daily B12 excretion rate (n = 4) was 0.7 ± 0.2 μg/d. The minimum daily requirement of B12 in these participants was derived at 1 μg /d. ConclusionsB12 is absorbed in the human colon. This observation confirms the potential contribution of the colon in daily B12 nutriture, and along with a possible lower requirement, could explain the absence of clinical deficiency in populations with marginal B12 intakes. Trial Registration NumberThis study was registered in Clinical Trials Registry of India (CTRI) with the registration number CTRI/2018/04/012957, available from https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=49319&EncHid=&userName=029108.

This study aimed to assess the agreement in EBF between maternal recall and the dose-to-mother (DTM) technique. Indonesia, Malaysia, Mongolia, Pakistan, Sri Lanka, Thailand, and Vietnam participated in the study. A total of 207 and 118 mother-infant pairs were assessed at 3 and 6 months of child's age. Using a standardized questionnaire, mothers were asked to recall child feeding during the previous 24 h, at 3 and 6 months. Those recalled to be EBF proceeded to be assessed using DTM technique. Non-milk oral intake (NMOI) cutoff of 86.6 g/d was used to classify EBF. According to DTM, 66% of infants were EBF at 3 months, while only 22% were EBF at 6 months. At 3 months, the overall % agreement between maternal recall and DTM method was 68%, kappa 0.06 (95% CI: 0.07-0.20), and at 6 months, the % agreement was only 21%, kappa -0.031 (95% CI -0.168 to 0.107). Human milk intakes were similar at 3 months and 6 months when expressed as g/d, but decreased when expressed as g/kg/d, with a large variation within and between countries; Pakistan being the lowest. This study showed there were declining levels of EBF from 3 to 6 months in the participating countries from Asia and the agreement between maternal recall and DTM technique to classify EBF was low. To ensure that the DTM technique can be more widely used in evaluating breastfeeding promotion programs, consensus on the appropriate NMOI cutoff and simplification of the DTM protocol is necessary.