MITOL deficiency triggers hematopoietic stem cell apoptosis via ER stress response.

Hematopoietic stem cell (HSC) divisional fate and function are determined by cellular metabolism, yet the contribution of specific cellular organelles and metabolic pathways to blood maintenance and stress-induced responses in the bone marrow remains poorly understood. The outer mitochondrial membrane-localized E3 ubiquitin ligase MITOL/MARCHF5 (encoded by the Mitol gene) is known to regulate mitochondrial and endoplasmic reticulum (ER) interaction and to promote cell survival. Here, we investigated the functional involvement of MITOL in HSC maintenance by generating MX1-cre inducible Mitol knockout mice. MITOL deletion in the bone marrow resulted in HSC exhaustion and impairment of bone marrow reconstitution capability in vivo. Interestingly, MITOL loss did not induce major mitochondrial dysfunction in hematopoietic stem and progenitor cells. In contrast, MITOL deletion induced prolonged ER stress in HSCs, which triggered cellular apoptosis regulated by IRE1α. In line, dampening of ER stress signaling by IRE1α inihibitor KIRA6 partially rescued apoptosis of long-term-reconstituting HSC. In summary, our observations indicate that MITOL is a principal regulator of hematopoietic homeostasis and protects blood stem cells from cell death through its function in ER stress signaling.

ATP citrate lyase controls hematopoietic stem cell fate and supports bone marrow regeneration.

In order to support bone marrow regeneration after myeloablation, hematopoietic stem cells (HSCs) actively divide to provide both stem and progenitor cells. However, the mechanisms regulating HSC function and cell fate choice during hematopoietic recovery remain unclear. We herein provide novel insights into HSC regulation during regeneration by focusing on mitochondrial metabolism and ATP citrate lyase (ACLY). After 5-fluorouracil-induced myeloablation, HSCs highly expressing endothelial protein C receptor (EPCRhigh ) were enriched within the stem cell fraction at the expense of more proliferative EPCRLow HSCs. These EPCRHigh HSCs were initially more primitive than EPCRLow HSCs and enabled stem cell expansion by enhancing histone acetylation, due to increased activity of ACLY in the early phase of hematopoietic regeneration. In the late phase of recovery, HSCs enhanced differentiation potential by increasing the accessibility of cis-regulatory elements in progenitor cell-related genes, such as CD48. In conditions of reduced mitochondrial metabolism and ACLY activity, these HSCs maintained stem cell phenotypes, while ACLY-dependent histone acetylation promoted differentiation into CD48+ progenitor cells. Collectively, these results indicate that the dynamic control of ACLY-dependent metabolism and epigenetic alterations is essential for HSC regulation during hematopoietic regeneration.

Pancreatic masses in children: a single-center experience over two decades.

Pancreatic masses are extremely rare in pediatric patients, with limited data available. This lack of data makes the diagnosis and management of these tumors in children extremely challenging. Therefore, we aimed to describe the presentations, clinical course, and outcomes of children with pancreatic tumors at our center. A retrospective analysis was performed of all pediatric patients diagnosed with pancreatic masses between 2003 and 2022 in an academic freestanding children's hospital. Data including demographics, clinical presentation, workup, management, and subsequent morbidity and mortality were collected and aggregated. Furthermore, we reviewed cases of pancreatic tumor resections in the National Surgical Quality Improvement Program - Pediatric (NSQIP-P) database to identify common adverse outcomes and measures for quality improvement. In total, 17 patients were identified at our institution. Diagnoses included solid pseudopapillary (n = 9), gastrinoma (n = 1), rhabdomyosarcoma (n = 2), pancreatoblastoma (n = 2), and insulinoma (n = 1). Two patients did not have a histopathologic diagnosis and were excluded from subsequent analysis. Overall, 12 patients underwent surgical intervention, with the most common procedures being pancreaticoduodenectomy and distal pancreatectomy, and all 12 were known to be alive at last contact. There were 3 deaths, all due to complications related to metastatic disease. Furthermore, 30-day postoperative outcomes in the NSQIP-P dataset for pancreatic surgeries in pediatric patients are excellent, with negligible morbidity and no mortalities after the index surgery. CONCLUSIONS: Children with pancreatic tumors amenable to surgical resection appear to have adequate long-term survival. Short-term outcomes at diagnosis are excellent and mainly appear to be influenced by the presence of metastatic disease at initial presentation. WHAT IS KNOWN: • Pancreatic masses are a rare entity in children with limited data on their presentation, management and surgical outcomes. • Solid Pseudopapillary tumors are one of the most common pancreatic tumors in children with a fair prognosis after surgical intervention. WHAT IS NEW: • Surgical management of pediatric patients with pancreatic tumors is safe and effective in patients who do not have aggressive tumor types or metastatic disease. • Our case series provides a notable cohort of these pancreatic tumors with insight into the presentation, management and outcomes of five of these tumor types.

Hepatic resections for pediatric hepatoblastoma: analysis of 30-day outcomes using the National Surgical Quality Improvement Program-Pediatric database.

BACKGROUND: Surgical resection remains the cornerstone of treatment for hepatoblastoma in children and offers the best chance of disease-free survival. We aimed to analyze the 30 day outcomes of hepatic resection for hepatoblastoma stratified by extent using the National Surgical Quality Improvement Program-Pediatric (NSQIP-P). METHODS: We queried NSQIP-P for children undergoing resection of Hepatoblastoma from 2012 to 2021. Relevant clinical characteristics and outcomes were extracted for multivariate logistic regression to identify predictors of common adverse outcomes. RESULTS: We included 458 children with a median age of 1.90 years. Overall complications were rare, and perioperative blood transfusion (64.2%) and postoperative ventilation > 48 h (10.0%) were the only adverse events prevalent in more than 5% of patients. Median transfusion volume was 15.7 ml/kg. On multivariate regression, only patients undergoing Trisectionectomy (aOR = 3.387, 95% C.I. = 1.348-8.510) had higher odds of receiving > 75th percentile blood transfusion. Furthermore, only perioperative transfusion and postoperative ventilation > 48 h were statistically more common in patients undergoing extended versus standard resections. CONCLUSIONS: Outcomes following resection of hepatoblastoma are excellent, with low rates of postoperative adverse events. Although children undergoing trisectionectomy likely require greater transfusion volume, extended hepatic resections do not appear to have worse 30 day outcomes despite greater operative complexity and duration.

The Novel Use of Rare Earth Magnets for the Extraction of Metallic Soft Tissue Foreign Bodies in Children.

INTRODUCTION: Metallic foreign bodies (mFB) are common following penetrating injuries in children. The mFB commonly occur in the head and neck region and extremity soft tissues. Removal may be indicated due to morbidity related to pain or migration. Extraction can be challenging to localize, often requiring wide exposure, and may be difficult to achieve in cosmetically sensitive areas. Different technological adjuncts have been used to facilitate foreign body removal including fluoroscopy, ultrasound, and more recently in adults, surgical magnets. The most powerful commercially available magnets are rare earth magnets comprised of neodymium iron and boron (Ndy). With the goal of reducing radiation exposure and the morbidity of mFB removal with associated soft tissue injury in children, a strategy was introduced utilizing Ndy to optimize extraction with minimal soft tissue surgical dissection. MATERIALS AND METHODS: Two children with extremity mFB treated with Ndy between January 2021 and July 2021 were analyzed. We utilized commercially available ring type neodymium-iron-boron magnets with dimensions of 1 3/8-inch outer diameter x 1/8-inch inner diameter and 1/16 inch thick with a power of 13 200 gauss that were processed for use according to our hospital protocols. Our main clinical indication was for the detection and retrieval of small ferromagnetic foreign bodies embedded in superficial extremity soft tissues. RESULTS: In the operating room under general anesthesia, the mFB were localized utilizing fluoroscopy. A 1.0 cm skin incision was made into the subdermal soft tissues overlying the area of the mFB. No surgical tissue dissection was performed. The mFB could not be visualized in the soft tissue. Using fluoroscopy to localize the mFB, the Ndy was then placed into the wound in close proximity to the mFB. The mFB were immediately magnetized to the Ndy and the mFB were extracted from the soft tissues without any further surgical dissection. Two simple interrupted nylon sutures were placed to close the incision. The total operative time was 2 and 2.5 minutes respectively. The children recovered uneventfully and are without complication. CONCLUSIONS: The use of Ndy to remove extremity soft tissue mFB in children appears to be feasible, safe, and efficient. Use of the Ndy allowed extraction via a small incision, optimizing the aesthetic result and avoiding the need for cross-sectional imaging, extensive surgical dissection, tissue reconstruction and prolonged operative time or x-ray exposure. The development of magnets of increasing energy density may be indicated to further optimize metallic soft tissue foreign body extraction in children in a minimally invasive manner.

Ribosome Incorporation Induces EMT-like Phenomenon with Cell Cycle Arrest in Human Breast Cancer Cell.

Although ribosomes are generally known to be a translational machinery, some ribosomal proteins also have accessory functions involving early development and differentiation. Previously, we reported that ribosome incorporation into human dermal fibroblasts generated embryoid body-like cell clusters, altered cellular fate, and differentiated into cells of all 3 germ layers. However, the molecular phenomena induced by ribosome incorporation in the cell remained unknown. Here, we demonstrate that ribosome incorporation into human breast cancer cell MCF7 leads to ribosome-induced cell clusters (RICs) formation accompanying with epithelial-mesenchymal transition (EMT)-like gene expression. Following ribosome incorporation, MCF7 cells cease proliferation, which is caused by inhibition of cell cycle transition from G0 to G1 phase. Further, MCF7 RICs show induced expression of EMT markers, TGF-ß1 and Snail along with autophagy markers and tumor suppressor gene p53. These findings indicate that the incorporation of ribosome into cancer cells induces an EMT-like phenomenon and changes the cancer cell characteristics.

Delay in Hip Fracture Repair in the Elderly: A Missed Opportunity Towards Achieving Better Outcomes.

BACKGROUND: Hip fractures are a major cause of morbidity and mortality in the elderly. The American Academy of Orthopedic Surgeons (AAOS) recommends surgical repair within 48 hours of admission, as this is associated with lower postoperative mortality and complications. This study demonstrates the association between patient demographics, level of care, and hospital region to delay in hip fracture repair in the elderly. METHODS: The National Trauma Data Bank (NTDB) was queried for elderly patients (age >65 years) who underwent proximal femoral fracture repair. Identified patients were subcategorized into two groups: hip fracture repair in <48 hours, and hip fracture repair > 48 hours after admission. Patient and hospital characteristics were collected. Outcome variables were timed from the day of admission to surgery and inpatient mortality. RESULTS: Out of 69,532 patients, 28,031 were included after inclusion criteria were applied. 23,470 (83.7%) patients underwent surgical repair within 48 hours. The overall median time to procedure was 21 (interquartile range [IQR] 7-38) hours. Females were less likely to undergo a delay in hip fracture repair (odds ratio [OR; 95% confidence interval {CI}]: 0.82 [0.76-0.88], P< 0.05), and patients with higher Injury Severity Score (ISS ≥25) had higher odds of delay in surgical repair (OR; 95% CI: 1.56 [1.07-2.29], P< 0.05). Patients treated at hospitals in the Western regions of the United States had lower odds of delay, and those treated in the Northeast and the South had higher odds of delay compared to the hospitals in the Midwest (taken as standard). There was no association between trauma level designation and odds of undergoing delay in hip fracture repair. CONCLUSION: Variables related to patient demographic and hospital characteristics are associated with delay in hip fracture repair in the elderly. This study delineates key determinants of delay in hip fracture repair in the elderly patients.

Methods for quantifying methane emissions using unmanned aerial vehicles: a review.

Methane is an important greenhouse gas, emissions of which have vital consequences for global climate change. Understanding and quantifying the sources (and sinks) of atmospheric methane is integral for climate change mitigation and emission reduction strategies, such as those outlined in the 2015 UN Paris Agreement on Climate Change. There are ongoing international efforts to constrain the global methane budget, using a wide variety of measurement platforms across a range of spatial and temporal scales. The advancements in unmanned aerial vehicle (UAV) technology over the past decade have opened up a new avenue for methane emission quantification. UAVs can be uniquely equipped to monitor natural and anthropogenic emissions at local scales, displaying clear advantages in versatility and manoeuvrability relative to other platforms. Their use is not without challenge, however: further miniaturization of high-performance methane instrumentation is needed to fully use the benefits UAVs afford. Developments in the models used to simulate atmospheric transport and dispersion across small, local scales are also crucial to improved flux accuracy and precision. This paper aims to provide an overview of currently available UAV-based technologies and sampling methodologies which can be used to quantify methane emission fluxes at local scales. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 1)'.

Tsukushi is essential for proper maintenance and terminal differentiation of mouse hippocampal neural stem cells.

Secreted proteoglycan molecule Tsukushi (TSK) regulates various developmental processes, such as early body patterning and neural plate formation by interacting with major signaling pathways like Wnt, BMP, Notch etc. In central nervous system, TSK inhibits Wnt signaling to control chick retinal development. It also plays important roles for axon guidance and anterior commissure formation in mouse brain. In the present study, we investigated the role of TSK for the development and proper functioning of mouse hippocampus. We found that TSK expression is prominent at hippocampal regions of early postnatal mouse until postnatal day 15 and gradually declines at later stages. Hippocampal dimensions are affected in TSK knockout mice (TSK-KO) as shown by reduced size of hippocampus and dentate gyrus (DG). Interestingly, neural stem cell (NSC) density at the neural niche of DG was higher in TSK-KO compared with wild-type. The ratio of proliferating NSCs as well as the rate of overall cell proliferation was also higher in TSK-KO hippocampus. Our in vitro study also suggests an increased number of neural stem/progenitor cells residing in TSK-KO hippocampus. Finally, we found that the terminal differentiation of NSCs in TSK-KO was disturbed as the differentiation to neuronal cell lineage was increased while the percentages of astrocytes and oligodendrocytes were decreased. Overall, our study establishes the involvement of TSK in hippocampal development, NSC maintenance and terminal differentiation at perinatal stages.

Akhirin regulates the proliferation and differentiation of neural stem cells/progenitor cells at neurogenic niches in mouse brain.

Specialized microenvironment, or neurogenic niche, in embryonic and postnatal mouse brain plays critical roles during neurogenesis throughout adulthood. The subventricular zone (SVZ) and the dentate gyrus (DG) of hippocampus in the mouse brain are two major neurogenic niches where neurogenesis is directed by numerous regulatory factors. Now, we report Akhirin (AKH), a stem cell maintenance factor in mouse spinal cord, plays a pivotal regulatory role in the SVZ and in the DG. AKH showed specific distribution during development in embryonic and postnatal neurogenic niches. Loss of AKH led to abnormal development of the ventricular zone and the DG along with reduction of cellular proliferation in both regions. In AKH knockout mice (AKH-/- ), quiescent neural stem cells (NSCs) increased, while proliferative NSCs or neural progenitor cells decreased at both neurogenic niches. In vitro NSC culture assay showed increased number of neurospheres and reduced neurogenesis in AKH-/- . These results indicate that AKH, at the neurogenic niche, exerts dynamic regulatory role on NSC self-renewal, proliferation and differentiation during SVZ and hippocampal neurogenesis.

Defining the Burden of Emergency General Surgery in Transplant Patients: A Nationwide Examination.

BACKGROUND: Transplant patients are at the risk of serious sequelae from medical and surgical intervention. The incidence and burden of emergency general surgery (EGS) in transplant patients are scarcely known. This study aims to identify predictors of outcomes in transplant patients with EGS needs. METHODS: The Nationwide Inpatient Sample (2007-2011) was queried for adult patients (aged ≥16 y) who underwent abdominal visceral transplantation. These were further queried for a secondary diagnosis of an American Association for the Surgery of Trauma-defined EGS condition. Outcome measures included mortality, complications, length of stay, and cost of care. Propensity scores were used to match patients across baseline characteristics. Multivariate analysis was used to further adjust propensity score quintiles and hospital-level characteristics. RESULTS: A total of 35,573 transplant patients were identified. Of these, 30% (n = 10,676) developed an EGS condition. Most common EGS conditions were resuscitation (7.7%), intestinal obstruction (7.3%), biliary conditions (3.9%), and hernias (3.2%). Patients with public insurance, those in the highest income quartile, and those treated at larger hospitals had a lower likelihood of developing an EGS condition (P < 0.05). Patients with an EGS condition had a ninefold higher likelihood of mortality and a threefold higher likelihood of developing complications (odds ratio [95% confidence interval (CI)]: 9.21 [1.80-10.89] and 3.17 [3.02-3.34], respectively). Transplant patients after EGS had a longer risk-adjusted length of stay and cost of index hospitalization (Absolute difference [95% CI]: 12.70 [12.14-13.26] and $57,797 [55,415-60,179], respectively]). CONCLUSIONS: Transplant patients fare poorly after developing an EGS condition. The results of this study will help in identifying at-risk patients and determining outcomes.

Assessing surgical care delivery at facilities caring for higher volumes of minority children utilizing the pediatric quality indicator for perforated appendicitis: a propensity-matched analysis.

INTRODUCTION: The pediatric quality indicator (PDI) measures released by the Agency for Healthcare Research and Quality (AHRQ) provide an impetus for benchmarking quality of care in children. The PDI-17, aimed at studying perforation in appendicitis, is one such measure that this study aims to utilize to assess surgical care delivery and outcomes in children managed at majority-minority hospitals. METHODS: The Kid Inpatient Database (2000-2012) was queried for pediatric patients (< 18 years) with a diagnosis of appendicitis, with and without perforation. Facilities were categorized into tertiles based on rates of perforation (PDI-17). Similarly, tertiles were generated based on volume of minority patients (Black and Hispanic) treated at each facility. Multivariable regression analysis adjusted for demographic parameters, hospital-level characteristics, propensity score quintiles, clinically relevant outcomes, and tertiles of minority patients treated. RESULTS: Of the 322,805 patients with appendicitis 28.7% had perforated appendicitis. Patients presenting to facilities caring for a higher volume of perforated appendicitis were younger with public insurance or no insurance and, however, these patients were less likely to belong to a minority group (p < 0.05). Additionally, these patients were less likely to belong to the highest income quartile (OR [95% CI] 0.45 [0.39-0.52]). Hospitals treating the highest volume of minority patients [majority-minority hospitals (MMHs)] had an 87% (OR [95% CI] 1.87 [1.77-1.98]) increased likelihood of also treating the highest rates of perforated appendicitis. CONCLUSION: Hospitals treating a high volume of complicated appendicitis are less likely to care for minority groups. Additionally, MMHs lacking experience and volume in caring for complicated appendicitis have an increased likelihood of patients with perforations which is indicative of poor healthcare access.

Autologous intestinal reconstruction: a single institution study of the serial transverse enteroplasty (STEP) and the longitudinal intestinal lengthening and tailoring (LILT).

PURPOSE: To review the effectiveness of the longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP) operations in a cohort of patients with short bowel syndrome (SBS). METHODS: We conducted a retrospective analysis of children with SBS treated at our institution from 2004 until 2014. Children aged 0 days to 18 years with SBS who underwent autologous intestinal reconstruction were included in the study. RESULTS: Twenty-two SBS patients underwent 31 different lengthening procedures (LP). Seventeen patients underwent their primary lengthening procedures at our institution: 9 (53%) patients underwent a LILT, 7 (41%) underwent a STEP and 1 (6%) had a simultaneous LILT and STEP procedure. 12/22 patients had a second STEP, two had a third STEP and one patient had an intestinal transplantation after the LP. Median intestinal length at the time of surgery was 25 cm (range 12-90 cm). There was no difference in gain of intestinal length after LILT vs. STEP (p = 0.74). Length of stay and initiation of feeds were similar. Serum albumin increased after autologous bowel lengthening (p < 0.001). 50% were weaned off parenteral nutrition (PN) (5/9 of the LILT, 1/7 of the STEP, 1/1 of the combined LILT/STEP). There were no surgical complications or deaths. CONCLUSION: In patients with SBS, LILT and STEP procedures are effective for autologous intestinal reconstruction and enable intestinal rehabilitation.

Suitability of a Non-Dispersive Infrared Methane Sensor Package for Flux Quantification Using an Unmanned Aerial Vehicle.

Point-source methane emission flux quantification is required to help constrain the global methane budget. Facility-scale fluxes can be derived using in situ methane mole fraction sampling, near-to-source, which may be acquired from an unmanned aerial vehicle (UAV) platform. We test a new non-dispersive infrared methane sensor by mounting it onto a small UAV, which flew downwind of a controlled methane release. Nine UAV flight surveys were conducted on a downwind vertical sampling plane, perpendicular to mean wind direction. The sensor was first packaged in an enclosure prior to sampling which contained a pump and a recording computer, with a total mass of 1.0 kg. The packaged sensor was then characterised to derive a gain factor of 0.92 ± 0.07, independent of water mole fraction, and an Allan deviation precision (at 1 Hz) of ±1.16 ppm. This poor instrumental precision and possible short-term drifts made it non-trivial to define a background mole fraction during UAV surveys, which may be important where any measured signal is small compared to sources of instrumental uncertainty and drift. This rendered the sensor incapable of deriving a meaningful flux from UAV sampling for emissions of the order of 1 g s-1. Nevertheless, the sensor may indeed be useful when sampling mole fraction enhancements of the order of at least 10 ppm (an order of magnitude above the 1 Hz Allan deviation), either from stationary ground-based sampling (in baseline studies) or from mobile sampling downwind of sources with greater source flux than those observed in this study. While many methods utilising low-cost sensors to determine methane flux are being developed, this study highlights the importance of adequately characterising and testing all new sensors before they are used in scientific research.

Transdifferentiation of human somatic cells by ribosome.

Ribosomes are intracellular organelles ubiquitous in all organisms, which translate information from mRNAs to synthesize proteins. They are complex macromolecules composed of dozens of proteins and ribosomal RNAs. Other than translation, some ribosomal proteins also have side-jobs called "Moonlighting" function. The majority of these moonlighting functions influence cancer progression, early development and differentiation. Recently, we discovered that ribosome is involved in the regulation of cellular transdifferentiation of human dermal fibroblasts (HDFs). In vitro incorporation of ribosomes into HDFs arrests cell proliferation and induces the formation of cell clusters, that differentiate into three germ layer derived cells upon induction by differentiation mediums. The discovery of ribosome induced transdifferentiation, that is not based on genetic modification, find new possibilities for the treatment of cancer and congenital diseases, as well as to understand early development and cellular lineage differentiation.

Differences in rural and urban outcomes: a national inspection of emergency general surgery patients.

BACKGROUND: About 19% of the United States population lives in rural areas and is served by only 10% of the physician workforce. If this misdistribution represents a shortage of available surgeons, it is possible that outcomes for rural patients may suffer. The objective of this study was to explore differences in outcomes for emergency general surgery (EGS) conditions between rural and urban hospitals using a nationally representative sample. METHODS: Data from the 2007-2011 National Inpatient Sample were queried for adult patients (≥18 years) with a primary diagnosis consistent with an EGS condition, as defined by the American Association for the Surgery of Trauma. Urban and rural patients were matched on patient-level factors using coarsened exact matching. Differences in outcomes including mortality, morbidity, length of stay (LOS), and total cost of hospital care were assessed using multivariable regression models. Analogous counterfactual models were used to further examine hypothetical outcomes, assuming that all patients had been treated at urban centers. RESULTS: A total of 3,749,265 patients were admitted with an EGS condition during the study period. Of 3259 hospitals analyzed, 40.2% (n = 1310) were rural; they treated 14.6% of patients. Relative to urban centers, EGS patients treated at rural centers had higher odds of in-hospital mortality (odds ratio [OR]: 1.24; 95% confidence interval [CI]: 1.21-1.28) and lower odds of major complications (OR: 0.98; 95% CI: 0.96-0.99). Rural patients had 0.51 d (95% CI: 0.50-0.53) shorter LOS and $744 (95% CI: 712-774) higher cost of hospitalization compared to urban patients. In counterfactual models overall odds of death decreased by 0.05%, whereas the overall odds of complications increased by 0.02%. Overall difference in LOS and total costs were comparable with absolute differences of 0.08 d and $98, respectively. CONCLUSIONS: Despite the statistically significant difference in mortality and cost of care at rural versus urban hospitals, the magnitude of absolute differences is sufficiently small to indicate limited clinical importance. Large urban centers are designed to manage complex cases, but our results suggest that for cases appropriate to treat in rural hospitals, equivalent outcomes are found. These findings will inform future work on rural outcomes and provide impetus for regionalization of care for complex EGS presentations.

Suitability of Different Food Grade Materials for the Encapsulation of Some Functional Foods Well Reported for Their Advantages and Susceptibility.

Functional foods find a very important place in the modern era, where different types of cancer, diabetes, cardiovascular diseases, etc. are on a high. Irrespective of the abundance of bioactive components in different fruits and vegetables, their low solubility in aqueous solution, vulnerability to destruction in different environmental and gastrointestinal conditions and a low intestinal absorption becomes a concern. Because it is quite difficult to commercialize non food materials for the food encapsulation purposes due to their safety concerns in the human body, scientists in the recent times have come up with the idea of encapsulating the different bioactive components in different food grade materials that are able to safeguard these bioactive components against the different environmental and gastrointestinal conditions and ensure their safe and targeted delivery at their absorption sites. Different food grade encapsulation materials including various oligosaccharides, polysaccharides (starch, cyclodextrins, alginates, chitosan, gum arabic, and carboxymethyl cellulose) and proteins and their suitability for encapsulating various bioactive components like flavonoids (catechins, rutin, curcumin, hesperetin, and vanillin), nonflavonoids (resveratrol), carotenoids (ß-carotene, lycopene, and lutein), and fatty acids (fish oil, flaxseed oil, and olive oil) of high medical and nutritional value are reviewed here.

Novel insights on ENTH domain-containing proteins in apicomplexan parasites.

The phylum Apicomplexa includes a large group of early branching eukaryotes having significant medical and economical importance. The molecular machinery responsible for protein trafficking is poorly understood in these apicomplexans. One of the most important proteins involved in clathrin-mediated protein trafficking is Epsin, which contains ENTH domain, a conserved domain crucial for membrane bending leading to vesicle formation. We undertook homology searching and phylogenetic analyses to produce a rigorously annotated set of Epsin homologs retrieved from diverse apicomplexan genomes. Genomic and phylogenetic comparisons revealed that apicomplexans contain unusual Epsin homologs that are distinct from those observed in mammals and yeast. Although there are four Epsin genes in mammalian system and five in the yeast genome, apicomplexan parasites consist only a single Epsin gene. The apicomplexan Epsin contains the conserved ENTH domain consisting of phosphoinositide (PtdIns)-binding sites which indicate about their functional significance in the formation of vesicles; however, the absence of ubiquitin-interacting motif (UIM) suggests a possible different mechanism for protein trafficking. The existence of dileucine motif in Plasmodium, Cryptosporidum parvum and Eimeria tenella Epsins might solve their functionality while lacking a lot of conserved motifs as this motif is known to interact with different adaptor protein complexes (AP1, AP2 and AP3). Other Epsin homologs are also shown to have different peptide motifs reported for possible interaction with α-ear appendage, γ-ear appendage and EH domain present in different adaptors. Bioinformatic and phylogenetic analyses suggest that the apicomplexan Epsins have unusual functionality from that of the mammalian Epsins. This detailed study may greatly facilitate future molecular cell biological investigation for the role of Epsins in these parasites.

Analgesic Access for Acute Abdominal Pain in the Emergency Department Among Racial/Ethnic Minority Patients: A Nationwide Examination.

BACKGROUND: Prior studies of acute abdominal pain provide conflicting data regarding the presence of racial/ethnic disparities in the emergency department (ED). OBJECTIVE: To evaluate race/ethnicity-based differences in ED analgesic pain management among a national sample of adult patients with acute abdominal pain based on a uniform definition. RESEARCH DESIGN/SUBJECTS/MEASURES: The 2006-2010 CDC-NHAMCS data were retrospectively queried for patients 18 years and above presenting with a primary diagnosis of nontraumatic acute abdominal pain as defined by the American Association for the Surgery of Trauma. Independent predictors of analgesic/narcotic-specific analgesic receipt were determined. Risk-adjusted multivariable analyses were then performed to determine associations between race/ethnicity and analgesic receipt. Stratified analyses considered risk-adjusted differences by the level of patient-reported pain on presentation. Secondary outcomes included: prolonged ED-LOS (>6 h), ED wait time, number of diagnostic tests, and subsequent inpatient admission. RESULTS: A total of 6710 ED visits were included: 61.2% (n=4106) non-Hispanic white, 20.1% (n=1352) non-Hispanic black, 14.0% (n=939) Hispanic, and 4.7% (n=313) other racial/ethnic group patients. Relative to non-Hispanic white patients, non-Hispanic black patients and patients of other races/ethnicities had 22%-30% lower risk-adjusted odds of analgesic receipt [OR (95% CI)=0.78 (0.67-0.90); 0.70 (0.56-0.88)]. They had 17%-30% lower risk-adjusted odds of narcotic analgesic receipt (P<0.05). Associations persisted for patients with moderate-severe pain but were insignificant for mild pain presentations. When stratified by the proportion of minority patients treated and the proportion of patients reporting severe pain, discrepancies in analgesic receipt were concentrated in hospitals treating the largest percentages of both. CONCLUSIONS: Analysis of 5 years of CDC-NHAMCS data corroborates the presence of racial/ethnic disparities in ED management of pain on a national scale. On the basis of a uniform definition, the results establish the need for concerted quality-improvement efforts to ensure that all patients, regardless of race/ethnicity, receive optimal access to pain relief.

Abdominal gunshot wounds-a comparative assessment of severity measures.

BACKGROUND: Penetrating abdominal trauma is a common feature of trauma treated in low- and middle-income countries (LMICs). The penetrating abdominal trauma index (PATI) and the injury severity score (ISS) are severity-measures most often used to gauge injury severity. It remains unclear which measure better accounts for the severity of sustained injuries. This study compares the predictive ability of both injury severity measures in patients presenting to an LMIC in South Asia. METHODS: All isolated gunshot wounds to the abdomen presenting to a university hospital between 2011 and 2012 were included. ISS and PATI were calculated for each case. Primary outcome measures included all-cause mortality and complications. Multivariable analysis adjusting for age, sex, referral status, hypotension, tachycardia, and injury severity measures was performed. The area under the receiver operating characteristic (AUROC) curve were further calculated to compare the respective abilities of ISS and PATI at predicting death and complications. RESULTS: A total of 70 patients were included. The average age on presentation was 34.5 y (±11.4) within a predominantly male (n = 68, 97.1%) cohort. Most gunshot wounds were intentionally inflicted (n = 67, 95.7%). The crude rates of death and complications were 34.3% and 15.7%, respectively. The median ISS was 14 (interquartile range: 11-21), and the median PATI was 16 (interquartile range: 9-26). AUROC analysis revealed that ISS was comparable with PATI at predicting mortality (AUROC [95% confidence interval]: 0.952 [0.902-1.00] versus 0.934 [0.860-1.00]) and complications (AUROC [95% confidence interval]: 0.868 [0.778-0.959] versus 0.895 [0.815-0.975]). CONCLUSIONS: The predictive ability of ISS and PATI severity measures was found to be comparable. The results suggest that both measures can be used to risk-stratify patients with isolated abdominal gunshot wounds in an LMIC.