Detecting horizontal gene transfer among microbiota: an innovative pipeline for identifying co-shared genes within the mobilome through advanced comparative analysis.
Horizontal gene transfer (HGT) is a key driver in the evolution of bacterial genomes. The acquisition of genes mediated by HGT may enable bacteria to adapt to ever-changing environmental conditions. Long-term application of antibiotics in intensive agriculture is associated with the dissemination of antibiotic resistance genes among bacteria with the consequences causing public health concern. Commensal farm-animal-associated gut microbiota are considered the reservoir of the resistance genes. Therefore, in this study, we identified known and not-yet characterized mobilized genes originating from chicken and porcine fecal samples using our innovative pipeline followed by network analysis to provide appropriate visualization to support proper interpretation.


Potent Antiviral and Antimicrobial Polymers as Safe and Effective Disinfectants for the Prevention of Infections.
Disinfection using effective antimicrobials is essential in preventing the spread of infectious diseases. This COVID-19 pandemic has brought the need for effective disinfectants to greater attention due to the fast transmission of SARS-CoV-2. Current active ingredients in disinfectants are small molecules that microorganisms can develop resistance against after repeated long-term use and may penetrate the skin, causing harmful side-effects. To this end, a series of membrane-disrupting polyionenes that contain quaternary ammoniums and varying hydrophobic components is synthesized. They are effective against bacteria and fungi. They are also fast acting against clinically isolated drug resistant strains of bacteria. Formulating them with thickeners and nonionic surfactants do not affect their killing efficiency. These polyionenes are also effective in preventing infections caused by nonenveloped and enveloped viruses. Their effectiveness against mouse coronavirus (i.e., mouse hepatitis virus-MHV) depends on their hydrophobicity. The polyionenes with optimal compositions inactivates MHV completely in 30 s. More importantly, the polyionenes are effective in inhibiting SARS-CoV-2 by >99.999% within 30 s. While they are effective against the microorganisms, they do not cause damage to the skin and have a high oral lethal dose. Overall, these polyionenes are promising active ingredients for disinfection and prevention of viral and microbial infections.


Primary admission and secondary transfer of trauma patients to Dutch level I and level II trauma centers: predictors and outcomes.
The importance and impact of determining which trauma patients need to be transferred between hospitals, especially considering prehospital triage systems, is evident. The objective of this study was to investigate the association between mortality and primary admission and secondary transfer of patients to level I and II trauma centers, and to identify predictors of primary and secondary admission to a designated level I trauma center. Data from the Dutch Trauma Registry South West (DTR SW) was obtained. Patients ≥ 18 years who were admitted to a level I or level II trauma center were included. Patients with isolated burn injuries were excluded. In-hospital mortality was compared between patients that were primarily admitted to a level I trauma center, patients that were transferred to a level I trauma center, and patients that were primarily admitted to level II trauma centers. Logistic regression models were used to adjust for potential confounders. A subgroup analysis was done including major trauma (MT) patients (ISS > 15). Predictors determining whether patients were primarily admitted to level I or level II trauma centers or transferred to a level I trauma center were identified using logistic regression models. A total of 17,035 patients were included. Patients admitted primarily to a level I center, did not differ significantly in mortality from patients admitted primarily to level II trauma centers (Odds Ratio (OR): 0.73; 95% confidence interval (CI) 0.51-1.06) and patients transferred to level I centers (OR: 0.99; 95%CI 0.57-1.71). Subgroup analyses confirmed these findings for MT patients. Adjusted logistic regression analyses showed that age (OR: 0.96; 95%CI 0.94-0.97), GCS (OR: 0.81; 95%CI 0.77-0.86), AIS head (OR: 2.30; 95%CI 2.07-2.55), AIS neck (OR: 1.74; 95%CI 1.27-2.45) and AIS spine (OR: 3.22; 95%CI 2.87-3.61) are associated with increased odds of transfers to a level I trauma center. This retrospective study showed no differences in in-hospital mortality between general trauma patients admitted primarily and secondarily to level I trauma centers. The most prominent predictors regarding transfer of trauma patients were age and neurotrauma. These findings could have practical implications regarding the triage protocols currently used.


Necrotizing fasciitis in a child: a rare complication of idiopathic nephrotic syndrome.
In nephrotic syndrome there is an increased tendency for bacterial infections due to immunological changes secondary to proteinuria, treatment (including steroids), and other as yet unknown causes. However, necrotizing fasciitis (NF) is an uncommon complication of the disease and has rarely been reported in nephrotic children. We report a 14-month-old boy with nephrotic syndrome who developed sepsis and NF as a complication. He was treated successfully with intensive medical and surgical treatment.


Prevalence & Factors Associated With Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Intervention at a Tertiary Healthcare Facility in Tanzania.
Coronary artery disease (CAD) is the leading cause of mortality and morbidity globally. Percutaneous coronary intervention (PCI) is a minimally-invasive lifesaving intervention for these patients; however, acute kidney injury (AKI) is a serious complication of the procedure commonly occurring due to radiocontrast-induced nephropathy. A retrospective cross-sectional analytical study was carried out at the Aga Khan Hospital, Dar es Salaam (AKH,D), Tanzania. A total of 227 adults who underwent a percutaneous coronary intervention from August 2014 to December 2020 were enrolled. The AKI was defined based on an increase in absolute and rise in percentage creatinine using the Acute Kidney Injury Network (AKIN), and contrast-induced acute kidney injury (CI-AKI) by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Bivariable and multivariable logistic regression was utilized to analyze factors associated with AKI and the outcomes of these patients. Twenty-two of the 227 (9.7%) participants sustained AKI. The majority of the study population was male and of Asian ethnicity. No statistically significant factors were associated with AKI. The in-hospital mortality rate was 9% for the AKI versus 2% for non-AKI groups. The AKI group had a longer hospital stay and required ICU care and organ support including hemodialysis. Nearly 1-in-10 patients undergoing PCI are likely to develop AKI. The in-hospital mortality rate is x4.5 times higher for patients with AKI post-PCI compared to those without AKI. Further larger studies are recommended to determine factors associated with AKI in this population.


Comparison of Long-Term Pneumonia Risk between Spleen Injury and Non-Spleen Injury after Total Splenectomy-A Population-Based Study.
Patients who undergo splenectomy are at a high risk of infection. We aimed to investigate the rate of pneumonia in patients who underwent splenectomy, specifically comparing those who had splenectomy due to spleen injury and those who had it for other reasons. A population-based cohort study was conducted. Overall, 17,498 patients who underwent splenectomy between 2000 and 2015 were enrolled, including 11,817 patients with a history of spleen injury and 5681 controls without spleen injury. The incidence of pneumonia was calculated at the end of 2016. A multivariable Cox proportional hazards regression model was used to compare the hazard ratio with 95% CI for pneumonia associated with the spleen injury-caused splenectomy and splenectomy due to other causes. The crude HR for patients with splenectomy due to spleen injury to develop pneumonia was 1.649. After adjusting for covariates, the adjusted hazard ratio was 1.567. There were statistically significant differences in all subgroups, except for the group with a tracking duration >10 years. We found an increase in pneumonia risk in the 'spleen injury' group when comparing it to that of the 'other causes' group, regardless of age, sex, and area of residence.


Comparing the Benefit of Duplex Ultrasound Surveillance Following Both Infrainguinal Bypass Surgery and Stenting for Femoro-Popliteal Disease.
Duplex ultrasound surveillance (DUS) is commonly used following infrainguinal vein bypass. The role of DUS following endovascular revascularisation is as yet unclear. This study focuses on the role of DUS in a contemporary group of patients undergoing infrainguinal bypass or stent insertion. All patients undergoing either an infrainguinal vein graft bypass or stent insertion into the femoro-popliteal segment (November 2014 - January 2017) were identified. Patients were followed up for 2 years. Data on entry into DUS, pre-operative characteristics, adjunctive pharmacotherapy and reintervention were collated. The primary outcomes were major lower limb amputation and mortality at 2 years post revascularisation. One hundred and thirty-five patients underwent infrainguinal vein bypass and 100 patients underwent stent insertion. 107 patients in the bypass cohort and 58 patients in the stent cohort entered DUS. For the bypass cohort, entering DUS was associated with a lower mortality rate (P = .003) but was not associated with an improvement in amputation rates. The odds ratio of major amputation or mortality was greater in the no surveillance group (4.58, 95% CI: 1.855 - 11.364). In the stent cohort, DUS was not associated with a significant improvement in either major amputation or death (odds ratio 2.13 (95% CI 0.903 - 5.051; P = .081). DUS was associated with improved survival rates in patients undergoing lower limb bypass but had no benefit in those patients undergoing stent insertion. The role of DUS following stent insertion in the femoropopliteal segment needs to be better defined.


Using publicly available data to identify priority communities for a SARS-CoV-2 testing intervention in a southern U.S. state.
The U.S. Southeast has a high burden of SARS-CoV-2 infections and COVID-19 disease. We used public data sources and community engagement to prioritize county selections for a precision population health intervention to promote a SARS-CoV-2 testing intervention in rural Alabama during October 2020 and March 2021. We modeled factors associated with county-level SARS-CoV-2 percent positivity using covariates thought to associate with SARS-CoV-2 acquisition risk, disease severity, and risk mitigation practices. Descriptive epidemiologic data were presented to scientific and community advisory boards to prioritize counties for a testing intervention. In October 2020, SARS-CoV-2 percent positivity was not associated with any modeled factors. In March 2021, premature death rate (aRR 1.16, 95% CI 1.07, 1.25), percent Black residents (aRR 1.00, 95% CI 1.00, 1.01), preventable hospitalizations (aRR 1.03, 95% CI 1.00, 1.06), and proportion of smokers (aRR 0.231, 95% CI 0.10, 0.55) were associated with average SARS-CoV-2 percent positivity. We then ranked counties based on percent positivity, case fatality, case rates, and number of testing sites using individual variables and factor scores. Top ranking counties identified through factor analysis and univariate associations were provided to community partners who considered ongoing efforts and strength of community partnerships to promote testing to inform intervention. The dynamic nature of SARS-CoV-2 proved challenging for a modelling approach to inform a precision population health intervention at the county level. Epidemiological data allowed for engagement of community stakeholders implementing testing. As data sources and analytic capacities expand, engaging communities in data interpretation is vital to address diseases locally.


Pyridoxal 5'-phosphate deficiency in uremic undialyzed, hemodialyzed, and non-uremic kidney transplant patients.
In this study, we have investigated plasma pyridoxal 5'-phosphate (PLP) concentrations in undialyzed and dialyzed uremic patients and in kidney transplant subjects, using an enzymatic technique with thermal deproteinization to liberate PLP from plasma proteins. The specificity of the reaction indicates no interference with pyridoxal and only 3% interference with pyridoxamine phosphate. In 17 hemodialyzed patients, a deficiency of about 50% of plasma PLP concentration is found as compared to 25 healthy subjects (22.2 +/- 2.47 vs. 48.8 +/- 3.00 nmol . l-1), as mean +/- SEM). In seven undialyzed uremic patients with end-stage renal failure, the plasma PLP concentration is also decreased (29.3 +/- 1.74 nmol . l-1). The absence of PLP in plasma ultrafiltrates demonstrates that no loss of PLP occurs due to hemodialysis. The daily oral supplementation with 250-750 mg pyridoxal induces a supraphysiological increase in plasma PLP concentration in hemodialyzed as well as in undialyzed patients. In 116 non-uremic kidney transplant subjects, the mean plasma PLP concentration was 33.8 +/- 3.50 nmol . l-1). In 65% of these patients, a marked deficit (below 20 nmol . l-1) was observed. In conclusion, uremic patients have a deficient vitamin B6 state. Its correction with pyridoxal to restore physiological plasma PLP concentration necessitates oral supplementation with lower doses that those widely used at present. In kidney transplant patients a similar plasma PLP deficiency is observed in the absence of chronic renal failure.


The Merits and the Pitfalls of Low Carbohydrate Diet: A Concise Review.
Low carbohydrate diets (LCD) may help body weight loss and glycemic control in diabetes but their long-term consequences are not known. The aim of this review is to highlight the contrast between the potential benefits of short term LCD and the adverse health effects of long-term consumption of LCD. LCD can enhance weight loss in the short term although its effect is small and not sustainable. In people with diabetes and insulin resistance, LCD is helpful in achieving glycemic control. However, there are untoward side effects especially when carbohydrates are severely restricted (< 50 gm a day) to induce ketosis. The latter curbs appetite but also may cause nausea, fatigue water and electrolyte losses and limits exercise capacity. In addition, observational studies suggest that low carbohydrate diets (< 40% energy form carbohydrates) as well as very high carbohydrate diets (> 70% energy from carbohydrate) are associated with increased mortality. The available scientific evidence supports the current dietary recommendations to replace highly processed carbohydrates with unprocessed carbohydrates as well as limiting added sugars in the diet.


Aiming for a shorter rheumatoid arthritis MRI protocol: can contrast-enhanced MRI replace T2 for the detection of bone marrow oedema?
To determine whether T1 post-gadolinium chelate images (T1Gd) can replace T2-weighted images (T2) for evaluating bone marrow oedema (BME), thereby allowing a shorter magnetic resonance imaging (MRI) protocol in rheumatoid arthritis (RA). In 179 early arthritis patients and 43 advanced RA patients, wrist and metacarpophalangeal joints were examined on a 1.5-T extremity MRI system with a standard protocol (coronal T1, T2 fat-saturated and coronal and axial T1 fat-saturated after Gd). BME was scored according to OMERACT RAMRIS by two observers with and without T2 images available. Agreement was assessed using intraclass correlation coefficients (ICCs) for semi-quantitative scores and test characteristics with T2 images as reference. Agreement between scores based on T2 and T1Gd images was excellent ICC (0.80-0.99). At bone level, sensitivity and specificity of BME on T1Gd compared to T2 were high for both patient groups and both readers (all ≥80 %). T1Gd and T2 images are equally suitable for evaluating BME. Because contrast is usually administered to assess (teno)synovitis, a short MRI protocol of T1 and T1Gd is sufficient in RA. • Bone marrow oedema scores are equal on T2 and T1-Gd-chelate enhanced sequences. • Agreement between scores based on T2 and T1-Gd-chelate images was excellent. • Sensitivity and specificity for presence of bone marrow oedema were high. • A short protocol without T2 images suffices in rheumatoid arthritis patients.


ERK signaling is a central regulator for BMP-4 dependent capillary sprouting.
Bone Morphogenetic Protein-4 (BMP-4) and Extracellular-Signal Regulated Kinases (ERK) play crucial roles in vascular diseases. Here, we demonstrate that BMP-4 not only signals through the classical Smad cascade but also activates ERK phosphorylation as an alternative pathway in human umbilical vein endothelial cells (HUVEC) and that Smad and ERK pathways communicate through signal crosstalk. HUVECs were treated with BMP-4 and/or MEK inhibitors. Smad 6 and constitutively active (ca) MEK1 were overexpressed. Loss of function of Smad 4 and Smad 6 was achieved by specific siRNA transfection. Cell lysates were analyzed by western blotting for Smad and ERK phosphorylation. HUVEC spheroids were generated for angiogenesis quantification. Treatment with BMP-4 results in a dose- and time-dependent activation of the MEK-ERK 1/2 pathway in addition to activation of the Smad pathway and is blocked by MEK inhibitors. Quantitative in-gel angiogenesis assays in the presence or absence of MEK inhibitors demonstrate that ERK signals are necessary for BMP-4 induced capillary sprouting. Furthermore sprouting is not blocked by inhibition of the Smad signaling pathway. Overexpression of the inhibitory Smad 6 inhibits ERK phosphorylation and ERK-induced capillary sprouting, whereas loss of function of Smad 4 has no effect. We demonstrate that ERK1/2 functions as an alternative pathway in BMP-4 signaling in HUVECs. Capillary sprouting induced by BMP-4 is dependent on ERK phosphorylation. ERK is essential for efficient transduction of BMP signals and serves as a positive feedback mechanism. On the other hand, stimulation of Smad 6 inhibits ERK activation and thus results in a negative feedback loop to fine-tune BMP signaling in HUVECs.


Non-destructive monitoring of forming quality of self-piercing riveting via a lightweight deep learning.
Self-piercing riveting (SPR) has been widely used in automobile body jointing. However, the riveting process is prone to various forming quality failures, such as empty riveting, repeated riveting, substrate cracking, and other riveting defects. This paper combines deep learning algorithms to achieve non-contact monitoring of SPR forming quality. And a lightweight convolutional neural network with higher accuracy and less computational effort is designed. The ablation and comparative experiments results show that the lightweight convolutional neural network proposed in this paper achieves improved accuracy and reduced computational complexity. Compared with the original algorithm, the algorithm's accuracy in this paper is increased by 4.5[Formula: see text], and the recall is increased by 1.4[Formula: see text]. In addition, the amount of redundant parameters is reduced by 86.5[Formula: see text], and the amount of computation is reduced by 47.33[Formula: see text]. This method can effectively overcome the limitations of low efficiency, high work intensity, and easy leakage of manual visual inspection methods and provide a more efficient solution for monitoring the quality of SPR forming quality.


The molecular basis of making spiral ganglion neurons and connecting them to hair cells of the organ of Corti.
The bipolar spiral ganglion neurons apparently delaminate from the growing cochlear duct and migrate to Rosenthal's canal. They project radial fibers to innervate the organ of Corti (type I neurons to inner hair cells, type II neurons to outer hair cells) and also project tonotopically to the cochlear nuclei. The early differentiation of these neurons requires transcription factors to regulate migration, pathfinding and survival. Neurog1 null mice lack formation of neurons. Neurod1 null mice show massive neuronal death combined with aberrant central and peripheral projections. Prox1 protein is necessary for proper type II neuron process navigation, which is also affected by the neurotrophins Bdnf and Ntf3. Neurotrophin null mutants show specific patterns of neuronal loss along the cochlea but remaining neurons compensate by expanding their target area. All neurotrophin mutants have reduced radial fiber growth proportional to the degree of loss of neurotrophin alleles. This suggests a simple dose response effect of neurotrophin concentration. Keeping overall concentration constant, but misexpressing one neurotrophin under regulatory control of another one results in exuberant fiber growth not only of vestibular fibers to the cochlea but also of spiral ganglion neurons to outer hair cells suggesting different effectiveness of neurotrophins for spiral ganglion neurite growth. Finally, we report here for the first time that losing all neurons in double null mutants affects extension of the cochlear duct and leads to formation of extra rows of outer hair cells in the apex, possibly by disrupting the interaction of the spiral ganglion with the elongating cochlea.


The rapeseed mitochondrial gene for subunit 2 of the NADH dehydrogenase complex: a trans-spliced structure is conserved in one of the smallest plant mitochondrial genomes.
The single-copy gene encoding NADH dehydrogenase subunit 2 (nad2) has been identified in the mitochondrial genome of rapeseed (Brassica napus L.). The rapeseed nad2 gene has the same gene organization in Oenothera and wheat: it consists of five exons located in two loci encoding the two first exons and the last three exons respectively. All exons are separated by group-II introns. A trans-splicing event is required to join exons B and C. Putative splicing intermediates were identified by transcriptional analysis of the nad2 gene. The complexity of organization of the nad2 gene is completely conserved even in one of the smallest mitochondrial genomes of higher plants.


Effect of monosodium glutamate on fetal development and progesterone level in pregnant Wistar Albino rats.
Monosodium glutamate (MSG) is a widespread flavor enhancer and stabilizer in manufactured or packaged foods that possess myriad adverse effects. This study aimed to evaluate the effect of MSG on placental progesterone receptors and fetal development. Thirty pregnant Wistar Albino rats were divided into three groups (ten/each). The control group (G1) gavaged distilled water only, low-dose treated group (G2) gavaged 3 g/kg MSG, and high-dose treated group (G3) gavaged 6 g/kg MSG from 1st to 18th days of gestation, and all pregnant rats were sacrificed on the 19th day of gestation. The effect of MSG on fetal weights, crown vertebral length (CVL), placental weight, placental ghrelin expression, and fetal skeleton examination were estimated. MSG induced a significant decrease in fetal weights, CVL lengths, placental weight, and ghrelin expression in both treatment groups compared to the control group. Several parts of the fetal skeleton showed incomplete ossification and delayed chondrification in which high-dose maternally treated fetuses were more affected. Many degenerative changes were detected in both maternal and fetal liver and kidney tissues in MSG-treated groups. Moreover, MSG caused a significant increase in serum ALT, ALP, and creatinine levels in pregnant rats' blood. Serum progesterone was only elevated in G3 on the 19th day of gestation. This study showed that the administration of MSG during pregnancy adversely influences fetal growth and skeletal development and caused several biochemical and histological changes in the maternal and fetal liver and kidney tissues which assure the toxic and teratogenic effects of MSG.


Uncovering genetic causes of hypophosphatemia.
Chronic hypophosphatemia can result from a variety of acquired disorders, such as malnutrition, intestinal malabsorption, hyperparathyroidism, vitamin D deficiency, excess alcohol intake, some drugs, or organ transplantation. Genetic disorders can be a cause of persistent hypophosphatemia, although they are less recognized. We aimed to better understand the prevalence of genetic hypophosphatemia in the population. By combining retrospective and prospective strategies, we searched the laboratory database of 815,828 phosphorus analyses and included patients 17-55 years old with low serum phosphorus. We reviewed the charts of 1287 outpatients with at least 1 phosphorus result ≤2.2 mg/dL. After ruling out clear secondary causes, 109 patients underwent further clinical and analytical studies. Among them, we confirmed hypophosphatemia in 39 patients. After excluding other evident secondary causes, such as primary hyperparathyroidism and vitamin D deficiency, we performed a molecular analysis in 42 patients by sequencing the exonic and flanking intronic regions of a panel of genes related to rickets or hypophosphatemia (CLCN5, CYP27B1, dentin matrix acidic phosphoprotein 1, ENPP1, FAM20C, FGFR1, FGF23, GNAS, PHEX, SLC34A3, and VDR). We identified 14 index patients with hypophosphatemia and variants in genes related to phosphate metabolism. The phenotype of most patients was mild, but two patients with X-linked hypophosphatemia (XLH) due to novel PHEX mutations had marked skeletal abnormalities. Genetic causes should be considered in children, but also in adult patients with hypophosphatemia of unknown origin. Our data are consistent with the conception that XLH is the most common cause of genetic hypophosphatemia with an overt musculoskeletal phenotype.


The treatment of dysmenorrhea with naproxen sodium: a report on two independent double-blind trials.
The efficacy of naproxen sodium (naproxen-Na) in dysmenorrhea has been established in two independent double-blind (placebo-controlled) studies. An initial dose of 550 mg. of naproxen-Na was followed by 275 mg. every six hours for a maximum of five days. Twenty patients were included in Study I (10 treated with naproxen-Na) and 23 patients in Study II (12 treated with naproxen-Na). Each patient received the medication during four dysmenorrheic episodes. Thus, a total of 172 treatment courses could be evaluated. A variety of efficacy criteria were measured: frequency of pill intake, changes in pain intensity, the degree of relief achieved by the medication, and need for additional analgesics. In both studies naproxen-Na was demonstrated to be superior to the placebo treatment with high statistical significance in each of these parameters.


Pt/MnO2 Nanoflowers Anchored to Boron Nitride Aerogels for Highly Efficient Enrichment and Catalytic Oxidation of Formaldehyde at Room Temperature.
The catalytic room temperature oxidation of formaldehyde (HCHO) is widely considered as a viable method for the abatement of indoor toxic HCHO pollution. Herein, Pt/MnO2 nanoflowers anchored to boron nitride aerogels (Pt/MnO2 -BN) were fabricated for the catalytic room temperature oxidation of HCHO. The three-dimensional Pt/MnO2 -BN aerogels demonstrated superior catalytic activity as a result of the improved diffusion of the reactant molecules within the porous structure. Furthermore, the porous aerogels displayed excellent HCHO adsorption capacities, which promote a rapid HCHO gas-phase concentration reduction and a subsequent complete oxidation of the adsorbed HCHO. The combined adsorption and oxidation properties of the Pt/MnO2 -BN aerogels enhance the oxidative removal of HCHO. The optimized Pt/MnO2 -BN demonstrated excellent catalytic activity toward HCHO (200 ppm) at room temperature, achieving a 96 % formaldehyde conversion after 50 min.


[Demonstration of circular ribonucleic acid in the Lumbo virus (Bunyavirus)].
Electron microscopy study of RNA extracted from Lumbovirus shows the existence of circular molecules, which are not susceptible to thermal or chemical denaturation. These facts suggest that the RNA is present inside the virion in a covalently closed circular form.


The spectrum of laparoscopic surgery.
Laparoscopic procedures have begun to replace many conventional operations because of the avoidance of major surgery and the rapid recovery of the patient. The majority of these traditional operations will be performed laparoscopically in the future. For example, patients who suffer from achalasia will be able to undergo laparoscopic cardiomyotomy and patients with non-cardiac chest pain of esophageal origin will be able to undergo thoracoscopic myotomy. Likewise, a viable alternative to long-term medication with H2 blockers or omeprazole will be laparoscopic posterior vagotomy and anterior lesser curve seromyotomy. As methods are developed to deal with the extraction of large specimens, many ablative procedures will be undertaken by the laparoscopic route. Extraction techniques must not compromise the need for histopathological examination of the resected specimen in cancer resections. The ultimate spectrum of laparoscopic surgery will be determined by the progress in remote handling technology, overcoming the manipulative restrictions inherent in the current instrumentation. Research evaluating the efficacy of new methods will be essential.


The evolution of the cooperative group.
A simple model, illustrating the transition from a population of free swimming, solitary cells (Chlamydomonas-type) to one consisting of small colonies (Gonium-type) serves as a basis to discuss the evolution of the cooperative group. The transition is the result of a mutation of the dynamics of cell division, delayed cell separation leads to colonies of four cells. With this mutation cooperative features appear, such as synchronised cell divisions within colonies and coordinated flagellar function which enables the colony to swim in definite directions. The selective advantages under given, environmental conditions are defined and the periods necessary for complete allelic replacement in small populations are calculated for asexual and sexual reproduction. The assumption of a steady-state population during allelic substitution is critically considered, particularly under conditions of competition. It is shown that density-dependent population control must operate in the process of selection, Sexual reproduction slows down the rate of selection even though all cells are haploid. This phenomenon can be explained in general terms of "organizational dominance', where individual units coordinate the function of their neighbours which may be of a different allelotype. Cooperativity is pointed out as an a priori systemic feature which resides in the sub-units of systems, group formation and coordination appears thus as an almost inevitable event. A particular type of system described as 'closed cycle of positive fitness interaction' is discussed in more detail. It has the remarkable feature that its members cannot compete with each other; selection takes place between whole cycles (in analogy to Eigen's 1971 model). Gonium has a wide spectrum of 'somatic plasticity' which enables it to assume various colonial configurations depending on physiological and environmental conditions. This feature can be explained as the result of dynamic flexibilities on the macro-molecular level. The particular relationship between the vast, molecular complexity and the relative simple dynamics of the cell cycle must lead eventually to the genetic fixation of an environmentally induced phenotype.


Analysis of 12,661 pediatric burns in Wuhan institute of burns: A retrospective study of fifteen years.
By analyzing the epidemic characteristics of pediatric burns in a burn center serving large areas of Hubei Provence and partly surrounding provinces around Wuhan City, the aim of this study is to provide better strategies for the prevention and care for pediatric burns. Pediatric burn patients who were younger than 13 years old in Wuhan Third Hospital from 2004 to 2018 were included. Demographic and clinical data were collected, analyzed and compared among groups. 12,661 pediatric burns, mean aged 2.37 ± 2.30 y, were admitted during the 15 years, with 7973 boys (62.97%) and 4688 girls (37.03%). By age groups, infant (<3y), preschool (>3-6y) and school children (>6-13y) accounted for 81.12% (10,270 cases), 12.08% (1530 cases) and 6.80% (861 cases) respectively. The most cause of injury was scalds (11,232, 88.71%), followed by flame burns (917, 7.24%), electric burns (201, 1.59%), contact burns (127, 1.00%), firework or firecracker (124, 0.98%), chemical burns (40, 0.32%) and hot crush injury (20, 0.16%). The mean age of firework or firecracker burns was 6.19 ± 2.83y, electric burns 5.18 ± 3.31y, flame burns 4.73 ± 3.53y, hot crush injury 3.85 ± 2.37 y, contact burns 3.66 ± 3.35y, chemical burns 3.03 ± 2.50y, and scald 2.06 ± 1.91y. Over half cases (57.34%) were small burns less than 10% total burn surface area (TBSA) and the larger TBSA, the fewer number of patients. The mortality rate was 0.11% and correlated with TBSA, age and etiology. The mean length of stay (LOS) was 12.63 ± 11.91 days and highly correlated with etiology and TBSA. The mean hospital cost was 11210.76 ± 21248.87 RMB (about 1600 USD) or 1626.91 ± 3957.59 RMB (about 230 USD) per % TBSA, which was correlated with depth of burn, TBSA, etiology, LOS and age. Pediatric burns in central China was still common and even increasing. Majority of the pediatric burn victims were boys under three years old, while the mean ages of different etiologies varied from about 2-6 years old. Education and prevention aiming the high risks are the key point to decrease pediatric burns.


A de novo ryanodine receptor 2 gene variant in a case of sudden cardiac death.
A 34-year-old man, who was previously fit and healthy, died suddenly on exercise. A post-mortem exam performed by forensic pathologists and a toxicological screening were normal; therefore, the cause of death was suspected to be sudden arrhythmic death syndrome, prompting the need for a molecular autopsy. Screening for genetic variations underlying arrhythmogenic genes by next-generation sequencing highlighted a heterozygous single-nucleotide variant in the exon n. 94 of the ryanodine receptor type 2 gene. This gene, encoding the cardiac ryanodine receptor, is one of the main genetic variants of catecholaminergic polymorphic ventricular tachycardia, estimated to affect 1 in 10,000 individuals. It manifests with syncope, seizures, or sudden death due to exercise- or emotional stress-induced bidirectional or polymorphic ventricular tachycardia, usually in children and young adults with morphologically normal hearts and normal baseline electrocardiograms. Even if this de novo missense mutation has not yet been associated with catecholaminergic polymorphic ventricular tachycardia, it is likely to be a disease-causing variant which leads to a defective protein responsible for disturbed ion flow.


Outline of a project for nursing health education on the Instagram social network.
to characterize the outline of a project for health education and its contributions to the propagation of information on the Instagram social network. exploratory and descriptive research on an Instagram profile called "@resenhadasaude";. Data collection: from July 23, 2020, to April 21, 2021. Interaction metrics were generated on 36 posts. Simple and percentage statistical analysis were applied. there are 1,016 followers in Brazil, with a 206.02% growth. The largest audience is teenagers, young people, and women, with a gender difference of 41.8%. The greatest interest was about covid-19, sexual health, and drugs. Followers' misconceptions reinforce the need for the dissemination of quality information. Instagram metrics point to the project's validation in terms of audience interest, mostly adolescents and youth. Instagram proved to be powerful for educational purposes and information dissemination, as well as an autonomous field for nursing.


Individual markers of cerebral small vessel disease and domain-specific quality of life deficits.
Cerebral small vessel disease (SVD) leads to reduced quality of life (QOL), but the mechanisms underlying this relationship remain unknown. This study investigated multivariate relationships between radiological markers of SVD and domain-specific QOL deficits, as well as potential mediators, in patients with SVD. Clinical and neuroimaging measures were obtained from a pooled sample of 174 SVD patients from the St. George's Cognition and Neuroimaging in Stroke and PRESsure in established cERebral small VEssel disease studies. Lacunes, white matter hyperintensities, and microbleeds were defined as radiological markers of SVD and delineated using MRI. QOL was assessed using the Stroke-Specific Quality of Life Scale. Multivariate linear regression was used to determine whether SVD markers were associated with domain-specific QOL deficits. Significant associations were further investigated using mediation analysis to examine whether functional disability or cognition was potential mediators. Multivariate regression analyses revealed that lacunes were associated with total QOL score (β = -8.22, p = .02), as well as reductions in mobility (β = -1.41, p = .008) and language-related subdomains (β = -0.69, p = .033). White matter hyperintensities and microbleeds showed univariate correlations with QOL, but these became nonsignificant during multivariate analyses. Mediation analyses revealed that functional disability, defined as reduced activities of daily living, and executive function, partially mediated the relationship between lacunes and total QOL, as well as mobility-related QOL, but not language-related QOL. Lacunar infarcts have the most detrimental effect on QOL in SVD patients, particularly in the mobility and language-related subdomains. These effects may be partially explained by a reduction in activities of daily living. These results may inform targeted interventions to improve QOL in patients with SVD.


The role of synovectomy in the management of recurrent haemarthroses in haemophilia.
Between August 1973 and May 1979, 18 patients suffering from severe haemophilia A underwent synovectomy for recurrent haemarthroses, resistant to medical management. A total of 23 joints (11 knees and 12 elbows) were subjected to operation, five patients undergoing two synovectomies on different joints. Post-operative follow-up period ranged from 12 to 58 months for elbow synovectomy and from 29 to 76 months for knee synovectomy. All patients experienced fewer haemarthroses, the average number of bleeding episodes per joint over a 12 month period being reduced from 19 to 3 for knee joints, and from 24 to 3 for elbow joints. This improvement was apparent in the immediate post-operative year and maintained thereafter. Over the same follow-up period nine of the 11 knee joints were found to have lost an average 42 degrees mobility. Following elbow synovectomy five out of 12 patients lost an average of 28 degrees mobility; six patients gained an average 11 degrees mobility. The post-operative complication rate was high for knee synovectomy, 54% suffering haemorrhage despite haemostatic factor VIII levels. For elbow synovectomy the rate was much lower, 75% of operations being uncomplicated. The average in-patient time for knee operation was 75 d, and for the elbow 19 d. We conclude that synovectomy of the knee joint is to be avoided when other means of reducing bleeding episodes are available, whereas elbow synovectomy retains a useful role in the treatment of recurrent haemarthroses which do not respond to clotting factor prophylaxis.


Enhancing global thinking can reduce the misconception of accumulation: A potential way to mitigate climate change.
Climate change and global warming have long been attention and concern all over the world. However, there is always a debate about when and to what degree to take action like reducing carbon dioxide emissions. Recently, researchers found that the public has misconceptions about climate dynamics, which might be a reason for people do not support prompt mitigation of greenhouse gas emissions. The core problem of misconceptions is the stock-flow (SF) problem, which refers to the difficulty of inferring the behavior of a stock variable given information regarding its inflows and outflows. We elaborated on the idea that global thinking is beneficial for comprehending SF problems and proposed that global thinking enhancing display based on highlighting the areas of difference could be a possible way to shift one's thinking process to the right one, which was proved by two studies. Theoretical and practical implications are discussed.


[Exergames to promote physical activity and mobility in inpatient long-term nursing-An overview].
Maintaining and promoting mobility is a key objective and central goal of nursing care. Active video games or so-called exergames can also be used for this purpose. In the group of older people some studies showed indications of positive effects with respect to mobility. In this article the focus is on studies that examined the use of exergames for the purpose of maintaining or promoting physical activity and mobility in the setting of long-term inpatient nursing. In summary, a literature search in databases indicated that individual studies on this topic found indications of positive effects: however, the informative value of the results is limited due to their heterogeneity and small samples.


Proteomic analysis of Tityus discrepans scorpion venom and amino acid sequence of novel toxins.
The Venezuelan scorpion Tityus discrepans is known to cause human fatalities. We describe the first complete proteomic analysis of its venom. By HPLC 58 different fractions were obtained and 205 different components were identified by MS analysis. Components having molecular masses from 272 to 57 908 amu were found. Forty homogeneous components had their N-terminal amino acid sequence determined by Edman degradation, from which two new peptides named TdK2 and TdK3 (meaning T. discrepans (Td) K(+) channel toxins 2 and 3) were fully characterized. The first contains 34 amino acid residues with a molecular mass of 3451 amu, and the second has 36 amino acids with 3832 amu. Both peptides are tightly bound by three disulfide bridges. TdK2 was shown to block reversibly the Shaker B K(+)-channel expressed heterologously in Sf9 cells. The systematic number assigned to TdK2 is alpha-KTx-18.2 and that of TdK3 is alpha-KTx-18.3. Comparative analysis of the amino acid sequences found suggests that this venom contains peptides highly similar to those that block K(+) channels, as well as those that modify the gating mechanisms of Na(+) channels, found in other scorpions. Additionally, peptides similar to defensins were also identified.


Conservation of biodiversity of the coastal resources of Sundarbans, Northeast India: an integrated approach through environmental education.
The Indian Sundarbans, a diversified coastal wetland on the southern fringe of the State of West Bengal, harbors a luxuriant biodiversity and acts as a potential refuge of living marine resources. Girdled with thick mangrove foliage, this estuarine delta system offers an excellent nursery ground for most of the brackishwater finfish and shellfish. Since supply of hatchery-produced tiger prawn seed (Penaeus monodon) is highly inadequate in West Bengal, the aquaculture farms of this region largely depend on the supply from natural resources. Being motivated by a regular cash income, the majority of coastal people from Sundarbans have adopted prawn seed collection as their profession almost throughout the year as an important source of earning. The users are neither trained nor guided at any stage from collection to marketing and are fully dependent on traditional methods. They first sort out the tiger prawn seeds (mainly the postlarval stage PL 20) accounting only 0.25-0.27% of the total catch and thereafter the major portion of the haul are thrown away on the beach flats or the tidal mudflats. This wasted by-catch contains the juveniles of economic and uneconomic varieties of finfish and shellfish along with a bulk of holoplankters and meroplankters (non-target species). This practice causes several ecological and occupational consequences, namely, (i) the huge destruction of the pelagic biota that can lead to severe stock depletion as well as hamper the energy transference through the marine ecosystem food webs; (ii) constant dragging of nets along the coast and tidal creeks paves the way for soil erosion, uprooting the mangrove seedlings and saltmarsh vegetation; (iii) the water quality is deteriorating in the catchment areas due to mud erosion and (iv) due to constant contact with the seawater, the collectors are affected with waterborne diseases, skin infections, reproductive tract disease in women and many other contagious diseases. This paper, in addition to identifying the challenge to environmental quality and resource abundance, emphasizes the need for grass-root public education so that local people come to understand, support and implement sustainable resource conservation and environmental protection activities now and in the future. As a follow-up course of action, the authors have initiated a general awareness program for developing consciousness among the coastal people regarding proper use of natural resources. Initiatives are taken for educating coastal people by holding workshops and seminars with the use of educational resource materials. Exclusive awareness camps and grass root level training for coastal people are also being proposed as a future course of action by means of exhibitions, audiovisuals etc. It is proposed that local government bodies come forward to mitigate this problem with scientific and rational approaches and to take proper actions towards conservation.


Studying Antibiotic Persistence During Infection.
This chapter contains the latest version of essential protocols established to study Salmonella persisters during macrophage infection . These methods, which can be applied to other pathogens, allow researchers to quantify, visualize, and characterize bacterial persisters within a population and within immune cells consistent with the recent consensus statement published by the research community working on antibiotic persistence (Balaban et al, Nat Rev Microbiol 17:441-448, 2019). These protocols notably allow the discrimination between tolerance and persistence during infection , which is essential to clarify which phenomenon is actually reported. Methods described in this chapter may contribute to the determination of key bacterial and host genes that contribute to antibiotic persistence.


Does the sex of a simulated patient affect CPR?
While males and females are equally at risk of sudden cardiac arrest (SCA), females are less likely to be resuscitated. Cardiopulmonary Resuscitation (CPR) may be inhibited by socio-cultural norms about exposing female victims' chests. Empirically confirming this hypothesis is limited by lack of patient simulators modeling realistic female physiques. A commercially-available patient simulator was transformed to evaluate how physical attributes of a patient's sex might influence lay participants who were asked to resuscitate a female versus a male during simulated cardiac arrest. Sixty-nine participants consented to be in the study. Participants were randomly assigned to provide CPR and defibrillation as instructed by a commercially-available automated external defibrillator on a patient simulator presented as either a male or female experiencing cardiac arrest. Rescuers removed significantly more clothing from the male than the female, with men removing less clothing from the female. More rescuers' initial hand placements for CPR were centered between the female's breasts compared to the male, on which placement was distributed across the chest towards the nipples. While rescuers had better hand placement for CPR on the female, both men and women rescuers were reluctant to remove the female's clothing, with men significantly more hesitant. Reticence to remove clothing was often articulated relative to social norms during structured interviews. We suggest that using only male simulators will not allow trainees to experience social differences associated with the care of a female simulated patient. Realistic female patient simulators are needed.


Environmental sustainability in orthopaedic surgery : a scoping review.
In the UK, the NHS generates an estimated 25 megatonnes of carbon dioxide equivalents (4% to 5% of the nation's total carbon emissions) and produces over 500,000 tonnes of waste annually. There is limited evidence demonstrating the principles of sustainability and its benefits within orthopaedic surgery. The primary aim of this study was to analyze the environmental impact of orthopaedic surgery and the environmentally sustainable initiatives undertaken to address this. The secondary aim of this study was to describe the barriers to making sustainable changes within orthopaedic surgery. A literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines through EMBASE, Medline, and PubMed libraries using two domains of terms: "orthopaedic surgery" and "environmental sustainability". A total of 13 studies were included in the final analysis. All papers studied the environmental impact of orthopaedic surgery in one of three areas: waste management, resource consumption, and carbon emissions. Waste segregation was a prevalent issue and described by nine studies, with up to 74.4% of hazardous waste being generated. Of this, six studies reported recycling waste and up to 43.9% of waste per procedure was recyclable. Large joint arthroplasties generated the highest amount of recyclable waste per procedure. Three studies investigated carbon emissions from intraoperative consumables, sterilization methods, and through the use of telemedicine. One study investigated water wastage and demonstrated that simple changes to practice can reduce water consumption by up to 63%. The two most common barriers to implementing environmentally sustainable changes identified across the studies was a lack of appropriate infrastructure and lack of education and training. Environmental sustainability in orthopaedic surgery is a growing area with a wide potential for meaningful change. Further research to cumulatively study the carbon footprint of orthopaedic surgery and the wider impact of environmentally sustainable changes is necessary.Cite this article: Bone Jt Open 2022;3(8):628-640.


Microcephalic osteodyplastic primordial dwarfism type II: case report with unique oral findings and a new mutation in the pericentrin gene.
Microcephalic osteodysplastic dwarfism (MOPD) type II (OMIM 210720) is a rare autosomal recessive form of primordial dwarfism, characterized by intrauterine and postnatal growth restriction, microcephaly, distinctive facial features, and osteodysplastic skeletal changes. The dental literature describing the oral manifestations of this syndrome is scarce. The aim of this article is to report the case of an 8-year-old male of Indian origin with MOPD type II and to describe his oral and dental manifestations. Genetic analysis was performed to confirm the diagnosis. The patient presented with interesting dental findings, including oligodontia, enamel hypoplasia, early exfoliation of primary dentition, accelerated eruption of permanent teeth with generalized grade II mobility, histopathologic features suggestive of dentin dysplasia, and a new mutation in the Pericentrin gene, which has not been documented earlier. This is the first report from India of a case with this syndrome. The article presents various dentomaxillofacial features that have not been documented in dental literature earlier with sufficient evidence.


Alkaline detergent combined with a routine ward bedpan washer disinfector cycle eradicates Clostridium difficile spores from the surface of plastic bedpans.
The cleaning efficiency of a ward bedpan washer disinfector was evaluated using various cycle parameters and detergent to determine which conditions could effectively eliminate Clostridium difficile spores from the surface of bedpans. Results revealed that the regular intensive cycle with thermal conditions of 85°C for 60 seconds plus the addition of an alkaline detergent was sufficient to eradicate C difficile spores. However, these thermal conditions alone, without detergent, were not adequate.


Pharmacy Quality Alliance: Five phase I demonstration projects: descriptions and lessons learned.
To describe the five Phase I Pharmacy Quality Alliance (PQA) demonstration projects and discuss lessons learned across the projects. Descriptive nonexperimental study. United States from July 2008 to November 2009. Community pharmacies from five states. Pharmacies viewed their performance scores on a reporting website and provided feedback. Pharmacy performance scores and pharmacist feedback about the scores and reporting websites. Considerable variation was found in the pharmacy performance scores. Some pharmacies did not have enough patients taking medications that were included in specific performance measures. Use of a website to report pharmacy performance was feasible across several different approaches. PQA has developed measures of pharmacy performance that can be used in programs intended to report pharmacy performance. It is feasible to calculate pharmacy performance scores and create Web-based pharmacy performance reports to provide feedback to community pharmacists. Further development of pharmacy performance reporting should occur.


Echocardiographic Assessment of Left Ventricular Systolic and Diastolic Functions in Dogs with Severe Sepsis and Septic Shock; Longitudinal Study.
The purpose of this study was to monitor left ventricular systolic dysfunction (LVSD) and diastolic dysfunction (LVDD) using transthoracic echocardiography (TTE) in dogs with severe sepsis and septic shock (SS/SS). A prospective longitudinal study using 23 dogs with SS/SS (experimental group) and 20 healthy dogs (control group) were carried out. All the clinical, laboratory and cardiologic examinations for the experimental dogs were performed at admission, 6 and 24 h after the start of treatment and on the day of discharge. LVSD was described as LV ejection fraction (LVEF) < 50%. LVDD was determined when the septal mitral annulus early diastolic velocity (LVEm) was <8 cm/s. LVSD and LVDD were present in 3 and 16 dogs with SS/SS, respectively, with both types of dysfunction present in 2 of the dogs. Although all the dogs with LVSD survived, 8 dogs with LVDD did not. The survival period was significantly shorter in dogs with an LVEm < 8 cm/s (1.3 ± 1.4 days). In conclusion, LVDD, rather than LVSD, was a common cardiovascular abnormality in the septic dogs, and this may be a negative prognostic factor. TTE is a useful tool for the identifying and monitoring of myocardial dysfunction in the dogs with SS/SS.


Compressed Sensing Real-Time Cine Reduces CMR Arrhythmia-Related Artifacts.
Cardiac magnetic resonance (CMR) is a key tool for cardiac work-up. However, arrhythmia can be responsible for arrhythmia-related artifacts (ARA) and increased scan time using segmented sequences. The aim of this study is to evaluate the effect of cardiac arrhythmia on image quality in a comparison of a compressed sensing real-time (CSrt) cine sequence with the reference prospectively gated segmented balanced steady-state free precession (Cineref) technique regarding ARA. A total of 71 consecutive adult patients (41 males; mean age = 59.5 ± 20.1 years (95% CI: 54.7-64.2 years)) referred for CMR examination with concomitant irregular heart rate (defined by an RR interval coefficient of variation >10%) during scanning were prospectively enrolled. For each patient, two cine sequences were systematically acquired: first, the reference prospectively triggered multi-breath-hold Cineref sequence including a short-axis stack, one four-chamber slice, and a couple of two-chamber slices; second, an additional single breath-hold CSrt sequence providing the same slices as the reference technique. Two radiologists independently assessed ARA and image quality (overall, acquisition, and edge sharpness) for both techniques. The mean heart rate was 71.8 ± 19.0 (SD) beat per minute (bpm) (95% CI: 67.4-76.3 bpm) and its coefficient of variation was 25.0 ± 9.4 (SD) % (95% CI: 22.8-27.2%). Acquisition was significantly faster with CSrt than with Cineref (Cineref: 556.7 ± 145.4 (SD) s (95% CI: 496.7-616.7 s); CSrt: 23.9 ± 7.9 (SD) s (95% CI: 20.6-27.1 s); p < 0.0001). A total of 599 pairs of cine slices were evaluated (median: 8 (range: 6-14) slices per patient). The mean proportion of ARA-impaired slices per patient was 85.9 ± 22.7 (SD) % using Cineref, but this was figure was zero using CSrt (p < 0.0001). The European CMR registry artifact score was lower with CSrt (median: 1 (range: 0-5)) than with Cineref (median: 3 (range: 0-3); p < 0.0001). Subjective image quality was higher in CSrt than in Cineref (median: 3 (range: 1-3) versus 2 (range: 1-4), respectively; p < 0.0001). In line, edge sharpness was higher on CSrt cine than on Cineref images (0.054 ± 0.016 pixel-1 (95% CI: 0.050-0.057 pixel-1) versus 0.042 ± 0.022 pixel-1 (95% CI: 0.037-0.047 pixel-1), respectively; p = 0.0001). Compressed sensing real-time cine drastically reduces arrhythmia-related artifacts and thus improves cine image quality in patients with arrhythmia.


Dynamics of SARS-CoV-2 variants of concern (VOC) in Bangladesh during the first half of 2021.
Bangladesh is the second-worst-affected country in South Asia by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study is to examine genome sequences from Bangladesh from January 2021 to June 2021 in order to monitor the SARS-CoV-2 VOC and the clades or lineages that are prevalent in the country. Within the study timeframe, at least eight Nextstrain clades were found: 20A, 20B, 20C, 20H (Beta, V2), 20I (Alpha, V1), 20 J (Gamma, V3), 21A (Delta), 21D (Eta), and six GISAID clades: four main (G, GH, GR, GRY) and two minors (GV, O) with an introduction of VOC B.1.1.7/Alpha, B.1.351/Beta and B.1.617.2/Delta. The introduction and recent occurrence of VOCs with substantial alterations in the receptor binding site of spike protein (K417 N, K417T, L452R, T478K, E484K, S494P, N501Y) are of particular importance. Specifically, VOC B.1.617.2/Delta has surpassed all prior VOCs in Bangladesh, posing a challenge to the existing disease management.


[Respiration and heat production in the embryonic development of chickens].
A marked increase in the rate of oxagen consumption and heat production, measured by the direct method, is observed in the chick embryogenesis. The intensity of respiration and heat production of the embryos decreases as the development proceeds. During development the data obtained by direct and indirect calorimetry diverge. This divergence, referred to as psi u-function, gradually decreases by the moment of hatching. Differences in the value of heat production and psi u-function were found in crosses of meat and egg directions, related to differences in the growth rate and productivity of adult fowl.


Behavioral Problems and Emotional Difficulties at Children and Early Adolescents of the Veterans of War with Post-Traumatic Stress Disorder.
Behavioral problems and emotional difficulties at children of the veterans of war with post-traumatic stress disorder (PTSD) have not been researched entirely. In our country, which has a lot of persons suffering from some psychological traumas, this trauma seems to continue. The aim of this study was to determine the exposure, manifestations of behavioral problems and emotional difficulties at children and early adolescents, whose fathers were the veterans of war demonstrating post-traumatic stress disorder symptoms. The analyzed group comprised 120 school age children (10-15 years of age), whose parents/fathers were the veterans of war. The children were divided into two groups, and each group into the following two age sub-groups: 10-12 (children) and 13-15 (early adolescents) according to PTSD presence at their fathers - veterans of war. PTSD symptoms at fathers, veterans of war, were assessed using the Harvard Trauma Questionnaire-Bosnia and Herzegovina version and MKB-10 - audit of criteria. To assess the behavioral problems of children, the Child Behavior Checklist for parents was used, and to evaluate the neuroticism at children Hanes-Scale of neuroticism-extraversion was used while the depression level was evaluated using the Depression self-rating scale (DSRS). To analyze the obtained results, SPSS 17 program was used. The value p <0. 05 is considered significant. Children of fathers, the veterans of war, demonstrating the PTSD symptoms show more problems in activity, social and school conduct as well as in symptoms of behavioral problems compared to the children whose fathers do not demonstrate the PTSD symptoms (p<0. 001). Children of the war veterans demonstrating the symptoms of the post-traumatic stress disorder show significant difference at neuroticism sub-scales (p<0.001). Negative correlation between PTSD and activity, social and school conduct has been determined (p <0. 01), while positive correlation was determined between PTSD of war veterans with symptoms and neuroticism at children (p <0. 01). Depression symptoms are found at 17.5% children, while 28.3% are in the risky group and the girls demonstrate higher depression level. Children and early adolescents of fathers - veterans of war with post-traumatic stress disorder show significant differences in competencies, behavior, emotional difficulties and neuroticism. Significant correlation was found between psychopathology of parents - fathers the veterans of war and their children. Impact of psychological conditions of fathers - the veterans of war with post-traumatic stress disorder to children is strong and they represent a significant risky group for development of mental disorders.


Local diagnostic reference levels for digital mammography: Two hospitals study in northwest, Nigeria.
Mammography involves the use of low energy X-rays to image the breast tissue. Although low dose radiation is used, the use of ionising radiation implies the risk of inducing breast cancer. Thus, the study established local DRLs for digital mammography for in-house dose optimisation. This was a retrospective study that had a total of 240 women that presented for mammography at the two tertiary institutions located in the Northwest region of Nigeria. Patient demographic information including compressed breast thickness (CBT), which is the breast tissue thickness across the imaging plate, and mean glandular dose (MGD) were recorded. Data were analysed based on descriptive and inferential statistics using SPSS statistical software. The DRLs based on MGD and CBT were established and compared with the relevant data in the literature. Local DRLs based on MGD and CBT were established at the 75th percentile (craniocaudal (CC): 1.50 mGy; 57 mm; mediolateral (MLO): 1.60 mGy; 63 mm) and 95th percentile (CC: 3.74 mGy; 69 mm; MLO: 3.61 mGy; 76 mm). The MGD based on manual exposure was significantly (p < 0.005) higher compared to the automatic optimisation parameter (AOP) mode which suggests the need to continuously adhere to the use of AOP mode for in-house dose optimisation. The study established local DRLs for the digital mammography systems at the 75th and 95th percentiles which compared well with the values established in the literature. Manual selection of parameters should only be employed where there are legitimate indications as it is associated with high exposure. Also, manual selection of parameters should be based on preset tables as a function of compressed breast thickness.


The translational value of rodent gastrointestinal functions: a cautionary tale.
Understanding relationships between gene complements and physiology is important, especially where major species-dependent differences are apparent. Molecular and functional differences between rodents (rats, mice, guinea pigs) and humans are increasingly reported. Recently, the motilin gene, which encodes a gastrointestinal hormone widely detected in mammals, was found to be absent in rodents where the receptors are pseudogenes; however, actions of motilin in rodents are sometimes observed. Although ghrelin shares common ancestry with motilin, major species-dependent abberations are not reported. The apparently specific absence of functional motilin in rodents is associated with specialised digestive physiology, including loss of ability to vomit; motilin is functional in mammals capable of vomiting. The exception is rabbit, the only other mammal unable to vomit, in which motilin might be conserved to regulate caecotrophy, another specialised digestive process. Motilin illustrates a need for caution when translating animal functions to humans. Nevertheless, motilin receptor agonists are under development as gastroprokinetic drugs.


Long-term chronic exposure to di-(2-ethylhexyl)-phthalate induces obesity via disruption of host lipid metabolism and gut microbiota in mice.
Numerous epidemiological findings have shown that di-(2-ethylhexyl)-phthalate (DEHP), one of industrial plasticizers with endocrine-disrupting properties, positively contributes to high incidence of obesity. However, potential pathogenesis of dietary DEHP exposure-induced obesity remains largely unknown. Chronic DEHP exposure at different doses (0.05 and 5 mg/kg body weight) to mice had been continuously lasted for 14 weeks through the diet. A combination of targeted quantitative metabolomics (LC/GC-MS) with global 1H NMR-based metabolic profiling to explore the effects of dietary DEHP exposure with different doses on host lipid metabolism of mice. Metagenomics (16S rRNA gene sequencing) was also employed to examine the alterations of gut microbiota composition in the cecal contents of mice after dietary DEHP exposure. Dietary exposure to DEHP at both doses induced weight gain and hepatic lipogenesis of mice by promoting the uptake of fatty acids and disrupting phospholipids and choline metabolism. Dietary DEHP exposure altered the gut microbiota community with disruption of intestinal morphology and reduction of Firmicutes to Bacteroidetes ratio in the cecal contents of mice. Furthermore, DEHP exposure activated gut microbiota fermentation process producing excess short chain fatty acids of mice. These findings provide systematic evidence that long-term chronic DEHP exposure induces obesity through disruption of host lipid metabolism and gut microbiota in mice, which not only confirm the epidemiological results, but also expand our understanding of metabolic diseases caused by environmental pollutants exposure.


Always returning: feedback and sensory processing in visual cortex and thalamus.
Feedback projections are an integral part of the mammalian visual system. Although it is tempting to relegate them to a subsidiary role in visual processing, because their supposed latency and lag might appear to be unfavourable for an involvement in fast processing, this is a dangerous simplification. Certainly for the world in motion, feedback from higher motion areas can influence the transfer of ascending input when, or even before, the input arrives. Here, we consider the circuit formed by layer 6 feedback cells in the visual cortex and how this straddles the retinothalamic and thalamocortical transfer of visual input. We discuss its links to feedback from the cortical motion area MT (V5), and suggest that motion perception involves a dynamic interplay between MT, V1 and the thalamus. This review is part of the TINS special issue on The Neural Substrates of Cognition.


Automatic eye localization for hospitalized infants and children using convolutional neural networks.
Reliable localization and tracking of the eye region in the pediatric hospital environment is a significant challenge for clinical decision support and patient monitoring applications. Existing work in eye localization achieves high performance on adult datasets but performs poorly in the busy pediatric hospital environment, where face appearance varies because of age, position and the presence of medical equipment. We developed two new datasets: a training dataset using public image data from internet searches, and a test dataset using 59 recordings of patients in a pediatric intensive care unit. We trained two eye localization models, using the Faster R-CNN algorithm to fine-tune a pre-trained ResNet base network, and evaluated them using the images from the pediatric ICU. The convolutional neural network trained with a combination of adult and child data achieved an 79.7% eye localization rate, significantly higher than the model trained on adult data alone. With additional pre-processing to equalize image contrast, the localization rate rises to 84%. The results demonstrate the potential of convolutional neural networks for eye localization and tracking in a pediatric ICU setting, even when training data is limited. We obtained significant performance gains by adding task-specific images to the training dataset, highlighting the need for custom models and datasets for specialized applications like pediatric patient monitoring. The moderate size of our added training dataset shows that it is feasible to develop an internal training dataset for clinical computer vision applications, and apply it with transfer learning to fine-tune existing pre-trained models.


[Changes in phenolic acids during maturation and lignification of Scots pine xylem].
The content and fractional composition of alcohol soluble phenolic acids (PhA) in cells with different degree maturation and lignification in the course of early and late timber formation in the pine (Pinus sylvestris) during vegetation were studied. Phenolic compounds (PhC), extracted by 80% ethanol, were divided into free and bound fractions of PhA. In turn, the esters and ethers were isolated from bound PhA. The contents of all substances were calculated per dry weight and per cell. Considerable differences have been found to exist in both the contents and the composition of the fractions PhA on successive stages oftracheid maturation of early and late xylem. Early timber tracheids at all secondary wall thickening steps contained PhC less and free PhA more than late timber tracheids. Throughout early timber tracheid maturation, the pool of free PhA per cell declined at the beginning oflignification and then increased gradually while that of bound PhA decreased. The maturation of late timber trecheids were accompanied by the rise of free PhA pool and the diminution of bound PhA pool. In the composition of bound PhA, the ethers were always dominant, and the amount of that in early timber cells was less than in late timber cells. The cells of early xylem at all steps of maturation contained more of ester. The sum total of free hydroxycinnamic acids, precursors of monolignols, gradually decreased during early xylem lignification as the result of the reduction of the pools of p-coumaric, caffeic, ferulic and synapic acids, while that of their ester rised. In the course of late xylem lignification, the pools of free p-coumaric, ferulic and, especially, synapic acids increased. Simultaneously, the amount of ferulic acid ester and synapic acid ether increased too. According to the data, lignin biosynthesis in early xylem and late xylem occurs with different dynamics and the structure of lignins of two xylem types might be different too.


Neurostructural differences associated with self-harm in youth bipolar disorder.
Youth with bipolar disorder (BD) are at greatly elevated risk for suicide. Self-harm, encompassing all self-injurious behaviors regardless of suicidal intent, is among one of the greatest risk factors for death by suicide. This study aims to extend the sparse literature regarding the neurostructural correlates of self-harm in youth with BD. Participants included 156 youth (17.14 ± 1.61 years): 38 BD with lifetime history of self-harm (BDSH+ ), 43 BD without history of self-harm (BDSH- ), and 75 healthy controls (HC). Measures of cortical thickness, surface area (SA), and volume were obtained using 3 T magnetic resonance imaging. Orbitofrontal and ventrolateral prefrontal cortices were examined in region-of-interest (ROI) analyses, complemented by exploratory vertex-wise analyses using a general linear model controlling for age, sex, and intracranial volume. In ROI analyses, there were no between-group differences after correction for multiple comparisons. Vertex-wise analysis revealed three significant clusters in precentral gyrus SA, inferior temporal gyrus SA, and caudal middle frontal gyrus volume. Post-hoc vertex-wise analyses showed BDSH+ had lower cortical SA and volume compared with both BDSH- and HC for all clusters. Significant vertex-wise findings were observed in frontotemporal regions relevant to BD and self-harm, with smaller neurostructural measures among BDSH+ compared with both BDSH- and HC. Future studies are needed to evaluate the temporal nature of the relationship of these neurostructural differences (i.e., potential risk indicators) to self-harm and to identify mechanisms underlying these findings.


Correction: Intratumoural-infiltrating CD4 + and FOXP3 + T cells as strong positive predictive markers for the prognosis of resectable colorectal cancer.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


FOLFIRINOX for locally advanced or metastatic pancreatic ductal adenocarcinoma: the Royal Marsden experience.
Pancreatic ductal adenocarcinoma (PDA) has a very poor prognosis. Treatment with FOLFIRINOX has been shown to improve outcomes, but can be associated with significant toxicity. A retrospective review was performed of all patients with locally advanced or metastatic PDA treated with FOLFIRINOX at the Royal Marsden between November 2010 and November 2013. Efficacy, tolerability, and potential prognostic factors were evaluated. Twenty-seven patients with metastatic PDA and 22 patients with locally advanced PDA were treated with FOLFIRINOX. Patients received a median of 9 cycles (range, 1-26) of FOLFIRINOX. The overall response rate was 41% (20 patients), and a further 17 patients (35%) had stable disease. Thirty-five patients (71%) received FOLFIRINOX in the first-line setting, with a median progression-free survival and overall survival, respectively, of 12.9 months and 18.4 months for patients with locally advanced disease; and 8.4 months and 12.2 months for patients with metastatic disease. The most frequently occurring Grade 3/4 toxicities were neutropenia (29%), fatigue (18%), febrile neutropenia (14%), thromboembolism (12%), and thrombocytopenia (10%). In a univariate analysis, reduction in CA 19-9 of >50% (P < .001), normalization of CA19-9 (P < .001), surgery after FOLFIRINOX (P = .004), and use of prophylactic pegfilgrastim (P = .005) were prognostic for overall survival. The efficacy and tolerability of FOLFIRINOX for PDA at our institution is similar to that reported in clinical trials. Careful selection of patients and monitoring of response (according to CA19-9) and toxicities can help maximize advantage in this patient population.


Two Cheers for Decentralisation: Unpacking Mechanisms, Politics and Accountability in the ICDS, Central India.
From long-term qualitative research this paper argues that Chhattisgarh's decentralised mechanisms in implementation of the Integrated Child Development Services (ICDS) foster increased stake of local communities and local politics, and that these work to enhance accountability and programme quality. A larger number of actors with financial interests in the scheme at the level of the sub-block ICDS 'sector' and down to the village leads to wider distribution of financial gains from delivery of ICDS Services, thereby increasing local competition and political interest from lower tiers of governance. Decentralised mechanisms work to enhance checks and balances via formal and informal routes to governance and accountability. Chhattisgarh's ICDS represents a 'hybrid model' between the short and long routes to accountability. While competing interests from local politics and institutions of governance work to improve ICDS accountability, they also work to appropriate the programme for political gain, or unfairly target ICDS workers. The paper unpacks mechanisms by which local politics relate with decentralised prescriptions in ICDS implementation. It gives the decentralised mechanisms a qualified two cheers.


Positional distribution of fatty acids in rabbit lung phospholipids and triacylglycerols and effect of prolonged hyperoxy.
Investigations have been carried out for the determination of the effect of high oxygen concentration in inspired gas mixutre on the positional distribution of fatty acids in rabbit lung phospholipids and triacylglycerols. The following results were obtained: 1. In the phosphatidylcholine fraction, the high oxygen concentration caused a quantitative increase of palmitic acid (16 : 0) at the alpha-position, and of myristic (14 : 0), heptadecenic (17 : 1) and arachidonic (20 : 4) acids at the beta-position. 2. In t-e phosphatidylethanolamine fraction, the high oxygen concentration caused an increase of oleic acid (18 : 1) at the alpha-position, and of palmitoleic (16 : 1) and heptadecenic (17 : 1) acids at the beta-position. 3. In the triacylglycerol fraction such changes were not observed. In connection with these effects of oxygen, its possible influence on membrane structures in the lung has been discussed.


Systemic inflammation with multiorgan dysfunction is the cause of death in murine ligation-induced acute pancreatitis.
We have previously shown that distal pancreatic duct ligation-induced acute pancreatitis in mice is associated with substantial mortality. We examined the cause of death in duct ligation-induced acute pancreatitis in mice by serial examination of multiple parameters in three experimental groups: distal pancreatic duct ligation (PD), bile duct ligation alone (BD), and sham operation (S). BD and S had no mortality, while PD had 94% mortality with most deaths between days 2 and 4. Characteristics of mice with acute pancreatitis included (ANOVA; p < 0.05): extracellular regulated kinase activation in the pancreas and lung; pancreatic neutrophil infiltration and acinar cell necrosis maximal on day 2; increased plasma cytokine and aspartate aminotransferase levels and bronchoalveolar lavage fluid neutrophil count and cytokine levels, peaked on day 3; hypotension and bradycardia were worst on day 4; pulmonary neutrophil infiltration and plasma creatinine level peaked on day 4. Liver injury evidenced by raised aspartate serum transaminase after hepatic obstruction was exacerbated by PD. Systemic inflammation with multiorgan dysfunction causes death in pancreatic duct ligation-induced acute pancreatitis in mice. This experimental model is a suitable experimental analogy of "early severe gallstone pancreatitis" to investigate disease pathogenesis and to evaluate novel therapeutic strategies.


A first-generation haplotype map (HapMap-1) of tea (Camellia sinensis L. O. Kuntz).
Tea is a cross-pollinated woody perennial plant, which is why, application of conventional breeding is limited for its genetic improvement. However, lack of the genome-wide high-density SNP markers and genome-wide haplotype information has greatly hampered the utilization of tea genetic resources toward fast-track tea breeding programs. To address this challenge, we have generated a first-generation haplotype map of tea (Tea HapMap-1). Out-crossing and highly heterozygous nature of tea plants, make them more complicated for DNA-level variant discovery. In this study, whole genome re-sequencing data of 369 tea genotypes were used to generate 2,334,564 biallelic SNPs and 1,447,985 InDels. Around 2928.04 million paired-end reads were used with an average mapping depth of ∼0.31× per accession. Identified polymorphic sites in this study will be useful in mapping the genomic regions responsible for important traits of tea. These resources lay the foundation for future research to understand the genetic diversity within tea germplasm and utilize genes that determine tea quality. This will further facilitate the understanding of tea genome evolution and tea metabolite pathways thus, offers an effective germplasm utilization for breeding the tea varieties. Supplementary data are available at Bioinformatics online.


The evaluation of Nesfatin-1 levels in patients with OSAS associated with metabolic syndrome.
The association of obstructive sleep apnea syndrome (OSAS) and metabolic syndrome (MS) has been demonstrated in studies and in recent years; the effect of OSAS on insulin resistance independent of the level of obesity is being investigated. Nesfatin-1 is a newly defined 82 amino acid protein with a precursor molecule of NUCB2 (nucleobindin 2). Nesfatin-1 is not only essential in regulation of food ingestion but also important in regulation of some brain functions, autonomic regulation, stress, mental state, and paradoxical sleep. We aimed to evaluate the relationship between OSAS and MS and the MS dependent or independent effect of Nesfatin-1 on this relationship. Patients admitted with clinical signs of OSAS are included. Patients are divided into three groups based on Apnea-Hypopnea Index (AHI) on Polysomnography (PSG) as mild, moderate, and severe OSAS. A total of 59 patients were included the control patients. Several OSAS parameters and laboratory findings which are and are not MS dependent are compared. Nesfatin-1 levels are evaluated in all OSAS patients with and without MS. There were significantly more males in all groups (p = 0.007). There was no significant difference between groups in terms of Nesfatin-1 levels. Nesfatin-1 levels were significantly lower in MS group compared to non-MS group (p = 0.021). Nesfatin-1 which is known to play a role in the pathophysiology of insulin resistance can be a beneficial target in developing new therapeutic targets for treatment of patients with obesity without any toxic effects in the future.


Ageotypes revisited: The brain and central nervous system dysfunction as a major nutritional and lifestyle target for healthy aging.
Undeniably, biological age can significantly differ between individuals of similar chronological age. Longitudinal, deep multi-omic profiling has recently enabled the identification of individuals with distinct aging phenotypes, termed 'ageotypes'. This effort has provided a plethora of data and new insights into the diverse molecular mechanisms presumed to drive aging. Translational opportunities stemming from this knowledge continue to evolve, providing an opportunity for the provision of nutritional interventions aiming to decelerate the aging process. In this framework, the contemporary ageotypes classification was revisited via in silico analyses, with the brain and nervous system being identified as the primary targets of age-related biomolecules, acting through inflammatory and metabolic pathways. Nutritional and lifestyle factors affecting these pathways in the brain and central nervous system that could help guide personalized recommendations for the attainment of healthy aging are discussed.


Re-use of water treatment works sludge to enhance particulate pollutant removal from sewage.
This paper attempted to study the feasibility of reusing water treatment works sludge ("alum sludge") to improve particulate pollutant removal from sewage. The main issues focused upon were: (1) the appropriate dosage of the alum sludge, (2) the appropriate operating conditions, and (3) the possible mechanisms for enhancement by adding alum sludge. Actual alum sludge and sewage were applied to a series of jar tests conducted under various conditions. It has been found that both the SS and COD removal efficiencies could be improved by the addition of the alum sludge, which was mainly attributed to the removal of relatively fine particles with a size of 48-200 microm. The appropriate dosage of the alum sludge was determined to be 18-20 mg of Al/L. Increasing the mixing speed or reducing the floc size of the alum sludge enhanced the SS and COD removal and the dispersed alum sludge could remove particulate contaminants with smaller size than the raw sewage. ToF-SIMS evidence revealed that the aluminum species at the surface of the alum sludge were effectively utilized for improving the SS and COD removal. It was postulated that the sweep flocculation and/or the physical adsorption might play key roles in the enhancement of particulate pollutant removal from sewage.


Use of propranolol to treat multicentric airway haemangioma.
To report our experience of using propranolol to treat an infantile airway haemangioma. A five-week-old girl presented with upper airway obstruction. Having started systemic steroids, concurrent propranolol therapy was commenced. Propranolol was given with close monitoring of the blood pressure, pulse and capillary glucose level. The dose of propranolol was gradually increased to 2 mg/kg total daily dose, with simultaneous reduction and withdrawal of steroids. Prior to propranolol treatment, laryngotracheobronchoscopy revealed an extensive haemangioma extending from the posterior pharyngeal wall to the subglottis. Following initiation of propranolol, a dramatic reduction in tumour bulk was seen on repeated laryngotracheobronchoscopy within 10 days of treatment. Eight months on, the patient remained asymptomatic on propranolol, with no endoscopic evidence of disease apart from mild telangiectasia. Haemangiomas of the airway can cause obstruction which may potentially be life-threatening. This case demonstrates the potential of propranolol to become a valuable therapeutic option in such clinical situations.


Limitations of universal newborn hearing screening in early identification of pediatric cochlear implant candidates.
To determine whether implementation of universal newborn hearing screening (UNHS) in the state of Illinois has affected the ages at diagnosis of hearing loss and implantation in children receiving cochlear implants and to determine how often children undergoing implantation had UNHS results with no indication of hearing loss (pass). Retrospective case review of 417 randomly selected pediatric implant recipients born before and after UNHS was mandated by law in Illinois. Data analyzed included hearing screening status, ages at initial diagnosis of sensorineural hearing loss (SNHL) and severe to profound SNHL, and age at implantation. Tertiary care medical center. Children receiving implants from 1991 through 2008. Ages at diagnosis of SNHL and implantation. Children born after legally mandated UNHS had significantly younger ages at diagnosis and implantation. However, a younger age at diagnosis of SNHL was not achieved in children who had passed UNHS or who were not screened. Approximately 30% of pediatric implant recipients passed UNHS, regardless of the cause of hearing loss or the presence or absence of known risk factors. Almost one-third of our pediatric implant recipients pass UNHS and are older at the time of initial diagnosis and implantation than their peers who fail UNHS. Delayed onset of SNHL limits our ability to achieve early diagnosis and implantation of a significant number of deaf children. This problem will not be solved by the current design of universal hearing screening programs.


An adaptive independence test for microbiome community data.
Advances in sequencing technologies and bioinformatics tools have vastly improved our ability to collect and analyze data from complex microbial communities. A major goal of microbiome studies is to correlate the overall microbiome composition with clinical or environmental variables. La Rosa et al. recently proposed a parametric test for comparing microbiome populations between two or more groups of subjects. However, this method is not applicable for testing the association between the community composition and a continuous variable. Although multivariate nonparametric methods based on permutations are widely used in ecology studies, they lack interpretability and can be inefficient for analyzing microbiome data. We consider the problem of testing for independence between the microbial community composition and a continuous or many-valued variable. By partitioning the range of the variable into a few slices, we formulate the problem as a problem of comparing multiple groups of microbiome samples, with each group indexed by a slice. To model multivariate and over-dispersed count data, we use the Dirichlet-multinomial distribution. We propose an adaptive likelihood-ratio test by learning a good partition or slicing scheme from the data. A dynamic programming algorithm is developed for numerical optimization. We demonstrate the superiority of the proposed test by numerically comparing it with that of La Rosa et al. and other popular approaches on the same topic including PERMANOVA, the distance covariance test, and the microbiome regression-based kernel association test. We further apply it to test the association of gut microbiome with age in three geographically distinct populations and show how the learned partition facilitates differential abundance analysis.


The binding of [3H]4-diphenylacetoxy-N-methylpiperidine methiodide to longitudinal ileal smooth muscle muscarinic receptors.
Muscarinic receptors present in longitudinal ileum were characterized using the non-selective radioligand [3H]N-methylscopolamine [( 3H]NMS) and the M3 selective radioligand [3H]4-diphenylacetoxy-N-methylpiperidine methiodide [( 3H]4DAMP). In saturation studies, [3H]4DAMP, but not [3H]NMS, identified two populations of binding sites with 17% of the sites (155 fmol/mg protein) displaying high affinity (Kd = 0.39 nM) for [3H]4DAMP and the remaining sites displaying low affinity for the radioligand (Kd = 4.43 nM). In competition studies gallamine and methoctramine, but not AF-DX 116, identified two populations of [3H]NMS binding sites. Affinity estimates for gallamine and methoctramine indicated that 80% of the [3H]NMS binding sites were of the M2 subtype. The minor population of [3H]NMS binding sites could not be readily characterized, due partly to the low selectivity of the competing ligands and also to the relatively low density of the sites. In studies using the M3 muscarinic receptor selective radioligand [3H]4DAMP, the minor population of sites could be preferentially labeled by using a low concentration (0.4 nM) of [3H]4DAMP. Under these conditions, [3H]4DAMP labeled approximately equal levels of the two muscarinic receptor binding sites present in the ileum. Competition studies with AF-DX 116, gallamine and methoctramine indicated that the two [3H]4DAMP binding sites displayed the pharmacology expected of the M2 and M3 receptors, respectively. These results provide additional evidence that longitudinal ileal smooth muscle membranes contain both M2 and M3 muscarinic receptors and indicate that [3H]4DAMP is a useful ligand for identifying heterogeneity of muscarinic receptor subtypes.


Lymph node ratio and pN staging show different superiority as prognostic predictors depending on the number of lymph nodes dissected in Chinese patients with luminal A breast cancer.
The lymph node ratio (LNR) classification has shown superiority to pN staging (the number of positive lymph nodes) in breast cancers, but it has not been examined according to whether sufficient lymph nodes have been dissected. All Chinese patients with luminal A breast cancer with positive lymph nodes seen at Sun Yat-sen University Cancer Center between 1995 and 2009 were enrolled. Disease-free survival (DFS) and overall survival (OS) were the endpoints, and the patients were further classified into 2 groups according to whether ≤ 10 or > 10 lymph nodes were dissected. For the whole group, the OS curves of the pN stages overlapped, whereas they were separated in the LNR survival curves. LNR was an independent prognostic factor for OS and DFS, whereas the pN stage was not. In the ≤ 10 lymph nodes dissected group, both OS and DFS curves were clearly separated in the pN staging but overlapped in the LNR classification. In the > 10 lymph nodes dissected group, LNR showed no overlap in the OS curves and was an independent prognostic factor of OS and DFS when compared with pN staging. In Chinese patients with luminal A breast cancer, LNR classification and the pN stage show different superiority as prognostic predictors according to whether > 10 or < 10 lymph nodes are dissected.


Escherichia coli mutants deficient in guanine-xanthine phosphoribosyltransferase.
We studied the purine phosphoribosyltransferases (PRTases) of Escherichia coli and were able to isolate a mutant that is defective in its ability to convert guanine and xanthine to their respective ribonucleotides. The affected gene (gpt) lies between metD and proA and is 78.6% co-transducible with proA. Both this point mutant and a strain with a pro-lac deletion contain less than 2% of wild-type xanthine PRTase activity, yet still contain about 30% of wild-type guanine PRTase activity. Thus, the gpt gene is only one of at least two genes responsible for guanine PRTase activity in E. coli.


Surface-mediated formation of PBDD/Fs from the high-temperature oxidation of 2-bromophenol on a CuO/silica surface.
As a model brominated hydrocarbon that may form brominated dioxins, we studied the surface-mediated, oxidative thermal degradation of 2-bromophenol on a supported copper oxide catalyst in a 1 mm i.d., fused silica flow reactor at a constant concentration of 90 ppm over a temperature range from 250 to 550 degrees C. Observed products included: dibenzo-p-dioxin (DD), 1-monobromodibenzo-p-dioxin (1-MBDD), dibromodibenzo-p-dioxin (DBDD), tribromodibenzo-p-dioxin (TrBDD), 4-monobromodibenzofuran (4-MBDF), 2,4,6-tribromophenol, 2,4- and 2,6-dibromophenol, and polybrominated benzenes. The results are compared and contrasted with previous work on surface catalyzed oxidative thermal degradation of 2-chlorophenol as well as our own work with the surface-catalyzed pyrolytic thermal degradation of 2-bromophenol. Typically 20 to 200x higher yields of PBDDs are observed for 2-bromophenol than for the analogous PCDDs for 2-chlorophenol. However the anticipated PBDF, 4,6-DBDF, was not observed and 4-MBDF was observed at very low yields. Surprisingly, the maximum yields of PBDDs were observed at higher temperatures than under pyrolytic conditions. This is attributed to regeneration of the catalytic surface due to the presence of oxygen. Higher yields of polybrominated phenols and polybrominated benzenes were also observed than for the analogous chlorinated phenols and benzenes from the oxidation of 2-chlorophenol. This can be attributed to the ease of bromination over chlorination based on the higher abundance of bromine atoms present for 2-bromophenol than chlorine atoms present for 2-chlorophenol.


Influence of fatigue loading on the performance of adhesive and nonadhesive luting cements for cast post-and-core buildups in maxillary premolars.
This study evaluated the influence of fatigue loading on the performance of an adhesive and a nonadhesive cement for cast post-and-core restorations in maxillary premolars. The adhesive cement used was Panavia 21, a resin-based composite cement, and the nonadhesive cement was PhosphaCem/C, a zinc-oxy-phosphate cement. The coronal sections of single-rooted human maxillary premolars were removed at the level of the proximal CEJ. After endodontic treatment, a cast post and core was prepared for each tooth and cemented into the root canal with either Panavia 21 (n = 8) or PhosphaCem/C (n = 8). Half of the specimens from each cement group were exposed to fatigue loading almost perpendicular to the axial axis; the other half were used as controls. Three parallel transverse root sections were cut from each specimen and used for evaluation of the influence of fatigue loading. For each section, cement integrity was studied by SEM, and retention strength of the cemented post section was determined with a push-out test. For SEM evaluation and the push-out test, Panavia 21 proved significantly better than PhosphaCem/C. However, fatigue loading did not show any effect. Under the conditions of this study, fatiguing of cemented cast post-and-core restorations was not decisive as a single test to evaluate the quality of the cement.


Value of transesophageal echocardiography combined with computed tomography for assessing repaired type A aortic dissection.
Thirty-two patients with repaired type A aortic dissection were examined by transthoracic echocardiography (TTE) (n = 32), transesophageal echocardiography (TEE) (n = 30), computed tomography (CT) (n = 29), or a combination of all 3, to assess course and complications as a function of the surgical procedure. The mean follow-up period was 55.7 months (range 3 to 132). Surgery consisted of a replacement of the ascending aorta in 25 patients (group 1) with extension to the transverse aorta in 7 (group 2). The transverse diameter of the aorta, the persistence of the false lumen, thrombus formation and flow dynamics in the false lumen were evaluated by TEE. Ten patients (31%) had a dilation in the initial ascending aorta (sinus of Valsalva aneurysm in 6 patients, and a false aneurysm in the other 4). Three of 4 patients with a proximal pseudoaneurysm underwent operation after TEE and CT evaluation. In the descending thoracic aorta, there was good agreement between TEE and CT scan determinations of transverse vessel diameter. Persistence of flow within the false lumen was significantly more frequent in patients with a dilated aorta (p < 0.05), whereas thrombosis was seen more often and false lumen less often in patients with nondilated aorta. No significant differences in vessel status or outcome were observed between the 2 groups, although this may have been due to the small size of group 2. TEE is thus a well-tolerated method for postoperative follow-up of type A aortic dissection whatever the type of surgery. For the upper ascending aorta, CT provided sufficient data.