Pharyngeal reconstruction using a U-shaped pectoralis major myocutaneous flap: an effective technique that should not be forgotten.
Although free tissue transfer is thought the best option for head and neck reconstruction, the pectoralis major myocutaneous flap (PMMCF) remains an important alternative method. The aim of this study was to assess the use of the PMMCF with the prevertebral fascia to close a pharyngeal defect. This was a retrospective study of 30 patients who underwent circumferential pharyngeal defect reconstruction with a U-shaped PMMCF from 2009 to 2018. The flap was primarily used to reconstruct defects after tumor extirpation. One patient (3.3%) died of an acute myocardial infarction within 24 h of the operation. Six cases (20.0%) developed a pharyngocutaneous fistula; one of them required debridement, while the others spontaneously healed with conservative treatment. Seven cases (23.3%) developed tracheal stomal stenosis. Twenty-four (80.0%) of these cases could eat a regular diet, while the other five cases needed tube feeding. In patients with late-stage laryngopharyngeal cancer, reconstructing circumferential pharyngeal defects with the U-shaped PMMCF is an expedient alternative to free tissue transfer.


Investing in a nest egg: intraspecific variation in the timing of egg laying across a latitudinal gradient.
Avian reproductive strategies vary widely, and many studies of life-history variation have focused on the incubation and hatching stages of nesting. Birds make proximate decisions regarding reproductive investment during the laying stage, and these decisions likely constrain and tradeoff with other traits and subsequent behaviors. However, we know relatively little about egg-laying stage behaviors given the difficulty of locating and monitoring nest sites from the onset of laying. We used non-invasive continuous video recording to quantify variation in the egg-laying behaviors of burrowing owls (Athene cunicularia) along a 1400-km latitudinal gradient in western North America. Burrowing owls laid eggs disproportionately in the morning hours, and that tendency was strongest among first eggs in a clutch. However, selection appeared to act more strongly on laying intervals (the time between laying of consecutive eggs) than on the diel time of laying, and laying intervals varied widely among and within clutches. Laying intervals declined seasonally and with increasing clutch size but increased with increasing burrow temperature and as a function of laying stage nest attentiveness, which may be a strategy to preserve egg viability. Laying interval was positively correlated with the duration of hatching intervals, suggesting that laying interval duration is one mechanism (along with timing of incubation onset) that generates variation in hatching asynchrony. Our results lend support to two general hypotheses to explain laying schedules; selection favors laying eggs in the morning, but other selective pressures may override that pattern. These conclusions indicate that allocation decisions during laying are an important part of avian life-history strategies which are subject to energetic constraints and tradeoffs with other traits.


The instrumented sheep knee to elucidate insights into osteoarthritis development and progression: A sensitive and reproducible platform for integrated research efforts.
Osteoarthritis of the knee is a very common condition that has been difficult to treat. The majority of cases are considered idiopathic. Much research effort remains focused on biology rather than the biomechanics of such joints. Some new methods were developed and validated to better appreciate the subtleties of the biomechanical integrity of joints, and how changes in biomechanics can contribute to osteoarthritis. Over the past 15 years our lab has enhanced the sensitivity of the assessment of knee biomechanics of an instrumented, trained large animal model (sheep) of osteoarthritis and integrated the findings with biological and histological assessments. These new methods include gait analysis before and after injury followed by robotic validation post-sacrifice, and more recently using Fibre Bragg Grating sensors to detect alterations in cartilage stresses. A review of the findings obtained with this model are presented. The findings indicate that sheep, like humans, exhibit individual characteristics. They also indicate that joint kinetics, rather than kinematics may better define the alterations induced by injury. With the addition of Fibre Bragg Grating sensors, it has been possible to measure with good accuracy, alterations to cartilage stresses following a controlled knee injury. Using this model as Proof of Concept, this sheep system can now be viewed as a sensitive platform to address many questions related to risk for development of idiopathic osteoarthritis of the human knee, the efficacy of potential interventions to correct biomechanical disruptions, and how joint biomechanics and biology are integrated during aging.


Exceptional abilities in autism: Theories and open questions.
The vast majority of research on autism spectrum disorder (ASD) focuses on characterizing and addressing the social communication deficits and restricted, repetitive patterns of behavior that constitute the diagnostic criteria for the disorder. Yet, a small but significant portion of individuals diagnosed with ASD exhibit exceptional cognitive abilities in one or more domains. These "twice-exceptional" individuals often have unique skills that enable them to make significant contributions to the workforce, while at the same time facing unique challenges during the transition to independent living due to a lack of services and broad public misperceptions regarding their condition. Here we review the current literature on cognitive divergence in ASD, focusing on cognitive theories, neural substrates, and clinical and societal implications for increasing understanding of this phenomenon.


Structural characterization of the N-linked carbohydrate chains from mouse zona pellucida glycoproteins ZP2 and ZP3.
N-linked oligosaccharides of mouse zona pellucida glycoproteins ZP2 and ZP3 were prepared as pyridylaminated derivatives. Anion-exchange HPLC revealed that 95% or more of them are acidic. About 80% of these acidic chains were neutralized by digestion with Arthrobacter ureafaciens sialidase and a small amount of sulfate was found in the residual acidic chains. The neutralized fractions (SN fractions) from ZP2 and ZP3 were similarly fractionated by size-fractionation HPLC into many peaks having different numbers of LacNAc in the non-reducing regions. The SN fractions from ZP2 were cleaved by endo-beta-galactosidase into the core and non-reducing regions. The tri- and tetra-antennary complex-type chains with a Fuc residue were predominant in the core region. On the other hand, four kinds of fragment containing the LacNAc sequence were obtained from the non-reducing region. Sialic acids were shown to be linked to the core fragments, as well as the non-reducing fragments. The N-linked oligosaccharides of ZP3 were suggested to have essentially the same structures as those of ZP2.


Mechanical behaviour of femoral prosthesis with various cross-section shape, implant configurations and material properties.
The maximum Von-Mises stress analysis introduced by dynamic body load on hip implant was considered in this research. The different hip stem shapes including elliptical, circular and oval cross sections with various configurations and material properties including that of Ti-6Al-4V, Co-Cr-Mo and SS316L alloys were simulated by 3D computational analysis to evaluate the "stress-shielding effect" on the implant surface. In order to categorise the various shapes and materials based on "stress-shielding effect", a factor called "stress distribution" (SD) was developed. Results showed that the highest Von-Mises stress levels are attributed to the elliptical cross-section, whereas oval cross-sections comprised the least figures with certain stem profiles. In terms of SD factor, titanium alloy with elliptical cross section indicated the lowest level, while the better results specified to the oval shape.


Psychiatric disorder in a South African general hospital. Prevalence in medical, surgical, and gynecological wards.
The aim was to elicit the individual and comparative prevalence of psychiatric disorder in medical, surgical, and gynecological wards in a South African hospital comprising a predominantly Third World patient population. Results indicated that 21%, 95% confidence interval (16;26) of the total sample of 230 patients had a DSM-III-R psychiatric disorder. Fifty-six percent had a diagnosis of substance dependence and 33% were found to have depressive disorders. Comparative analysis between disciplines indicated that the highest prevalence was in surgical wards. There was a statistically significant difference between the sexes. The variables associated with the presence of a psychiatric disorder and implications for better recognition and treatment are discussed.


The Escherichia coli ribosomal protein L11 suppresses release factor 2 but promotes the release factor 1 activities in peptide chain termination.
The incubation of the 50 S ribosomal subunits of Escherichia coli with 1.5 M LiCl yields 1.5c core particles depleted in 14 proteins and inactive in peptide chain termination. In codon-dependent peptidyl-tRNA hydrolysis the release factor 1 (RF-1)-induced reaction essentially depends on both L11 and L16 whereas the release factor 2 (RF-2)-induced reaction is depressed by L11 and stimulated by L16. Omission of L11 results in a several-fold increase in the specific activity of the RF-2. Functional complexes are formed with RF-2 at an apparent Km (dissociation constant) for the termination codon 5-fold lower than with reconstituted ribosomes containing L11; the Vmax for the hydrolysis is unchanged. L11 suppresses this effect when added to the core at close to molar equivalence. In contrast, RF-1 has a very low activity if ribosomes lack L11 and this can be restored by titration of L11 back to the core. This is the first example of a differential or an opposite effect of a ribosomal component on the activities of the two release factors, and the studies suggest that L11 has a critical role in the binding domain for the two factors.


Diaschisis Profiles in the Cerebellar Response to Hemodynamic Stimuli: Insights From Dynamic Measurement of Cerebrovascular Reactivity to Identify Occult and Transient Maxima.
Crossed cerebellar diaschisis (CCD) refers to depressions in perfusion and metabolism within the cerebellar hemisphere contralateral to supratentorial disease. Prior investigation into CCD in cerebrovascular reactivity (CVR) has been limited to terminal CVR estimations (CVRend ). We recently have demonstrated the presence of unsustained CVR maxima (CVRmax ) using dynamic CVR analysis, offering a fully dynamic characterization of CVR to hemodynamic stimuli. To investigate CCD in CVRmax from dynamic blood oxygen level-dependent (BOLD) MRI, by comparison with conventional CVRend estimation. Retrospective. A total of 23 patients (median age: 51 years, 10 females) with unilateral chronic steno-occlusive cerebrovascular disease, without prior knowledge of CCD status. A 3-T, T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) and acetazolamide-augmented BOLD imaging performed with a gradient-echo echo-planar imaging (EPI) sequence. A custom denoising pipeline was used to generate BOLD-CVR time signals. CVRend was established using the last minute of the BOLD response relative to the first-minute baseline. Following classification of healthy versus diseased cerebral hemispheres, CVRmax and CVRend were calculated for bilateral cerebral and cerebellar hemispheres. Three independent observers evaluated all data for the presence of CCD. Pearson correlations for comparing CVR across hemispheres, two-proportion Z-tests for comparing CCD prevalence, and Wilcoxon signed-rank tests for comparing median CVR. The level of statistical significance was set at P ≤ 0.05. CCD-related changes were observed on both CVRend and CVRmax maps, with all CCD+ cases identifiable by inspection of either map. Diseased cerebral and contralateral cerebellar hemispheric CVR correlations in CCD+ patients were stronger when using CVRend (r = 0.728) as compared to CVRmax (r = 0.676). CVR correlations between healthy cerebral hemispheres and contralateral cerebellar hemispheres were stronger for CVRmax (r = 0.739) than for CVRend (r = 0.705). CCD-related alterations could be observed in CVR examinations. Conventional CVRend may underestimate CVR and could exaggerate CCD. 4. Stage 3.


The effect of face patch microstimulation on perception of faces and objects.
What is the range of stimuli encoded by face-selective regions of the brain? We asked how electrical microstimulation of face patches in macaque inferotemporal cortex affects perception of faces and objects. We found that microstimulation strongly distorted face percepts and that this effect depended on precise targeting to the center of face patches. While microstimulation had no effect on the percept of many non-face objects, it did affect the percept of some, including non-face objects whose shape is consistent with a face (for example, apples) as well as somewhat facelike abstract images (for example, cartoon houses). Microstimulation even perturbed the percept of certain objects that did not activate the stimulated face patch at all. Overall, these results indicate that representation of facial identity is localized to face patches, but activity in these patches can also affect perception of face-compatible non-face objects, including objects normally represented in other parts of inferotemporal cortex.


Development and Use of Cellular Systems to Assess and Correct Splicing Defects.
A significant proportion of mutations underlying genetic disorders affect pre-mRNA splicing, generally causing partial or total skipping of exons, and/or inclusion of pseudoexons. These changes often lead to the formation of aberrant transcripts that can induce nonsense-mediated decay, and a subsequent lack of functional protein. For some genetic disorders, including inherited retinal diseases (IRDs), reproducing splicing dynamics in vitro is a challenge due to the specific environment provided by, e.g. the retinal tissue, cells of which cannot be easily obtained and/or cultured. Here, we describe how to engineer splicing vectors, validate the reliability and reproducibility of alternative cellular systems, assess pre-mRNA splicing defects involved in IRD, and finally correct those by using antisense oligonucleotide-based strategies.


Fast-track recovery program after cardiac surgery in a teaching hospital: a quality improvement initiative.
Fast-track cardiac anesthesia (FTCA) is a technique that may improve patient access to surgery and maximize workforce utilization. However, feasibility and factors impacting FTCA implementation remain poorly explored both locally and internationally. We describe the specific intraoperative and postoperative protocols for our FTCA program, assess protocol compliance and identify reasons for FTCA failure. We tested the program in 16 patients undergoing elective cardiac surgery requiring cardiopulmonary bypass. There was 100% compliance with the FTCA protocols. Four (25%) patients successfully completed the FTCA protocol (extubated < 4 h postoperatively and discharged from the intensive care unit on the same operative day).


Alterations in seminal plasma proteomic profile in men with primary and secondary infertility.
Proteome of seminal plasma provides profound information related to the male reproductive health. This pilot study was conducted to characterize proteomic profile of seminal plasma from men with primary, or secondary infertility and compare it with proven fertile men. Study participants (n = 59) were recruited at the Cleveland Clinic and divided according to their fertility status: proven fertile (n = 39); primary infertility (n = 11) and secondary infertility (n = 9). Proteomic shotgun analysis revealed a total of 515 peptides common to primary infertility and control group; whereas 523 peptides were common to secondary infertility and control group. Bioinformatic analysis revealed dysregulation of biological processes such as cell secretion and vesicle mediated transport in primary infertility, whereas immune system response, regulation of proteolysis and iron homeostasis were dysregulated in secondary infertility. Western blot validation showed overexpression of ANXA2 and CDC42, and underexpression of SEMG2 proteins in primary infertility; and overexpression of ANXA2 and APP proteins in secondary infertility. This study elucidates the potential role of differentially expressed proteins in the seminal plasma as diagnostic biomarker for primary and secondary infertility. Furthermore, our results suggest maturation failure and immune reaction response as the main cause of infertility in men with primary and secondary infertility, respectively. Additional validation of the proteins involved in the above pathways is warranted.


The prevalence of and risk factors for non-carious cervical lesions in adults in Hubei Province, China.
To describe the prevalence of non-carious cervical lesions (NCCLs) and to assess the relative affects of risk factors on NCCLs in middle-aged and elderly people in Hubei Province, China. A sample of 2,160 adults, aged 35-44 years and 65-74 years and balanced by age, gender, and urbanization, participated in the cross sectional epidemiological survey. Non-carious cervical lesions were examined using a modified Tooth Wear Index. Data were collected based on structured questionnaires that assessed general information as well as oral health. The prevalence of non-carious cervical lesions was 38.8% for 35-44-year-olds and 56.6% for 65-74-year-olds. The first premolars, canines, and second premolars showed the highest prevalence of lesions, while the second molars demonstrated the least. Several risk factors such as age (OR = 2.45, p < 0.001), location (OR = 1.68, p = 0.001), frequency of toothbrushing (OR = 1.33, p = 0.016), bruxism (OR = 1.37, p < 0.001), and family income (OR = 1.44, p < 0.001) were found to be associated with lesion occurrence. The prevalence of non-carious cervical lesions was relatively high in the middle-aged and elderly persons in China and was also associated with socio-behavioural risk factors.


Self-report vs. laboratory measures of aggression as predictors of substance abuse.
Measures of aggressive behavior, antisocial personality, criminality, and impulsivity were obtained on a sample of 85 drug abusing volunteers for studies at the Addiction Research Center in Baltimore. Measures included the Buss-Durkee Hostility Inventory, Diagnostic Interview Schedule Antisocial Personality Disorder diagnosis, Elliott-Huizinga Lifetime Events Scale, Eysenck's Impulsiveness-Venturesomeness-Empathy scales, and a laboratory measure of aggression patterned after the Buss 'aggression machine'. All of the self-report measures of aggression and antisocial personality were moderately correlated with each other, but did not correlate with the laboratory aggression measure. This laboratory measure, nevertheless, made a significant contribution to the prediction of certain substance abuse diagnoses over and above the contributions of the other measures.


Acute kidney injury predicts poor left ventricular function for patients with peripartum cardiomyopathy.
The aim of this study was to explore the risk factors associated with a poor left ventricular (LV) function among patients with peripartum cardiomyopathy (PPCM) and to determine the influence of acute kidney injury (AKI) on the LV function of the patients. Sixty patients with PPCM were recruited between January 2007 and June 2018, among which 11 had AKI. The participants were divided into two groups, the recovery group (32 cases) and the nonrecovery group (28 cases), with their clinical features, echocardiography and electrocardiogram findings, laboratory results, and treatments compared between groups. We further determined the risk factors associated with nonrecovery and the influence posed by AKI on the LV function of the patients. Compared with the patients in the recovery group, those in the nonrecovery group had higher proportions of multiparity [78.6% (22/28) vs. 43.8% (14/32)], function class III- IV heart failure [92.9% (26/28) vs. 71.9% (23/32)], and a higher incidence of AKI [35.7% (10/28) vs. 3.1% (1/32)]. Logistic regression analysis showed that having AKI [odds ratio (OR): 10.556; 95% confidence interval (CI) 1.177-94.654; P = 0.035] and left ventricular ejection fraction (LVEF) < 40% [OR: 4.533; 95% CI 1.118-18.382; P = 0.034] were independently associated with nonrecovery of PPCM. The prognosis of patients with PPCM and AKI during hospitalization was poor compared to those without AKI; therefore, clinicians should pay more attention to this phenomenon.


A prospective, randomized, double-masked trial to evaluate the role of topical anesthetics in controlling pain after photorefractive keratectomy.
To investigate the role of 1% tetracaine in controlling pain after photo-refractive keratectomy (PRK) and determining its effect, if any, on epithelial healing, refractive outcome, and visual performance. In this study, 44 patients were randomized to receive either Gutt. 1% tetracaine or placebo after undergoing PRK. Drops were instilled at 30-minute intervals during waking hours for 24 hours postoperatively. In addition, all patients received two coproxamol (paracetamol + dextropropoxyphene) tablets every 6 hours for 2 days. Visual Analogue Pain Charts were used to record pain levels for 4 days after surgery. Serial digitized retro-illumination photography was used to assess rates of epithelial healing, and surface epithelial quality was monitored using topography. At fixed intervals over a 6-month period visual performance was assessed by measuring refractive outcome, best-corrected visual acuity, objective haze, halo, and glare. Patients in the tetracaine group had significantly less pain (P < 0.0001). Both groups demonstrated full epithelial closure within 72 hours. Similar numbers of patients in both groups at 1 week showed topographic irregularity that completely resolved by 1 month. No statistically significant difference was seen in any of the parameters monitoring visual performance. Tetracaine in conjunction with coproxamol is effective in reducing pain after PRK without adversely affecting corneal wound healing or visual performance.


Human Pluripotent Stem Cell-Derived Kidney Organoids with Improved Collecting Duct Maturation and Injury Modeling.
Maximizing the potential of human kidney organoids for drug testing and regenerative medicine and to model development and disease requires addressing cell immaturity, the lack of a mature collecting system, and off-target cell types. By independently generating two kidney progenitor cell populations-metanephric mesenchyme and ureteric bud (UB)-like cells-we could generate kidney organoids with a collecting system. We also identify the hormones aldosterone and arginine vasopressin (AVP) as critical to promote differentiation of collecting duct cell types including both principal cells (PCs) and intercalated cells (ICs). The resulting PCs express aquaporin-2 (AQP2) protein, which undergoes translocation to the apical membrane after vasopressin or forskolin stimulation. By single-cell RNA sequencing (scRNA-seq), we demonstrate improved proximal tubule maturation and reduced off-target cell populations. We also show appropriate downregulation of progenitor cell types, improved modeling of tubular injury, the presence of urothelium (Uro), and the ability of Notch pathway modulation to regulate PC:IC ratios during organoid development.


A systematic review of medical science students' knowledge and related factors towards burns first aids.
This systematic review aims to examine the knowledge of medical science students about burn first aid. A comprehensive, systematic search was performed in different international electronic databases, such as Scopus, PubMed, Web of Science, and Persian electronic databases such as Iranmedex, and Scientific Information Database (SID) using keywords extracted from Medical Subject Headings such as "Knowledge", "First aid", "Medical science student" and "Burn" from the earliest to February 1, 2023. The quality of the studies included in this systematic review was evaluated by using the appraisal tool for cross-sectional studies (AXIS tool). Thirteen studies had a total of 5046 students studying medical sciences. Among them, 62.24% were female and 77.67% were medical students. The studies included in this systematic review were conducted in Saudi Arabia, Pakistan, Syria, Egypt, and Malaysia. Medical science students' average knowledge of first aid for burns is 56.92 out of 100, which is considered to be a moderate level of knowledge. Factors such as the experience of first aid training, academic year, clinical experience, and economic status had a significant positive relationship with the knowledge of medical science students about first aid for burns. Also, factors such as age, academic specialisation, academic year, information sources, and fathers' occupation had a significant relationship with the knowledge of medical students about first aid for burns. Therefore, it is suggested that healthcare managers and policymakers make the necessary plans to ensure that first aid training courses are implemented during medical science students' studies as a part of their curriculum.


Caries Status and Salivary Alterations of Type-1 Diabetes Mellitus in Children and Adolescents: A Systematic Review and Meta-analysis.
The association between dental caries, salivary alterations, and type-1 diabetes mellitus (D1TM) remains inconclusive in children and adolescents. This systematic review evaluated the caries status and salivary alterations of children and adolescents suffering from D1TM. Meta-analysis searched from 5 electronic databases was performed considering the decay-missing-filled teeth (DMFT), decay-missing-filled surfaces, and decay-missing-filled primary teeth (dmft) index for caries and the stimulated flow rate, unstimulated flow rate, and buffering capacity for salivary alterations. Quality assessments were performed using the Healthcare Research and Quality Agency. Eleven studies satisfied the eligibility criteria. The meta-analysis revealed that DMF(T) (0.61; 95% confidence interval [CI], 0.14-1.08, P = .01) and dmft (-0.43; 95% CI, -0.71 to -0.15, P = .002) were significantly higher in D1TM group than the non-D1TM group. Stimulated flow rate (-0.40; 95% CI, -0.57 to -0.23, P < .00001) was significantly lower in D1TM group than in the non-D1TM group. No significant differences in decay-missing-filled surfaces and the buffering capacity were observed between the D1TM and the non-D1TM groups. The level of DMF(T) and dmft was higher in children/adolescents with D1TM than that with non-D1TM, and the salivary flow could be considered decreased with D1TM. The strength of the evidence of the studies analyzed, however, was deemed to be moderate and low.


Phosphorylated l-caldesmon is involved in disassembly of actin stress fibers and postmitotic spreading.
The function of the ubiquitous actin-binding protein, caldesmon (l-CaD) in mammalian non-muscle cells remains elusive. During mitosis, l-CaD becomes markedly phosphorylated at Ser497 and Ser527 (in the rat sequence), therefore, it has been suggested that l-CaD is involved in cytokinesis by inhibiting the actomyosin interaction until it is phosphorylated, although direct in vivo evidence is still missing. In the present study, we used F-actin staining and specific antibodies against these two phosphorylation sites of l-CaD to simultaneously monitor actin assembly and l-CaD phosphorylation. Our observations demonstrated that the level of l-CaD phosphorylation undergoes dynamic changes during the cell cycle. The spatial and temporal distributions of phospho-CaD do not correlate with cytokinesis per se, but rather, with the level of actin bundles in a reciprocal manner. The highest l-CaD phosphorylation level coincides with the disassembly of actin cytoskeleton during mitotic cell rounding. Ser-to-Ala mutations at these two positions prevent stress fibers from disassembly upon migratory stimulation. In addition, phospho-CaD appears to colocalize with nascent focal adhesion complexes during postmitotic spreading. These findings suggest that l-CaD phosphorylation plays an important role not only in cytoskeleton remodeling during cell shape changes, but also in cell spreading and migration.


Comparison of bioprosthetic and mechanical valve replacement for active endocarditis.
The choice between bioprosthetic or mechanical prosthetic valve replacement for active valvular endocarditis has been controversial. To establish the role of each, we reviewed the case histories of 185 patients who underwent valve replacement for active valvular endocarditis during the past 5 years. All patients had life-threatening, active bacterial endocarditis of a native or prosthetic valve. Group I (88 patients) had replacement with the Ionescu-Shiley pericardial valve and Group II (97 patients) with the St. Jude Medical valve. The male/female distribution, age range, and functional classification were the same in the two groups. Mean follow-up was approximately 20 months for both groups. Valve replacement was done because of native valve endocarditis in 76 patients in Group I and 49 patients in Group II. Of the remainder of the Group I patients, six had endocarditis of a bioprosthesis and six of a mechanical valve; of the remainder of Group II patients, 30 had endocarditis of a bioprosthesis and 18 of a mechanical valve. Early mortality was not significantly different between the two groups (14 deaths in each group). Of the 74 survivors in Group I, 15 underwent valve reoperation, 10 because of recurrent endocarditis and five because of sterile perivalvular leakage. The frequency of reoperation was significantly different (p less than 0.01) from that in Group II, in which only five patients underwent valve reoperation, four for recurrent endocarditis and one for sterile perivalvular leakage. The actuarial rate for freedom from reoperation was also significantly higher in Group II patients; 94.6% were free from reoperation at 4 years compared to 75% at 4 years in Group I patients (p less than 0.01). The actuarial survival rate, which also differed significantly between groups, was 78.7% at 4 years in Group I and 87.4% at 4 years in Group II (p less than 0.05). Patients receiving a bioprosthesis for active endocarditis had a significantly higher reoperation rate and a significantly greater incidence of recurrent endocarditis (p less than 0.01). Therefore, we prefer to use a mechanical valve for valve replacement in most patients who have active endocarditis.


Functional variants in cytochrome b5 type A (CYB5A) are enriched in Southwest American Indian individuals and associate with obesity.
This study aimed to identify genetic variants enriched in Southwest American Indian (SWAI) individuals that associate with BMI. Whole genome sequencing data (n = 296) were used to identify potentially functional variants that are common in SWAI individuals (minor allele frequency ≥10%) but rare in other ethnic groups (minor allele frequency < 0.1%). Enriched variants were tested for association with BMI in 5,870 SWAI individuals. One variant was studied using a luciferase reporter, and haplotypes that included this variant were analyzed for association with various measures of obesity (n = 917-5,870), 24-hour energy expenditure (24-h EE; n = 419), and skeletal muscle biopsy expression data (n = 207). A 5' untranslated region variant in cytochrome b5 type A (CYB5A), rs548402150, met the enrichment criteria and associated with increased BMI (β = 2%, p = 0.004). Functionally, rs548402150 decreased luciferase expression by 30% (p = 0.003) and correlated with decreased skeletal muscle CYB5A expression (β = -0.5 SD, p = 0.0008). Combining rs548402150 with two splicing quantitative trait loci in CYB5A identified a haplotype carried almost exclusively in SWAI individuals that associated with increased BMI (β = 3%, p = 0.0003) and decreased CYB5A expression, whereas the most common haplotype in all ethnic groups associated with lower BMI and percentage of body fatness, increased 24-h EE, and increased CYB5A expression. Further studies on the effects of CYB5A on 24-h EE and BMI may provide insights into obesity-related physiology.


The "Transport Specificity Ratio": a structure-function tool to search the protein fold for loci that control transition state stability in membrane transport catalysis.
In establishing structure-function relationships for membrane transport proteins, the interpretation of phenotypic changes can be problematic, owing to uncertainties in protein expression levels, sub-cellular localization, and protein-folding fidelity. A dual-label competitive transport assay called "Transport Specificity Ratio" (TSR) analysis has been developed that is simple to perform, and circumvents the "expression problem," providing a reliable TSR phenotype (a constant) for comparison to other transporters. Using the Escherichia coli GABA (4-aminobutyrate) permease (GabP) as a model carrier, it is demonstrated that the TSR phenotype is largely independent of assay conditions, exhibiting: (i) indifference to the particular substrate concentrations used, (ii) indifference to extreme changes (40-fold) in transporter expression level, and within broad limits (iii) indifference to assay duration. The theoretical underpinnings of TSR analysis predict all of the above observations, supporting that TSR has (i) applicability in the analysis of membrane transport, and (ii) particular utility in the face of incomplete information on protein expression levels and initial reaction rate intervals (e.g., in high-throughput screening situations). The TSR was used to identify gab permease (GabP) variants that exhibit relative changes in catalytic specificity (kcat/Km) for [14C]GABA (4-aminobutyrate) versus [3H]NA (nipecotic acid). The TSR phenotype is an easily measured constant that reflects innate molecular properties of the transition state, and provides a reliable index of the difference in catalytic specificity that a carrier exhibits toward a particular pair of substrates. A change in the TSR phenotype, called a Delta(TSR), represents a specificity shift attributable to underlying changes in the intrinsic substrate binding energy (DeltaGb) that translocation catalysts rely upon to decrease activation energy (Delta G(T)(++). TSR analysis is therefore a structure-function tool that enables parsimonious scanning for positions in the protein fold that couple to the transition state, creating stability and thereby serving as functional determinants of catalytic power (efficiency, or specificity).


In vitro cytotoxicity of organic pollutants to bluegill sunfish (BF-2) cells.
BF-2 cells, an established cell line derived from bluegill sunfish, (Lepomis macrochirus), were exposed to 18 organic toxicants, with cytotoxicity being assayed by the neutral red (NR) technique. Based on the concentration of toxicant that reduced lysosomal uptake of neutral red by 50% (NR50), the rank order of cytotoxicity was methyl mercury greater than pentachlorophenol greater than 2,3,5,6-tetrachlorophenol greater than 2,3,5-trichlorophenol greater than 2,3-dinitrotoluene greater than 2,4,6-trichlorophenol greater than 2,4-dichlorophenol greater than 2,4-dichlorotoluene greater than 6-chloro-3-hydroxytoluene greater than o-chlorotoluene greater than 4-chlorophenol greater than 2-chlorophenol, 2,4-dimethylphenol greater than 2,4-dinitrophenol greater than 4-nitrophenol greater than 3-methylphenol greater than phenol greater than toluene. Published in vivo LC50 values were identified for 11 of the 18 test agents and, with the exception of 2,4-dinitrophenol, there was a good correlation between the in vitro cytotoxicity of the test agents and their in vivo waterborne acute toxocity. The potencies of the substituted phenolics and chlorinated toluenes as determined by the in vitro cytotoxicity assay correlated strongly with their log octanol/water partition coefficients (log P). However, the toxicity of 2,3-dinitrotoluene in vitro, and apparently also in vivo, was not a function of its log P value.


Can Co-Grazing Waterfowl Reduce Brainworm Risk for Goats Browsing in Natural Areas?
Goats browsing in woodlands, whether for livestock production goals or vegetation management (e.g., targeted grazing to control invasive plants), are at risk of meningeal worm (Parelaphostrongylus tenuis) infection. Indeed, up to 25% incidence has been observed in goats employed in vegetation management. Infection, which occurs via the consumption of an infected gastropod intermediate host, is potentially deadly in goats. We experimentally tested whether co-grazing with waterfowl could reduce goats' exposure via waterfowl consumption of gastropods. Gastropods were sampled in a deciduous woodland before and after the addition of goats alone, goats and waterfowl, or a control with no animal addition. We found that goats browsing on their own increased the abundance of P. tenuis intermediate hosts; however, when goats co-grazed with waterfowl, these increases were not observed. Importantly, waterfowl did not significantly affect overall gastropod abundance, richness, or diversity. Thus, waterfowl co-grazing may effectively reduce goat contact with infectious gastropods without detrimentally affecting the gastropod community. While co-grazing goats with waterfowl may decrease their P. tenuis exposure risk, additional research is needed to confirm whether waterfowl can actually lower P. tenuis incidence.


Rarely seen infections.
There are many rare cutaneous infections of the face. This phrase seems irrelevant, because rare infections in certain parts of the world are common in others. This is more apparent if applied to different sites of the body (eg, face). For instance, cutaneous leishmaniasis (CL) is common in Central and South America and uncommon in the United States. Because most medical practitioners in this country have never seen a case, it is easy for them to miss a diagnosis. Cutaneous leishmaniasis, a protozoan infection transmitted by phlebotomine sand flies, is typically divided into two forms: one found in the Middle East, Asia, Africa, and southern Europe, called Old World leishmaniasis, and one found in Latin and Central America, called New World leishmaniasis. Also atypical mycobacterial infection has been described in the medical literature since the mid-1950s. The development and introduction of a rapid radiometric mycobacterial detection system has advanced the field of mycobacteriology over the past 20 years. This method has allowed the distinction of Mycobacterium tuberculosis from other mycobacteria and enabled the performance of antimicrobial susceptibility testing of mycobacteria. The increased frequency of atypical mycobacterial infection stems from advances in the diagnostic procedures concerning the infection paired with the prevalence of mycobacterial disease in immunocompromised patients infected with HIV. Erysipelas and facial cellulitis are covered briefly in this paper.


Hypoxia signaling in renal pericytes-is it safe to activate?
While excitement has grown for the use of hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors for treating renal anemia, multiple preclinical studies have shown the complex and cell-type-dependent roles of HIFs in kidney disease pathogenesis, including renal fibrosis. Pan et al. now clearly show that activating the HIF signaling in the Gli1-lineage myofibroblasts restores erythropoietin production while not adversely affecting matrix production, mitigating the concerns of exacerbated fibrosis by HIF prolyl hydroxylase inhibitors.


Factors affecting composition and thermostability of mengovirus virions.
The composition of mengovirus virions produced by infected cells varies with the incubation temperature. Virons produced at 37.0 or 39.5 degrees contain four major polypeptides (alpha, beta, gamma, and delta) and one minor polypeptide (beta'). Virons produced at 31.5 degrees C contain two additional polypeptides (D1 and E). The virions of two temperature-sensitive (ts) and thermolabile mutants of mengovirus (ts25 and ts88) contain an increased amount of polypeptide beta', with a corresponding decrease in polypeptide beta when compared with the wild-type mengovirus.


Lipid analysis of the response of a sedimentary microbial community to polycyclic aromatic hydrocarbons.
Polycyclic aromatic hydrocarbons (PAH) are widespread environmental contaminants that can, under proper conditions, be degraded by microorganisms. The responses of a riverine sedimentary microbial community to PAH contamination were examined using an integrated biochemical assay that yielded data on PAH concentration, total microbial biomass, and microbial community structure and were interpreted using perturbation theory and the subsidy-stress gradient. Microbial mineralization of naphthalene, anthracene, fluorene, and phenanthrene was observed 24 h after their addition to all sediments sampled and ranged from 0.9 to 16.3% in ambient sediments and from 14.8 to 35.8% in contaminated sediments. Total microbial biomass, determined by phospholipid phosphate, increased in response to intermediate PAH concentration and decreased at sites with the highest PAH concentration (p < 0.05) during seven out of nine (78%) seasonal sampling periods. The two sampling periods that were not statistically different followed periods of high water and cold temperatures. Phospholipid fatty acid analysis of microbial community structure analysis indicated that increases in the relative abundance of gram-negative aerobes and heterotrophic eukaryotes were responsible, in part, for these observed increases in total microbial biomass. These findings (increased degradation rates, increased biomass at intermediate PAH concentrations, and altered community structure) indicate that a component of the microbial community responded to PAH as a usable input and are consistent with the predictions of perturbation theory and a subsidy-stress gradient.


Morphology of the interaction of collagen fibrils with normal human platelets and thrombasthenic platelets.
The ultrastructure of the platelet contacts with collagen fibrils (CF) as well as the course taken by CF on the platelet surface were studied on ultrathin sections of platelets and CF. Platelets from normal donors and from a patient with thrombasthenia were incubated in citrated plasma with collagen. For electron microscopy a protein-stabilizing fixation procedure was applied. Platelet-collagen contacts (PCC) are characterized by a distance of 7 +/- 3 nm between the platelet membrane and the CF; the gap contains electron-dense bridges. The PCC of normal and thrombasthenic platelets are morphologically identical. Hence, it is unlikely that the glycoproteins IIb/IIIa-complex, which is absent in thrombasthenic platelets, plays a significant role in the platelet collagen interaction. The CF induce random movements of the platelets and their pseudopods, whereby the fibrils, which often show multisite attachment, coil up around the platelet surface; they become bent and often display drastic directional changes. CF are found inside invaginations of the platelet membrane as well as in depressions of the platelet surface. These processes require an involvement of the platelet's contractile system, which appears to interact reversibly with the platelet plasma membrane.


Mast Cell Activation During Suspected Perioperative Hypersensitivity: A Need for Paired Samples Analysis.
Perioperative hypersensitivity (POH) reactions constitute a significant clinical and diagnostic challenge. A transient increase in serum tryptase during POH reflects mast cell activation (MCA) and helps to recognize an underlying hypersensitivity mechanism. To determine the diagnostic performance of different tryptase decision thresholds based on single and paired measurements to document MCA in suspected POH. Acute serum tryptase (aST) and baseline serum tryptase (bST) samples were obtained from patients referred to our outpatients clinic because of clinical POH. Tryptase samples from controls were obtained before induction (Tt0) and 1.5 hours after induction (Tt1) in uneventful anesthesia. Different cutoff points for tryptase increase over bST and the percentage increase in tryptase (%T) were calculated and compared with existing thresholds: aST > [1.2 × (bST) + 2] (consensus formula), aST higher than 11.4 ng/mL, and aST higher than 14 ng/mL. Patients with POH had higher bST and aST levels compared with controls (respectively 5.15 vs 2.28 ng/mL for bST and 20.30 vs 1.92 ng/mL for aST). The consensus formula and a tryptase increase over bST of greater than or equal to 3.2 ng/mL held the highest accuracies to document MCA in POH (respectively 81% and 82%). A bST of higher than 8 ng/mL was present in 4% of controls, 5% of patients with grade 1 POH, 24% of patients with grade 2 POH, 15% of patients with grade 3 POH, and 17% of patients with grade 4 POH. Our data endorse the consensus formula for detection of MCA in POH. Furthermore, it shows that a bST of higher than 8 ng/mL was associated with occurrence of anaphylaxis.


Ethical and methodological challenges slowing progress in primary care-based suicide prevention: Illustrations from a randomized controlled trial and guidance for future research.
Despite the pressing need for primary care-based suicide prevention initiatives and growing acknowledgement of recruitment difficulties and Institutional Review Board (IRB) challenges in suicide research, we are aware of no illustrative examples describing how IRB decisions in the design of a primary care trial can compound recruitment challenges. The CDC-funded trial (NCT02986113) of Men and Providers Preventing Suicide aimed to examine the effects of a tailored computer program encourage men with suicidal thoughts (n = 304, ages 35-64) to discuss suicide with a primary care clinician and accept treatment. Before a visit, participants viewed MAPS or a non-tailored control video. Post-visit, both arms were offered telephone collaborative care, as mandated by the institutional review board (IRB). We previously showed that exposure to MAPs led to improvements in communication about suicide in a primary care visit. In this paper, we report data on the study's primary outcome, suicide preparatory behaviors. After screening nearly 4100 men, 48 enrolled. Recruitment challenges, which were exacerabted by an IRB mandate narrowing post-intervention patient management differences between trial arms, limited detection of the effects of MAPS on suicide preparatory behaviors. While primary care settings are key sites for suicide prevention trials, issues such as recruitment difficulties and overly restrictive IRB requirements may limit their utility. Methodological innovation to improve recruitment and ethical guidance to inform IRB decision-making are needed.


[The effect of alpha/beta and gamma interferon preparations on the functional activity of macrophages in experimental staphylococcal infections].
The preparations of alpha/beta- and gamma-interferons have been shown to stimulate the functional activity characteristics of mouse macrophages (phagocytosis, spreading, contacts with lymphocytes, bactericidal properties) obtained from the peritoneal exudate of intact animals and those infected with staphylococci. The immunomodulating action of gamma-interferon is more pronounced than that of the preparation of alpha/beta-interferon.


[Pilot study on pain response patterns in chronic low back pain. The influence of pain response patterns on quality of life, pain intensity and disability].
The variables pain intensity (SI), disability (DS) and quality of life (QoL) belong to a set of primary patient-based outcomes in chronic low back pain (CLBP). The avoidance-endurance model (AEM) assumes three maladaptive and one adaptive pain response pattern. The purpose of this study was to study the level and course of the outcomes with regard to the four AEM patterns. A total of 52 CLBP inpatients were investigated at 2 points in time: during the first days after admission and 6 months after the acute exacerbation of pain. Differences between AEM patterns were analyzed with repeated measurement analyses of variance. Groups differences were found for SI (F((3, 48))=2.82, p<0.05), general (F((3, 48))=6.78, p<0.05) and health-related QoL (F((3, 48))=5.99, p <0.05). In contrast, for the variable disability only a significant time effect was found. The results show differences in the level and process of SI, DS and QoL between the subgroups. An AEM-based classification of subgroups is also reasonable for CLPB patients.


Genomics approaches to synthesize plant-based biomolecules for therapeutic applications to combat SARS-CoV-2.
COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is devastative to the humankind for which neither vaccines nor precise therapeutic molecules for treatment are identified. The search for new drugs and repurposing of existing drugs are being performed; however, at the same time, research on plants to identify novel therapeutic compounds or testing the existing ones is progressing at a slower phase. In this context, genomics and biotechnology offer various tools and strategies to manipulate plants for producing those complex biopharmaceutical products. This review enumerates the scope for research on plant-based molecules for their potential application in treating SARS-CoV-2 infection. Strategies to edit gene and genome, overexpression and silencing approaches, and molecular breeding for producing target biomolecules in the plant system are discussed in detail. Altogether, the present review provides a roadmap for expediting research on using plants as a novel source of active biomolecules having therapeutic applications.


DRESS syndrome with fatal results induced by sodium valproate in a patient with brucellosis and a positive cytoplasmic antineutrophilic cytoplasmic antibody test result.
DRESS syndrome is a life-threatening adverse reaction characterized by skin rashes, fever, leukocytosis with eosinophilia or atypical lymphocytosis, lymph node enlargement, and liver or renal dysfunctions. DRESS syndrome related to valproic acid use is very rarely observed. We present a case of DRESS syndrome induced by sodium valproate, which developed and progressed fatally in a brucellosis patient with a positive c-ANCA test. A 19-year-old female patient presented with fever, cough, jaundice, and rash all over her body. Brucella Coombs test was positive at 1:1280 titers, and the Rose Bengal test was also positive. The involuntary movements were thought to be due to chorea, and the patient was started on sodium valproate 500 mg 2 1, as well as streptomycin 1 g flk 1 1 and tetradox capsules 2 1 for the brucellosis and was discharged. DRESS syndrome was suspected in the patient, and she was taken off sodium valproate and tetradox; N-acetylcysteine, ceftriaxon, prednizolone, and support treatment were started. When sodium valproate is used on its own, it carries no risk of inducing DRESS syndrome. However, in the case presented, another co-morbidity such as brucellosis and c-ANCA positivity was present. We believe that the presence of further co morbidity not yet reported in literature is important from the perspective of the risk of valproate-induced DRESS syndrome. Therefore, if sodium valproate treatment is to be started in patients, especially those with co morbidity, they must be closely monitored with clinical and laboratory observations. At the slightest suspicion of DRESS syndrome, all medication should be ceased immediately and the patient should be placed under continuous observation.


A systematic review and dose-response meta-analysis of sleep duration and the occurrence of cognitive disorders.
Previous researches have shown inconsistent findings on the relationship between sleep duration and cognitive disorders (including cognitive decline, dementia, Alzheimer's disease, and cognitive impairment). Furthermore, the possible dose-response association of sleep duration and cognitive disorders is still not clear. Two databases (PubMed and Embase) were searched for relevant studies from inception to May 4, 2016. We used the generic inverse-variance method to combine the outcomes with a random-effects model for the association between sleep duration (the shortest or longest vs. middle category) and cognitive disorders. Additionally, we used the generalized least-squares trend estimation model to estimate the potential dose-response association. Finally, nine eligible cohort studies involving 22,187 participants were included in the present systematic review and meta-analysis. Compared with the middle category, both short and long sleep duration were accompanied by a significantly higher incident risk of cognitive disorders, and the relative risks (RRs) and 95% confidence intervals (CIs) were 1.34 (1.15, 1.56) and 1.21 (1.06, 1.39), respectively. Moreover, an approximately "U-shaped" dose-response relationship was observed. Stratified analyses showed that the association between short sleep duration and cognitive disorders was more robust in the subgroup of the measurement of sleep duration based on self-report. The lowest incident risk of cognitive disorders was found at the sleep duration of 7-8 h per day. The present study includes a small number of studies, and the study participants mostly consist of Caucasian population. In the future, researches are also warranted to confirm the association in different groups of people.


The Role of Dopamine Agonists in Pituitary Adenomas.
Dopamine agonist therapy is the primary therapy for prolactin-secreting adenomas and usually results in normoprolactinemia, eugonadism, and tumor reduction. Cabergoline is superior to bromocriptine with regard to efficacy and tolerance. Withdrawal of cabergoline can be attempted in patients with normal prolactin levels on low doses of medication and evidence of radiographic tumor involution. Dopamine agonists have been used off label in patients with acromegaly, Cushing disease, and nonfunctioning adenomas. A trial of cabergoline monotherapy can be effective in patients with biochemically mild acromegaly. Cabergoline combination with somatostatin receptor ligands or pegvisomant improves insulin-like growth factor level 1 in majority of patients.


Predictive importance of the visceral adiposity index and atherogenic index of plasma of all-cause and cardiovascular disease mortality in middle-aged and elderly Lithuanian population.
Two indices: visceral adiposity index (VAI) and atherogenic index of plasma (AIP) during several recent years were implemented into epidemiological studies for predicting of cardiovascular diseases (CVD) and mortality risk. Our study aimed to evaluate the association of VAI and AIP with the risk of all-cause and CVD mortality among the Lithuanian urban population aged 45-72 years. In the baseline survey (2006-2008), 7,115 men and women 45-72 years of age were examined within the framework of the international study Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE). Six thousand six hundred and seventy-one participants (3,663 women and 3,008 men) were available for statistical analysis (after excluding 429 respondents with the missed information on study variables) and for them, VAI and AIP were calculated. The questionnaire evaluated lifestyle behaviors, including smoking and physical activity. All participants in the baseline survey were followed up for all-cause and CVD mortality events until December 31st, 2020. Multivariable Cox regression models were applied for statistical data analysis. After accounting for several potential confounders, higher levels of VAI (compared 5th quintile to 1st quintile) were associated with significantly higher CVD mortality in men [Hazards ratio (HR) = 1.38] and all-cause mortality in women (HR = 1.54) after 10-year follow-up. CVD mortality significantly increased in men with 0 the highest AIP quintile compared with that for the lowest quintile (HR = 1.40). In women, all-cause mortality was significantly higher for the 4th quintile of AIP as compared with the 1st quintile (HR = 1.36). High-risk VAI levels were statistically significantly associated with all-cause mortality risk in men and women groups. The higher AIP level (5th quintile vs. 1st quintile-in men and 4th quintile vs. 1st quintile-in women) was significantly associated with increased mortality from CVD in the men group and increased all-cause mortality in the women group.


Improving Broadband White-Light Emission Performances of 2D Perovskites by Subtly Regulating Organic Cations.
Recently, 2D organic-inorganic hybrid lead halide perovskites have attracted intensive attention in solid-state luminescence fields such as single-component white-light emitters, and rational optimization of the photoluminescence (PL) performance through accurate structural-design strategies is still significant. Herein, by carefully choosing homologous aliphatic amines as templates, isotypical perovskites [DMEDA]PbCl4 (1, DMEDA=N,N-dimethylethylenediamine) and [DMPDA]PbCl4 (2, DMPDA=N,N-dimethyl-1,3-diaminopropane) having tunable and stable broadband bluish white emission properties were rationally designed. The subtle regulation of organic cations leads to a higher degree of distortion of the 2D [PbCl4 ]2- layers and enhanced photoluminescence quantum efficiencies (<1 % for 1 and 4.9 % for 2). The broadband light emissions could be ascribed to self-trapped excitons on the basis of structural characterization, time-resolved PL, temperature-dependent PL emission, and theoretical calculations. This work gives a new guidance to rationally optimize the PL properties of low-dimensional halide perovskites and affords a platform to probe the structure-property relationship.


Risk of incomplete pyloromyotomy and mucosal perforation in open and laparoscopic pyloromyotomy.
Despite randomized controlled trials and meta-analyses, it remains unclear whether laparoscopic pyloromyotomy (LP) carries a higher risk of incomplete pyloromyotomy and mucosal perforation compared with open pyloromyotomy (OP). Multicenter study of all pyloromyotomies (May 2007-December 2010) at nine high-volume institutions. The effect of laparoscopy on the procedure-related complications of incomplete pyloromyotomy and mucosal perforation was determined using binomial logistic regression adjusting for differences among centers. Data relating to 2830 pyloromyotomies (1802 [64%] LP) were analyzed. There were 24 cases of incomplete pyloromyotomy; 3 in the open group (0.29%) and 21 in the laparoscopic group (1.16%). There were 18 cases of mucosal perforation; 3 in the open group (0.29%) and 15 in the laparoscopic group (0.83%). The regression model demonstrated that LP was a marginally significant predictor of incomplete pyloromyotomy (adjusted difference 0.87% [95% CI 0.006-4.083]; P=0.046) but not of mucosal perforation (adjusted difference 0.56% [95% CI -0.096 to 3.365]; P=0.153). Trainees performed a similar proportion of each procedure (laparoscopic 82.6% vs. open 80.3%; P=0.2) and grade of primary operator did not affect the rate of either complication. This is one of the largest series of pyloromyotomy ever reported. Although laparoscopy is associated with a statistically significant increase in the risk of incomplete pyloromyotomy, the effect size is small and of questionable clinical relevance. Both OP and LP are associated with low rates of mucosal perforation and incomplete pyloromyotomy in specialist centers, whether trainee or consultant surgeons perform the procedure.


[Carcinoids of pancreas and digestion canal clinical signs, diagnostics and surgical treatment].
The review of the literature is presented and results of diagnostics and treatment of 28 patients with carcinoid tumours of the digestion canal of various localization are analysed. Carcinoids were both hormone-active, and hormone-inactive. Before the operation the diagnosis of carcinoid syndrome has been established only for two patients. Carcinoid tumours of a liver were in 4 patients, a gall bladder - in 1, a pancreas - in 5, a stomach - in 1, a duodenum - in 1. Results of methods of laboratory and instrumental examination are given and corresponding conclusions are made.


Correlations between cyclooxygenase-2 expression and angiogenic factors in primary tumors and liver metastases in colorectal cancer.
Angiogenesis is required for growth and metastasis of colorectal cancer (CRC), and several positive regulators of tumor angiogenesis have been identified. Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing angiogenic factors. The aim of this study was to clarify the levels and evaluate the relationships of COX-2, vascular endothelial growth factor A and C, thymidine phosphorylase (TP) and microvascular density (MVD) in paired tissue specimens between primary CRC and corresponding metastatic liver cancer. Tissue samples from pairs of primary tumors and corresponding metastatic liver tumors from 44 patients with CRC were immunohistochemically evaluated for COX-2, VEGF-A, VEGF-C, TP and MVD. The primary and corresponding metastatic liver tumors tended to show concordant immunoreactivity for COX-2 (P = 0.005, rs = 0.428), VEGF-A (P = 0.039, rs = 0.314), TP (P = 0.005, rs = 0.422) and MVD (P = 0.046, rs = 0.304) by Spearman rank test. The rate of COX-2 immunoreactivity was higher in liver metastases than in primary tumors (P = 0.002), while the rate of VEGF-A was higher in primary tumors than in liver metastases (P = 0.0004). The incidence of TP immunoreactivity and the level of MVD did not differ between primary and metastatic liver tumors (P = 0.247; P = 0.229). Significant correlations were found between COX-2 immunoreactivity and VEGF-A immunoreactivity in metastatic liver tumors (P = 0.033) as well as in primary tumors (P = 0.008). The positive correlations between COX-2, VEGF-A, TP and MVD in primary CRC and liver metastasis as demonstrated here will help to predict the angiogenic activity of liver metastasis by analyzing primary tumors, allowing for individualized cancer treatment options.


[The challenges and contributions of digital technology to improve the performance of the health system].
The digital transformation is already under way in our health system. The deployment of data-driven management and artificial intelligence supports the transition towards treatment methods oriented more towards chronic diseases. Understanding the ethical issues associated with this transformation is a key priority for the future of our health system.


A new species of Rheumatobates Bergroth (Hemiptera: Heteroptera: Gerridae) from mangroves of the Colombian Caribbean region, new records, and a key to species recorded from the country.
Rheumatobates urabaensis sp. nov. (Gerridae: Rhagadotarsinae) is described from a mangrove of the Colombian Caribbean region. R. urabaensis sp. nov. is differentiated from other species of the genus by features of the male antennae, fore legs, and genitalia. New distribution records are presented for R. bergrothi Meinert, R. crassifemur esakii Schroeder, and R. spinosus Hungerford. A key to the species of Rheumatobates from Colombia is also provided.


Human lymph node immune dynamics as driver of vaccine efficacy: an understudied aspect of immune responses.
During the last century, changes in hygiene, sanitation, and the advent of childhood vaccination have resulted in profound reductions in mortality from infectious diseases. Despite this success, infectious diseases remain an enigmatic public health threat, where effective vaccines for influenza, human immunodeficiency virus (HIV), tuberculosis, and malaria, among others remain elusive. In addition to the immune evasion tactics employed by complex pathogens, our understanding of immunopathogenesis and the development of effective vaccines is also complexified by the inherent variability of human immune responses. Lymph nodes (LNs) are the anatomical sites where B cell responses develop. An important, but understudied component of immune response complexity is variation in LN immune dynamics and in particular variation in germinal center follicular helper T cells (Tfh) and B cells which can be impacted by genetic variation, aging, the microbiome and chronic infection. We describe the contribution of genetic variation, aging, microbiome and chronic infection on LN immune dynamics and associated Tfh responses and offers perspective on how inclusion of LN immune subset and cytoarchitecture analyses, along with peripheral blood biomarkers can supplement systems vaccinology or immunology approaches for the development of vaccines or other interventions to prevent infectious diseases.


Case of fulminant giant-cell myocarditis associated with polymyositis, treated with a biventricular assist device and subsequent heart transplantation.
Giant-cell myocarditis is an autoimmune myocarditis that rapidly progresses to heart failure, and is often associated ventricular tachycardia. We describe an otherwise healthy patient who was acutely ill with decompensated heart failure and ventricular tachycardia associated with rash and polymyositis, who then developed cardiogenic shock and multiorgan failure due to giant-cell myocarditis.


Hypertonic saline solution stimulated CLC-3 production in primary cultured human nasal epithelial cells.
To determine the molecular mechanisms of hypertonic saline on nasal disorders. Primary human nasal epithelial cells (HNECs) were treated with 0.9 and 3% saline for 12h. CLC-3 was detected in HNECs by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. Positive expression of CLC-3 was detected in HNECs in all subjects by immunohistochemistry. The relative density of CLC-3 mRNA was 0.22+/-0.09 and 0.12+/-0.05 in HNECs treated with 3 and 0.9% saline, respectively. The effect of 3% saline on the expression of CLC-3 in HNECs was observed in a time-dependent manner. Hypertonic saline decreases the nasal edema and influences the mucocilliary function through the fluid secretion in vitro and may be associated with the upregulation of CLC-3.


Worry about COVID-19 contagion and general anxiety: Moderation and mediation effects of cognitive emotion regulation.
The global pandemic caused by coronavirus disease 2019 (COVID-19) occasioned that most of the population in Spain was confined to home to reduce the risk of contagion. This affected mental health, increasing anxiety and worry about COVID-19 contagion. The aim of this study was assessing the moderation and mediation effect of cognitive emotion regulation strategies (CERS) on general anxiety and whether the mediation effect was moderated by gender and/or age. A total of 1753 Spanish adults (78,6% female; M = 40.4 years, SD = 12.9) participated in an online survey that was available from March 26 to April 25 (2020) during the time period in which the population in Spain was confined. Participants completed measures of worry about COVID-19 contagion, the Cognitive Emotion Regulation Questionnaire-Short (CERQ-Short) and the Generalized Anxiety Disorder-7 (GAD-7). Several models were tested through structural equation modelling. Moderation analyses reported that maladaptive strategies moderated positively anxiety, whereas adaptive strategies moderated negatively anxiety. Also, the best fitted mediation model found that worry about COVID-19 contagion and general anxiety was mediated by CERS in different directions. Maladaptive CERS increased anxiety, whereas adaptive CERS reduced anxiety. Age (not gender) also moderated this mediation, were younger adults presented an indirect effect only through maladaptive CERS, but older adults through both adaptive and maladaptive. Limitations are related to the study design which was a convenience sample. CERS moderated and mediated between worry about COVID-19 contagion and general anxiety. Prevention programs for mental health problems during the pandemic must be provided, especially for younger adults.


Melanocortin 4 receptor antagonists attenuates morphine antinociceptive tolerance, astroglial activation and cytokines expression in the spinal cord of rat.
Chronic use of morphine is accompanied by the development of morphine tolerance, which is one of the major problems associated with opiate treatment. Experimental evidence indicates that melanocortin 4 receptor (MC4R) is involved in development of morphine tolerance. Therefore, we investigated the influence of repeated intrathecal injection of a MC4R antagonist (HS014) on the development of morphine tolerance as measured by hot-plate test. It was also examined whether a single i.t. HS014 administration could counteract the loss of analgesic potency of morphine in morphine tolerant rats. We examined also the influence of i.t. HS014 administration on astrocytes activation and cytokines expression in the spinal cord of rat during morphine tolerance. Morphine treatment (10mg/kg, i.p. twice daily) over 5 days induced tolerance as reflected by a significant reduction of withdrawal latency from 29.67±1.81s to 8.67±1.70s in the hot-plate test. Repeated coadministration of HS014 and morphine, significantly prevented the development of morphine tolerance. A single administration of an MC4R antagonist restored morphine analgesic potency in morphine tolerant rats. Using immunohistochemical staining, we demonstrated the administration of MC4R during the induction of morphine tolerance inhibited the activation of astrocytes; reduced the expression of proinflammatory cytokines interleukin-1β, IL-6, and tumor necrosis factor-α; upregulated the expression of anti-inflammatory cytokines IL-10 at the L5 lumbar spinal cord. These results suggest that MC4R may be involved in the mechanisms of morphine tolerance and antagonists of this receptor may be a possible new target in the search for strategies preventing the development of morphine tolerance.


About Your Child's Eating: factor structure and psychometric properties of a feeding relationship measure.
Conducted exploratory and confirmatory factor analysis of the About Your Child's Eating (AYCE) inventory with 763 parents. Parent subjects were drawn from a community study of families with physically healthy and chronically ill children between 8 and 16 years of age. Three correlated factors were identified: Child Resistance to Eating, Positive Mealtime Environment, and Parent Aversion to Mealtime. The internal consistency of the factors remained satisfactory across all examined demographic subgroups. Evidence for convergent validity was found by comparing the AYCE factors to higher order factors of the Family Environment Scale. Empirically derived clinical range cut-off scores are presented. Results support the AYCE as a psychometrically sound measure of the parent-child feeding relationship for school-aged children.


3D printing restorative materials using a stereolithographic technique: a systematic review.
To present through a systematic review a qualitative analysis of studies published on stereolithography-based 3D printing of restorative materials and their clinical applicability. The literature search was conducted based on the question: "What is the state-of-the-art of available restorative materials for 3D printing based on stereolithography?" Online search was conducted in three databases (MEDLINE/PubMed, Scopus and Web of Science) with no restriction for year of publication. Data are reported based on PRISMA, including publication details such as authors and their countries, year and journal of publication, and study design. The synthesis is focused on describing the dental restorative materials and properties evaluated, applied methods, 3D printers used and clinical applicability. Studies that fit the inclusion criteria were performed in Asia (21), Europe (16) and USA (10), mostly using polymer-based restorative materials (38) for 3D printing constructs. Stereolithographic-printed ceramic-based restorative structures were evaluated by 9 studies. Many studies reported on dimensional accuracy (14), strength (11) and surface morphology (9) of the printed structures. Antibacterial response, cytotoxicity, internal and marginal fit, fracture and wear resistance, density, viscosity, elastic modulus, hardness, structural shrinkage and reliability, degree of conversion, layer cure depth, fatigue, and color were also evaluated by the included studies. Many of them (11) published a proof of concept as an attempt to demonstrate the clinical feasibility and applicability of the technology to print restorative materials, but only 5 studies actually applied the 3D printed restorative structures in patients, which highlights an increasing interest but limited early-stage translation. The fast expansion of stereolithographic-based 3D printing has been impressive and represents a great technological progress with significant disruptive potential. Dentistry has demonstrated an incredible willingness to adapt materials, methods and workflows to this promising digital technology. However, esthetic appearance, wear resistance, wet strength and dimensional accuracy are the main current clinical limitations restricting the progression to functional part production with 3D printing, which may explain the absence of clinical trials and reports on permanent/definitive dental restorative materials and structures.


Successful return to work after burnout: an evaluation of job, person- and private-related burnout determinants as determinants of return-to-work quality after sick leave for burnout.
Burnout literature has primarily studied determinants and rehabilitation. Remarkably, ways to enable qualitative return to work after burnout are considered considerably less and were studied here. Specifically, building on the Job Demands-Resources model and Effort-Recovery model, this study investigated determinants of the quality of return to work. Hierarchical regression analyses were conducted to evaluate the quality of reintegration among 786 workers who were surveyed about their return to work after a burnout episode. Restarting work at a new employer and especially getting supervisor support appeared beneficial, whereas remaining burnout symptoms, stressors in one's private environment and - mostly - neuroticism hampered the quality of return to work. Given the high prevalence and important costs burnout entails, primary prevention alone proves insufficient. Current study findings inform on how to optimize the quality of reintegration in the workplace after a burnout episode, demonstrating that supportive managers and inclusive workplaces (i.e., open to hire applicants with a burnout history) are important levers for qualitative return to work, next to ensuring workers are not (so much) impaired by their burnout rest symptoms.Implications for RehabilitationReintegration trajectories after burnout should not only be evaluated by sick leave duration but also by the clients' subjective experience of quality of return to work.Rehabilitation professionals should ensure clients prepare return to work early so they return timely and are not (so much) impaired by their burnout rest symptoms.Rehabilitation professionals should propose reorientation towards a new employer in case of irreversible work ability problems at the current workplace.The clients' current work situation should allow for sufficient supervisor social support.Also stressors in private life (like divorce) and personality characteristics (like neuroticism) should be considered as they may hamper quality of return to work.


The RNA-mediated estrogen receptor α interactome of hormone-dependent human breast cancer cell nuclei.
Estrogen Receptor alpha (ERα) is a ligand-inducible transcription factor that mediates estrogen signaling in hormone-responsive cells, where it controls key cellular functions by assembling in gene-regulatory multiprotein complexes. For this reason, interaction proteomics has been shown to represent a useful tool to investigate the molecular mechanisms underlying ERα action in target cells. RNAs have emerged as bridging molecules, involved in both assembly and activity of transcription regulatory protein complexes. By applying Tandem Affinity Purification (TAP) coupled to mass spectrometry (MS) before and after RNase digestion in vitro, we generated a dataset of nuclear ERα molecular partners whose association with the receptor involves RNAs. These data provide a useful resource to elucidate the combined role of nuclear RNAs and the proteins identified here in ERα signaling to the genome in breast cancer and other cell types.


Adherence to self-glucose monitoring recommendations and perinatal outcomes in pregnancies complicated by diabetes mellitus.
Self-glucose monitoring is critical for the management of diabetes mellitus in pregnancy; yet, validated reports of adherence to testing recommendations and associated perinatal outcomes are limited. Using cloud-based, self-glucose monitoring technology, we sought to answer the following questions: (1) Are there differences in the rates of testing adherence based on type of diabetes mellitus in pregnancy? (2) Is adherence to glucose monitoring recommendations associated with perinatal outcomes in pregnancies that are complicated by diabetes mellitus? We hypothesized that adherence to glucose testing recommendations varies by type of diabetes mellitus and that increased adherence to testing recommendations would be associated with improved perinatal outcomes. This single-center, prospective cohort study included women with type 2 diabetes mellitus and gestational diabetes mellitus who were enrolled in a perinatal diabetes program at <29 weeks gestation between December 2015 and June 2018. All women received a cellular-enabled glucometer that uploaded glucose values to a cloud-based, Health Insurance Portability and Accountability Act-compliant platform in real time that ensured transmission of accurate glucose values. The primary outcome was adherence to self-glucose monitoring recommendations. Four glucose checks were advised daily, and percentage of adherence was calculated. Secondary outcomes were preeclampsia, cesarean delivery, large-for-gestational-age neonates, and neonatal hypoglycemia. The study was powered to detect a 10% difference in the primary outcome of adherence to advised self-glucose monitoring by diabetes mellitus type. Adjusted risk ratios and 95% confidence intervals were generated with the use of logistic regression. This study included 103 eligible women. Baseline characteristics differed between groups, with women with type 2 diabetes mellitus having higher initial HgbA1c and body mass index when compared with women with gestational diabetes mellitus. No differences were noted in age or parity. Adherence was calculated over 20±6 weeks for women with type 2 diabetes mellitus compared with 9±4 weeks for women with gestational diabetes mellitus. Overall adherence to glucose monitoring was significantly less for women with type 2 diabetes mellitus compared with those with gestational diabetes mellitus. Mean testing adherence rates were 51%, 66%, and 70% for type 2 diabetes mellitus, and gestational diabetes mellitus, class A1 and A2, respectively (P=.016). We found that, for every 10% increase in adherence to testing recommendations, the odds of cesarean delivery, neonatal hypoglycemia, and large-for-gestational-age fetuses decreases by 15-20%. There was no association between adherence and rates of preeclampsia. This study shows that overall adherence to testing recommendations differs by diabetes mellitus type and is associated with neonatal outcomes. Improved outcomes with higher adherence may reflect more timely medication adjustments in response to real-time glucose values. Programs aimed at improving adherence could prove beneficial.


Adverse events related to colonic endoscopic mucosal resection and polypectomy.
Colonoscopy is a commonly performed procedure. The rate of adverse events is 2.8 per 1000 screening colonoscopies. These adverse events include cardiovascular and pulmonary events, abdominal pain, hemorrhage, perforation, postpolypectomy syndrome, infection, and death. Serious adverse events, such as hemorrhage and perforation, occur most frequently when colonoscopy is performed with polypectomy. This article highlights the prevention and management of adverse events associated with polypectomy and endoscopic mucosal resection of colonic lesions.


Visual Evoked Potentials as an Early-Stage Biomarker in the rTg4510 Tauopathy Mouse Model.
Tauopathies such as Alzheimer's disease (AD) and frontotemporal dementia (FTD) are characterized by formation of neurofibrillary tangles consisting of hyperphosphorylated tau protein. Early pathophysiological and functional changes related to neurofibrillary tangles formation are considered to occur prior to extensive neurodegeneration. Hyperphosphorylated tau has been detected in postmortem retinas of AD and FTD patients, and the visual pathway is an easily accessible system in a clinical setting. Hence, assessment of the visual function may offer the potential to detect consequences of early tau pathology in patients. The aim of this study was to evaluate visual function in a tauopathy mouse model in relation to tau hyperphosphorylation and neurodegeneration. In this study we explored the association between the visual system and functional consequences of tau pathology progression using a tauopathy rTg4510 mouse model. To this end, we recorded full-field electroretinography and visual evoked potentials in anesthetized and awake states at different ages. While retinal function remained mostly intact within all the age groups investigated, we detected significant changes in amplitudes of visual evoked potential responses in young rTg4510 mice exhibiting early tau pathology prior to neurodegeneration. These functional alterations in the visual cortex were positively correlated with pathological tau levels. Our findings suggest that visual processing could be useful as a novel electrophysiological biomarker for early stages of tauopathy.


Identification and characterization of critical genes associated with tamoxifen resistance in breast cancer.
Tamoxifen resistance in breast cancer is an unsolved problem in clinical practice. The aim of this study was to determine the potential mechanisms of tamoxifen resistance through bioinformatics analysis. Gene expression profiles of tamoxifen-resistant MCF-7/TR and MCF-7 cells were acquired from the Gene Expression Omnibus dataset GSE26459, and differentially expressed genes (DEGs) were detected with R software. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was generated, and we analyzed hub genes in the network with the Search Tool for the Retrieval of Interacting Genes database. Finally, we used siRNAs to silence the target genes and conducted the MTS assay. We identified 865 DEGs, 399 of which were upregulated. GO analysis indicated that most genes are related to telomere organization, extracellular exosomes, and binding-related items for protein heterodimerization. PPI network construction revealed that the top 10 hub genes-ACLY, HSPD1, PFAS, GART, TXN, HSPH1, HSPE1, IRAS, TRAP1, and ATIC-might be associated with tamoxifen resistance. Consistently, RT-qPCR analysis indicated that the expression of these 10 genes was increased in MCF-7/TR cells comparing with MCF-7 cells. Four hub genes (TXN, HSPD1, HSPH1 and ATIC) were related to overall survival in patients who accepted tamoxifen. In addition, knockdown of HSPH1 by siRNA may lead to reduced growth of MCF-7/TR cell with a trend close to significance (P = 0.07), indicating that upregulation of HSPH1 may play a role in tamoxifen resistance. This study revealed a number of critical hub genes that might serve as therapeutic targets in breast cancer resistant to tamoxifen and provided potential directions for uncovering the mechanisms of tamoxifen resistance.


The neurodevelopmental consequences of prenatal alcohol exposure.
During pregnancy, ingestion of alcohol, a known teratogen, can cause harm to the fetus. Prenatal alcohol exposure is one of the leading causes of birth defects, developmental disorders, and mental retardation in children. The fetal central nervous system is particularly vulnerable to alcohol; this vulnerability contributes to many of the long-term disabilities and disorders seen in individuals with prenatal alcohol exposure. Diagnoses associated with prenatal alcohol exposure include fetal alcohol syndrome (FAS), partial fetal alcohol syndrome, fetal alcohol effects, alcohol-related neurodevelopmental disorder, and alcohol-related birth defects. Once diagnosed, early intervention improves the long-term outcome of affected children. Without documentation of maternal alcohol use, a diagnosis, and consequently treatment, is often difficult to attain. It is imperative that nurses, physicians, and other healthcare providers become comfortable with obtaining a history of, and providing anticipatory guidance and counseling about, alcohol use.


Fatal train accidents on Europe's railways: An update to 2019.
This paper presents an analysis of fatal train accident rates and trends on Europe's main line railways from 1990-2019. It is a sequel to the paper Fatal train accidents on Europe's railways: 1980-2009 (Evans (2011), which covers the three decades 1980-2009. The present paper discards the data for the 1980s, but adds the data for 2010-2019. The data cover the 28 countries of the European Union as in 2019, together with Norway and Switzerland. The source of the recent data is largely the European Union Agency for Railways. The estimated overall trend in the number of fatal train collisions and derailments per train-kilometre was -5.6 % per year from 1990-2019, with a 95 % confidence interval of -7.1 % to -4.2 %. The estimated accident rate in 2019 was 0.85 fatal collisions or derailments per billion train-kilometres, which represents a fall of 78 % since 1990. This gives an estimated mean number of fatal accidents in Europe in 2019 of 3.89. The data and results for 2010-2019 closely match the extrapolation of the results for 1990-2009, so that in 2009 extrapolation would have given a good forward projection for 2019. By the same argument this paper gives a forward projection of the mean number of accidents in 2029 of 2.12, assuming no change in train-kilometres, or pro-rata changes with changes in train-kilometres. The paper investigates the causes of accidents. A notable finding is that the proportion of accidents caused by signals passed at danger (SPADs) fell from 40 % in 1990-1999 to 21 % in 2010-2019. This is probably due to the increasing deployment of train protection systems. The number of fatalities in individual accidents has a skew distribution: most accidents have a small number of fatalities, but a few have a large number. The overall observed number of fatalities per accident is 4.23, and there is no indication that this mean changes with time. This implies that the mean number of fatalities per year has the same downward trend of 5.6 % per year as the mean number of accidents per year.


Knocking down Trim47 ameliorated sevoflurane-induced neuronal cell injury and cognitive impairment in rats.
Sevoflurane (SEV), usually causing neuronal damage and cognitive dysfunction, is one of the most commonly used anesthetics in clinical practice. However, the function of Trim47 in SEV-induced neuronal impairment remains elusive. The aim of this study was to study the effect of knocking down Trim47 on the nerve injury induced by SEV. Nerve injury was induced in rats by 3% SEV, and H19-7 was used to establish a pathological model, and sh-Trim47 was transfected into H19-7 to study the function of Trim47. The effects of SEV on the expression of Trim47 in the hippocampus and cognitive function of rats were studied by neurological function score and Moris water maze (MWM). The mRNA and protein expression of TNF-α, IL-1β and IL-6 in the cells, along with the neuronal apoptosis in the hippocampus of rats in each group were studied by TUNEL or WB. Flow cytometry was used to study the effect of knockdown of Trim47 on cell apoptosis. CCK-8 was used to detect cell viability of H19-7 cells. Finally, the potential signaling pathway affected by knockdown of Trim47 after abrogation of SEV induction was investigated by WB. The results showed that, knockdown of Trim47 ameliorated SEV-induced neurological damage and cognitive deficits, inflammation and neuronal cell apoptosis in rats, and promoted hippocampal neuronal activity. Knockdown of Trim47 can inhibit the NF-κB signaling pathway and improve neuronal cell damage and cognitive impairment induced by SEV in neonatal rats by regulating NF-κB signaling pathway, alleviating inflammatory response, and inhibiting neuronal apoptosis.


Validated spreadsheet for the identification of PE, PET, PP and PS microplastics by micro-ATR-FTIR spectra with known uncertainty.
The monitoring of microplastics in the environment is crucial to determine the relevance and trends of this contamination necessary to plan environmental protection policies. Monitoring data reliability is essential for this purpose. This work describes a methodology for the reliable identification of the most abundant polymer types in aquatic sediments (polyethylene, PE, polypropylene, PP, polyethylene terephthalate, PET, and polystyrene, PS) by micro-ATR-FTIR. Identifications with true and false result rates greater than 95% and lower than 5% are performed, respectively. The analysis is based on defining spectra requirements regarding characteristic and interfering bands intensity and selecting optimal assessed wavenumber range, signal processing, and algorithm to quantify the match/agreement between particle and reference spectra. It is also defined the minimum match value, P5»P, for reliable identifications. Examinations are performed in two stages where in the first stage PE and PP, PE&PP, are distinguished from other microplastics by taking the [4000-500] cm-1 spectra and various Match Methods and P5»P depending on the polymer type. PE and PP are distinguished by quantifying weighted or unweighted Pearson correlation coefficients against a reference spectrum in the [3000-2800] cm-1 range. The defined P5»P are above the 0.6 value considered in many references that do not quantify identification uncertainty. The MS-Excel files used in method development and validation are made available as Supplementary Material being applicable to other spectral techniques and analytical fields.


PSAC-PDB: Analysis and classification of protein structures.
This paper presents a novel framework, called PSAC-PDB, for analyzing and classifying protein structures from the Protein Data Bank (PDB). PSAC-PDB first finds, analyze and identifies protein structures in PDB that are similar to a protein structure of interest using a protein structure comparison tool. Second, the amino acids (AA) sequences of identified protein structures (obtained from PDB), their aligned amino acids (AAA) and aligned secondary structure elements (ASSE) (obtained by structural alignment), and frequent AA (FAA) patterns (discovered by sequential pattern mining), are used for the reliable detection/classification of protein structures. Eleven classifiers are used and their performance is compared using six evaluation metrics. Results show that three classifiers perform well on overall, and that FAA patterns can be used to efficiently classify protein structures in place of providing the whole AA sequences, AAA or ASSE. Furthermore, better classification results are obtained using AAA of protein structures rather than AA sequences. PSAC-PDB also performed better than state-of-the-art approaches for SARS-CoV-2 genome sequences classification.


[Pulmonary function in children following community-acquired pneumonia contracted at pre-school age].
Some studies relate pulmonary function (PF) during adult life to community-acquired pneumonia (CAP) suffered during infancy. The aim of the present work was to evaluate PF in children following CAP, contracted at pre-school age, which required hospitalisation. The hypothesis was that, once resolved, CAP in pre-school age children does not affect PF; further monitoring should therefore be unnecessary. PF was studied in a cohort of children who had suffered CAP at pre-school age, for which they were hospitalised. Children aged over 4 years were selected to try to ensure adequate collaboration, and a forced spirometry test was attempted in all of them. Of the initial 49 patients, 42 (85.7%) correctly performed the forced spirometry test. All were asymptomatic at the time of examination. The mean age of these patients was 6,6 ± 1,2 years; 25 were boys (54,3%). The mean time between CAP and the test was 19,5 ± 7,6 months. The results (mean ± SD) obtained with respect to theoretical values were: forced respiratory volume in the first second 107.73 ± 14.56% and forced vital capacity 101,6 ± 15,35%. The PF of children who have suffered CAP at pre-school age is normal following the resolution of the condition. No further PF studies are required after CAP resolves.


KRAS mutation and NF-κB activation indicates tolerance of chemotherapy and poor prognosis in colorectal cancer.
Evidence shows a strong relationship between KRAS mutations and the NF-κB signaling pathway. In colorectal cancer, however, the study of this subject has been very limited and results are inconsistent. To examine the relationship between KRAS mutations and NF-κB activation and their effect on chemotherapy response and survival of colorectal cancer patients. NF-κB activation was analyzed by immunohistochemistry in 167 primary colorectal cancer specimens in which the KRAS mutation status was confirmed. Clinical and pathologic data were extracted from the medical records and reviewed. Of 167 tumors screened, 63 (37.7 %) had NF-κB activation, 59 (35.3 %) had KRAS mutations, and 30 (18.0 %) had both NF-κB activation and KRAS mutations. The frequency of NF-κB activation in tumors with KRAS mutations was significantly higher than in tumors with wild type KRAS; 50.8 versus 30.6 %, P = 0.012. Patients with both KRAS mutations and NF-κB activation had a lower objective response to first-line chemotherapy than patients with other tumors, 23.8 versus 49.4 % (P = 0.035). Compared to patients with both KRAS mutations and NF-κB activation, overall survival of patients in other groups was significantly higher; median overall survival was 28.4 months (95 % CI 21.0-35.8) versus 46.3 months (95 % CI 39.4-53.2), hazard ratio 0.259 (95 % CI 0.125-0.538), P = 0.005. NF-κB activation was associated with KRAS mutation, and both KRAS mutation and NF-κB activation were indicative of high tolerance of chemotherapy and poor prognosis for colorectal cancer patients. Tumors with KRAS mutations and NF-κB activation may be a unique subtype of colorectal cancer.


Coronary artery calcium score: has anything changed?
Calcium deposition along the coronary artery walls is a surrogate biomarker for atherosclerosis, and its presence in the coronary arteries could reflect the severity of coronary artery disease (CAD) High coronary artery calcium score (CACS) correlates with advanced disease and a higher likelihood of coronary stenoses. Many studies have supported the role of CACS as a screening tool for CAD. Historically, CACS was introduced with electron beam computed tomography (EBCT), but in the last 30 years, many changes have occurred in CT, where the development of multidetector spiral technology has made reliable the noninvasive study of the heart and coronary arteries. Correlation studies with intravascular ultrasound (IVUS) and histology have demonstrated the capability of multidetector CT (MDCT) to provide information useful for characterising atherosclerotic plaque in a noninvasive manner. This has shifted the interest from heavily calcified deposits to plaque with a low-density core and small, superficial calcified nodules, features more frequently present in atherosclerotic plaque prone to rupture and responsible for acute coronary events (culprit lesions). The purpose of this review article is to summarise the recent evolution and revolution in the field of CT, strengthen the importance of a coronary CT study not limited to CACS evaluation and CAD grading but also used to obtain information about plaque composition, and to improve stratification of the patient at risk for acute coronary events.


Wide-Field Calcium Imaging of Dynamic Cortical Networks during Locomotion.
Motor behavior results in complex exchanges of motor and sensory information across cortical regions. Therefore, fully understanding the cerebral cortex's role in motor behavior requires a mesoscopic-level description of the cortical regions engaged, their functional interactions, and how these functional interactions change with behavioral state. Mesoscopic Ca2+ imaging through transparent polymer skulls in mice reveals elevated activation of the dorsal cerebral cortex during locomotion. Using the correlations between the time series of Ca2+ fluorescence from 28 regions (nodes) obtained using spatial independent component analysis (sICA), we examined the changes in functional connectivity of the cortex from rest to locomotion with a goal of understanding the changes to the cortical functional state that facilitate locomotion. Both the transitions from rest to locomotion and from locomotion to rest show marked increases in correlation among most nodes. However, once a steady state of continued locomotion is reached, many nodes, including primary motor and somatosensory nodes, show decreases in correlations, while retrosplenial and the most anterior nodes of the secondary motor cortex show increases. These results highlight the changes in functional connectivity in the cerebral cortex, representing a series of changes in the cortical state from rest to locomotion and on return to rest.