Monitoring of pulmonary arterial diastolic pressure through a right ventricular pressure transducer.
Pulmonary arterial diastolic pressure is an important parameter for hemodynamic monitoring in congestive heart failure. It is traditionally obtained through a pulmonary arterial catheter. If it could be obtained from a sensor in the right ventricle, chronic monitoring would be possible without the use of a pulmonary arterial catheter. This study is based on the hypothesis that pulmonary valve opening and pulmonary arterial diastolic pressure occur at the time of maximum positive rate of pressure development (dP/dt) in the right ventricle, when the pressures should be equal. Thus, right ventricular pressure at the time of maximum dP/dt (PAD index) should be a reasonable estimate of pulmonary arterial diastolic pressure. Eight patients with heart failure were catheterized and exposed to hemodynamic stress. Right ventricular and pulmonary arterial pressures were simultaneously recorded from a Millar (Houston, TX) catheter with two pressure transducers. The distal transducer was positioned in the bifurcation of the pulmonary artery and the proximal transducer was placed in the right ventricle. Pulmonary arterial diastolic pressure and PAD index were stored beat by beat on a bed-side computer. Acceptable recordings were obtained in all patients. Recordings from the individual patients showed a good covariation between PAD index and pulmonary arterial pressure during different hemodynamic manuevers, except during infusion of dobutamine, when the correlation was not as good. Pulmonary arterial diastolic pressure may be estimated from a transducer in the right ventricle, thus eliminating the need for a permanent pulmonary arterial catheter in an implantable hemodynamic monitoring system. Further studies are needed to verify the correlation on a long-term basis.


Video colorimetry of single-chromophore systems based on vector analysis in the 3D color space: Unexpected hysteresis loops in oscillating chemical reactions.
Colorimetry, the quantitative determination of color, usually of a digital image, has useful applications in diverse areas of research. Many methods have been proposed for translating the RGB data of an image to obtain concentration information. Among the many methods for RGB analysis, we focus on the vector projection method (VP), which is based on a vector analysis in 3D RGB color space. This method has the major advantages of being conceptually intelligible and generalizable to various systems. For solutions with variable concentrations of one chromophore, we will show that the analysis of the trace in RGB color space allows for a judgment about the reliability of the linear concentration dependence of the chromapostasi parameter. We discuss the theoretical underpinnings of the method in two test cases, a simple dye solution and a titration of an organic acid with phenolphthalein indicator. The VP method was then applied to the Ce-catalyzed Belousov-Zhabotinsky reaction with the expectation that the colorimetry would quantify [Ce4+] oscillations. Surprisingly, the 3D color space analysis revealed hysteresis loops and the origin and implications of this observation are discussed.


Anastomotic leak prophylaxis using a vapor-heated fibrin sealant: report on 738 gastric bypass patients.
Excluding pulmonary embolism, anastomotic leak is the leading cause of death and major morbidity in patients undergoing open or laparoscopic gastric bypass operations. We observed a number of these leaks (11 out of 1,120 Micropouch(SM) gastric bypass [MGB] patients; 0.9%). The majority (80%) required emergency laparotomy and drainage, massive fluid resuscitation, and aggressive nutritional support. Therefore, we designed a 2-year, prospective study to determine the therapeutic efficacy of vapor-heated fibrin sealant to prevent anastomotic leaks at the gastro-jejunostomy (GJS) site. Between April, 2000 and March, 2002, 738 patients underwent a primary (n=671) or revisionary (n=67) MGB procedure. The gastric reservoir was limited to the cardia of the stomach. Vapor-heated fibrin glue 1 cc was applied circumferentially to a 12-mm, non-banded GJS anastomosis. Once activated, fibrin sealant polymerized into a soft, closely adherent gel. No omental patch was used to cover the fibrin-sealed anastomosis. Of 738 patients, 2 required emergency laparotomy for leaks and 2 for adhesive bands that contributed to a distal small bowel obstruction. There were no anastomotic leaks at the fibrin-sealed GJS sites. No gastro-gastric or gastro-enteric fistulas were recorded. Fibrin sealant applied to the GJS site appears to have eliminated anastomotic leaks in our Micropouch(SM) gastric bypass patients. These results suggest that fibrin glue application may contribute to "leak prophylaxis" in patients undergoing open Rouxen-Y gastric bypass. Glue placements may also benefit patients undergoing a laparoscopic Roux-en-Y procedure, wherein anastomotic leaks have been reported early in the learning curve.


Effect of albumin administration on outcomes in hypoalbuminemic patients hospitalized with community-acquired pneumonia (ALBUCAP): a prospective, randomized, phase III clinical controlled trial-a trial protocol.
Community-acquired pneumonia (CAP) remains a leading cause of death worldwide, and hypoalbuminemia is associated with worse outcomes. However, it remains uncertain whether albumin administration could have any beneficial effects. We aim to assess whether the administration of albumin in hypoalbuminemic patients with CAP increases the proportion of clinically stable patients at day 5 compared with the standard of care alone. This is a trial protocol for a superiority, non-blinded, multicenter, randomized, phase 3, interventional controlled clinical trial. The primary endpoint will be the proportion of clinical stable patients at day 5 (intention to treat), defined as those with stable vital signs for at least 24 h. The secondary endpoints will be time to clinical stability, duration of intravenous and total antibiotic treatment, length of hospital stay, intensive care unit admission, duration of mechanical ventilation and vasopressor treatment, adverse events, readmission within 30 days, and all-cause mortality. The trial has been approved by the Spanish Medicines and Healthcare Products Regulatory Agency. The investigators commit to publish the data in peer-reviewed journals within a year of the study completion date. Subjects will be recruited from three Spanish hospitals over a planned enrolment period of 2 years. A follow-up visit will be performed 1 month after discharge. We have estimated the need for a sample size of 360 patients at a two-sided 5% alpha-level with a power of 80% based on intention to treat. Eligible participants must be hospitalized, hypoalbuminemic (≤ 30 g/L), non-immunosuppressed, adults, and diagnosed with CAP. They will be randomly assigned (1:1) to receive standard care plus albumin (20 g in 100 mL) every 12 h for 4 days or standard care alone. If this randomized trial confirms the hypothesis, it should lead to a change in current clinical practice for the management of hypoalbuminemic patients with CAP. European Clinical Trials Database (EudraCT) 2018-003117-18 . Registered on 12 April 2019. ClinicalTrials.gov NCT04071041 . Registered on 27 August 2019.


Adsorption of basic and reactive dyes from aqueous solution onto Intsia bijuga sawdust-based activated carbon: batch and column study.
The adsorption behavior of basic, methylene blue (MB), and reactive, remazol brilliant violet 5R (RBV), dyes from aqueous solution onto Intsia bijuga sawdust-based activated carbon (IBSAC) was executed via batch and column studies. The produced activated carbon was characterized through Brunauer-Emmett-Teller (BET) surface area and pore structural analysis, proximate and ultimate, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). Batch studies were performed to investigate the effects of contact time, initial concentration, and solution pH. The equilibrium data for both MB and RBV adsorption better fits Langmuir model with maximum adsorption capacity of 434.78 and 212.77 mg/g, respectively. Kinetic studies for both MB and RBV dyes showed that the adsorption process followed a pseudo-second-order and intraparticle diffusion kinetic models. For column mode, the breakthrough curves were plotted by varying the flow rate, bed height, and initial concentration and the breakthrough data were best correlated with the Yoon-Nelson model compared to Thomas and Adams-Bohart model. The adsorption activity of IBSAC shows good stability even after four consecutive cycles.


Neural bases of reward anticipation in healthy individuals with low, mid, and high levels of schizotypy.
A growing body of research has placed the ventral striatum at the center of a network of cerebral regions involved in anticipating rewards in healthy controls. However, little is known about the functional connectivity of the ventral striatum associated with reward anticipation in healthy controls. In addition, few studies have investigated reward anticipation in healthy humans with different levels of schizotypy. Here, we investigated reward anticipation in eighty-four healthy individuals (44 females) recruited based on their schizotypy scores. Participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI.Participants showed the expected decrease in response times for highly rewarded trials compared to non-rewarded trials. Whole-brain activation analyses replicated previous results, including activity in the ventral and dorsal striatum. Whole-brain psycho-physiological interaction analyses of the left and right ventral striatum revealed increased connectivity during reward anticipation with widespread regions in frontal, parietal and occipital cortex as well as the cerebellum and midbrain. Finally, we found no association between schizotypal personality severity and neural activity and cortico-striatal functional connectivity. In line with the motivational, attentional, and motor functions of rewards, our data reveal multifaceted cortico-striatal networks taking part in reward anticipation in healthy individuals. The ventral striatum is connected to regions of the salience, attentional, motor and visual networks during reward anticipation and thereby in a position to orchestrate optimal goal-directed behavior.


Differentiation of Trypanosoma rangeli: high production of infective Trypomastigote forms in vitro.
In the present study, we report a simple method to induce high Trypanosoma rangeli differentiation in vitro, producing a large number of infective trypomastigote forms. Parasites from SC-58 (Brazil) and Choachi (Colombia) strains were cultivated at 27 degrees C in TC-100, Grace and DMEM media, each supplemented with 5% fetal bovine serum and prepared at three distinct pHs (6.0, 7.0, 8.0). Differentiation was microscopically evaluated at 0, 3 and 6 days after cultivation in each medium by determining the percentage of trypomastigotes in Giemsa-stained smears. Our data revealed similar results for both T. rangeli strains, showing (after 6 days of cultivation in DMEM medium, pH 8.0) the presence of about 80% of trypomastigotes. These culture-derived trypomastigotes proved to be infective to both Balb-C mice and Rhodnius spp, reaching the triatomine's salivary glands. Our results describe a new and easy method to induce high T. rangeli differentiation in vitro, allowing further studies on the antigenic constitution of trypomastigotes.


Targeted Next Generation Sequencing reveals previously unidentified TSC1 and TSC2 mutations.
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in TSC1 and TSC2. Conventional DNA diagnostic screens identify a TSC1 or TSC2 mutation in 75 - 90% of individuals categorised with definite TSC. The remaining individuals either have a mutation that is undetectable using conventional methods, or possibly a mutation in another as yet unidentified gene. Here we apply a targeted Next Generation Sequencing (NGS) approach to screen the complete TSC1 and TSC2 genomic loci in 7 individuals fulfilling the clinical diagnostic criteria for definite TSC in whom no TSC1 or TSC2 mutations were identified using conventional screening methods. We identified and confirmed pathogenic mutations in 3 individuals. In the remaining individuals we identified variants of uncertain clinical significance. The identified variants included mosaic changes, changes located deep in intronic sequences and changes affecting promoter regions that would not have been identified using exon-only based analyses. Targeted NGS of the TSC1 and TSC2 loci is a suitable method to increase the yield of mutations identified in the TSC patient population.


Genomic prediction using subsampling.
Genome-wide assisted selection is a critical tool for the genetic improvement of plants and animals. Whole-genome regression models in Bayesian framework represent the main family of prediction methods. Fitting such models with a large number of observations involves a prohibitive computational burden. We propose the use of subsampling bootstrap Markov chain in genomic prediction. Such method consists of fitting whole-genome regression models by subsampling observations in each round of a Markov Chain Monte Carlo. We evaluated the effect of subsampling bootstrap on prediction and computational parameters. Across datasets, we observed an optimal subsampling proportion of observations around 50% with replacement, and around 33% without replacement. Subsampling provided a substantial decrease in computation time, reducing the time to fit the model by half. On average, losses on predictive properties imposed by subsampling were negligible, usually below 1%. For each dataset, an optimal subsampling point that improves prediction properties was observed, but the improvements were also negligible. Combining subsampling with Gibbs sampling is an interesting ensemble algorithm. The investigation indicates that the subsampling bootstrap Markov chain algorithm substantially reduces computational burden associated with model fitting, and it may slightly enhance prediction properties.


A review of Aleurodaphis (Hemiptera, Aphididae, Hormaphidinae) with the description of one new species and keys to species.
The genus Aleurodaphis van der Goot is reviewed. One new species Aleurodaphis sinojackiae Qiao & Jiang, sp. n. on Sinojackia xylocarpa from Jiangsu and Zhejiang, China is described. Aleurodaphis sinisalicis Zhang, 1982 is synonymised with Aleurodaphis blumeae van der Goot, 1917. Keys to species, morphological description and features of the new species, host plants, and distribution are provided. The specimens including types are deposited in British Natural History Museum, London (BMNH), Kôgakkan University, Japan and the National Zoological Museum of China, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (NZMC).


Epinephrine, vasopressin, and nitroglycerin improve neurologic outcome in porcine asphyxial cardiac arrest.
The aim of the present study was to assess whether the combination of epinephrine, vasopressin, and nitroglycerin would improve initial resuscitation success, 24-hour survival, and neurologic outcome compared with epinephrine alone in a swine model of asphyxial cardiac arrest (CA). This prospective randomized experimental study was conducted at a laboratory research department. Twenty male Landrace/Large-White pigs 12 to 15 weeks of age were investigated. Asphyxial CA was induced by occlusion of the endotracheal tube. Pigs remained untreated for 4 minutes before attempting resuscitation by unclamping the endotracheal tube, mechanical ventilation, chest compressions, and epinephrine (group E) or a combination of epinephrine with vasopressin and nitroglycerin (group EVN) administered intravenously. In case of restoration of spontaneous circulation, the animals were supported for 30 minutes and then observed for 24 hours. Coronary perfusion pressure and mean arterial pressure were significantly increased during cardiopulmonary resuscitation in group EVN. In both groups, restoration of spontaneous circulation and survival rates were comparable (P value, nonsignificant). At 24 hours after CA, neurologic deficit score was significantly better in animals treated with the combination pharmacotherapy (P < .001). Brain histologic damage score was also higher in group EVN compared with group E (P < .001). Total histologic damage score and neurologic deficit score showed a statistical significant correlation (P < .001). In this porcine model of asphyxial CA, the addition of nitroglycerin to vasopressin and epinephrine maintained elevated coronary perfusion pressure during asphyxia CA and resulted in significantly better neurologic and histopathologic outcome in comparison with epinephrine alone.


Psychometric assessment of the Behavior and Attitudes Questionnaire for Healthy Habits: measuring parents' views on food and physical activity.
To assess parents' perspectives of their home environments to establish the validity of scores from the Behavior and Attitudes Questionnaire for Healthy Habits (BAQ-HH). In the present descriptive study, we surveyed a cross-sectional sample of parents of pre-school children. Questionnaire items developed in an iterative process with community-based programming addressed parents' knowledge/awareness, attitudes/concerns and behaviours about healthy foods and physical activity habits with 6-point rating scales. Exploratory and confirmatory factor analyses were used to psychometrically evaluate scores from the scales. English and Spanish versions of the BAQ-HH were administered at parent-teacher conferences for pre-school children at ten Head Start centres across a five-county agency in autumn 2010. From 672 families with pre-school children, 532 parents provided responses to the BAQ-HH (79 % response rate). The majority was female (83 %), Hispanic (66 %) or white (16 %), and ages ranged from 20 to 39 years (85 %). Exploratory and confirmatory analyses revealed a knowledge scale (seven items), an attitude scale (four items) and three behaviour subscales (three items each). Correlations were identified between parents' perceptions of home activities and reports of children's habits. Differences were identified by gender and ethnicity groupings. As a first step in psychometric testing, the dimensionality of each of the three scales (Knowledge, Attitudes and Behaviours) was identified and scale scores were related to other indicators of child behaviours and parents' demographic characteristics. This questionnaire offers a method to measure parents' views to inform planning and monitoring of obesity-prevention education programmes.


Genetic associations of surfactant protein D and angiotensin-converting enzyme with lung disease in preterm neonates.
To replicate genetic associations with respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in genes related to surfactant deficiency, inflammation and infection, and the renin-angiotensin system. We examined eight candidate genes for associations with RDS and BPD in 433 preterm birth (PTB-<37 weeks) infants (251 with RDS and 134 with BPD). Both case-control and family-based analyses were performed in preterm (<37 weeks) and very preterm birth (VPTB-<32 weeks) infants. We replicated a previous finding that rs1923537, a marker downstream of surfactant protein D (SFTPD) is associated with RDS in VPTB infants in that the T allele was overtransmitted from parents to offspring with RDS (P=8.4 × 10(-3)). We also observed the A allele of rs4351 in the angiotensin-converting enzyme (ACE) gene was overtransmitted from parents to VPTB offspring with BPD (P=9.8 × 10(-3)). These results give further insight into the genetic risk factors for complex neonatal respiratory diseases and provide more evidence of the importance of SFTPD and ACE in the etiology of RDS and BPD, respectively.


A CRM-Positive variant of factor-VII deficiency and the detection of heterozygotes with the assay of factor-like antigen.
Nine patients with severe factor-VII deficiency, belonging to seven pedigrees were studied for the presence of factor-VII-CRM with an inhibitor neutralization assay. The antibody, raised in rabbits, did not precipitate the antigen and could only be used in a fluid phase assay to measure the capacity of plasma to neutralize inhibitory activity directed against factor-VII activity. In one of these nine patients normal amounts of factor-VII-CRM could be demonstrated. The CRM + patient did not show a clinical picture at variance with that of the CRM-patients. The investigation into this CRM+ pedigree revealed heterozygosity in nine out of 12 persons when using the ratio between biological factor-VII activity and factor-VII-CRM as the criterion.


[Plastic surgical reconstruction methods in interdisciplinary treatment of chronic wounds].
Chronic wounds are an increasingly serious socioeconomic problem. Their most frequent underlying causes are peripheral arterial occlusive disease, chronic venous insufficiency, and diabetic foot syndrome. Such wounds are also found in post-traumatic conditions or as pressure sores in nonambulatory patients. This review presents the reconstructive plastic surgical options and decision-making algorithms embedded for an interdisciplinary approach.


Mechano-transduction in tumour growth modelling.
The evolution of biological systems is strongly influenced by physical factors, such as applied forces, geometry or the stiffness of the micro-environment. Mechanical changes are particularly important in solid tumour development, as altered stromal-epithelial interactions can provoke a persistent increase in cytoskeletal tension, driving the gene expression of a malignant phenotype. In this work, we propose a novel multi-scale treatment of mechano-transduction in cancer growth. The avascular tumour is modelled as an expanding elastic spheroid, whilst growth may occur both as a volume increase and as a mass production within a cell rim. Considering the physical constraints of an outer healthy tissue, we derive the thermo-dynamical requirements for coupling growth rate, solid stress and diffusing biomolecules inside a heterogeneous tumour. The theoretical predictions successfully reproduce the stress-dependent growth curves observed by in vitro experiments on multicellular spheroids.


Sleeping sound with autism spectrum disorder (ASD): study protocol for an efficacy randomised controlled trial of a tailored brief behavioural sleep intervention for ASD.
Sleep problems are a characteristic feature of children with autism spectrum disorder (ASD) with 40% to 80% of children experiencing sleep difficulties. Sleep problems have been found to have a pervasive impact on a child's socio-emotional functioning, as well as on parents' psychological functioning. The Sleeping Sound ASD project aims to evaluate the efficacy of a brief behavioural sleep intervention in reducing ASD children's sleep problems in a fully powered randomised controlled trial (RCT). Intervention impact on child and family functioning is also assessed. The RCT aims to recruit 234 children with a diagnosis of ASD, aged 5-13 years, who experience moderate to severe sleep problems. Participants are recruited from paediatrician clinics in Victoria, Australia, and via social media. Families interested in the study are screened for eligibility via phone, and then asked to complete a baseline survey online, assessing child sleep problems, and child and family functioning. Participants are then randomised to the intervention group or treatment as usual comparator group. Families in the intervention group attend two face-to-face sessions and a follow-up phone call with a trained clinician, where families are provided with individually tailored behavioural sleep strategies to help manage the child's sleep problems. Teacher reports of sleep, behavioural and social functioning are collected, and cognitive ability assessed to provide measures blind to treatment group. The primary outcome is children's sleep problems as measured by the Children's Sleep Habits Questionnaire at 3 months post-randomisation. Secondary outcomes include parent and child quality of life; child social, emotional, behavioural and cognitive functioning; and parenting stress and parent mental health. Cost-effectiveness of the intervention is also evaluated. Findings from this study will be published in peer-reviewed journals and disseminated at national and international conferences, local networks and online. ISRCTN14077107 (ISRCTN registry dated on 3 March 2017).


Multiple scattering and resolution effects in small-angle neutron scattering experiments calculated and corrected by the software package MuScatt.
This article deals with multiple scattering effects that are important for the method of small-angle neutron scattering (SANS). It considers three channels for the coherent elastic, the incoherent elastic and the incoherent inelastic scattering processes. The first channel contains the desired information on the experiment. Its multiple scattering effects can be desmeared, as shown in the later sections of the article. The other two channels display a nearly constant background as a function of the scattering angle. The incoherent elastic scattering is treated by the theory of Chandrasekhar, allowing for multiple scattering even at large scattering angles. The transfer to a single representative thermalized wavelength by the inelastic scattering - as a simplification - is assumed to happen by a single scattering event. Once the transition to this altered wavelength has happened, further incoherent multiple scattering is considered. The first part of the paper deals with the multiple scattering effects of light water. In the later part of the article, deconvolution algorithms for multiple scattering and instrumental resolution of the elastic coherent signal as implemented in the program MuScatt are described. All of these considerations are interesting for both reactor-based instruments with velocity selectors and time-of-flight SANS instruments and may improve the reliability of the data treatment.


[Immunohistochemical detection of pS2 protein in paraffin sections of breast carcinoma tissue. Comparison with results of an immunoradiometry assay].
The synthesis of pS2 protein is induced through estrogen-dependent transcription of the pS2 gene. The presence of the pS2 protein in breast cancer is thought to be as valuable as receptor status, or even more so, in predicting the response to hormonal therapy. Furthermore, pS2 appears to be a prognostic factor for primary breast cancer. In 162 cases of primary breast cancer, pS2 was tested by immunohistochemical procedures on formalin-fixed and paraffin-embedded tissues. Staining was evaluated semi-quantitatively using an immunoreactive score (IRS). The concentrations of pS2 in tumor cytosol were determined using an immunoradiometric assay. Positive staining for pS2 (IRS > or = 2) was seen in 27% of the tumors. Comparison of immunohistochemical and biochemical detection (26% of tumors had pS2 cytosol concentrations above the cut-off value of 26 ng/mg cell protein) revealed an 81% concordance rate (r = 0.76; P < 0.0001). Univariate analysis showed no significant correlation of immunohistochemical pS2 detection and age or menopausal status of patients, tumor size, tumor grade or nodal status. However, the immunohistochemical pS2 status correlated significantly with the immunohistochemical detection of the estrogen (ER; P < 0.001) and progesterone receptor status (PR; P < 0.0001). pS2-positive tumors were ER-positive in 66% of cases and PR-positive in 73%; 89% of pS2-positive tumors were positive for ER and/or PR. The incidence of immunohistochemical pS2 detection was 41% in the group of steroid receptor positive carcinomas (ER- and/or PR-positive) in contrast to 7% in steroid receptor negative tumors (ER- and PR-negative).


A new porphyrin as selective substrate-based inhibitor of breast cancer resistance protein (BCRP/ABCG2).
The ABCG2 transporter plays a pivotal role in multidrug resistance, however, no clinical trial using specific ABCG2 inhibitors have been successful. Although ABC transporters actively extrude a wide variety of substrates, photodynamic therapeutic agents with porphyrinic scaffolds are exclusively transported by ABCG2. In this work, we describe for the first time a porphyrin derivative (4B) inhibitor of ABCG2 and capable to overcome multidrug resistance in vitro. The inhibition was time-dependent and 4B was not itself transported by ABCG2. Independently of the substrate, the porphyrin 4B showed an IC50 value of 1.6 μM and a mixed type of inhibition. This compound inhibited the ATPase activity and increased the binding of the conformational-sensitive antibody 5D3. A thermostability assay confirmed allosteric protein changes triggered by the porphyrin. Long-timescale molecular dynamics simulations revealed a different behavior between the ABCG2 porphyrinic substrate pheophorbide a and the porphyrin 4B. Pheophorbide a was able to bind in three different protein sites but 4B showed one binding conformation with a strong ionic interaction with GLU446. The inhibition was selective toward ABCG2, since no inhibition was observed for P-glycoprotein and MRP1. Finally, this compound successfully chemosensitized cells that overexpress ABCG2. These findings reinforce that substrates may be a privileged source of chemical scaffolds for identification of new inhibitors of multidrug resistance-linked ABC transporters.


[Evaluation of self-medication practices and their characteristics among Uvira in Democratic Republic of Congo students].
self-medication poses a threat to public health. The purpose of this study was to evaluate self-medication practices among Uvira students in the Democratic Republic of the Congo (DRC). we conducted a cross-sectional descriptive study based on an indirect interview of 700 students, using a self-administered survey questionnaire. Data were processed using XLSTAT. according to the survey conducted on these 700 students, the prevalence of self-medication was 99.3% (n=695), of which 42.3% (n=294) started during adolescence. Of the total respondents, 57.4% (n=399) said they resorted to self-medication every time they fell ill and were short of money (n=471, 67.7%) for a consultation. The most commonly cited pathology encountered during this practice was malaria (n=212, 30.5%). Of all drugs used, paracetamol was in the first place (n=106, 15.3%) while the tablet was the form most used by these students (n=598, 86%). In terms of the drug combination, Fansidar-Coartem (n=106, 17.2%) was the most common; the dosage was age-dependent in 65.6% (n=456) of cases. This study also showed that 37.4% (n=695) of the students interviewed used phytotherapy, mainly to treat malaria (n=124, 47.3%). among Uvira students, self-medication is extremely used, especially against malaria. Efforts must be made by healthcare personnel in collaboration with policymakers to raise awareness about the rational use of medications, in order to better control and potentially eradicate this practice that is harmful to health.


Comprehensive metagenomic analysis of stress-resistant and -sensitive Listeria monocytogenes.
Listeria monocytogenes is a pathogenic bacterium which can live in adverse environments (low pH, high salinity, and low temperature). Even though there are various whole genome sequencing (WGS) data on L. monocytogenes, investigations on genetic differences between stress-resistant and -sensitive L. monocytogenes grown under stress environments have been not fully examined. This study aims to investigate and compare genetic characteristics between stress-resistant and -sensitive L. monocytogenes using whole genome sequencing (WGS). A total of 47 L. monocytogenes strains (43 stress-resistant and 4 stress-sensitive) were selected based on the stress-resistance tests under pH 3, 5% salt concentration, and 1 °C. The sequencing library for WGS was prepared and sequenced using an Illumina MiSeq. Genetic characteristics of two different L. monocytogenes groups were examined to analyze the pangenome, functionality, virulence, antibiotic resistance, core, and unique genes. The functionality of unique genes in the stress-resistant L. monocytogenes was distinct compared to the stress-sensitive L. monocytogenes, such as carbohydrate and nucleotide transport and metabolism. The lisR virulence gene was detected more in the stress-resistant L. monocytogenes than in the stress-sensitive group. Five stress-resistant L. monocytogenes strains possessed tet(M) antibiotic resistance gene. This is the first study suggesting that deep genomic characteristics of L. monocytogenes may have different resistance level under stress conditions. This new insight will aid in understanding the genetic relationship between stress-resistant and -sensitive L. monocytogenes strains isolated from diverse resources. KEY POINTS: • Whole genomes of L. monocytogenes isolated from three different sources were analyzed. • Differences in two L. monocytogenes groups were identified in functionality, virulence, and antibiotic resistance genes. • This study first examines the association between resistances and whole genomes of stress-resistant and -sensitive L. monocytogenes.


Using the time of maximum effect site concentration to combine pharmacokinetics and pharmacodynamics.
To simulate the time course of drug effect, it is sometimes necessary to combine the pharmacodynamic parameters from an integrated pharmacodynamic-pharmacodynamic study (e.g., volumes, clearances, k(e0) [the effect site equilibration rate constant], C(50) [the steady state plasma concentration associated with 50% maximum effect], and the Hill coefficient) with pharmacokinetic parameters from a different study (e.g., a study examining a different age group or sampling over longer periods of time). Pharmacokinetic-pharmacodynamic parameters form an interlocked vector that describes the relationship between input (dose) and output (effect). Unintended consequences may result if individual elements of this vector (e.g., k(e0)) are combined with pharmacokinetic parameters from a different study. The authors propose an alternative methodology to rationally combine the results of separate pharmacokinetic and pharmacodynamic studies, based on t(peak), the time of peak effect after bolus injection. The naive approach to combining separate pharmacokinetic and pharmacodynamic studies is to simply take the k(e0) from the pharmacodynamic study and apply it naively to the pharmacokinetic study of interest. In the t(peak) approach, k(e0) is recalculated using the pharmacokinetics of interest to yield the correct time of peak effect. The authors proposed that the t(peak) method would yield better predictions of the time course of drug effect than the naive approach. They tested this hypothesis in three simulations: thiopental, remifentanil, and propofol. In each set of simulations, the t(peak) method better approximated the postulated "true" time course of drug effect than the naive method. T(peak) is a useful pharmacodynamic parameter and can be used to link separate pharmacokinetic and pharmacodynamic studies. This addresses a common difficulty in clinical pharmacology simulation and control problems, where there is usually a wide choice of pharmacokinetic models but only one or two published pharmacokinetic-pharmacodynamic models. The results will be immediately applicable to target-controlled anesthetic infusion systems, where linkage of separate pharmacokinetic and pharmacodynamic parameters into a single model is inherent in several target-controlled infusion designs.


Efficient path-based computations on pedigree graphs with compact encodings.
A pedigree is a diagram of family relationships, and it is often used to determine the mode of inheritance (dominant, recessive, etc.) of genetic diseases. Along with rapidly growing knowledge of genetics and accumulation of genealogy information, pedigree data is becoming increasingly important. In large pedigree graphs, path-based methods for efficiently computing genealogical measurements, such as inbreeding and kinship coefficients of individuals, depend on efficient identification and processing of paths. In this paper, we propose a new compact path encoding scheme on large pedigrees, accompanied by an efficient algorithm for identifying paths. We demonstrate the utilization of our proposed method by applying it to the inbreeding coefficient computation. We present time and space complexity analysis, and also manifest the efficiency of our method for evaluating inbreeding coefficients as compared to previous methods by experimental results using pedigree graphs with real and synthetic data. Both theoretical and experimental results demonstrate that our method is more scalable and efficient than previous methods in terms of time and space requirements.


The Effect of Preoperative Oral Versus Parenteral Dextrose Supplementation on Pain, Nausea, and Quality of Recovery After Laparoscopic Cholecystectomy.
Earlier studies suggest that carbohydrate loading is effective in reducing preoperative nausea. This study was conducted to investigate the effect of preoperative oral versus parenteral carbohydrate loading on the postoperative pain, nausea, and quality of recovery (QoR). Three-arm randomized, single-blind clinical trial. In this study, 95 adult patients scheduled for elective laparoscopic cholecystectomy were randomly assigned into three groups of preoperative intravenous dextrose 10% infusion, oral carbohydrate (OCH)-rich drink, and control. The pain and nausea severity scores were measured during recovery, 6 hours, and 24 hours thereafter. The 40-item QoR score was evaluated the day after surgery. In recovery, nausea severity was comparable among three groups, whereas pain score in the OCH group was significantly less than the controls (P = .009). Pain score in patients who received intravenous dextrose was mediocre and not statistically different from two other groups. Six and 24 hours after surgery, nausea and pain scores in OCH and dextrose infusion groups were significantly lower than the control group (P < .05). The 40-item QoR score was significantly higher in intervention groups than control participants (P < .05). Blood glucose levels were comparable in three groups before and after surgery. Preoperative carbohydrate loading significantly improves the QoR after laparoscopic cholecystectomy without significant effect on blood glucose levels. Oral route more effectively controls nausea and pain than parenteral dextrose administration.


[Volvulus of the spiral colon in a pygmy goat buck].
In small ruminants intestinal volvulus is a rare finding and therefore only scarcely mentioned in the literature. The case report summarizes findings and clinical development of a pygmy goat with a volvulus of the spiral colon. The animal presented with a highly disturbed general condition and clinical signs of shock. It showed a painful abdomen and a balloon-shaped structure in the right dorsal abdomen. Diagnostic laparotomy revealed a rotation of the spiral colon of 360° to the right. Due to cardiovascular failure the animal died during surgery. The cause of the volvulus remains undetermined.


Institution Based Prospective Cross-Sectional Study on Patterns of Neonatal Morbidity at Gondar University Hospital Neonatal Unit, North-West Ethiopia.
Every year, millions of babies are born and a large proportion of them are being admitted to hospital for various indications. This study was conducted to identify the general characteristics, disease spectrum and common causes of Neonatal morbidity and mortality at Gondar University Hospital, Neonatal Unit. Institution based prospective cross-sectional study was conducted at Gondar University Hospital (GUH), Neonatal Unit, from January 1(st) to March 31(st), 2014. The study included 325 newborns who were admitted to the unit during the study period. The neonates were followed up using structured checklist and neonatal parameters like Neonatal sex, place of delivery, address, length of stay, gestational age, diagnosis and discharge conditions were transcribed into an electronic database for all observations. The primary outcome measures were death and cause of death. A total of 325 neonates were admitted during the study period. Of these, 75.1%, 23.1%, 1.2% and 0.6% were discharged improved, died, discharged with same condition and disappeared, respectively. Ten variables were found to have significant statistical associations with neonatal mortality after adjusting for demographic covariates: Prematurity (p < 0.001), Meningitis (p <0.001), Hemorrhagic Diseases (P <0.001), Hyaline Membrane Disease (P<0.001), Neonatal Sepsis (p <0.05), Meningitis (<0.05), Perinatal Asphyxia (p <0.05), Neonatal Seizure (p <0.05), Home delivery (p <0.05) and Meconium Aspiration (p <0.05). Our study showed that the common causes of neonatal mortality are almost similar with the previous evidences (problems of prematurity, Asphyxia and Sepsis).


Physical activity, but not environmental complexity, facilitates HPA axis response habituation to repeated audiogenic stress despite neurotrophin mRNA regulation in both conditions.
Stress exacerbates several physical and psychological disorders. Voluntary exercise can reduce susceptibility to many of these stress-associated disorders. In rodents, voluntary exercise can reduce hypothalamic-pituitary-adrenocortical (HPA) axis activity in response to various stressors as well as upregulate several brain neurotrophins. An important issue regarding voluntary exercise is whether its effect on the reduction of HPA axis activation in response to stress is due to the physical activity itself or simply the enhanced environmental complexity provided by the running wheels. The present study compared the effects of physical activity and environmental complexity (that did not increase physical activity) on HPA axis habituation to repeated stress and modulation of brain neurotrophin mRNA expression. For six weeks, male rats were given free access to running wheels (exercise group), given 4 objects that were repeatedly exchanged (increased environmental complexity group), or housed in standard cages. On week 7, animals were exposed to 11 consecutive daily 30-min sessions of 98-dBA noise. Plasma corticosterone and adrenocorticotropic hormone were measured from blood collected directly after noise exposures. Tissue, including brains, thymi, and adrenal glands was collected on Day 11. Although rats in both the exercise and enhanced environmental complexity groups expressed higher levels of BDNF and NGF mRNA in several brain regions, only exercise animals showed quicker glucocorticoid habituation to repeated audiogenic stress. These results suggest that voluntary exercise, independent from other environmental manipulations, accounts for the reduction in susceptibility to stress.


Effects of pulsatile reperfusion on postischemic recovery of myocardial function after global hypothermic cardiac arrest.
It has been postulated that pulsatile blood flow helps to preserve the myocardium after ischemia. However, its effect on postischemic myocardium during cardiopulmonary bypass has not been clearly defined. To determine if pulsatile reperfusion improves postischemic recovery of cardiac metabolism and performance, we subjected 20 dogs to 60 minutes of aortic cross-clamping followed by 45 minutes of pulsatile (P group; 10 dogs) or nonpulsatile (NP group; 10 dogs) reperfusion. Left ventricular function was measured at a controlled preload in both groups before induction of global ischemia and after termination of bypass. Segmental length (assessed by sonomicrometry) was used to determine dimensional changes. Ventricular pressures were measured with solid-state micromanometers. Percent recovery of left ventricular peak systolic pressure, its first derivative, and stroke work were 66%, 59%, and 38%, respectively in the NP group and 82%, 76%, and 65% in the P group. The postarrest decrease in segmental shortening was minimized in the P group; left ventricular function curves and the slope of the end-systolic pressure-length relationship also indicated better performance after pulsatile reperfusion than after nonpulsatile reperfusion. Myocardial lactate extraction was transiently improved during the early pulsatile reperfusion period. We conclude that pulsatile reperfusion provides better myocardial preservation than nonpulsatile perfusion after 60 minutes of induced global ischemia.


Improving clinical instruction: comparison of literature.
Clinical education in radiologic technology and athletic training is similar in that both programs use clinical sites and clinical instructors to instruct and evaluate student competency. The purpose of this paper is to review and compare the literature from radiologic technology and athletic training clinical education. The literature for this review was obtained using ProQuest and PubMed databases, from the years 1998 to 2006. Research is available for both radiologic technology and athletic training and provides a good comparison. Radiologic technology students experience various clinical stressors that can be remedied by properly trained clinical instructors and instructors who spend quality time with students. The opinions regarding the necessary behaviors of clinical instructors vary between program directors, clinical instructors and students. Cooperation and communication between programs and clinical instructors is important for students to achieve clinical success. A comparison of the literature demonstrates that radiologic technology and athletic training programs are similar; thus, ideas from athletic training can be applied to radiologic technology clinical education.


Distribution and function of organized concentrations of actin filaments in mammalian spermatogenic cells and Sertoli cells.
Actin filaments are concentrated in specific regions of spermatogenic cells and Sertoli cells. In spermatogenic cells they occur in intercellular bridges and in the subacrosomal space. In Sertoli cells they are abundant in ectoplasmic specializations and in regions adjacent to tubulobulbar processes of spermatogenic cells. At all of these sites, the filaments are morphologically related to the plasma membrane and+or intercellular membranes, and, as in many other cell types, are arranged in either bundles or networks. In at least two of the locations just indicated (ectoplasmic specializations and intercellular bridges), elements of the ER are closely related to the actin filaments. In tubulobulbar complexes, ER is present but is more distantly related to the filaments. Elements of the ER, when present, may serve a regulatory function. The filaments in ectoplasmic specializations and in regions adjacent to tubulobulbar processes of spermatogenic cells are suspected to be involved with the mechanism by which intercellular junctions are established, maintained, and degraded. In intercellular bridges, actin filaments may serve to reinforce and perhaps regulate the size of the cytoplasmic connections between differentiating germ cells. Filaments in the subacrosomal space may serve as a linking network between the acrosome and nucleus and may also be involved in the capping process. Because of the possibility that the actin filaments discussed before may be related to specific membrane domains involved with intercellular or interorganelle attachment, and that changes in these membrane domains are prerequisite to processes such as sperm release, turnover of the blood-testis barrier, formation of the acrosome, and coordination of spermatogenic cell differentiation, an understanding of exactly how these actin filaments are related to elements in the membrane and how this interaction is controlled is fundamental to our understanding, and perhaps our manipulating, of male fertility. I suspect that working out the molecular organization of these actin filament-containing sites and determining how their organization is controlled will be the major focus of research in this field over the next few years.


(How) do aluminium adjuvants work?
The aluminium compounds, originally identified as adjuvants over 70 years ago, remain unique in their widespread application to human vaccines. Given this history, it is surprising that the physicochemical interactions between aluminium compounds and antigens are relatively poorly understood. This has clearly been a contributing factor to vaccine failures, for example, through inappropriate selection of aluminium species or buffers. Similarly, the mechanism(s) of action of aluminium adjuvants are relatively unstudied, although it appears that these agents fail to fit within the current principles underlying activation of the immune response. This review aims to examine recent developments in our understanding of the physicochemical and biological aspects of research into aluminium adjuvants.


Single-cell profiling reveals the trajectory of FOLR2-expressing tumor-associated macrophages to regulatory T cells in the progression of lung adenocarcinoma.
An immunosuppressive microenvironment enriched with regulatory CD4+ T lymphocytes (Tregs) facilitates the progression of lung adenocarcinoma (LUAD). This study aims to investigate the cellular mechanism underlying the formation of the immunosuppressive microenvironment in LUAD. LUAD samples (n = 12) and normal lung samples (n = 3) were obtained from patients with different pathological stages of LUAD. Single-cell RNA sequencing was performed to classify cellular components and analyze the transcriptomes, including transcription factors/targets and chemokine ligands/receptors, followed by bioinformatics study such as pseudotime analysis. Myeloid cells and T cells were the most abundant cell types in tumors and normal lung tissues, while tumor-associated macrophage-folate receptor 2 (TAM-FOLR2) and CD4+ nuclear receptor subfamily 4 group A member 3 (NR4A3) exhibited sharp increases in invasive adenocarcinoma (IA). The enrichment of TAM-FOLR2 in IA might result from alveolar resident macrophage-resistin (ARM-RETN) transformation and recruitment of dendritic cells (DCs) and other TAMs, as evidenced by temporal trajectories and differential expression profiles of chemokine ligands/receptors versus those in the early stages of tumors. High expression of CCL17/19/22 was observed in IA as well as in DCs, along with the strong interaction of TAM-FOLR2 with DCs. The results of pseudotime analysis suggested that CD4+NR4A3 might potentially convert to CD4+FOXP3, further supported by the high expression of NR4A3 target genes in CD4+FOXP3 cells. This study provides a single-cell transcriptome atlas from preinvasive to invasive LUAD and reveals a potential ARM-RETN/TAM-FOLR2/DCs/CD4+NR4A3/CD4+FOXP3 trajectory in shaping the immune suppressive microenvironment along the pathogenesis of LUAD.


Go protein as signal transducer in the pertussis toxin-sensitive phosphatidylinositol pathway.
Receptors stimulating phospholipase C do so through heterotrimeric GTP-binding proteins to produce two second messengers, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol. In spite of the detailed understanding of phospholipase C structure and phosphatidyl inositol signalling, the identity of the GTP-binding protein involved is so far unknown. To address this issue, we have used the Xenopus oocyte in which muscarinic receptors couple to phospholipase C through a pertussis toxin-sensitive GTP-binding protein. In this cell, InsP3 mobilizes intracellular Ca2+ to evoke a Cl- current. The magnitude of this Cl- current is proportional to the amount of InsP3 in the cell, and therefore can be used as an assay for InsP3 production. We report here that the activated alpha-subunit of the GTP-binding protein GO, when directly injected into oocytes, evokes a Cl- current by mobilizing Ca2+ from intracellular InsP3-sensitive stores. We also show that holo-GO, when injected into oocytes, can specifically enhance the muscarinic receptor-stimulated Cl- current. These data indicate that GO can serve as the signal transducer of the receptor-regulated phospholipase C in Xenopus oocytes.


[Conventional radiology and computerized axial tomography in the diagnosis of pneumothorax in intensive therapy. Retrospective study of 2 years of activity].
The role played by chest radiograph and CT scan in diagnosis of pneumothorax is analyzed in a retrospective study based on two years of activity in Intensive Care Unit. The sensibility of traditional chest radiography was 75% while the sensibility of CT scan resulted higher (87.5%). In the authors opinion, when pneumothorax is suspected, particularly in patients with polytrauma, CT scan of the chest is mandatory unless patient's conditions or logistic difficulties related with transport of the patient contraindicate it.


Effect of educational intervention on knowledge and attitude about the role of vitamins, minerals and nutraceuticals in COVID-19 and other disorders among medical and nursing undergraduates of a tertiary care teaching hospital.
There must be a perfect balance between Food and Dietary supplements (DS) to ensure optimal well-being. The purpose of this study was to evaluate the impact of a webinar on the change in knowledge and attitude about the role of vitamins, minerals and DS among medical and nursing undergraduates so that they could bring about a positive change in popular practices, as well-informed Health Care Professionals (HCPs). The study was a cross-sectional analytical study comprising 12 knowledge and 11 attitude questions administered to medical and nursing undergraduates with the help of semi-structured and pre-validated google form both before and after a webinar explaining the role of key nutrients and also the evidence and recommendations surrounding DS. Data were analyzed using STATA.12 to assess the impact of the webinar. There were 415 participants, with 265 medical and 150 nursing students. There was a significant improvement both in the knowledge (4.95 (±1.45), 7.76 (±1.69) and attitude scores (pre-webinar mean score 31.8 (±5.57) post-webinar mean score 27.7 (±4.90))of the participants after the webinar. An overall positive correlation before the webinar changed to a more significant negative correlation, indicating a positive impact of the webinar (0.0054-0.0701). The study suggests that continuing education informing various HCPs and undergraduate students about the absolute necessity of a diet rich in nutrients, vitamins, minerals, and probiotics is the need of the hour. Additionally, the efficacy and safety concerns, appropriate indications and dosages of various DS should be adequately stressed so that informed decisions can be made. Such training programs might have a far-reaching impact on the nutrition choices of the population at large.


Scoliosis Progression After the Nuss Procedure for Pectus Excavatum: A Case Report.
Pectus excavatum and scoliosis are associated conditions with a high rate of coincidence. However, there are no reports to guide surgeons on the management of adolescents with moderate scoliosis and pectus excavatum, because there are conflicting conclusions in the literature regarding how the Nuss procedure with substernal bar affects scoliosis. In 2017, we encountered two patients with moderate scoliosis treated with a spinal orthosis. After undergoing the Nuss procedure for pectus excavatum, their scoliosis acutely progressed into surgical magnitude requiring posterior instrumented spinal fusion. The first patient progressed 26° despite the pre-Nuss radiographs showing him to be Risser 4/5, while the second patient also progressed 26° from the Nuss procedure. Both patients acknowledged noncompliance with brace wear because of discomfort after the Nuss procedure. However, their progression rate still doubles the rate of reported rapid accelerators, indicating that a significant component of curve progression is directly attributed to forces on the spine from the corrective maneuver with substernal bar. The purpose of this case report is to describe the features of these two patients to help with clinical decision-making in patients with moderate scoliosis (curves >25°) who are contemplating the Nuss procedure for correction of pectus excavatum. We caution patients and providers that spinal deformity could worsen with surgical intervention of the pectus excavatum via the Nuss procedure and necessitate scoliosis surgery.


Paraesophageal bronchogenic cyst associated with multiple epithelial splenic cysts.
Bronchogenic cysts are rare congenital cystic lesions of foregut origin. They are the result of abnormal budding of the primitive tracheobronchial tube. Nonparasitic, true splenic cysts are another rare entity that might occur as incidental findings but may lead to deleterious courses in case of ruptures. We report here the first case of the uncommon association of a paraesophageal bronchogenic cyst and multiple primary splenic cysts in a 23-year-old woman suffering from dysphagia and chest pain. Successful complete resection of the paraesophageal cyst was performed using an abdominal, transhiatal approach and splenic cysts were subjected to organ-preserving TA stapler resection. Thus far there is no proof or genetic indication for a direct association of bronchogenic cysts and multiple splenic cysts, however, the uncommon coincidence of both lesions in our patient might suggest a common origin. Difficulties in preoperative diagnosis, histopathological characteristics and surgical treatment modalities are presented.


Erythematous reactions to two ultraviolet excimer therapy devices with different irradiance levels: Reconsidering the reciprocity law.
Few studies have examined the effectiveness of the reciprocity law in ultraviolet excimer therapy. This study aimed to examine the difference in erythematous reaction in human skin when the irradiance of ultraviolet excimer treatment devices differed while the irradiation dose was constant. This study, conducted at the Department of Dermatology, Chiba University, included 15 healthy adults aged 20-65 years (mean age, 46.3 years; seven men). Using ultraviolet excimer treatment devices with different irradiances (50 or 150 mW/cm2 ), the upper abdomen of each participant was irradiated with ultraviolet light at set irradiation doses (80, 100, 120, 140, 160, 180, and 200 mJ/cm2 ). The erythema index of each irradiated site was measured using a melanin- and erythema-measuring device, and the difference in erythema index before and 24 h after irradiation was the primary endpoint. The change in erythema index was significantly higher for an irradiance of 150 mW/cm2 . Significant differences (p < 0.05) were observed between these irradiance levels at irradiation doses of 100-200 mJ/cm2 . Even for the same irradiation dose, stronger erythematous reactions occurred at higher irradiances in ultraviolet excimer treatment. This suggests that the reciprocity law may not always hold true in excimer therapy.


Evaluation of the spoilage heterogeneity of meat-borne Leuconostoc mesenteroides by metabonomics and in-situ analysis.
Leuconostoc mesenteroides are generally recognized as a group of specific spoilage organisms in meat and poultry products, which cause acidification and blown pack spoilage of meat. In this study, a total of 6 representative strains selected from 55 L. mesenteroides isolated from spoiled meat were tested to evaluate the spoilage ability by metabonomics and in-situ analysis. The intra-species spoilage heterogeneity was observed. The results showed that the acidifying and gas production capacity of L. mesenteroides was distinct between in broth and on meat. The pH of inoculated MRS broth was 1.38 to 1.49 units lower than that of the sterile broth and the height of gas column in Durham tube ranged from 8 mm to 11 mm at 72 h, all significantly different from the sterile group. Metabonomic analysis revealed that the main produced organic acids were myristic acid, butyric acid, lactic acid, valeric acid and enoic acid. It also illustrated that the UHPLC-MS/MS profiles of L4 and L5 was distinct from the other strains. In terms of meat inoculated with L. mesenteroides, most pH values did not show significant difference from that of the meat without inoculation, and vacuum packaging distension was not observed. Increase of TVB-N was very limited as well. The growth rate of L2, L4 and L5, as well as the pH changes of L3 and L6, varied wildly between different growth matrix. The differences between L5 and the other strains were the most obvious. The growth rate of L5 was the highest in vitro but the lowest in situ, and its acid- and gas-producing rate was relatively lower than that of the other groups. The results exhibited that it is limited to judge the bacteria-derived meat spoilage only by in-vitro growth. What should be focused on is the spoilage strengths in situ rather than the pure standard culture. In conclusion, the present study analyses profiles related to growth, acidification and gas production of L. mesenteroides in vitro and in situ, and provides references for emphasis on future research to reduce the loss of meat in consequence of spoilage.


Effect of sialoadenectomy on adaptive cytoprotection in the rat.
In the present study we have investigated the effect of sialoadenectomy in the rat on adaptive cytoprotection induced by intragastric instillation of an irritant concentration of ethanol (10% wt/vol). Gastric mucosae were examined 1 h after oral administration of 100% ethanol. In animals with intact salivary glands, pretreatment with saline was followed 15 min later by 100% ethanol. This treatment was associated with a significant degree of mucosal damage. However, prior administration of 10% ethanol in place of saline reduced the area of ulceration. In sialoadenectomized rats, the irritant concentration of ethanol did not protect the gastric mucosa from the damaging actions of absolute ethanol. The effect was partially restored if sialoadenectomized rats were treated for 3 days with an aqueous extract of rat salivary gland tissue. Histologic examination revealed no differences in the extent of epithelial damage or adherent mucus between rats with intact salivary glands and sialoadenectomized rats following pretreatment with either saline or 10% ethanol. Although adaptive cytoprotection in animals with intact salivary glands was not associated with increases in mucosal capacities for prostaglandin E2 or 6-keto prostaglandin F1 alpha biosynthesis, sialoadenectomy resulted in a reduction in the mucosal biosynthetic capacities for both prostanoids. Salivary gland extract administration to sialoadenectomized rats did not significantly alter mucosal prostaglandin biosynthesis levels. These data suggest that salivary gland factors affected adaptive cytoprotection induced by an irritant dose of ethanol. Although endogenous prostaglandin biosynthesis capabilities do not appear to be altered in adaptive cytoprotection, salivary factors appear to influence mucosal generation of prostaglandins.


A seismic metamaterial: The resonant metawedge.
Critical concepts from three different fields, elasticity, plasmonics and metamaterials, are brought together to design a metasurface at the geophysical scale, the resonant metawedge, to control seismic Rayleigh waves. Made of spatially graded vertical subwavelength resonators on an elastic substrate, the metawedge can either mode convert incident surface Rayleigh waves into bulk elastic shear waves or reflect the Rayleigh waves creating a "seismic rainbow" effect analogous to the optical rainbow for electromagnetic metasurfaces. Time-domain spectral element simulations demonstrate the broadband efficacy of the metawedge in mode conversion while an analytical model is developed to accurately describe and predict the seismic rainbow effect; allowing the metawedge to be designed without the need for extensive parametric studies and simulations. The efficiency of the resonant metawedge shows that large-scale mechanical metamaterials are feasible, will have application, and that the time is ripe for considering many optical devices in the seismic and geophysical context.


Effects of preoperative nutritional status on postoperative quality of recovery: a prospective observational study.
Quality of Recovery-15 (QoR-15) has received attention as a postoperative patient-reported outcome measure. Preoperative nutritional status has negative effects on postoperative outcomes; however, these associations have not yet been investigated. We included inpatients aged ≥ 65 years who underwent elective abdominal cancer surgery under general anaesthesia between 1 June 2021 and 7 April 2022 at our hospital. Preoperative nutritional status was assessed using the Mini Nutritional Assessment Short-Form (MNA-SF), and patients with an MNA-SF score ≤ 11 were categorised into the poor nutritional group. The outcomes in this study were the QoR-15 scores at 2 d, 4 d and 7 d after surgery, which were compared between groups by unpaired t test. Multiple regression analysis was applied to assess the effects of poor preoperative nutritional status on the QoR-15 score on postoperative day 2 (POD 2). Of the 230 included patients, 33·9 % (78/230) were categorised into the poor nutritional status group. The mean QoR-15 value was significantly lower in the poor nutritional group than in the normal nutritional group at all postoperative time points (POD 2:117 v. 99, P = 0·002; POD 4:124 v. 113, P < 0·001; POD 7:133 v. 115, P < 0·001). Multiple analyses showed that poor preoperative nutritional status was associated with the QoR-15 score on POD 2 (adjusted partial regression coefficient, -7·8; 95 % CI -14·9, -0·72). We conclude that patients with a poor preoperative nutritional status were more likely to have a lower QoR-15 score after abdominal cancer surgery.


Fauna access outweighs litter mixture effect during leaf litter decomposition.
Decomposition rates of litter mixtures reflect the combined effects of litter species diversity, litter quality, decomposers, their interactions with each other and with the environment. The outcomes of those interactions remain ambiguous and past studies have reported conflicting results (e.g., litter mixture richness effects). To date, how litter diversity and soil fauna interactions shape litter mixture decomposition remains poorly understood. Through a sixteen month long common garden litter decomposition experiment, we tested these interaction effects using litterbags of three mesh sizes (micromesh, mesomesh, and macromesh) to disentangle the contributions of different fauna groups categorized by their size at Wuhan botanical garden (subtropical climate). We examined the decomposition of five single commonly available species litters and their full 26 mixtures combination spanning from 2 to 5 species. In total, 2325 litterbags were incubated at the setup of the experiment and partly harvested after 1, 3, 6, 9, and 16 months after exposure to evaluate the mass loss and the combined effects of soil fauna and litter diversity. We predicted that litter mixture effects should increase with increased litter quality dissimilarity, and soil fauna should enhance litter (both single species litter and litter mixtures) decomposition rate. Litter mass loss ranged from 26.9 % to 87.3 %. Soil fauna access to litterbags accelerated mass loss by 29.8 % on average. The contribution of soil mesofauna did not differ from that of soil meso- and macrofauna. Incubation duration and its interactions with litter quality dissimilarities together with soil fauna determined the litter mixture effect. Furthermore, the litter mixture effect weakened as the decomposition progresses. Faunal contribution was broadly additive to the positive mixture effect irrespective of litter species richness or litter dissimilarity. This implies that combining the dissimilarity of mixture species and contributions of different soil fauna provides a more comprehensive understanding of mixed litter decomposition.


Syntaxin 4a Regulates Matrix Vesicle-Mediated Bone Matrix Production by Osteoblasts.
Osteoblasts secrete matrix vesicles and proteins to bone surfaces, but the molecular mechanisms of this secretion system remain unclear. The present findings reveal the roles of important genes in osteoblasts involved in regulation of extracellular matrix secretion. We especially focused on "soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor" (SNARE) genes and identified notable Syntaxin 4a (Stx4a) expression on the basolateral side of the plasma membrane of osteoblasts. Furthermore, Stx4a overexpression was found to increase mineralization by osteoblastic cells, whereas Stx4a knockdown reduced levels of mineralization. Also, BMP-4 and IGF-1 induced the localization of Stx4a to the basolateral side of the cells. To examine the function of Stx4a in osteoblasts, we generated osteoblast-specific Stx4a conditional knockout mice, which demonstrated an osteopenic phenotype due to reduced matrix secretion. Bone mineral density, shown by peripheral quantitative computed tomography (pQCT), was reduced in the femur metaphyseal and diaphyseal regions of Stx4a osteoblast-specific deficient mice, whereas bone parameters, shown by micro-computed tomography (μCT) and bone histomorphometric analysis, were also decreased in trabecular bone. In addition, primary calvarial cells from those mice showed decreased mineralization and lower secretion of matrix vesicles. Our findings indicate that Stx4a plays a critical role in bone matrix production by osteoblasts. © 2016 American Society for Bone and Mineral Research.


Leptin: linking obesity, the metabolic syndrome, and cardiovascular disease.
The incidence and prevalence of obesity and the metabolic syndrome have risen markedly in the past decade, representing a serious cardiovascular health hazard with significant morbidity and mortality. The etiology of the metabolic syndrome and its various pathogenic mechanisms are incompletely defined and under intense investigation. Contemporary research suggests that the adipocyte-derived hormone leptin may be an important factor linking obesity, the metabolic syndrome, and cardiovascular disorders. Although recent evidence indicates that under normal conditions leptin may be an important factor in regulating pressure and volume, during situations of chronic hyperleptinemia and leptin resistance, this hormone may function pathophysiologically for the development of hypertension and cardiac and renal diseases. Future research will determine if reduction of circulating leptin and/or blockade of its peripheral actions can confer cardiovascular and renal protection in hyperleptinemic patients with obesity and the metabolic syndrome.


Axial volvulus of Meckel's diverticulum: a rare cause of acute abdominal pain.
We present the case of a 29-year-old woman with abdominal pain. Because of uncertainty about the diagnosis, a nondiagnostic laparoscopy was performed, necessitating an exploratory laparotomy. A torsed, incarcerated Meckel's diverticulum was discovered and resected. The patient recovered uneventfully.


Simple Prognostic Criteria can Definitively Identify Patients who Develop Severe Versus Non-Severe Dengue Disease, or Have Other Febrile Illnesses.
SEVERE DENGUE DISEASE (SDD) (DHF/DSS: dengue hemorrhagic fever/dengue shock syndrome) results from either primary or secondary dengue virus (DENV) infections, which occur 4 - 6 days after the onset of fever. As yet, there are no definitive clinical or hematological criteria that can specifically identify SDD patients during the early acute febrile-phase of disease (day 0 - 3: < 72 hours). This study was performed during a SDD (DHF/DSS) epidemic to: 1) identify the DENV serotypes that caused SDD during primary or secondary DENV infections; 2) identify simple clinical and hematological criteria that could significantly discriminate between patients who subsequently developed SDD versus non-SDD (N-SDD), or had a non-DENV fever of unknown origin (FUO) during day 0 - 3 of fever; 3) assess whether DENV serotype co-infections resulted in SDD. First serum samples, with clinical and hematological criteria, were collected from 100 patients during the early acute febrile-phase (day 0 - 3: < 72 hours), assessed for DENV or FUO infections by IgM- and IgG-capture ELISAs on paired serum samples and by DENV isolations, and subsequently graded as SDD, N-SDD or FUO patients. IN THIS STUDY: 1) Thirty-three patients had DENV infections, predominantly secondary DENV-2 infections, including each SDD (DHF/DSS) case; 2) Secondary DENV-2/-3 and DENV-2/-4 serotype co-infections however resulted in N-SDD; 3) Each patient who subsequently developed SDD, but none of the others, displayed three clinical criteria: abdominal pain, conjunctival injection and veni-puncture bleeding, therefore each of these criteria provided definitively significant prognostic (P < 0.001) values; 4) Petechia, positive tourniquet tests and hepatomegaly, and neutrophilia or leukopenia also significantly identified those who: a) subsequently developed SDD versus N-SDD, or had a FUO; b) subsequently developed SDD versus N-SDD; c) subsequently developed N-SDD versus FUOs, respectively. This is the first report of simple definitively prognostic criteria for SDD patients, including the first assessment and confirmation of conjunctival injection. The three definitive clinical criteria used alone, or supported by the other four criteria, could be essential for specifically identifying those patients needing prompt hospital-based therapies to lessen or avert SDD, without unnecessary hospitalization of the other patients. Dengue virus; Severe dengue; Dengue fever; Diagnostic; Criteria; Hemorrhage; Shock.


Evidence for improved cerebral function after minimally invasive bypass surgery.
Neurological impairment is a major cause of morbidity after cardiac surgery and may be associated with occurrence of cerebral microemboli generated during cardiopulmonary bypass (CPB). This study evaluates cerebral dysfunction following coronary artery surgery on-pump and off-pump. Neurological outcome was evaluated in 322 patients with a coronary artery bypass graft (CABG). Conventional CPB was used (on-pump) in 305 patients and in 17 patients no CPB was used (off-pump). Intraoperatively, a pulsed-wave transcranial Doppler with a 2-MHZ probe measured high-intensity transient signals (HITS) by ultrasonic insonnation of the middle cerebral artery indicating the presence of emboli within the vessel lumen. Transcranial near-infrared spectroscopy measured cerebral venous oxygen saturation for adequate perfusion. Postoperatively, all patients were subjected to the antisaccadic eye movement (ASEM) test, a sensitive indicator of neurocognitive deficits secondary to frontal lobe dysfunction. While there was no significant difference in O2 saturation, the number of microemboli HITS generated was significantly higher in the on-pump group than the off-pump group. In the off-pump group, 16 (94%) of 17 patients had perfect scores on the ASEM test, while only 108 (35.4%) of 305 patients achieved a perfect score in the on-pump group (p < 0.01). Furthermore, while all patients in the off-pump group achieved at least 90%, 28% (86/305) in the on-pump group scored "zero" on the ASEM test. Cerebral dysfunction as evidenced by ASEM errors is common following coronary bypass on-pump, but rare with off-pump bypass surgery. Cerebral microemboli generated during CPB may account for this difference.


Treatment of chronic myelogenous leukemia with interferons alpha and gamma.
A 23-year-old male patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) was treated with both IFN alpha and IFN gamma. Normalization of leukocyte counts was reached after 3 months of treatment. Southern blot analysis failed to detect the neoplastic cell clone after 19 months of therapy. Cytogenetically, complete suppression of Ph positive cells in the patient's bone marrow and blood was observed after 20 months and 25 months, respectively. This response was achieved with doses of IFN alpha and IFN gamma which were considerably lower than the dosage of IFN used in single agent therapy of CML.


Immunofluorescence and ultrastructural analysis of the chromatoid body during spermatogenesis of Triatoma platensis and T. rubrovaria (Hemiptera, Triatominae).
This study sought to analyze spermatogenesis in two species of triatomines (Triatoma rubrovaria and T. platensis) by focusing on the chromatoid body (CB) during three stages of spermatogenesis (spermatocytogenesis, meiosis, and spermiogenesis). The cytochemistry technique known as silver impregnation revealed nucleolar persistence. We suggest that this phenomenon is fundamental to the formation of the CB during spermatogenesis, as it allows for the nucleolus or nucleolar fragments to maintain their transcriptional activity during the entire meiosis phase and to apply all transcribed RNA to CB formation. The ultrastructural analysis of T. platensis and T. rubrovaria spermatids revealed the presence of the nucleolus within the spermatid nucleus, as well as the CB near the nuclear membrane. Immunofluorescence for fibrillarin revealed the presence of protein in both the nucleolus and the cytoplasm of spermatogonia. Based on these findings, we suggest that the formation of the CB begins during the first phase of spermatogenesis, or spermatocytogenesis. Furthermore, we also observed the presence of fibrillarin protein in the CB near the elongating spermatids. Unlike the spermatogonia, spermatids showed no fibrillarin markings in the nucleolar region, a finding which is consistent with the lack of post-meiotic transcriptional activity during triatomine spermiogenesis. Thus, this study suggests that the formation of the CB begins during spermatocytogenesis and is intensified by transcriptional activity when nucleolar persistence occurs in meiosis. Moreover, the findings are consistent with the absence of transcriptional activity in the nucleolus during spermiogenesis, and they demonstrate that all transcriptional activity during spermatid differentiation is supported by the CB.


Observation of Brillouin scattering from single muscle fibres.
The propagation of sound waves along relaxed single fibres of glycerinated rabbit psoas muscle has been observed using Brillouin scattering at frequencies up to 1.6 GHz. Two types of waves were observed: one with a velocity of 1508 +/- 7 m s-1, which is attributed to sound waves in intra-cellular saline, the other with a velocity of 912 +/- 25 m s-1, which is attributed to waves propagating along the protein filaments within individual sarcomeres. The latter sound velocity is much higher than that which has been reported by Stienen and Blangé (1985) for 50 microseconds tension transients, and the difference is attributed to the much higher stiffness of the protein filaments compared to the cross-bridges which determine the low-frequency elasticity of muscle fibres.


Epigenetic changes and alternate promoter usage by human colon cancers for expressing DCLK1-isoforms: Clinical Implications.
DCLK1 specifically marks colon/pancreatic cancers in mice, and is expressed by human colon adenocarcinomas (hCRCs). Down-regulation of DCLK1 results in loss of cancer-stem-cells (CSCs), and inhibits spheroidal/xenograft growths from hCRC-cells. The 5'-promoter of DCLK1-gene is reportedly hypermethylated in hCRCs, resulting in loss of expression of DCLK1-transcripts, originating from 5'(α)-promoter (termed DCLK1-L, in here). However, in mouse colon-tumors, 5'-promoter of DCLK1-gene remains unchanged, and DCLK1-L, originating from 5'(α)-promoter, is expressed. We hypothesized that elevated levels of DCLK1-protein in hCRC-cells, may be transcribed/translated from an alternate-promoter. Several in silico and molecular biology approaches were used to test our hypothesis. We report for the first time that majority of hCRCs express short-transcripts of DCLK1 (termed DCLK1-S, in here) from an alternate β-promoter in IntronV of the gene, while normal-colons mainly express DCLK1-L from 5'(α)-promoter. We additionally report an important role of β-catenin and TCF4/LEF binding-sites for activating (α)-promoter, while activated NF-κBp65 (bound to NF-κB-cis-element), activates (β)-promoter in cancer-cells. DCLK1-S expression was examined in a cohort of 92 CRC patients; high-expressors had significantly worse overall-survival compared to low-expressors. Our novel findings' regarding usage of alternate (β)-promoter by hCRCs, suggests that DCLK1-S may represent an important target for preventing/inhibiting colon-cancers, and for eliminating colon-CSCs.


Fluorodesulfurization of Thionobenzodioxoles with Silver(I) Fluoride.
Difluorobenzodioxole is an important functional group found in both pharmaceuticals and agrochemicals. The late-stage introduction of this functional group is challenged by typical fluorination conditions of HF and strong oxidants. Here, we demonstrate that a range of difluorobenzodioxoles can be prepared from catechols in two steps through conversion into thionobenzodioxoles, followed by desulfurative fluorination with silver(I) fluoride. These mild reaction conditions are compatible with a variety of functional groups and enable access to a range of functionalized difluorobenzodioxoles.


Early life history responses and phenotypic shifts in a rare endemic plant responding to climate change.
Changes in species ranges are anticipated with climate change, where in alpine settings, fragmentation and contraction are likely. This is especially true in high altitude biodiversity hotspots, where warmer growing seasons and increased drought events may negatively impact populations by limiting regeneration. Here, we test for high-altitude species responses to the interactive effects of warming and drought in Heterotheca brandegeei, a perennial cushion plant endemic to alpine outcroppings in Sierra de San Pedro Mártir National Park, Baja California, México. We exposed H. brandegeei seedlings to experimental warming and drought conditions to document early life history responses and the species ability to tolerate climate change. Drought negatively influenced seedling growth, with overall reductions in above- and belowground biomass. Warming and drought each led to substantial reductions in leaf development. At the same time, individuals maintained high specific leaf area and carbon investment in leaves across treatments, suggesting that existing phenotypic variation within populations may be high enough to withstand climate change. However, warming and drought interacted to negatively influence leaf-level water-use efficiency (WUE). Seedling mortality rates were nearly three times higher in warming and drought treatments, suggesting bleak prospects for H. brandegeei populations in future climate conditions. Overall, our results suggest H. brandegeei populations may experience substantial declines under future warmer and drier conditions. Some individuals may be able to establish, albeit, as smaller, more stressed plants. These results further suggest that warming alone may not be as consequential to populations as drought will be in this already water-limited system.


The pharmacokinetics of the bispecific antibody MDX-H210 when combined with interferon gamma-1b in a multiple-dose phase I study in patients with advanced cancer.
MDX-H210 is a Fab'xFab' bispecific antibody (BsAb) constructed chemically by crosslinking Fab' mAb 520C9 (anti-HER-2/neu) and humanized Fab' mAbH22 (anti-CD64). This was a phase I dose-escalation study of intravenous MDX-H210 (1-70 mg/m(2)) combined with subcutaneous IFN-gamma, 50 microg/m(2) given 24 h before the BsAb, both drugs being given three times a week for 3 weeks. The major objectives of the study were to define the safety, tolerability and pharmacokinetics of MDX-H210 when given with IFN-gamma on this schedule. The study group comprised 23 patients (19 female, 4 male; median age 51.5 years, range 25-72 years) with advanced HER-2/neu-positive cancers (19 breast, 3 prostate and 1 lung). Inspection of the log plasma MDX-H210 concentrations-time data for both days 1 and 17 of treatment revealed monoexponential decay in the majority of patients with adequate concentration-time data points. The MDX-H210 T(1/2) ranged from 2.9 to 21.9 h. The MDX-H210 C(max) on day 1 (means+/-SD) increased from 0.30+/-0.22 microg/ml at the 1-mg/m(2) dose tier to 86.91+/-6.46 microg/ml at 70 mg/m(2). Equivalent day-17 values were 0.27+/-0.30 microg/ml increasing to 147.85+/-40.23 microg/ml. The MDX-H210 T(max) occurred at or after the end of the infusion for all treatments. The mean MDX-H210 total body clearance (Cl) was in the range 0.01-0.34 ml/min per kg and the mean MDX-H210 apparent volume of distribution at steady-state (Vd(ss)) in the range 20-170 ml/kg, compatible with distribution primarily limited to the intravascular space. MDX-H210 T(1/2) increased with dose (ANOVA P=0.001) and Cl decreased with dose (ANOVA P=0.006). There were no significant changes in MDX-H210 C(max), AUC, Cl or Vd(ss) between day 1 and day 17. MDX-H210 pharmacokinetics appeared saturable over the dose range 1-70 mg/m(2), and there was no significant change in MDXH210 pharmacokinetics over the course of the study, or evidence of excessive accumulation of MDX-H210 on this multiple dosing schedule. When MDX-H210 was combined with IFN-gamma, the estimated MDX-H210 pharmacokinetic parameters were similar to the published data for single-agent MDX-H210.


Anal endosonographic assessment of the accuracy of clinical diagnosis of obstetric anal sphincter injury.
Obstetric anal sphincter injuries (OASIS) are a common cause of maternal morbidity with an overall incidence in the UK of 2.9% (range 0-8%). They can cause a range of physical symptoms and psychological distress. This study aims to assess the accuracy of clinical diagnosis of OASIS using endoanal ultrasound (EAUS) and the correlation between confirmed injury and change to anorectal physiology squeeze pressure and the incidence of bowel symptoms. Retrospective study of prospectively collected data from 1135 women who attended the Third- and Fourth-Degree Tears Clinic at our institution, 12 weeks post-delivery, between June 2008 and October 2019. OASIS was confirmed in 876 (78.8%) women and 236 (21.3%) had no injury. Of the women who underwent anorectal physiology, 45.6% had a mean maximal resting pressure below the normal range and 68.8% had a mean incremental squeeze pressure below normal. Women with confirmed OASIS had significantly lower pressures (p < 0.001) than those without a confirmed sphincter injury. Three hundred ninety-three (34.8%) women reported bowel symptoms, with those with endosonographic evidence of injury more likely to develop flatus incontinence. Of the women in this study with a suspected OASIS, 21.2% could be reassured that they did not have an injury. This information is useful for women considering future mode of delivery. Those with confirmed injury are more likely to complain of flatus incontinence and have reduced anal sphincter pressures.


Idiopathic renal arteriovenous fistula demonstrating a huge aneurysm with a high risk of rupture: report of a case.
This paper reports a case of an idiopathic renal arteriovenous fistula demonstrating a huge guitar-shaped aneurysm, which required a total nephrectomy. Although the patient insisted on having been asymptomatic, echocardiography and cardiac catheterization clearly revealed that the influence on hemodynamics was unexpectedly significant. Interestingly, the aneurysm was also considered to have a high risk of rupture, which was preoperatively suggested by an aneurysm wall projection discernible on both computerized tomograms and angiograms, and this suspicion was also convincingly supported by the perioperative and histopathological findings.


Negative pressure in pharyngo-oral cavity can treat lymphedema and related disorders.
With the finding of specific markers and growth factors for lymphatic vessels, more and more attentions were paid to research on lymphatic vascular system. But the treatment of lymphedema and related disorders is still difficult. Waldeyer's ring is the lymphoid tissues that form a ring around the opening of the throat including tonsils laterally, adenoids superiorly, and lingual tonsil at the base. We hypothesized that negative pressure in pharyngo-oral cavity can improve lymphatic system circulation by affect Waldeyer's ring. And this treatment is proved to be useful in the therapy of lymphedema and chyloperitoneum. So we came to the conclusion that negative pressure in pharyngo-oral cavity was helpful in the treatment of lymphedema and related disorders. But the mechanism of this treatment still need further study. The future of this field of research is very promising and may eventually lead to better treatment of lymphedema and related disorders.


Post COVID 19 acute acalculous cholecystitis raising the possibility of underlying dysregulated immune response, a case report.
Novel Coronavirus disease 2019 or COVID-19 has rapidly spread throughout the world and has become an unprecedented pandemic. It has a vast spectrum of clinical presentations and can affect various organs. Rarely, it has been reported to cause acalculous cholecystitis in a non ICU setting patient. Here we report a rare association of COVID 19 with acalculous cholecystitis in a 40 years old healthy woman. She developed fever, malaise, generalized body weakness, and right hypochondrial pain after fourteen days of COVID 19 infection, raising the possibility of Post COVID dysregulated immune response resulting in acalculous cholecystitis. She was managed conservatively with broad spectrum antibiotics. Acalculous cholecystitis primarily occurs due to the gall bladder's hypomotility and most commonly seen in critically ill patients such as severe burns, mechanically ventilated patients, and prolonged parenteral nutrition. The management depends upon treating the underlying pathology and, in some severe cases, may need surgical intervention as well. Up to our knowledge, COVID 19, causing acalculous cholecystitis, is a rare association described only in a few critically ill patients but not in young, healthy patients. It can be attributed to the body's dysregulated immunological response against the virus resulting in systemic inflammation. Currently, there is are no clear guidelines for managing acute cholecystitis in COVID-19 patients. It depends on the patient's clinical state and disease severity. We aim to highlight the importance of early diagnosis and management in such clinical scenarios to avoid fatal complications.


Negative regulatory regions are present upstream in the three mouse neurofilament genes.
We have cloned and examined the 5' flanking regions of the heavy (NF-H), light (NF-L) and mid-sized (NF-M) mouse neurofilament (NF) genes in order to begin to characterize the regions of each gene that regulate NF transcription. Chimeric plasmids bearing the CAT reporter gene and deletion mutants of the upstream NF genes were transiently transfected into neuronal (PC12 and Neuro 2A) and non-neuronal (HeLa) cell lines. Constructs bearing upstream regions to -4000 in NF-H, to -5600 in NF-L and to -4500 in NF-M were expressed at low levels in neuronal and in non-neuronal cells. Progressive deletion of 5' flanking sequence to -385 in NF-H, to -325 in NF-L and to -505 in NF-M caused a several-fold increase of transcription from the transfected plasmids. Increases of transcription by deletion mutants followed a similar pattern in neuronal and in non-neuronal cell lines. Negative upstream regions are located between -1314 and -385 in NF-H, between -936 and -325 in NF-L and between -874 and -505 in NF-M. Additional negative regions are present further upstream in NF-L and in NF-H. The negative regions of NF-H and of NF-L suppress transcription when placed in either orientation in front of the SV40 or a heterologous NF promoter. These studies demonstrate that the three mouse NF genes possess similar functional features, namely, that of a relatively strong and promiscuous promoter with negative upstream elements. The role of the negative elements in regulating NF expression remains unclear.


Contribution of Round vs. Rectangular Expandable Cage Endcaps to Spinal Stability in a Cadaveric Corpectomy Model.
Expandable cages are gaining popularity in anterior reconstruction of the thoracolumbar spine following corpectomy as they can provide adjustable distraction and deformity correction. Rectangular, rather than circular, endcaps provide increased resistance to subsidence by spanning the apophyseal ring; however their impact on construct stability is not known. The objective of this study was to investigate the contribution of expandable corpectomy cage endcap shape (round vs. rectangular) and fixation method (anterior plate vs. posterior pedicle screws) to the stability of an L1 sub-total corpectomy construct. Eight fresh-frozen cadaveric specimens (T11-L3) were subjected to multi-directional flexibility testing to 6 N·m with a custom spine simulator. Test conditions were: intact, L1 sub-total corpectomy defect, expandable cage (round endcap) alone, expandable cage (round endcap) with anterior plate, expandable cage (round endcap) with bilateral pedicle screws, expandable cage (rectangular endcap) alone, expandable cage (rectangular endcap) with anterior plate, expandable cage (rectangular endcap) with bilateral pedicle screws. Range-of-motion across T12-L2 was measured with an optoelectronic system. The expandable cage alone with either endcap provided significant stability to the corpectomy defect, reducing motion to intact levels in flexion-extension with both endcap types, and in lateral bending with rectangular endcaps. Round endcaps allowed greater motion than intact in lateral bending, and axial rotation ROM was greater than intact for both endcaps. Supplemental fixation provided the most rigid constructs, although there were no significant differences between instrumentation or endcap types. These results suggest anterior-only fixation may be adequate when using an expandable cage in a sub-total corpectomy application and choice of endcap type may be driven by other factors such as subsidence resistance.


Photographic analysis of faces of 20-year-old students in Iran.
We studied 100 20-year-old students at the University of Kerman in Iran. On life-sized frontal and profile photographs, we measured nine linear and seven angular indices. The mean (S.D.) distance in mm between the two medial canthi was 31 (3), width of alar base 37 (3), length of nose 48 (4), width of mouth 50 (4), length of upper lip 20 (2), nasolabial angle 98 degrees (10 degrees ), nasofrontal angle 130 degrees (9 degrees ), and angle of throat 120 degrees (14 degrees ). Most of the indices were similar in men and women. When we compared our results with studies elsewhere we found many differences and this shows the need to record the facial indices in different races and ethnic groups separately. The use of these indices in maxillofacial surgery, rhinoplasty, and plastic surgery should take account of these differences.


Multi-oscillatory control of circadian rhythms in human performance.
Circadian rhythms are known to exist in many measures of human performance efficiency as well as in physiological processes. The demands of a task, and in particular its 'working memory' load, play a large part in determining the time of day at which it is best performed. Furthermore, task demands may affect the speed with which performance rhythms adjust to the altered sleep/wake schedules occasioned by shift-work and rapid time-zone transitions. These differences in rate of adjustment may be explained by a similar multi-oscillatory model to those proposed for physiological rhythms. These assume any given circadian rhythm to be jointly controlled by two endogenous oscillators. The first is thought to be relatively immune to exogenous factors and to control the temperature rhythm, while the second is thought to be more influenced by exogenous factors and to have the major role in governing the sleep/wake cycle. Normally, the pronounced 24-h time cues, or 'zeitgebers', in our environment result in both oscillators, and hence all circadian rhythms, running with a period of 24 h. However, under altered sleep/wake schedules, and in conditions of temporal isolation, the temperature rhythm and sleep/wake cycle may separate from one another and run with distinctly different periods. When such 'internal desynchronization' occurs, other physiological rhythms have been found to run in synchrony with one or other of these two functions. This finding forms the basis of current multi-oscillatory models. However, studies of abnormal sleep/wake schedules suggest that the rhythm in working memory performance may sometimes separate from both the sleep/wake cycle and temperature rhythm by running with a period of less than 24 h. We have investigated this possibility here and our results indicate control of working memory performance rhythms by a previously unidentified oscillator with an autonomous period of about 21 h.


Effect of teriparatide on the healing of mandibular condylar osteochondral defects: a preclinical study.
This study was performed to evaluate the effect of teriparatide therapy on the healing of osteochondral defects of the mandibular condylar. Ninety-six rats underwent surgery to create a defect in the condylar head on one side of the mandible, and were divided into two groups. One group received subcutaneous injection of 2 µg/kg/day teriparatide, and the other group received normal saline until sacrifice. On postoperative days 20, 40, and 60, 16 animals from each group were sacrificed, and bone and cartilage healing was histologically evaluated and semiquantitatively scored (1-5). The mean difference in healing score of the cartilaginous and subchondral parts of the defect between the teriparatide and control groups at days 20, 40 and 60 were 0.438 and 0.438, 0.813 and 0.750, and 1.125 and 0.813, respectively. The healing scores of the osteochondral defects in the teriparatide group were significantly (p< 0.05) higher than that in the control group at days 40 and 60. This study has shown beneficial effects of teriparatide on the healing of condylar osteochondral defects in rats. Clinical trials are required to extrapolate these findings to humans.