The arterial blood supply of the parametrium.
The possible influence of tubal sterilization on the ovarian function is still debated. In this study, we have investigated the course of the main arteries in the parametrium. This study concludes that it is unlikely, from an anatomical point of view, that the ovarian function can be disturbed after tubal sterilization with bipolar cautery, silicone-rings or Filshieclips due to changes in the arterial blood supply.


Informed shared decision-making supported by decision coaches for women with ductal carcinoma in situ: study protocol for a cluster randomized controlled trial.
Women with breast cancer want to participate in treatment decision-making. Guidelines have confirmed the right of informed shared decision-making. However, previous research has shown that the implementation of informed shared decision-making is suboptimal for reasons of limited resources of physicians, power imbalances between patients and physicians and missing evidence-based patient information. We developed an informed shared decision-making program for women with primary ductal carcinoma in situ (DCIS). The program provides decision coaching for women by specialized nurses and aims at supporting involvement in decision-making and informed choices. In this trial, the informed shared decision-making program will be evaluated in breast care centers. A cluster randomized controlled trial will be conducted to compare the informed shared decision-making program with standard care. The program comprises an evidence-based patient decision aid and training of physicians (2 hours) and specialized breast care and oncology nurses (4 days) in informed shared decision-making. Sixteen certified breast care centers will be included, with 192 women with primary DCIS being recruited. Primary outcome is the extent of patients' involvement in shared decision-making as assessed by the MAPPIN-Odyad (Multifocal approach to the 'sharing' in shared decision-making: observer instrument dyad). Secondary endpoints include the sub-measures of the MAPPIN-inventory (MAPPIN-Onurse, MAPPIN-Ophysician, MAPPIN-Opatient, MAPPIN-Qnurse, MAPPIN-Qpatient and MAPPIN-Qphysician), informed choice, decisional conflict and the duration of encounters. It is expected that decision coaching and the provision of evidence-based patient decision aids will increase patients' involvement in decision-making with informed choices and reduce decisional conflicts and duration of physician encounters. Furthermore, an accompanying process evaluation will be conducted. To our knowledge, this is the first study investigating the implementation of decision coaches in German breast care centers. Current Controlled Trials ISRCTN46305518 , date of registration: 5 June 2015.


Comparison of effectiveness of different training tools on the level of knowledge about emergency management of avulsed teeth in non-dentists.
Tooth avulsion is a type of trauma requiring an emergency response, and the level of knowledge of non-dentists on the emergency management of avulsed teeth is important for the prognosis of affected teeth. This study aimed to compare the effectiveness of training given using different tools on the level of knowledge about the emergency management of avulsed teeth in non-dentists. A total of 125 individuals (female, 32.8%; male, 67.2%; mean age, 38.5 ± 7.32 years) participated in the study. The participants were randomly assigned to three groups, and the training was offered to these groups using different training tools (group 1, storybook; group 2, poster; group 3, ToothSOS App). A survey was conducted on all participants to measure their knowledge levels before training (T0), immediately after (T1), and 1 month later (T2). The Mann-Whitney U, Kruskal-Wallis, Wilcoxon, and Friedman tests were used for statistical analysis. The participants' mean correct answer scores on a scale from 0 to 21 were 7.76 ± 4.00, 5.47 ± 4.71, and 7.38 ± 2.96 at T0 in groups 1, 2, and 3, respectively, and their mean scores increased to 14.68 ± 4.10, 13.74 ± 3.28, and 13.86 ± 3.01 at T1 and 13.41 ± 3.34, 12.34 ± 3.77, and 13.66 ± 3.56 at T2. The correct answer scores increased significantly at both T1 and T2 in all groups (p < 0.001). None of the training tools used in the study was superior in increasing the level of knowledge. More comprehensive and long-term studies on this subject are needed.


Designing for implementation: user-centered development and pilot testing of a behavioral economic-inspired electronic health record clinical decision support module.
Current guidelines recommend less aggressive target hemoglobin A1c (HbA1c) levels based on older age and lower life expectancy for older adults with diabetes. The effectiveness of electronic health record (EHR) clinical decision support (CDS) in promoting guideline adherence is undermined by alert fatigue and poor workflow integration. Integrating behavioral economics (BE) and CDS tools is a novel approach to improving adherence to guidelines while minimizing clinician burden. We will apply a systematic, user-centered design approach to incorporate BE "nudges" into a CDS module and will perform user testing in two "vanguard" sites. To accomplish this, we will conduct (1) semi-structured interviews with key informants (n = 8), (2) a 2-h, design-thinking workshop to derive and refine initial module ideas, and (3) semi-structured group interviews at each site with clinic leaders and clinicians to elicit feedback on three proposed nudge module components (navigator section, inbasket refill protocol, medication preference list). Detailed field notes will be summarized by module idea and usability theme for rapid iteration. Frequency of firing and user action taken will be assessed in the first month of implementation via EHR reporting to confirm that module components and related reporting are working as expected as well as assess utilization. To assess the utilization and feasibility of the new tools and generate estimates of clinician compliance with the Choosing Wisely guideline for diabetes management in older adults, a 6-month, single-arm pilot study of the BE-EHR module will be conducted in six outpatient primary care clinics. We hypothesize that a low burden, user-centered approach to design will yield a BE-driven, CDS module with relatively high utilization by clinicians. The resulting module will establish a platform for exploring the ability of BE concepts embedded within the EHR to affect guideline adherence for other use cases.


Molecular characterization of carbapenem-resistant Pseudomonas aeruginosa isolated from four medical centres in Iran.
Understanding the mechanisms of antibiotic resistance is important for designing new therapeutic options and controlling resistant strains. The goal of this study was to look at the molecular epidemiology and mechanisms of resistance in carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates from Tabriz, Iran. One hundred and forty P. aeruginosa were isolated and antibiotic susceptibility patterns were determined. Overproduction of AmpC and efflux pumps were discovered using phenotypic techniques. Polymerase chain reaction (PCR) was used to determine the presence of carbapenemase-encoding genes. In addition, the expressions of OprD and efflux pumps were evaluated by the Real-Time PCR. Random amplified polymorphic DNA typing (RAPD) was performed for genotyping. Among 140 P. aeruginosa isolates, 74 (52.8%) were screened as CRPA. Overexpression of efflux systems was observed in 81% of isolates, followed by decreased expression of OprD (62.2%), presence of carbapenemase genes (14.8%), and overproduction of AmpC (13.5%). In most isolates, carbapenem resistance was multifactorial (60.8%). According to our results, the prevalence of CRPA is at alarming levels. Overexpression of efflux systems was the most common mechanism of carbapenem resistance. Most isolates may originate in patients themselves, but cross-infection is possible. Therefore, we suggest a pattern shift in the strategy of CRPA in our setting.


The first-born child: patterns of development.
209 first-born infants and their mothers were studied at birth and again two months later in order to learn how they had adapted to post-natal life. Only a small minority had escaped ill-health and also achieved the ideal of a contented breast-fed baby with an established routine. At two months 33-5 per cent were still breast feeding. Difficulties with feeding were reported by 55 per cent of mothers. 24-4 per cent of the babies were having a night feed at two months and 24-8 per cent had not yet established a daytime routine. The daily number of feeds ranged from three to seven, with a median of five. Medical problems had occurred in 46-5 per cent of the babies. Bottle-fed babies had more infections, and were more likely to use a dummy than breast-fed babies. Wakefulness during the daytime ranged from less than four hours to more than 10 hours. Many of these women were over-anxious. The primary care teams and paediatric services face a major task in helping today's primiparous mothers and their infants make a good start in life together.


A quantitative histochemical study of three oxidative enzymes in solar keratoses and Bowen's disease.
Succinate dehydrogenase (SDH), glucose-6-phosphate dehydrogenase (G6PDH) and lactate dehydrogenase (LDH) activities have been studied using quantitative enzyme histochemical techniques in the epidermis of five patients with solar keratoses and Bowen's disease. 'Non sun-exposed' buttock skin was compared with the skin from the actual lesion and adjacent, clinically normal paralesional skin. SDH activity was significantly increased in the basal layer and decreased in the granular layer in the epidermis of both lesion and paralesional skin, although the total epidermal activities were unchanged when compared to 'non-exposed' buttock skin. G6PDH activity was increased in the granular layer of paralesional epidermis and of lesions. No change in LDH activity was detected. Inclusion of phenazine methosulphate in the reaction mixtures resulted in a three-fold increase in formazan deposition without altering the localization. It is concluded that the quantitative changes and alteration in localization of SDH and G6PDH reported in solar keratoses are accompanied by similar changes in adjacent, clinically normal 'sun-exposed' skin and differ from normal 'non-exposed' skin. It is suggested that these changes may precede the development of the solar keratoses and that these findings may indicate a significant metabolic alteration in the events that lead to neoplasia.


Concerted vs. sequential. Two activation patterns of vast arrays of intracellular Ca2+ channels in muscle.
To signal cell responses, Ca(2+) is released from storage through intracellular Ca(2+) channels. Unlike most plasmalemmal channels, these are clustered in quasi-crystalline arrays, which should endow them with unique properties. Two distinct patterns of local activation of Ca(2+) release were revealed in images of Ca(2+) sparks in permeabilized cells of amphibian muscle. In the presence of sulfate, an anion that enters the SR and precipitates Ca(2+), sparks became wider than in the conventional, glutamate-based solution. Some of these were "protoplatykurtic" (had a flat top from early on), suggesting an extensive array of channels that activate simultaneously. Under these conditions the rate of production of signal mass was roughly constant during the rise time of the spark and could be as high as 5 microm(3) ms(-1), consistent with a release current >50 pA since the beginning of the event. This pattern, called "concerted activation," was observed also in rat muscle fibers. When sulfate was combined with a reduced cytosolic [Ca(2+)] (50 nM) these sparks coexisted (and interfered) with a sequential progression of channel opening, probably mediated by Ca(2+)-induced Ca(2+) release (CICR). Sequential propagation, observed only in frogs, may require parajunctional channels, of RyR isoform beta, which are absent in the rat. Concerted opening instead appears to be a property of RyR alpha in the amphibian and the homologous isoform 1 in the mammal.


Rapid screening of monoclonal antibodies by spin adherence double immunosorbent test (SADIST).
The spin adherence double immunosorbent test (SADIST) is a simple, rapid immunoassay with sensitivity similar to the enzyme-linked immunosorbent assay (ELISA). A 1-step SADIST has been found suitable for rapid screening of hybridomas for antigen-specific monoclonal antibodies (MAb). In this procedure hybridoma supernatants are added to antigen coated microplates followed by commercially available antiglobulin beads. The microplate is immediately centrifuged. Wells containing antigen-specific MAb produce a mat of beads whilst wells without antigen-specific MAb produce a button of beads. No washing or incubation steps are necessary and results are read within minutes of adding beads to test supernatants. By comparison, ELISA tests require several hours to perform with multiple wash steps and further reagent additions. A 2-step SADIST was also assessed. Supernatants are incubated in the microplate as for an ELISA and a wash step precedes the addition of antiglobulin beads. A panel of 117 hybridoma supernatants was selected to assess the suitability of the SADIST techniques for hybridoma screening. The supernatants were added to antigen-coated microplates and SADIST and ELISA tests performed. The SADIST correctly discriminated most hybridoma supernatants that were clearly positive or negative by ELISA. It was also found possible to perform SADIST followed by ELISA tests on the same microplate well without significantly affecting ELISA values.


Dynamics of hepatitis B virus resistance to entecavir in a nucleoside/nucleotide-naïve patient.
The genotypic evolution of HBV quasi-species was analyzed in a nucleoside/nucleotide-naïve patient who developed resistance to entecavir. The lamivudine resistant quasi-species (rtM204V+/-rtL180M), absent at baseline, were emerged as early as 48 weeks after entecavir administration. Entecavir-resistant quasi-species (rtM204V+/-rtL180M plus S202G) were found after week 112 and gradually became the predominant mutations afterwards. The lamivudine- and entecavir-resistant mutations emerged closely in combination with the rtV207L, rtA222T, rtP237T or rtI163V substitutions. Our results indicated that the lamivudine-resistant mutations were developed first and may serve as a prequisite for subsequent entecavir-resistant mutations in this nucleoside/nucleotide-naïve patient.


3D positioning scheme exploiting nano-scale IR-UWB orthogonal pulses.
In these days, the development of positioning technology for realizing ubiquitous environments has become one of the most important issues. The Global Positioning System (GPS) is a well-known positioning scheme, but it is not suitable for positioning in in-door/building environments because it is difficult to maintain line-of-sight condition between satellites and a GPS receiver. To such problem, various positioning methods such as RFID, WLAN, ZigBee, and Bluetooth have been developed for indoor positioning scheme. However, the majority of positioning schemes are focused on the two-dimension positioning even though three-dimension (3D) positioning information is more useful especially in indoor applications, such as smart space, U-health service, context aware service, etc. In this paper, a 3D positioning system based on mutually orthogonal nano-scale impulse radio ultra-wideband (IR-UWB) signals and cross array antenna is proposed. The proposed scheme uses nano-scale IR-UWB signals providing fine time resolution and high-resolution multiple signal specification algorithm for the time-of-arrival and the angle-of-arrival estimation. The performance is evaluated over various IEEE 802.15.4a channel models, and simulation results show the effectiveness of proposed scheme.


Increased serum potassium and intraventricular hemorrhage revisited.
Increased serum potassium and intraventricular hemorrhage occur frequently in preterm infants. To retrospectively analyze data obtained on infants with severe IVH in relation to blood K+ concentrations. We identified all patients with severe IVH bom between July 1997 and July 2000. Each patient was pair-matched with a control infant of the same gestational age (+/- 1 week) without IVH in terms of head ultrasound findings on day 5 and whole blood K+ on days 3-5. There were 24 infants in each group. The IVH group had significantly lower 1 minute Apgar scores and pH and higher blood K+ than the control group. Blood pH and K+ were inversely correlated. Stepwise regression analysis, taking into account blood pH and 1 minute Apgar score, showed a correlation only between blood K+ and IVH status. Severe IVH is significantly associated with higher blood K+ concentrations. A causal relationship cannot be ascertained at this point.


Association between inflammation and hemostatic markers in atherothrombotic stroke.
It has been reported that the influence of fibrinogen on the incidence of ischemic events is related to inflammation processes and reflects an association with advance atherosclerosis. The aim of this study was to evaluate the association of thrombogenic and inflammatory profiles in patients who have suffered a stroke. The study involved 17 patients with atherothrombotic stroke and 34 healthy subjects as control group. The patients were examined 48 h, 3 and 6 months after the stroke occurred. To determine the inflammatory and thrombogenic profiles, plasma levels of fibrinogen, total sialic acid (TSA), C-reactive protein (CRP), tissue factor (TF) and fibrin D-dimer (D-dimer) were measured. The study showed that at 48 h and 3 months the levels of fibrinogen, TF, D-dimer, TSA and CRP were significantly higher than control group. TF, D-dimer and TSA remains significantly elevated throughout the entire study period. TF and D-dimer decreased over time without reaching the normal values. The multiple regression analysis showed that, at 48 h, 68% of the variance of fibrinogen and 22% of the variance of TF could be explained by the influence of CRP. At 3 and 6 months, 78% of the variance of fibrinogen could be explained by the influence of TSA. The results suggest a relation among inflammation markers, fibrinogen and TF in the acute phase of stroke. As TF and D-dimer are still elevated at 6 months, an increased thrombogenicity for a longer period following the acute event is present.


A new model of reverse cholesterol transport: enTICEing strategies to stimulate intestinal cholesterol excretion.
Cardiovascular disease (CVD) remains the largest cause of mortality in most developed countries. Although recent failed clinical trials and Mendelian randomization studies have called into question the high-density lipoprotein (HDL) hypothesis, it remains well accepted that stimulating the process of reverse cholesterol transport (RCT) can prevent or even regress atherosclerosis. The prevailing model for RCT is that cholesterol from the artery wall must be delivered to the liver where it is secreted into bile before leaving the body through fecal excretion. However, many studies have demonstrated that RCT can proceed through a non-biliary pathway known as transintestinal cholesterol excretion (TICE). The goal of this review is to discuss the current state of knowledge of the TICE pathway, with emphasis on points of therapeutic intervention.


Origin of the glial processes responsible for the spontaneous postnatal phagocytosis of boutons on cat spinal motoneurons.
Previous studies have demonstrated that astrocyte processes are responsible for a spontaneously occurring phagocytosis of boutons on cat spinal motoneurons during the second postnatal week. In the present investigation, the astrocytes and the astrocyte processes in contact with the motoneurons were studied qualitatively and quantitatively during the early postnatal period. It could be concluded that the cells responsible for the phagocytosis of boutons are immature astrocytes. These cells were present not only during the period of phagocytosis but also prior to this period. The type of process responsible for the phagocytosis was present not only during the period of phagocytosis but also prior to and after that period although the relative contribution of such processes to the glia-covered membrane area of the motoneurons was reduced in the older animals. On the basis of these results, the possible specificity of the immature astrocyte as the element responsible for the phagocytosis of boutons during normal development is discussed.


Antoine-Laurent de Lavoisier (1743-1794) and the birth of respiratory physiology.
For more than 1500 years, the status of knowledge concerning the physiology of human respiration has remained almost unchanged. In the 18th century, the French chemist Antoine-Laurent de Lavoisier conducted breathing experiments on human and animal respiration. The main bibliographic sources concerning Lavoisier's life and work on respiration have been investigated and analysed. Using an ice-calorimeter, Lavoisier proved that combustion and respiration were one and the same. He also measured the oxygen consumed during respiration and concluded that the amount changes depending on human activities: exercise, eating, fasting, and sitting in a warm or cold room. Moreover, he found variations in pulse and breathing rate. Lavoisier's work on respiration is of great historical significance as it represents the first effort to measure human respiratory gas metabolism contributing significantly to the development of respiratory physiology.


An autopsy case of cholangiocarcinoma with hypercalcemia.
Au autopsy case of cholangiocarcinoma which showed clinically hypercalcemia and hypophosphatemia without bone metastases is presented in this report. Although parathyroid hormone (PTH)-like substance of 520 ng/g. dry weight was measured in neoplastic tissue by the radioimmunoassay, membrane-limited secretory granules as those of parathyroid gland were not found in the fine structure. The significance of an existence of secretory granules in ectopic PTH producing tumor is discussed.


Synthesis and biological activity of 3-substituted 3-desoxynaltrindole derivatives.
The 3-unsubstituted and substituted analogs of naltrindole (NTI) were synthesized using palladium-catalyzed transformations, and their binding affinity to opioid receptors was determined. Although the 3-desoxy analog showed comparable delta selectivity with that of NTI, all of the novel compounds possessed low affinity for delta receptors indicating the important role of the 3-oxygen atom of NTI for interaction with delta-opioid receptors.


Lipoproteins, macrophage function, and atherosclerosis: beyond the foam cell?
Atherogenesis requires and is highly influenced by the interaction between lipoproteins and macrophages. Most of the focus to date has been on the ability of atherogenic lipoproteins (such as low-density lipoproteins, LDL) to promote and of anti-atherogenic lipoproteins (such as high-density lipoproteins, HDL) to prevent the development of the cholesteryl ester-enriched macrophage-derived foam cell. However, lipoprotein-macrophage interactions have the potential to modulate macrophage function in a variety of additional ways that may impact on atherosclerosis. These include modulating cellular cholesterol and oxysterol content, providing fatty acids as ligands for PPARs, and acting as ligands for macrophage scavenger and Toll-like receptors. We suggest that atherogenic lipoproteins promote and anti-atherogenic lipoproteins inhibit atherogenesis by modulating macrophage function in a variety of ways beyond cholesteryl ester accumulation and foam cell formation.


A Review and Analysis of the National Dog Population Management Program in Chile.
Free-roaming dogs are a worldwide problem, with Chile having some of the highest human-to-dog ratios in the world. In 2017, Law 21.020 was promulgated and the federal government developed a national responsible pet ownership program. The objectives of this article are to describe and discuss the dog-related components of the program, to design a tool for determining human-to-dog ratios in Chile, and to make recommendations to managers to improve the program outcomes. The overarching goal of the program was to mitigate the conflict between humans and dogs, but many of the interventions were animal-focused and the indicators did not consider the perception of the Chilean public. Using human density data and known dog populations, we found that as the human density increased, there were fewer dogs per person. Veterinary services and sterilizations were the mainstay of the program and were offered for free to citizens. Education was offered to all ages through public events, as well as municipality and organization activities. The identification of dogs was obligatory for dog owners. Enforcement was not included in the program. The recommendations are to conduct preintervention baseline data collections and to tailor interventions and indicators appropriately; to use dog population size estimates determined at the local level rather than a country-wide estimate; to replace free veterinary services with low-cost sterilization campaigns; to create sustainable plans for education; and to create enforcement teams in communities.


Renal artery stenosis: changes in intrarenal Doppler waveform following percutaneous transluminal angioplasty.
To examine the extent of the changes in the intrarenal spectral waveform patterns after percutaneous transluminal angioplasty (PTA) and whether there is a correlation with the angiographic and clinical results. In 44 patients with 68 PTAs we analyzed the intrarenal spectral waveform regarding the existence of a tardus-parvus pattern before and after PTA. In 51 of the 60 cases with a tardus-parvus pattern prior to PTA, a complete normalization of the spectral wave-form was noted. There was no correlation between the Doppler result after PTA and the angiographic and clinical result. In contrast there was a significant correlation between the Doppler result before PTA and the clinical outcome: patients with a normal intrarenal spectral waveform before PTA showed no improvement in their arterial hypertension. Our results indicate that a patient with a normal spectral waveform analysis does not response to PTA. However, there is still an unpredictable clinical response even if a patient has an abnormal intrarenal spectral waveform prior to PTA and a complete normalization after PTA.


Application of deglycosylation to SDS PAGE analysis improves calibration of influenza antigen standards.
Each year the production of seasonal influenza vaccines requires antigen standards to be available for the potency assessment of vaccine batches. These are calibrated and assigned a value for haemagglutinin (HA) content. The calibration of an antigen standard is carried out in a collaborative study amongst a small number of national regulatory laboratories which are designated by WHO as Essential Regulatory Laboratories (ERLs) for the purposes of influenza vaccine standardisation. The calibration involves two steps; first the determination of HA protein in a primary liquid standard by measurement of total protein in a purified influenza virus preparation followed by determination of the proportion of HA as determined by PAGE analysis of the sample; and second, the calibration of the freeze-dried reference antigen against the primary standard by single radial immunodiffusion (SRD) assay. Here we describe a collaborative study to assess the effect of adding a deglycosylation step prior to the SDS-PAGE analysis for the assessment of relative HA content. We found that while the final agreed HA value of the samples tested was not significantly different with or without deglycosylation, the deglycosylation step greatly improved between-laboratory agreement.


Outcomes of highly active antiretroviral therapy and its predictors: a cohort study focusing on tuberculosis co-infection in South West Ethiopia.
In this study, we hypothesized that TB co-infection independently increases the risk of poor treatment outcomes in such patients even if they are on antiretroviral therapy (ART). Therefore, this study was aimed at investigating this hypothesis among cohort of adult PLWHs in South West Ethiopia. Cohort study comparing the immunologic and clinical outcomes of 130 HIV/TB co-infected and 520 only HIV patients starting ART was enrolled. Chi square and student t test were used to compare outcome variables and logistic regression was used to assess the effect of TB on treatment failure. In this study, TB co-infection didn't increase immunologic failure even in univariate analysis at both 6 [OR, 1.10 (0.59-1.69), P = 0.85] and 12 months [OR, 1.06 (0.58-1.93), P = 0.89] of ART initiation. However, it increased the risk of clinical failure at both 6 [Adjusted Odd Ratio (AOR), 2.90 (1.41-6.09), P = 0.028] and 12 months [AOR, 2.93 (1.41-6.09), P = 0.004] of ART initiation. This study showed that TB co-infection didn't adversely affect the immunologic outcomes, weight and hemoglobin responses even though it increased the risk of clinical failure nearly three times. Therefore, beside the concern given for TB prevention and treatment, several patient and policy related factors need to be addressed to maximally benefit from highly active antiretroviral therapy rollout in resource limited settings.


Seminal plasma modulates post-thaw longevity and motility of frozen sperm in dromedary camel.
This study investigated the effect of adding seminal plasma to frozen-thawed semen on the quality of sperm and pregnancy following insemination in dromedary camels. In experiment 1, the frozen-thawed semen from 9 collections (3 bulls) was further diluted with either the base extender or homologous seminal plasma (HSP). In the second experiment, a pooled sample of frozen-thawed semen was diluted with either seminal plasma from another three bulls. Live percentage, total and progressive motility, functional and acrosome integrity, and sperm kinematics were evaluated at 15, 60, and 120 minutes post-thawing and compared to the non-treated control. In experiment 3, frozen semen was used to inseminate camels in the following experimental groups: 1-Single insemination with double dose undiluted frozen semen (n = 9); 2-Re-insemination in 6 hours with undiluted semen (n = 13); 3-Single insemination with HSP treated sperm (n = 14). Frozen-thawed sperm diluted in HSP or the non-homologous seminal plasma from Bull C indicated an improvement in all parameters after 1 hour post-thawing incubation (p<0.05). The proportion of total and progressively motile sperm did not drop significantly at 60 minutes post-thawing when diluted with the seminal plasma of Bull C (p>0.05). Double insemination with nontreated sperm and single insemination with HSP-treated sperm resulted in similar pregnancy rates (15.3% vs 21.4%, p>0.05). None of the camels conceived with double-dose single insemination of nontreated sperm. Seminal plasma improves sperm longevity and motility after thawing in dromedary camel with a significant between-bull variation in effect. Low post-thaw sperm longevity might be the cause behind the low pregnancy rates in frozen semen insemination of dromedary camels.


Blp1 protein shows virulence-associated features and elicits protective immunity to Acinetobacter baumannii infection.
Multidrug resistant Acinetobacter baumannii is one of the major infection agents causing nosocomial pneumonia. Therefore, new therapeutic approaches against this bacterium are needed. Surface-exposed proteins from bacterial pathogens are implicated in a variety of virulence-related traits and are considered as promising candidates for vaccine development. We show in this study that a large Blp1 protein from opportunistic pathogen A. baumannii is encoded in all examined clinical strains of globally spread international clonal lineages I (IC I) and II (IC II). The two blp1 gene variants exhibit lineage-specific distribution profile. By characterization of blp1 deletion mutants and their complementation with blp1 alleles we show that blp1 gene is required for A. baumannii biofilm formation and adhesion to epithelial cells in IC I strain but not in the IC II strain. Nevertheless both alleles are functional in restoring the deficient phenotypes of IC I strain. Moreover, the blp1 gene is required for the establishing of A. baumannii virulence phenotype in nematode and murine infection models. Additionally, we demonstrate that C-terminal 711 amino acid fragment of Blp1 elicits an efficient protection to lethal A. baumannii infection in a murine model using active and passive immunization approaches. Antiserum obtained against Blp1-specific antigen provides opsonophagocytic killing of A. baumannii in vitro. Lineage-specific variants of surface-exposed components of bacterial pathogens complicate the development of new therapeutic approaches. Though we demonstrated different impact of Blp1 variants on adherence of IC I and IC II strains, Blp1-specific antiserum neutralized A. baumannii strains of both clonal lineages. Together with the observed increased survival rate in vaccinated mice these results indicate that A. baumannii Blp1 protein could be considered as a new vaccine candidate.


The spider acylpolyamine Mygalin is a potent modulator of innate immune responses.
Mygalin is an antibacterial molecule isolated from the hemocytes of the spider Acanthoscurria gomesiana. It was identified as bis-acylpolyamine spermidine. We evaluated the modulator effects of synthetic Mygalin in the innate immune response. We demonstrate that Mygalin induces IFN-γ synthesis by splenocytes increasing the nitrite secretion by splenocytes and macrophages. A specific inhibitor of iNOS abrogated Mygalin-induced nitrite production in macrophages independent of IFN-γ activation. In addition, Mygalin-activated macrophages produced TNF-α but not IL-1β, demonstrating that Mygalin does not act directly on the inflammasome. Furthermore, this compound did not affect spontaneous or Concanavalin A-induced proliferative responses by murine splenocytes and did not induce IL-5 or apoptosis of splenocytes or bone marrow-derived macrophages. These data provide evidence that Mygalin modulates the innate immune response by inducing IFN-γ and NO synthesis. The combined immune regulatory and antibacterial qualities of Mygalin should be explored as a strategy to enhance immune responses in infection.


Anatomical Repair of an Unusual Combination of Tetralogy of Fallot and Atrioventricular Septal Defect With Unroofed Coronary Sinus.
A 30-month-old female was admitted with recurrent spells and severe cyanosis. Preoperative echocardiography was diagnostic of tetralogy of Fallot with an atrial septal defect of the primum type, unroofed coronary sinus, and a left superior vena cava draining into the left atrium. At surgery the patient was found to have a complete atrioventricular septal defect in addition to these anomalies. Complete anatomical correction was achieved through the right atrial approach.


The microsomal ethanol oxidizing system mediates metabolic tolerance to ethanol in deermice lacking alcohol dehydrogenase.
Metabolic tolerance to ethanol has been attributed to enhanced mitochondrial reoxidation of reducing equivalents produced in the alcohol dehydrogenase (ADH) pathway or to non-ADH mechanisms. To resolve this issue, deermice lacking low Km hepatic ADH were fed for 2 weeks a liquid diet containing ethanol or isocaloric carbohydrate and hepatocytes were isolated. Ethanol (50 mM) oxidation increased (9.8 vs 4.5 nmol/min/10(6) cells in controls). To differentiate which of two non-ADH pathways (the microsomal ethanol oxidizing system (MEOS) or catalase) was responsible for the induction, four approaches were used. First, MEOS was assayed in hepatic microsomes and found to be increased (24.4 vs 6.8 nmol/min/mg protein in controls). Second, hepatocyte ethanol metabolism was measured after addition of the catalase inhibitor azide (0.1 mM) and found to be unchanged. By contrast, the competitive MEOS inhibitor, 1-butanol, depressed metabolism in a concentration-dependent manner. A third approach relied on measurement of isotope effects known to be different for MEOS and catalase. From the isotope effect values, MEOS was calculated to contribute 85% or more of total ethanol oxidation by cells from both ethanol-fed and control animals. A fourth approach involved in vivo pretreatment with pyrazole (300 mg/kg/day for 2 days), which reduced peroxidation by catalase to 13% of control values in liver homogenates while inducing MEOS activity to 152% of controls. Hepatocytes from pyrazole-treated deermice showed a 47% increase in ethanol metabolism, paralleling the MEOS induction and contrasting with the catalase suppression. These results indicate that since metabolic tolerance occurs in the absence of ADH, it is not necessarily ADH mediated, and further, that MEOS rather than catalase accounts for basal ethanol metabolism and its increase after chronic ethanol treatment.


An Italian family with autosomal recessive quadriceps-sparing inclusion-body myopathy (ARQS-IBM) linked to chromosome 9p1.
We report an Italian family with autosomal recessive quadriceps-sparing inclusion-body myopathy (ARQS-IBM). The patients (two second cousins) developed a slowly progressive distal and proximal myopathy with complete sparing of the quadriceps. Muscle biopsy showed rimmed vacuoles in numerous muscle fibers, and electron microscopy documented accumulation of 15-21 nm filaments. DNA analysis established linkage to 9p1 and haplotype analysis revealed that the patients shared a recombined common haplotype. The gene locus of ARQS-IBM was initially mapped to chromosome 9p1-q1 in families of Iranian-Jewish origin and later confirmed in a few other ethnic groups. This is the first report of Italian patients with ARQS-IBM showing positive linkage to chromosome 9p1. Our data suggest that patients having distal and proximal myopathy with rimmed vacuoles and possible recessive inheritance, often classified as distal myopathies, should be thoroughly investigated according to the diagnostic criteria of h-IBM and, when positive, studied for linkage to chromosome 9p1.


The macrophage scavenger receptor CD163.
Mature tissue macrophages form a first line of defense to recognize and eliminate potential pathogens; these specialized cells are capable of phagocytosis, degradation of self and foreign materials, establishment of cell-cell interactions, and the production of inflammatory mediators. Mature tissue macrophages express a variety of receptors, including the scavenger receptor cystein-rich (SRCR) superfamily members. CD163 is a member of the SRCR family class B and is expressed on most subpopulations of mature tissue macrophages. The best characterized function of CD163, which is essentially a homeostatic one, is related to the binding of Hemoglobin:Haptoglobin complexes. Furthermore, it has been suggested that CD163 positive macrophages or the soluble form of CD163 plays a role in the resolution of inflammation, as they are found in high numbers in inflamed tissue.


CCL2-targeted ginkgolic acid exerts anti-glioblastoma effects by inhibiting the JAK3-STAT1/PI3K-AKT signaling pathway.
Glioblastoma (GBM) with aggressive nature and poor prognosis has become the most common intracranial tumor. Most clinical chemotherapeutic drugs fail to achieve the anticipated therapeutic outcome. This study identified the anti-GBM effects of ginkgolic acids (GAs) and elucidated the potential molecular mechanisms, exploiting the significant antitumor effects of GAs, which are widely present in the outer bark of Ginkgo biloba. Two GBM cell lines, U251 and T98G, were selected for in vitro experiments to evaluate the antitumor effects of GA. Cell viability and proliferation were examined by MTT and colony formation assay. The effect of GA on apoptosis and the cell cycle was examined by flow cytometry. Scratch and Transwell assays reflected the migration and invasion ability. The molecular mechanisms were explored by using immunoblot analysis, RNA sequencing and bioinformatics. In the nude mouse transplantation tumor model, preclinical treatment effects were assessed by ultrasound and MRI. The present study showed that GA inhibited the proliferation, migration, invasion, stemness, epithelial-to-mesenchymal transition (EMT) of GBM cells and induced apoptosis by inhibiting CCL2, affecting the JAK-STAT and PI3K-AKT signaling pathways, and inhibiting the EMT regulators Snail and Slug. Finally, GA showed significant control of tumors in a GBM xenograft model. GA inhibits the progression of GBM cells by targeting CCL2, affecting the JAK-STAT and PI3K-AKT signaling pathways, and inhibiting the EMT regulators Snail and Slug. The outstanding antitumor properties of GA provide a novel strategy for the GBM therapy.


Renal function of chrome-plating workers and welders.
The influence of occupational exposure to water-soluble chromium (VI) on renal function was examined. In male chrome-plating workers (n = 29), stainless steel welders (n = 45), boilermakers (n = 18) and a control group of workers (n = 71), the level of chromium in the urine (Cr-U), the chromium clearance, and sensitive renal function parameters were determined. The glomerular-function parameters of the chrome-plating workers (Cr-U 1 to 34 micrograms/g creat) and welders (Cr-U 1 to 62 micrograms/g creatine) appeared to differ from those of the boilermakers (Cr-U 0.3 to 1.5 micrograms/g creatine) and controls (Cr-U 0.1 to 2 micrograms/g creatine). The renal function parameters were not related to chromium concentration in the urine or to chromium clearance.


Practical applications of brief screening questionnaires for autism spectrum disorder in a psychiatry outpatient setting.
This study was designed to examine the diagnostic performance of the social and communication disorders checklist (SCDC) and strength and difficulties questionnaire (SDQ) to detect autism spectrum conditions (ASC), along with the social responsiveness scale-second edition (SRS-2) as reference, in a psychiatry outpatient setting. We translated the SCDC into Japanese since its Japanese version was unavailable. We examined its test-retest reliability as well as the internal consistency reliability and diagnostic performance of the three questionnaires among 41 Japanese psychiatric outpatients, using the best-estimate diagnosis of ASC based on the diagnostic interview for social and communication disorders, as a gold standard. The test-retest reliability was high for the SCDC. Although the internal consistency reliability was high for the SCDC and SRS-2, that was low for the prosocial and peer problem subscales of the SDQ. The performance of the SCDC, SDQ, and SRS-2 to detect ASC was moderate: the area under the ROC curve of 0.78, 0.78, and 0.84, respectively. Although questionnaires to detect ASC, including the three examined, generally have only moderate performance in this setting, these can be successfully applied to high-risk populations such as psychiatry outpatients, when multi-level rather than dichotomous likelihood ratios are used.


Autonomic dysfunction heralding acute motor axonal neuropathy in COVID-19.
Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of neurological and neuropsychological effects. However, the pathogenesis of COVID-19-induced neurological manifestations is still in its infancy. Autonomic dysfunction preceding acute motor axonal neuropathy (AMAN) has not been yet associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We herein report one patient who developed acute onset dysautonomia heralding AMAN during SARS-CoV-2 infection.


Neoadjuvant Chemotherapy of Patients with Early Breast Cancer Is Associated with Increased Detection of Disseminated Tumor Cells in the Bone Marrow.
Preclinical data suggest that neoadjuvant chemotherapy (NAT) may promote micrometastatic spread. We aimed to compare the detection rate and prognostic relevance of disseminated tumor cells (DTCs) from the bone marrow (BM) of patients with early-stage breast cancer (EBC) after NAT with that of therapy-naive EBC patients. DTCs were identified from BM samples, collected during primary surgery. Patients who received NAT were compared to patients who received chemotherapy after surgery. In total, 809 patients were analyzed. After NAT, 45.4% of patients were DTC-positive as compared to 19.9% of patients in the adjuvant chemotherapy group (p < 0.001). When sampled in patients who had undergone NAT, the detection of DTCs in the BM was significantly increased (OR: 3.1; 95% confidence interval (CI): 2.1-4.4; p < 0.001). After NAT, DTC-positive patients with ≥2 DTCs per 1.5 × 106 mononuclear cells in their BM had an impaired disease-free survival (HR: 4.8, 95% CI: 0.9-26.6; p = 0.050) and overall survival (HR: 4.2; 95% CI: 1.4-12.7; p = 0.005). The higher rate of DTC-positive patients after NAT as compared to a treatment-naive comparable control cohort suggests that NAT supports tumor cell dissemination into the bone marrow. DTC positivity in BM predicted relapse in various distant organs, implying that tumor cell dissemination was not restricted to the bone marrow.


The mINO80 chromatin remodeling complex is required for efficient telomere replication and maintenance of genome stability.
The INO80 (inositol requiring mutant 80) chromatin remodeling complex plays important roles in transcriptional regulation and DNA replication and repair, and consists of several functional protein subunits, including the critical Ino80 ATPase catalytic subunit. While the function of INO80 has been studied in yeast and mammalian cell lines, we do not know how mIno80 contributes to the maintenance of genome stability to prevent cancer development in mice. Here, we use a conditional knockout approach to explore the cellular and organismal functions of mIno80. Deletion of mIno80 results in profound cellular proliferative defects and activation of p21-dependent cellular senescence. While mIno80 is required for efficient repair of DNA double strand breaks, its depletion did not impact upon the formation of γ-H2AX and 53BP1 DNA damage foci, or the activation of the ATM-CHK2-dependent DNA damage response. mIno80 deletion inhibited the generation of single-strand DNA, resulting in defects in homology-directed DNA repair (HDR) at telomeres. Fragile telomeres were prominent in mIno80(Δ/Δ) MEFs, suggesting that chromatin remodeling is required for efficient telomere replication. mIno80(-/-) mouse embryos die early during embryogenesis, while conditional deletion of mIno80 in adult mice results in weight loss and premature death. In a p53(-/-) tumor-prone background, mIno80 haploinsufficiency favored the development of sarcomas. Our studies suggest that the mIno80 chromatin remodeling complex plays important roles in telomere replication, HDR-mediated repair of dysfunctional telomeres, and maintenance of genome stability.


The BAM H1 restriction site in the bacteriophage T4 chromosome is located in or near gene 8.
Bacteriophage T4 cytosine-containing DNA is cleaved at a single site by the restriction endonuclease, Bam H1. The site lies within the late region of the T4 genome, close to, or within, gene 8, one of the structural genes of the phage particle baseplate.


Disruption of Escherichia coli transaldolase into catalytically active monomers: evidence against half-of-the-sites mechanism.
Disruption of the hydrogen bonding network at the interface of Escherichia coli transaldolase by substitution of R300 to a glutamic acid residue resulted in a monomeric enzyme at basic pH values, with almost no change in the kinetic parameters. The stability of the R300A and R300E mutants towards urea and thermal inactivation is similar to that of the wild-type enzyme. X-ray analysis showed that no structural changes occurred as a consequence of the side chain replacement. This indicates that the quaternary structure is not required for catalytic activity nor does it contribute significantly to the stability of the enzyme. The results are not consistent with a proposed half-of-the-sites reaction mechanism.


Identification of distinct clinical phenotypes of cardiogenic shock using machine learning consensus clustering approach.
Cardiogenic shock (CS) is a complex state with many underlying causes and associated outcomes. It is still difficult to differentiate between various CS phenotypes. We investigated if the CS phenotypes with distinctive clinical profiles and prognoses might be found using the machine learning (ML) consensus clustering approach. The current study included patients who were diagnosed with CS at the time of admission from the electronic ICU (eICU) Collaborative Research Database. Among 21,925 patients with CS, an unsupervised ML consensus clustering analysis was conducted. The optimal number of clusters was identified by means of the consensus matrix (CM) heat map, cumulative distribution function (CDF), cluster-consensus plots, and the proportion of ambiguously clustered pairs (PAC) analysis. We calculated the standardized mean difference (SMD) of each variable and used the cutoff of ± 0.3 to identify each cluster's key features. We examined the relationship between the phenotypes and several clinical endpoints utilizing logistic regression (LR) analysis. The consensus cluster analysis identified two clusters (Cluster 1: n = 9,848; Cluster 2: n = 12,077). The key features of patients in Cluster 1, compared with Cluster 2, included: lower blood pressure, lower eGFR (estimated glomerular filtration rate), higher BUN (blood urea nitrogen), higher creatinine, lower albumin, higher potassium, lower bicarbonate, lower red blood cell (RBC), higher red blood cell distribution width (RDW), higher SOFA score, higher APS III score, and higher APACHE IV score on admission. The results of LR analysis showed that the Cluster 2 was associated with lower in-hospital mortality (odds ratio [OR]: 0.374; 95% confidence interval [CI]: 0.347-0.402; P < 0.001), ICU mortality (OR: 0.349; 95% CI: 0.318-0.382; P < 0.001), and the incidence of acute kidney injury (AKI) after admission (OR: 0.478; 95% CI: 0.452-0.505; P < 0.001). ML consensus clustering analysis synthesized the pattern of clinical and laboratory data to reveal distinct CS phenotypes with different clinical outcomes.


Vagal activity, gastric motility, and weight gain in massaged preterm neonates.
Multiple studies have documented an increase in weight gain after 5 to 10 days of massage therapy for preterm neonates. The massaged preterm neonates did not consume more calories than the control neonates. One potential mechanism for these effects might involve massage-induced increases in vagal activity, which in turn may lead to increased gastric motility and thereby weight gain. The present randomized study explored this potential underlying mechanism by assessing gastric motility and sympathetic and parasympathetic nervous system activity in response to massage therapy (moderate pressure) versus sham massage (light pressure) and control conditions in a group of preterm neonates. Compared with preterm neonates receiving sham massage, preterm neonates receiving massage therapy exhibited greater weight gain and increased vagal tone and gastric motility during and immediately after treatment. Gastric motility and vagal tone during massage therapy were significantly related to weight gain. The weight gain experienced by preterm neonates receiving moderate-pressure massage therapy may be mediated by increased vagal activity and gastric motility.


[Recent advances in bladder urothelial carcinogenesis].
Bladder cancer is the sixth cause of cancer mortality in France and prognosis of muscle-invasive tumors remains poor due to lack of effective treatments. Recent advances in molecular biology applied to tumors and results of recent genome-wide studies have brought a important impact on the understanding of bladder carcinogenesis. Main molecular alterations concern FGFR3, TP53 and HER2, and it is now possible to distinguish three subgroups of tumors according to molecular profile. This paper proposes a review of different genetic and epigenetic alterations in bladder cancer, their potential role as theranostic markers in clinical oncology and new targeted therapies according to the concept of personalized medicine.


Catalytic Diverse Radical-Mediated 1,2-Cyanofunctionalization of Unactivated Alkenes via Synergistic Remote Cyano Migration and Protected Strategies.
A catalytic radical protocol for 1,2-cyanofunctionalization of unactivated alkenes involving remote cyano migration triggered by addition of diverse carbon- and heteroatom-centered radicals to alkenes has been developed. This powerful strategy provides a diverse platform for the collection of a variety of synthetically important β-functionalized alkyl nitriles bearing densely functionalized carbonyl, cyano, and other various functional groups within the same molecules. The substrates TMS (trimethylsilyl)-protected alkenyl cyanohydrins are straightforwardly accessible via simple cyanosilylation of the corresponding ketones.


Obese and lean Zucker rats demonstrate differential sensitivity to rates of food reinforcement in a choice procedure.
The obese Zucker rat carries two recessive fa alleles that result in the expression of an obese phenotype. Obese Zuckers have higher food intake than lean controls in free-feed studies in which rats have ready access to a large amount of one type of food. The present study examined differences in obese and lean Zucker rats using concurrent schedules of reinforcement, which more ecologically models food selection using two food choices that have limited, but generally predictable availability. Lever-pressing of ten lean (Fa/Fa or Fa/fa) and ten obese (fa/fa) Zucker rats was placed under three concurrent variable interval variable interval (conc VI VI) schedules of sucrose and carrot reinforcement, in which the programmed reinforcer ratios for 45-mg food pellets were 5:1, 1:1, and 1:5. Allocation of responses to the two food alternatives was characterized using the generalized matching equation, which allows sensitivity to reinforcer rates (a) and bias toward one alternative (log k) to be quantified. All rats showed a bias toward sucrose, though there were no differences between lean and obese Zucker rats. In addition, obese Zucker rats exhibited higher sensitivity to reinforcement rates than lean rats. This efficient pattern of responding was related to overall higher deliveries of food pellets. Effective matching for food, then, may be another behavioral pattern that contributes to an obese phenotype.


TdT-accessible breaks are scattered over the immunoglobulin V domain in a constitutively hypermutating B cell line.
Searching for an in vitro model for somatic hypermutation, we have identified an IgM-expressing Burkitt lymphoma line that constitutively diversifies its immunoglobulin V domain at high rate during culture. As in in vivo, the mutations are largely nucleotide substitutions with the pattern of substitutions revealing a component of the human hypermutation program that is preferentially targeted to G/C residues. The substitutions frequently create stop codons with IgM-loss variants also being generated by V domain-specific deletions and duplications. However, in transfectants expressing terminal deoxynucleotidyl transferase, many IgM-loss variants additionally arise through short nontemplated nucleotide insertions into the V (but not C) domain. Thus, antibody hypermutation is likely accompanied by DNA strand breaks scattered within the mutation domain.


Successful biosynthesis of natural antioxidant ergothioneine in Saccharomyces cerevisiae required only two genes from Grifola frondosa.
Ergothioneine (EGT) has a unique antioxidant ability and diverse beneficial effects on human health. But the content of EGT is very low in its natural producing organisms such as Mycobacterium smegmatis and mushrooms. Therefore, it is necessary to highly efficient heterologous production of EGT in food-grade yeasts such as Saccharomyces cerevisiae. Two EGT biosynthetic genes were cloned from the mushroom Grifola frondosa and successfully heterologously expressed in Saccharomyces cerevisiae EC1118 strain in this study. By optimization of the fermentation conditions of the engineered strain S. cerevisiae EC1118, the 11.80 mg/L of EGT production was obtained. With daily addition of 1% glycerol to the culture medium in the fermentation process, the EGT production of the engineered strain S. cerevisiae EC1118 can reach up to 20.61 mg/L. A successful EGT de novo biosynthetic system of S. cerevisiae containing only two genes from mushroom Grifola frondosa was developed in this study. This system provides promising prospects for the large scales production of EGT for human health.


cis-Bis(acetonitrile-κN)bis-(2,2'-bipyridine-κN,N')ruthenium(II) tetra-fluoridoborate.
In the cation of the title compound, [Ru(CH(3)CN)(2)(C(10)H(8)N(2))(2)](BF(4))(2), the Ru(II) atom is six-coordinated in a distorted octa-hedral geometry by the N atoms of the two 2,2'-bipyridine (bpy) ligands and two cis-arranged acetonitrile mol-ecules. The dihedral angles formed by the pyridine rings of the bpy ligands are 8.86 (12) and 10.12 (14)°. In the crystal, the cations and anions are linked by C-H⋯F hydrogen bonds into a three-dimensional network.


Ultrasound Assessment of the Ulnar Nerve Around the Elbow and Diagnosis of Cubital Tunnel Syndrome, Clinical Outcomes.
There is increased interest in ultrasound (US) for the diagnosis of cubital tunnel syndrome (CuTS). We hypothesize that ulnar nerve cross-sectional area (CSA) correlates with disease severity and electrodiagnostic studies (EDX). ARetrospective review was performed at a tertiary medical center. One hundred seventeen patients (166 ulnar nerves) were evaluated. Maximum CSA at 3 points around the elbow (proximal, groove, and distal) and EDX results (American Board of Electrodiagnostic Medicine-certified physiatrist's interpretations) were collected. US was positive (CSA > 0.1 cm2) in 95/117 cases (81.20%) versus 84/117 (71.79%) positive for EDX. CuTS patients treated surgically had significantly greater (0.13 cm2, standard deviation [SD] 0.038) preoperative CSA than non-operative patients (0.10 cm2, SD 0.033) (p = .003). CSA increased as EDX increased in severity; mild (0.116 cm2, SD 0.031), moderate (0.121 cm2, SD 0.035), and severe (0.163 cm2, SD 0.047) with a significant difference between the mild and severe groups (P = .001) and between the moderate and severe groups (p = .01). Significant differences were seen between patients with positive US and EDX studies compared to those with negative US and EDX in the average physical function scores (57.26, SD 8.57 versus 43.18, SD 7.70; p < .001); average sleep scores (50.14, SD 9.53 versus 56.62, SD 7.31; p = .02); average physical function scores (43.04, SD 8.68 versus 57.08, SD 6.34; p < .001) and average depression scores (49.10, SD 10.88 versus 45.043, SD 7.06; p = .02). US is a reliable tool for diagnosis and surgical decision-making for CuTS. Diagnostic/III.


A novel membrane bioreactor enhanced by effective microorganisms for the treatment of domestic wastewater.
The activated sludge membrane bioreactor (MBR) has been shown to have some advantages for the processing and reclamation of domestic wastewater. We hypothesized that certain microorganisms, chosen for their abilities to decompose the chemical components of raw sewage, would, when coupled with the MBR, significantly improve the stability and efficiency of this system. We selected environmental bacterial strains which oxidize ammonia and nitrites and produce protease, amylase, and cellulase for the development and testing of a novel biologically enhanced MBR (eMBR). We compared the eMBR with the activated sludge MBR. With the eMBR, the average values of effluent quality were: chemical oxygen demand (COD), 40 mg/l(average efficiency of removal 90.0%); and NH(4) (+)-N, 0.66 mg/l(average efficiency of removal 99.4%). Effluent qualities met the standard and were stable during the entire 90 days of this study. For the activated sludge MBR, the COD removal rate was 91.7%, and the NH(4) (+)-N removal (94.8%) was less than that of the eMBR. Start-up time for the eMBR was only 24-48 h, much shorter than the 7-8 days required to initiate function of the standard MBR. The biomass concentrations of total heterotrophic bacteria and autotrophic bacteria in the eMBR did not fluctuate significantly during the course of the study. Various kinds of microorganisms will establish an ecological balance in the reactor. Compared with the activated sludge MBR, the eMBR not only produced an excellent and stable quality of effluent but also resulted in a shorter time to start-up and significantly improved the efficiency of NH(4) (+)-N removal.


Wide-awake local anesthesia no tourniquet and dexamethasone (WALANT-D) for modified Camitz opponens plasty in severe carpal tunnel syndrome-a retrospective study of 30 cases.
To analyze the outcome of modified Camitz opponens plasty using the wide-awake local anesthesia no tourniquet with dexamethasone (WALANT-D) technique in severe carpal tunnel syndrome (CTS). A retrospective review was performed in 30 hands of 27 patients who underwent Camitz opponens plasty for severe CTS between 2019 and 2021. All patients had 8 mg of dexamethasone mixed with WALANT. Preoperative active palmar abduction, grip strength, side, and pulp pinch strength, Kapandji score, and electrophysiological assessment of compound muscle action potential (CMAP) for abductor pollicis brevis (APB) were compared with the postoperative values. The palmaris longus had dual insertion into the abductor pollicis brevis and extensor expansion. The time interval of post-operative pain-free was noted. The Disabilities of the Arm, Shoulder, and Hand (DASH) and Carpal Tunnel Syndrome instrument (CTSI) also assessed the functional outcome. The mean age of patients was 35 years (range 32-58 years). There were five male and 22 female patients. Of the female patients, three females had severe bilateral CTS. Twenty right and ten left hands were affected. The mean follow-up of our study was 12.5 months (range 10-14 months). The patients were pain-free for an average of 19.5 h postoperatively. There was a significant improvement in the thumb palmar abduction, grip strength, side, and pulp pinch strength, DASH score, CTSI, and APB-CMAP (p < 0.05) at the final follow-up. Modified Camitz opponens plasty with a dual insertion into APB and extensor expansion effectively improves thumb opposition and daily activities. The tendon tensioning, checking the pulley impingement, appreciation of active movements, and a comfortable patient operative experience are advantages of the WALANT. Adding dexamethasone as an adjuvant to WALANT prolongs the analgesia and duration of the nerve block. IV, Retrospective case study.


Co-infections with cytomegalovirus and human herpesvirus type 7 in adult Polish allogeneic haematopoietic stem cell transplant recipients.
Human herpesvirus 7 (HHV-7) is widespread around the world and may also be a possible cofactor for cytomegalovirus (CMV) infection in haematopoietic stem cell transplant (HSCT) recipients. In case of viral diseases where specific treatment is available, real-time PCR assays constitute reliable diagnostic tools enabling timely initiation of appropriate therapy and rapid assessment of the efficacy of antiviral treatment strategies. The presence of CMV and HHV-7 was confirmed by the detection of viral DNA isolated from 1,027 plasma samples. A group of 69 allogeneic HSCT (alloHSCT) recipients was examined in early post-transplant period using quantitative real-time PCR methods. Within the study period, 62 % of patients had at least once CMV DNA-emia, while HHV-7 DNA was found in 43 % of subjects. Co-infection between these β-herpesviruses was detected in the plasma samples collected from 18 patients (26 %). Patients with concomitant HHV-7 DNA-emia had significantly higher number of CMV DNA copies compared with those without HHV-7 infection (1986 vs. 432 copies/ml, p < 0.001) but there was no difference in duration of CMV DNA-emia between these groups. On the other hand, while the load of HHV-7 DNA was comparable between patients with CMV DNA-emia and without CMV DNA-emia, the duration of HHV-7 DNA-emia was significantly longer in the first group (38.5 vs. 14 days, p < 0.001). HHV-7 DNA-emia is very frequently detected in Polish alloHSCT recipients. In those, who have subsequent CMV reactivation, the coexistence of the viruses may negatively affect the kinetics of infection with either of them. Therefore the investigation of concomitant HHV-7 DNA-emia could affect the prognosis of post-transplant patients suffering from CMV reactivation.


Effects of cyclic mechanical stimulation of the cellular components of the heart: in vitro.
The response of the cellular components of the heart to cyclic mechanical stimulation is of particular importance because these cells are continually subjected to mechanical forces as a result of changes in blood volume and pressure. To directly investigate how mechanical tension affects these cellular components of the heart, an in vitro system that exposes the particular cell type (cardiac myocytes, endothelial cells, or fibroblasts) to a calibrated increase in cyclical linear stretch was developed. Cells were grown on silastic membranes coated with laminin and subjected to a 10% cyclical distention 10 times a minute for 72 h. Within 24 h of being exposed to the mechanical stretch, the cells became elongated and oriented perpendicular to the direction of the stretch. These results indicate that cyclical mechanical stimulation directly influences the cellular organization of the heart cells in vitro.


Impact of body mass index on the oncological outcomes of patients treated with radical cystectomy for muscle-invasive bladder cancer.
Body mass index (BMI) has been associated with worse outcomes in several solid malignancies. We aimed to evaluate the association between BMI and oncological outcomes in patients treated with radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB). We retrospectively reviewed 701 consecutive patients treated with RC and pelvic lymphadenectomy for UCB at our institution between 1995 and 2011. Univariable and multivariable Cox regression models investigated the association of BMI with disease recurrence and cancer-specific mortality. BMI was analyzed as both continuous and categorical variable (<25 vs. 25-29 vs. ≥30 kg/m2). From the 701 patients, 275 (39.2 %) had a BMI < 25 kg/m2, 280 (39.9 %) had a BMI between 25 and 29.9 kg/m2, and 146 (20.9 %) had a BMI ⩾ 30 kg/m2. Within a median follow-up of 45 months (IQR 23-75), 163 patients (23.3 %) experienced a disease recurrence and 127 (18.1 %) died from the disease. In univariable analyses, BMI ⩾ 30 kg/m2 was associated with a higher risk of disease recurrence and cancer-specific mortality (both p values <0.01). In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI ⩾ 30 kg/m2 was associated with both higher risks of disease recurrence (HR 1.58; 95 % CI 1.06-2.34, p = 0.02) and cancer-specific mortality (HR 1.58; 95 % CI 1.01-2.48; p = 0.04). Obesity was independently associated with higher risks of disease recurrence and cancer-specific mortality in patients treated with RC for muscle-invasive UCB. BMI is a modifiable feature that may have significant individual and public health implications in patients with muscle-invasive UCB.


The prevalence of hepatitis B virus and hepatitis C virus infection among patients with chronic liver disease in South India.
Determining the identity of hepatitis C virus (HCV) genotypes in liver disease has key implications for ascertaining the duration of antiviral therapy and disease prognosis. We investigated the presence of various genotypes of HCV among 69 chronic liver diseased (CLD) patients with chronic HCV infection. Sixty-nine consecutive subjects with underlying chronic hepatitis (n=28), cirrhosis (n=35), and hepatocellular carcinoma (n=6), diagnosed by clinical, biochemical, and histological means, were studied. Hepatitis B virus (HBV) and HCV diagnostic markers were used. HCV-RNA was extracted from sera of HCV-infected subjects and subsequently the HCV genotypes were determined using a commercial line probe assay (Inno-LiPA HCV II). Of the 69 CLD cases screened for possible markers of HBV and HCV infection, 39 (57%) were positive for HBV and 30 (43%) were HCV infected. The overall HCV-RNA positivity was 77% (23/30). Of these, the majority were genotype 1b (13/23, 57%), followed by 1a (6/23, 26%), mixed genotypes 3 and 4(3/23, 13%), and mixed pattern of 1a, 1b, and 4 (1/23, 4.3%). The genotype 1b infected subjects demonstrated significantly elevated transaminase (ALT) levels (p<0.05) as compared with the other non-1b HCV genotypes. The predominance of HCV genotype 1b among CLD patients could pose a major challenge for the efficient management of HCV disease and the development of effective therapeutic interventions in peninsular India.


Follow-up angiography of intracranial aneurysms treated with endovascular placement of Guglielmi detachable coils.
The success of endovascular treatment of intracranial aneurysms with Guglielmi detachable coils (GDCs) is dependent on the long-term exclusion of the aneurysm from the circulation. We reviewed our experience with the long-term angiographic follow-up monitoring of aneurysms that had been treated with GDCs. All patients whose aneurysms had been treated with GDCs between January 1995 and August 1999 and who subsequently underwent follow-up angiography at 6 months or more were included in this study. We reviewed all of the angiographic findings, to determine the percentage of aneurysm occlusion on the initial angiograms and on the last available follow-up angiograms. The categories of aneurysm occlusion used were 100%, >or=95%, and less than 95% occlusion. One hundred thirty patients with 141 aneurysms underwent 143 endovascular coiling procedures and subsequently underwent angiographic follow-up monitoring of 6 months or more. There were 102 female and 28 male patients. The mean angiographic follow-up period was 16.7 months (range, 6-62 mo). The initial rates of occlusion were 100% for 56 aneurysms (39%), >or=95% for 65 aneurysms (46%), and less than 95% for 22 aneurysms (15%). Recurrence of one aneurysm (1.8%) was observed. Of the 87 aneurysms that were incompletely occluded initially, there was progressive thrombosis in 40 (46%), stable neck remnants in 23 (26%), and enlargement of the residual neck in 24 (28%). The final occlusion rates, determined on the last available angiograms, were 100% for 88 aneurysms (61%), >or=95% for 31 aneurysms (22%), and less than 95% for 24 aneurysms (17%). No patient experienced repeat or new subarachnoid hemorrhage more than 6 months after the initial treatment. Late angiographic follow-up monitoring of aneurysms that have been treated with GDCs demonstrates the durability of the treatment. Aneurysms with large residual neck remnants were subjected to further treatment, whereas aneurysms with small residual neck remnants remain under observation.


PAPP-A: a new anti-aging target?
This article focuses on the role of PAPP-A in mammalian aging. It introduces PAPP-A and a little of its history, briefly discusses the function of PAPP-A in the insulin-like growth factor (IGF) system and the regulators of PAPP-A expression, and then reviews data concerning PAPP-A in aging and age-related diseases especially in regard to the PAPP-A knockout (KO) mouse. The PAPP-A KO mouse is a valuable new model to test hypotheses concerning the control of the tissue availability of IGF, independent from systemic levels, on healthspan as well as lifespan.


Leptin and the regulation of the hypothalamic-pituitary-adrenal axis.
Leptin, the product of the obesity gene (ob) predominantly secreted from adipocytes, plays a major role in the negative control of feeding and acts via a specific receptor (Ob-R), six isoforms of which are known at present. Evidence has been accumulated that leptin, like other peptides involved in the central regulation of food intake, controls the function of the hypothalamic-pituitary-adrenal (HPA) axis, acting on both its central and peripheral branches. Leptin, along with Ob-R, is expressed in the hypothalamus and pituitary gland, where it modulates corticotropin-releasing hormone and ACTH secretion, probably acting in an autocrine-paracrine manner. Only Ob-R is expressed in the adrenal gland, thereby making it likely that leptin affects it by acting as a circulating hormone. Although in vitro and in vivo findings could suggest a glucocorticoid secretagogue action in the rat, the bulk of evidence indicates that leptin inhibits steroid-hormone secretion from the adrenal cortex. In keeping with this, leptin was found to dampen the HPA axis response to many kinds of stress. In contrast, leptin enhances catecolamine release from the adrenal medulla. This observation suggests that leptin activates the sympathoadrenal axis and does not appear to agree with its above-mentioned antistress action. Leptin and/or Ob-R are also expressed in pituitary and adrenal tumors, but little is known about the role of this cytokine in the pathophysiology.


[Determination and significance of plasma P-selectin in patients with allergic rhinitis].
To study the level of plasma P-selectin in patients with allergic rhinitis(AR) and to investigate its significance. The concentration of P-selectin in plasma of 58 patients with AR and 30 normal volunteers were detected with ELISA method. The levels of plasma P-selectin in AR group was higher than that in normal control group(P < 0.01). There is relationship between the level of P-selectin in plasma and AR. It suggests that the P-selectin may play an important role in the pathogenesis of AR.


Assessment of Caregivers' Burden When Caring for Patients With Pancreatic and Periampullary Cancer.
Family and other unpaid caregivers play an active role in the recovery of individuals with pancreatic and periampullary cancer after pancreatectomy. However, little is known about caregivers' experiences and how to better support them. Caregivers accompanying patients to 1-month postpancreatectomy visits at 3 hospitals completed an electronic survey between November 2018 and February 2020. We examine measures of absenteeism and work productivity loss among the subset of caregivers who reported working for pay and comparatively assess caregiver experiences by employment status. All analyses were performed as 2-sided tests. Of 265 caregivers approached for study participation, 240 (90.6%) enrolled. Caregivers were primarily female (70.8% female, 29.2% male) and spouses (58.3%) or adult children (25.8%) of patients, with a median age of 60 years. Of the 240 caregivers included in the study, 107 (44.6%) worked for pay. Nearly half (44.4%) of working caregivers reported being absent from work because of caregiving amounting to a 14% loss in work hours. While at work, 58.9% of working caregivers reported increased work difficulty as a result of caregiving. Taken together, an estimated 59.7% loss in work productivity was experienced because of caregiving in the month following pancreatectomy. After adjustment for sociodemographic factors, working (vs nonworking) caregivers reported increased financial (odds ratio [OR] = 2.32; P = .04) and emotional (OR = 1.93; P = .04) difficulties and daily activity restrictions (OR = 1.85; P = .048). Working caregivers of patients with pancreatic and periampullary cancer experience negative impacts on work and productivity, and caregiving-related financial and emotional difficulties may be amplified. This study highlights the need for workplace policies to support unpaid cancer caregiving.


The Dual Nature of Early-Life Experience on Somatosensory Processing in the Human Infant Brain.
Every year, 15 million preterm infants are born, and most spend their first weeks in neonatal intensive care units (NICUs) [1]. Although essential for the support and survival of these infants, NICU sensory environments are dramatically different from those in which full-term infants mature and thus likely impact the development of functional brain organization [2]. Yet the integrity of sensory systems determines effective perception and behavior [3, 4]. In neonates, touch is a cornerstone of interpersonal interactions and sensory-cognitive development [5-7]. NICU treatments used to improve neurodevelopmental outcomes rely heavily on touch [8]. However, we understand little of how brain maturation at birth (i.e., prematurity) and quality of early-life experiences (e.g., supportive versus painful touch) interact to shape the development of the somatosensory system [9]. Here, we identified the spatial, temporal, and amplitude characteristics of cortical responses to light touch that differentiate them from sham stimuli in full-term infants. We then utilized this data-driven analytical framework to show that the degree of prematurity at birth determines the extent to which brain responses to light touch (but not sham) are attenuated at the time of discharge from the hospital. Building on these results, we showed that, when controlling for prematurity and analgesics, supportive experiences (e.g., breastfeeding, skin-to-skin care) are associated with stronger brain responses, whereas painful experiences (e.g., skin punctures, tube insertions) are associated with reduced brain responses to the same touch stimuli. Our results shed crucial insights into the mechanisms through which common early perinatal experiences may shape the somatosensory scaffolding of later perceptual, cognitive, and social development.


A novel combination of promoter and enhancers increases transgene expression in vascular smooth muscle cells in vitro and coronary arteries in vivo after adenovirus-mediated gene transfer.
Recombinant adenoviruses are employed widely for vascular gene transfer. Vascular smooth muscle cells (SMCs) are a relatively poor target for transgene expression after adenovirus-mediated gene delivery, however, even when expression is regulated by powerful, constitutive viral promoters. The major immediate-early murine cytomegalovirus enhancer/promoter (MIEmCMV) elicits substantially greater transgene expression than the human cytomegalovirus promoter (MIEhCMV) in all cell types in which they have been compared. The Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) increases transgene expression in numerous cell lines, and fragments of the smooth muscle myosin heavy chain (SMMHC) promoter increase expression within SMC from heterologous promoters. We therefore, compared the expression of beta-galactosidase after adenovirus-mediated gene transfer of lacZ under the transcriptional regulation of a variety of combinations of the promoters and enhancers described, in vitro and in porcine coronary arteries. We demonstrate that inclusion of WPRE and a fragment of the rabbit SMMHC promoter along with MIEmCMV increases beta-galactosidase expression 90-fold in SMC in vitro and approximately 40-fold in coronary arteries, compared with vectors in which expression is regulated by MIEhCMV alone. Expression cassette modification represents a simple method of improving adenovirus-mediated vascular gene transfer efficiency and has important implications for the development of efficient cardiovascular gene therapy strategies.


Comparative bioavailability of a microcrystalline theophylline tablet and uncoated aminophylline tablets.
The bioavailability of a rapidly dissolving tablet of theophylline and three brands of standard aminophylline tablets was estimated in a four way cross-over study involving 8 healthy adult volunteers. The relative extent of bioavailability as assessed by the measurement of the total area under the plasma concentration time curves showed no difference between the products (P greater than 0.05). Computed estimates of the rate of drug absorption were similar for all 4 products tested. The results indicate that the rapidly dissolving tablet offers no advantage in respect to rate and extent of absorption over conventional aminophylline tablets.


COVID-19 drugs: potential interaction with ATP-binding cassette transporters P-glycoprotein and breast cancer resistance protein.
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has resulted in acute respiratory distress, fatal systemic manifestations (extrapulmonary as well as pulmonary), and premature mortality among many patients. Therapy for COVID-19 has focused on the treatment of symptoms and of acute inflammation (cytokine storm) and the prevention of viral infection. Although the mechanism of COVID-19 is not fully understood, potential clinical targets have been identified for pharmacological, immunological, and vaccinal approaches. Pharmacological approaches including drug repositioning have been a priority for initial COVID-19 therapy due to the time-consuming nature of the vaccine development process. COVID-19 drugs have been shown to manage the antiviral infection cycle (cell entry and replication of proteins and genomic RNA) and anti-inflammation. In this review, we evaluated the interaction of current COVID-19 drugs with two ATP-binding cassette transporters [P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)] and potential drug-drug interactions (DDIs) among COVID-19 drugs, especially those associated with P-gp and BCRP efflux transporters. Overall, understanding the pharmacodynamic/pharmacokinetic DDIs of COVID-19 drugs can be useful for pharmacological therapy in COVID-19 patients.


[Gynecological tumors of the true pelvis: Radiological diagnosis for pelvic tumors made simple].
Tumors of the reproductive organs are among the most common female tumors. Computed tomography (CT) and magnetic resonance imaging (MRI) are used for establishing the differential diagnosis, for staging and increasingly for treatment stratification. Sonography is the first line imaging modality for assessing benign and malignant tumors of the uterus as well as ovarian and adnexal lesions. In sonographically indeterminate masses MRI is used for clarification as it allows not only a prediction of the dignity but also in most cases a specific diagnosis. The MRI examination is also superior to CT in the assessment of tumors resembling benign pelvic lesions. Whereas MRI has become established as the modality of choice for local staging and treatment planning in cancers of the uterine cervix and endometrial cancer, CT is used for staging of ovarian cancer due to the propensity for peritoneal spread outside the pelvis at the time of initial diagnosis.


Photoreaction pathways and photointermediates of retinal-binding photoreceptor proteins as revealed by in situ photoirradiation solid-state NMR spectroscopy.
Photoirradiation solid-state NMR spectroscopy is a powerful means to study photoreceptor retinal-binding proteins by the detection of short-lived photointermediates to elucidate the photoreaction cycle and photoactivated structural changes. An in situ photoirradiation solid-state NMR apparatus has been developed for the irradiation of samples with extremely high efficiency to enable observation of photointermediates which are stationary trapped states. Such observation enables elucidation of the photoreaction processes of photoreceptor membrane proteins. Therefore, in situ photoirradiation is particularly useful study the photocycle of retinal-binding proteins such as sensory rhodopsin I (SRI) and sensory rhodopsin II (SRII) because functional photointermediates have relatively longer half-lives than other photointermediates. As a result, several photointermediates have been trapped as stationary state and their detailed structures and photoreaction cycles have been revealed using photoirradiation solid-state NMR spectroscopy at low temperature. Photoreaction intermediates of bacteriorhodopsin, which functions to provide light-driven proton pump activity, were difficult to trap because the half-lives of the photointermediates were shorter than those of sensory rhodopsin. Therefore, these photointermediates are trapped in a freeze-trapped state at a very low temperature and the NMR signals were observed using a combination of photoirradiation and dynamic nuclear polarization (DNP) experiments.


Ab initio optimization of phonon drag effect for lower-temperature thermoelectric energy conversion.
Although the thermoelectric figure of merit zT above 300 K has seen significant improvement recently, the progress at lower temperatures has been slow, mainly limited by the relatively low Seebeck coefficient and high thermal conductivity. Here we report, for the first time to our knowledge, success in first-principles computation of the phonon drag effect--a coupling phenomenon between electrons and nonequilibrium phonons--in heavily doped region and its optimization to enhance the Seebeck coefficient while reducing the phonon thermal conductivity by nanostructuring. Our simulation quantitatively identifies the major phonons contributing to the phonon drag, which are spectrally distinct from those carrying heat, and further reveals that although the phonon drag is reduced in heavily doped samples, a significant contribution to Seebeck coefficient still exists. An ideal phonon filter is proposed to enhance zT of silicon at room temperature by a factor of 20 to ∼ 0.25, and the enhancement can reach 70 times at 100 K. This work opens up a new venue toward better thermoelectrics by harnessing nonequilibrium phonons.


Bovine herpesvirus-1 vaccines.
Vaccination has been important in controlling a wide variety of viral and bacterial infections of man and animals. Vaccines to herpesvirus infection of cattle are no exception. The present review describes the different types of conventional vaccines that have been used to date and furthermore describes the novel approaches which are presently being implemented to develop more effective vaccines. These include subunit vaccines as well as genetically engineered modified live deletion mutants. Both these novel vaccine approaches appear to be more efficacious than conventional vaccines. Furthermore, these vaccines provide an additional dimension for control and eradication of infection by providing an opportunity to develop companion diagnostic tests to differentiate infected animals from vaccinated animals. This review summarizes these developments as well as present knowledge regarding the important host defence mechanisms required for preventing infection and aiding recovery from infection.


Second esophageal neoplasms after head and neck index tumor: Incidence, risk factors and prognosis.
Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of second esophageal neoplasms. The aim of the present study is to evaluate the incidence, risk factors and prognosis of second esophageal neoplasms in patients with HNSCC. A retrospective study of 4711 patients with index tumor in the oral cavity, oropharynx, hypopharynx or larynx between 1985 and 2020 was conducted. During the period analysed 149 patients (3.2%) had a second esophageal neoplasm. The incidence of second esophageal neoplasia was 0.42% per year and remained nearly constant throughout the follow-up period. According to the results of a multivariate study, the risk factors related to the appearance of second esophageal neoplasms were a history of high alcohol consumption and the location of the primary tumor in the oropharynx or hypopharynx. The 5-year disease-specific survival rate in patients with a second esophageal neoplasm, calculated from the diagnosis of this second neoplasm, was 10.5%. Patients with a HNSCC have an increased risk of developing of a second esophageal neoplasm. The risk factors associated with the appearance of a second esophageal neoplasm were severe alcohol consumption and the location of the primary tumor in the oropharynx or hypopharynx.


I Can't Forget What You Couldn't Tell Me: A Psychoanalyst Listens to Asylum Seekers.
This paper details my psychoanalytic process evaluating refugees as part of their application for asylum. It focuses on the emergence of unrepresented content and abject states within the intersubjective matrix that lead to collaborative creation of a story of trauma. Such intra- and inter-personal encounters are structured by the larger social, political, and cultural contexts that support, limit, structure, erase, and determine what can be known and told. Knowledge of traumatic inscription necessitates attunement to nonverbal affective states in both survivor and witness as well a receptive society that is able to tolerate grief, acknowledge the degradation and depravity unleashed in victim and victimizer during violence, and absorb survivors' mournful morality tales.


YY1 is a cis-regulator in the organoid models of high mammographic density.
Our previous study has shown that ERBB2 is overexpressed in the organoid model of MCF10A when the stiffness of the microenvironment is increased to that of high mammographic density (MD). We now aim to identify key transcription factors (TFs) and functional enhancers that regulate processes associated with increased stiffness of the microenvironment in the organoid models of premalignant human mammary cell lines. 3D colony organizations and the cis-regulatory networks of two human mammary epithelial cell lines (184A1 and MCF10A) are investigated as a function of the increased stiffness of the microenvironment within the range of MD. The 3D colonies are imaged using confocal microscopy, and the morphometries of colony organizations and heterogeneity are quantified as a function of the stiffness of the microenvironment using BioSig3D. In a surrogate assay, colony organizations are profiled by transcriptomics. Transcriptome data are enriched by correlative analysis with the computed morphometric indices. Next, a subset of enriched data are processed against publicly available ChIP-Seq data using Model-based Analysis of Regulation of Gene Expression to predict regulatory transcription factors. This integrative analysis of morphometric and transcriptomic data predicted YY1 as one of the cis-regulators in both cell lines as a result of the increased stiffness of the microenvironment. Subsequent experiments validated that YY1 is expressed at protein and mRNA levels for MCF10A and 184A1, respectively. Also, there is a causal relationship between activation of YY1 and ERBB2 when YY1 is overexpressed at the protein level in MCF10A. Supplementary data are available at Bioinformatics online.


Providing open imaging data at scale: An EMBL-EBI perspective.
Biological imaging is one of the primary tools by which we understand living systems across scales from atoms to organisms. Rapid advances in imaging technology have increased both the spatial and temporal resolutions at which we examine those systems, as well as enabling visualisation of larger tissue volumes. These advances have huge potential but also generate ever increasing amounts of imaging data that must be stored and analysed. Public image repositories provide a critical scientific service through open data provision, supporting reproducibility of scientific results, access to reference imaging datasets and reuse of data for new scientific discovery and acceleration of image analysis methods development. The scale and scope of imaging data provides both challenges and opportunities for open sharing of image data. In this article, we provide a perspective influenced by decades of provision of open data resources for biological information, suggesting areas to focus on and a path towards global interoperability.


Cervical extradural arteriovenous fistula with radiculopathy managed endovascularly.
Extradural arteriovenous fistulas (AVFs) of the cervical spine are extremely rare, and typically manifest as slowly progressive myelopathy caused by mass effect. This is a unique case of extradural AVF of the cervical spine manifesting with purely radicular symptoms and treated endovascularly with coil and liquid embolization. A 55-year-old woman presented with neck pain and right upper extremity radiculopathy persisting for 9 months. Imaging studies demonstrated an AVF spanning from C4-C6 with extension into the C5-C6 foramen supplied primarily from the deep cervical branch of the costocervical trunk. The patient underwent successful coil and liquid (Onyx) embolization. Six-week postoperatively, the patient's symptoms completely resolved and magnetic resonance imaging and angiographic imaging confirmed complete obliteration of the fistula. While extradural AVFs typically present with myelopathic symptoms, they may present with solely radicular symptoms and can be successfully treated endovascularly.


The role of SVZ-derived neural precursors in demyelinating diseases: from animal models to multiple sclerosis.
We will review the role of endogenous neural stem cells in myelin repair both in animal models of demyelination and multiple sclerosis. The mammalian sub-ventricular zone (SVZ) is the largest germinative zone of the adult brain, which contains a well characterized stem cell niche. While most studies highlight the neurogenic potential of SVZ progenitors, recent data indicate that SVZ cells become reactived in response to different pathological cues, like trauma, ischemia, neurodegeneration, inflammation and demyelination. Experimental models of demyelination in rodent demonstrate enhanced proliferation and recruitment of SVZ progenitors into myelin lesions, in response to demyelination. Moreover, cell lineage tracing experiments showed that SVZ progenitor cells can give rise to oligodendrocytes in demyelinated lesions, that could potentially contribute to remyelination. To examine the relevance of these studies in myelin diseases, we recently examined the human SVZ in post-mortem MS brains. The human SVZ is characterized by a ribbon of SVZ astrocytes lining the ependymal border of the lateral ventricles and which behave as multipotential progenitors in vitro. We showed that cellular density and proliferation were enhanced in MS SVZ compared to non-neurological controls. This high cellular density was correlated with the increased number of progenitor cells in MS SVZ, as well as in sub-ventricular lesions. Interestingly, some of these progenitors expressed transcription factors involved in oligodendrogenesis, such as Sox9, Olig2 and Sox10. These data indicate that gliogenesis occurs also in MS SVZ and suggest the recruitment of SVZ-derived oligodendrocyte precursors to peri-ventricular demyelinated lesions. Further investigation of adult neural stem cells and their progenitors in the brain of rodents and non-human primates should help to gain insights in their process of activation in response to demyelination and their role in myelin repair.


Human infections due to Salmonella Blockley, a rare serotype in South Africa: a case report.
Infections due to nontyphoidal Salmonella have increased worldwide over the last couple of decades. Salmonella enterica serotype Blockley (Salmonella Blockley) infections is associated with chickens and is a rarely isolated serotype in human infections in most countries. We report a case of human infections due to Salmonella Blockley in KwaZulu-Natal, South Africa in 2011. Three African males (aged 4, 14 and 16) presented to a clinic with diarrhoea, stomach cramps and headache. They started experiencing signs of illness a day after they consumed a common meal, consisting of meat, rice and potatoes. Stool specimens from the patients cultured Salmonella Blockley. The strains showed an indistinguishable pulsed-field gel electrophoresis pattern. This is the first recorded case of human infections due to Salmonella Blockley in South Africa.


Inventory of Varroa destructor susceptibility to amitraz and tau-fluvalinate in France.
Varroa destructor is one of the greatest threats for the European honeybee, Apis mellifera. Acaricides are required to control mite infestation. Three conventional chemical acaricide substances are used in France: tau-fluvalinate, flumethrin and amitraz. Tau-fluvalinate was used for over 10 years before experiencing a loss of effectiveness. In 1995, bioassay trials showed the first mite resistance to tau-fluvalinate. In some countries, amitraz was widely used, also leading to resistance of V. destructor to amitraz. In France, some efficiency field tests showed a loss of treatment effectiveness with amitraz. We adapted the bioassay from Maggi and collaborators to determine mite susceptibility to tau-fluvalinate and amitraz in France in 2018 and 2019. The lethal concentration (LC) which kills 90% of susceptible mite strains (LC90) is 0.4 and 12 µg/mL for amitraz and tau-fluvalinate, respectively. These concentrations were chosen as the determining factors to evaluate mite susceptibility. Some mites, collected from different apiaries, present resistance to amitraz and tau-fluvalinate (71% of the mite samples show resistance to amitraz and 57% to tau-fluvalinate). As there are few active substances available in France, and if mite resistance to acaricides continues to increase, the effectiveness of the treatments will decrease and therefore more treatments per year will be necessary. To prevent this situation, a new strategy needs to be put in place to include mite resistance management. We suggest that a bioassay would be a good tool with which to advise the policymakers.