A health education booklet for young families--its need, use and effect.
The objective was to describe the effect of a mailed health education booklet for families with children in relation to parents' need for health education. It was a randomized controlled trial. The parents' anxiety and use of doctors were registered in a questionnaire, together with selected psychosocial conditions, during a retrospective period of six months. An age-stratified random sample of 3913 families--1953 study families and 1960 control families was drawn in the county of Ringkjøbing, Denmark. The booklet was used a lot; it reduced parents' anxiety and use of doctors in children's illnesses. The effect was most pronounced in those parents who had least need for health education. This method of health education was not very efficient. The possibilities and value of combining written health education with personal individual instruction by the general practitioner are discussed.


FcγRIIIa-158V/F polymorphism affects the performance of FcγRIIIa-related bioassay.
Bioassays are important for estimating biosimilarity between biological products. Comparability studies including bioassays are needed to demonstrate that a biosimilar product has no meaningful differences that affect safety and efficacy compared with the reference product. Among the most important biological characteristics of therapeutic mAbs are Fc-mediated functions, which induce immune-cell activation which can affect both efficacy and safety. Thus, when developing biosimilar products of therapeutic mAbs, it is necessary to compare the Fc-mediated functions by using various bioassays. Though it is reported that polymorphism of Fcγ receptors (FcγRs) affects Fc-mediated cellular activations of therapeutic mAbs, the impacts of the polymorphism of FcγRs on bioassay performance are still unclear. In this study, we evaluated the impact of FcγRIIIa-158V/F polymorphism on assay performance in distinguishing differences in the biological activities of therapeutic mAbs. The results showed that different bioassay methods produced different assessments of biological activities of mAbs, and that the FcγRIIIa-158V/F polymorphism clearly affected the performance of the FcγRIIIa-binding assay using recombinant proteins and FcγRIIIa-expressing reporter assays. That is, the assays using the FcγRIIIa-158F variant were superior to those using the FcγRIIIa-158V variant in distinguishing the difference in FcγRIIIa-binding and -activation properties. These results indicate that we should evaluate the comparability of biosimilars by considering the impacts of FcγRIIIa-158V/F polymorphism on bioassay performance.


pH-dependent hydrolysis of acetylcholine: Consequences for non-neuronal acetylcholine.
Acetylcholine is inactivated by acetylcholinesterase and butyrylcholinesterase and thereby its cellular signalling is stopped. One distinguishing difference between the neuronal and non-neuronal cholinergic system is the high expression level of the esterase activity within the former and a considerably lower level within the latter system. Thus, any situation which limits the activity of both esterases will affect the non-neuronal cholinergic system to a much greater extent than the neuronal one. Both esterases are pH-dependent with an optimum at pH above 7, whereas at pH values below 6 particularly the specific acetylcholinesterase is more or less inactive. Thus, acetylcholine is prevented from hydrolysis at such low pH values. The pH of the surface of the human skin is around 5 and therefore non-neuronal acetylcholine released from keratinocytes can be detected in a non-invasive manner. Several clinical conditions like metabolic acidosis, inflammation, fracture-related haematomas, cardiac ischemia and malignant tumours are associated with local or systemic pH values below 7. Thus, the present article describes some consequences of an impaired inactivation of extracellular non-neuronal acetylcholine.


The effect of psychosocial factors on lung cancer mortality at one year.
In this study newly diagnosed male and female lung cancer patients admitted to two Ontario Cancer Foundation treatment clinics were interviewed. Information was obtained on demographic variables, presence of other chronic illness and the following psychosocial attributes: locus of control, social support and personality traits. From the clinic charts, information on stage of disease and pathological diagnosis was obtained. After controlling for the effects of stage and pathological diagnosis, the following psychological variables were found to increase the odds of death from lung cancer among males and females combined at one year after diagnosis: a high need for one aspect of social support, a reserved personality and the extremes of the personality trait soberness vs enthusiasm.


Religious construction of a first episode of psychosis in urban Brazil.
Religion plays an important role in the lives of people with psychosis. Based on fieldwork with 21 families living in poor neighborhoods of São Paulo, Brazil, this article examines how youth suffering a first episode of psychosis resort to religion for help (including, Catholicism, Pentecostalism, Candomblé, and Umbanda) and how this frames their experience of psychosis and that of their family members. For young people, the personal articulation of religious idioms and signifiers served to communicate, elaborate and transform their experience of psychosis. Family members resorted to religion as a source of healing, complementary to psychiatric treatment, as well as for personal relief and comfort. For youth, involvement with religion worked in both 'progressive' and 'regressive' ways, to improve and, at times, to diminish functioning and well-being.


Cardiac-specific overexpression of catalase prevents diabetes-induced pathological changes by inhibiting NF-κB signaling activation in the heart.
Catalase is an antioxidant enzyme that specifically catabolizes hydrogen peroxide (H2O2). Overexpression of catalase via a heart-specific promoter (CAT-TG) was reported to reduce diabetes-induced accumulation of reactive oxygen species (ROS) and further prevent diabetes-induced pathological abnormalities, including cardiac structural derangement and left ventricular abnormity in mice. However, the mechanism by which catalase overexpression protects heart function remains unclear. This study found that activation of a ROS-dependent NF-κB signaling pathway was downregulated in hearts of diabetic mice overexpressing catalase. In addition, catalase overexpression inhibited the significant increase in nitration levels of key enzymes involved in energy metabolism, including α-oxoglutarate dehydrogenase E1 component (α-KGD) and ATP synthase α and β subunits (ATP-α and ATP-β). To assess the effects of the NF-κB pathway activation on heart function, Bay11-7082, an inhibitor of the NF-κB signaling pathway, was injected into diabetic mice, protecting mice against the development of cardiac damage and increased nitrative modifications of key enzymes involved in energy metabolism. In conclusion, these findings demonstrated that catalase protects mouse hearts against diabetic cardiomyopathy, partially by suppressing NF-κB-dependent inflammatory responses and associated protein nitration.


Mental health in the Family Health Strategy as perceived by health professionals.
to analyze the management of mental health needs in primary care as perceived by Family Health Strategy professionals. this was a qualitative descriptive exploratory study developed within the coverage area of five family health teams. The data were collected using observation, group interviews, individual semi-structured interviews, and focus groups. Content analysis was conducted using text analysis software and interpretation was based on the corresponding analytical structures. numerous and challenging mental health demands occur in this setting, for which the teams identified care resources; however, they also indicated difficulties, especially related to the operationalization and integration of such resources. there is a need for a care network sensitive to mental health demands that are better coordinated and more effectively managed. analisar o manejo das necessidades de saúde mental na atenção primária à saúde de acordo com a percepção dos profissionais da Estratégia Saúde da Família. estudo qualitativo, descritivo exploratório, desenvolvido no território de abrangência de cinco equipes de saúde da família. Os participantes foram cinco enfermeiras, cinco coordenadores e 17 agentes comunitários de saúde. Os dados foram coletados utilizando observação, entrevistas grupais, entrevistas individuais semiestruturadas e grupos focais. Fez-se a análise de conteúdo com o auxílio de um Software de análise textual, e a interpretação baseou-se nas estruturas analíticas correspondentes. inúmeras e desafiadoras demandas de saúde mental têm sido acolhidas nesse setting, para as quais as equipes identificaram recursos de atendimento; no entanto, apontaram dificuldades, sobretudo relacionadas à operacionalização e integração destes recursos. destaca-se a necessidade de uma rede de cuidados sensível a tais demandas, mais articulada e gerida de modo eficaz.


Circadian profiling reveals distinct regulation of endocannabinoid system in the rat plasma, liver and adrenal glands by light-dark and feeding cycles.
Circadian clocks coordinate physiological and behavioral rhythms that allow the organism to anticipate and adapt to daily changes in environment. The clock-driven cellular oscillations are highly tissue specific to efficiently fine-tune local signaling, manage energy use and segregate incompatible processes. In most peripheral tissues, food acts as the main cue that entrains the oscillations to external time. Food intake and energy balance are under control of endocannabinoid (EC) signaling. Despite this obvious link between the circadian and EC systems, evidence for their interaction started to emerge only recently. We used targeted lipidomics to analyze circadian variations in EC tone in rat plasma, liver and adrenal tissue. The results provide the evidence that ECs, monoacylglycerols, N-acylethanolamines and their precursors oscillate with a tissue-specific circadian phase in plasma and liver. We then identified a set of rhythmically expressed genes likely responsible for the variations in EC tissue tone. In contrast to the liver, EC levels did not oscillate in the adrenal glands. Instead, we revealed that local EC receptor genes are under circadian regulation. To explore the impact of metabolic signals on expression of these genes, we used daytime-restricted feeding schedule. We subsequently showed that daytime feeding strongly suppressed liver-expressed fatty acid binding protein 5 (Fabp5) and adrenal-expressed non-canonical endocannabinoid receptors Gpr55 and Trpv1, whereas it upregulated liver-expressed Trpv1 and glycerophosphodiester phosphodiesterase 1 (Gde1). Our results reveal tissue-specific mechanisms involved in interaction between endocannabinoid signaling, circadian system and metabolism.


Use of geospatial analyses to address snakebite hotspots in mid-northern Brazil - A direction to health planning in shortfall biodiversity knowledge areas.
Knowing the distribution of venomous snakes of medical importance is essential to identify areas at risk for snakebites. Thus, we used an integrative approach based on the application of geographic distribution data of venomous snakes, species distribution modeling (SDM), spatial organization of snakebites, and information on human population density for mapping the potential distribution of snakes and identifying areas at risk of snakebites in the state of Maranhão (mid-northern Brazil). From a compiled database of venomous snake records deposited in biological collections and the literature, we predict the potential distribution of venomous snakes in Maranhão, a state whose diversity and geographic distribution of venomous snake species are poorly known. With this, we constructed potential distribution maps for each venomous snake species with at least one occurrence record within state boundaries, as well as generalized maps by family (Viperidae and Elapidae) and the total number of venomous snakes in Maranhão State. We also obtained data on the number of snakebites recorded in each municipality of Maranhão over a decade (2009-2019) and we ran a Generalized Linear Model to test for relationships between the number of venomous snakebites, the area of occurrence of snakes, and human population density. We obtained 1046 records of venomous snake species for Maranhão, represented by 17 viperid and elapid species. Most of the records were from Viperidae (mostly Bothrops atrox and B. marajoensis) and were concentrated mainly in the Amazon of the northern portion of the state. The models showed accurate predictive performance for all modeled species. The entire area of Maranhão exhibits environmental conditions for the occurrence of venomous snakes, with higher suitability indices in the northern region, in the Amazon rainforest. The number of snakebites was positively correlated with the interaction between high-risk areas (i.e., greater distribution of venomous snakes) and human population density. Our study is a pioneer in using species distribution modeling in mid-northern Brazil to address the scarcity of data on snakebite-causing species, directly contributing to the theme of neglected tropical diseases of the World Health Organization.


[Dorsal occipito-cerivale spondylodesis with plate fixation of the wire to the occiput (author's transl)].
In occipito-cervical spondylodesis, performed because of instability in this area, there is quite a high incidence of pseudarthrosis. We tried to achieve a biomechanically stable spondylodesis by anchoring the temporary stabilizing wire-loop with a small osteosynthesis plate in the occiput and with a cortical screw in the spinous processus. Our two cases operated by this method showed a favorable result with good reduction. The bone graft consolidated without complications, the wire-loop did not break. This method seems to be less complicated that the fixation with a special plate according to Cabot and Mordent.


Inhibitory effect of glybenclamide on mitochondrial chloride channels from rat heart.
Glybenclamide is used as a pharmacological tool in studies of mitochondrial functions supposing its main role to block ATP-dependent potassium (KATP) channel. The aim of this study was to test whether glybenclamide might interact with the mitochondrial chloride channels. Mitochondrial membranes, isolated from rat heart muscle, were incorporated into lipid bilayer membrane and single chloride channel currents were measured in 250/50 mM KCl cis/trans solutions. The observed chloride channels (N=11) with mean conductance 120±14 pS were sensitive to glybenclamide, which decreased the open probability (IC50=129 μM) and affected the channel gating kinetics (IC50=12 μM) by perturbing its open state. It did not influence the channel conductance or reversal potential. These results indicate that glybenclamide interacts with chloride channels what should be taken into consideration, when glybenclamide is used as a specific inhibitor of KATP channels.


Induction of mammary tumors, estrous cycle abnormalities and endometrial hyperplasia in rats exposed to different doses of N-nitrosomethylurea.
Groups of female Sprague--Dawley strain rats were given 3 i.v. injections of N-nitrosomethylurea in doses of 0.5, 1, 2, 3, 4 or 5 mg/100 g body weight at 4-week intervals. The first dose was given when they were 50 days old. By 23 weeks after the first injection, mammary tumors had developed in 0, 0, 33, 54, 72 and 100% of animals respectively. There was a direct relationship between the total dose of carcinogen administered and the degree of tumor anaplasia observed on histological examination. All of the tumors contained assayable amounts of estrogen and progesterone receptors, and the receptor concentrations were not related to the dose of carcinogen. Twenty-one rats, all exposed to the 4 highest doses of N-nitrosomethylurea, had arrest of the estrous cycle at the stage of estrus. In 15 of the 21 the walls of the uterine horns were thickened and grossly distended by fluid. Histological examination demonstrated the presence of endometrial hyperplasia. These uterine abnormalities were usually accompanied by polycystic disease of the ovaries. Both endometrial hyperplasia and abnormal estrous cycles without uterine changes were associated with elevated progesterone receptor to estrogen receptor ratios in the corresponding mammary carcinomas.


Permanent middle ear aeration: long-term follow-up of transosseous ventilating tubes.
A technique for achieving permanent middle ear aeration by inserting a flanged silicone tube (SPAT) through a hole drilled in the external auditory canal was introduced in 1970. Since 1970, we have used the transosseous procedure in 36 patients (11%) of cases that required middle ear ventilation. The average length of time the transosseous SPAT functioned was 51 months (range 0-138). Best results were obtained in patients over 16 years of age, when chronic ear surgery was not performed simultaneously. Transient otorrhea occurred in 23% of cases. Forty-four percent of tubes became blocked and required removal or were extruded. No patient developed facial weakness, middle ear cholesteatoma, or persistent tympanic membrane perforation. In selected cases, the transosseous SPAT provides long-term middle ear aeration without the risk of permanent tympanic membrane perforation.


Sirtuins, nuclear hormone receptor acetylation and transcriptional regulation.
Endocrine signaling via nuclear receptors (NRs) is known to play an important role in normal physiology as well as in human tumor progression. Hormones regulate gene expression by altering local chromatin structure and, thereby, accessibility of transcriptional co-regulators to DNA. Recently it has been shown that non-histone proteins involved in hormone signaling, such as nuclear receptors and NR co-activators, are regulated by acetylation, resulting in their altered transcriptional activity. NAD-dependent protein deacetylases, the sirtuins (Sir2-related enzymes), directly modify NRs. Because sirtuins have been shown to regulate tumor cellular growth, aging, metabolic signaling and endocrine hormone signaling, they might play a role in cancer progression. This review focuses on the role of acetylation and the sirtuins in nuclear hormone receptor signaling.


Thyroid hormones in alcoholic liver disease. Effect of treatment with 6-n-propylthiouracil.
The relationship between alcoholic liver disease and circulating thyroid hormones was investigated in 124 hospitalized patients treated with placebo or propylthiouracil (PTU) for a maximum of 46 days in a double-blind study. Serum triiodothyronine (T3) levels on admission were significantly (P less than 10(-6) and inversely correlated with the severity of alcoholic liver disease. After hospitalization, changes in T3-levels in patients with low admission T3 significantly correlated (P less than 0.001) with the degree of spontaneous improvement of liver function (placebo group). Treatment with 300 mg of PTU daily (Orrego et al. Gastroenterology 76:105--115, 1979) markedly increased the rate of improvement in severely ill patients with low T3 on admission. In this group, serum T3-levels were also increased after PTU, but this increase did not correlate with the change in the patient's condition. It is suggested that the known inhibitory effect of PTU on peripheral deiodination of T4 to T3 is marked by a more marked improvement in liver function in this group. PTU treatment in this group reduced the free T4-index and increased TSH levels markedly (16%; P less than 0.02) toward levels found in hypothyroidism. PTU did not improve the condition of mildly ill patients with normal admission T3-levels, nor did it alter free T4-index or serum TSH levels in these patients. Serum T3-levels provide a sensitive indicator of the severity of alcoholic liver disease and of its response to conventional treatment. Serum T3-levels also distinguish between a group of patients, in whom low-dose PTU administration results in a beneficial effect, and another group, in whom no therapeutic effect of PTU is observed.


A compact model for early electromigration failures of copper dual-damascene interconnects.
A compact model for early electromigration failures in copper dual-damascene interconnects is proposed. The model is based on the combination of a complete void nucleation model together with a simple mechanism of slit void growth under the via. It is demonstrated that the early electromigration lifetime is well described by a simple analytical expression, from where a statistical distribution can be conveniently obtained. Furthermore, it is shown that the simulation results provide a reasonable estimation for the lifetimes.


Exploring the working environment of Hospital Managers: a mixed methods study investigating stress, stereotypes, psychological safety and individual resilience.
Hospital managers are responsible for the delivery of organisational strategy, development of clinical services and maintaining quality standards. There is limited research on hospital managers, in particular how stress manifests and impacts managers and the presence of individual resilience. Managers must work closely with clinical colleagues, however these relationships can be hindered by the perception of stereotyping and differing priorities. This study aimed to explore the working environment of hospital managers, focusing upon the unique stresses faced, psychological safety and the presence of resilience. This study utilised mixed methodology using an embedded approach. Participants were purposively recruited from all levels of hospital management within one National Health Service Trust in London, United Kingdom. An exploration of managers experiences was undertaken using semi-structured qualitative interviews. Psychological safety and individual resilience were additionally assessed using validated surveys. Qualitative data were analysed iteratively using inductive thematic analysis, and triangulated with quantitative data. Kruskal-Wallis statistical analysis was performed to evaluate differences in resilience and psychological safety according to seniority and background experience. Twenty-two managers were recruited and interviewed, with 20 returning completed surveys. Key findings from the thematic analysis included the importance of good working relationships with clinical colleagues, the persistence of some stereotyping, and feeling unsupported in times of challenge. Stresses described included the bureaucracy involved when delivering change, conflict with colleagues and target driven expectations. Participants described their own psychological safety as lower than desired, supported by quantitative data; but recognised its importance and strived to create it within their own teams. Sixteen participants had 'normal' scores for resilience, with senior managers more likely to have higher scores than those more junior (p=0.011). Positive working relationships, high psychological safety and individual resilience are important for organisational safety and individual wellbeing. Our data illustrate unique stressors faced by hospital managers, provide detail on sometimes challenging working relationships, and demonstrate scope to improve both the psychological safety and resilience of those in managerial positions. A map for senior healthcare leaders was constructed, facilitating the identification of modifiable areas within their organisation to promote good working relationships and improve the working environment of hospital managers.


Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging.
Characterizing biological mechanisms dependent upon the interaction of many cell types in vivo requires both multiphoton microscope systems capable of expanding the number and types of fluorophores that can be imaged simultaneously while removing the wavelength and tunability restrictions of existing systems, and enhanced software for extracting critical cellular parameters from voluminous 4D data sets. We present a procedure for constructing a two-laser multiphoton microscope that extends the wavelength range of excitation light, expands the number of simultaneously usable fluorophores and markedly increases signal to noise via 'over-clocking' of detection. We also utilize a custom-written software plug-in that simplifies the quantitative tracking and analysis of 4D intravital image data. We begin by describing the optics, hardware, electronics and software required, and finally the use of the plug-in for analysis. We demonstrate the use of the setup and plug-in by presenting data collected via intravital imaging of a mouse model of breast cancer. The procedure may be completed in ∼24 h.


Habitual toe-walking: evaluation and approach to treatment.
Habitual toe-walking has been presented as a prolongation of a normal stage of development that requires conservative treatment to prevent or ameliorate associated gait abnormalities such as tripping and falling. An approach to the evaluation of a child with toe-walking should include (1) medical history (prenatal, intrapartum, and postnatal), (2) gait evaluation, (3) musculoskeletal examination, and (4) neurologic examination. Pathologic entities producing toe-walking have been explored in order to differentiate those conditions from idiopathic (habitual) toe-walking. The most common etiologies of toe-walking (nonhabitual) would include gastrosoleus equinus, clubfoot, or cerebral palsy. Treatment of habitual toe-walkers might include shoe therapy, orthosis therapy, auditory feedback, and surgery.


Energetics of enzyme catalysis. II. Oversaturation, case diagrams, reversible and irreversible behaviour.
Most enzymes react in vivo under reversible conditions where the substrate and product concentrations are not far removed from equilibrium values. Under these conditions when the concentration of substrate is increased, in addition to the usual unsaturated and saturated behaviour we find a third type of kinetic regime at high substrate concentration-oversaturation. In this regime the rate limiting transition state involves interconversion of free enzyme forms. For a one substrate/one product enzyme, case diagrams can be constructed which depict the kinetic behaviour as a function of substrate and product concentrations. Six different cases are found and are discussed with the relevant free energy profiles. A systematic procedure is described for the investigation and construction of the case diagram.


Progression before local control in osteosarcoma: Outcome and prognosis-predictive factors.
The prognosis and impact of early disease progression in patients with osteosarcoma prior to local control (LC), and the potential therapeutic benefits of ifosfamide/etoposide (IE) remain underexplored in the medical literature. A retrospective study was conducted on pediatric patients (≤18 years) with osteosarcoma who presented to King Hussein Cancer Center between June 2006 and March 2022. We studied patients with disease progression before LC. Among 195 patients, 31 (17males) exhibited disease progression before LC. The median age at diagnosis was 14.1 years, and patients were followed for a median of 23.1 months (range: 5.8-94.7). The majority of tumors were located in the extremities (n = 28). Ten patients (48%) had lung-only metastasis. Twenty-five patients showed progression at the local site only, and six showed progression both at local/metastatic sites. For the 25 patients with local-site-only progression, the decision for 24 was immediate LC via LSS (n = 9), amputation (n = 10), hemimandibulectomy (n = 1), and radiation therapy (n = 1). Three families refused amputation. Among the six patients with combined local/metastatic site progression, the decision was for two to intensify chemotherapy by adding IE, while the other four were recommended immediate LC. However, two of them refused surgery. In total, five patients received IE as intensification for progression, all of whom subsequently progressed. The 5-year event-free survival and overall survival were 27.2% and 31.3%, respectively. Our findings suggest that early disease progression before LC in patients with osteosarcoma is associated with poor prognosis. However, patients initially diagnosed with localized disease and who later exhibited local-disease-only progression appeared to have better outcomes. The potential role of IE in the treatment of patients exhibiting early progression merits further investigation in a larger study cohort.


An unusual PR interval alternans during 2:1 atrio-ventricular block.
In a case of a 2:1 second degree A-V block during sinus rhythm, PR intervals of two different durations occur, either separately or alternating beat-by-beat. The longer intervals are not caused by concealed conduction in the A-V junction of the preceding blocked impulses and the shorter ones are not due to supernormal conduction induced by the blocked impulses. This primary PR interval alternans is alternating from a pathophysiological point of view; it only concerns every other impulse alternately traveling along the faster and slower A-V junctional pathway.


Does peripheral vestibular disorder increase the risk of attempted suicide: A retrospective cohort study.
This study aimed to investigate the risk of attempted suicide in the population of patients diagnosed with peripheral vestibular disorders (PVD). We conducted a retrospective cohort study. We extracted data on patients diagnosed with PVD (72,569 study patients) and a 3:1 ratio of propensity-score matched comparison patients without PVD (217,707 patients) from Taiwan's Longitudinal Health Insurance Database 2010. The claims records of sampled patients were tracked for a one-year period from their index date to identify claims showing a diagnosis of suicide attempt. Cox proportional hazards regression analyses were performed to calculate the one-year hazard ratio (HR) of suicide attempt following the PVD diagnosis among PVD patients relative to comparison patients. Of total 290,276 sampled patients, the rate of attempted suicide was 0.158 per 100 person-years, being 0.460 and 0.057, respectively, among PVD patients and comparison patients. Cox proportional hazard analysis showed that PVD patients had a high relative hazard of suicide attempt (adjusted HR = 7.622, 95 % CI = 6.196-9.376) during one-year follow-up relative to comparison patients. We also found that subcategories of PVD, showed similar adjusted hazard ratios as all PVDs: Meniere's disease (HR = 7.608, 95 % CI = 4.350-13.305), benign paroxysmal positional vertigo (HR = 8.201, 95 % CI = 4.716-14.260), and vestibular neuritis (HR = 9.399, 95 % CI = 5.036-17.544). The incidence of suicide attempts could be underestimated in both the study group and comparison group, if the suicide attempt did not cause a medical emergency and the patient did not seek medical assistance. We found a high magnitude of association between PVD and subsequent suicide attempt.


Which of the preventive agents perform best for prevention of early childhood caries?
A comprehensive search strategy was planned a priori and accordingly three electronic databases including Medline, Embase, and Cochrane CENTRAL with no language and time restrictions were searched for finding the relevant literature. Hand searching of the relevant articles was also done to retrieve other possible studies. Both parallel and split-mouth RCTs with a minimum follow-up period of 2 years were included. Non-randomised studies were also selected. Data about study characteristics, demographic and clinical parameters, assessed outcome, outcome assessment methods etc. were retrieved by two independent authors. Network meta-analysis (NMA) was carried for two different outcomes viz caries increment and caries incidence. For the purpose of NMA, standardized mean difference (SMD) was calculated for analysing the continuous outcome (caries increment) while Odds ratio was used for dichotomous outcome (caries incidence at individual level). A total of 3807 publication were retrieved and after sifting 33 RCTs and other quasi-randomised/ non-randomized studies were selected for this NMA. Network diagrams were created and two NMAs were carried; one for caries increment and another for caries incidence. A total of 18 preventive agents were explored for caries increment and amongst these, only Fluoride-foam and Fluoride-salt exhibited significant better prevention than the control; with SMD and confidence interval values of 0.69 (0.32-1.06) and 0.66 (0.13-1.20) respectively. While for caries incidence outcome 11 preventive agents could be included out of which, Probiotic-milk + LowF toothpaste, Fluoride-foam, Fluoride-Varnish, and FV + HFTP exhibited significant higher odds of caries prevention; and the odds ratio with 95% confidence intervals were 0.34 (CI = 0.15-0.77), 0.48 (CI = 0.37-0.63), 0.63 (CI = 0.48-0.81), and 0.73 (CI = 0.57-0.93) respectively. SUCRA rankings were also obtained for both the outcomes. Fluoride preparations, namely Fluoride-Foam (FF), Fluoride-Salt(FS) and Probiotic Milk+ Low-F toothpaste(PMLFTP), Fluoride-varnish(FV) and Fluoride-varnish+ High-F toothpaste (FVHFTP) were found to be effective in preventing early childhood caries.


Graphene Oxide/Polyethyleneimine-Modified Cation Exchange Membrane for Efficient Selective Recovery of Ammonia Nitrogen from Wastewater.
Competition for the migration of interfering cations limits the scale-up and implementation of the Donnan dialysis process for the recovery of ammonia nitrogen (NH4+-N) from wastewater in practice. Highly efficient selective permeation of NH4+ through a cation exchange membrane (CEM) is expected to be modulated via tuning the surface charge and structure of CEM. In this work, a novel CEM was designed to form a graphene oxide (GO)-polyethyleneimine (PEI) cross-linked layer by introducing self-assembling layers of GO and PEI on the surface of a commercial CEM, which rationally regulates the surface charge and structure of the membrane. The resulting positively charged membrane surface exhibits stronger repulsion for divalent cations compared to monovalent cations according to Coulomb's law, while, simultaneously, GO forms π-metal cation conjugates between metal cations (e.g., Mg2+ and Ca2+), thus limiting metal cation transport across the membrane. During the DD process, higher NH4+ concentrations resulted in a longer time to reach Donnan equilibrium and higher NH4+ flux, while increased Mg2+ concentrations resulted in lower NH4+ flux (from 0.414 to 0.213 mol·m-2·h-1). Using the synergistic effect of electrostatic interaction and non-covalent cross-linking, the designed membrane, referred to as GO-PEI (20) and prepared by a 20 min impregnation in the GO-PEI mixture, exhibited an NH4+ transport rate of 0.429 mol·m-2·h-1 and a Mg2+ transport rate of 0.003 mol·m-2·h-1 in single-salt solution tests and an NH4+/Mg2+ selectivity of 15.46, outperforming those of the unmodified and PEI membranes (1.30 and 5.74, respectively). In mixed salt solution tests, the GO-PEI (20) membrane showed a selectivity of 15.46 (~1.36, the unmodified membrane) for NH4+/Mg2+ and a good structural stability after 72 h of continuous operation. Therefore, this facile surface charge modulation approach provides a promising avenue for achieving efficient NH4+-selective separation by modified CEMs.


Laboratory-based experimental research into the effect of diagenesis on heated bone: implications and improved tools for the characterisation of ancient fire.
The use of fire is considered to be one of the most important cultural innovations in human evolution. Understanding the taphonomy of fire remains is an important prerequisite for valid interpretations of hominin fire-related behaviour. Presented here are the results of a series of laboratory-based experiments testing the effect of different pH conditions (acidic, neutral, alkaline) on the physical and chemical properties of heated bone (charred and combusted). By taking a fundamental-research approach the study gives insight into the specific effect of pH exposure and its underlying chemical processes, and provides data that can be applied to heated bone from any context and time period. Results show that diagenesis has a significant impact on the preservation potential of heated bones, as well as on the reliability of the analytical techniques used to reconstruct past heating conditions. The study provides reference data and a toolkit for the analysis of heated bone, that explicitly takes diagenesis into account, and in doing so offers a significant improvement to the accuracy with which we can reconstruct heating conditions and fire-related human behaviour in the past.


Optimization of normal-phase chromatographic separation of compounds with primary, secondary and tertiary amino groups.
The retention behavior of primary, secondary and tertiary amines was studied using normal-phase-HPLC on silica, diol, and cyano stationary phases. Several classes of amines, including benzylamines, anilines, ephedrines, tryptamines, and azatryptamines were chromatographed using mixtures of hexane and ethoxynonafluorobutane with methylene chloride and methanol. Peak tailing, diminished selectivity and low plate count were minimized by the addition of volatile amines to the mobile phase. The optimal additive was n-propylamine at 0.1% concentration. On diol columns, the elution order of free primary, N-N-methyl, and N,N-dimethylamines was predictable, while the elution order of primary and secondary amines on cyano columns varied depending on the alcohol modifier concentration. The feasibility of preparative normal-phase chromatography was demonstrated by the separation of a mixture of primary, secondary and tertiary amines obtained by direct methylation of norephedrine. The procedures described may provide a practical alternative to traditional methods of analysis and purification of potential drug candidates.


Ambulatory Minimally Invasive Endoscopic Combined Intrarenal Surgery in Management of Large Impacted Proximal Ureteral Calculi: A Feasibility Study at a Tertiary Referral Center.
Aim: To conduct a comparative, nonrandomized study to assess the feasibility of mini-Endoscopic Combined Intrarenal Surgery (ECIRS) using supine Mini-percutaneous nephrolithotomy (PCNL) access (16F) in Galdakao-Modified Supine Valdivia position for managing proximal large-volume impacted ureteral calculi as ambulatory day-care surgery vis-a-vis standalone ureteroscopy (URS) with push-back PCNL, if needed. The primary aim was to study the outcomes and stone-free rates (SFRs). Secondary aim was to compare the intraoperative and short-term postoperative complications. Materials and Methods: Data of 60 patients undergoing ECIRS (Group 1) from January 2016 to December 2019 were collected prospectively in a nonrandomized fashion from a single center after Ethics Committee approval. A matched-paired analysis was performed with retrospectively collated data of 60 patients undergoing standard URS/pushback PCNL (Group 2) using analysis of variance, Fisher's exact test, and Chi-square test. p < 0.05 was considered statistically significant. Outcomes and Results: Group 1 patients had a significantly shorter procedure time vs Group 2 (42.1 ± 11.2 minutes vs 52.1 ± 13.7 minutes; p < 0.001). Group 1 (59/60) patients had an overall single stage SFR of 98.3%, which was significantly higher than single-stage SFR of 83% in Group 2 (50/60) (p < 0.002). Group 2 patients had a higher incidence of fever (10 vs 4, p = 0.01). However, there were no cases of sepsis in either group. Rest of the complications were comparable for both, as the need for ancillary procedures was significantly higher in Group 2 (10% vs 1.7%, p < 0.001). Patients were discharged on the same day in both groups. Conclusions: The findings of our study suggest that, in large and impacted proximal ureteric stones, combined minimally invasive endoscopic approach offers the best option to render the patient stone free by a single intervention. With better intra- and postoperative outcomes and safety profile, Mini-ECIRS may be considered as an ambulatory procedure in this setting.


Resuscitative balloon occlusion of the aorta in the modern era: Expanding indications, optimal techniques, unresolved issues, and current results.
Resuscitative endovascular balloon occlusion of the aorta has been used by trauma surgeons at the bedside for more than a decade in civilian and military settings. Translational and clinical research suggests it is superior to resuscitative thoracotomy for select patients. Clinical research suggests outcomes are superior in patients who received resuscitative balloon occlusion of the aorta compared with those who did not. Technology has advanced considerably in the past several years, leading to the improved safety profile and wider adoption of resuscitative balloon occlusion of the aorta. In addition to trauma patients, resuscitative balloon occlusion of the aorta has been rapidly implemented for patient with nontraumatic hemorrhage.


Inter- and intra-observer variability in fetal ductus venosus blood flow measurements in high-risk fetuses at 26-32 weeks.
Early preterm fetal growth restriction is a significant contributor to perinatal morbidity and mortality. The ductus venosus pulsatility index for veins (DV PIV) is proposed as a monitoring tool because it appears to improve perinatal outcomes. The test characteristics and robustness of DV PIV have been inadequately described. The aim of this study was to investigate inter- and intra-observer variability of DV PIV. Nineteen women with a gestational age between 26 and 32 completed weeks were included in this study. Doppler sonographic fetal assessment was performed by two independent maternal-fetal medicine specialists. Each sonographer alternately performed three flow tracings for each participant, in the absence of the other sonographer (six tracings in total per patient). DV PIV was calculated automatically from stored tracings by a third researcher. Inter- and intra-observer variability of DV PIV and limits of agreement were assessed using the Bland-Altman method. Comparison of the distribution was performed with Kendall's related samples test, and the intraclass correlation coefficient (ICC) was calculated. In total, 114 DV measurements were taken from 19 participants with a median age of 31 years [interquartile range (IQR) 26-34 years] at a median gestational age of 28 weeks (IQR 27-29 weeks). The proportional limits of agreement for intra-observer variation were -0.48 to 0.48 and -0.39 to 0.62 for the two observers. ICCs were 0.66 [95% confidence interval (CI) 0.42-0.84] and 0.68 (95% CI 0.45-0.85). The proportional limits of agreement for inter-observer variation were -0.29 to 0.19 with an ICC of 0.89 (95% CI 0.73-0.96). Inter-observer variation was far less than intra-observer variation, probably due to mitigation of biological variation by averaging three measurements. DV PIV has acceptable test characteristics for use in a clinical setting when the average of at least three consecutive measurements is used.


Neonatal intestinal obstruction.
Our experience in the management of 138 infants with various causes of intestinal obstruction has provided us with important principles of diagnosis and treatments that we adhere to in the course of our practice. 1. The overall mortality of neonates suffering from intestinal obstruction should be fewer than 5 per cent. The high survival rate is accounted for by improved care these patients receive in specialized units. 2. Prematurity did not appear to play a significant factor in the outcome of these infants with intestinal obstruction. Our experience shows that premature infants tolerate operative procedures well, even in those instances in which an associated surgically correctable lesion is simultaneously repaired. 3. The major risk factor in any neonate with intestinal obstruction is the delay in diagnosis and operative intervention, especially in infants diagnosed to have midgut volvulus. The additional second risk factor is the association of chromosome abnormality. 4. Traditional diagnostic studies such as plain films of the abdomen supplemented by either an upper GI or lower GI contrast study for specific indications have been very effective in obtaining an accurate diagnosis of intestinal bowel obstruction. 5. Hirschsprung's disease can be diagnosed in the neonatal period if the index of suspicion for this is high. 6. Special surgical techniques as described should be used whenever indicated to minimize morbidity. 7. The traditional Wangensteen-Rice evaluation of a patient with imperforate anus is accurate, and specialized studies should be deferred for the postoperative period. Collaborative care provided by the neonatologist, pediatric anesthesiologist, and pediatric surgeon for these patients is the key to a favorable outcome.


Quantitative Measurement and Thermodynamic Modeling of Fused Enhancers Support a Two-Tiered Mechanism for Interpreting Regulatory DNA.
Computational models of enhancer function generally assume that transcription factors (TFs) exert their regulatory effects independently, modeling an enhancer as a "bag of sites." These models fail on endogenous loci that harbor multiple enhancers, and a "two-tier" model appears better suited: in each enhancer TFs work independently, and the total expression is a weighted sum of their expression readouts. Here, we test these two opposing views on how cis-regulatory information is integrated. We fused two Drosophila blastoderm enhancers, measured their readouts, and applied the above two models to these data. The two-tier mechanism better fits these readouts, suggesting that these fused enhancers comprise multiple independent modules, despite having sequence characteristics typical of single enhancers. We show that short-range TF-TF interactions are not sufficient to designate such modules, suggesting unknown underlying mechanisms. Our results underscore that mechanisms of how modules are defined and how their outputs are combined remain to be elucidated.


Correction to: Moral Intuitions About Stigmatizing Practices and Feeding Stigmatizing Practices: How Haidt's Moral Foundations Theory Relates to Infectious Disease Stigma.
[This corrects the article DOI: 10.1093/phe/phad002.].


Primary intestinal Burkitt's lymphoma in a Syrian child with a challenging initial presentation: A case report and literature review.
Burkitt's lymphoma is an aggressive type of non-Hodgkin lymphoma that represents approximately 30% of pediatric lymphomas and less than 5% of all pediatric malignancies. Although the involvement of the gastrointestinal tract is a common finding in sporadic Burkitt's lymphoma, primary intestinal lymphomas still represent a rare entity. We are reporting the case of an 11-year-old Syrian male who presented to our hospital with complaints of abdominal pain, distention, and tenderness. Clinical and radiologic examinations demonstrated moderate ascites with an abdominal mass. Interestingly, the cytological study of the ascites revealed the diagnosis of Burkitt's lymphoma which was later confirmed by histopathological and immunohistochemical examinations. Pleural effusions are a common finding in extranodal lymphomas, whereas ascites is considered a rare initial presentation constituting less than 2% of lymphoma cases. We aimed to present an extremely rare case of a primary intestinal Burkitt's lymphoma initially presenting with ascites, highlighting the major role of the cytological study of ascites in the primary diagnosis, and the essential role of histological and immunohistochemical examinations in confirming the diagnosis in challenging cases.


Different thermostabilities of sarcoplasmic reticulum (Ca2+ + Mg2+)-ATPases from rabbit and trout muscles.
Trout and rabbit (Ca2+ + Mg2+)-ATPases from sarcoplasmic reticulum were compared for differences in thermal inactivation and susceptibility to trypsin digestion. The trout ATPase is more heat-sensitive than the rabbit ATPase and is stabilized by Ca2+, Na+, K+ and nucleotides. Solubilization of both ATPases shows that the two ATPases have different protein-intrinsic inactivation kinetics. When digested by trypsin, the two ATPases display different cleavage patterns. The present results indicate that the trout and rabbit ATPases have dissimilarities in protein structure that may explain the differences in thermal inactivation kinetics.


Repression of neu-induced clonogenicity by dimethylsulfoxide correlates with decreased levels of neu-encoded cell-surface p185 and changes in phosphotyrosine content of endogenous proteins.
Treatment of neu-transformed fibroblasts with dimethylsulfoxide (DMSO), results in change in morphology and loss of clonogenicity. Although the total amount of neu-encoded p185 protein and mRNA remained constant after DMSO treatment, cell-surface p185 decreased by 60%, indicating that transmembrane p185 protein is not located in its physiological position. The aberrant location of p185 induced by DMSO resulted in increased tyrosine phosphorylation of p185 and concomitant decreased tyrosine phosphorylation of potential substrate proteins of p185 in the cell. However, the autophosphorylation activity of p185 in vitro was unaffected by DMSO. Thus, DMSO-induced loss of clonogenicity may be due to inappropriate location of p185, which prevents interaction between p185 and its substrates and therefore inhibits p185-mediated signal transduction pathway.


Lymphocyte lineage-restricted tyrosine-phosphorylated proteins that bind PLC gamma 1 SH2 domains.
Epidermal growth factor (EGF) or platelet-derived growth factor binding to their receptor on fibroblasts induces tyrosine phosphorylation of PLC gamma 1 and stable association of PLC gamma 1 with the receptor protein tyrosine kinase. Similarly in lymphocytes, cross-linking of antigen receptors induces the formation of molecular complexes incorporating PLC gamma 1; however, associated kinase activity is thought to be mediated through cytoplasmic protein tyrosine kinase(s). In this report, we generated a fusion protein containing the SH2 domains of human PLC gamma 1 and human IgG1 heavy chain constant region to identify lymphocyte phosphoprotein-binding PLC gamma 1 SH2 domains following cellular activation. As in EGF- or platelet-derived growth factor-stimulated fibroblasts, PLC gamma 1 is coprecipitated in activated lymphocytes, complexed with associated tyrosine-phosphorylated proteins. One of these, a 35/36-kDa protein found prominently in T cells and at lower levels in B cells, bound to the fusion protein in immunoprecipitation experiments. The fusion protein showed lineage restricted association with a 74-kDa phosphoprotein in T cells and a 93-kDa phosphoprotein in B cells. It bound to activated EGF receptor in fibroblasts as expected, and protein tyrosine kinase activity was precipitated from EGF-stimulated cells. However, PLC gamma 1-associated protein tyrosine kinase activity was not detected in activated lymphocytes. These data suggest that lymphocyte PLC gamma 1 SH2-binding proteins are cell lineage specific and may be transiently associated with activated PLC gamma 1.


Nipple reduction using a three-dimensional Z-shaped incision technique.
Nipple hypertrophy is a seldom-discussed aesthetic problem. Many patients feel uncomfortable with it and seek for correction. However, it is difficult to reshape nipples to an actual cylindrical form with the published methods. This study presented a novel three-dimensional Z-shaped incision technique, which can not only decrease the height and diameter of a hypertrophic nipple but also narrow the nipple base without destroying its function. A total of 44 nipple reductions were performed for 22 women using the three-dimensional Z-shaped incision technique between July 2008 and June 2011. It consists of two circles, one quadrangle and one triangle incision lines on the top, body and base of the nipple to reduce the nipple's height, diameter and base. Bilateral nipples were designed symmetrically. A total of 44 operated nipples in 22 healthy female patients, aged 18-42 years (mean age, 28 years) were corrected with this method. The mean follow-up period was 28 months (range, 14-48 months). A survey was also performed to evaluate long-term patient satisfaction. Our survey showed that our surgical technique was capable of producing satisfactory results. No complications such as nipple necrosis, infection or numbness occurred. The three-dimensional Z-shaped incision technique could reduce the height and diameter and, most importantly, reduce the basal shape of all types of hypertrophic nipples to create a desired new nipple cylindrical in shape without compromising neurovascular supply and functions.


Short inverted-repeat transposable elements in teleost fish and implications for a mechanism of their amplification.
Angel is the first miniature inverted-repeat transposable element (MITE) isolated from fish. Angel elements are imperfect palindromes with the potential to form stem-loop structures in vitro. Despite sequence divergence of elements of up to 55% within and between species, their inverted repeat structures have been maintained, implying functional importance. We estimate that there are about 10(3)-10(4) Angels scattered throughout the zebrafish genome, evidence that this family of transposable elements has been significantly amplified over the course of evolution. Angel elements and Xenopus MITEs carry common sequence motifs at their termini, indicating common origin and/or related mechanisms of transposition. We present a model in which MITEs take advantage of the basic cellular mechanism of DNA replication for their amplification, which is dependent on the characteristic inverted repeat structures of these elements. We propose that MITEs are genomic parasites that transpose via a DNA intermediate, which forms by a folding-back of a single strand of DNA, that borrow all of the necessary factors for their amplification from products encoded in the genomes in which they reside. DNA polymorphisms in different lines of zebrafish were detected by PCR using Angel-specific primers, indicating that such elements, combined with other transposons in vertebrate genomes, will be useful molecular tools for genome mapping and genetic analyses of mutations.


The fate of women requesting reversal of tubal sterilization.
Although it was not possible to identify by simple demographic measurements those women who would elect not to pursue full investigation, this study has highlighted the high drop-out rate of women requesting reversal, and suggested that discussion with the couple at the first visit is a valid procedure, particularly if it allows as many as one-third of patients to elect not to proceed to invasive procedures. Finally, this study underscores that when gynecologists are counseling patients with respect to sterilization and the question of reversibility is opened, the success rate is not in excess of 50% when it is considered a function of the number of women regretting reversal rather than a function of women who undergo surgery.


Serum selenium levels in cirrhotic patients are not influenced by the disease severity index.
Selenium (Se) is an antioxidant element that protects against cellular damage by reactive oxygen species. Therefore, total serum Se concentration may reflect protection during the development of cirrhosis, an oxidative stress-related disease. We hypothesized that serum Se levels are diminished in cirrhotic patients due to their enhanced oxidative stress, and serum Se levels are reduced the most in patients with the highest severity of cirrhosis. A case-control study was performed to determine whether cirrhosis is associated with changes in serum Se levels. Blood samples from 30 healthy controls and 93 cirrhotic patients were analyzed for total serum Se by hydride generation atomic absorption spectrometry. The Child-Pugh index score was used to evaluate the severity of liver disease. The mean serum Se concentration was significantly lower in patients vs controls (0.721 ± 0.239 vs 0.926 ± 0.241 μmol/L; P = .001). Mean serum Se levels were not significantly lower in patients with higher severity of cirrhosis (0.691 ± 0.229 vs 0.755 ± 0.255 μmol/L; P = .144). A positive and significant correlation was found between age and serum Se levels in patients (r = 0.277, P = .007). Patients showed significant sex differences in serum Se level (higher in male) and severity index (higher in female). The significantly decreased serum Se level in patients indicates that the Se component of the antioxidant system is severely impaired in cirrhosis. However, serum Se levels were not influenced by the severity of the disease.


Non-giant cell temporal arteritis. Three cases and a review of the literature.
We report two cases of polyarteritis and some of hypersensitivity angiitis diagnosed by temporal artery biopsy. Autopsies showed no evidence of giant cell arteritis. A review of the English literature provides seven further autopsy cases of necrotizing vasculitis diagnosed by temporal artery biopsy. The term temporal arteritis includes many types of vasculitis, giant cell arteritis being one of them.


Coadministration of tianeptine alters behavioral parameters and levels of neurotrophins in a chronic model of Maple Syrup Urine disease.
Maple Syrup Urine Disease (MSUD) is caused by the deficiency in the activity of the branched-chain α-ketoacid dehydrogenase complex (BCKDC), resulting in the accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, and their respective branched-chain α-keto acids. Patients with MSUD are at high risk of developing chronic neuropsychiatric disorders; however, the pathophysiology of brain damage in these patients remains unclear. We hypothesize that MSUD can cause depressive symptoms in patients. To test our hypothesis, Wistar rats were submitted to the BCAA and tianeptine (antidepressant) administration for 21 days, starting seven days postnatal. Depression-like symptoms were assessed by testing for anhedonia and forced swimming after treatments. After the last test, the brain structures were dissected for the evaluation of neutrophins. We demonstrate that chronic BCAA administration induced depressive-like behavior, increased BDNF levels, and decreased NGF levels, suggesting a relationship between BCAA toxicity and brain damage, as observed in patients with MSUD. However, the administration of tianeptine was effective in preventing behavioral changes and restoring neurotrophins levels.


Diversity of immunoglobulin lambda light chain gene usage over developmental stages in the horse.
To further studies of neonatal immune responses to pathogens and vaccination, we investigated the dynamics of B lymphocyte development and immunoglobulin (Ig) gene diversity. Previously we demonstrated that equine fetal Ig VDJ sequences exhibit combinatorial and junctional diversity levels comparable to those of adult Ig VDJ sequences. Herein, RACE clones from fetal, neonatal, foal, and adult lymphoid tissue were assessed for Ig lambda light chain combinatorial, junctional, and sequence diversity. Remarkably, more lambda variable genes (IGLV) were used during fetal life than later stages and IGLV gene usage differed significantly with time, in contrast to the Ig heavy chain. Junctional diversity measured by CDR3L length was constant over time. Comparison of Ig lambda transcripts to germline revealed significant increases in nucleotide diversity over time, even during fetal life. These results suggest that the Ig lambda light chain provides an additional dimension of diversity to the equine Ig repertoire.


Depression increases the length of hospitalization for patients undergoing thoracic surgery: a preliminary study.
Surgical treatment, especially thoracic surgery, is a burdensome prospect for many patients. Depression-related anxiety, insomnia, and stress are common complaints in preoperative patients. Such depressive complaints are currently thought to affect the patients' physiological status. We examined the effect of mental status on the length of hospitalization following thoracic surgery. The study population was comprised of 52 patients (lung cancer 88%) who underwent operative treatment for thoracic disease. Patient depressive status was evaluated using the Self-Rating Depression Scale (SDS) at admission and again at discharge. Demographic data were collected retrospectively and included age, thoracotomy, and number of days in the hospital. SDS scores did not differ between admission and discharge (37.7 ± 9.9 vs. 40.4 ± 8.9, respectively; ns). The length of hospitalization in patients with depression (SDS score > 40) was significantly greater than for those without depression (P < 0.05). The length of hospitalization significantly correlated with the SDS score at admission (r = 0.492, P < 0.001). Multiple regression analyses revealed that the length of hospitalization correlated with the SDS score at admission (P < 0.01) and with endoscopic surgery (P < 0.05). This study suggests that depression increases the length of hospitalization for malignancy patients undergoing thoracic surgery; early intervention or treatment for depression may be required for these patients to improve outcomes.


Calcium and the contractile response to prostaglandin in the smooth muscle of guinea-pig stomach.
In the longitudinal smooth muscle of guinea-pig stomach, verapamil (10(-5) M) which showed marked suppression of high K-induced contractures, did not suppress the contractile response to PGE1 (1.5 X 10(-9) to 10(-6) M) markedly. These results suggest that the contractile mechanism of PGE1 in guinea-pig stomach may mainly depend on a release of bound Ca in the cell and partly depend on a Ca influx from the extracellular origin.


Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer's disease.
Pathological features in Alzheimer's brains include mitochondrial dysfunction and dystrophic neurites (DNs) in areas surrounding amyloid plaques. Using a mouse model that overexpresses reticulon 3 (RTN3) and spontaneously develops age-dependent hippocampal DNs, here we report that DNs contain both RTN3 and REEPs, topologically similar proteins that can shape tubular endoplasmic reticulum (ER). Importantly, ultrastructural examinations of such DNs revealed gradual accumulation of tubular ER in axonal termini, and such abnormal tubular ER inclusion is found in areas surrounding amyloid plaques in biopsy samples from Alzheimer's disease (AD) brains. Functionally, abnormally clustered tubular ER induces enhanced mitochondrial fission in the early stages of DN formation and eventual mitochondrial degeneration at later stages. Furthermore, such DNs are abrogated when RTN3 is ablated in aging and AD mouse models. Hence, abnormally clustered tubular ER can be pathogenic in brain regions: disrupting mitochondrial integrity, inducing DNs formation and impairing cognitive function in AD and aging brains.


Mucosal 5-aminosalicylic acid concentration inversely correlates with severity of colonic inflammation in patients with ulcerative colitis.
The treatment of ulcerative colitis (UC) with 5-aminosalicylic acid (5-ASA) does not have the same therapeutic effect in all patients. We tested the hypothesis that the effectiveness of the drug is related to its mucosal concentration. Twenty one UC patients receiving oral 5-ASA (2.4-3.2 g/day) were enrolled in the study. Four were also receiving topical treatment (2 g/day). Six endoscopic biopsies were taken from the rectum for measurement of 5-ASA concentrations (ng/mg) by HPLC; soluble interleukin 2 receptor (sIL-2R) concentrations (U/ml) were measured by ELISA and histology. Endoscopic and histological appearance was graded on a four point scale (0-3). The Wilcoxon's rank test and Pearson's correlation coefficient were used for statistical analysis. Mucosal concentrations of 5-ASA were significantly higher (p=0.03) in patients with endoscopic scores of 0-1 compared with those with scores of 2-3 (16.1 (range 10.2-45) v 5. 5 (3.5-17.4), respectively) and in patients with lower histological inflammation compared with those with more severe scores (17.4 (10. 5-45) v 8.9 (3.5-17.2), respectively) (p<0.01). In contrast, mucosal sIL2-R concentrations were significantly lower in patients with slight endoscopic and histological lesions than in those with more severe disease. A significative inverse correlation (r=-0.85) was found between 5-ASA and sIL-2R mucosal concentrations (p=0.00008). In patients with UC, in the same area of the intestinal tract, we found that the higher the 5-ASA mucosal concentrations, the lower the IL-2R levels and endoscopic and histological scores. We hypothesise that maintenance of high mucosal 5-ASA concentrations in all colonic segments could contribute to improve clinical outcome in UC patients.


Comparative Analysis of MMP-8 and MMP-9 Concentrations in Crevicular and Peri-Implants Sulcular Fluids.
The concentrations of MMP-8 and MMP-9 were measured in the crevicular and the peri-implant sulcular fluids at the different stages of the prosthetic treatment. The concentration MMP-8 and MMP-9 in the peri-implant sulcular fluids were significantly higher (p<0.05) then in the gingival crevicular fluid. The determined parameters are the references values for dynamic observation over the functional state of the dental "implant-bone-soft" tissue system. The detected the correlations attest to synergy between secretion of MMP-8 and MMP-9 in the peri-implant sulcular fluid and allow analysis of the dependence of the secretion of these metalloproteinases on clinical and physiological peculiarities of the gingiva, which will help to better customize implant-supported prosthetic treatment of the patients.


Assessment of lymph node tuberculosis in northern Germany: a clinical review.
To evaluate patient profiles, diagnostic approaches, and treatment strategies in patients with lymph node tuberculosis. Demographic data, diagnostic findings, and therapies were retrospectively analyzed in 60 patients with lymph node tuberculosis who were hospitalized between 1992 and 1999. Thirty percent (n = 18) of patients were natives, and 70% were immigrants (n = 42). The cervical lymph nodes were most frequently involved (63.3%), followed by the mediastinal lymph nodes (26.7%) and the axillary lymph nodes (8.3%). All patients (except one patient who was HIV-positive) showed a positive response to tuberculin skin testing. Lymph node excision and fine-needle aspiration (FNA) were similarly effective in obtaining sufficient material for histologic and microbiological analysis. Mycobacterium tuberculosis was identified in 43.3% of patients by microbiological testing, and culture methods showed the highest sensitivity. Despite standard treatment, the initial enlargement of the lymph nodes occurred in 20% of patients and local complications occurred in 10%. Lymph node tuberculosis is still an important issue in developed countries and has to be considered in differential diagnosis. The best approach appears to be a combination of skin testing and FNA. Negative results in the identification of M tuberculosis do not exclude the diagnosis of lymph node tuberculosis.


Mercury in indigenous, introduced and farmed fish from the semiarid region of the Jaguaribe river Basin, NE Brazil.
Indigenous, introduced and farmed fish species were collected from the Jaguaribe Basin, NE Brazil to assess total and methyl mercury concentrations in muscle tissue and to determine its relationship with fish origin. The results obtained from introduced species were compared to the Hg content of their original area of occurrence, which is located in the Amazon region. Farmed and wild individuals of Oreochromis niloticus (tilapia) were also compared. Introduced species presented lower Hg contents compared to their Amazonian counterparts. Wild individuals of O. niloticus also presented higher Hg contents than farmed individuals with similar sizes. However, methyl Hg concentrations were not significantly different between the two groups. Total Hg and methyl Hg concentrations were higher in carnivorous species, especially those from the Amazon region, and surpassed the Brazilian guidelines for fish consumption. Based on their Hg content, Jaguaribe basin fish do not pose a significant threat to human consumption.


Hemoglobin components and plasma proteins in Pitymys duodecimcostatus.
Six different hemoglobins have been demonstrated by polyacrylamide disc gel electrophoresis in a species of vole Pitymys duodecimcostatus. Plasma proteins of the Pitymys duodecimcostatus were analyzed by polyacrylamide disc gel electrophoresis and there was no significant difference with the electrophoretic patterns of the rat (Rattus norvegicus). The hematological values, hematocrit, hemoglobin concentration and erythrocyte number have been analyzed.


Association of genomic instability, and the methylation status of imprinted genes and mismatch-repair genes, with neural tube defects.
We studied the genomic instability and methylation status of the mismatch-repair (MMR) genes hMLH1 and hMSH2, and the imprinted genes H19/IGF2, in fetuses with neural tube defects (NTDs) to explore the pathogenesis of the disease. Microsatellite instability (MSI) was observed in 23 of 50 NTD patients. Five NTD patients showed high-degree MSI (MSI-H) and 18 showed low-degree MSI (MSI-L). The frequencies of mutated microsatellite loci were 3/50 (6%) for BatT-25, 10/50 (20%) for Bat-26, 3/50 (6%) for Bat34C4, 6/50 (12%) for D2S123, 4/50 (8%) for D2S119, and 3/50 (6%) for D3S1611. The promoter regions of the hMLH1 and hMSH2 genes were unmethylated in NTD patients, as determined by methylation-specific PCR. The hMLH1 and hMSH2 promoter methylation patterns, the methylation levels of H19 DMR1, and IGF2 DMR0 were detected by bisulfite sequencing PCR, sub-cloning, and sequencing. The hMSH2 promoter sequence was unmethylated, and the hMLH1 promoter showed a specific methylation pattern at two CpG sites. The methylation levels of H19 DMR1 in the NTD and control groups are 73.3% ± 15.9 and 58.3% ± 11.2, respectively. The methylation level of the NTD group was higher than that of the control group (Student's t-test, P<0.05). There is no significant difference in IGF2 DMR0 methylation level between the two groups. All of the results presented here suggest that genomic instability, the MMR system, and hyper-methylation of the H19 DMR1 may be correlated with the occurrence of NTDs.


[Optimization of phacoemulsification in complicated cataract with lens subluxation].
Purpose - to optimize the process of phacoemulsification in patients with cataract complicated by degree I-II lens subluxation by using the scaffold technique, and to determine the indications for its application. The patients were divided into two groups: group 1 - the main group - included 29 patients (29 eyes; 47.54%) who underwent cataract phacoemulsification with implantation of iris retractors and capsular ring using the scaffold technique. Group 2 - the comparison group - included 32 patients (32 eyes; 54.46%) who underwent cataract phacoemulsification with implantation of iris retractors and capsular ring using standard technique. Patients' visual acuity improved up to 0.53 (0.35; 0.80) in group 1, and up to 0.50 (0.45; 0.80) in group 2 by the time of hospital discharge. At 6 months and 1 year follow-ups, visual functions were equal, in group 1 - 0.70 (0.65; 0.80), in group 2 - 0.70 (0.60; 0.90). The number of intraoperative complications decreased from 8.20% in standard phacoemulsification to 1.64% in scaffold technique. The latter reduces endothelial cell loss by 1.95% in comparison with traditional phacoemulsification over 1 year follow-up. With the scaffold technique, the number of intraoperative complications decreased from 15.63% in group 2 to 3.45% in group 1, the number of postoperative complications - from 43.75% to 31.04%, respectively. The scaffold technique is indicated in pseudoexfoliation syndrome with weakness of zonular apparatus, degree I-II lens subluxation, in hard nucleus with absence of posterior cortical layer, in intumescent cataract, Morgagnian cataract to stabilize the posterior capsule and protect it from rupture.


Rapamycin Attenuates High Glucose-Induced Inflammation Through Modulation of mTOR/NF-κB Pathways in Macrophages.
Background: The NLRP3 inflammasome is one of the key contributors to impaired wound healing in diabetes. In this study, we assessed the role of rapamycin on high glucose-induced inflammation in THP-1-derived macrophages and investigated the underlying signaling mechanisms. Methods: THP-1-derived macrophages were treated with high glucose to induce NLRP3 inflammasome activation. The cells were pretreated with rapamycin, BAY 11-7082, or PDTC before exposure to HG. mTOR, NF-κB, and NLRP3 inflammasome expression were measured by western blotting. Results: We found that rapamycin reduced NLRP3 inflammasome activation in macrophages. Rapamycin reduced NLRP3 inflammasome activation by inhibiting mTOR phosphorylation and NF-κB activation. Moreover, mTOR siRNA inhibited NF-κB activation, leading to the suppression of NLRP3 inflammasome activation. Conclusion: Rapamycin can ameliorate high glucose-induced NLRP3 inflammasome activation by attenuating the mTOR/NF-κB signaling pathway in macrophages. Rapamycin may act as a possible therapeutic option for high glucose-induced inflammatory response in impaired wound healing in the future.


Dietary Advanced Glycation End Products in an Elderly Population with Diabetic Nephropathy: An Exploratory Investigation.
Advanced glycation end products (AGEs) are important in pathophysiology of type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Dietary AGEs (dAGEs) contribute to the overall AGE pool in the body. Forty elderly T2DM patients with DKD were randomly allocated to a low-AGE (n = 20) or regular diabetic (n = 20) diet group. A three-day meal questionnaire was used to estimate average quantity of dAGEs. AGE accumulation was measured using skin autofluorescence and urine spectroscopy. sRAGE (soluble receptor AGE) was quantified using ELISA. After 8 weeks, the mean consumption of dAGEs was considerably reduced, both in the low-AGE diet (p = 0.004) and the control (p = 0.019) group. The expected urinary emission peak at 490 nm was shifted to 520 nm in some spectra. dAGEs did not correspond with urine AGE output. An AGE-limited diet for two months did not affect AGE content in skin and urine, or sRAGE concentration in the blood. The role of glycemia is likely to be greater than the impact of dAGE consumption. The unique observation of a fluorescence pattern at 520 nm warrants further examination, since it might point to genetic differences in AGE regulation, which could have clinical consequences, as AGE content depends on its formation and elimination.


Nameless desire: alexithymia and the anorexic patient.
In this article, the author attempts to provide a psychoanalytic understanding of the anorexic patient who is disconnected from her affective experience and is considered to be alexithymic. Through her restrictive food ritual, this type of patient may organize her internal states by repeatedly creating an illusion of what it is that she needs and desires. The author asserts that the task of the therapist working with the anorexic patient with alexithymia is to be aware of his own sensation-based reverie as lived within the intersubjective arena. This will enable the therapist to assist the patient in building an affective vocabulary to accurately identify, differentiate, and label the internal signals of her body. It is suggested that the subjective emotional experience of the patient will continue to be reorganized, expanded, and enriched as the therapist and patient mutually influence one another in this unique relational matrix. A clinical vignette is provided to illustrate intersubjective treatment interventions with a difficult-to-reach anorexic patient.


Formalin-induced pain antagonizes the development of opiate dependence in the rat.
Clinical studies have suggested that patients who take morphine for pain relief do not show a high degree of dependence. The present study examined the development of naloxone-precipitated withdrawal in rats receiving morphine in the presence or absence of formalin-induced pain. Morphine (10 mg/kg, i.p.) or saline was administered for 4 consecutive days 10 min after a subcutaneous injection of 50 microliters of 2.5% formalin or saline into the hind-paw. On the 5th day, rats were injected with naloxone (1 mg/kg, i.p.) and observed for signs of precipitated withdrawal (ptosis, teeth chattering and excretion/diarrhea). Naloxone-precipitated withdrawal symptoms were significantly greater in rats that received morphine in the absence of pain than in rats that received morphine in the presence of pain.


EB virus-induced ATR activation accelerates nasopharyngeal carcinoma growth via M2-type macrophages polarization.
Chronic inflammation induced by persistent viruses infection plays an essential role in tumor progression, which influenced on the interaction between the tumor cells and the tumor microenvironment. Our earlier study showed that ATR, a key kinase participant in single-stranded DNA damage response (DDR), was obviously activated by Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC). However, how EBV-induced ATR activation promotes NPC by influencing inflammatory microenvironment, such as tumor-associated macrophages (TAMs), remains elusive. In this study, we showed that EBV could promote the expression of p-ATR and M2-type TAMs transformation in clinical NPC specimens. The expression of p-ATR and M2-type TAMs were closely correlated each other and involved in TNM stage, lymph node metastasis and poor prognosis of the patients. In addition, the expression levels of CD68+CD206+, Arg1, VEGF, and CCL22 were increased in EB+ CNE1 cells, and decreased when ATR was inhibited. In the nude mice, EBV-induced ATR activation promoted subcutaneous transplanted tumor growth, higher expression of Ki67 and lung metastasis via M2-type TAMs recruitment. Experimental data also showed that the polarization of M2, the declined tumor necrosis factor-α (TNF-α) and increased transforming growth factor-β (TGF-β) were associated with ATR. Meanwhile, ATR activation could promote PPAR-δ and inhibited c-Jun and p-JNK expression, then downregulate JNK pathway. Collectively, our current study demonstrated the EBV infection could activate the ATR pathway to accelerate the transition of TAMs to M2, suggesting ATR knockdown could be a potential effective treatment strategy for EBV-positive NPC.


Positive Parenting and Callous-Unemotional Traits: Their Association With School Behavior Problems in Young Children.
The current study tested the associations of both positive (i.e., warm and responsive) and negative (i.e., harsh and inconsistent) aspects of parenting with callous-unemotional (CU) traits and conduct problems. Caregivers and teachers of 92 ethnically diverse (33% African American) kindergarten students (61% female) were recruited to complete a series of survey measures. Students' average age was 6.2 (SD = 0.42) years. Parent report of positive parenting practices, but not negative parenting practices, was associated with teacher report of conduct problems. Further, positive parenting interacted with CU traits in their association with conduct problems. Parental use of positive reinforcement was more strongly negatively related to conduct problems for youth with high levels of CU traits, whereas parent-child cooperation was positively related to conduct problems only for youth with low levels of CU traits. Finally, only parental warmth was negatively correlated with CU traits after controlling for level of conduct problems. Results were generally not moderated by the child's gender or ethnicity. These findings highlight the importance of positive parenting practices for understanding CU traits and as potential targets in clinical interventions to treat children who show elevated levels of these traits.


Temperamental factors associated with rapid weight gain and obesity in middle childhood.
Studies of the perplexing problem of childhood obesity have considered etiological factors in the child and environment, but have largely ignored the child's temperament or style of interaction with the environment. In this report, a significant relationship is demonstrated between temperament and both rapid weight gain and actual obesity in middle childhood. In a longitudinal study of 138 children, weight-for-height percentile gains between 4 to 5 years and 8 to 9 years were significantly correlated with eight of nine difficult temperament characteristics and with a cumulative "index of difficulty." A separate cross-sectional study of 21 obese (greater than or equal to the 95th percentile weight for height) 6- to 12-year-old children found them to be significantly less rhythmical/predictable and lower in persistence/attention span than matched controls. These normal behavioral style characteristics, interacting with metabolic, dietary, and environmental factors, may predispose some children to inappropriate eating habits or make it harder to maintain a dietary plan to remedy the problem.


Sialorrhea in children with cerebral palsy.
To review the literature on sialorrhea in children with cerebral palsy. Non-systematic review using the keywords "sialorrhea" and "child" carried out in the PubMed®, LILACS®, and SciELO® databases during July 2015. A total of 458 articles were obtained, of which 158 were analyzed as they were associated with sialorrhea in children; 70 had content related to sialorrhea in cerebral palsy or the assessment and treatment of sialorrhea in other neurological disorders, which were also assessed. The prevalence of sialorrhea is between 10% and 58% in cerebral palsy and has clinical and social consequences. It is caused by oral motor dysfunction, dysphagia, and intraoral sensitivity disorder. The severity and impact of sialorrhea are assessed through objective or subjective methods. Several types of therapeutic management are described: training of sensory awareness and oral motor skills, drug therapy, botulinum toxin injection, and surgical treatment. The most effective treatment that addresses the cause of sialorrhea in children with cerebral palsy is training of sensory awareness and oral motor skills, performed by a speech therapist. Botulinum toxin injection and the use of anticholinergics have a transient effect and are adjuvant to speech therapy; they should be considered in cases of moderate to severe sialorrhea or respiratory complications. Atropine sulfate is inexpensive and appears to have good clinical response combined with good safety profile. The use of trihexyphenidyl for the treatment of sialorrhea can be considered in dyskinetic forms of cerebral palsy or in selected cases.


Preparing nurses and nursing students to care for older adults in lower and middle-income countries: A scoping review.
The aim of this review was to examine the extent and nature of published literature on nurses' and nursing students' preparedness to care for older adults in lower and middle-income countries. A scoping review with 27 articles, guided by the Arksey and O'Malley (2005) framework was conducted. The following electronic databases were searched: MEDLINE, CINAHL, ERIC and SCOPUS. Grey literature using Google Scholar and ProQuest were also searched. Key search terms and subject headings such as "nursing students", "nurses", "stakeholders", "ministry of health", "readiness", "knowledge", "attitudes", "elder care", "seniors care" and "older adults" were used to identify relevant articles. Studies that reported on gerontological nursing, nursing students' and nurses' knowledge and attitudes towards older adults, and stakeholders/employers' views about nursing students' knowledge and attitudes towards older adults were included. Nurses reported having moderate to insufficient knowledge in the care of older adults in the majority of the studies. Nursing students reported insufficient knowledge in the care of older adults. However, both nurses and nursing students reported positive attitudes towards the care of older adults but held misconceptions about caring for older adults. Nursing students also reported a low preference for working with older adults. The inadequate preparation of nurses and nursing students in the care of older adults means there are opportunities to enhance knowledge about health and nursing care in lower and middle-income countries and build on the positive attitudes towards older adults.


Efficacy and safety of standard of care with/without bevacizumab for platinum-resistant ovarian/fallopian tube/peritoneal cancer previously treated with bevacizumab: The Japanese Gynecologic Oncology Group study JGOG3023.
We investigated the efficacy and safety of further bevacizumab therapy in patients with platinum-resistant ovarian cancer whose disease had progressed after bevacizumab plus chemotherapy. In this multicenter, open-label, phase II trial (JGOG3023), patients were randomized 1:1 to a single-agent chemotherapy alone (either pegylated liposomal doxorubicin [40 or 50 mg/m2 administered intravenously], topotecan [1.25 mg/m2 intravenously], paclitaxel [80 mg/m2 intravenously], or gemcitabine [1000 mg/m2 intravenously]) or single-agent chemotherapy + bevacizumab (15 mg/m2 intravenously). The primary endpoint was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary endpoints were overall survival (OS), objective response rate (ORR), and response rate according to Gynecological Cancer Intergroup cancer antigen 125 criteria. In total, 103 patients were allocated to chemotherapy (n = 51) or chemotherapy + bevacizumab (n = 52). Median investigator-assessed PFS was 3.1 and 4.0 mo in each group, respectively (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.32-0.90, P = .0082). Median OS was 11.3 and 15.3 mo in each group, respectively (HR = 0.67, 95% CI: 0.38-1.17, P = .1556). Respective ORRs were 13.7% and 25.0% (P = .0599) and response rates were 16.7% and 21.4% (P = .8273). The incidence of grade ≥3 treatment-related AEs was 42.0% in the chemotherapy group and 54.9% in the chemotherapy + bevacizumab group; AEs were well tolerated, with only 2 and 12 events leading to discontinuation of therapy, respectively. Bevacizumab was effective beyond progressive disease and AEs were manageable. The observed improvement in PFS requires further verification.


A system for stereotactic irradiation and magnetic resonance evaluations in the rat brain.
A stereotactic fixation and localization device developed for small animal stereotactic radiosurgery is described. Irradiated volumes of spherical shape down to 1.7 mm in diameter at the 80% isodose level are attainable. The fixation device can also be used for magnetic resonance imaging (MRI) and allows target localization during magnetic resonance (MR) image content measurement. The capabilities of the entire system were investigated using a phantom that permitted measurement and localization of the three-dimensional dose distribution. Localization of target isocenter coordinates in MR images was also checked with the phantom. An overall spatial error of about 1 mm for subsequent stereotactic irradiation was obtained. The accuracy of the fixation and localization techniques is adequate to investigate radiation-induced changes in the rat brain.


Radiation-induced cytogenetic and hematologic effects on aquatic biota within the Chernobyl exclusion zone.
During 1998-2014 the rate of chromosomal aberrations in embryo tissues of the pond snail (Lymnaea stagnalis) and root meristems of higher aquatic plants, and also hematologic indexes of mantle liquid of the adult snails and peripheral blood of fishes in water bodies within the Chernobyl exclusion zone (EZ) was studied. The absorbed dose rate for hydrobionts from water bodies of the EZ registered in a range from 0.25 to 420 μGy h(-1) and in the reference ones - up to 0.09 μGy h(-1). The level of chromosomal aberrations in the molluscs from the most contaminated water bodies of the EZ was registered within range of 18-27% and for the molluscs from the reference lakes this index was on the average 1.5% with the maximal values 2.3%. The rate of chromosomal aberrations in root meristematic cells of higher aquatic plants from the contaminated lakes of the EZ was in range of 7-17% and in the plants from reference water bodies was not exceed 2.1%. The positive correlation between chromosomal aberration rate and absorbed dose rate in the pond snail's embryos and root meristems of higher aquatic plants in water bodies of the EZ was registered. Analysis of hemolymph structure of snails from the most contaminated water bodies showed a high rate of dead and phagocytic cells as well as decrease of the young amoebocytes quantity. Hematologic research of fish allows to determine on the one hand an insignificant changes of leukogram structure, and from the other hand a high level of red cells with different abnormalities in the peripheral blood of fishes from the water bodies with high levels of radioactive contamination. It is suppose that qualitative indexes of red cells in peripheral blood of fish are more sensitive to long-term radiation impact in comparison with elements of white blood, which can be used for conducting of the hematologic monitoring of radioactive contaminated water bodies.


In-vitro maturation of human oocytes.
Immature human oocytes can be matured and fertilized in vitro. However, subsequent embryonic development is different when the immature oocytes are retrieved in different situations. Exposure to the LH surge in vivo may be important for the oocytes to acquire the competence for maturation and subsequent embryonic development. The size of the follicles may also be an important feature for subsequent embryonic development. However, the developmental competence of oocytes derived from small antral follicles does not seem to be adversely affected by the presence of a dominant follicle. Oocyte maturation in vitro is profoundly affected by culture conditions. Gonadotrophins are required for oocyte maturation in vivo, but any requirement in vitro is still unclear. Recent clinical results from in-vitro matured (IVM) human oocytes are promising, although further research remains to be done in order to address the mechanisms of oocyte maturation and to improve culture conditions and also the implantation rate of embryos generated from IVM oocytes.


Elevated Hs-CRP Levels Are Associated with Higher Risk of Intracranial Arterial Stenosis.
Correlation between the level of high-sensitivity C-reactive protein (hs-CRP) and the incidence of intracranial arterial stenosis (ICAS) is unclear. We aim to investigate the relationship between hs-CRP levels and ICAS. A total of 1458 patients aged ≥ 40 years were enrolled in this study. All the participants had a magnetic resonance angiography (MRA) examination for the evaluation of ICAS. Participants were classified into four groups according to stroke and ICAS. Multivariable logistic regression models were used to assess the relationship of hs-CRP levels and ICAS status. A total of 432 (29.63%) subjects had ICAS. The levels of hs-CRP in stroke group were significantly higher than those in non-stroke group (p < 0.001). Patients with ICAS tend to have higher hs-CRP levels (p < 0.001). In multivariate analysis, the fourth hs-CRP quartile had the strongest association with ICAS in both stroke group and non-stroke group (OR 2.512, 95% CI 1.651-3.853, p < 0.001 for stroke group, and OR 2.534, 95% CI 1.435-4.595, p = 0.002 for non-stroke group) among the four quartiles of hs-CRP levels. Our study suggests that elevated serum hs-CRP levels are associated with higher risk of ICAS, in both stroke patients and non-stroke participants.


Long-term study on electrophysiological characteristics and catheter ablation of idiopathic ventricular arrhythmias originating from the left ventricular posterior papillary muscles guided by intracardiac ultrasound.
This study aimed to investigate the electrophysiological characteristics of idiopathic ventricular arrhythmias (VAs) originating from the left ventricular posterior papillary muscles (LPPM) and explore the efficiency of catheter ablation using three-dimensional intracardiac ultrasound technology. Twenty-seven cases of premature ventricular contraction/ventricular tachycardia (PVC/VT) originating from the left ventricular posterior papillary muscles were recorded from July 2015 to June 2019 in the Central Hospital of Shengli Oil Field and the First Affiliated Hospital of Zhengzhou University. Electrophysiological mapping and radiofrequency catheter ablation (RFCA) were performed using three-dimensional intracardiac ultrasound technology. The characteristics of the body surface and intracavity electrocardiogram were analyzed. All cases were followed up for 24 months after the operation. The VAs of all 27 cases were successfully eliminated by catheter ablation. QRS complexes were observed with a right bundle branch block (RBBB) pattern and a steep slope in the initial segment. Lead I appeared with an Rs pattern, and inferior leads (lead II, III, and aVF) were usually with an S wave. The lead aVR appeared with a qR pattern, while the R wave was commonly found in aVL. The main wave in leads V1 -V3 was positive but negative in V5 and V6 . Ventricular arrhythmias originating from the left ventricular posterior papillary muscles have similar electrophysiological characteristics. The origin site was accurately located using three-dimensional intracardiac ultrasound technology. Catheter ablation effectively eliminated VAs.


IBS subjects with methane on lactulose breath test have lower postprandial serotonin levels than subjects with hydrogen.
We have previously shown that methane on lactulose breath test (LBT) is highly associated with constipation in IBS and that methane gas itself slows small bowel transit in dogs. Previous studies suggest that serotonin may have a role in the control of transit in IBS. In this study, we aim to evaluate the role of serotonin in methane producing IBS subjects. Rome I-positive IBS subjects were recruited into the study after exclusion criteria were met. A fasting LBT was performed after subjects filled out a questionnaire rating the degree of constipation and diarrhea. Within 7 days of this test, subjects returned fasting for determination of serotonin before and after a 75-g oral glucose meal. The serotonin response was compared between hydrogen and methane producing IBS subjects. After 2 subjects were excluded for inadequate blood samples, 18 subjects completed the study. Four of 18 subjects produced methane. The postprandial serotonin level in methane producing IBS subjects was lower than in hydrogen producers (P < 0.05). Methane producers had a reduction in serotonin after glucose. Methane producing IBS subjects have reduced postprandial serotonin. Whether methane is a surrogate marker of constipation or contributing to the reduced serotonin remains to be determined.


Risk of fracture prevention in spina bifida patients: correlation between bone mineral density, vitamin D, and electrolyte values.
The aim of our study was to investigate the relationship between bone mineral density (BMD), vitamin D, and electrolyte blood values in patients with spina bifida, to find a possible therapeutic regimen and an intervention to reduce the risk of fractures in this population. BMD values were measured in 49 patients (32 females, 17 males; aged 14.1 ± 3.86 years; range 5-20 years) using dual-energy X-ray absorptiometry (DEXA) and were analyzed based on sex, the level of spinal involvement, vitamin D, and electrolyte values, physical activity, body mass index (BMI), and ambulatory status [patients were divided into three subgroups: full-time wheelchair (FTWC), limited ambulator (LA), and full-time ambulator (FTA)]. These data were analyzed considering sex-, age-, and BMD-matched values and compared with those of normal population. BMD was significantly lower in these patients compared with that in the general healthy population (Z-score: -1.2 ± 1.8); in particular, females had Z-score values significantly lower that of the males (Z-score: -2.43 ± 2.02; P < 0.0004). In FTWC subgroup, Z-score was lower than that of the other two subgroups (P < 0.009). Vitamin D values were significantly lower compared with those in the general healthy population (vitamin D spina bifida group: 14.6 ± 8.7 mg/dL; normal subjects: 35 ± 9.8 mg/dL; P < 0.001). Subjects with spina bifida showed hypophosphatemia (<3 mg/dL) because of the lower levels of vitamin D (3.1 ± 0.9 mg/dL; P < 0.001). Spina bifida patients showed lower BMD, vitamin D, and electrolyte values than the healthy population; hence, they have an increase risk of developing pathological fractures. Vitamin D supplementation for a longer time period could reduce this risk.


Text mining-based identification of promising miRNA biomarkers for diabetes mellitus.
MicroRNAs (miRNAs) are small, non-coding RNAs that play a critical role in diabetes development. While individual studies investigating the mechanisms of miRNA in diabetes provide valuable insights, their narrow focus limits their ability to provide a comprehensive understanding of miRNAs' role in diabetes pathogenesis and complications. To reduce potential bias from individual studies, we employed a text mining-based approach to identify the role of miRNAs in diabetes and their potential as biomarker candidates. Abstracts of publications were tokenized, and biomedical terms were extracted for topic modeling. Four machine learning algorithms, including Naïve Bayes, Decision Tree, Random Forest, and Support Vector Machines (SVM), were employed for diabetes classification. Feature importance was assessed to construct miRNA-diabetes networks. Our analysis identified 13 distinct topics of miRNA studies in the context of diabetes, and miRNAs exhibited a topic-specific pattern. SVM achieved a promising prediction for diabetes with an accuracy score greater than 60%. Notably, miR-146 emerged as one of the critical biomarkers for diabetes prediction, targeting multiple genes and signal pathways implicated in diabetic inflammation and neuropathy. This comprehensive approach yields generalizable insights into the network miRNAs-diabetes network and supports miRNAs' potential as a biomarker for diabetes.