Role of maternal 5-HT(1A) receptor in programming offspring emotional and physical development.
Serotonin(1A) receptor (5-HT(1A)R) deficiency has been associated with anxiety and depression and mice with genetic receptor inactivation exhibit heightened anxiety. We have reported that 5-HT(1A)R is not only a genetic but also a maternal 'environmental' factor in the development of anxiety in Swiss-Webster mice. Here, we tested whether the emergence of maternal genotype-dependent adult anxiety is preceded by early behavioral abnormalities or whether it is manifested following a normal emotional development. Pups born to null or heterozygote mothers had significantly reduced ultrasonic vocalization (USV) between postnatal day (P) 4 and 12, indicating an influence of the maternal genotype. The offspring's own genotype had an effect limited to P4. Furthermore, we observed reduced weight gain in the null offspring of null but not heterozygote mothers, indicating that a complete maternal receptor deficiency compromises physical development of the offspring. Except a short perinatal deficit during the dark period, heterozygote females displayed normal maternal behavior, which, with the early appearance of USV deficit, suggests a role for 5-HT(1A)R during pre-/perinatal development. Consistent with this notion, adult anxiety in the offspring is determined during the pre-/perinatal period. In contrast to heterozygote females, null mothers exhibited impaired pup retrieval and nest building that may explain the reduced weight gain of their offspring. Taken together, our data indicate an important role for the maternal 5-HT(1A)R in regulating emotional and physical development of their offspring. Because reduced receptor binding has been reported in depression, including postpartum depression, reduced 5-HT(1A)R function in mothers may influence the emotional development of their offspring.


Multi-centre, three arm, randomized controlled trial on the use of methylprednisolone and unfractionated heparin in critically ill ventilated patients with pneumonia from SARS-CoV-2 infection: A structured summary of a study protocol for a randomised controlled trial.
To assess the hypothesis that an adjunctive therapy with methylprednisolone and unfractionated heparin (UFH) or with methylprednisolone and low molecular weight heparin (LMWH) are more effective in reducing any-cause mortality in critically-ill ventilated patients with pneumonia from SARS-CoV-2 infection compared to LMWH alone. The study is designed as a multi-centre, interventional, parallel group, superiority, randomized, investigator sponsored, three arms study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the three treatment groups in a ratio 1:1:1. Inpatients will be recruited from 8 Italian Academic and non-Academic Intensive Care Units INCLUSION CRITERIA (ALL REQUIRED): 1. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) 2. Positive pressure ventilation (either non-invasive or invasive) from > 24 hours 3. Invasive mechanical ventilation from < 96 hours 4. PaO2/FiO2 ratio lower than 150 mmHg 5. D-dimer level > 6 times the upper limit of normal reference range 6. C-reactive Protein > 6-fold upper the limit of normal reference range EXCLUSION CRITERIA: 1. Age < 18 years 2. On-going treatment with anticoagulant drugs 3. Platelet count < 100.000/mm3 4. History of heparin-induced thrombocytopenia 5. Allergy to sodium enoxaparin or other LMWH, UFH or methylprednisolone 6. Active bleeding or on-going clinical condition deemed at high risk of bleeding contraindicating anticoagulant treatment 7. Recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery 8. Chronic assumption or oral corticosteroids 9. Pregnancy or breastfeeding or positive pregnancy test. In childbearing age women, before inclusion, a pregnancy test will be performed if not available 10. Clinical decision to withhold life-sustaining treatment or "too sick to benefit" 11. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) 12. Lack or withdrawal of informed consent INTERVENTION AND COMPARATOR: • LMWH group: patients in this group will be administered enoxaparin at standard prophylactic dosage. • LMWH + steroid group: patients in this group will receive enoxaparin at standard prophylactic dosage and methylprednisolone. • UFH + steroid group: patients in this group will receive UFH at therapeutic dosages and methylprednisolone. UFH will be administered intravenously in UFH + steroid group at therapeutic doses. The infusion will be started at an infusion rate of 18 UI/kg/hour and then modified to obtain aPTT Ratio in between the range of 1.5-2.0. aPTT will be periodically checked at intervals no longer than 12 hours. The treatment with UFH will be administered up to ICU discharge. After ICU discharge anticoagulant therapy may be interrupted or switched to prophylaxis with LMWH in the destination ward up to clinical judgement of the attending physician. Enoxaparin will be administered in both LMWH group and LMWH + steroid group at standard prophylactic dose (i.e., 4000 UI once day, increased to 6000 UI once day for patients weighting more than 90 kg). The treatment will be administered subcutaneously once a day up to ICU discharge. After ICU discharge it may be continued or interrupted in the destination ward up to clinical judgement of the attending physician. Methylprednisolone will be administered in both LMWH + steroid group and UHF + steroid group intravenously with an initial bolus of 0,5 mg/kg followed by administration of 0,5 mg/kg 4 times daily for 7 days, 0,5 mg/kg 3 times daily from day 8 to day 10, 0,5 mg/kg 2 times daily at days 11 and 12 and 0,5 mg/kg once daily at days 13 and 14. Primary Efficacy Endpoint: All-cause mortality at day 28 Secondary Efficacy Endpoints: - Ventilation free days (VFDs) at day 28, defined as the total number of days that patient is alive and free of ventilation (either invasive or non-invasive) between randomization and day 28 (censored at hospital discharge). - Need of rescue administration of high-dose steroids or immune-modulatory drugs; - Occurrence of switch from non-invasive to invasive mechanical ventilation during ICU stay; - Delay from start of non-invasive ventilation to switch to invasive ventilation; - All-cause mortality at ICU discharge and hospital discharge; - ICU free days (IFDs) at day 28, defined as the total number of days between ICU discharge and day 28. - Occurrence of new infections from randomization to day 28; including infections by Candida, Aspergillus, Adenovirus, Herpes Virus e Cytomegalovirus - Occurrence of new organ dysfunction and grade of dysfunction during ICU stay. - Objectively confirmed venous thromboembolism, stroke or myocardial infarction; Safety endpoints: - Occurrence of major bleeding, defined as transfusion of 2 or more units of packed red blood cells in a day, bleeding that occurs in at least one of the following critical sites [intracranial, intra-spinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal], bleeding that necessitates surgical intervention and bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death); - Occurrence of clinically relevant non-major bleeding, defined ad acute clinically overt bleeding that does not meet the criteria for major and consists of any bleeding compromising hemodynamic; spontaneous hematoma larger than 25 cm2, intramuscular hematoma documented by ultrasonography, haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures; haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention or any other bleeding requiring temporary cessation of a study drug. A block randomisation will be used with variable block sizes (block size 4-6-8), stratified by 3 factors: Centre, BMI (<30/≥30) and Age (<75/≥75). Central randomisation will be performed using a secure, web-based, randomisation system with an allocation ratio of 1:1:1. The allocation sequence will be generated by the study statistician using computer generated random numbers. Participants to the study will be blinded to group assignment. The target sample size is based on the hypothesis that the combined use of UHF and steroid versus the LMWH group will significantly reduce the risk of death at day 28. The overall sample size in this study is expected to be 210 with a randomization 1:1:1 and seventy patients in each group. Assuming an alpha of 2.5% (two tailed) and mortality rate in LMWH group of 50%, as indicated from initial studies of ICU patients, the study will have an 80% power to detect at least a 25 % absolute reduction in the risk of death between: a) LMHW + steroid group and LMWH group or b) UHF + steroid group and LMWH group. The study has not been sized to assess the difference between LMHW + steroid group and UHF + steroid group, therefore the results obtained from this comparison will need to be interpreted with caution and will need further adequately sized studies confirm the effect. On the basis of a conservative estimation, that 8 participating sites admit an average of 3 eligible patients per month per centre (24 patients/month). Assuming that 80 % of eligible patients are enrolled, recruitment of 210 participants will be completed in approximately 10 months. Protocol version 1.1 of April 26th, 2020. Recruitment start (expected): September 1st, 2020 Recruitment finish (expected): June 30th, 2021 TRIAL REGISTRATION: EudraCT number 2020-001921-30 , registered on April 15th, 2020 AIFA approval on May 4th, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


[Anxiety models on mice: experimental evaluation and criticism of the method].
The analysis of publications in the field of experimental psychopharmacology (in particular, anxiety models) shows a lack of data concerning the general methodological problems such as reproducibility and reliability of data. There are only a few works where important characteristics concerning solution pH, sham injections, body temperature, locomotion indices (basal and injection-modulated), etc, are reported. Figures on the illumination level in experimental chambers are generally missing. Three simplest, fastest, and most commonly used anxiety models (dark-light compartments, social isolation test, elevated plus-maze) are considered with special attention to the mistakes and artifacts most frequently encountered in registration of the experimental animal behavior and in the data interpretation.


[Somatoform vertigo: a guide for the general practitioner].
The symptoms associated with somatoform vertigos take on many forms and often appear to be organic in origin. Only a complete medical history in connection with a clinical neurootological examination and psychiatric/psychosomatic exploration can differentiate between organic (e.g., vestibular) and somatoform vertigos. The patients must be informed about this disorder so that the symptoms are taken seriously. Even though they cannot be ascribed to an organic impairment, the symptoms are still clinically significant. Somatoform vertigo is primarily treated with behavior therapy (if necessary, combined with supportive psychopharmacotherapy). Many patients have good prognosis, particularly when therapy is initiated early.


[Surgical treatment of tachycardia: experience and prospects].
The paper analyzes current methods of diagnosis, outcomes of surgical management of tachyarrhythmias, and future trends of studies. Clinical experience has been gained with 723 surgeries made in patients with life-threatening arrhythmias, out of them 594 surgeries were performed on open heart, 327 in patients with preexcitation syndrome, 151 for supraventricular, 101 for ventricular tachycardias, and 155 for concurrent abnormalities. A total of ill children were 123. The main results of treating patients are analyzed in the same sequence: preexcitation syndromes, supraventricular and ventricular tachyarrhythmias, multiple arrhythmias, and the latter concurrent with congenital and acquired heart diseases, and coronary heart disease. An emphasis is also laid on pediatric surgical practice. Although there are evident advances in each above areas, a number of serious problems are available, which the world lead clinics are dealing with. Attention is paid to the application of laser and development of surgical management techniques used in children, radical operations for atrial fibrillation and flutter, organ-preserving surgeries on sinus and atrioventricular nodes while these are considered to be promising.


In vivo desensitization of the beta, but not the alpha 2-adrenoreceptor-coupled-adenylate cyclase system in hamster white adipocytes after administration of epinephrine.
To assess the physiological relevance of the changes in adrenergic receptor observed in adipocyte membranes after in vitro exposure to catecholamines, hamster white adipocytes, which possess both beta- and alpha-adrenergic receptors, were studied after a 6-day in vivo epinephrine administration (1 mg/kg, daily). This treatment resulted in a 3-fold increase in total plasma catecholamine levels and in the following changes in the adipocytes. The lipolytic and cAMP responses to beta-agonists, ACTH, and theophylline were decreased by 55-60%, but the sensitivity of these responses to (-)isoproterenol was unchanged. Although basal adenylate cyclase activity was unaffected, (-)isoproterenol-, ACTH- or fluoride-stimulated activities were reduced by half, a defect which persisted in the presence of guanosine 5'-[beta, gamma-imido]triphosphate. Furthermore, the number of beta-adrenergic receptors was also decreased by 54%. In contrast, epinephrine treatment failed to impair the adipocyte antilipolytic response to the alpha 2-agonist clonidine, the alpha 2-component of epinephrine, and the adenosine analog N6-phenylisopropyladenosine, the adenylate cyclase inhibitory response to these compounds, and the number of alpha 2-adrenergic receptors. These results indicate that in vivo epinephrine administration does not alter the alpha 2-adrenergic system of hamster white adipocyte, but desensitizes the lipolytic response to beta-agonists and also to nonadrenergic lipolytic agents. It is therefore suggested that the likely mechanism(s) responsible for this lipolysis desensitization mainly consists in impaired adenylate cyclase coupling and possibly in altered intracellular processes, rather than in the observed beta-adrenergic receptor down-regulation.


Vein-first vs artery-first surgical technique for lobectomy of non-small cell lung cancer: A protocol for systematic review and meta-analysis.
The operation of lung cancer may squeeze the tumor and further promote the spread of tumor cells to the circulation, which may be one of the reasons for the metastasis and recurrence of lung cancer. The potential risk of tumor cell dissemination can theoretically be minimized if the effluent veins were ligated first (via the vein-first [V-first] technique), instead of having the artery ligated first (via the artery-first [A-first] technique). However, this technical concept has not yet been widely accepted as a standard of surgical oncology in current guidelines owing to a lack of sufficient evidence. This systematic review and meta-analysis will be performed to determine which technique during lobectomy will achieve longer patient survival and be more beneficial for patients. We will search PubMed, Web of Science, EMBASE, Cancerlit, the Cochrane Central Register of Controlled Trials, and Google Scholar databases for relevant clinical trials published in any language before October 1, 2020. Randomized controlled trials (RCTs), quasi-RCTs, propensity score-matched comparative studies, and prospective cohort studies of interest, published or unpublished, that meet the inclusion criteria will be included. Subgroup analysis of the type of operation, tumor pathological stage, and ethnicity will be performed. INPLASY registration number: INPLASY202050060. The results of this study will be published in a peer-reviewed journal. As far as we know, this study will be the first meta-analysis to compare the efficacy of the vein-first and artery-first surgical technique of lobectomy for patients diagnosed with resectable non-small cell lung cancer. Due to the nature of the disease and intervention methods, randomized controlled trials may be inadequate, and we will carefully consider inclusion in high-quality, non-randomized controlled trials, but this may result in high heterogeneity and affect the reliability of the results.


Global lung cancer risk from PAH exposure highly depends on emission sources and individual susceptibility.
The health impacts of polycyclic aromatic hydrocarbons (PAHs), the most concerning organic pollutants, depend not only on the locations and strengths of emission sources, but also on individual susceptibility. Moreover, trans-boundary transport makes them a global concern. In this study, a comprehensive analysis of the global health impacts of polycyclic aromatic hydrocarbons (PAHs) in ambient air is presented. Model resolution is critical in exposure modelling. Globally, incremental lifetime lung cancer risk (ILCR) induced by ambient PAH exposure is 3.1 × 10(-5). If the individual susceptibility was not taken into consideration, the overall risk would be underestimated by 55% and the proportion of highly vulnerable population would be underestimated by more than 90%. Emphasizing on individual susceptibility, our study provides an instrumental revision of current risk assessment methodology. In terms of lung cancer risk, the most important sources are combustion of biomass fuels (40%) and fossil fuels (14%) in the residential/commercial sector, coke (13%) and aluminium (12%) production, and motor vehicles (9%). PAHs can travel long distance globally especially within the Eurasian continent. Still, the risk is dominantly contributed by local.


Erythrocyte adducin: a calmodulin-regulated actin-bundling protein that stimulates spectrin-actin binding.
Adducin is an erythrocyte membrane skeletal phosphoprotein comprised of two related subunits of 105,000 and 100,000 Mr. These peptides form a functional heterodimer, and the smaller of the two binds calmodulin in a calcium-dependent fashion. Although this protein has been physicochemically characterized, its function remains unknown. We have examined the interaction of human adducin with actin and with human erythrocyte spectrin using sedimentation, electrophoretic, and morphologic techniques. Purified adducin binds actin at physiologic ionic strength and bundles it into arrays of laterally arranged filaments, the adducin forming cross-bridges between the filaments at 35.2 /- 3.8 (2 SD) nm intervals. The stoichiometry of high affinity adducin binding to actin at saturation is 1:7, corresponding to a dimer of adducin for every actin helical unit. Adducin also promotes the binding of spectrin to actin independently of protein 4.1. At saturation, each adducin promotes the association of one spectrin heterodimer. The formation of this ternary spectrin-actin-adducin complex is independent of the assembly path, and the complex exists in a readily reversible equilibrium with the free components. The binding of adducin to actin and its ability to stimulate spectrin-actin binding is down-regulated by calmodulin in a calcium-dependent fashion. These results thus identify a putative role for adducin, and define a calcium- and calmodulin-dependent mechanism whereby higher states of actin association and its interaction with spectrin in the erythrocyte may be controlled.


Geometric constraint-triggered collagen expression mediates bacterial-host adhesion.
Cells living in geometrically confined microenvironments are ubiquitous in various physiological processes, e.g., wound closure. However, it remains unclear whether and how spatially geometric constraints on host cells regulate bacteria-host interactions. Here, we reveal that interactions between bacteria and spatially constrained cell monolayers exhibit strong spatial heterogeneity, and that bacteria tend to adhere to these cells near the outer edges of confined monolayers. The bacterial adhesion force near the edges of the micropatterned monolayers is up to 75 nN, which is ~3 times higher than that at the centers, depending on the underlying substrate rigidities. Single-cell RNA sequencing experiments indicate that spatially heterogeneous expression of collagen IV with significant edge effects is responsible for the location-dependent bacterial adhesion. Finally, we show that collagen IV inhibitors can potentially be utilized as adjuvants to reduce bacterial adhesion and thus markedly enhance the efficacy of antibiotics, as demonstrated in animal experiments.


Dietary patterns and the risk of postmenopausal breast cancer.
The association between individual foods and breast cancer has been inconsistent. Therefore, we examined the association between diet and risk of postmenopausal breast cancer by the alternative approach of dietary patterns. Dietary patterns were identified with factor analysis from food consumption data collected from a food frequency questionnaire in 1984. Relative risks were computed using proportional hazard models and adjusted for known risk factors for breast cancer. Between 1984 and 2000, we ascertained 3,026 incident cases of postmenopausal breast cancer. We identified 2 major dietary patterns. The prudent pattern is characterized by higher intake of fruits, vegetables, whole grains, low-fat dairy products, fish and poultry, while the Western pattern is characterized by higher intake of red and processed meats, refined grains, sweets and desserts and high-fat dairy products. Neither of the patterns was associated with overall risk of postmenopausal breast cancer. However, a positive association between the Western pattern score was observed among smokers at baseline (relative risk = 1.44, comparing top to bottom quintiles; 95% CI = 1.02-2.03; p for trend = 0.03). An inverse association was observed between the prudent pattern and estrogen receptor-negative cancer (relative risk = 0.62; 95% CI = 0.45-0.88; p for trend = 0.006). Among the major food groups, higher consumptions of fruits (relative risk for 1 serving/day increase = 0.88; 95% CI = 0.80-0.97; p = 0.009) and vegetables (relative risk = 0.94; 95% CI = 0.88-0.99; p = 0.03) were significantly associated with decreased risk for ER(-) breast cancer. In conclusion, we did not observe an overall association between the prudent or Western pattern and overall breast cancer risk. However, a Western-type diet may elevate risk of breast cancer among smokers, and a prudent diet may protect against estrogen receptive-negative tumors.


X-ray characterisation of normal and neoplastic breast tissues.
Normal and neoplastic breast tissues have been characterised in terms of x-ray attenuation. Samples of normal fat and fibrous tissue were obtained from reduction mammoplasty and autopsy, and infiltrating duct carcinoma specimens from mastectomy and lumpectomy. A high-purity germanium spectroscopy system and a beam of 120 kV constant potential x-rays were used to determine the linear attenuation coefficient from 18 to 110 keV. Densities were determined from buoyancy measurements and were used to obtain mass attenuation coefficients. Infiltrating duct carcinomas and fat are well distinguished by x-ray attenuation. For photon energies used for film-screen mammography, infiltrating duct carcinomas are more attenuating than fibrous tissue. Above 31 keV, the ranges of attenuation of the two tissue types overlap. The attenuation coefficients of tissues have been concisely represented by equivalent thicknesses of lucite and aluminium. Analysis based on the average attenuation properties of tissues indicates that dual-energy mammography, using an ideal imaging system, would require 0.06 cGy to provide images in which 1 cm infiltrating duct carcinomas are displayed with a signal to noise ratio of 5 against a background over which the fat/fibrous contrast has been suppressed. This dose is similar to that currently used in conventional film-screen mammography.


[Changes of hypothalamic ventromedial nucleus structure in rats of different age with experimental diabetes mellitus].
This work describes morpho-functional organization of the hypothalamic ventromedial nucleus (VMN) in rats of different age with streptozotocin-induced diabetes mellitus (DM). On day 7 of experimental DM, the development of a stress reaction was observed in 3-month-old animals, which was characterized by the ultrastructural signs of increased functional activity of light neurosecretory cells (NSC) of the VMN. Meanwhile, NSC of the VMN of 24-month-old animals remained intact. These changes in the VMN of 3-month-old animals with DM mellitus are probably related to much higher levels of glucose. On day 28 of experimental DM, the decrease in NSC numbers in the VMN was observed in the animals of both age groups because of apoptosis and hydropic degeneration. Such changes were accompanied by the deterioration in NSC trophism due to the development of the initial stages of diabetic microangiopathy and destructive changes in glial cells.


Role of naloxone in newborn resuscitation.
Because of questions about the basis for the use of naloxone in resuscitation of the newborn, we wished to evaluate the use of naloxone at our institution and an affiliated hospital. Evaluation of the actual use of naloxone at a university hospital and a community hospital: we document naloxone use by daily survey for a month in one; in the other, we perform a retrospective record review of 1 year's use. The university hospital had 240 births during February, 1998. Naloxone was given twice: once, 7 minutes before delivery to a woman at term who had received opiates about 2 hours previously; and once, intramuscularly, to a premature infant for apnea, before being intubated. The community hospital had 2044 births during fiscal 1998. Twenty-six neonates were identified as having received naloxone. Of the 26, 13 received naloxone without needing ventilatory support; all 13 with respiratory depression had a predisposing perinatal complication. The use of naloxone in practice may not conform to the American Academy of Pediatrics' guidelines for use in resuscitation of the newborn. The use of naloxone in resuscitation of the newborn should be reevaluated.


A look at the components and effectiveness of sports drinks.
The confusion about sports drinks is lessened if the types are understood. Types include: fluid replacers, carbohydrate loaders, and nutrient supplements. The athletic activity and the timing of the consumption of the drink need to complement the type of drink. Fluid replacement is a must before, during, and after activity to maintain heart rate and body temperature. Whether water or a sports drink is consumed is the athlete's choice. The carbohydrate concentration of a fluid-replacing drink should not exceed 10%, which is comparable to the gastric emptying characteristics of water. Glucose, sucrose, and glucose polymers are all well tolerated by athletes during activity, although fructose in high concentrations may not be. Electrolytes are present in drinks to enhance absorption; high levels usually are not needed, except in certain populations.


Synthesis, photophysics and reverse saturable absorption of bipyridyl platinum(II) bis(arylfluorenylacetylide) complexes.
A series of Pt(II) bipyridyl complexes with different aryl substituents (Ar = naphthyl (1a), anthryl (1b), pyrenyl (1c) and phenothiazyl (1d)) on the fluorenylacetylide ligands are synthesized and investigated. The influence of the aryl substituent on the photophysics of these complexes is systematically investigated by spectroscopic methods and simulated by time dependent density functional theory (TD-DFT). All complexes exhibit ligand-centered (1)π,π* transitions significantly admixed with the metal-to-ligand charge transfer ((1)MLCT)/ligand-to-ligand charge transfer ((1)LLCT) transitions in the UV and blue spectral region, and broad, structureless (1)MLCT/(1)LLCT absorption bands in the visible spectral region. All complexes are emissive in solution at room temperature, with the fluorescence originating predominantly from the (1)MLCT/(1)LLCT states. The triplet emitting state is dominated by the (3)π,π* state localized on the fluorenylacetylide motif and mixed with some (3)ML'CT character (metal-to-fluorenylacetylide ligand charge transfer) for 1a, 1b and 1d. For 1c, the phosphorescence predominantly originates from the pyrene localized (3)π,π* state. The variation in the photophysical properties is related to the twisting angle of the aryl substituent from the fluorenyl plane, which defines the conjugation between the substituents and fluorenylacetylide ligands and, consequently, alters the energy and intensity of absorption and emission in these complexes. also exhibit broadband triplet excited-state absorption in the visible spectral region. Therefore, they show strong reverse saturable absorption at 532 nm for nanosecond laser pulses as demonstrated by the nonlinear transmission experiment.


The Effects and Mechanism of Quercetin Dietary Supplementation in Streptozotocin-Induced Hyperglycemic Arbor Acre Broilers.
Quercetin, a flavonoid found in fruits and vegetables, is widely distributed as a secondary metabolite in the plant kingdom. Oxidative stress plays a role in the pathogenesis of diabetes mellitus (DM). The present study investigated the effects of quercetin dietary supplementation on streptozotocin- (STZ-) induced hyperglycemic Arbor Acre (AA) broilers by determining the levels of fasting blood glucose (FBG), fasting insulin (FINS), biochemical indicators, oxidative stress markers, inflammatory cytokines content, antioxidant enzymes activities in tissues, and mRNA expression of genes relating to the insulin signaling pathway. Three hundred one-day-old healthy AA broilers were randomly assigned into 5 treatments; A, control healthy broilers; B, STZ-induced broilers; C, STZ-induced broiler dietary supplemented with 0.02% quercetin; D, STZ-induced broiler dietary supplemented with 0.04% quercetin; and E, STZ-induced broiler dietary supplemented with 0.06% quercetin. The results showed that quercetin supplementation relieved the side effects of STZ-induced oxidative stress by changing activities of antioxidant enzymes, decreasing malondialdehyde (MDA) and nitric oxide (NO) levels, activating expression of genes relating to PI3K/PKB signaling pathway that modulate glucose metabolism and reduce oxidative damage, thereby decreasing FBG and increasing FINS levels. These findings suggest that quercetin exhibits a protective effect in STZ-induced hyperglycemic AA broilers via decreasing oxidative stress.


Serum antibodies against feline oncornavirus-associated cell membrane antigen in cats bearing virally induced uveal melanomas.
The humoral immune response to a virally induced feline model of human uveal melanoma was studied by examining sera from cats bearing iridal and choroidal melanomas for antibody to the feline oncornavirus-associated cell membrane antigen (FOCMA). Anti-FOCMA antibodies appeared earlier and in higher titers in cats that ultimately expressed nonprogressing uveal melanomas. By 8 weeks after virus inoculation 56% of the cats with nonprogressing lesions had anti-FOCMA antibodies, whereas only 7% of the cats with progressive tumors produced demonstrable antibodies against FOCMA. Mean serum antibody titers were approximately 10 times higher in cats with nonprogressive lesions than in cats with progressive tumors. Similar trends were observed throughout the 28-week study period. Early appearance and a high titer of serum antibody against FOCMA correlated with nonprogressing uveal melanoma. The results indicated that uveal melanomas could be immunogeneic and successfully managed by the host's immune system.


[Clinical evaluation of BRL 25000 (clavulanic acid-amoxicillin) in the fields of obstetrics and gynecology].
BRL 25000 was administered to 37 cases with infections in the fields of obstetrics and gynecology, and the following results were obtained. The drug was administered to 17 cases with adnexitis, 13 cases with intrauterine infection and 7 cases with parametritis and/or inflammation of pelvic dead space, etc. The percentage of efficacy (excellent and good) was 74.3%. Of 7 cases where no therapeutic effect was obtained with other drugs, the percentage of efficacy was 57.1%. Antibacterial effect of BRL 25000 was studied in terms of percentage of eradication (including replacement) of clinical isolates. A high percentage of eradication (94.4% or 17/18) was obtained. Among all clinical isolates, 37.9% or 11/29 were beta-lactamase producing organisms. Eradication or replacement by BRL 25000 was noted in all these 9 strains, and BRL 25000 was proved to have a high efficacy also against penicillin or cephalosporin resistant organisms. No abnormality was noted in any patient in hematological, hepatic and renal function before and after administration of BRL 25000. As adverse reaction, diarrhea was found in 1 of 37 cases (2.7%), but it reduced after off-dose.


Supervised pathway analysis of blood gene expression profiles in Alzheimer's disease.
Early identification and treatment of Alzheimer's disease (AD) is hampered by the lack of easily accessible biomarkers. Currently available fluid biomarkers of AD provide indications of the disease stage; however, these are measured in the cerebrospinal fluid, requiring invasive procedures, which are not applicable at the population level. Thus, gene expression profiling of blood provides a viable alternative as a way to screen individuals at risk of AD. Previous studies have shown that despite the limited permeability of the blood-brain barriers, expression profiles of blood genes can be used for the diagnosis and prognosis of several brain disorders. Here, we propose a new approach to pathway analysis of blood gene expression profiles to classify healthy (control [CTL]), mildly cognitively impaired (mild cognitive impairment [MCI]; preclinical stage of AD), and AD subjects. In the pathway analysis, gene expression data are mapped to pathway scores according to a predefined gene set instead of considering each gene separately. The robustness of the analysis enables detection of weak differences between groups owing to the inherent dimension reduction. Our proposed method for pathway analysis takes advantage of linear discriminant analysis for identifying a linear combination of features best separating groups of subjects within each gene set. The gene expression data were retrieved from Gene Expression Omnibus (batch 1: GSE63060; batch 2: GSE63061). Predefined gene sets for pathway analysis were obtained from the Broad Institute Collection of Curated Pathways. The method achieved a 10-fold cross-validated area under receiver operating characteristic curve of 0.84 for classification of AD versus CTL and 0.80 for classification of mild cognitive impairment versus CTL. These results reveal the good potential of blood-based biomarkers for assisting early diagnosis and disease monitoring of AD.


CA19-9 in Combination with Methylated HOXA1 and SST Is Useful to Diagnose Stage I Pancreatic Cancer.
We previously developed a novel methylation assay, the combined restriction digital PCR (CORD) assay, consisting of treatment of DNA with methylation-sensitive restriction enzymes and droplet digital PCR. In this study, we assessed the diagnostic performance of serum methylated Homeobox A1 (mHOXA1) and methylated somatostatin (mSST) using the CORD assay in combination with CA19-9 for pancreatic cancer using serum samples from 82 healthy individuals, 13 patients with benign pancreatic disease, 3 patients with branched-duct intraductal papillary mucinous neoplasm, and 91 patients with pancreatic cancer. For the single marker tests, sensitivity for all stages of pancreatic cancer, stage I cancer, and specificity were, respectively, 71.4%, 50.0%, and 94.9% for CA19-9; 51.6%, 68.8%, and 90.8% for mHOXA1; and 50.1%, 68.8%, and 94.9% for mSST. Those for the combined marker tests were, respectively, 86.8%, 81.3%, and 85.7% for combined mHOXA1 and CA19-9; 86.8%, 87.5%, and 89.8% for combined mSST and CA19-9; and 89.0%, 87.5%, and 85.7% for all three markers combined. The combination of mHOXA1 and mSST with CA19-9 appears to be useful to detect pancreatic cancer even at an early stage.


Uncertainties of internal dose assessment for animals and plants due to non-homogeneously distributed radionuclides.
The dose conversion coefficients (DCCs) for the assessment of internal absorbed dose rate in reference animals and plants have been generally calculated assuming a homogeneous distribution of radionuclides within the body. Realistic scenarios of internal exposure must account for some radionuclides which tend to concentrate in specific organs or tissues. To study the effect of such inhomogeneous distributions, internal DCCs have been calculated assuming both a central and an eccentric point source. The analysis of the results showed that uncertainties of the whole body DCC due to non-homogeneous radionuclide distribution are less than 30% for photons and electrons for all considered organisms. For electrons, the uncertainties are negligible below certain energies, dependent on the size of the organisms. Additionally, the organ doses due to the accumulation of the radionuclide in an organ are also described and organ/whole body doses ratios are estimated.


Kidney Outcome in Primary Focal Segmental Glomerulosclerosis (FSGS) by Using a Predictive Model.
Focal segmental glomerulosclerosis (FSGS) is one of the important causes of end stage kidney disease (ESKD). We evaluated the progression risk factors of primary FSGS to chronic kidney disease (CKD) or ESKD with a predictive model including clinical and histological predictors. 201 patients with primary FSGS (59% male, mean age: 38 ± 15 years), were studied. Time-dependent Cox model and C statistics were used for the predictive model. Interaction and correlation between independent variables were estimated. During 55 ± 27 months of follow-up, 82 patients (41%) developed CKD (46) or ESKD (36) patients. In adjusted model, 1 unit of higher serum creatinine (SCr) at baseline (HR = 1.39, 95% CI: 1.15 to 1.70) and 1% increase in glomeruli with segmental glomerulosclerosis (SGS) (HR = 1.03, 95% CI: 1.02 to 1.04) or interstitial fibrosis/tubular atrophy (IF/TA) (HR = 1.03, 95% CI: 1.01 to 1.05) increased the risk of CKD/ESKD. In adjusted model, higher baseline proteinuria and collapsing variant were not associated with risk of CKD/ESKD. By adding SGS and IF/TA scores to baseline SCr in the model, discrimination by C statistics was 0.83 (95% CI: 0.77 to 0.90). Median renal survival was 3.1 years (95% CI: 2.2 to 4.1 years) in patients with highest risk score (baseline eGFR < 25 mL/min/1.73m2 + IF/TA/SGS > 50%), and 8.1 years (95% CI: 7.7 to 8.6 years).in those with lowest score (baseline eGFR > 75 mL/ min/1.73m2 + IF/TA/SGS < 5%). In primary FSGS, higher baseline SCr, increased SGS and IF/TA, but not baseline proteinuria and collapsing pathology, were the predictors for CKD/ESKD. These findings indicated the importance of timely detection and referral in prognosis of primary FSGS. DOI: 10.52547/ijkd.6442.


The same or different psychiatrists for in- and out-patient treatment? A multi-country natural experiment.
A core question in the debate about how to organise mental healthcare is whether in- and out-patient treatment should be provided by the same (personal continuity) or different psychiatrists (specialisation). The controversial debate drives costly organisational changes in several European countries, which have gone in opposing directions. The existing evidence is based on small and low-quality studies which tend to favour whatever the new experimental organisation is.We compared 1-year clinical outcomes of personal continuity and specialisation in routine care in a large scale study across five European countries. This is a 1-year prospective natural experiment conducted in Belgium, England, Germany, Italy and Poland. In all these countries, both personal continuity and specialisation exist in routine care. Eligible patients were admitted for psychiatric in-patient treatment (18 years of age), and clinically diagnosed with a psychotic, mood or anxiety/somatisation disorder.Outcomes were assessed 1 year after the index admission. The primary outcome was re-hospitalisation and analysed for the full sample and subgroups defined by country, and different socio-demographic and clinical criteria. Secondary outcomes were total number of inpatient days, involuntary re-admissions, adverse events and patients' social situation. Outcomes were compared through mixed regression models in intention-to-treat analyses. The study is registered (ISRCTN40256812). We consecutively recruited 7302 patients; 6369 (87.2%) were followed-up. No statistically significant differences were found in re-hospitalisation, neither overall (adjusted percentages: 38.9% in personal continuity, 37.1% in specialisation; odds ratio = 1.08; confidence interval 0.94-1.25; p = 0.28) nor for any of the considered subgroups. There were no significant differences in any of the secondary outcomes. Whether the same or different psychiatrists provide in- and out-patient treatment appears to have no substantial impact on patient outcomes over a 1-year period. Initiatives to improve long-term outcomes of psychiatric patients may focus on aspects other than the organisation of personal continuity v. specialisation.


Perfluorophenyl azides: new applications in surface functionalization and nanomaterial synthesis.
A major challenge in materials science is the ongoing search for coupling agents that are readily synthesized, capable of versatile chemistry, able to easily functionalize materials and surfaces, and efficient in covalently linking organic and inorganic entities. A decade ago, we began a research program investigating perfluorophenylazides (PFPA) as the coupling agents in surface functionalization and nanomaterial synthesis. The p-substituted PFPAs are attractive heterobifunctional coupling agents because of their two distinct and synthetically distinguishable reactive centers: (i) the fluorinated phenylazide, which is capable of forming stable covalent adducts, and (ii) the functional group R, which can be tailored through synthesis. Two approaches have been undertaken for material synthesis and surface functionalization. The first method involves synthesizing PFPA bearing the first molecule or material with a functional linker R and then attaching the resulting PFPA to the second material by activating the azido group. In the second approach, the material surface is first functionalized with PFPA via functional center R, and coupling of the second molecule or material is achieved with the surface azido groups. In this Account, we review the design and protocols of the two approaches, providing examples in which PFPA derivatives were successfully used in material surface functionalization, ligand conjugation, and the synthesis of hybrid nanomaterials. The methods developed have proved to be general and versatile, and they are applicable to a wide range of materials (especially those that lack reactive functional groups or are difficult to derivatize) and to various substrates of polymers, oxides, carbon materials, and metal films. The coupling chemistry can be initiated by light, heat, and electrons. Patterned structures can be generated by selectively activating the areas of interest. Furthermore, the process is easy to perform, and light activation occurs in minutes, greatly facilitating the efficiency of the reaction. PFPAs indeed demonstrate many benefits as versatile surface coupling agents and offer opportunities for further exploration.


Analysis of patterning in the occurrence of skeletal lesions used as indicators of vitamin D deficiency in subadult and adult skeletal remains.
Paleopathological investigations of conditions linked to vitamin D deficiency have increased in the last twenty years, and a suite of skeletal lesions has been established to aid in the diagnosis of vitamin D deficiency disease in subadults and adults. This paper analyzes the occurrence of these lesions in a large skeletal series comprising 3541 Roman period individuals (1st-6th century AD). Sixteen lesions reported in rickets in subadults, and 13 associated with residual rickets and osteomalacia in adults, were analyzed. Among subadults, there were clear associations among post-cranial lesions. Porotic cranial changes were associated with each other, but not with post-cranial lesions. A range of conditions could have produced the cranial lesions. There was a general paucity of correlations between indicators found in adults, and the difficulty in recording bending deformities was clear. Pseudofractures appear to provide a useful means of investigating osteomalacia in adults. In general, a simple algorithmic approach using presence or absence of lesions is unlikely to provide an adequate means of diagnosing vitamin D deficiency in paleopathology. Knowledge and consideration of the underlying physiological mechanisms involved in lesion formation, combined with individual judgement, will be required to differentially diagnose cases.


Enhanced transport of materials into enamel nanopores via electrokinetic flow.
The ability to infiltrate various molecules and resins into dental enamel is highly desirable in dentistry, yet transporting materials into dental enamel is limited by the nanometric scale of their pores. Materials that cannot be infiltrated into enamel by diffusion/capillarity are often considered molecules with sizes above a critical threshold, which are often considered to be larger than the pores of enamel. We challenge this notion by reporting the use of electrokinetic flow to transport solutions with molecules with sizes above a critical threshold-namely, an aqueous solution with a high refractive index (Thoulet's solution) and a curable fluid resin infiltrant (without acid etching)-deep into the normal enamel layer. Volume infiltration by Thoulet's solution is increased by 5- to 6-fold, and resin infiltration depths as large as 600 to 2,000 µm were achieved, in contrast to ~10 µm resulting from diffusion/capillarity. Incubation with demineralization solution for 192 h resulted in significant demineralization at noninfiltrated histologic points but not at resin infiltrated. These results open new avenues for the transport of materials in dental enamel.


Bovine Vaccinia: Insights into the Disease in Cattle.
Bovine vaccinia (BV), caused by Vaccinia virus (VACV), is a zoonosis characterized by exanthematous lesions in the teats of dairy cows and the hands of milkers and is an important public health issue. Severe VACV-induced lesions in the teats and udder of cows and buffaloes could lead to mastitis and other secondary infections, thereby reducing productivity and resulting in economic losses to the dairy industry. In Brazil, BV re-emerged in the late 1990s and is now endemic in most of the Brazilian territory. In the last 15 years, much effort has been made to know more about this disease and its epidemiology, etiologic agents, and interactions with the host and the environment. In this review, we describe the known dynamics of VACV infection in cattle and the viral shedding routes, as well as the relevance of BV for animal and public health.


Drought-induced changes in flow regimes lead to long-term losses in mussel-provided ecosystem services.
Extreme hydro-meteorological events such as droughts are becoming more frequent, intense, and persistent. This is particularly true in the south central USA, where rapidly growing urban areas are running out of water and human-engineered water storage and management are leading to broad-scale changes in flow regimes. The Kiamichi River in southeastern Oklahoma, USA, has high fish and freshwater mussel biodiversity. However, water from this rural river is desired by multiple urban areas and other entities. Freshwater mussels are large, long-lived filter feeders that provide important ecosystem services. We ask how observed changes in mussel biomass and community composition resulting from drought-induced changes in flow regimes might lead to changes in river ecosystem services. We sampled mussel communities in this river over a 20-year period that included two severe droughts. We then used laboratory-derived physiological rates and river-wide estimates of species-specific mussel biomass to estimate three aggregate ecosystem services provided by mussels over this time period: biofiltration, nutrient recycling (nitrogen and phosphorus), and nutrient storage (nitrogen, phosphorus, and carbon). Mussel populations declined over 60%, and declines were directly linked to drought-induced changes in flow regimes. All ecosystem services declined over time and mirrored biomass losses. Mussel declines were exacerbated by human water management, which has increased the magnitude and frequency of hydrologic drought in downstream reaches of the river. Freshwater mussels are globally imperiled and declining around the world. Summed across multiple streams and rivers, mussel losses similar to those we document here could have considerable consequences for downstream water quality although lost biofiltration and nutrient retention. While we cannot control the frequency and severity of climatological droughts, water releases from reservoirs could be used to augment stream flows and prevent compounded anthropogenic stressors.


Initial results of a genome survey for novel Alzheimer's disease risk genes: association with a locus on the X chromosome.
As the initial step in a systematic genome survey, 16 simple sequence tandem repeat polymorphisms that span the X chromosome at an average spacing of 10 cM were examined for allelic associations with typical-onset Alzheimer's disease (AD). The efficiency of this survey was substantially enhanced by genotyping pools of genomic DNA from 50 autopsy-confirmed AD cases and 50 autopsied controls who were similar in sex ratio, race, and age at death. The frequency of the DXS1047 202-bp allele was twice as common among AD cases (0.45 +/- S.E. 0.06) than controls (0.22 +/- S.E. 0.05), a finding that was reproduced in an independent and geographically disparate sample. Consistent with Hardy-Weinberg equilibrium, the proportion of women with AD who carried the 202-bp allele, 73% was nearly double that observed for men with AD, 38%. However, the frequency of the 202-bp allele was similar for men and women and the presence of this allele did not affect the age at onset of dementia in either sex. Furthermore, the frequency of the DXS1047 202-bp allele in AD cases and controls was unaffected by the APOE genotype, indicating that these two loci modulate AD risk independently. Finally, the frequency of the 202-bp allele among 50 autopsy-confirmed cases of Parkinson's disease (0.29 +/- S.E. 0.06) was indistinguishable from the control value, reflecting relative specificity for this allelic association with AD.


Fenofibrate-associated changes in renal function and relationship to clinical outcomes among individuals with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) experience.
Fenofibrate has been noted to cause an elevation in serum creatinine in some individuals. Participants in the Action to Control Cardiovascular Risk in Diabetes Lipid Study were studied to better characterise who is at risk of an increase in creatinine level and to determine whether those with creatinine elevation have a differential risk of adverse renal or cardiovascular outcomes. A fenofibrate-associated creatinine increase (FACI) was defined as an increase in serum creatinine of at least 20% from baseline to month 4 in participants assigned to fenofibrate. Baseline patient characteristics, and baseline and 4-month drug, clinical, laboratory characteristics and study outcomes were examined by FACI status. Of the sample, 48% of those randomised to receive fenofibrate had at least a 20% increase in serum creatinine within 4 months. In multivariable analysis, participants who were older, male, used an ACE inhibitor at baseline, used a thiazolidinedione (TZD) at 4 months post-randomisation, had baseline CVD, and had lower baseline serum creatinine and LDL-cholesterol levels were all more likely to meet the criteria for FACI. Participants in the FACI group were also more likely to have a decrease in their serum triacylglycerol level from baseline to 4 months. No differences in study outcomes were seen by FACI criteria. Several characteristics predict a rapid rise in serum creatinine upon starting fenofibrate. Participants who met the criteria for FACI also had a greater change in triacylglycerol levels. In the setting of careful renal function surveillance and reduction of fenofibrate dose as indicated, no increase in renal disease or cardiovascular outcome was seen in those individuals demonstrating FACI. ClincalTrials.gov: NCT00000620. The ACCORD Trial was supported by grants (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035 and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute; by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; by General Clinical Research Centers and by the Clinical and Translational Science Awards. Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, sanofi-aventis US and Takeda Pharmaceuticals provided study medications, equipment or supplies.


The Effect of Diabetes Mellitus Type 1 on the Energy Metabolism of Hepatocytes: Multiphoton Microscopy and Fluorescence Lifetime Imaging.
A decrease in the regenerative potential of the liver during the development of non-alcoholic fatty liver disease (NAFLD), which is observed in the vast majority of patients with diabetes mellitus type 1, significantly increases the risk of postoperative liver failure. In this regard, it is necessary to develop new approaches for the rapid intraoperative assessment of the condition of liver tissue in the presence of concomitant liver pathology. A modern label-free approach based on multiphoton microscopy, second harmonic generation (SHG), and fluorescence lifetime imaging microscopy (FLIM) allow for the evaluation of the structure of liver tissue as well as the assessment of the metabolic state of hepatocytes, even at the cellular level. We obtained optical criteria and identified specific changes in the metabolic state of hepatocytes for a reduced liver regenerative potential in the presence of induced diabetes mellitus type 1. The obtained criteria will expand the possibilities for the express assessment of the structural and functional state of liver tissue in clinical practice.


Validity of the RAI-MDS for ascertaining diabetes and comorbid conditions in long-term care facility residents.
This study assessed the validity of the Resident Assessment Instrument Minimum Data Set (RAI-MDS) Version 2.0 for diagnoses of diabetes and comorbid conditions in residents of long-term care facilities (LTCFs). Hospital inpatient, outpatient physician billing, RAI-MDS, and population registry data for 1997 to 2011 from Saskatchewan, Canada were used to ascertain cases of diabetes and 12 comorbid conditions. Prevalence estimates were calculated for both RAI-MDS and administrative health data. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated using population-based administrative health data as the validation data source. Cohen's κ was used to estimate agreement between the two data sources. 23,217 LTCF residents were in the diabetes case ascertainment cohort. Diabetes prevalence was 25.3% in administrative health data and 21.9% in RAI-MDS data. Overall sensitivity of a RAI-MDS diabetes diagnoses was 0.79 (95% CI: 0.79, 0.80) and the PPV was 0.92 (95% CI: 0.91, 0.92), when compared to administrative health data. Sensitivity of the RAI-MDS for ascertaining comorbid conditions ranged from 0.21 for osteoporosis to 0.92 for multiple sclerosis; specificity was high for most conditions. RAI-MDS clinical assessment data are sensitive to ascertain diabetes cases in LTCF populations when compared to administrative health data. For many comorbid conditions, RAI-MDS data have low validity when compared to administrative data. Risk-adjustment measures based on these comorbidities might not produce consistent results for RAI-MDS and administrative health data, which could affect the conclusions of studies about health outcomes and quality of care across facilities.


Relationships between stigma, depression, and treatment in white and African American primary care patients.
Although many depressed patients are treated in primary care, depression in these settings has been underdetected and undertreated, which may be influenced by mental health beliefs such as stigma. This study examined the relationships among depression, mental health stigma, and treatment in African American and white primary care patients. Data were collected at 3 primary care settings from 1103 patients who completed surveys measuring depression, stigma, and treatment use. Overall, African American patients reported greater mental health stigma than whites. African American women reported greater stigma than white women. White patients were found to be more likely to use depression treatment than African American patients. Multivariate analyses showed that greater depression severity fully mediated the relationship between stigma and treatment use, and that patients with the highest depression scores had significantly higher stigma scores as well. These results suggest that greater severity of depressive symptoms may override stigma and other beliefs about mental health in determining treatment use, but may be important to address for patients with more moderate levels of symptomatology.


Effects of Altitude/Hypoxia on Single- and Multiple-Sprint Performance: A Comprehensive Review.
Many sport competitions, typically involving the completion of single- (e.g. track-and-field or track cycling events) and multiple-sprint exercises (e.g. team and racquet sports, cycling races), are staged at terrestrial altitudes ranging from 1000 to 2500 m. Our aim was to comprehensively review the current knowledge on the responses to either acute or chronic altitude exposure relevant to single and multiple sprints. Performance of a single sprint is generally not negatively affected by acute exposure to simulated altitude (i.e. normobaric hypoxia) because an enhanced anaerobic energy release compensates for the reduced aerobic adenosine triphosphate production. Conversely, the reduction in air density in terrestrial altitude (i.e. hypobaric hypoxia) leads to an improved sprinting performance when aerodynamic drag is a limiting factor. With the repetition of maximal efforts, however, repeated-sprint ability is more altered (i.e. with earlier and larger performance decrements) at high altitudes (>3000-3600 m or inspired fraction of oxygen <14.4-13.3%) compared with either normoxia or low-to-moderate altitudes (<3000 m or inspired fraction of oxygen >14.4%). Traditionally, altitude training camps involve chronic exposure to low-to-moderate terrestrial altitudes (<3000 m or inspired fraction of oxygen >14.4%) for inducing haematological adaptations. However, beneficial effects on sprint performance after such altitude interventions are still debated. Recently, innovative 'live low-train high' methods, in isolation or in combination with hypoxic residence, have emerged with the belief that up-regulated non-haematological peripheral adaptations may further improve performance of multiple sprints compared with similar normoxic interventions.


High glucose environment induces NEDD4 deficiency that impairs angiogenesis and diabetic wound healing.
Healing of diabetic wounds, characterized by impaired angiogenesis, remains a clinical challenge. E3 ligase have been identified as potential therapeutic targets of wound healing. We assessed the role of E3 ligase NEDD4 in the context of angiogenesis and diabetic wound healing. The mRNA expression levels of NEDD4, TSP1 and VEGF were determined by real-time PCR. Western blotting was used to evaluate the protein expression of NEDD4, TSP1 and VEGF. The ubiquitination of TSP1 was evaluated by immunoprecipitation. MTT assay, wound healing assay and tube formation assay were performed to assess the proliferation, migration and angiogenic functions of endothelial cells. The epigenetic modification in the promoter of NEDD4 was confirmed using BSP assay and ChIP-qPCR assay. The role of NEDD4 in wound healing was further verified in diabetic mouse model. NEDD4 promotes proliferation, migration and tube formation of endothelial cells. It binds to and ubiquitinates TSP1, which lead to TSP1 degradation and thus increased VEGF expression. The inhibitory effect of NEDD4 silencing on the angiogenesis ability of endothelial cells can be restored by TSP1 knockdown. NEDD4 is reduced in diabetic patients, which may due to hypermethylation of NEDD4 promoter mediated via DNMT1 under high glucose condition. Furthermore, inhibition of NEDD4 represses wound healing in diabetic mouse model. NEDD4 might promote angiogenesis and wound healing by inhibiting TSP1 via ubiquitination in diabetic patients.


Coagulation parameters as predictors of DIC in patients with intact aortic aneurysm.
Clinically overt, preoperative, disseminated intravascular coagulation (DIC) is not common in patient with aortic aneurysm. However, cases with large and expanding aneurysm are especially prone for this coagulopathy. Contrary to the clinically overt form compensated DIC in patients with aortic aneurysm seems frequent and is probably underdiagnosed. The compensated DIC may be recognized, even without bleedings, by laboratory tests documenting the activated coagulation and fibrinolysis. We show that in about one third of patients with abdominal aorta aneurysm (AAA) compensated DIC can be identified. This enables the application of preoperative anticoagulation treatment to improve the intraoperative haemostasis.


Modifying ICD-9-CM coding of secondary diagnoses to improve risk-adjustment of inpatient mortality rates.
To assess the effect on risk-adjustment of inpatient mortality rates of progressively enhancing administrative claims data with clinical data that are increasingly expensive to obtain. Data Sources. Claims and abstracted clinical data on patients hospitalized for 5 medical conditions and 3 surgical procedures at 188 Pennsylvania hospitals from July 2000 through June 2003. Risk-adjustment models for inpatient mortality were derived using claims data with secondary diagnoses limited to conditions unlikely to be hospital-acquired complications. Models were enhanced with one or more of 1) secondary diagnoses inferred from clinical data to have been present-on-admission (POA), 2) secondary diagnoses not coded on claims but documented in medical records as POA, 3) numerical laboratory results from the first hospital day, and 4) all available clinical data from the first hospital day. Alternative models were compared using c-statistics, the magnitude of errors in prediction for individual cases, and the percentage of hospitals with aggregate errors in prediction exceeding specified thresholds. More complete coding of a few under-reported secondary diagnoses and adding numerical laboratory results to claims data substantially improved predictions of inpatient mortality. Little improvement resulted from increasing the maximum number of available secondary diagnoses or adding additional clinical data. Increasing the completeness and consistency of reporting a few secondary diagnosis codes for findings POA and merging claims data with numerical laboratory values improved risk adjustment of inpatient mortality rates. Expensive abstraction of additional clinical information from medical records resulted in little further improvement.


Molecular Sets (MOSES): A Benchmarking Platform for Molecular Generation Models.
Generative models are becoming a tool of choice for exploring the molecular space. These models learn on a large training dataset and produce novel molecular structures with similar properties. Generated structures can be utilized for virtual screening or training semi-supervized predictive models in the downstream tasks. While there are plenty of generative models, it is unclear how to compare and rank them. In this work, we introduce a benchmarking platform called Molecular Sets (MOSES) to standardize training and comparison of molecular generative models. MOSES provides training and testing datasets, and a set of metrics to evaluate the quality and diversity of generated structures. We have implemented and compared several molecular generation models and suggest to use our results as reference points for further advancements in generative chemistry research. The platform and source code are available at https://github.com/molecularsets/moses.


Cell-free synthesis and processing of the heavy and light chains of HLA-DR antigens.
Antisera have been prepared against the separated glycoprotein chains (p29 and p34) of HLA-DR antigens (p29,34) isolated from membranes of the B lymphoblastoid cell line JY (DRw4,6). These antisera (anti-p29 and anti-p34) were characterized by immunoprecipitation of in vivo labeled, detergent-solubilized extracts of JY cells grown in the presence and absence of tunicamycin, an inhibitor of N-linked glycosylation. Anti-p29 and anti-p34 specifically immunoprecipitated the precursors to p29 and p34, respectively, from the cell-free translation products of a rabbit reticulocyte lysate system supplemented with polyadenylic acid-containing messenger RNA (mRNA) isolated from JY cells. These precursors, pre-p34 and two pre-p29s, appeared to be 1,500-3,000 daltons larger than their counterparts from tunicamycin-treated cells and presumably were synthesized with N-terminal extensions (signal sequences). Processing of pre-p29 and pre-p34 occurred during cell-free translation in the presence of dog pancreatic microsomes, which resulted in cleavage of the polypeptide, addition of glycan moieties, and segregation of the two chains in the cisternal portion of the microsome. the precursors of p29 and p34 were not appreciably different in isoelectric points on two-dimensional gels from p26 and p28, the light and heavy chains from antigens arise from separate mRNA, and not as a single polypeptide, which is endoproteolytically cleaved.


Super resolution convolutional neural network for feature extraction in spectroscopic data.
Two dimensional (2D) peak finding is a common practice in data analysis for physics experiments, which is typically achieved by computing the local derivatives. However, this method is inherently unstable when the local landscape is complicated or the signal-to-noise ratio of the data is low. In this work, we propose a new method in which the peak tracking task is formalized as an inverse problem, which thus can be solved with a convolutional neural network (CNN). In addition, we show that the underlying physics principle of the experiments can be used to generate the training data. By generalizing the trained neural network on real experimental data, we show that the CNN method can achieve comparable or better results than traditional derivative based methods. This approach can be further generalized in different physics experiments when the physical process is known.


Invasive pulmonary mucormycosis: rare presentation with pulmonary eosinophilia.
Fungi can cause a variety of infectious diseases, including invasive mycosis and non-invasive mycosis, as well as allergic diseases. The different forms of mycosis usually have been described as mutually exclusive, independent entities, with few descriptions of overlapping cases. Here, we describe the first reported case of a patient with the complication of pulmonary eosinophilia in the course of invasive mucormycosis. A 74-year-old Japanese man with asthma-COPD overlap underwent emergency surgery for a ruptured abdominal aortic aneurysm. The surgery was successful, but fever and worsening dyspnea appeared and continued from postoperative day (POD) 10. A complete blood count showed leukocytosis with neutrophilia and eosinophilia, and the chest X-ray showed consolidation of the left upper lung at POD 15. We suspected nosocomial pneumonia together with an exacerbation of the asthma-COPD overlap, and both antibiotics and bronchodilator therapy were initiated. However, the symptoms, eosinophilia and imaging findings deteriorated. We then performed a bronchoscopy, and bronchoalveolar lavage (BAL) fluid analysis revealed an increased percentage of eosinophils (82% of whole cells) as well as filamentous fungi. We first suspected that this was a case of allergic bronchopulmonary mycosis (ABPM) caused by Aspergillus infection and began corticosteroid therapy with an intravenous administration of voriconazole at POD 27. However, the fungal culture examination of the BAL fluid revealed mucormycetes, which were later identified as Cunninghamella bertholletiae by PCR and DNA sequencing. We then switched the antifungal agent to liposomal amphotericin B for the treatment of the pulmonary mucormycosis at POD 29. Despite replacing voriconazole with liposomal amphotericin B, the patient developed septic shock and died at POD 39. The autopsy revealed that filamentous fungi had invaded the lung, heart, thyroid glands, kidneys, and spleen, suggesting that disseminated mucormycosis had occurred. We describe the first reported case of pulmonary mucormycosis with pulmonary eosinophilia caused by Cunninghamella bertholletiae, which resulted in disseminated mucormycosis. Although it is a rather rare case, two important conclusions can be drawn: i) mycosis can simultaneously cause both invasive infection and a host allergic reaction, and ii) Cunninghamella bertholletiae rarely infects immunocompetent patients.


The incidence of plantar fasciitis in the United States military.
Although plantar fasciitis is the most common cause of heel pain, little has been reported on the incidence rates of this disorder. We sought to determine the incidence rate and demographic risk factors of plantar fasciitis in an ethnically diverse and physically active population of United States military service members. A query was performed with use of the Defense Medical Epidemiology Database for the International Classification of Diseases, Ninth Revision, Clinical Modification, code for plantar fasciitis (728.71). Multivariate Poisson regression analysis was used to estimate the rate of plantar fasciitis per 1000 person-years, while controlling for sex, race, rank, service, and age. The overall unadjusted incidence rate of plantar fasciitis was 10.5 per 1000 person-years. Compared with men, women had a significantly increased adjusted incidence rate ratio for plantar fasciitis of 1.96 (95% confidence interval, 1.94 to 1.99). The adjusted incidence rate ratio for black service members compared with white service members was 1.12 (95% confidence interval, 1.09 to 1.12). With junior officers as the referent category, junior enlisted, senior enlisted, and senior officer rank groups had a significantly increased adjusted incidence rate ratio for plantar fasciitis: 1.20 (95% confidence interval, 1.18 to 1.23), 1.19 (95% confidence interval, 1.17 to 1.22), and 1.56 (95% confidence interval, 1.52 to 1.61), respectively. Compared with service members in the Air Force, those in the Army and Marines had a significantly increased adjusted incidence rate ratio for plantar fasciitis of 1.85 (95% confidence interval, 1.82 to 1.87) and 1.28 (95% confidence interval, 1.25 to 1.30), respectively. The adjusted incidence rate ratio for the age group of forty years old or more compared with the twenty to twenty-four-year-old group was 3.42 (95% confidence interval, 3.34 to 3.51). Female sex; black race; junior enlisted, senior enlisted, and senior officer rank groups; service in the Army or Marines; and increasing age are all risk factors for plantar fasciitis.


Turning virtual reality into reality: a checklist to ensure virtual reality studies of eating behavior and physical activity parallel the real world.
Virtual reality (VR) provides a potentially powerful tool for researchers seeking to investigate eating and physical activity. Some unique conditions are necessary to ensure that the psychological processes that influence real eating behavior also influence behavior in VR environments. Accounting for these conditions is critical if VR-assisted research is to accurately reflect real-world situations. The current work discusses key considerations VR researchers must take into account to ensure similar psychological functioning in virtual and actual reality and does so by focusing on the process of spontaneous mental simulation. Spontaneous mental simulation is prevalent under real-world conditions but may be absent under VR conditions, potentially leading to differences in judgment and behavior between virtual and actual reality. For simulation to occur, the virtual environment must be perceived as being available for action. A useful chart is supplied as a reference to help researchers to investigate eating and physical activity more effectively.


Transcranial sonography of the substantia nigra: digital image analysis.
Increased echogenicity of the substantia nigra is a typical transcranial sonography finding in Parkinson disease. Experimental software for digital analysis of the echogenic substantia nigra area has been developed. The aim of this study was to compare the evaluation of substantia nigra echogenicity by using digital analysis with a manual measurement in patients with Parkinson disease and healthy volunteers. One hundred thirteen healthy volunteers were enrolled in the derivation cohort, and 50 healthy volunteers and 30 patients with Parkinson disease, in the validation cohort. The substantia nigra was imaged from the right and left temporal bone window by using transcranial sonography. All subjects were examined twice by using different sonographic machines by an experienced sonographer. DICOM images of the substantia nigra were encoded; then, digital analysis and manual measurement of the substantia nigra were performed. The 90th percentile of the derivation cohort values was used as a cut-point for the evaluation of the hyperechogenic substantia nigra in the validation cohort. The Spearman coefficient was used for assessment of the correlation between both measurements. The Cohen κ coefficient was used for the assessment of the correlation between both measurements and Parkinson disease diagnosis. The Spearman coefficient between measurements by using different machines was 0.686 for digital analysis and 0.721 for manual measurement (P < .0001). Hyperechogenic substantia nigra was detected in the same 26 (86.7%) patients with Parkinson disease by using both measurements. Cohen κ coefficients for digital analysis and manual measurement were 0.787 and 0.762, respectively (P < .0001). The present study showed comparable results when measuring the substantia nigra features conventionally and by using the developed software.


Evidence for tissue-specific Jak/STAT target genes in Drosophila optic lobe development.
The evolutionarily conserved JAK/STAT pathway plays important roles in development and disease processes in humans. Although the signaling process has been well established, we know relatively little about what the relevant target genes are that mediate JAK/STAT activation during development. Here, we have used genome-wide microarrays to identify JAK/STAT targets in the optic lobes of the Drosophila brain and identified 47 genes that are positively regulated by JAK/STAT. About two-thirds of the genes encode proteins that have orthologs in humans. The STAT targets in the optic lobe appear to be different from the targets identified in other tissues, suggesting that JAK/STAT signaling may regulate different target genes in a tissue-specific manner. Functional analysis of Nop56, a cell-autonomous STAT target, revealed an essential role for this gene in the growth and proliferation of neuroepithelial stem cells in the optic lobe and an inhibitory role in lamina neurogenesis.


Developing control points for halal slaughtering of poultry.
Halal (permissible or lawful) poultry meat production must meet industry, economic, and production needs, and government health requirements without compromising the Islamic religious requirements derived from the Qur'an and the Hadiths (the actions and sayings of the Prophet Muhammad, peace and blessings be upon him). Halal certification authorities may vary in their interpretation of these teachings, which leads to differences in halal slaughter requirements. The current study proposes 6 control points (CP) for halal poultry meat production based on the most commonly used halal production systems. CP 1 describes what is allowed and prohibited, such as blood and animal manure, and feed ingredients for halal poultry meat production. CP 2 describes the requirements for humane handling during lairage. CP 3 describes different methods for immobilizing poultry, when immobilization is used, such as water bath stunning. CP 4 describes the importance of intention, details of the halal slaughter, and the equipment permitted. CP 5 and CP 6 describe the requirements after the neck cut has been made such as the time needed before the carcasses can enter the scalding tank, and the potential for meat adulteration with fecal residues and blood. It is important to note that the proposed halal CP program is presented as a starting point for any individual halal certifying body to improve its practices.


Alzheimer's disease and diabetes: new insights and unifying therapies.
Several research groups have begun to associate the Alzheimer Disease (AD) to Diabetes Mellitus (DM), obesity and cardiovascular disease. This relationship is so close that some authors have defined Alzheimer Disease as Type 3 Diabetes. Numerous studies have shown that people with type 2 diabetes have twice the incidence of sporadic AD. Insulin deficiency or insulin resistance facilitates cerebral β-amyloidogenesis in murine model of AD, accompanied by a significant elevation in APP (Amyloid Precursor Protein) and BACE1 (β-site APP Cleaving Enzime 1). Similarly, deposits of Aβ produce a loss of neuronal surface insulin receptors and directly interfere with the insulin signaling pathway. Furthermore, as it is well known, these disorders are both associated to an increased cardiovascular risk and an altered cholesterol metabolism, so we have analyzed several therapies which recently have been suggested as a remedy to treat together AD and DM. The aim of the present review is to better understand the strengths and drawbacks of these therapies.


Wegener granulomatosis: CT features of parenchymal lung disease.
Chest CT from eight patients with pulmonary Wegener granulomatosis were reviewed. The CT features of parenchymal lung involvement included multiple nodules or masses (seven of eight; 88%), ranging in size from 0.3 to 5.0 cm. Lung nodules demonstrated distinct feeding vessels in seven of eight patients (88%); and lesions similar to pulmonary infarcts, i.e., peripheral wedge-shaped lesions abutting the pleura, were identified in seven cases (88%). Scarring, spiculation, and pleural tags emanating from pulmonary nodules were prominent features (seven of eight; 88%). Other findings included cavitation (four of eight; 50%), air bronchograms through nodules (two of eight; 25%), and pleural effusions (two of eight; 25%). One patient on immunosuppressant therapy also demonstrated scattered ground glass infiltrates due to complicating pneumocystis pneumonia. In comparison to corresponding conventional chest radiography, CT examinations revealed more parenchymal lesions in five of eight cases (63%) and bilateral disease instead of unilateral disease in one of eight cases (13%). Feeding vessels were only identified on CT. Wegener granulomatosis is a primary necrotizing granulomatous vasculitis, and when it affects the lung it demonstrates CT features that are similar to other vessel-related disorders of the lung such as septic emboli, pulmonary infarcts, and tumor emboli of hematogenous metastases. We believe that these CT features--nodules with feeding vessels and wedge-shaped lesions abutting the pleura--are related to the necrotizing angiitis that affects pulmonary arteries and veins in this disease.


Retrospective study of the effect of intra-articular treatment of osteoarthritis of the distal tarsal joints in 51 horses.
Osteoarthritis of the distal tarsal joints, affecting the centrodistal and tarsometatarsal joints, is a common cause of hindlimb lameness in horses. This paper describes the outcome of the intra-articular treatment of 51 horses with the condition with either methylprednisolone acetate (mpa) or triamcinolone acetonide (tr), either with or without hyaluronic acid (ha). The outcome was assessed in terms of the changes in the horses' grade of lameness. Follow-up information was obtained from the owners by means of a telephone questionnaire. Horses treated once with mpa or tr, either with or without ha, improved after a median of 56 days (P<0.0001), and there was no significant difference between mpa and tr. There was no significant further improvement in the horses treated twice. In the horses in which there was a diffuse increase in the uptake of a radiopharmaceutical by the distal tarsal joints, identified by scintigraphy, the lameness tended to improve (P=0.032), whereas in the horses in which the uptake was focal, it did not. At telephone follow-up 13 of 34 horses were reported to have had a positive outcome, but the outcome in the other 21 was reported to have been negative.


Intramedullary lesion expansion on magnetic resonance imaging in patients with motor complete cervical spinal cord injury.
The authors performed a study to determine if lesion expansion occurs in humans during the early hours after spinal cord injury (SCI), as has been established in rodent models of SCI, and to identify factors that might predict lesion expansion. The authors studied 42 patients with acute cervical SCI and admission American Spinal Injury Association Impairment Scale Grades A (35 patients) and B (7 patients) in whom 2 consecutive MRI scans were obtained 3-134 hours after trauma. They recorded demographic data, clinical information, Injury Severity Score (ISS), admission MRI-documented spinal canal and cord characteristics, and management strategies. The characteristics of the cohort were as follows: male/female ratio 37:5; mean age, 34.6 years; and cause of injury, motor vehicle collision, falls, and sport injuries in 40 of 42 cases. The first MRI study was performed 6.8 ±2.7 hours (mean ± SD) after injury, and the second was performed 54.5 ± 32.3 hours after injury. The rostrocaudal intramedullary length of the lesion on the first MRI scan was 59.2 ± 16.1 mm, whereas its length on the second was 88.5 ± 31.9 mm. The principal factors associated with lesion length on the first MRI study were the time between injury and imaging (p = 0.05) and the time to decompression (p = 0.03). The lesion's rate of rostrocaudal intramedullary expansion in the interval between the first and second MRI was 0.9 ± 0.8 mm/hour. The principal factors associated with the rate of expansion were the maximum spinal cord compression (p = 0.03) and the mechanism of injury (p = 0.05). Spinal cord injury in humans is characterized by lesion expansion during the hours following trauma. Lesion expansion has a positive relationship with spinal cord compression and may be mitigated by early surgical decompression. Lesion expansion may be a novel surrogate measure by which to assess therapeutic effects in surgical or drug trials.


Determinants of adherence to physical cancer rehabilitation guidelines among cancer patients and cancer centers: a cross-sectional observational study.
To tailor implementation strategies that maximize adherence to physical cancer rehabilitation (PCR) guidelines, greater knowledge concerning determinants of adherence to those guidelines is needed. To this end, we assessed the determinants of adherence to PCR guidelines in the patient and cancer center. We investigated adherence variation of PCR guideline-based indicators regarding [1] screening with the Distress Thermometer (DT), [2] information provision concerning physical activity (PA) and physical cancer rehabilitation programs (PCRPs), [3] advice to take part in PA and PCRPs, [4] referral to PCRPs, [5] participation in PCRPs, and [6] PA uptake (PAU) in nine cancer centers. Furthermore, we assessed patient and cancer center characteristics as possible determinants of adherence. Regression analyses were used to determine associations between guideline adherence and patient and cancer center characteristics. In these analyses, we assumed the patient (level 1) nested within the cancer center (level 2). Nine hundred and ninety-nine patients diagnosed with cancer between January 2014 and June 2015 were included. Of the 999 patients included in the study, 468 (47%) received screening with the DT and 427 (44%) received information provision concerning PA and PCRPs. Subsequently, 550 (56%) patients were advised to take part in PA and PCRPs, which resulted in 174 (18%) official referrals. Ultimately, 280 (29%) patients participated in PCRPs, and 446 (45%) started PAU. Screening with the DT was significantly associated with information provision concerning PA and PCRPs (OR 1.99, 95% CI 1.47-2.71), advice to take part in PA and PCRPs (OR 1.79, 95% CI 1.31-2.45), referral to PCRPs (OR 1.81, 95% CI 1.18-2.78), participation in PCRPs (OR 2.04, 95% CI 1.43-2.91), and PAU (OR 1.69, 95% CI 1.25-2.29). Younger age, male gender, breast cancer as the tumor type, ≥2 cancer treatments, post-cancer treatment weight gain/loss, employment, and fatigue were determinants of guideline adherence. Less variation in scores of the indicators between the different cancer centers was found. This variation between centers was too low to detect any association between center characteristics with the indicators. The implementation of PCR guidelines is in need of improvement. We found determinants at the patient level associated with guideline-based PCR care. Implementation strategies that deal with the determinants of adherence to PCR guidelines might improve the implementation of PCR guidelines and the quality of life of cancer survivors.


Renal structural and functional changes and sodium balance in hypothyroid rats.
Significant retardation in body and kidney growth and in renal glomerular and proximal tubular development was observed in hypothyroid rats in comparison with euthyroid controls. Body mass was found to increase by 40% but kidney mass only by 3.5% over a period of 3 weeks following thyroidectomy in contrast to an average increment of 178 and 113%, respectively, in normal animals. Dissociation was found also in the development of glomeruli and proximal tubules: glomerular size correlated with body weight while tubular size with kidney weight. Single nephron glomerular filtration rate was adapted not to the glomerular as normally but rather to the tubular volume thereby compensating functionally for the dimensional glomerulotubular imbalance. However, despite the decreased filtered and excreted amount of sodium relative to the body weight sodium balance was maintained by depressed tubular reabsorption which was uniformly observed in thyroid deficiency. Because of the uncertainty regarding the direct action of thyroid hormones on the tubular function it is assumed that decreased tubular sodium reabsorption is principally caused by the mechanism subserving the maintenance of sodium balance also in salt loaded normal and sodium sensitive Dahl's rats. This seems to be supported by the exaggerated natriuresis observed both in hypothyroid and sodium sensitive Dahl's rats after saline infusion. Justification of the proposed mechanism needs further investigation.


[Diseases of the exocrine pancreas in infants and children. A review. 3. Pseudocysts, cysts, tumors: functional disorders of the exocrine pancreas secretion; pseudo-pancreatic insufficiency].
The aim of the present work is to provide a new classification of the exocrine pancreatic diseases in childhood by means of a simple and practicable scheme which is in line with the recognized classification of Internal Medicine. The article presents a definite distinction between organic diseases of the pancreas -- such as deformities, congenital insufficiences, pancreatitis, cysts and tumors -- functional disturbances of the pancreas secretion and pseudo-pancreas insufficiency caused by extrapancreatic factors. New investigative methods help to distinguish between various disorders encountered.


High pressure activation of the Mrr restriction endonuclease in Escherichia coli involves tetramer dissociation.
A sub-lethal hydrostatic pressure (HP) shock of ∼100 MPa elicits a RecA-dependent DNA damage (SOS) response in Escherichia coli K-12, despite the fact that pressure cannot compromise the covalent integrity of DNA. Prior screens for HP resistance identified Mrr (Methylated adenine Recognition and Restriction), a Type IV restriction endonuclease (REase), as instigator for this enigmatic HP-induced SOS response. Type IV REases tend to target modified DNA sites, and E. coli Mrr activity was previously shown to be elicited by expression of the foreign M.HhaII Type II methytransferase (MTase), as well. Here we measured the concentration and stoichiometry of a functional GFP-Mrr fusion protein using in vivo fluorescence fluctuation microscopy. Our results demonstrate that Mrr is a tetramer in unstressed cells, but shifts to a dimer after HP shock or co-expression with M.HhaII. Based on the differences in reversibility of tetramer dissociation observed for wild-type GFP-Mrr and a catalytic mutant upon HP shock compared to M.HhaII expression, we propose a model by which (i) HP triggers Mrr activity by directly pushing inactive Mrr tetramers to dissociate into active Mrr dimers, while (ii) M.HhaII triggers Mrr activity by creating high affinity target sites on the chromosome, which pull the equilibrium from inactive tetrameric Mrr toward active dimer.


Bcl-x protects primary B cells against Fas-mediated apoptosis.
Primary murine splenic B cells are rendered sensitive or resistant to Fas-mediated apoptosis in a receptor-specific fashion. B cells stimulated though CD40 are Fas sensitive unless they also receive a signal though surface Ig that produces a state of resistance to Fas killing. Protection from Fas-mediated apoptosis takes time to develop and requires ongoing macromolecular synthesis; therefore, it appears to involve the induction and accumulation of one or more gene products. The role of Bcl-x was evaluated by examining the expression and function of this gene in primary B cells. bcl-x mRNA was induced by anti-IgM treatment of otherwise sensitive (CD40 ligand-treated) B cells. Bcl-x protein expression was induced by anti-IgM and appeared in a time frame that correlates well with the onset of anti-IgM-induced Fas resistance. Further, B cells from Bcl-x Tg mice were found to be resistant to Fas-mediated apoptosis. These results strongly suggest that the protection against Fas killing afforded by cross-linking surface Ig is mediated, at least in part, by an increase in Bcl-x.


[Situational reactions in suicidologic practice].
The paper is devoted to the description of suicidal manifestations in mentally normal adolescents among typical behavioural disorders characteristic of situational reactions of this age. Three types of suicido-dangerous situational responses of adolescents were specified with regard to their age and auto-and heteaggressiveness ratio: reaction of deprivation, explosive reaction and reaction of auto-elimination. Suicidogenic conflicts were analyzed and spheres of age-specific suicidal conflicts were defined. It is advisable that outpatient management of mentally normal adolescents with a history of a suicidal attempt be conducted in a special room of presentive suicidological service.


Comparative genomic analysis of primary tumors and paired brain metastases in lung cancer patients by whole exome sequencing: a pilot study.
Lung cancer brain metastases (BMs) are frequent and associated with poor prognosis despite a better knowledge of lung cancer biology and the development of targeted therapies. The inconstant intracranial response to systemic treatments is partially due to tumor heterogeneity between the primary lung tumor (PLT) and BMs. There is therefore a need for a better understanding of lung cancer BMs biology to improve treatment strategies for these patients. We conducted a study of whole exome sequencing of paired BM and PLT samples. The number of somatic variants and chromosomal alterations was higher in BM samples. We identified recurrent mutations in BMs not found in PLT. Phylogenic trees and lollipop plots were designed to describe their functional impact. Among the 13 genes mutated in ≥ 1 BM, 7 were previously described to be associated with invasion process, including 3 with recurrent mutations in functional domains which may be future targets for therapy. We provide with some insights about the mechanisms leading to BMs. We found recurrent mutations in BM samples in 13 genes. Among these genes, 7 were previously described to be associated with cancer and 3 of them (CCDC178, RUNX1T1, MUC2) were described to be associated with the metastatic process.


The state of serum lipids profiles in sub-clinical hypothyroidism: a review of the literature.
Thyroid disorders usually associated with lipid abnormalities. Overt hypothyroidism is a state with thyroid hormone deficiency. Sub clinical hypothyroidism is defined as condition, in which thyroid stimulating hormone concentration elevated when serum thyroid hormones are at normal levels. Whether sub-clinical hypothyroidism associated with lipid alteration, it is the main concept behind this study. Although, in this study, we found cases with normal thyroxin and elevated thyroid stimulating hormone are common, but whether the sub-clinical hypothyroidism finally converted to overt hypothyroidism are not universally accepted. The findings also indicated subjects with sub-clinical hypothyroidism usually are accompanied with dyslipidemia and in general the total cholesterol level is higher among sub-clinical hypothyroid patients, with eventual risk of arthrosclerosis. This study indicated that there is not a common findings to support the benefit of thyroxin therapy in sub-clinical hypothyroidism. It is concluded that it seems sub-clinical hypothyroidism is a common thyroid abnormality which can be diagnosed by the medical diagnostic laboratory through thyroid function test and it is mainly accompanied with lipid disorder.


Arsenic speciation in rice-based food for adults with celiac disease.
Celiac disease (CD) may affect up to 1% of the Western population. It is a disease whose diagnosis has been made mainly in childhood, but now the profile has changed, with one out of five newly diagnosed individuals being over 65 years old. The only treatment for this population is a gluten-free diet. Therefore, the objective of this study was to analyse the occurrence of arsenic (As) in gluten-free products, basically those rice-based, intended for celiac adult consumers. The current study demonstrated that these rice-based products contained important contents of total arsenic (t-As) (up to 120 μg kg(-1)) and inorganic arsenic (i-As) (up to 85.8 μg kg(-1)). It was estimated that the contents of t-As and i-As in rice used as the main ingredient of these foods were as high as 235 and 198 μg kg(-1), respectively. The estimated daily intake of i-As was 0.46 and 0.45 μg kg(-1) bw in women and men of 58 and 75 kg of body weight (bw), respectively. These values indicate that a health risk to these consumers cannot be excluded. Finally, legislation is needed to delimit the safety intake by health agencies and to improve the labelling of these special rice-based foods for celiac adult consumers. The label should include information about percentage, geographical origin and cultivar of the rice used; besides and if companies want to clearly prove the safety of their products, the exact content of i-As should also be included.


ReGaGe2: an intermetallic compound with semiconducting properties and localized bonding.
ReGaGe2 is a new member of the family of intermetallic compounds with non-metallic properties. It displays highly localized covalent bonding patterns. Its electronic structure is governed by mixing of Re d orbitals with the s and p orbitals of Ga and Ge and features the Fermi level falling into the opened band gap, ensuring experimentally confirmed semiconducting properties.