Return of fertility after autologous stem cell transplantation.
To study cases where bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT)-induced menopause was entirely reversed. Retrospective analysis. An inpatient BMT unit and an ambulatory fertility center in a university hospital. Two patients with Hodgkin's disease and two with advanced breast carcinoma requiring stem cell transplantation. Estrogen treatment, monitoring of follicle-stimulating hormone (FSH) and estradiol (E(2)) levels, and, ultimately, monitoring of pregnancy. Pregnancy. All four patients established pregnancies, but two of them elected to terminate due to the use of tamoxifen early in pregnancy. Menopausal changes resulting from BMT may spontaneously reverse, with reestablishment of normal hormonal function and viable pregnancies.


[Lung transplantation in cystic fibrosis: perioperative mortality].
To determine the incidence and causes of perioperative mortality following lung transplant for cystic fibrosis. We analyzed the cases of 57 patients. Fifty-five patients received double lung transplants, 1 received a heart-double lung transplant, and 1 received a combined double lung and liver transplant. Information related to the organ donor, recipient, lung graft, and early postoperative period was gathered. Perioperative mortality was defined as death resulting from anesthesia or surgery regardless of how many days had passed. The Kaplan-Meier method was used to analyze survival. A Cox logistic regression model was used to determine variables affecting mortality. Survival was 83.7% at 1 year after transplantation, 77.3% at 2 years, and 66.9% at 5 years. Five (8.7%) patients died as a result of anesthesia or surgery. A ratio of PaO2 to inspired oxygen fraction (FiO2) less than 200 mm Hg in the early postoperative period was observed in 8 (14%) patients. Primary graft failure occurred in 4 patients, due to pneumonia in 2 and to biventricular dysfunction in 2. Three of those patients died. Two patients with PaO2/FiO2 greater than 200 mm Hg died after surgery, one from septic shock due to Pseudomonas cepacia and the other from massive cerebral infarction. PaO2/FiO2 upon admission to the recovery care unit was the only variable significantly associated with perioperative mortality in the logistic regression model (P=.0034). The only factor significantly related to perioperative mortality in patients receiving transplants for cystic fibrosis was PaO2/FiO2 upon admission to the recovery unit.


Low efficacy of three non-alcohol-based hand disinfectants utilizing silver polymer, lactic acid and benzalkonium chloride on inactivation of bacteria on the fingertips of healthcare workers.
Recently, new non-alcohol-based hand disinfection formulae have come to the market. Although they have passed the EN1500 test, data on their clinical efficacy compared with alcohol-based hand rubs are scarce, mainly covering benzalkonium chloride (BAC). To test the efficacy of silver-polymer-based, lactic-acid-based and BAC-based hand disinfectant foams and an alcohol-based hand rub gel to reduce bacterial counts on the fingertips of healthcare workers working on hospital wards. Each of the 84 participants tested one of the four products during their morning shift on a hospital ward using the 'fingertips on Petri dish' method before and after rubbing their hands with the product. After incubation, two independent readers assessed bacterial counts on the culture plates. The alcohol-based hand rub efficiently reduced bacteria on testers' fingertips in the test situation, whereas the lactic-acid- and BAC-based disinfectants did not have any detectable efficacy. The silver-polymer-based formula had some effect but requires further study. Non-alcohol-based hand rubs require careful consideration and further study before they can be accepted for clinical use.


An Interface for the Direct Coupling of Small Liquid Samples to AMS.
We describe the moving wire interface attached to the 1-MV AMS system at LLNL's Center for Accelerator Mass Spectrometry for the analysis of nonvolatile liquid samples as either discrete drops or from the direct output of biochemical separatory instrumentation, such as high-performance liquid chromatography. Discrete samples containing at least a few 10s of nanograms of carbon and as little as 50 zmol 14C can be measured with a 3-5% precision in a few minutes. The dynamic range of our system spans approximately 3 orders in magnitude. Sample to sample memory is minimized by the use of fresh targets for each discrete sample or by minimizing the amount of carbon present in a peak generated by an HPLC containing a significant amount of 14C. Liquid Sample AMS provides a new technology to expand our biomedical AMS program by enabling the capability to measure low-level biochemicals in extremely small samples that would otherwise be inaccessible.


Determination of perfluorocarboxylic acids by gas-liquid chromatography in rat tissues.
A method for the determination of tissue perfluorocarboxylic acids (PFCA) was developed using gas-liquid chromatography with an electron capture detector (ECD). Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were efficiently extracted from rat liver, methylated with diazomethane, and separated on GLC. Internal standards that were added to liver homogenates were used in the quantitative analysis of PFCAs to correct the loss during the extraction and derivatization. The concentration of PFDA in rat liver 24 h after intraperitoneal administration at a dose of 20 mg/kg body weight was 113.9 +/- 11.4 microg/g liver. The value corresponds to the previously reported results that were obtained using [14C]PFDA.


On deriving Murray's law from constrained minimization of flow resistance.
Murray's law, which states that the cube of the radius of a parent vessel equals the sum of the cubes of the radii of the daughter vessels, was originally derived by minimizing the cost of operation of blood flow in a single cylindrical tube. An alternative widely cited derivation by Sherman is based upon the optimization problem of minimizing the total flow resistance subject to a material constraint, and that study claimed that "Conservation of the sum of the cubes of the radii is the condition for minimal resistance whether the parent vessel divides symmetrically or asymmetrically, and whether it divides into two, three, four, or, presumably, any number of daughter vessels." In this paper we show that Sherman's analysis is flawed, since with N daughter vessels there are 2N-N-1 sets of vessel radii which satisfy Murray's law but which do not yield minimal total flow resistance. Moreover, we show that when there are N daughter vessels, each with the same radius, the minimal total flow resistance is an increasing function of N for N⩾1. Since N=1 corresponds to the degenerate case of no branching at all, our result implies that bifurcation (N=2) achieves the minimal total flow resistance. Our analysis thus offers an explanation for the preponderance of bifurcations (as opposed to trifurcations or higher level branchings) in many biological systems.


Reversible inhibitors of the gastric (H+/K+)-ATPase. 2. 1-Arylpyrrolo[3,2-c]quinolines: effect of the 4-substituent.
Further work on compounds 1 has identified the 4-position as a site where substantial modifications are tolerated, leading to analogues which are more potent and less toxic than those described previously. The best compound in the series is 13a (SK&F 96356), which is a potent inhibitor of gastric acid secretion in both the pentagastrin-stimulated rat and the histamine-stimulated dog. This compound shows reversible, K(+)-competitive binding to the enzyme. Because of its fluorescent properties, it is also proving useful in vitro as a probe of the structure and function of the (H+/K+)-ATPase.


Overweight and Obesity in a Sample of Children With Autism Spectrum Disorder.
To determine the prevalence of overweight/obese status in children with autism spectrum disorders (ASD), identify associated characteristics, and develop a model to predict weight status. The prevalence of overweight and obesity was determined in 2769 children with ASD enrolled in the Autism Speaks Autism Treatment Network, a collaboration of 17 academic centers, and compared with a national sample matched for age, sex, and race. Associations in the ASD sample between weight status and demographic and clinical variables, such as age, race, head circumference, and adaptive functioning, were tested using ordinal logistic regression. The accuracy of a final model that predicted weight status based on early life variables was evaluated in a validation sample. The prevalence of overweight and obesity were 33.9% and 18.2%, respectively; ASD was associated with a higher risk of obesity (but not overweight) relative to the national sample (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.05-1.28; P = .003). In the adjusted analysis, overweight/obese status was significantly associated with Hispanic ethnicity (OR, 1.99; 95% CI, 1.37-2.89), parental high school education (OR, 1.56; 95% CI, 1.09-2.21), high birth weight (OR, 1.56; 95% CI, 1.11-2.18), macrocephaly (OR, 4.01; 95% CI, 2.96-5.43), and increased somatic symptoms (OR, 1.41; 95% CI, 1.01-1.95). A prediction model designed to have high sensitivity predicted low risk of overweight/obesity accurately, but had low positive predictive value. The prevalence of obesity in children with ASD was greater than a national sample. Independent associations with increased weight status included known risk factors and macrocephaly and increased level of somatic symptoms. A model based on early life variables accurately predicted low risk of overweight/obesity.


Extended-FAST plus MDCT in pneumothorax diagnosis of major trauma: time to revisit ATLS imaging approach?
Pneumothorax (PNX) detection is of the utmost clinical relevance because it may quickly progress to cause hemodynamic instability as a consequence of invasive ventilation. Radiography is characterized by a low sensitivity to detect this disease; in recent years, chest ultrasound (US) has gained increased visibility in the diagnosis of acute respiratory emergencies including PNX. The aim of this retrospective study was to evaluate the clinical impact of extended focused assessment with sonography in trauma (E-FAST) during the past 6 years of experience with this technique in our Level I trauma center. Between January 2013 and December 2018, we performed a retrospective case-series study including 3320 consecutive patients admitted to the emergency department of our hospital because of major trauma. Extended-US was always performed and reported immediately after FAST during primary survey and before multidetector computed tomography (MDCT) scans. The presence of PNX was determined using the well-known accepted US criteria. US findings were compared with computed tomography (CT) findings, the reference standard for PNX detection. Of the 6640 lungs observed with E-FAST, there were 1244 PNX cases, while 1328 PNX cases were detected either on the basis of MDCT or on the basis of the presence of air flush during the thoracic decompression in the emergency room. Among the 84 false negatives, 12 patients had subcutaneous emphysema, 38 had a body mass index higher than 27, 6 had a thoracic wall hematoma, and 4 had chest penetrating trauma. There were 10 false positives in the diagnosis of PNX at US examination, with mild extension and not clinically significant. The overall sensitivity of E-FAST for PNX detection was 93.6% (1244/1328), the specificity of E-FAST was 99.8% (5312/5322), the negative predictive value (NPV) was 98.4% (5312/5396), and the positive predictive value (PPV) was 99.2% (1328/1338). Our results demonstrate that bedside thoracic US is characterized by a very good accuracy in the diagnostic work-up of major trauma patients, even in difficult conditions, allowing rapid diagnosis of PNX. The novelty of this research lies in the possibility of diagnosing potential life-threatening conditions in a very short time by means of US, thus proposing a revision of the Advanced Trauma Life Support (ATLS) guidelines in order to incorporate it in the work-up of high-energy injured patients.


A protein kinase CK2 site flanking the nuclear targeting signal enhances nuclear transport of human cytomegalovirus ppUL44.
The processivity factor of the human cytomegalovirus (HCMV) DNA polymerase phosphoprotein ppUL44 plays an essential role in viral replication, showing nuclear localization in infected cells. The present study examines ppUL44's nuclear import pathway for the first time, ectopic expression of ppUL44 revealing a strong nuclear localization in transfected COS-7 and other cell types, implying that no other HCMV proteins are required for nuclear transportation and retention. We show that of the two potential nuclear localization signals (NLSs) located at amino acids 162-168 (NLS1) and 425-431 (NLS2), NLS2 is necessary and sufficient to confer nuclear localization. Moreover, using enzyme-linked immunosorbent assays and gel mobility shift assays, we show that NLS2 is recognized with high affinity by the importin (IMP) alpha/beta heterodimer. Using gel mobility shift and transient transfection assays, we find that flanking sequences containing a cluster of potential phosphorylation sites, including a consensus site for protein kinase CK2 (CK2) at Ser413 upstream of the NLS, increase NLS2-dependent IMP binding and nuclear localization, suggesting a role for these sites in enhancing UL44 nuclear transport. Results from site-directed mutagenic analysis and live-cell imaging of green fluorescent protein (GFP)-UL44 fusion protein-expressing cells treated with the CK2-specific inhibitor 4,5,6,7-tetrabromobenzotriazole are consistent with phosphorylation of Ser413 enhancing ppUL44 nuclear transport.


Increase in ACC oxidase levels and activities during paradormancy release of leafy spurge (Euphorbia esula) buds.
The plant hormone ethylene is known to affect various developmental processes including dormancy and growth. Yet, little information is available about the role of ethylene during paradormancy release in underground adventitious buds of leafy spurge. In this study, we examined changes in ethylene evolution and the ethylene biosynthetic enzyme ACC oxidase following paradormancy release (growth induction). Our results did not show an obvious increase in ethylene during bud growth. However, when buds were incubated with 1 mM ACC, ethylene levels were higher in growing than non-growing buds, suggesting that the levels of ACC oxidase increased in growing buds. Real-time qPCR indicated that the transcript of a Euphorbia esula ACC oxidase (Ee-ACO) increased up to threefold following growth induction. In addition, a 2.5- to 4-fold increase in ACO activity was observed 4 days after decapitation, and the Ee-ACO accounted for 40 % of the total ACO activity. Immunoblot analyses identified a 36-kD Ee-ACO protein that increased in expression during bud growth. This protein was highly expressed in leaves, moderately expressed in crown buds, stems and meristems, and weakly expressed in roots and flowers. Immunolocalization of Ee-ACO on growing bud sections revealed strong labeling of the nucleus and cytoplasm in cells at the shoot apical meristem and leaf primordia. An exception to this pattern occurred in cells undergoing mitosis, where labeling of Ee-ACO was negligible. Taken together, our results indicated an increase in the levels of Ee-ACO during paradormancy release of leafy spurge that was not correlated with an increase in ethylene synthesis.


Infection reporting in patients undergoing irreversible electroporation of locally advanced pancreatic cancer.
Intraoperative bile cultures (IOBCs) taken during pancreatic surgery are commonly performed and there has been limited evidence that a positive IOBC could aid in perioperative adverse event (AE) management. Therefore, this study aims to describe infection management in patients undergoing irreversible electroporation (IRE). An Institutional Review Board (IRB)-approved prospective database was utilized from 8/2016 to 6/2022, with 127 pancreatic adenocarcinoma patients included. A total of 28 patients that underwent IRE also had a simultaneous positive IOBC and the remaining 99 patients that underwent IRE had negative IOBC. A total of 11(39%) of the patients with a positive IOBC had AE's, and 38 (38%) of the patients with negative IOBC had AE's. Both groups had similar rates of AEs leading to new hospitalization and prolonged hospitalizations. Overall, there was no correlation between a positive IOBC and a patient developing an AE. The findings of this study provide insights that improve the infectious management of patients undergoing IRE.


Spinocerebellar Ataxia 36 is a Frequent Cause of Hereditary Ataxia in Eastern Spain.
Autosomal dominant spinocerebellar ataxia 36 (SCA36) is caused by hexanucleotide repeat expansion in the NOP56 gene. To assess frequency, clinical and genetic features of SCA36 in Eastern Spain. NOP56 expansion was tested in a cohort of undiagnosed cerebellar ataxia families (n = 84). Clinical characterization and haplotype studies were performed. SCA36 was identified in 37 individuals from 16 unrelated families. It represented 5.4% of hereditary ataxia patients. The majority were originally from the same region and displayed a shared haplotype. Mean age at onset was 52.5 years. Non-ataxic features included: hypoacusis (67.9%), pyramidal signs (46.4%), lingual fasciculations/atrophy (25%), dystonia (17.8%), and parkinsonism with evidence of dopaminergic denervation (10.7%). SCA36 is a frequent cause of hereditary ataxia in Eastern Spain, and is associated with a strong founder effect. SCA36 analysis should be considered prior to other studies, especially in AD presentations. Parkinsonism reported here broadens SCA36 clinical spectrum.


A new ear oximeter for assessment of exercise-induced arterial desaturation in patients with pulmonary diseases.
Changes in arterial oxygen saturation during exercise were measured with a new eight-wavelength ear oximeter and calculated from blood gas measurements on simultaneously drawn arterial blood samples from 48 patients with pulmonary diseases. When the calculated oxygen saturation during exercise was more than 80% there change in oxygen saturation (SEE 1.0%). This non-invasive, simple and rapid method seems to be clinically useful for detecting the development of significant arterial hypoxaemia during exercise in patients with pulmonary diseases.


Impact of sex, age, body mass index and handedness on finger joint space width in patients with prolonged rheumatoid arthritis using computer-aided joint space analysis.
To evaluate the associations between sex, age, body mass index (BMI) and handedness regarding the radiogeometric detectable joint space distances of the finger articulations in patients suffering from a prolonged course of rheumatoid arthritis (RA). The joint space widths were measured by a new available Computer-aided joint space analysis (CAJSA); 128 patients with RA underwent computerized semi-automated joint space analysis of joint space distances at the metacarpal-phalangeal articulation (JSD-MCP II-V), proximal-interphalangeal joint (JSD-PIP II-V) and distal-interphalangeal joint (JSD-DIP II-V) based on digitally performed radiographs of the hand (Radiogrammetry Kit, Version 1.3.6; Sectra; Sweden). The joint space distance (JSD) of each articulation was expressed as JSD total in millimeter. The patient cohort was differentiated for gender, age, handedness and BMI (BMI < 20; BMI 20-25, BMI > 25). JSD revealed a significant age-related narrowing of 24.8% (JSD-MCP), 22.6% (JSD-PIP) and 28.7% (JSD-DIP) between the ages of 20 and 79. Additionally, males showed a significantly wider JSD compared to the female cohort for all age groups. All JSD-distances were varied between the right and left hand. The JSD-MCP demonstrated significant differences regarding the BMI groups. In contrast to JSD-MCP an effect of the BMI on measurements of JSD-PIP and JSD-DIP could not be observed. These influences must be differentiated from disease-related alterations caused by RA.


Mutations in Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands of Dendritic Growth and Synaptic Integrity.
Mutations in the Golgi SNARE (SNAP [soluble NSF attachment protein] receptor) protein Membrin (encoded by the GOSR2 gene) cause progressive myoclonus epilepsy (PME). Membrin is a ubiquitous and essential protein mediating ER-to-Golgi membrane fusion. Thus, it is unclear how mutations in Membrin result in a disorder restricted to the nervous system. Here, we use a multi-layered strategy to elucidate the consequences of Membrin mutations from protein to neuron. We show that the pathogenic mutations cause partial reductions in SNARE-mediated membrane fusion. Importantly, these alterations were sufficient to profoundly impair dendritic growth in Drosophila models of GOSR2-PME. Furthermore, we show that Membrin mutations cause fragmentation of the presynaptic cytoskeleton coupled with transsynaptic instability and hyperactive neurotransmission. Our study highlights how dendritic growth is vulnerable even to subtle secretory pathway deficits, uncovers a role for Membrin in synaptic function, and provides a comprehensive explanatory basis for genotype-phenotype relationships in GOSR2-PME.


[Docetaxel-based systemic chemotherapy in elderly Korean men with castration-resistant prostate cancer].
The aim of this study was to determine the efficacy and safety of docetaxel-based systemic chemotherapy in elderly patients with castration-resistant prostate cancer (CRPC). We retrospectively reviewed the clinical records of 36 patients with CRPC who were treated with docetaxel-based systemic chemotherapy at a single institution between May 2005 and April 2010. After screening, 30 patients met the eligibility criteria, and were included. Patients were placed into 2 groups: group 1 consisted of 9 patients aged <70 years, and group 2 consisted of 21 patients aged ≥70 years. The treatment consisted of prednisolone (5mg) twice daily and docetaxel (75 mg/m(2)) once every 3 weeks. The median age was 72 years, and the median performance status was 0. The median baseline prostate specific antigen (PSA) was 33.8 ng/mL. The mean number of docetaxel chemotherapy cycles was 5.8. The PSA response rate was 48.2%, and the measurable disease response rate was 15.0%, and these rates did not differ between the two groups. The median time to PSA progression and median overall survival were 6 and 9 months, respectively. Five patients experienced grade 3 or higher neutropenia. The drug-related toxicity was not different between the two groups. The response of elderly CRPC patients with good performance status to docetaxel-based systemic chemotherapy was similar to that of younger patients. Docetaxel-based systemic chemotherapy is generally tolerated in elderly patients with good performance status.


Food allergy is associated with recurrent respiratory tract infections during childhood.
To find out whether children with food allergy have an increased risk of recurrent upper and lower respiratory tract infections and of asthma. To describe the clinical profile of children diagnosed with food allergy referred to the Allergy Clinic. We conducted a retrospective study to assess the patients' demographic, anthropometric and clinical data. The analysis included data of all children by the age of 10 years (registered with the Allergy Clinic between 2012 and 2013) in whom IgE mediated food allergy had been diagnosed during 18 months of observation. We included 280 children into the analysis. Recurrent respiratory tract infections (rRTI), asthma and gastrointestinal (GI) symptoms were observed in 153 (54.6%), 96 (34.3%), 39 (13.9%), respectively, with a significant increasing trend across age-subgroups. In children from 1 to 2 years old, sensitization to β-lactoglobulin increased the risk of rRTI (OR = 3.91; 95% CI: 1.03-14.87). In older children sensitization to allergens other than milk or egg decreases the risk of rRTI (OR = 0.25; 95% CI: 0.10-0.62); sensitization to egg decreased the risk of asthma diagnosis (OR = 0.09; 95% CI: 0.01-0.75). We did not identify food allergens which change the risk of GI symptoms in children. This finding was consistent throughout all age-subgroups. Sensitization to β-lactoglobulin increased the risk of rRTI in children under 2 years of age nearly four times. The presence of sensitization to food allergens above 3 years of age did not increase the risk of developing clinical presentation of food allergy other than atopic dermatitis.


Increased prevalence of metabolic syndrome in patients with bipolar disorder compared to a selected control group-a Northern Netherlands LifeLines population cohort study.
Metabolic syndrome (MetS) is highly prevalent among patients with bipolar disorder (BD). The aims of this cross-sectional study were to determine the prevalence of MetS in Dutch BD subjects and compare it with a control group, to examine the association of demographic and clinical characteristics with MetS in BD, and to determine the extent to which metabolic dysregulation is treated in those patients. 493 Dutch adult patients (≥ 18 years) with BD receiving psychotropic drugs and 493 matched control subjects were compared using data from the biobank Lifelines. We determined MetS according to the National Cholesterol Education Program Adult Treatment Panel III-Adapted (NCEP ATP III-A) criteria. The difference in the prevalence of MetS and the associations with characteristics were analyzed with logistic regression. BD subjects (30.6%) showed a significantly higher prevalence of MetS compared to the control group (14.2%) (p < .001, OR:2.67, 95% CI:1.94-3.66). Univariate analysis showed that smoking, body mass index (BMI) and antidepressant drug use were associated with MetS. Multivariate analysis showed that smoking (OR:2.01) was independently associated with MetS in BD. For hypertension, hyperglycemia and lipid disorder pharmacological treatment was provided to respectively 69.5%, 24% and 18.4% of the BD subjects in our sample. Duration of illness of BD subjects was unknown. This study demonstrated a higher prevalence of MetS in Dutch BD subjects compared to persons without BD. In addition, a remarkable undertreatment of some of the components of MetS was found.


Effects of novelty and pain on behavior and hippocampal extracellular ACh levels in male and female rats.
In vivo microdialysis was used to assess the effects of novelty and pain on hippocampal ACh release in male and female rats. Experiments were carried out during the dark phase and consisted of 2 days of tests: on Day 1, after Baseline 1, animals were exposed to a new cage (Novelty) to which, 30 min later, a plastic cylinder (Object) was introduced. On Day 2, after Baseline 2, the Formalin test (50 microl of formalin 10%, s.c. injected in the dorsal hindpaw) was carried out in the animal's home cage. All behaviors were recorded. The extracellular levels of ACh in the dorsal hippocampus were estimated, in 10-min samples, by assay of ACh in the dialysates by HPLC. On Day 1 the raw values of ACh were higher in females than in males, but no sex difference was present when the percentage of change was considered. In both sexes the Novelty and Object tests induced an increase in ACh levels with respect to Baseline. Higher levels of exploration were present in females than males during the first 10 min of Novelty. On Day 2, ACh release increased in both sexes during the Formalin test. No sex difference in either ACh raw values or the percentages of change were found. Females showed higher levels of licking and lower levels of activity than males. The present study shows that novelty and pain induce similar hippocampal cholinergic activation in male and female rats but different behaviors. The results are discussed in light of the several anatomical and functional sex differences present in the hippocampus.


The dispersal of Culicoides mississippiensis (Diptera: Ceratopogonidae) in a salt marsh near Yankeetown, Florida.
Of the estimated 40,000 Culicoides mississipiensis adults released, 567 (approximately 1.5%) were recovered over two, 4-day periods. Individuals traveled a mean distance of 2 km following the first release and 2.2 km after the second release. Their movement did not appear to be aided by wind. One specimen was recovered 3.2 km from the release point in 24-h.


Relation of glomerular filtration to insulin resistance and related risk factors in obese children.
Childhood obesity is associated with later development of significant renal morbidity. We evaluated the impact of the degree of insulin sensitivity on estimated glomerular filtration rate (eGFR) and determined the factors associated with eGFR in obese children. We further tested the relation of eGFR to clinical outcomes such as blood pressure and microalbuminuria. We evaluated the relation of whole body insulin sensitivity and estimated glomerular filtration rate (eGFR) across the spectrum of obesity in children and adolescents. eGFR was calculated using the iCARE formula, which has been validated in obese children with varying glucose tolerance. 1080 children and adolescents with overweight and obesity (701 females and 379 males) participated. Insulin sensitivity was a strongly negatively associated with (B = -2.72, p < 0.001) eGFR), even after adjustment for potential confounders. Male sex emerged to be significantly associated with eGFR with boys having greater values than girls (B = 18.82, p < 0.001). Age was a positively associated (B = 2.86, p < 0.001) with eGFR. Whole body and hepatic insulin sensitivity decreased across eGFR quartiles. Adjusted eGFR was tightly positively associated with systolic blood pressure (B = 0.09, p = 0.003) and negatively associated with the presence of microalbuminuria (B = -2.18, p = 0.04). eGFR tends to increase with greater degrees of insulin resistance in children and adolescents representing hyperfiltration and is associated with cardiovascular risk factors. Longitudinal studies are needed to determine the natural history of childhood insulin resistance related hyperfiltration in regards to future kidney disease.


In vitro translation of RNA from the German cockroach Blattella germanica.
The translation of mRNA within total RNA of German (Blattella germanica) cockroaches was performed using a rabbit reticulocyte lysate system. Analysis of the translation products by SDS-PAGE and combined autoradiography revealed several synthesized proteins with apparent molecular weights ranging from 20 kD to 110 kD. SDS-PAGE/Western blotting of non-radiolabeled translation products and incubation with human serum with IgE to cockroach allergens showed the presence of a 36 kD and 50 kD allergen. The confirmation of the translation of the cockroach allergens from total RNA is an important first step in the cloning of cockroach allergens.


Evaluation of a method to re-use electropositive cartridge filters for concentrating viruses from tap and river water.
Electropositively charged filters are frequently used for concentrating enteric viruses from large volumes of water. A major disadvantage to the use of these filters, however, is that they are not cost-effective. At US$ 150-180 per filter, routine viral monitoring of water is cost-prohibitive. This study describes the development of a method which allows a filter to be used up to three times, achieving comparable recoveries to new filters. Zetapor 1MDS and N66 Posidyne electropositive filters were tested. The method was analyzed using tap water and Ohio River water that was spiked with poliovirus. Tap water recoveries averaged 32% for new filters, 30% for filters used twice, and 38% for filters used three times. River water recoveries averaged 68% for new filters, 83% for filters used twice, and 100% for filters used three times. RT-PCR and dot-blot hybridization were performed on sample concentrates to ensure that all viral nucleic acid from the previous test had been removed from the filters by the treatment process.


Temporal modulation of sodium current kinetics in neuron cells by near-infrared laser.
Near-infrared laser provides a novel nerve stimulation modality to regulate the cell functions. Understanding its physiological effect is a prerequisite for clinic laser therapy applications. Here, the whole-cell sodium (Na) channel kinetics of neuron cell was employed to determine the temporal roles of infrared laser. The Na currents were elicited by electrical pulses that were synchronized at the rising and falling edges of the 980 nm laser pulses, respectively, to investigate the different infrared effect on cell functions. The time constants of activation (τ(m)) and inactivation (τ(h)) kinetics were extracted from fitting of the Na current (m(3)h) according to the Hodgkin-Huxley (HH) model. By comparing the time constants without and with the laser irradiation, we obtained that laser pulses changed the Na current kinetics by accelerating τ(h)-phase and slowing down τ m-phase at the beginning of the laser pulse, whereas both phases were accelerated at the end of the pulse. After relating the ratios of the time constants to the temperature characteristics of Na channel by Q10, we found that the accelerating in Na current kinetics could be related to the average temperature of extracellular solution in the corresponding time span by choosing Q10 = 2.6. The results of this study demonstrated that there was a positive correlation between the acceleration of the Na current kinetics and increases in temperature of the extracellular solution.


Computing the Pathogenicity of Wilson's Disease ATP7B Mutations: Implications for Disease Prevalence.
Genetic variations in the gene encoding the copper-transport protein ATP7B are the primary cause of Wilson's disease. Controversially, clinical prevalence seems much smaller than the prevalence estimated by genetic screening tools, causing fear that many people are undiagnosed, although early diagnosis and treatment is essential. To address this issue, we benchmarked 16 state-of-the-art computational disease-prediction methods against established data of missense ATP7B mutations. Our results show that the quality of the methods varies widely. We show the importance of optimizing the threshold of the methods used to distinguish pathogenic from nonpathogenic mutations against data of clinically confirmed pathogenic and nonpathogenic mutations. We find that most methods use thresholds that predict too many ATP7B mutations to be pathogenic. Thus, our findings explain the current controversy on Wilson's disease prevalence because meta-analysis and text search methods include many computational estimates that lead to higher disease prevalence than clinically observed. As proteins and diseases differ widely, a one-size-fits-all threshold cannot distinguish pathogenic and nonpathogenic mutations efficiently, as shown here. We also show that amino acid changes with small evolutionary substitution probability, mainly due to amino acid volume, are more associated with the disease, implying a pathological effect on the conformational state of the protein, which could affect copper transport or adenosine triphosphate recognition and hydrolysis. These findings may be a first step toward a more quantitative genotype-phenotype relationship of Wilson's disease.


Study of in vitro effects of hydralazine metabolites--comparative evaluation of products of hydroxylation, hydrolysis and conjugation.
K+ contractures were induced in paired strips of rabbit aortic smooth muscle. The relationship between relaxant effects and the bath concentration of hydralazine acetone hydrazone (HA), 4-OH-hydralazine (HH) and phthalazine (P) was studied over the concentration range 10(-5)-10(-3)M. All compounds were active, HA = HH greater than P (p less than 0.05; n = 6) at concentrations in the range 10(-4)-10(-3M, HA greater than HH at a concentration of 10(-3M (pgreater than 0.01). The activity of HA did not depend on significant reconversion to hydralazine (H) in the bath ( less than 0.5%). A range of H derivatives may contribute to the hypotensive effects of administered H.


[Pulmonary textiloma revealed by hemoptysis 12 years after thoracotomy].
Pulmonary textiloma or retained surgical sponge is rare but can have detrimental consequences. Its diagnosis is difficult, even when using computerized tomography (CT) scan and is always a medical and legal problem. We report the case of a 46-year-old man with a history of pulmonary tuberculosis diagnosed by thoracotomy in 1986, who was admitted to hospital for hemoptysis. CT scan showed the existence of a pulmonary lesion. Clinical, radiological and fiberoptic endoscopy features mimicked an abscess or bronchiectasis. The patient underwent left inferior lobectomy. Anatomical findings led to the diagnosis of textiloma. This case shows the difficult in diagnosing pulmonary textiloma, even when using CT scan. Textiloma should be considered when an atypical pulmonary mass is found in a patient with past history of thoracotomy.


Unforeseen Computed Tomography Resimulation for Initial Radiation Planning: Associated Factors and Clinical Impact.
Repeat computed tomography (CT) simulation is problematic because of additional expense of clinic resources, patient inconvenience, additional radiation exposure, and treatment delay. We investigated the factors and clinical impact of unplanned CT resimulations in our network. We used the billing records of 18,170 patients treated at 5 clinics. A total of 213 patients were resimulated before their first treatment. The disease site, location, use of 4-dimensional CT (4DCT), contrast, image fusion, and cause for resimulation were recorded. Odds ratios determined statistical significance. Our total rate of resimulation was 1.2%. Anal/colorectal (P < .001) and head and neck (P < .001) disease sites had higher rates of resimulation. Brain (P = .001) and lung/thorax (P = .008) had lower rates of resimulation. The most common causes for resimulation were setup change (11.7%), change in patient anatomy (9.8%), and rectal filling (8.5%). The resimulation rate for 4DCTs was 3.03% compared with 1.0% for non-4DCTs (P < .001). Median time between simulations was 7 days. The most common sites for resimulation were anal/colorectal and head and neck, largely because of change in setup or changes in anatomy. The 4DCT technique correlated with higher resimulation rates. The resimulation rate was 1.2%, and median treatment delay was 7 days. Further studies are warranted to limit the rate of resimulation.


Collagen-producing mesothelial cells in adriamycin-induced pleuritis in rat. Microautoradiographic study utilizing tritiated proline.
By the microautoradiographic method using 3H-proline, collagen production by mesothelial cells was investigated in adriamycin-induced pleuritis in rats. In subpleural granulation tissue formed at 4 to 7 days after the intrapleural injection of adriamycin, proliferating fibroblasts and primitive mesenchymal cells were most intensely labeled, and abundant deposition of collagen and acid mucopolysaccharides were demonstrated about these cells. It is thus concluded that these subpleural mesenchymal cells are mainly responsible for the fibrosing process. Labeling was also observed in some reactive mesothelial cells and macrophages free-floating in the pleural exudate. Several ultrastructural differences between labeled mesothelial cells floating in the fluid and lining the pleural surface were confirmed, suggesting a change in ability to synthesize collagen during mesothelial desquamation. It seems likely that these labeled mononuclear cells in the effusion, attached to the pleural wound surface, support fibrosis performed by underlying collagen-synthesizing mesenchymal cells. Pleural fibrosis disappeared by 10 days, when mesothelial regeneration was almost complete. Probably this change may be due to fibrinolytic activity caused by regenerative mesothelial cells derived from subpleural mesenchymal cells.


The Mechanisms of Regulation of Aerobic Glycolysis (Warburg Effect) by Oncoproteins in Carcinogenesis.
According to modern concepts, tumor formation is associated with impairments in the structure of protooncogenes and/or deactivation of suppressor genes, regardless of the nature of carcinogenic factor. As a consequence, unregulated oncoproteins activate extracellular proteases, resulting in the destruction of the extracellular matrix, which facilitates cell invasion, deterioration of the cell-cell contacts, and metastasis. Tumor development requires activation of certain transcription factors; however, many oncoproteins are not transcription factors. It can be assumed that these oncoproteins are not the ultimate effectors of tumor development, but rather transmitters of the carcinogenic signal to the transcription factors promoting tumorigenesis. Here, we describe the mechanisms of carcinogenesis caused by various oncogenes/oncoproteins. We conclude that the common feature of these mechanisms is stimulation of aerobic glycolysis (Warburg effect) regulated, as a rule, through the activation of the HIFα transcription factor. The role of aerobic glycolysis at the early stages of carcinogenesis is discussed.


Exercise performance and quality of life in children with cystic fibrosis and mildly impaired lung function: relation with antibiotic treatments and hospitalization.
This study evaluates the impact of antibiotic treatments and hospitalization on exercise performance and health-related quality of life (QOL) in children with mild cystic fibrosis (CF) lung disease. Forty-seven children between 7 and 17 years with mild CF underwent a maximal exercise test including spiro-ergometry and filled out a QOL-questionnaire (PedsQL™). Amount of antibiotic treatments (AB) and hospitalization days in the last 3 years were reviewed. FEV1% was mildly decreased (91.7 ± 17.9 L/min, p = 0.02). Maximal oxygen consumption (VO2max), test duration and anaerobic threshold were lower compared to a control population (VO2max% 94 ± 15 vs 103 ± 13, p = 0.009). FEV1% correlated with AB and hospitalization episodes in the last year and 3 years before testing, VO2max% only correlated with AB in the last 3 years. Domains of school functioning and emotional functioning were low. Children with higher VO2max% and less AB in the last 3 years had better physical health. Physical health and school functioning were negatively correlated with hospitalization days in the last year. Patients with mild CF lung disease have good exercise performance although still lower than the normal population. VO2max% is affected by number of antibiotic treatments over a longer period. There is an impact of hospitalization days on quality of life. What is Known: • Children with CF have lower exercise performance; there is an association between hospitalization frequency and exercise performance • Quality of life is diminished in children with CF and influenced by respiratory infections What is New: • Even patients with mild CF lung disease have lower maximal exercise performance (VO 2 max) and a lower anaerobic threshold; VO 2 max is lower in children who had more antibiotic treatments in the last 3 years • School and emotional functioning are diminished in children with mild CF lung disease; hospitalization is negatively correlated with school functioning and physical functioning.


AnnexinA7 promotes epithelial-mesenchymal transition by interacting with Sorcin and contributes to aggressiveness in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and metastasis is the major cause of the high mortality of HCC. In this study, we identified that AnnexinA7 (ANXA7) and Sorcin (SRI) are overexpressed and interacting proteins in HCC tissues and cells. In vitro functional investigations revealed that the interaction between ANXA7 and SRI regulated epithelial-mesenchymal transition (EMT), and then affected migration, invasion, and proliferation in HCC cells. Furthermore overexpression/knockdown of ANXA7 was remarkably effective in promoting/inhibiting tumorigenicity and EMT in vivo. Altogether, our study unveiled a mechanism that ANXA7 promotes EMT by interacting with SRI and further contributes to the aggressiveness in HCC, which provides a novel potential therapeutic target for preventing recurrence and metastasis in HCC.


In-vitro evaluation of commonly used beverages on tensile strength of different suture materials used in dental surgeries.
Sutures are used for the approximation of incised flaps, assistance in primary healing, and hemorrhage control. In oral and periodontal surgery, the appropriate selection of suture material is vital for favorable healing.The aim of the present in-vitro experiment was to evaluate the tensile strengths of 4 different types of suture materials (silk, polygalactine 910, polypropylene, chromic catgut) by simulating potential short-term intraoral exposure to various beverages (saliva, Arabic coffee, tea, cola).A total of 280 suture specimens were prepared, out of which 10 specimens from each group were selected for pre-immersion testing. Remaining suture specimens were immersed in 4 different thermostatically controlled media (1 control [artificial saliva], 3 tests [Cola drink, Arabic coffee, Tea]). Tensile strength was measured at pre-immersion, 3, 7, and 14 days using a universal tensile testing machine. The maximum load required to break the suture material was recorded in Newton.At day 3, tea caused significant reduction in tensile strength of silk and cola caused significant reduction in tensile strengths of polygalactine 910 and chromic catgut. Whereas, at day 7, silk and polypropylene retained their tensile strengths better than others.The authors recommend precaution in the use of these beverages in the first postoperative week, to avoid adverse effect on the mechanical strength of sutures. When exposure to these beverages are anticipated, it is better to use polypropylene sutures that resists rapid fall in tensile strengths in the early postoperative period.


Isolation of murine embryonic stem and embryonic germ cells by selective ablation.
The isolation of murine embryonic stem (ES) cells has been almost exclusively from the 129 mouse strain. Other mouse strains, such as CBA, have proven refractory to ES cell isolation by conventional means. We previously reported the isolation of 87.5% CBA ES lines by selective ablation of differentiating cells (McWhir et al., 1996). Here, we report the isolation of ES and EG cells from 94% CBA embryos hemizygous and homozygous for a neomycin-resistance transgene under the transcriptional control of the Oct3/4 promoter (Oct/neo). Since expression of the Oct/neo transgene only confers drug resistance to undifferentiated cells of the inner cell mass, selection results in the ablation of differentiating cells from the culture. The efficiency of ES isolation by selective ablation in homozygotes is twice that in heterozygotes. ES isolation frequency in permissive strain 129 embryos is enhanced by treatment with an inhibitor of the extracellular-signal-regulated kinase (ERK) pathway but this effect is not sufficient to permit ES isolation from the CBA strain.


Diarrhea and associated factors among under-5 children in Ethiopia: A secondary data analysis.
Diarrhea is a major contributing factor for preventable childhood morbidity and death. Despite the occurrence of diarrhea is decreasing, its effect is increasing at an alarming rate among under-5 children particularly in developing countries. The survey was aimed to assess diarrhea and associated factors among children less than 5 years (0-59 months) in Ethiopia with nationally representative data. The data were extracted from the Ethiopian National Survey of 2016. A logistic regression model was undertaken to identify the contributing factors for childhood diarrhea. Variables with p < 0.05 were considered as independent predictors of childhood diarrhea. From a total of 10,641 under-5 children, 5483(51.5%) were males and most of the children (62.3%) were above 24 months. About 10.2% had diarrhea 14 days before data collection, and the majority (93.1%) were born to married mothers. Receiving no treatment or advice for fever/cough (adjusted odd ratio (AOR) = 0.170, 95% confidence interval (CI): 0.139-0.208, p = 0.001), being permanent residence (AOR = 0.583, 95% CI: 0.347-0.982, p = 0.043), initiating breastfeeding after 24 h of birth (AOR = 1.553, 95% CI: 1.197-2.015, p = 0.001), and lack of prenatal care (AOR = 2.142, 95% CI: 0.624-0.875, p = 0.001) were independent predictors of diarrhea among under-5 children's in Ethiopia. The result of this survey indicated that diarrhea is a significant health challenge among under-5 children. To tackle this illness, sufficient education on child and maternal health has to be provided for mothers focusing on predictive factors.


Efficacy and safety of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of esophageal squamous cell cancer: A prospective, open label, randomized phase II study.
Esophageal squamous cell cancer (ESCC) accounts for approximately 90% of esophageal cancer cases in China. There are no standard regimens for second or third-line chemotherapy of metastatic squamous esophageal cancer. The objective of this study was to investigate the security and effectiveness of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of ESCC. One hundred and twenty-eight patients with metastatic ESCC confirmed by histopathology were enrolled into this study. These patients had failure of the first-line chemotherapy combination of fluorouracil or platinum or paclitaxel and had not undergone chemotherapy with irinotecan or raltitrexed previously. Patients were randomly divided into irinotecan combined with raltitrexed group (experiment group) and irinotecan monotherapy group (control group). Overall survival (OS) and progression-free survival (PFS) were the primary endpoint. In the control group, the median PFS (mPFS) and median OS (mOS) of patients were 3.37 and 5.3 months. In the experiment group, mPFS and mOS were 3.91 and 7.0 months. There was statistical significance of PFS and OS between two groups (PFS P = 0.002, OS P = 0.01). In subgroup analysis, in the second-line treatment, the mPFS of control and experiment group, was 3.90 and 4.60 months, mOS was 6.95 and 8.5 months, which was statistically significant differences between the two groups. (PFS P = 0.001, OS P = 0.005), In the third-line and beyond treatment, mPFS of control and experiment group was 2.80 and 3.19 months, mOS were 4.5 and 4.8 months. But there was no significant difference of PFS or OS between the two groups (PFS P = 0.19, OS P = 0.31). There was no statistical significance of toxicity side effects between two groups. The PFS and OS of irinotecan plus raltitrexed may be better than that of irinotecan monotherapy, especially in second line treatment, which should be confirmed with a phase III study including much more patients.


Stroking me softly: Body-related effects in effect-based action control.
Empirical investigations of ideomotor effect anticipations have mainly focused on action effects in the environment. By contrast, action effects that apply to the agent's body have rarely been put to the test in corresponding experimental paradigms. We present a series of experiments using the response-effect compatibility paradigm, in which we studied the impacts of to-be-produced tactile action effects on action selection, initiation, and execution. The results showed a robust and reliable impact if these tactile action effects were rendered task-relevant (Exp. 1), but not when they were task-irrelevant (Exps. 2a and 2b). We further showed that anticipations of tactile action effects follow the same time course as anticipations of environment-related effects (Exps. 3 and 4). These findings demonstrate that body-related action effects affect action control much as environment-related effects do, and therefore support the theoretical assumption of the functional equivalence of all types of action effects.


A contemporary prospective review of 205 consecutive patients with penetrating colon injuries.
Management of colon injuries has significantly evolved in the recent decades resulting in considerably decreased morbidity and mortality. We set out to investigate penetrating colon injuries in a high-volume urban academic trauma center in South Africa. All patients with penetrating colon injuries admitted between 1/2015 and 1/2018 were prospectively enrolled. Data collection included demographics, injury profile and outcomes. Primary outcome was in-hospital mortality. Secondary outcome was morbidity. Two-hundred and five patients were included in the analysis. Stab and gunshot wounds constituted 18% and 82% of the cases, respectively. Mean age was 28.9 (10.2) years and 96.1% were male. Median injury severity score (ISS) and penetrating abdominal trauma index (PATI) were 16 (9-25) and 19 (10-26), respectively. A total of 47.8% of the patients had a complication per Clavien-Dindo classification. Colon leak rate was 2.4%. Wound and abdominal organ/space infection rate was 15.1 and 6.3%, respectively. Overall in-hospital mortality was 9.3%. Risk factors for mortality were higher ISS and PATI, shock on admission, need for blood transfusion, intra-abdominal vascular injury, damage control surgery, and extra-abdominal severe injuries. Contemporary overall complication rate remains high in penetrating colon injuries, however, anastomotic leak rate is decreasing. Colon injury associated mortality is related to overall injury burden and hemorrhage rather than to colon injuries.


Liposome-entrapped GABA modifies behavioral and electrographic changes of penicillin-induced epileptic activity.
We studied Sprague-Dawley rats with spike activity and myoclonus after intraperitoneal injections of penicillin. Twenty minutes after penicillin injection, one group received a random crossover treatment by intraperitoneal GABA (gamma-aminobutyric acid) or liposome-entrapped GABA (LEG) or phosphatidylserine alone. The other group received GABA, LEG, or phosphatidylserine followed 15 minutes later by the injection of penicillin. LEG decreased or prevented the epileptic activity, whereas no significant changes were seen with either GABA or phosphatidylserine given alone. LEG may enhance penetration of GABA across the blood-brain barrier because of the carrier action of the liposomes.


Refractory psychotic symptoms in a patient with homozygous sickle cell disease: a 24-month follow-up.
The present report describes a case of a 33-year old male patient with homozygous sickle cell disease (SCD) with comorbid psychotic symptoms. The systematical evaluation revealed an intimate association between acute SCD complications, associated with hematological abnormalities, and psychotic symptoms worsening. Clozapine was effective in controlling psychotic symptoms refractory to previous antipsychotic trials.


Tailed bacteriophages: the order caudovirales.
Tailed bacteriophages have a common origin and constitute an order with three families, named Caudovirales. Their structured tail is unique. Tailed phages share a series of high-level taxonomic properties and show many facultative features that are unique or rare in viruses, for example, tail appendages and unusual bases. They share with other viruses, especially herpesviruses, elements of morphogenesis and life-style that are attributed to convergent evolution. Tailed phages present three types of lysogeny, exemplified by phages lambda, Mu, and P1. Lysogeny appears as a secondary property acquired by horizontal gene transfer. Amino acid sequence alignments (notably of DNA polymerases, integrases, and peptidoglycan hydrolases) indicate frequent events of horizontal gene transfer in tailed phages. Common capsid and tail proteins have not been detected. Tailed phages possibly evolved from small protein shells with a few genes sufficient for some basal level of productive infection. This early stage can no longer be traced. At one point, this precursor phage became perfected. Some of its features were perfect enough to be transmitted until today. It is tempting to list major present-day properties of tailed phages in the past tense to construct a tentative history of these viruses: 1. Tailed phages originated in the early Precambrian, long before eukaryotes and their viruses. 2. The ur-tailed phage, already a quite evolved virus, had an icosahedral head of about 60 nm in diameter and a long non-contractile tail with sixfold symmetry. The capsid contained a single molecule of dsDNA of about 50 kb, and the tail was probably provided with a fixation apparatus. Head and tail were held together by a connector. a. The particle contained no lipids, was heavier than most viruses to come, and had a high DNA content proportional to its capsid size (about 50%). b. Most of its DNA coded for structural proteins. Morphopoietic genes clustered at one end of the genome, with head genes preceding tail genes. Lytic enzymes were probably coded for. A part of the phage genome was nonessential and possibly bacterial. Were tailed phages general transductants since the beginning? 3. The virus infected its host from the outside, injecting its DNA. Replication involved transcription in several waves and formation of DNA concatemers. Novel phages were released by burst of the infected cell after lysis of host membranes by a peptidoglycan hydrolase (and a holin?). a. Capsids were assembled from a starting point, the connector, and around a scaffold. They underwent an elaborate maturation process involving protein cleavage and capsid expansion. Heads and tails were assembled separately and joined later. b. The DNA was cut to size and entered preformed capsids by a headful mechanism. 4. Subsequently, tailed phages diversified by: a. Evolving contractile or short tails and elongated heads. b. Exchanging genes or gene fragments with other phages. c. Becoming temperate by acquiring an integrase-excisionase complex, plasmid parts, or transposons. d. Acquiring DNA and RNA polymerases and other replication enzymes. e. Exchanging lysin genes with their hosts. f. Losing the ability to form concatemers as a consequence of acquiring transposons (Mu) or proteinprimed DNA polymerases (phi 29). Present-day tailed phages appear as chimeras, but their monophyletic origin is still inscribed in their morphology, genome structure, and replication strategy. It may also be evident in the three-dimensional structure of capsid and tail proteins. It is unlikely to be found in amino acid sequences because constitutive proteins must be so old that relationships were obliterated and most or all replication-, lysogeny-, and lysis-related proteins appear to have been borrowed. However, the sum of tailed phage properties and behavior is so characteristic that tailed phages cannot be confused with other viruses.


Pectinases in leaf degradation by aquatic hyphomycetes I: the field study : The colonization-pattern of aquatic Hyphomycetes on leaf packs in a surrey stream.
The colonization-pattern of aquatic Hyphomycetes on five-gram leaf packs of oak and alder submerged in a stream was quantified and compared. There were three series of alder leaves, submerged two weeks apart, and one series of oak. Colonization of leaves by pectolytic bacteria was also measured. There were marked similarities in the colonization of all four series. Total spore counts/g dry wt of leaf rose to a peak followed by a decline. The time taken to peak colonization was slower in oak than in alder, and in alder depended on the level of inoculum in the stream, as did the extent of colonization. Pectolytic bacteria counts followed the pattern of total spore counts, suggesting the exploitation of the same substrates by bacteria and fungi. Temperature and micro-environmental factors influence the overall rate of leaf degradation. Alder I was skeletonized in 10 wks, Alders II and III in 12 wks and oak in 25 wks.The resource was shown to have an upper limit of microbial colonization, and within this 'unit-community' of microbes, there was an association of four dominant species of aquatic Hyphomycetes, together with about ten occasional species. The dominant species are subject to selection from the inoculum available in the stream and the formation and maintenance of the association appears to be the result of competitive interactions between species which results in a dynamic equilibrium. There is a low degree of resource specificity. The species equilibrium is 14 for all series, and species numbers are initially low, rise to a peak, then tend to decline. There is a taxonomic similarity of about 60% between successive stands of all series and between matched stands of alder.


'Pathway drug cocktail': targeting Ras signaling based on structural pathways.
Tumors bearing Ras mutations are notoriously difficult to treat. Drug combinations targeting the Ras protein or its pathway have also not met with success. 'Pathway drug cocktails', which are combinations aiming at parallel pathways, appear more promising; however, to be usefully exploited, a repertoire of classified pathway combinations is desirable. This challenge would be facilitated by the availability of the structural network of signaling pathways. When integrated with functional and systems level clinical data, they can be powerful in advancing novel therapeutic platforms. Based on structural knowledge, drug cocktails may tear into multiple cellular processes that drive tumorigenesis, and help in deciphering the interrelationship between Ras mutations and the rewired Ras network. The pathway drug cocktail paradigm can be applied to other signaling protein targets.


Higher Risk Taking and Impaired Probability Judgment in Behavioral Addiction.
Accumulating evidence suggests that deficits in decision-making and judgment may be involved in several psychiatric disorders, including addiction. Behavioral addiction is a conceptually new psychiatric condition, raising a debate of what criteria define behavioral addiction, and several impulse control disorders are equivalently considered as types of behavioral addiction. In this preliminary study with a relatively small sample size, we investigated how decision-making and judgment were compromised in behavioral addiction to further characterize this psychiatric condition. Healthy control subjects (n = 31) and patients with kleptomania and paraphilia as behavioral addictions (n = 16) were recruited. A battery of questionnaires for assessments of cognitive biases and economic decision-making were conducted, as was a psychological test for the assessment of the jumping-to-conclusions bias, using functional near-infrared spectroscopy recordings of prefrontal cortical (PFC) activity. Although behavioral addicts exhibited stronger cognitive biases than controls in the questionnaire, the difference was primarily due to lower intelligence in the patients. Behavioral addicts also exhibited higher risk taking and worse performance in economic decision-making, indicating compromised probability judgment, along with diminished PFC activity in the right hemisphere. Our study suggests that behavioral addiction may involve impairments of probability judgment associated with attenuated PFC activity, which consequently leads to higher risk taking in decision-making.


TILs Immunophenotype in Breast Cancer Predicts Local Failure and Overall Survival: Analysis in a Large Radiotherapy Trial with Long-Term Follow-Up.
To determine the prognostic significance of the immunophenotype of tumour-infiltrating lymphocytes (TILs) within a cohort of breast cancer patients with long-term follow-up. Multiplexed immunofluorescence and automated image analysis were used to assess the expression of CD3, CD8, CD20, CD68, Fox P3, PD-1 and PD-L1 in a clinical trial of local excision and radiotherapy randomised to a cavity boost or not (n = 485, median follow-up 16 years). Kaplan-Meier and Cox multivariate analysis (MVA) methodology were used to ascertain relationships with local recurrence (LR), overall survival (OS) and disease-free survival (DFS). NanoString BC360 gene expression panel was applied to a subset of luminal patients to identify pathways associated with LR. LR was predicted by low CD8 in MVA in the whole cohort (HR 2.34, CI 1.4-4.02, p = 0.002) and luminal tumours (HR 2.19, CI 1.23-3.92, p = 0.008) with associations with increased stromal components, decreased Tregs (FoxP3), inflammatory chemokines and SOX2. Poor OS was associated with low CD20 in the whole cohort (HR 1.73, CI 1.2-2.4, p = 0.002) and luminal tumours on MVA and low PD-L1 in triple-negative cancer (HR 3.44, CI 1.5-7, p = 0.003). Immunophenotype adds further prognostic data to help further stratify risk of LR and OS even in TILs low-luminal tumours.


Determination of aconitine, hypaconitine and mesaconitine in urine using hollow fiber liquid-phase microextraction combined with high-performance liquid chromatography.
Hollow fiber liquid-phase microextraction (HF-LPME) coupled with high-performance liquid chromatography was used to simultaneously determine three Aconitum alkaloids, including aconitine (AC), hypaconitine (HA) and mesaconitine (MA) in human urine sample. Analytes were extracted from 5mL urine sample containing 1.0mmol/L NaOH into 1-octanol membrane phase impregnated in the pores of hollow fiber wall, and then back extracted into acidified aqueous solution in the lumen of the hollow fiber. After extraction, 10μL of the acceptor phase was analyzed directly by HPLC. In this method, some important extraction parameters, such as organic solvent, extraction time, stirring rate, pH of donor phase and acceptor phase, temperature, and the volume of acceptor phase were optimized. This method provided 98- to 288-fold enrichment factors within 60min of extraction and good repeatability with RSDs of 0.99-7.22%. The calibration curves were linear over the ranges of 16.0-128.0μg/L for AC, 11.0-88.0μg/L for HA and 8.1-64.8μg/L for MA in human urine sample, with correlation coefficients of 0.9949, 0.9969 and 0.9904, respectively. Limits of detection were from 0.7 to 1.5μg/L, and recoveries from spiked urine sample varied from 84.4% to 106.2% for AC, 77.3% to 85.6% for HA and 90.1% to 100.8% for MA.


Ouabain blocks some rapid concentration-induced clamp acetylcholine responses on Helix neurons.
1. The effects of ouabain, a potent inhibitor of Na(+)-K+ ATPase, were determined on the transmembrane responses of internally dialyzed Helix neurons to rapid acetylcholine (ACh) application using the "concentration clamp" technique. 2. Ouabain selectively depressed "A"-type responses to ACh, which are due to a selective increase in membrane permeability to chloride. In contrast, the "B"-type responses, due primarily to an increase in monovalent cation permeability, was unaffected. 3. The blockade of the Cl- responses was not associated with a change of the reversal potential of the response. Ouabain depressed the maximal response without shifting the dose-response curve. 4. Ouabain caused an increase in the time constant of decay of the ACh current, but the value in the presence of ouabain was not different from that of a lower concentration of ACh determined so as to give a response of the same peak amplitude. Therefore, the effect of ouabain is not on the process of receptor desensitization directly.


Factors propelling fatalities during road crashes: A detailed investigation and modelling of historical crash data with field studies.
One of the major concerns in developing countries like India is to maintain traffic safety under mixed and heterogenous scenario. Although zero accidents is the need of the hour, the first step to attain it is ensuring zero deaths and no serious long-term disabling injuries in road crashes. To reduce the road crash fatalities, explicit and detailed studies have been conducted by utilising historical road crash data of two emerging smart cities of India - Bhubaneswar and Visakhapatnam. Traffic flow data and characteristics of road infrastructure has also been collected by performing field studies at accident prone locations. Various factors including vehicular characteristics, road user characteristics, and road infrastructure have been analyzed using various non-parametric tests to identify the contributing factors resulting in fatalities. It is observed that out of 14 variables used for study, 8 factors were significantly related to fatal crashes. These included categories of victim and accused, 85th percentile speed, presence of road markings, availability of sight distance, etc. The significant factors were subjected to binary logistic regression to determine the odd's ratio of significant factors. The logistic regression predicted 79% of deaths correctly. Crash fatality prediction models are developed using both Classification and Regression Tree (CART) classification tree with 83% accuracy. Although CART classification led to higher accuracy, binary logistic regression is more robust as it considered more significant factors as compared to CART. Subsequently, a severity index has been proposed based on proportions of actual fatal crashes and usage of K-means clustering technique. The proposed indices shall be really helpful in traffic safety management, specifically in reduction of fatalities during road crashes.


Yarrowia lipolytica as a potential producer of citric acid from raw glycerol.
To study the biochemical response of Yarrowia lipolytica LGAM S(7)1 during growth on raw glycerol (the main by-product of bio-diesel production units) in order to produce metabolic products of industrial significance. Yarrowia lipolytica was cultivated on raw glycerol or glucose in flasks. Although nitrogen-limited media were employed, growth was not followed by production of reserve lipid. Nitrogen limitation led to citric acid excretion. Growth and citric acid production parameters on glycerol were similar to those obtained on glucose. When high initial glycerol media were used, citric acid up to 35 g l(-1) (yield 0.42-0.44 g acid g(-1) glycerol consumed) was produced. Raw glycerol was an adequate substrate for Y. lipolytica. Growth was not followed by reserve lipid accumulation, but amounts of citric acid were produced. Raw glycerol is an industrial feedstock appearing in increasing quantities as the main by-product of bio-diesel production facilities. The present study describes an alternative way of glycerol valorization, with the production of remarkable amounts of citric acid, in addition to its main valorization way (production of 1,3-propanediol by bacteria).


Bone Health Status in Indian Overweight/Obese Children.
This cross-sectional study, to assess bone health in Indian overweight, obese children in comparison with healthy controls was conducted in 245 (126 girls) children and adolescents aged 6-17 y in Pune, India. It was found that total body bone mineral content, bone area and bone mineral density adjusted for Tanner stage and weight were significantly lower in obese children as compared to overweight children, which in turn, was significantly lower than normal weight children (p < 0.05). Thus, overweight and obesity is negatively related to bone health in children and adolescents. Interventions need to be planned to increase peak bone mass accrual in overweight and obese children to reduce future risk of fracture and osteoporosis.


A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors.
The mechanisms that control the precisely regulated switch from gene repression to gene activation represent a central question in mammalian development. Here, we report that transcriptional activation mediated by liganded nuclear receptors unexpectedly requires the actions of two highly related F box/WD-40-containing factors, TBL1 and TBLR1, initially identified as components of an N-CoR corepressor complex. TBL1/TBLR1 serve as specific adaptors for the recruitment of the ubiquitin conjugating/19S proteasome complex, with TBLR1 selectively serving to mediate a required exchange of the nuclear receptor corepressors, N-CoR and SMRT, for coactivators upon ligand binding. Tbl1 gene deletion in embryonic stem cells severely impairs PPARgamma-induced adipogenic differentiation, indicating that TBL1 function is also biologically indispensable for specific nuclear receptor-mediated gene activation events. The role of TBLR1 and TBL1 in cofactor exchange appears to also operate for c-Jun and NFkappaB and is therefore likely to be prototypic of similar mechanisms for other signal-dependent transcription factors.


Innovative procedures for micro-elimination of HCV infection in persons who use drugs.
People who use drugs are a key population in global HCV control. We evaluated the efficacy of an innovative model to eliminate HCV infection in a high-risk population of PWUD in a service for substance use disorder (SUD). Between January 2018 and December 2018, we conducted a prospective, interventional, before and after study, based on audits performed by Infectious Diseases physicians in a SUD facility in Piedimonte Matese, in southern Italy, to improve the knowledge about HCV infection; a shared protocol for screening and linkage to care of patients was implemented. The pre-intervention period was defined as January-December 2017 and the post-intervention period as January-December 2018. The subjects followed up at SUD facility in the pre-intervention and post-intervention periods were 318 and 275, respectively. Compared with the pre-intervention period, the number of anti-HCV-positive subjects tested for HCV RNA was higher in the post-intervention period (91% vs 27%, P < .0001), as was the number who started directly acting antivirals (DAAs). Of the 18 HCV RNA-positive subjects in the pre-intervention period, only 3 (16.6%) started DAA, a percentage decisively lower than that observed after the start of the programme, 63 (84%) of 75 subjects (P < .0001), and all obtained SVR. The data were similar for people who inject drugs (PWID) and non-PWID sub-populations. The use of our innovative model with close interaction between the Infectious Disease Unit and the SUD facility determined a significant increase in HCV RNA testing, linkage to care and the start of DAA in the PWUD population.


Testing non-autonomous antimalarial gene drive effectors using self-eliminating drivers in the African mosquito vector Anopheles gambiae.
Gene drives for mosquito population modification are novel tools for malaria control. Strategies to safely test antimalarial effectors in the field are required. Here, we modified the Anopheles gambiae zpg locus to host a CRISPR/Cas9 integral gene drive allele (zpgD) and characterized its behaviour and resistance profile. We found that zpgD dominantly sterilizes females but can induce efficient drive at other loci when it itself encounters resistance. We combined zpgD with multiple previously characterized non-autonomous payload drives and found that, as zpgD self-eliminates, it leads to conversion of mosquito cage populations at these loci. Our results demonstrate how self-eliminating drivers could allow safe testing of non-autonomous effector-traits by local population modification. They also suggest that after engendering resistance, gene drives intended for population suppression could nevertheless serve to propagate subsequently released non-autonomous payload genes, allowing modification of vector populations initially targeted for suppression.


An event-related potential study of age-related changes in sensitivity to stimulus deviance.
The mismatch negativity (MMN) of the event-related (brain) potential (ERP) has been shown to reflect the storage of information in sensory memory and is thought to reflect the operation of a mechanism that compares frequently occurring standard with infrequently occurring deviant acoustic events. The MMN was recorded from young (mean = 23 years) and elderly (mean = 72 years) adults to small (50 Hz) and large (300 Hz) frequency deviants and to a variety of novel, environmental sounds. At each level of deviance, MMN amplitude was smaller in the ERPs of older relative to younger adults. Young, but not older adults showed robust MMNs at the smallest level of deviance. Moreover, a P3 component was observed in the ERPs of the young to both large tonal and novel deviants, whereas a robust P3 component was evident only to the novel deviants in the ERPs of the old. The data suggest that older adults demonstrate less sensitivity to stimulus deviance and that only highly deviant events are likely to involuntarily capture their attention.


Adsorption of Acid Blue 193 from aqueous solutions onto DEDMA-sepiolite.
The adsorption of Acid Blue 193 (AB193) onto dodecylethyldimethylammonium (DEDMA)-sepiolite was investigated in aqueous solution in a batch system with respect to contact time, pH and temperature. The surface modification of DEDMA-sepiolite was examined by the FT-IR technique. The pseudo-first-order, pseudo-second-order kinetic models and the intraparticle diffusion model were used to describe the kinetic data and the rate constants were evaluated. The experimental data fitted very well with the pseudo-second-order kinetic model and also followed the simple external diffusion model up to initial 10 min and then by intraparticle diffusion model up to 75 min, whereas diffusion is not only the rate-controlling step. The adsorption capacities of natural sepiolite and DEDMA-sepiolite at pH 1.5 and 20 degrees C were (1.19 and 2.57) x 10(-4) mol g(-1), respectively. The above results indicate that DEDMA-sepiolite has around two times higher adsorption capacity than natural sepiolite. The Langmuir and Freundlich adsorption models were applied to describe the equilibrium isotherms and the isotherm constants were also determined. The Freundlich model agrees with experimental data well. The activation energy, change of Gibbs free energy, enthalpy and entropy of adsorption were also evaluated for the adsorption of AB193 onto DEDMA-sepiolite.


Size exclusion chromatography with evaporative light scattering detection: Method for the determination of polydimethylsiloxanes. II. Application of TSK-GEL H HR GMH HR -M column to determine and separate molecular weight of linear polydimethylsiloxanes.
Issues concerned with molecular weight distribution analysis of linear polydimethylsiloxanes have not been extensively investigated and mastered, yet. Current publications do not provide detailed research data on the evaluation of the polymerization degree of polydimethylsiloxanes (PDMS) present in variable matrices: e.g. pharmaceuticals, cosmetics, foodstuffs nor indicate molecular weights of the polymer used. However, the information on molecular weight, i.e. viscosity, is of primary importance as it directly affects PDMS toxicity, absorption and migration in the living organism. The vast majority of currently applied methods prove to be insufficiently specific for PDMS of a particular molecular weight and therefore alternative analytical methods have to be further researched. In this paper the results of determination of molecular weights in linear polydimethylsiloxanes, using size exclusion chromatography with the evaporative light scattering detector are described. The column calibration curve obtained from low-dispersion standard polystyrene of molecular weights ranging 376-2,570,000 Da was used to determine PDMS molecular weights. Precision and accuracy of determination was obtained. For the mobile phase flow-rate of 0.3 ml/min relative standard deviation RSD ranged to 0.45% and the accuracy of measurement amounted to -0.42%, whereas for flow-rate of 1.0 ml/min RSD ranged to 0.38% and accuracy to +2.15%.


[House dust mold in Istanbul. I. Detection of mold flora in bed dust].
In our study, mycological analyses were carried out on 110 randomly chosen houses for bed dusts. 748 mould strains belonging to 117 genus and species were isolated and identified. Air-borne pathogenic fungi, fungi that are causative agents of pulmonary allergy such as Cladosporium spp., Aspergillus glaucus group, Alternaria, Ulocladium, Aureobasidium pullulans, Aspergillus niger group were isolated.


Improving the health of cisgender men who identify as bisexual: What do they want from interventions?
Self-identified bisexual men are at increased risk for negative health outcomes, but there are no interventions tailored to their unique needs. In order to develop interventions for this population, it is first necessary to understand their preferences. As part of a larger study, 128 cisgender men who identified as bisexual reported on their preferences for different intervention components. Large proportions of participants prioritized addressing both health (e.g., mental health, HIV/STI) and psychosocial experiences (e.g., dating/relationships, discrimination/victimization). A slightly larger proportion of participants preferred an intervention for gay and bisexual men together compared to an intervention for bisexual men only. However, those who reported more discrimination and recent female sexual partners were more likely to prefer an intervention for bisexual men only. Larger proportions of participants preferred a group intervention compared to an individual intervention and an in-person intervention compared to an online intervention. These findings highlight the importance of addressing both health and psychosocial experiences in tailored interventions for self-identified bisexual men. Further, while in-person and group interventions may appeal to larger proportions of self-identified bisexual men, the appeal of an intervention for gay and bisexual men together compared to an intervention for bisexual men only may depend on individual and social/contextual factors.


A SEM-study of a keratoconus and an artificially aged human cornea.
The substructure of both the epithelial and endothelial surfaces of a keratoconus and an artificially aged cornea was compared with that of a healthy cornea by investigating them with a scanning electron microscope. From the depressions around the protruding centre of the epithelial surface of the keratoconus cornea, and from the whole epithelial surface of the artificially aged cornea, cells detached themselves, assuming a more or less rounded shape. The endothelial surface of both the keratoconus and the aged cornea showed areas of cells with an almost completely disintegrated cell membrane, exposing the cell contents. On the endothelial surface of the keratoconus cells were found with a missing cell-nucleus and a perforated cell membrane, due to a 'Kammerwasser Einbruch' effect.


Microbiome and Vulvovaginitis.
Vulvovaginitis occurs in mostly reproductive aged women. Recurrent vaginitis affects overall quality of life, with a large financial burden on the patient, family, and health system. This review discusses a clinician's approach to vulvovaginitis with specific attention to the 2021 updated Center for Disease Control and Prevention guidelines. The authors discuss the role of the microbiome in vaginitis and evidence-based approaches for diagnosis and treatment of vaginitis. This review also provides updates on new considerations, diagnosis, management, and treatment of vaginitis. Desquamative inflammatory vaginitis and genitourinary syndrome of menopause are discussed as differential diagnosis of vaginitis symptoms.


Text mining analysis of newspaper editorials concerning the COVID-19 pandemic from a healthcare perspective.
Objective: This pilot study aimed to examine the content of Japanese newspaper editorials concerning the coronavirus disease 2019 (COVID-19) pandemic and its change over time using text mining analysis. Materials and Methods: The authors analyzed qualitative data from the editorials of five national and 12 regional newspapers on April 7 and 8, 2020 (first state of emergency) and January 8, 2021 (second state of emergency). All analyses were conducted using KH Coder version 3. Results: The co-occurrence network showed a low level of content diversity and a high degree of politicization in the COVID-19 news coverage. The top five high frequency words from the newspapers were "infection", "declaration", "healthcare", "government", and "emergency" at the first state of emergency, and were "declaration", "measures", "government", and "restaurant" at the second one. Conclusion: The results suggest a lack of detailed information and recommendations concerning the public health challenges of the COVID-19 pandemic in Japanese newspaper editorials, even one year after the first wave of the pandemic. This study provides a data-driven foundation for the effectiveness of newspapers in COVID-19 public health communications. The extent to which the quantity and quality of information from newly emerging communication channels, such as social media, influences public understanding of public health measures remains to be established.


Spatiotemporal Patterns of Cholera Hospitalization in Vellore, India.
Systematically collected hospitalization records provide valuable insight into disease patterns and support comprehensive national infectious disease surveillance networks. Hospitalization records detailing patient's place of residence (PoR) can be utilized to better understand a hospital's case load and strengthen surveillance among mobile populations. This study examined geographic patterns of patients treated for cholera at a major hospital in south India. We abstracted 1401 laboratory-confirmed cases of cholera between 2000-2014 from logbooks and electronic health records (EHRs) maintained by the Christian Medical College (CMC) in Vellore, Tamil Nadu, India. We constructed spatial trend models and identified two distinct clusters of patient residence-one around Vellore (836 records (61.2%)) and one in Bengal (294 records (21.5%)). We further characterized differences in peak timing and disease trend among these clusters to identify differences in cholera exposure among local and visiting populations. We found that the two clusters differ by their patient profiles, with patients in the Bengal cluster being most likely older males traveling to Vellore. Both clusters show well-aligned seasonal peaks in mid-July, only one week apart, with similar downward trend and proportion of predominant O1 serotype. Large hospitals can thus harness EHRs for surveillance by utilizing patients' PoRs to study disease patterns among resident and visitor populations.


Sex differences in the accumulation of chlorinated dioxins in the cormorant (Phalacrocorax carbo): implication of hepatic sequestration in the maternal transfer.
This study focuses on gender-specific accumulation features of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/DFs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in common (great) cormorants (Phalacrocorax carbo) collected from Lake Biwa, Japan. Male cormorants showed a tendency to have higher levels of PCDD/DFs and DL-PCBs than did females. For PCDDs, the male-to-female concentration ratio (M/F ratio) for each congener significantly decreased with the liver-to-muscle concentration ratio (Li/Mu ratio). For PCDFs, there also was a weak negative relationship between Li/Mu ratio and M/F ratio. In contrast, for DL-PCBs, M/F ratios showed no correlation with Li/Mu ratios, but increased with an increase in lipophilicity. These results, together with observations from prior studies, suggest that congener-specific hepatic sequestration may be a factor limiting the maternal transfer of PCDDs and, to a lesser extent, PCDFs. Maternal transfer of DL-PCBs seems to favor more lipophilic congeners in the cormorants.


Intensive care admissions due to poisoning.
Poisoning represents a significant part of admissions to intensive care units. The aim of this nationwide study was to describe recent national quality register data of demographics and mortality for these patients. A retrospective national observational study including all patients over 19 years admitted to an ICU in Sweden, between 1 January 2010 and 31 December 2011, with an ICD-10 code for poisoning. The data were collected from three national registers (The Swedish Intensive Care Register, The National Patient Register, and The Cause of Death Register). The incidence of ICU-treated poisonings was 43/100,000. Twenty-one per cent (n = 8155) of all poisoned patients seeking medical care were admitted to the ICU. Their median age was 38 years (q1-q3: 26-51), as many men as women and 46.5% (n = 3790) had a previous registered poisoning. A mix of different substances was the most common type of suspected poisoning (29.7%, n = 2424). The in-hospital mortality was 1.9% and was correlated to invasive mechanical ventilation (OR 6.91 CI 95% 4.59-10.42), age > 40 (OR 4.54 CI 95% 2.86-7.21) and no previous hospitalisation for poisoning (OR 3.23 CI 95% 2.06-5.07). For 78.3% (n = 119) of the deceased patients, the fatal poisoning was their first diagnosed poisoning. The 30-day mortality was 2.7%, a majority died from poisoning (P < 0.01). In Sweden, patients treated in the ICU due to poisoning represent a fifth of all poisoned patients seeking medical care. Older men with no previous poisoning were considered a high-risk group.


Association between single nucleotide polymorphism rs9534275 and the risk of coronary artery disease and ischemic stroke.
The present study was to detect the association of single nucleotide polymorphism (SNP) in the breast susceptibility gene 2 (BRCA2) and the risk of coronary artery disease (CAD) and ischemic stroke (IS). Genotypes of the BRCA2 rs9534275 in 1822 unrelated subjects (CAD, 606; IS, 569; and healthy controls, 647) were determined by the polymerase chain reaction and restriction fragment length polymorphism and then confirmed by direct sequencing. The genotypic and allelic frequencies of rs9534275 were significantly different between the CAD, IS patients and controls (P = 0.033 and P = 0.027; respectively). The GG, GT/GG genotypes and G allele were associated with an increased risk of CAD and IS (CAD: P = 0.005 for GG vs. TT, P = 0.004 for GT/GG vs. TT, P = 0.005 for G vs. T; IS: P = 0.003 for GG vs. TT, P = 0.005 for GT/GG vs. TT; P = 0.002 for G vs. T). The GG, GT and GT/GG genotypes in the CAD, but not in healthy controls and IS patients, were associated with an increased serum total cholesterol (TC) and apolipoprotein B (ApoB) concentration. The present study shows that the G allele carriers of BRCA2 rs9534275 were associated with increased serum TC and ApoB levels in the CAD patients and increased risk of CAD and IS. Retrospectively registered.


[The situation of students on placement, a real obstacle to the attractiveness of hospitals].
Complementing theoretical courses, hospital internships are intended to encourage learners to apply their acquired knowledge while experiencing the field. In fact, this is becoming more and more complicated, and students are direct witnesses of the crisis affecting the hospital. The degraded working conditions of professionals do not allow them to properly supervise trainees, and even allow reprehensible behavior to flourish. Suffering on the job, the students desert the hospital after graduation.


COVID-19 associated mucormycosis: A Descriptive Multisite Study from India.
Mucormycosis is an invasive fungal infection and carries a significant morbidity and mortality. A number of cases of mucormycosis have been reported in association with COVID-19. In this study, a consortium of clinicians from various parts of India studied clinical profile of COVID-19 associated mucormycosis (CAM) and this analysis is presented here. Investigators from multiple sites in India were involved in this study. Clinical details included the treatment and severity of COVID-19, associated morbidities, as well as the diagnosis, treatment and prognosis of mucormycosis. These data were collected using google spreadsheet at one centre. Descriptive analysis was done. There were 115 patients with CAM. Importantly, all patients had received corticosteroids. Diabetes was present in 85.2% of patients and 13.9% of patients had newly detected diabetes. The most common site of involvement was rhino-orbital. Mortality occurred in 25 (21.7%) patients. On logistic regression analysis, CT scan-based score for severity of lung involvement was associated with mortality. Universal administration of corticosteroids in our patients is notable. A large majority of patients had diabetes, while mortality was seen in ∼1/5th of patients, lower as compared to recently published data.


Evaluation of age-related plantar-surface insensitivity and onset age of advanced insensitivity in older adults using vibratory and touch sensation tests.
Age-related decline in plantar-surface sensitivity has been cited as one of the reasons for balance problems in older adults. This study investigated the level of plantar-surface sensitivity in older adults compared to young adults. Additionally, this study attempted to identify the onset age of advanced insensitivity in older adults and how well monofilament testing was able to predict insensitivity and onset age of advanced insensitivity. Vibration thresholds were assessed at four frequencies (3, 25, 100 and 250 Hz) and four foot sole locations (heel, first metatarsal, fifth metatarsal and great toe). Touch thresholds were evaluated with Semmes-Weinstein monofilaments at the same four locations. Results indicated that older adults showed insensitivity to vibratory (25 and 100 Hz) and touch stimuli when compared to young adults. Vibration testing at 100 Hz indicated that early in the seventh decade (72-73 years old) participants started to show a doubling of their detection threshold as compared to their younger counterparts (65-71 years old). Regression analysis indicated a significant predictive value of the monofilaments to 100 Hz vibration thresholds, but a caution is noted that this type of testing is not as sensitive to the onset of advanced plantar-surface insensitivity. Therefore, older adults have significant plantar-surface insensitivity as compared to young adults and have an onset of advanced insensitivity in the seventh decade of life. Monofilaments are useful to assess the age-related insensitivity but are not when attempting to identify the onset of advanced insensitivity.


Sclerostin: from bench to bedside.
Skeletal integrity is maintained by a meticulous balance between bone resorption and bone formation, and recent studies have revealed the essential role of canonical Wnt signaling pathways in maintaining skeletal homeostasis. The SOST gene, which encodes sclerostin, a member of Dan family glycoproteins, was originally identified as the gene responsible for two sclerosing bone dysplasias, sclerosteosis and van Buchem disease. Sclerostin is highly expressed by osteocytes, negatively regulates canonical Wnt signaling pathways by binding to low-density lipoprotein receptor-related protein (LRP) 5/6, and suppresses osteoblast differentiation and/or function. Romosozumab, a specific anti-sclerostin antibody, inhibits sclerostin-LRP5/6 interactions and indirectly activates canonical Wnt signaling pathways and bone formation. This review focuses on the mechanism of action of sclerostin and summarizes clinical studies that demonstrated the efficacy of romosozumab to increase bone mineral density and reduce osteoporotic fractures, as well as its cardiovascular safety.


[Culture of normal and pathological human growth cartilage. Action of vitamin D derivatives and somatomedin].
Chondrocytes from normal cartilage of a 2 month old child have been cultured. In vitro the cells maintained their morphological identity and synthesised proteoglycans with electrophoretic properties similar to those synthesised by cartilage in vivo. Sulphation was stimulated by vitamin D metabolites and by somatomedin. This technique has been used to study biopsies of abnormal cartilage.


A facile method for the synthesis of dihydroquinoline-azide from the Lewis acid-catalyzed reaction of alkylidenecyclopropanes with TMSN3.
A facile synthetic method for the formation of dihydroquinoline-azide from alkylidenecyclopropanes and TMSN3 under the catalysis of a Lewis acid has been developed, and a number of azide-containing compounds can be instantly accessed in moderate to good yields. A click reaction with these azido compounds was also realized along with a mechanistic investigation.


Opioid receptor-dependent long-term potentiation at the lateral perforant path-CA3 synapse in rat hippocampus.
The involvement of opioid receptors in the induction of long-term potentiation (LTP) was investigated in the lateral and medial perforant path projections to area CA3 of the hippocampus in anesthetized rats. The opioid receptor antagonist naloxone (10 nmol), applied to the hippocampal CA3 region 10 min prior to tetanization, blocked the induction lateral perforant path-CA3 LTP induced by high-frequency stimulation. By contrast, LTP induction in medial perforant path-CA3 was not attenuated by a 10 nmol quantity of naloxone. (+)-Naloxone (10 nmol), the inactive stereoisomer of naloxone, was without effect on the induction of lateral perforant path-CA3 LTP. Naloxone applied 1 h following LTP induction did not reverse established lateral perforant path-CA3 LTP, indicating that opioid receptors are involved in the induction but not the maintenance of LTP in this pathway. LTP of medial perforant path responses developed immediately, while LTP of lateral perforant path responses was slow to develop. The latter pattern is similar to the time course of the development of LTP observed at the mossy fiber-CA3 synapse and suggests that lateral and medial perforant path synapses may use distinct mechanisms of both induction and expression of LTP. These data extend previous findings demonstrating opioid receptor-dependent mechanisms of LTP induction at both the mossy fiber-CA3 synapse and the lateral perforant path-dentate gyrus synapse. We suggest that lateral perforant path and mossy fiber synapses may utilize similar, opioid receptor-dependent, mechanisms of LTP induction and expression.