Brief overview of solubility methods: Recent trends in equilibrium solubility measurement and predictive models.
Solubility is a crucial physicochemical parameter affecting the whole process of drug discovery and development. Thus, understanding of the methods and concepts to measure and predict this propensity are of utmost importance for the pharmaceutical scientist. Despite their inherent limitations, kinetic solubility screening methods became routine assays by mimicking bioassay conditions and guiding the lead optimization process. In contrast, thermodynamic solubility methods show a clear evolution: miniaturized high throughput assays coupled to analytical techniques such as solid-state characterization, ultra performance liquid chromatography, or polychromatic turbidimetry, have been developed, thereby enabling a more complex physicochemical profiling at the early discovery stage. Solubility prediction still poses a significant challenge at the industrial level. Classification and critical evaluation of recent in silico models are provided. Discussion of experimental and computational methods: was based on relevant industrial references.


Patterns of gastritis in patients with gastro-oesophageal reflux disease.
The cause of inflammation in cardiac mucosa at the gastro-oesophageal junction (GOJ) is unclear, both gastro-oesophageal reflux disease (GORD) and Helicobacter pylori having been implicated. To describe patterns of gastritis in patients with symptomatic GORD. In 150 patients (126 normally located Z-line, 24 Barrett's oesophagus) with symptoms of GORD, biopsies were taken of the GOJ, corpus, and antrum. Inflammation was assessed using the updated Sydney System. For the 126 patients with a normally located Z-line, biopsies of the GOJ revealed cardiac mucosa in 96, fundic mucosa in 29, and squamous mucosa in one. Inflammation in glandular mucosa at the GOJ was present in 99/125 specimens (79%), including 87/96 (91%) with cardiac mucosa and 12/29 (41%) with fundic mucosa. Inflammation in fundic mucosa was closely related to H pylori and active inflammation was only seen in its presence. Inflammation in cardiac mucosa was less closely linked to H pylori. When H pylori was present in cardiac mucosa (28/96, 29%) active inflammation was usually present (25/28, 89%). However, active inflammation was also found in 34/68 (50%) cardiac mucosa specimens without H pylori. Overall, 28/87 (32%) biopsies with carditis were colonised with H pylori and 59/87 (68%) were not. In H pylori colonised patients, inflammation was seen throughout the stomach, while in non-colonised patients, it was confined to cardiac mucosa. Patients with symptomatic GORD had a high prevalence of carditis. This was of two types, H pylori associated and unassociated. Except on Giemsa staining, the two were morphologically identical, suggesting mediation by a similar immunological mechanism.


Chromosomal abnormalities in 457 Turkish patients with MCA/MR.
The evaluation of multiple congenital abnormalities and/or mental retardation (MCA/MR) is always a challenge to clinicians. The recognition of specific physical or behavioral characteristics can vastly improve diagnostic yield. Chromosomal abnormalities account for a high percentage in the etiology of MCA/MR. In this study, frequency of chromosomal abnormalities was 4.81% of 457 patients. Chromosomal abnormalities and polymorphisms were detected in 65 (14.21%) (structural and numerical chromosomal abnormalities in 22 patients and polymorphisms in 43) of 457 MR and/or MCA patients. Our results show that chromosomal abnormalities contribute much to the causation of multiple malformations and/or MR. It is essential that fluorescence in situ hybridization (FISH) be used in conjunction with standard methods in order to maximize obtainable information for better management of patients with MR and/or MCA.


Exercise-induced activation of STAT3 signaling is increased with age.
Activation of the transcription factor signal transducers and activators of transcription (STAT) 3 is common to many inflammatory cytokines and growth factors, with recent evidence of involvement in skeletal muscle regeneration. The purpose of this study was to determine whether STAT3 signaling activation is regulated differentially, at rest and following intense resistance exercise, in aged human skeletal muscle. Skeletal muscle biopsies were harvested from healthy younger (n = 11, 20.4 +/- 0.8 years) and older men (n = 10, 67.4 +/- 1.3 years) under resting conditions and 2 h after the completion of resistance exercise. No differences were evident at rest, whereas the phosphorylation of STAT3 was significantly increased in old (23-fold) compared to young (5-fold) subjects after exercise. This correlated with significantly higher induction of the STAT3 target genes including; interleukin-6 (IL-6), JUNB, c-MYC, and suppressor of cytokine signaling (SOCS) 3 mRNA in older subjects following exercise. Despite increased SOCS3 mRNA, cellular protein abundance was suppressed. SOCS3 protein is an important negative regulator of STAT3 activation and cytokine signaling. Thus, in aged human muscle, elevated responsiveness of the STAT3 signaling pathway and suppressed SOCS3 protein are evident following resistance exercise. These data suggest that enhanced STAT3 signaling responsiveness to proinflammatory factors may impact on mechanisms of muscle repair and regeneration.


Maternal and perinatal morbidity of caesarean delivery at full cervical dilatation compared with caesarean delivery in the first stage of labour.
To estimate maternal and perinatal morbidity associated with caesarean delivery at full cervical dilatation, a population-based cohort study from 1997 to 2002 was used, which included 1623 nullipara with singleton pregnancies at 37-42 weeks of gestation requiring caesarean delivery in labour. Compared to caesarean delivery at less than full dilatation, women undergoing caesarean delivery at full dilatation were more likely to have complications of intraoperative trauma (RR 2.6, P < 0.001) and infants with perinatal asphyxia (RR 1.5, P < 0.05). There was no difference in maternal or perinatal morbidity when duration of the second stage of labour or when failed assisted vaginal delivery was considered.


EPR sensing of metal and organic cations using a novel spin-labelled dibenzo-24-crown-8-ether.
The synthesis of novel dibenzo-24-crown ether substituted nitroxides and their use as spin probes for the detection of cation guests by EPR are reported. Formation of a host-guest complex between the proposed spin probes and several cations, both organic and inorganic, was evidenced by a significant change in the value of the benzylic and nitrogen EPR hyperfine splittings upon complexation. This favorable feature provided a reliable EPR sensor that is able to selectively distinguish different cationic guests.


Nitrosoureas in multiple myeloma.
A number of cooperative-group and single-institution studies have shown that BCNU used in combination with prednisone alone or with melphalan,cyclophosphamide, and prednisone is useful for remission induction in patients with previously untreated multiple myeloma. In this setting, results with BCNU (and probably CCNU) are as good as (but not superior to)the results obtained to the frequency of remission induction, duration of remission, and survival. BCNU plus prednisone also appears to be equal to melphalan plus prednisone for remission-maintenance therapy, although it is still unclear whether maintenance therapy is superior to discontinuation of therapy during remission. At the present time, the major use of the nitrosoureas in multiple myeloma appears to be for patients who enter remission with conventional alkylating-agent therapy and later relapse. BCNU and CCNU are occasionally effective when used as single agents or in combination with other alkylating agents for relapsing patients. Results of a pilot study at the University of Arizona with low doses of BCNU and adriamycin for patients relapsing on alkylating-agent therapy have been encouraging, with a 54% (seven of 13 patients) incidence of CRs and PRs. The use of this combination in conjunction with vincristine and prednisone for relapsing patients is under investigation by the Southwest Oncology Group.


Lumbopelvic rhythm in the sagittal plane: A review of the effects of participants and task characteristics.
Abnormalities of lumbopelvic coordination have been suggested to relate to risk of developing low back pain. The objective of this study is to review and summarize the findings of studies that have implemented and reported on lumbopelvic rhythm during trunk forward bending and backward return. The PUBMED and CINAHL databases were searched for studies related to LPR using appropriate keywords. The references of each study from the database search were further investigated to identify any missed study. The findings includes results related to lumbopelvic rhythm, and how it varies due to participant characteristics such as age, gender, and presence of low back pain as well as due to variations in the experimental procedures such as pace of motion, presence of external load, and muscle fatigue. In general, the magnitude of lumbar contribution is smaller in people with low back pain, in the elderly and females, as well as with greater pace of motion, but is larger with greater external load or back muscle fatigue. The compiled data in this review are expected to serve as a foundation for implementation of this kinematic-based measure in the conduct of future research.


Dose-dependent binding of trichloroethylene to hepatic DNA and protein at low doses in mice.
Trichloroethylene (TCE) is a widely used industrial chemical and a low level contaminant of surface and ground water in industrialized areas. It is weakly mutagenic in several test systems and carcinogenic in rodents. However, the mechanism for its carcinogenicity is not known. We investigated the binding of [1,2-14C]TCE ([14C]TCE) to liver DNA and proteins in male B6C3F1 mice at doses more relevant to humans than used previously. The time course for the binding was studied in animals dosed with 4.1 micrograms [14C]TCE/kg body weight (b.w.) and sacrificed between 0.5 and 120 h after i.p. injection. A dose response study was carried out in mice given [14C]TCE at doses between 2 micrograms/kg and 200 mg/kg b.w. and sacrificed 2 h post-treatment. [14C]TCE associated with the DNA and protein extracts was measured using accelerator mass spectrometry. The highest level of protein binding (2.4 ng/g protein) was observed 1 h after the treatment followed by a rapid decline, indicating pronounced instability of the adducts and/or rapid turnover of liver proteins. DNA binding was biphasic with the first peak (75 pg/g DNA) at 4 h. However, the highest binding (120 pg/g DNA) was found between 24 and 72 h after the treatment. Dose response curves were linear for both protein and DNA binding. The binding of TCE metabolites to DNA was ca. 100-fold lower than to proteins when calculated per unit weight of macromolecules and when measured 2 h post-exposure. This study shows that TCE metabolites bind to DNA and proteins in a dose-dependent manner in liver, one of the target organs for its tumorigenicity. Thus, protein and DNA adduct formation should be considered as a factor in the tumorigenesis of TCE.


Comparison of postoperative pain intensity following the use of three different instrumentation techniques: A randomized clinical trial.
Background. The aim of this study was to compare the postoperative pain intensity following the root canal preparation carried out with XP-endo Shaper (XPS; FKG Dentaire SA, La Chauxde-Fonds, Switzerland), iRace (iRC; FKG Dentaire SA) and Reciproc Blue (REC Blue; VDW, Munich, Germany) files. Methods. Mandibular molar teeth with asymtomatic necrotic pulps in 69 patients were randomly divided into three groups (n=23). The root canals were prepared using XPS, iRC or REC Blue instruments and obturated using the lateral condensation technique. The patients were asked to record their pain intensity at 24-, 48- and 72-hour and 1-week postoperative intervals on VAS. For intolerable pain after the procedure, ibuprofen (400 mg) was prescribed. Data were analyzed using chi-squared, Friedman, Kruskal-Wallis, and Mann-Whitney U tests. Results. The postoperative pain gradually decreased during the study period in all the groups (P<0.05). No statistically significant difference was found between iRC system and the two other systems at 12-, 24- 48-hour and 1-week intervals (P>0.05). When compared to XPS system, a higher level of postoperative pain was observed with REC Blue system at 24- and 48-hour intervals (P<0.05). Conclusion. The XPS group exhibited less postoperative pain than the REC Blue group at 24- and 48-hour intervals. iRC, XPS and REC Blue systems were found to be similar in terms of postoperative pain severity.


Re-design of Rhodobacter sphaeroides dimethyl sulfoxide reductase. Enhancement of adenosine N1-oxide reductase activity.
The periplasmic DMSO reductase from Rhodobacter sphaeroides f. sp. denitrificans has been expressed in Escherichia coli BL21(DE3) cells in its mature form and with the R. sphaeroides or E. coli N-terminal signal sequence. Whereas the R. sphaeroides signal sequence prevents formation of active enzyme, addition of a 6x His-tag at the N terminus of the mature peptide maximizes production of active enzyme and allows for affinity purification. The recombinant protein contains 1.7-1.9 guanines and greater than 0.7 molybdenum atoms per molecule and has a DMSO reductase activity of 3.4-3.7 units/nmol molybdenum, compared with 3.7 units/nmol molybdenum for enzyme purified from R. sphaeroides. The recombinant enzyme differs from the native enzyme in its color and spectrum but is indistinguishable from the native protein after redox cycling with reduced methyl viologen and Me2SO. Substitution of Cys for the molybdenum-ligating Ser-147 produced a protein with DMSO reductase activity of 1.4-1.5 units/nmol molybdenum. The mutant protein differs from wild type in its color and absorption spectrum in both the oxidized and reduced states. This substitution leads to losses of 61-99% of activity toward five substrates, but the adenosine N1-oxide reductase activity increases by over 400%.


Search for common targets of lithium and valproic acid identifies novel epigenetic effects of lithium on the rat leptin receptor gene.
Epigenetics may have an important role in mood stabilizer action. Valproic acid (VPA) is a histone deacetylase inhibitor, and lithium (Li) may have downstream epigenetic actions. To identify genes commonly affected by both mood stabilizers and to assess potential epigenetic mechanisms that may be involved in their mechanism of action, we administered Li (N = 12), VPA (N = 12), and normal chow (N = 12) to Brown Norway rats for 30 days. Genomic DNA and mRNA were extracted from the hippocampus. We used the mRNA to perform gene expression analysis on Affymetrix microarray chips, and for genes commonly regulated by both Li and VPA, we validated expression levels using quantitative real-time PCR. To identify potential mechanisms underlying expression changes, genomic DNA was bisulfite treated for pyrosequencing of key CpG island 'shores' and promoter regions, and chromatin was prepared from both hippocampal tissue and a hippocampal-derived cell line to assess modifications of histones. For most genes, we found little evidence of DNA methylation changes in response to the medications. However, we detected histone H3 methylation and acetylation in the leptin receptor gene, Lepr, following treatment with both drugs. VPA-mediated effects on histones are well established, whereas the Li effects constitute a novel mechanism of transcriptional derepression for this drug. These data support several shared transcriptional targets of Li and VPA, and provide evidence suggesting leptin signaling as an epigenetic target of two mood stabilizers. Additional work could help clarify whether leptin signaling in the brain has a role in the therapeutic action of Li and VPA in bipolar disorder.


An online tool for fetal fraction prediction based on direct size distribution analysis of maternal cell-free DNA.
The discovery of circulating fetal DNA in the plasma of pregnant women has greatly promoted advances in noninvasive prenatal testing. Screening performance is enhanced with higher fetal fraction and analysis of samples whose fetal DNA fraction is lower than 4% are unreliable. Although current approaches to fetal fraction measurement are accurate, most of them are expensive and time consuming. Here we present a simple and cost-effective solution that provides a quick and reasonably accurate fetal fraction by directly evaluating the size distribution of circulating DNA fragments in the extracted maternal cell-free DNA. The presented approach could be useful in the presequencing stage of noninvasive prenatal testing to evaluate whether the sample is suitable for the test or a repeat blood draw is recommended.


EPR/ENDOR, Mössbauer, and quantum-chemical investigations of diiron complexes mimicking the active oxidized state of [FeFe]hydrogenase.
Understanding the catalytic process of the heterolytic splitting and formation of molecular hydrogen is one of the key topics for the development of a future hydrogen economy. With an interest in elucidating the enzymatic mechanism of the [Fe(2)(S(2)C(2)H(4)NH)(CN)(2)(CO)(2)(μ-CO)] active center uniquely found in [FeFe]hydrogenases, we present a detailed spectroscopic and theoretical analysis of its inorganic model [Fe(2)(S(2)X)(CO)(3)(dppv)(PMe(3))](+) [dppv = cis-1,2-bis(diphenylphosphino)ethylene] in two forms with S(2)X = ethanedithiolate (1edt) and azadithiolate (1adt). These complexes represent models for the oxidized mixed-valent Fe(I)Fe(II) state analogous to the active oxidized "H(ox)" state of the native H-cluster. For both complexes, the (31)P hyperfine interactions were determined by pulse electron paramagnetic resonance and electron nuclear double resonance (ENDOR) methods. For 1edt, the (57)Fe parameters were measured by electron spin-echo envelope modulation and Mössbauer spectroscopy, while for 1adt, (14)N and selected (1)H couplings could be obtained by ENDOR and hyperfine sublevel correlation spectroscopy. The spin density was found to be predominantly localized on the Fe(dppv) site. This spin distribution is different from that of the H-cluster, where both the spin and charge densities are delocalized over the two Fe centers. This difference is attributed to the influence of the "native" cubane subcluster that is lacking in the inorganic models. The degree and character of the unpaired spin delocalization was found to vary from 1edt, with an abiological dithiolate, to 1adt, which features the authentic cofactor. For 1adt, we find two (14)N signals, which are indicative for two possible isomers of the azadithiolate, demonstrating its high flexibility. All interaction parameters were also evaluated through density functional theory calculations at various levels.


Genetic diversity among sapoviruses.
Norovirus and Sapovirus are two genera of the family Caliciviridae that contain viruses that can cause acute gastroenteritis in humans. Noroviruses (NOR) are genetically highly diverse but limited studies of the genetic diversity of sapoviruses (SAP) have been reported. In this study we characterized twenty-five SAP detected in our laboratory from outbreaks or sporadic cases of acute gastroenteritis in children from different geographical locations and in adults involved in a cruise ship outbreak investigation and a nursing home outbreak. Based on significant differences of partial RNA polymerase sequences (278-286 nt), the 25 strains were grouped into 12 genetic clusters, including 9 potential new clusters. Extended sequence analysis of the capsid gene of selected strains representing five potential new clusters supported this grouping. Four strains (Hou7-1181/90, Mex340/90, Cruise ship/00 and Argentina39) had <84% amino acid (aa) identity to each other and to the published sequences in the GenBank. Mex14917/00 was almost identical to Stockholm/97/SE whose RNA polymerase sequence was unknown. Phylogenetic and distance analyses of the capsid region of the four new strains showed that Hou7-1181/90 and Argentina39 represent two new genogroups and Mex340/90 and Cruise ship/00 belong to two new clusters within the London/92 genogroup. Thus, based on the capsid sequences we propose to classify the currently known SAP into nine genetic clusters within five genogroups, including one genogroup that is represented by an animal calicivirus, the porcine enteric calicivirus (PEC).


Deformation-dependent polydimethylsiloxane permeability measured using osmotic microactuators.
In soft solids, large deformations significantly alter molecular structure and device geometry, which can impact other properties. In the case of mass transport, an interplay between flux and mechanical deformation results. Here we demonstrate a platform for the simultaneous characterization of mechano-permselectivity using the (slow) transport of water through polydimethylsiloxane (PDMS) as a challenging test case. The platform uses micron-sized, cylindrical, NaCl solution-filled PDMS chambers encapsulated by selectively-permeable PDMS thin film membranes. When placed in a high chemical potential environment (high water potential) the osmotic pressure difference between the chamber and environment induces water to flow through the PDMS membrane into the chamber, resulting in membrane bulging. A model combining membrane flux and nonlinear elasticity captures the time-dependent response well, but only when a deformation-dependent permeability is used. Notably, the permeability of water through PDMS decreases by nearly an order of magnitude, from 2 × 10-12 to 5 × 10-13 m2 s-1, due primarily to its thickness decreasing by nearly an order of magnitude as the average biaxial stretch increases from 1 to 2.75.


Translesion DNA Synthesis Across Lesions Induced by Oxidative Products of Pyrimidines: An Insight into the Mechanism by Microscale Thermophoresis.
Oxidative stress in cells can lead to the accumulation of reactive oxygen species and oxidation of DNA precursors. Oxidized nucleotides such as 2'-deoxyribo-5-hydroxyuridin (HdU) and 2'-deoxyribo-5-hydroxymethyluridin (HMdU) can be inserted into DNA during replication and repair. HdU and HMdU have attracted particular interest because they have different effects on damaged-DNA processing enzymes that control the downstream effects of the lesions. Herein, we studied the chemically simulated translesion DNA synthesis (TLS) across the lesions formed by HdU or HMdU using microscale thermophoresis (MST). The thermodynamic changes associated with replication across HdU or HMdU show that the HdU paired with the mismatched deoxyribonucleoside triphosphates disturbs DNA duplexes considerably less than thymidine (dT) or HMdU. Moreover, we also demonstrate that TLS by DNA polymerases across the lesion derived from HdU was markedly less extensive and potentially more mutagenic than that across the lesion formed by HMdU. Thus, DNA polymerization by DNA polymerase η (polη), the exonuclease-deficient Klenow fragment of DNA polymerase I (KF-), and reverse transcriptase from human immunodeficiency virus type 1 (HIV-1 RT) across these pyrimidine lesions correlated with the different stabilization effects of the HdU and HMdU in DNA duplexes revealed by MST. The equilibrium thermodynamic data obtained by MST can explain the influence of the thermodynamic alterations on the ability of DNA polymerases to bypass lesions induced by oxidative products of pyrimidines. The results also highlighted the usefulness of MST in evaluating the impact of oxidative products of pyrimidines on the processing of these lesions by damaged DNA processing enzymes.


Response to chemotherapy is not related to chromosome instability in synovial sarcoma.
Synovial sarcoma (SS) is an aggressive soft-tissue tumor. Despite being considered as a chemosensitive disease, the real impact of perioperative chemotherapy on metastasis-free survival (MFS) is controversial. We have shown that metastatic relapse of SS is strongly associated with genomic complexity. There are no data regarding the potential correlation between genomic complexity and response to chemotherapy. The study population included 65 SS patients diagnosed between 1991 and 2013 and with available tissue material. Genomic profiling was carried out by using array-CGH. Forty-five SS out of the 65 patients were treated with neoadjuvant anthracycline/ifosfamide-based chemotherapy. Radiological response was assessed according to RECIST criteria. Histological response was defined by the percentage of recognizable tumor cells on the surgical specimen. Genomic complexity was significantly associated with MFS. However, there was no statistically significant association between radiological or histological response and genomic complexity. The absence of significant association between response to chemotherapy and genomic complexity suggests that the prognostic value of chromosome instability in SS is independent of response to chemotherapy; mechanisms leading to metastatic relapse of SS are intrinsic to the biology of the tumor and current cytotoxic drugs are only poorly efficient to prevent it.


A thermal video database for studying deception in real life.
In this paper, we have developed a database based on almost real-life theft incidents with due diligence using isolated subjects over a period of time at a government hospital under the plea of free health checkup. The experiment has been conducted at Midnapore Medical College and Hospital, West Bengal, India, with proper ethical committee approval. The participants are selected at the behest of the police department with habitual crime records. Most of them have been repeatedly charged with petty crimes of pick-pocketing and stealing. They are invited individually at different instances of time under the plea of medical checkup where they have been enticed to steal cash. It is followed by a two-stage process, a friendly interaction followed by a slightly tougher interrogation. Facial thermal imaging could be more effective as it is noninvasive and could be a stealth method of tracking the facial blood flow and temperature patterns.


Progressive paresis in sheep due to delayed neurotoxicity of triaryl phosphates.
This report describes the history, signs, histopathology, and diagnosis of a delayed neurotoxicity in Suffolk sheep caused by transmission oil. The signs of toxicity included hyperexcitability, a stiff gait, tetraparesis and inability to maintain sternal recumbency. The circumstances involved in exposure to the transmission oil were determined. Histopathology revealed widespread degeneration of axons in the spinal cord, especially their more distal portions.


Targeting alpha7-nicotinic receptor for the treatment of pleural mesothelioma.
Human malignant pleural mesothelioma (MPM) is a dreadful disease and there is still no standard therapy available for a consistent therapeutic approach. This research is aimed at the evaluation of the potential therapeutic effect of a specific nicotinic receptor (nAChR) antagonist, namely alpha-Cobratoxin (alpha-CbT). Its effectiveness was tested in mesothelioma cell lines and in primary mesothelioma cells in vitro, as well as in vivo, in orthotopically xenotransplanted NOD/SCID mice. Cells showed alpha7-nAChR expression and their growth was significantly inhibited by alpha-CbT. Severe induction of apoptosis was observed after exposure to alpha-CbT [IC(80-90)]. Apoptosis was characterised by: change in mitochondrial potential, caspase-3 cleavage, down-regulation of mRNA and protein for survivin, XIAP, IAP1, IAP2 and Bcl-XL, inhibition by caspase-3 inhibitor. In vivo, the alpha-CbT acute LD(50) was 0.15 mg/kg. The LD(100) [0.24 mg/kg] induced fatal respiratory failure and massive kidney necrosis. Phase II experiments with 0.12 ng/kg alpha-CbT (1/1000 of LD(10)) were done in 53 xenotransplanted mice, inhibiting tumour development as confirmed by chest X-ray examinations, autopsy and microscopical findings. The growth of human proliferating T lymphocytes and of mesothelial cells in primary culture was not affected by alpha-CbT. Non-immunogenic derivatives of the alpha-CbT molecule need to be developed for possible human use.


[Interconversion of spiral D- and L-enantiomorphs of vascular muscles].
Possibilities of mutual transformation of the right coiled enantiomorphs of the smooth muscle elements in the vascular walls into the left ones and vice versa have been studied. The circular smooth muscle cells make the base of similar transformation. They are coiled in one plane and connected by their ends with longitudinally situating cells. When the longitudinal cells contractile at both sides, the circular cells, stretching along the longitudinal axis of the vessel, arrange on the cylinder surface in the form of the right or left spirals. Their transformation into one another is reached by means of contracting the profile element at one or other side of the point where the circular element is fixed. The common regularity of this interreorganization is transition across the right-left form of the Archimedean spiral. Similar enantiomorphism of mutual reorganization is considered in the model and determined as a reaction to gravitational-heat effect, contributing to better movement of the liquid biological medium along the blood vessel canals.


Are Breast Cancer Outcomes Compromised by General Surgical Resident Participation in the Operation?
The effect of surgery resident participation on breast cancer recurrence has not been previously reported. The objectives of this study were to determine if resident participation was associated with either immediate postoperative or long-term breast cancer outcomes. We retrospectively reviewed a prospectively collected breast center database to identify all patients with breast cancer undergoing surgery in a single center during a 9-year period ending 1 January 2010. Patients were divided into 2 groups based on whether surgery residents completed more than 50% of the critical portions of the case (Resident group) or not. The outcomes of operation length, reoperative rates, morbidity, and the long-term outcomes of cancer recurrence were compared by group. Comparisons of immediate postoperative outcomes were made with chi-square and Fisher exact tests. Comparisons of operation length were analyzed by Wilcoxon rank-sum testing. Survival analyses were calculated using the Kaplan-Meier method with log-rank comparison. Multivariate analysis with Cox regression was also performed. The study occurred at a community-based hospital that has an accredited general surgery training program. In all, 1107 consecutive patients with stage 0-3 breast cancer undergoing breast cancer operations were included. Median age of patients was 64 years (range: 24-97). Median and longest follow-up were 5.5 and 12.5 years, respectively. Initial operation was breast conserving in 796 (72%) and mastectomy in 311 (28%). Of the 1107 patients, 887 (80.1%) had resident participation. The Resident group was associated with longer operative times. We identified no differences in operative morbidity, reoperations, overall survival, disease-free survival, or local-regional recurrence in the Resident and No Resident groups. Resident involvement in breast cancer operations was associated with longer operative times but did not affect any other perioperative or cancer outcome in our institution. This information can be used to reassure program directors, attending surgeons, and patients if they have questions or concerns about the safety or effectiveness of cancer surgery when there is surgical resident participation.


Transcytotic efflux from early endosomes is dependent on cholesterol and glycosphingolipids in polarized hepatic cells.
We examined the role that lipid rafts play in regulating apical protein trafficking in polarized hepatic cells. Rafts are postulated to form in the trans-Golgi network where they recruit newly synthesized apical residents and mediate their direct transport to the apical plasma membrane. In hepatocytes, single transmembrane and glycolipid-anchored apical proteins take the "indirect" route. They are transported from the trans-Golgi to the basolateral plasma membrane where they are endocytosed and transcytosed to the apical surface. Do rafts sort hepatic apical proteins along this circuitous pathway? We took two approaches to answer this question. First, we determined the detergent solubility of selected apical proteins and where in the biosynthetic pathway insolubility was acquired. Second, we used pharmacological agents to deplete raft components and assessed their effects on basolateral-to-apical transcytosis. We found that cholesterol and glycosphingolipids are required for delivery from basolateral early endosomes to the subapical compartment. In contrast, fluid phase uptake and clathrin-mediated internalization of recycling receptors were only mildly impaired. Apical protein solubility did not correlate with raft depletion or impaired transcytosis, suggesting other factors contribute to apical protein insolubility. Examination of apical proteins in Fao cells also revealed that raft-dependent sorting does not require the polarized cell context.


A very rare cause of acute pancreatitis: Berardinelli-Seip congenital lipodystrophy.
Pancreatitis is among rare diseases in pediatrics clinics. It is usually presented with a sign of underlying systemic disease. Berardinelli-Seip congenital lipodystrophy (BSCL) is a very rare disease characterized by near absence of adipose tissue resulting in apparent muscle hypertrophy from birth or early infancy associated with severe insulin resistance. Common clinical features are hypertriglyceridemia, acanthosis nigricans, hepatomegaly with or without splenomegaly and high stature. Acromegaloid features, cardiomyopathy and mental retardation can also be present. We describe a 7-year-old Turkish boy with these clinical features of BSCL and presented with acute pancreatitis.


Description of Globodera ellingtonae n. sp. (Nematoda: Heteroderidae) from Oregon.
A new species of cyst nematode, Globodera ellingtonae, is described from soil collected from a field in Oregon. Second-stage juveniles (J2) of the species are characterized by body length of 365-515 μm, stylet length of 19-22.5 μm, basal knobs rounded posteriorly and pointed anteriorly, tail 39-55 μm, hyaline tail terminus 20-32.5 μm, and tail tapering uniformly but abruptly narrowing and constricted near the posterior third of the hyaline portion, ending with a peg-like, finely rounded to pointed terminus. Cysts are spherical to sub-spherical, dark to light brown and circumfenestrate and cyst wall pattern is ridge-like with heavy punctations. Males have a stylet length of 21-25 μm and spicule length of 30-37 μm with a pointed thorn-like tip. Females have a stylet length of 20-22.5 μm, one head annule and labial disc, heavy punctations on the cuticle, and short vulval slit 7.5-8 μm long. Morphologically this new, round-cyst species differs from the related species G. pallida, G. rostochiensis, G. tabacum complex and G. mexicana by its distinctive J2 tail, and by one or another of the following: shorter mean stylet length in J2, females and males; number of refractive bodies in the hyaline tail terminus of J2; cyst morphology including Granek's ratio; number of cuticular ridges between the anus and vulva; and in the shape and length of spicules in males. Its relationship to these closely related species are discussed. Based upon analysis of ribosomal internal transcribed spacer (ITS) sequences, G. ellingtonae n. sp. is distinct from G. pallida, G. rostochiensis, G. tabacum and G. mexicana. Bayesian and Maximum Parsimony analysis of cloned ITS rRNA gene sequences indicated three clades, with intraspecific variability as high as 2.8%. In silico analysis revealed ITS restriction fragment length polymorphisms for enzymes Bsh 1236I, Hinf I, and Rsa I that overlap patterns for other Globodera species.


Neurocognitive Predictors of Academic Outcomes Among Childhood Leukemia Survivors.
Acute lymphoblastic leukemia is the most common pediatric cancer, and survival approaches 90%. Acute lymphoblastic leukemia survivors are more likely than healthy peers or siblings to experience academic underachievement, yet little is known about neurocognitive predictors of academic outcomes. Objectives were to compare neurocognitive abilities to age-adjusted standardized norms, examine change over time in neurocognitive abilities, and establish neurocognitive predictors of academic outcomes. Seventy-one children were followed over the course of therapy. Cognitive abilities were assessed during induction when the child was in remission (baseline) and annually for 3 years (years 1, 2, and 3). Reading and mathematics abilities were assessed at year 3. Fine motor dexterity was significantly below age-adjusted norms at all data points but showed improvement over time. Baseline visual-motor integration was within the reference range but significantly declined by year 3, and mean scores at years 2 and 3 were significantly below age-adjusted norms. Verbal short-term memory was significantly below age-adjusted norms at all assessments. Visual-motor integration predicted reading and mathematics abilities. Verbal short-term memory predicted reading abilities, and visual short-term memory predicted mathematics abilities. Central nervous system-directed therapy is associated with specific neurocognitive problems. Visual-spatial skills and verbal and visual short-term memory predict academic outcomes. Early assessment of visual-spatial perception and short-term memory can identify children at risk of academic problems. Children who are at risk of academic problems could benefit from a school-based individual educational program and/or educational intervention.


Extracellular vesicles secreted by Saccharomyces cerevisiae are involved in cell wall remodelling.
Extracellular vesicles (EVs) are membranous vesicles that are released by cells. In this study, the role of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery in the biogenesis of yeast EVs was examined. Knockout of components of the ESCRT machinery altered the morphology and size of EVs as well as decreased the abundance of EVs. In contrast, strains with deletions in cell wall biosynthesis genes, produced more EVs than wildtype. Proteomic analysis highlighted the depletion of ESCRT components and enrichment of cell wall remodelling enzymes, glucan synthase subunit Fks1 and chitin synthase Chs3, in yeast EVs. Interestingly, EVs containing Fks1 and Chs3 rescued the yeast cells from antifungal molecules. However, EVs from fks1∆ or chs3∆ or the vps23∆chs3∆ double knockout strain were unable to rescue the yeast cells as compared to vps23∆ EVs. Overall, we have identified a potential role for yeast EVs in cell wall remodelling.


Chronic alcohol drinking persistently suppresses thalamostriatal excitation of cholinergic neurons to impair cognitive flexibility.
Exposure to addictive substances impairs flexible decision making. Cognitive flexibility is mediated by striatal cholinergic interneurons (CINs). However, how chronic alcohol drinking alters cognitive flexibility through CINs remains unclear. Here, we report that chronic alcohol consumption and withdrawal impaired reversal of instrumental learning. Chronic alcohol consumption and withdrawal also caused a long-lasting (21 days) reduction of excitatory thalamic inputs onto CINs and reduced pause responses of CINs in the dorsomedial striatum (DMS). CINs are known to inhibit glutamatergic transmission in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) but facilitate this transmission in D2-MSNs, which may contribute to flexible behavior. We discovered that chronic alcohol drinking impaired CIN-mediated inhibition in D1-MSNs and facilitation in D2-MSNs. Importantly, in vivo optogenetic induction of long-term potentiation of thalamostriatal transmission in DMS CINs rescued alcohol-induced reversal learning deficits. These results demonstrate that chronic alcohol drinking reduces thalamic excitation of DMS CINs, compromising their regulation of glutamatergic transmission in MSNs, which may contribute to alcohol-induced impairment of cognitive flexibility. These findings provide a neural mechanism underlying inflexible drinking in alcohol use disorder.


Ischemic priapism: Can eosinophil count and platelet functions be positive predictive factors in etiopathogenesis.
We evaluated the relation between ischemic priapism (IP) and blood count parameters in IP patients. We especially wanted to examine the contribution of eosinophil count (EC), platelet count (PC), and mean platelet volume (MPV) values, which are suspected predictive parameters for vascular endothelium damage and venoocclusive pathogenesis and etiopathogenesis, particularly in IP. A total of 40 IP patients fulfilled the study criteria. Forty healthy volunteers in a similar age group were included as the control group. Complete blood count values were compared between the two groups. Intergroup comparisons were performed using the Mann-Whitney U test, and the chi-square test was used to assess the relationship between categorical variables in the patient groups. The area under the curve was calculated by receiver operating characteristic (ROC) regression analyses. Epidemiological diagnosis percentages were calculated by finding cutoff values. The IP group's high MPV, PC, and EC values compared to those of the control group were detected to be statistically significant (p<0.001, p=0,03, p=0.001, respectively). No statistically significant difference was observed between the two groups for other blood count parameters. Statistically significant values for IP were measured as MPV: positive predictive value: 84%; EC: positive predictive value: 71.4%; and PC: positive predictive value: 61.4%. High MPV, PC, and EC values are significant positive predictive factors in IP etiopathogenesis. No proof was detected for other blood count parameters playing an active role in IP etiopathogenesis.


Short-term results of a 5-week comprehensive cardiac rehabilitation program after first-time myocardial infarction.
A prospective single-center interventional cohort study was conducted to evaluate the effects of a 5-week comprehensive cardiac rehabilitation program on terms exercise capacity, quality of life, echocardiographic findings and autonomic modulation after first-time myocardial infarction. We studied 37 consecutive post-myocardial infartion patients (mean age 66 years). All patients began a 5-week cardiac rehabilitation supervised training. The exercise program consisted of 40 minutes of training, three times a week, on a cycle ergometer at 60-80% of the maximal heart rate. At baseline and after training program we analyzed: the distance walked after the Six-Minutes Walking Test (6MWT); quality of life (QoL) assesed using the Psychological General Well-Being Inventory (PGWBI) questionnaire; echocardiographic finding and autonomic balance assesed heart rate variability (HRV). We observed statistically significant improvement in exercise capacity (from 423±94 to 496±13 m; P<0.05). Also we observed statistically significant improvements in the many PGWBI dimensions; particularly, anxiety +5.8% (from 18.11±5.2 to 19.12±4.4); depression +6.0% (from 12.00±3.0 to 12.73±2.4); positive well-being +6% (from 11.55±3.5 to 12.23±4.0); general health +10.3% (from 9.48±3.5 to 10.46±2.87); vitality +6.8% (from 12.96±4.2 to 13.85±4.2). Finally, we observed changes in HRV indices after training program: RR (from 903±169 ms to 952±163 ms; P<0.05), pNN50% (from 4.74±4.89 to 6.23±5.53; P<0.05), in time-domain; LF (from 274±169 to 362±233 ms2; P<0,05); HF (from 214±154 to 314±194 ms2; P<0.05) and LF/HF (from 1.53±0.54 to 1.24±0.47; P<0.05) in frequency-domain. The study suggest that a cardiac rehabilitation program in postmyocardial infarction improves exercise capacity, QoL and autonomic modulation.


An aquarium hobbyist poisoning: Identification of new palytoxins in Palythoa cf. toxica and complete detoxification of the aquarium water by activated carbon.
Palytoxin (PLTX) is a lethal natural toxin often found in Palythoa zoantharians that, together with its congeners, may induce adverse effects in humans after inhalation of toxic aerosols both in open-air and domestic environments, namely in the vicinity of public and private aquaria. In this study, we describe a poisoning of an aquarium hobbyist who was hospitalized after handling a PLTXs-containing zoantharian hexacoral. Furthermore, we provide evidence for water detoxification. The zoantharian was morphologically and genetically identified as Palythoa cf. toxica (Cnidaria: Anthozoa). Palytoxin itself and two new PLTX congeners, a hydroxyPLTX and a deoxyPLTX, were detected and structurally identified by liquid chromatography high resolution multiple stage mass spectrometry (LC-HRMSn, n = 1, 2). Total and individual toxins were quantified by LC-HRMS and sandwich ELISA both in the zoantharian (93.4 and 96.80 μg/g, respectively) and in the transport water (48.3 and 42.56 μg/mL, respectively), with an excellent mean bias of 1.3% between the techniques. Activated carbon adsorbed 99.7% of PLTXs contained in the seawater and this represents a good strategy for preventing aquarium hobbyist poisonings.


[From the Cochrane Library: the use of peer review is still under discussion].
Peer review is generally considered to be an invaluable part of the editorial process of biomedical journals. It is widely assumed that peer review has positive effects on the quality of submitted papers and of biomedical research. This is why improvements in peer reviewing have been studied for some years. According to the authors of a recent Cochrane methodology review, peer review does improve the quality of papers, but there is insufficient evidence that it also improves the quality of biomedical research. A major study on this subject is called for, since its results could have implications for patient care and scientific research.


Dental injuries in Swiss soccer supporters: A comparative study of regular fans, ultras, and hooligans for public health strategies.
Violence among soccer supporters continues to pose a significant public health concern in many parts of the world. In Switzerland, hooliganism is largely uninvestigated. This study aimed to examine incidents of violence and associated dental injuries among different groups of soccer supporters, as well as assess the impact of intoxicants on their behavior, using survey data from regular fans, ultras, and hooligans in the Swiss Football League. A cross-sectional survey using a standardized questionnaire was conducted among distinct factions of soccer supporters in the Swiss Football League in 2022. A total of 165 participants self-identified as belonging to one of three subgroups: "regular fan," "ultra," or "hooligan." Data were gathered on physical altercations, dental injuries, possession of mouthguards, intoxicant use, and medical assistance. Descriptive statistics, logistic regression models, and significance tests were used for data analysis (α = .05). Hooligans had a higher frequency of dental injuries resulting from fights than ultras and regular fans. Hooligans with 11-20 fights per soccer season had a 9.6 times higher probability of dental trauma than those with 0-5 fights (p = .048). Possession of a mouthguard was associated with a lower risk of dental injuries for hooligans but an increased risk for ultras. Additionally, hooligans were found to differ significantly from other groups in their consumption of amphetamines and cocaine (p < .001). The study found a strong link between physical altercations and dental injuries among soccer supporters. To promote better prevention, there is a necessity for enhanced educational initiatives facilitated by dentists to amplify the dissemination of mouthguards. Furthermore, it is crucial to raise awareness regarding their proper fitting to minimize the occurrence of combat-related dental injuries. Health authorities and other stakeholders should take a comprehensive approach to addressing some of the root causes of violent behavior, which include alcohol abuse and illicit substance consumption.


Greater dietary fat oxidation in obese compared with lean men: an adaptive mechanism to prevent liver fat accumulation?
Liver fat represents a balance between input, secretion, and oxidation of fatty acids. As humans spend the majority of a 24-h period in a postprandial state, dietary fatty acids make an important contribution to liver fat metabolism. We compared hepatic fatty acid partitioning in healthy lean (n = 9) and abdominally obese (n = 10) males over 24 h. Volunteers received three mixed meals adjusted for basal metabolic rate. U-13C-labeled fatty acids were incorporated into the meals, and [2H2]palmitate was infused intravenously to distinguish between sources of fatty acids incorporated into VLDL-TG. Immunoaffinity chromatography was used to isolate VLDL-TG of hepatic origin. Liver and whole body fatty acid oxidation was assessed by isotopic enrichment of 3-hydoxybutyrate and breath CO2. We found a similar contribution of dietary fatty acids to VLDL-TG in the two groups over 24 h. The contribution of fatty acids from splanchnic sources was higher (P < 0.05) in the abdominally obese group. Ketogenesis occurred to a significantly greater extent in abdominally obese compared with lean males, largely due to lessened downregulation of postprandial ketogenesis (P < 0.001). The appearance of 13C in breath CO2 was also greater (P < 0.001) in abdominally obese compared with lean men. Hepatic elongation and desaturation of palmitic acid were higher (P < 0.05) in abdominally obese than in lean males. Oxidation of dietary fatty acids and hepatic desaturation and elongation of palmitic acid occurred to a greater extent in abdominally obese men. These alterations may represent further pathways for redirection of fatty acids into export from the liver or oxidation to prevent liver fat accumulation.


Clinically relevant concentrations of fosfomycin combined with polymyxin B, tobramycin or ciprofloxacin enhance bacterial killing of Pseudomonas aeruginosa, but do not suppress the emergence of fosfomycin resistance.
Fosfomycin resistance occurs rapidly with monotherapy. This study systematically investigated bacterial killing and emergence of fosfomycin resistance with fosfomycin combinations against Pseudomonas aeruginosa. Four clinical isolates and a reference strain of P. aeruginosa were employed. Combinations of fosfomycin plus polymyxin B, tobramycin or ciprofloxacin were examined over 24 h using time-kill studies (inocula ∼10(6) cfu/mL) incorporating clinically relevant concentrations (fosfomycin, 30, 150 or 300 mg/L; polymyxin B, 0.5, 1 or 2 mg/L; tobramycin, 0.5, 1.5 or 4 mg/L; ciprofloxacin, 0.5, 1 or 2.5 mg/L). Microbiological response was examined by log changes and population analysis profiles. Against susceptible isolates, monotherapy produced varying degrees of initial killing followed by rapid regrowth. Fosfomycin plus polymyxin B or tobramycin produced greater initial killing (up to ∼4 log10 cfu/mL) with many concentrations compared with monotherapy against fosfomycin-susceptible (FOF(S)) isolates. With these combinations, synergy or additivity was observed in 54 (67%) and 49 (60%) of 81 cases (nine combinations across three isolates at three timepoints) for polymyxin B and tobramycin, respectively. Substantial improvements in killing were absent against fosfomycin-resistant (FOF(R)) isolates. For fosfomycin/ciprofloxacin combinations, synergy or additivity was observed against FOF(R) isolates in 33 of 54 (61%) cases (nine combinations across two isolates at three timepoints), while improvements in killing were largely absent against FOF(S) isolates. No combination prevented emergence of fosfomycin resistance. Against P. aeruginosa, fosfomycin in combination with polymyxin B or tobramycin (FOF(S) isolates) or ciprofloxacin (FOF(R) isolates) increased bacterial killing, but did not suppress emergence of fosfomycin resistance.


Proteomic analysis of Escherichia coli associated with urinary tract infections.
Escherichia coli is a major cause of urinary tract infections (UTIs) where the initial infection arises from bacteria originating in the bowel. However, significant differences are observed between the genomes of intestinal and urinary E. coli strains with the latter possessing many adaptations that promote growth in the urinary tract. To define further the adaptation of urinary E. coli isolates, the cellular proteomes of 41 E. coli strains, collected from cases of UTIs or random faecal samples, were compared by 2-D gel electrophoresis and principal component analysis. The data indicated that individual patients carried relatively homogenous E. coli populations, as defined by their cellular proteomes, but the populations were distinct between patients. For one patient, E. coli, isolated during two recurrent infections 3 months apart, were indistinguishable, indicating that for this patient the infections were possibly caused by the same bacterial population. To understand the basis of the discrimination of the bacteria, selected protein spots were identified by peptide fragment fingerprinting. The identified proteins were involved in a variety of metabolic and structural roles. The data obtained for these E. coli strains provide a basis from which to target key bacterial proteins for further investigation into E. coli pathogenesis.


A general theory of rehabilitation: Rehabilitation catalyses and assists adaptation to illness.
There is no general theory of rehabilitation, only definitions and descriptions, with the biopsychosocial model of illness as a structure. To develop a general theory of rehabilitation that explains how healthcare rehabilitation changes outcomes and to evaluate its validity. A general rehabilitation theory would help research, improve services, increase understanding, modify resource allocation and explain some anomalies, such as how rehabilitation helps when no natural recovery occurs. People adapt to change throughout their lives. Illness is a change, and people adapt to their illness. Adaptation's purpose is to maintain an equilibrium in a person's life. The balanced components are related to Maslow's five needs: basic, safety, affiliation, status and self-fulfilment. The general theory of behaviour suggests that a person's behaviours change to maintain balance, regulated by a central homeostatic mechanism. Rehabilitation aids adaptation to changes associated with illness through accurate diagnosis and formulation, catalysing adaptation, optimising the environment and assisting the person in making necessary changes by safely practising activities and teaching self-management. The theory makes the person the central active agent, emphasises the importance of the environment in facilitating adaptation, explains why all conditions may benefit, including progressive and static conditions, suggests that health can be equated to someone maintaining their equilibrium and explains why a small dose may be very effective. The general theory of rehabilitation emphasises the catalytic effects of rehabilitation in facilitating and guiding adaptation and suggests areas for research and improvement.


Accidental anal intercourse: does it really happen?
A postal survey was conducted of members of the Association of Forensic Physicians (UK) to determine whether accidental anal intercourse occurs in heterosexual relationships and, if so, whether intoxication by alcohol or drugs and sexual inexperience were likely to be causative factors. Of the 512 (47.9%) replies, there were 498 individuals who had had a previous heterosexual relationship and may have experienced accidental anal intercourse. Of these, there were 26 (7.2%) males and 14 (10.4%) females who reported at least one lifetime episode of accidental anal intercourse. Amongst those with a history of accidental anal intercourse, 79% reported that they were sexually experienced at the time and 83% reported that their partners were sexually experienced. Personal intoxication by alcohol or drugs at the time of accidental anal intercourse was reported by 43%, with 41% reporting that their partners were intoxicated.


In vitro and in silico cloning of Xenopus laevis SOD2 cDNA and its phylogenetic analysis.
By using the methodology of both wet and dry biology (i.e., RT-PCR and cycle sequencing, and biocomputational technology, respectively) and the data obtained through the Genome Projects, we have cloned Xenopus laevis SOD2 (MnSOD) cDNA and determined its nucleotide sequence. These data and the deduced protein primary structure were compared with all the other SOD2 nucleotide and amino acid sequences from eukaryotes and prokaryotes, published in public databases. The analysis was performed by using both Clustal W, a well known and widely used program for sequence analysis, and AntiClustAl, a new algorithm recently created and implemented by our group. Our results demonstrate a very high conservation of the enzyme amino acid sequence during evolution, which proves a close structure-function relationship. This is to be expected for very ancient molecules endowed with critical biological functions, performed through a specific structural organization. The nucleotide sequence conservation is less pronounced: this too was foreseeable, due to neutral mutations and to the species-specific codon usage. The data obtained by using AntiClustAl are comparable with those produced with Clustal W, which validates this algorithm as an important new tool for biocomputational analysis. Finally, it is noteworthy that evolutionary trees, drawn by using all the available data on SOD2 nucleotide sequences and amino acid and either Clustal W or AntiClustAl, are comparable to those obtained through phylogenetic analysis based on fossil records.


Mediterranean marine biodiversity under threat: Reviewing influence of marine litter on species.
The Mediterranean Sea is one of the most polluted seas worldwide, especially with regard to plastics. The presence of this emerging man made contaminant in marine environments precludes large effects and interactions with species exposed to massive litter quantities. In this review, available data of floating and seafloor litter around Mediterranean sub-basins are reported. A review of scientific literature on the interaction of plastic with marine biota resulted in the identification of 134 species, several taxa and feeding strategies affected from 1986 to 2014. Data from 17,334 individuals showed different levels of ingestion and effects on catalogued IUCN species (marine mammals and sea turtles) in addition to several pelagic fish and elasmobranchs. Biodiversity is certainly under threat, and knowledge of the extent of taxa affected is of concern considering the increasing plastic loads in the Mediterranean Sea and worldwide.


The potential value and toxicity of chromium picolinate as a nutritional supplement, weight loss agent and muscle development agent.
The element chromium apparently has a role in maintaining proper carbohydrate and lipid metabolism in mammals. As this role probably involves potentiation of insulin signalling, chromium dietary supplementation has been postulated to potentially have effects on body composition, including reducing fat mass and increasing lean body mass. Because the supplement is absorbed better than dietary chromium, most studies have focused on the use of chromium picolinate [Cr(pic)(3)]. Cr(pic)(3) has been amazingly popular with the general public, especially with athletes who may have exercise-induced increased urinary chromium loss; however, its effectiveness in manifesting body composition changes has been an area of intense debate in the last decade. Additionally, claims have appeared that the supplement might give rise to deleterious effects. However, over a decade of human studies with Cr(pic)(3) indicate that the supplement has not demonstrated effects on the body composition of healthy individuals, even when taken in combination with an exercise training programme. Recent cell culture and in vivo rat studies have indicated that Cr(pic)(3) probably generates oxidative damage of DNA and lipids and is mutagenic, although the significance of these results on humans taking the supplement for prolonged periods of time is unknown and should be a focus for future investigations. Given that in vitro studies suggest that other forms of chromium used as nutritional supplements, such as chromium chloride, are unlikely to be susceptible to generating this type of oxidative damage, the use of these compounds, rather than Cr(pic)(3), would appear warranted. Potential neurological effects (both beneficial and deleterious) from Cr(pic)(3) supplementation require further study.


Positive experiences associated with acquired hearing loss, Ménière's disease, and tinnitus: a review.
It is common to study and understand how various illness and disorders result in negative consequences. However, positive experiences have been reported in a range of disabling conditions including multiple sclerosis, heart disease, physical and sensory disabilities. This paper presents a literature review of studies that have explored positive experiences associated with acquired hearing loss, Ménière's disease, and tinnitus. A review of the peer reviewed scientific literature. A comprehensive search strategy identified 15 articles after applying inclusion criteria. A range of positive experiences have been reported by patients with hearing and balance disorders and by their significant others. Associations between demographic variables (e.g. age, gender), audiological variables (e.g. severity of the condition, duration) and the reported positive experiences are low. In Ménière's disease, self-reported positive experiences can predict the impact of the condition. However, this phenomenon has not yet been demonstrated in relation to hearing loss and tinnitus. Positive experiences associated with audio-vestibular disorders have been demonstrated. Further research is needed on the long-term benefits of the encouragement of such experiences and positive attitudes in persons with hearing loss, tinnitus, and imbalance.


Parentage and relatedness in polyandrous comb-crested jacanas using ISSRs.
In this article we present the first analysis of parentage and relatedness in a natural vertebrate population, using Intersimple Sequence Repeat (ISSR) markers. Thus, 28 ISSR markers were used in a study of a sex-role reversed, simultaneously polyandrous shorebird from northeastern Australia, the comb-crested jacana (Irediparra gallinacea). Assessment of parentage was based on comparison of field observations, novel bands, individual-specific bands found in 7/9 males and 4/6 females, and a 99% CI exclusion criteria. Integrating results from these approaches resulted in confirmation of paternity in all 36 chicks. In only one case (2.8% of chicks) was a co-mate assigned paternity. Thus, comb-crested jacanas appear to be genetically monogamous. These results showed resemblance to sequentially polyandrous birds but differed from the simultaneously polyandrous wattled jacana ( Jacana jacana; Emlen et al. 1998). A significant relationship between relatedness and ISSR similarity resulted in recognition that 14/15 adults sampled may be related to at least one other adult by 0.25 or more. Lack of dispersal may be explained by physical limitations and adequate regional habitat. ISSRs proved to be simple and helpful in resolving these issues.


Physical fitness predicts technical-tactical and time-motion profile in simulated Judo and Brazilian Jiu-Jitsu matches.
Among combat sports, Judo and Brazilian Jiu-Jitsu (BJJ) present elevated physical fitness demands from the high-intensity intermittent efforts. However, information regarding how metabolic and neuromuscular physical fitness is associated with technical-tactical performance in Judo and BJJ fights is not available. This study aimed to relate indicators of physical fitness with combat performance variables in Judo and BJJ. The sample consisted of Judo (n = 16) and BJJ (n = 24) male athletes. At the first meeting, the physical tests were applied and, in the second, simulated fights were performed for later notational analysis. The main findings indicate: (i) high reproducibility of the proposed instrument and protocol used for notational analysis in a mobile device; (ii) differences in the technical-tactical and time-motion patterns between modalities; (iii) performance-related variables are different in Judo and BJJ; and (iv) regression models based on metabolic fitness variables may account for up to 53% of the variances in technical-tactical and/or time-motion variables in Judo and up to 31% in BJJ, whereas neuromuscular fitness models can reach values up to 44 and 73% of prediction in Judo and BJJ, respectively. When all components are combined, they can explain up to 90% of high intensity actions in Judo. In conclusion, performance prediction models in simulated combat indicate that anaerobic, aerobic and neuromuscular fitness variables contribute to explain time-motion variables associated with high intensity and technical-tactical variables in Judo and BJJ fights.


Lipoprotein-associated phospholipase A2: a new therapeutic target.
Lipoprotein-associated phospholipase A2 is an enzyme produced by inflammatory cells, which binds to apolipoprotein B-containing lipoproteins and degrades oxidatively modified phospholipids in low-density lipoprotein cholesterol particles, leading to formation of proinflammatory and cytotoxic products. Experimental studies suggest a role for lipoprotein-associated phospholipase A2 in the formation of advanced rupture-prone atherosclerotic lesions, and epidemiological investigations have linked it to increased cardiovascular risk. Ongoing trials are evaluating the role of novel pharmacological inhibitors of this enzyme, such as darapladib, in the management of high-risk coronary artery disease patients.


Immunologic structures and functions of the gut.
The intestine is richly populated with lymphoid tissue capable of initiating and effecting a wide variety of immunologic reactions. These reactions have consequences not only for the gut itself but for the body in general, and have established the importance of the gut as an immunologic organ. Among the outer and inner surfaces of our body, the 200 to 300 m2 of the gut contrast with the 2 m2 of the skin, and the 80 m2 of the lung. At the inner surface of the intestine, our organism contacts intimately bacteria, parasites, enzymes, toxins, a wide variety of dietary substances and their breakdown products. The essential barrier against the permanent antigenic burden is the mucosa. Its integrity depends on the continual replication, maturation, and metabolism of its constituents. Additional defense functions are exerted by the mucus, lysozyme, phagocytes, other cells, humoral factors and biological response modifiers involved in inflammatory and immune reactions. Some of these factors are being produced very close to the surface at which they act. The sum of the mechanical, humoral, cellular, immunologic and non-immunologic defense factors of the intestinal mucosa constitutes the mucosal block. However, the block is not complete. Rather, a continuous antigenic uptake through the epithelial layer takes place. The specialized structures of Peyer's patches, solitary lymph follicles, appendix vermiformis and their associated epithelium allow a controlled antigen uptake (sampling). Because of the heavy antigenic load, the intestine can be described as the most important immunologic contact organ of our body. The antigens may give rise to local and systemic immune reactions with antibody production, or the suppression of systemic immunologic responses to ingested antigens ("oral tolerance").


Resource-use strategies of native and invasive plants in Eastern North American forests.
Studies in disturbed, resource-rich environments often show that invasive plants are more productive than co-occurring natives, but with similar physiological tradeoffs. However, in resource-limited habitats, it is unclear whether native and invasive plants have similar metabolic constraints or if invasive plants are more productive per unit resource cost - that is, use resources more efficiently. Using a common garden to control for environment, we compared leaf physiological traits relating to resource investments, carbon returns, and resource-use efficiencies in 14 native and 18 nonnative invasive species of common genera found in Eastern North American (ENA) deciduous forest understories, where growth is constrained by light and nutrient limitation. Despite greater leaf construction and nitrogen costs, invaders exhibited greater instantaneous photosynthetic energy-use efficiency (PEUE) and marginally greater photosynthetic nitrogen-use efficiency (PNUE). When integrated over leaf lifespan (LL), these differences were magnified. Differences in efficiency were driven by greater productivity per unit leaf investment, as invaders exhibited both greater photosynthetic abilities and longer LL. Our results indicate that woody understory invaders in ENA forests are not constrained to the same degree by leaf-based metabolic tradeoffs as the native understory flora. These strategy differences could be attributable to pre-adaptation in the native range, although other explanations are possible.


Tachykinin-induced phosphoinositide breakdown in airway smooth muscle and epithelium: relationship to contraction.
We have studied the contractile response and phosphoinositide hydrolysis induced by substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and Alp-Phe-Phe(R)-Gly[ANC-2]-Leu-Met-NH2 (L 363851), a selective NK2-receptor agonist, in guinea pig tracheal smooth muscle. The four tachykinins elicited a concentration-dependent contraction in tracheal smooth muscle devoid of epithelium, with the following order of potency: NKA greater than L 363851 greater than NKB greater than SP, (EC50 1.0 x 10(-9) M, 3.2 x 10(-9) M, 7.5 x 10(-9) M and 1.2 x 10(-7) M, respectively), which suggests that NK2 receptors predominate in airway smooth muscle. In the presence of epithelium, the sensitivity of airway smooth muscle to tachykinins was decreased, and the concentration response curves to tachykinins were shifted rightward by 30-fold for SP, 9-fold for NKA, and 5-fold for NKB. The concentration response curve to L 363851 was not significantly shifted in the presence of epithelium. This suggests that epithelium may release a relaxant factor in response to tachykinins via an NK1 receptor. In airway smooth muscle, we found that tachykinins elicited phosphoinositide breakdown with an order of potency similar to that for contractile response (EC50 2.2 x 10(-5) M, 3.6 x 10(-5) M, 4.4 x 10(-5) M, and 5.9 x 10(-5) M). In epithelium, SP alone elicited a significant phosphoinositide breakdown, suggesting that epithelial receptors to tachykinins may be of the NK1 subtype. Since it is established that phosphoinositide derivatives can elicit mobilization of intracellular calcium, our results suggest that phosphoinositide breakdown is the coupling mechanism for tachykinin-induced contraction of airway smooth muscle.


Lingguizhugan Decoction, a Chinese herbal formula, improves insulin resistance in overweight/obese subjects with non-alcoholic fatty liver disease: a translational approach.
Lingguizhugan Decoction (LGZG) has been investigated in basic studies, with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease (NAFLD). This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting. A randomized, double-blinded, placebo-controlled trial was performed. A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG (two groups: standard dose and low dose) or placebo for 12 weeks on the basis of lifestyle modifications. The primary efficacy variable was homeostasis model assessment of insulin resistance (HOMA-IR). Analyses were performed in two populations in accordance with body mass index (BMI; overweight/obese, BMI ⩾ 24 kg/m2; lean, BMI < 24 kg/m2). For overweight/obese participants, low-dose LGZG significantly decreased their HOMA-IR level compared with placebo (-0.19 (1.47) versus 0.08 (1.99), P = 0.038). For lean subjects, neither dose of LGZG showed a superior effect compared with placebo. Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and autophagy related 3 (ATG3) significantly increased after LGZG intervention in overweight/obese population. Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD. The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3. Lean subjects may not be a targeted population for LGZG.


The effective number of a population that varies cyclically in size. I. Discrete generations.
We consider a dioecious population having numbers of males and females that vary over time in cycles of length k. It is shown that if k is small in comparison with the numbers of males and females in any generation of the cycle, the effective population number (or size), N(e), is approximately equal to the harmonic mean of the effective population sizes during any given cycle. This result holds whether the locus under consideration is autosomal or sex-linked and whether inbreeding effective population numbers or variance effective population numbers are involved in the calculation of N(e). If, however, only two successive generations in the cycle are considered and the population changes in size between these generations, the inbreeding effective population number, N(eI), differs from the variance effective population number, N(eV). The mutation effective population number turns out to be the same as the number derived using calculations involving probabilities of identity by descent. It is also shown that, at least in one special case, the eigenvalue effective population number is the same as N(eV).


Histone underacetylation is an ancient component of mammalian X chromosome inactivation.
Underacetylation of histone H4 is thought to be involved in the molecular mechanism of mammalian X chromosome inactivation, which is an important model system for large-scale genetic control in eukaryotes. However, it has not been established whether histone underacetylation plays a critical role in the multistep inactivation pathway. Here we demonstrate differential histone H4 acetylation between the X chromosomes of a female marsupial, Macropus eugenii. Histone underacetylation is the only molecular aspect of X inactivation known to be shared by marsupial and eutherian mammals. Its strong evolutionary conservation implies that, unlike DNA methylation, histone underacetylation was a feature of dosage compensation in a common mammalian ancestor, and is therefore likely to play a central role in X chromosome inactivation in all mammals.


Effect of chloramphenicol and cyanide on the increase in UV resistance of intracellular bacteriophage T1.
The effects of chloramphenicol and cyanide on the increase in UV resistance of intracellular phage T1 infecting cells of E. coli B or E. coli Bs-1 were investigated. The inhibitiors were added to the cells 3 min prior to infection and to the complexes of phage-bacteria 3.5 and 6.5 min after adsorption of phage by the cells. The data obtained are not in agreement with the suggestion that increase in UV resistance of intracellular phage is mainly due to the accumulation of phage DNA inside the host cells. It is suggested that a very important role in this resistance is played by the interaction of phage DNA with the cell membranes.


Hepatitis G virus RNA in the serum of patients with elevated gamma glutamyl transpeptidase and alkaline phosphatase: a specific liver disease? [corrected].
We tested the sera of 67 consecutive patients for hepatitis G virus (HGV) RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). These patients (42 males and 25 females, median age 35 years, range 13-64 years) had liver disease of unknown aetiology and were without markers of hepatitis (A-E) viruses or signs of genetically determined, autoimmune, alcoholic or drug-induced liver disease. The controls in this study were 110 patients (50 females and 60 males, median age 45 years, range 9-65 years) with chronic hepatitis B virus (HBV) infection (19 patients) or hepatitis C virus (HCV) infection (91 patients). Ten of 67 (14.9%) patients with cryptogenic disease were positive for HGV RNA by at least three separate tests; HGV RNA was also detected in one of 19 (5.3%) hepatitis B surface antigen (HBsAg) carriers and in nine of 91 (16.6%) patients with antibody to HCV. These data suggest that HGV occurs as frequently in HCV-infected patients as in those with cryptogenic disease. Elevated serum gamma glutamyl transpeptidase (gamma-GT) (higher than twice the normal value) and alkaline phosphatase levels were found in eight of 10 (80%) HGV RNA positive patients and in six of 57 (10.5%) HGV RNA negative patients (P < 0.0001). Five (50%) HGV RNA positive patients had non-specific inflammatory bile duct lesions. A statistically significant difference was observed between HGV RNA positive and negative patients with chronic HBV or HCV infections (P < 0.029). Therefore, the spectrum of liver disease associated with HGV is wide, but a characteristic lesion of the bile duct leading to elevation of cholestatic enzymes might be specific for this virus.


Unraveling the genetics of Joubert and Meckel-Gruber syndromes.
Joubert (JBTS) and Meckel-Gruber (MKS) syndromes are recessive neurodevelopmental conditions caused by mutations in proteins that are structural or functional components of the primary cilium. In this review we provide an overview of their clinical diagnosis, management and molecular genetics. Both have variable phenotypes, extreme genetic heterogeneity, and display allelism both with each other and other ciliopathies. Recent advances in genetic technology have significantly improved diagnosis and clinical management of ciliopathy patients, with the delineation of some general genotype-phenotype correlations. We highlight those that are most relevant for clinical practice, including the correlation between TMEM67 mutations and the JBTS variant phenotype of COACH syndrome. The subcellular localization of the known MKS and JBTS proteins is now well-described, and we discuss some of the contemporary ideas about ciliopathy disease pathogenesis. Most JBTS and MKS proteins localize to a discrete ciliary compartment called the transition zone (TZ), and act as structural components of the so-called "ciliary gate" to regulate the ciliary trafficking of cargo proteins or lipids. Cargo proteins include enzymes and transmembrane proteins that mediate intracellular signaling. The disruption of TZ function may contribute to the ciliopathy phenotype by altering the composition of the ciliary membrane or axoneme, with impacts on essential developmental signaling including the Wnt and Shh pathways as well as the regulation of secondary messengers such as inositol-1,4,5-trisphosphate (InsP3) and cAMP. However, challenges remain in the interpretation of the pathogenic potential of genetic variants of unknown significance, and in the elucidation of the molecular mechanisms of phenotypic variability in JBTS and MKS. The further genetic and functional characterization of these conditions is essential to prioritize patients for new targeted therapies.


[Use of hemodialysis in intensive care of organophosphorus insecticide poisoning].
A total of 163 hemoperfusions carried out in order to remove poison in patients with acute poisoning with organophosphorous insecticides (OPI) showed that this treatment modality effectively removes OPI from te organism. In patients with the most severe forms of acute poisoning hemoperfusion may be effectively combined with hemadsorption and peritoneal dialysis. This variant of detoxication ensures a good clinical effect and a stable decrease of the toxic agent in the blood. The proposed method of blood stabilization with sodium citrate in the extracorporeal contour provides a reliable extracorporeal stabilization of the blood and does not deteriorate the efficacy of hemoperfusion.


Pk-fit: a pharmacokinetic/pharmacodynamic and statistical data analysis software.
This paper presents a new software, Pk-fit, to fit nonlinear models to kinetic and dynamic data. Directly connected to the spreadsheet, a statistical software component manager is available. In the data manager, Pk-fit includes the noncompartmental analysis module, the compartmental analysis module, the nonlinear kinetic process module, the drug absorption module, the pharmacodynamic data modeling module, the simultaneous fitting module, and the user-defined library module. In this paper, we present a detailed comparison of the kinetic analysis using Pk-fit and common software packages, PCNONLIN, MODFIT, MKMODEL, NONMEM, and SIPHAR, based on the textbook published by Gabrielsson in 1992, "Compilation of Analyzed Data Sets for Pharmacokinetic Software Evaluation." The comparison of Pk-fit with the reference softwares revealed that the parameters and their dispersion found with Pk-fit are consistent with the ones estimated with the other programs. In conclusion, Pk-fit constituted a valid tool for pharmacokinetic/pharmacodynamic data analysis.


Crystal structure of the M intermediate of bacteriorhodopsin: allosteric structural changes mediated by sliding movement of a transmembrane helix.
Structural changes in the proton pumping cycle of wild-type bacteriorhodopsin were investigated by using a 3D crystal (space group P622)prepared by the membrane fusion method. Protein-protein contacts in the crystal elongate the lifetime of the M intermediate by a factor of approximately 100,allowing high levels of the M intermediate to accumulate under continuous illumination. When the M intermediate generated at room temperature was exposed to a low flux of X-rays (approximately 10(14) photons/mm2), this yellow intermediate was converted into a blue species having an absorption maximum at 650 nm. This color change is suggested to accompany a configuration change in the retinal-Lys216 chain. The true conformational change associated with formation of the M intermediate was analyzed by taking the X-radiation-induced structural change into account. Our result indicates that, upon formation of the M intermediate, helix G move stowards the extra-cellular side by, on average, 0.5 angstroms. This movement is coupled with several reactions occurring at distal sites in the protein: (1) reorientation of the side-chain of Leu93 contacting the C13 methyl group of retinal, which is accompanied by detachment of a water molecule from the Schiff base; (2) a significant distortion in the F-G loop, triggering destruction of a hydrogen bonding interaction between a pair of glutamate groups (Glu194 and Glu204); (3) formation of a salt bridge between the carboxylate group of Glu204 and the guanidinium ion of Arg82, which is accompanied by a large distortion in the extra-cellular half of helix C; (4)noticeable movements of the AB loop and the cytoplasmic end of helix B. But, no appreciable change is induced in the peptide backbone of helices A,D, E and F. These structural changes are discussed from the viewpoint of translocation of water molecules.


Endometrial curettage in abnormal uterine bleeding and efficacy of progestins for control in cases of hyperplasia.
Abnormal uterine bleeding (AUB) is the most important symptom of endometrial hyperplasia and endometrial curettage (EC) is the gold standard diagnostic procedure. We present the results of patients who underwent EC for AUB and the efficacy of progestin administration in those with endometrial hyperplasia. A total of 415 female patients who presented to Duzce Public Hospital in 2011-2012 for AUB and who underwent EC were included. We determined the reasons for AUB, and females with hyperplasia were treated with 10 mg/day medroxyprogesterone acetate for 14 days/month or 160 mg/day megestrol acetate continuously for 3 months. We evaluated the efficacy of progestins for periods of three and/or six cycles by repeating EC. A statistical analysis of specific endometrial causes according to age of presentation was conducted using the chi-square test. Among the 415 females (average age, 53.5 years) followed for 6 months, 186 had physiological changes (44.8%), 89 had simple hyperplasia (21.44%), 1 had atypical hyperplasia (0.2%), 6 had (1.44%) complex hyperplasia, 3 had (0.72%) atypical complex hyperplasia, and 5 had adenocarcinoma (1.2%). Regression rates were 72.7-100%, and the optimum results were observed after 6 months of hormonal therapy. The main cause of AUB was physiological change. Progestin therapy resulted in significant regression even in females with atypical hyperplasia.


Repetition suppression and plasticity in the human brain.
The suppression of neuronal responses to a repeated event is a ubiquitous phenomenon in neuroscience. However, the underlying mechanisms remain largely unexplored. The aim of this study was to examine the temporal evolution of experience-dependent changes in connectivity induced by repeated stimuli. We recorded event-related potentials (ERPs) during frequency changes of a repeating tone. Bayesian inversion of dynamic causal models (DCM) of ERPs revealed systematic repetition-dependent changes in both intrinsic and extrinsic connections, within a hierarchical cortical network. Critically, these changes occurred very quickly, over inter-stimulus intervals that implicate short-term synaptic plasticity. Furthermore, intrinsic (within-source) connections showed biphasic changes that were much faster than changes in extrinsic (between-source) connections, which decreased monotonically with repetition. This study shows that auditory perceptual learning is associated with repetition-dependent plasticity in the human brain. It is remarkable that distinct changes in intrinsic and extrinsic connections could be quantified so reliably and non-invasively using EEG.


Emotional reactions toward people with dementia - results of a population survey from Germany.
Emotional reactions toward people with disorders are an important component of stigma process. In this study, emotional reactions of the German public toward people with dementia were analyzed. Analyses are based on a national mail survey conducted in 2012. Sample consists of persons aged 18 to 79 years living in private households in Germany. In all 1,795 persons filled out the questionnaire, reflecting a response rate of 78%. Respondents were asked about their emotional reactions and beliefs about dementia. A vast majority of the respondents expressed pro-social reactions, i.e. they felt pity, sympathy, and the need to help a person with dementia. Dementia patients rarely evoked anger (10% or less). Between 25% and 50% of the population showed reactions indicating fear. Respondents who had contacts with a person having dementia or had cared for a dementia patient tended to show less negative reactions (fear, anger) and more pro-social reactions. Respondents who showed pronounced fearful reactions were less likely to believe that dementia patients had a high quality of life, were less willing to care for a family member with dementia at home, and were more skeptical about early detection of dementia. Comparison with the results of another study suggests that fearful reactions toward persons with dementia are much more pronounced than in the case of depression, and less pronounced than in the case of schizophrenia. Fearful reactions toward people with dementia are quite common in the German general public. To reduce fear, educational programs and contact-based approaches should be considered.


Uterine atony prophylaxis with carbetocin versus oxytocin and the risk of major haemorrhage during caesarean section: A retrospective cohort study.
Carbetocin and oxytocin are commonly recommended agents for active management of the third stage of labour. Evidence is inconclusive whether either one more effectively reduces the occurrence of important postpartum haemorrhage outcomes at caesarean section. We examined whether carbetocin is associated with a lower risk of severe postpartum haemorrhage (blood loss ≥ 1000 ml) in comparison with oxytocin for the third stage of labour in women undergoing caesarean section. This was a retrospective cohort study among women undergoing scheduled or intrapartum caesarean section between 1 January 2010 and 2 July 2015 who received carbetocin or oxytocin for the third stage of labour. The primary outcome was severe postpartum haemorrhage. Secondary outcomes included blood transfusion, interventions, third stage complications and estimated blood loss. Outcomes were examined overall and by timing of birth, scheduled versus intrapartum, using propensity score-matched analysis. Among 21,027 eligible participants, 10,564 women who received carbetocin and 3836 women who received oxytocin at caesarean section were included in the analysis. Carbetocin was associated with a lower risk of severe postpartum haemorrhage overall (2.1% versus 3.3%; odds ratio, 0.62; 95% confidence interval 0.48 to 0.79; P < 0.001). This reduction was apparent irrespective of timing of birth. Secondary outcomes also favoured carbetocin over oxytocin. In this retrospective cohort study, the risk of severe postpartum haemorrhage associated with carbetocin was lower than that associated with oxytocin in women undergoing caesarean section. Randomised clinical trials are needed to further investigate these findings.


Associations between county and municipality zoning ordinances and access to fruit and vegetable outlets in rural North Carolina, 2012.
Zoning ordinances and land-use plans may influence the community food environment by determining placement and access to food outlets, which subsequently support or hinder residents' attempts to eat healthfully. The objective of this study was to examine associations between healthful food zoning scores as derived from information on local zoning ordinances, county demographics, and residents' access to fruit and vegetable outlets in rural northeastern North Carolina. From November 2012 through March 2013, county and municipality zoning ordinances were identified and double-coded by using the Bridging the Gap food code/policy audit form. A healthful food zoning score was derived by assigning points for the allowed use of fruit and vegetable outlets. Pearson coefficients were calculated to examine correlations between the healthful food zoning score, county demographics, and the number of fruit and vegetable outlets. In March and April 2013, qualitative interviews were conducted among county and municipal staff members knowledgeable about local zoning and planning to ascertain implementation and enforcement of zoning to support fruit and vegetable outlets. We found a strong positive correlation between healthful food zoning scores and the number of fruit and vegetable outlets in 13 northeastern North Carolina counties (r = 0.66, P = .01). Major themes in implementation and enforcement of zoning to support fruit and vegetable outlets included strict enforcement versus lack of enforcement of zoning regulations. Increasing the range of permitted uses in zoning districts to include fruit and vegetable outlets may increase access to healthful fruit and vegetable outlets in rural communities.


[Diagnostic value of left ventricular diastolic function using pulsed Doppler echocardiography in patients with ischemic heart disease].
Transesophageal atrial pacing was performed in 54 patients (mean age 50.0 +/- 6.8 years) to diagnose coronary heart disease (CHD). ECG was recorded in 12 leads during the test. Echocardiography was used to assess local contractile disorders. The diastolic function of the left ventricle was examined by pulsed Doppler echocardiography in the postpacing period. Thirty eight patients were found to have altered Doppler parameters for transmitral blood flow in the postpacing period as compared to the resting period. Sixteen patients without CHD displayed no changes in the left ventricular diastolic function in the postpacing period. Two types of transmitral blood flow disorders were identified in CHD patients in the postpacing period. The so-called "pseudonormal" type of transmitral blood flow was typical of patients with the most severe contractile impairments and grave course. Abnormalities in local contractility and signs of left ventricular diastolic dysfunction were ascertained to be a sensitive marker for myocardial ischemia.


Ocular perineuritis secondary to neurosyphilis.
Syphilis is a condition caused by the spirochete Treponema pallidum (T. pallidum). Because of its ubiquitous nature, it has been coined as "the great masquerader." Syphilis can present with a wide array of clinical symptoms and manifestations, making it difficult to diagnose. The spectrum of visual system manifestations is broad and involves the anterior and posterior segments. We report a rare case of ocular perineuritis in an HIV-positive patient with neurosyphilis. A 33-year-old HIV-positive white male presented with blurred vision and floaters of 2 weeks duration. He reported coinciding neurological symptoms including headaches, nausea, and extreme weight loss. He also manifested an erythematous rash on his scalp. Fundoscopy revealed bilateral disc edema. Syphilitic ocular perineuritis is a condition that manifests with swollen optic discs in the absence of raised intracranial pressure or visual disturbance. This condition is due to inflammation of the optic nerve sheath and is often mistaken for papilledema or papillitis. Optic perineuritis is an infrequently reported complication of syphilitic disease. Early diagnosis of neurosyphilis and its complications is critical, because it is easily treated with penicillin when initiated early on.


[Magnetic oesophageal sphincter for the treatment of gastro-oesophageal reflux disease: results of a prospective clinical trial].
The authors report the preliminary results of a prospective study in 30 patients with gastro-oesophageal reflux disease. The aim was to assess the efficacy of an-original device designed to augment the lower oesophageal sphincter barrier using magnetic force. The device was placed laparoscopically around the oesophagogastric junction, at the level of the z line identified by intraoperative endoscopy. Transient dysphagia not requiring any treatment was recorded in 45% of patients. At 3 months postoperatively, the GORD-HRQL score was fond to be significantly decreased from 24.4 to 2.2 (p < 0.001) and the DeMeester score was normalised in 80% of patients. At one year follow-up, 100% of patients were off proton pump inhibitors, and 70% of them had a normal DeMeester score. All patients preserved the ability to belch.


Discrimination of Small Forms in a Deviant-Detection Paradigm by 10-month-old Infants.
Using eye tracking, we investigated if 10-month-old infants could discriminate between members of a set of small forms based on geometric properties in a deviant-detection paradigm, as suggested by the idea of a core cognitive system for Euclidian geometry. We also investigated the precision of infants' ability to discriminate as well as how the discrimination process unfolds over time. Our results show that infants can discriminate between small forms based on geometrical properties, but only when the difference is sufficiently large. Furthermore, our results also show that it takes infants, on average, <3.5 s to detect a deviant form. Our findings extend previous research in three ways: by showing that infants can make similar discriminative judgments as children and adults with respect to geometric properties; by providing a first crude estimate on the limit of the discriminative abilities in infants, and finally; by providing a first demonstration of how the discrimination process unfolds over time.


Excess Ascorbate is a Chemical Stress Agent against Proteins and Cells.
Excess ascorbate (as expected in intravenous treatment proposed for COVID-19 management, for example) oxidizes and/or degrades hemoglobin and albumin, as evidenced by UV-vis spectroscopy, gel electrophoresis, and mass spectrometry. It also degrades hemoglobin in intact blood or in isolated erythrocytes. The survival rates and metabolic activities of several leukocyte subsets implicated in the antiviral cellular immune response are also affected. Excess ascorbate is thus an unselective biological stress agent.


Promoting resilience in persons with serious mental health conditions during the Coronavirus pandemic.
This article highlights the profound and far-reaching impact of the Coronavirus disease 2019 (COVID-19) health crisis on persons with serious mental health conditions. To understand and mitigate against the negative effects of the crisis on this population, we offer a resilience intervention framework that attends to three key resilience processes, namely control, coherence, and connectedness (3Cs). We then detail interventions and associated evidence-informed intervention strategies at the individual, interpersonal, and systemic levels that behavioral health professionals can employ to bolster each of the 3Cs for persons with serious mental health conditions. These intervention strategies, which must be implemented in a flexible manner, are designed to enhance the biopsychosocial functioning of persons with serious mental health conditions during the COVID-19 pandemic and beyond and strengthen their interpersonal and systemic environments. We conclude with recommendations for future directions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).