Timing of elective surgery and risk assessment after SARS-CoV-2 infection: 2023 update: A multidisciplinary consensus statement on behalf of the Association of Anaesthetists, Federation of Surgical Specialty Associations, Royal College of Anaesthetists and Royal College of Surgeons of England.
Guidance for the timing of surgery following SARS-CoV-2 infection needed reassessment given widespread vaccination, less virulent variants, contemporary evidence and a need to increase access to safe surgery. We, therefore, updated previous recommendations to assist policymakers, administrative staff, clinicians and, most importantly, patients. Patients who develop symptoms of SARS-CoV-2 infection within 7 weeks of planned surgery, including on the day of surgery, should be screened for SARS-CoV-2. Elective surgery should not usually be undertaken within 2 weeks of diagnosis of SARS-CoV-2 infection. For patients who have recovered from SARS-CoV-2 infection and who are low risk or having low-risk surgery, most elective surgery can proceed 2 weeks following a SARS-CoV-2 positive test. For patients who are not low risk or having anything other than low-risk surgery between 2 and 7 weeks following infection, an individual risk assessment must be performed. This should consider: patient factors (age; comorbid and functional status); infection factors (severity; ongoing symptoms; vaccination); and surgical factors (clinical priority; risk of disease progression; grade of surgery). This assessment should include the use of an objective and validated risk prediction tool and shared decision-making, taking into account the patient's own attitude to risk. In most circumstances, surgery should proceed unless risk assessment indicates that the risk of proceeding exceeds the risk of delay. There is currently no evidence to support delaying surgery beyond 7 weeks for patients who have fully recovered from or have had mild SARS-CoV-2 infection.


Gender inequality in leadership and academic rank in academic reproductive endocrinology programs.
To identify gender differences in leadership and academic rank within academic reproductive endocrinology (REI) programs with fellowships in the USA. Official institutional websites of the 2017-2018 American Board of Obstetrics and Gynecology (ABOG)-accredited reproductive endocrinology fellowship programs were reviewed, and gender representation at each leadership position and academic rank (Division and Fellowship Director and Full, Associate, and Assistant Professor) was recorded. Univariate comparisons were performed using Chi-square tests, with significance at p < 0.05. Among 49 ABOG-accredited reproductive endocrinology programs, 263 faculty were identified, 129 (49.0%) male and 134 (51.0%) female. Division directors were 69.3% male and 30.7% female (p = 0.006). Similarly, fellowship directors were 65.3% male and 34.6% female (p = 0.03). Full professors (n = 101) were more frequently male (70.3% vs. 29.7%, p < 0.001). There was no difference in gender among associate professors (n = 60, 51.7% male vs. 48.3% female, p = 0.79), while significantly more assistant professors were female than male (n = 102, 73.6% vs. 26.4%, p < 0.001). While a majority of residents in obstetrics and gynecology and half of reproductive endocrinology academic faculty are female, women are still underrepresented among leadership positions and full professors in academic reproductive endocrinology programs with fellowship programs.


Effect of the nasal airflow inducing manoeuvre on olfaction and quality of life after laryngectomy.
To assess the effectiveness of the nasal airflow inducing manoeuvre or 'polite yawn' technique in improving olfaction and quality of life in laryngectomised patients. Using a prospective study design, 42 patients scheduled to undergo laryngectomy at a tertiary care centre were subjected to olfaction testing before surgery and two weeks following the surgery. The nasal airflow inducing manoeuvre was taught, and the olfaction test was repeated with the patient performing the nasal airflow inducing manoeuvre. Quality of life was assessed using the Appetite, Hunger and Sensory Perception questionnaire with calculation of scores after the patient had learnt the nasal airflow inducing manoeuvre. There was a significant reduction in the composite olfaction score, from a mean (standard deviation) baseline value of 4.01 (1.39) to 0.44 (0.51), two weeks after surgery (p < 0.001). After practising the nasal airflow inducing manoeuvre, the olfaction scores increased to 3.05 (1.32) (p < 0.001). Appetite, Hunger and Sensory Perception questionnaire scores ranged from 52 to 110 (normal range, 29-145), suggesting an improvement in the quality of life of patients. The nasal airflow inducing manoeuvre, an inexpensive, simple, patient-friendly manoeuvre, can be used in the olfaction rehabilitation of patients undergoing laryngectomy.


Prevalence of Thyroid Dysfunction in a Chinese Population with Different Glucose Intolerance Status: A Community-Based Cross-Sectional Study.
Impaired glucose metabolism and thyroid dysfunction (TD) are the two most common chronic metabolic disorders. This study aimed to investigate the epidemiological characteristics of TD in different status of glucose tolerance in a community-based Chinese population and to understand the association between TD and glucose metabolism. A community-based population study of metabolic disease was conducted from June 2013 to September 2014 in Beijing, China. Residents aged 26-76 years were selected according to gender and age composition using multi-stage stratified random sampling process. All participants underwent serum thyroid function and thyroid-associated antibody tests. The status of glucose tolerance was determined using 75g-oral glucose tolerance test. Chi-square test was used to compare the differences in prevalence. Multivariate logistic regression analysis was used to determine the impact of insulin resistance (IR) on thyroid function. By analyzing 3986 participants who were included in the survey, the prevalence of type 2 diabetes (T2DM) and pre-diabetes (pre-DM) was 18.59% and 26.79%, respectively. The prevalence of TD was 8.81%, with overt hyperthyroidism accounting for 0.38%; subclinical hyperthyroidism, 1.86%; overt hypothyroidism, 0.70%; and subclinical hypothyroidism, 5.87%. The prevalence of TD increased with gradually deteriorated glucose tolerance (7.63% in those with normal glucose tolerance, 9.27% in pre-DM, and 11.61% in T2DM) in both men and women. Each unit of higher HOMA-IR was associated with 7% higher likelihood of having subclinical hypothyroidism. The coexisting of TD with T2DM and pre-DM is high in this community-based Chinese population, suggesting a close relationship between TD and glucose metabolism.


Helicobacter pylori seropositivity is associated with enhanced platelet activation in patients with intermittent claudication.
Patients with intermittent claudication have a significantly increased risk of mortality from cardiovascular and cerebrovascular causes. Helicobacter pylori infection and abnormal platelet function have been shown to be associated with atherosclerosis as well as with acute ischemic events. The aim of this study was to assess for the first time the relation between H pylori serology status, platelet activation, and endothelial injury in patients with intermittent claudication. Design of study : A prospective observational study of 125 patients with intermittent claudication suitable for angioplasty was conducted at the Vascular Unit of the Aberdeen Royal Infirmary. Main outcome measures Main outcome measures were (1) H pylori serology using ELISA kit for immunoglobulin G antibody to H pylori and (2) whole blood flow cytometric analysis of resting platelet P-selectin expression and fibrinogen binding as measures of platelet activation. Results are presented as platelet percentage. von Wildebrand factor levels were measured using ELISA as a marker of endothelial injury. Carstair deprivation scores were calculated for all patients. H pylori serology was positive in 62 patients (49.6%), negative in 56 (44.8%) and equivocal in 7 (5.6%). Median P-selectin expression was significantly increased in H pylori-positive patients compared with seronegative patients (0.815 vs 0.65; P =.039). Median platelet fibrinogen binding was higher in seropositive patients, but this failed to reach statistical significance (2.135 vs 1.85%; P =.11). There was no difference in von Wildebrand factor levels between the two groups (P =.51). There was no difference in socioeconomic status between the two groups. Patients with intermittent claudication who are H pylori positive show enhanced platelet activation that does not appear to be mediated by means of endothelial cell injury.


In vitro metabolism of azasqualene derivatives and their effects on aminopyrine N-demethylase activity in rat liver microsomes.
The metabolism of squalene dimethylamine (I), a potent inhibitor of 2,3-oxidosqualene (SO) cyclase, and of sixteen other squalene derivatives was investigated in rat liver microsomes. N-oxidation was the only metabolic pathway observed, squalene dimethylamine N-oxide being the only metabolite isolated from incubation of I. The azasqualane and quaternary ammonium derivatives did not form N-oxides during their metabolism. The inhibition of aminopyrine N-demethylase activity was also studied and the IC50, for compound I, which shows weak competitive inhibition, was determined. At 1 mM concentration the other squalene derivatives showed a range of inhibition activity possibly due to their different lipophilicity.


Properties and mechanisms of long-term synaptic plasticity in the mammalian brain: relationships to learning and memory.
Long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum are two forms of long-lasting synaptic plasticity that currently serve as our primary experimental models of learning and memory formation in mammals. In recent years, there have been considerable advances in our understanding of the cellular and molecular mechanisms of these and other forms of synaptic plasticity. This article presents an overview of these developments, considers the relationship of long-term synaptic plasticity mechanisms to learning and memory in view of these developments, and suggests future directions for research in this rapidly growing area of neuroscience.


Cryptic branch point activation allows accurate in vitro splicing of human beta-globin intron mutants.
The excised introns of pre-mRNAs and intron-containing splicing intermediates are in a lariat configuration in which the 5' end of the intron is linked by a 2'-5' phosphodiester bond (RNA branch) to a single adenosine residue near the 3' end of the intron. To determine the role of the specific sequence surrounding the RNA branch, we have mutated the branch point sequence of the human beta-globin IVS1. Pre-mRNAs lacking the authentic branch point sequence are accurately spliced in vitro; processing of the mutant pre-mRNAs generates RNA lariats due to the activation of cryptic branch points within IVS1. The cryptic branch points always occur at adenosine residues, but the sequences surrounding the branched nucleotide vary. Regardless of the type of mutation or the sequences remaining within IVS1, the cryptic branch points are 22 to 37 nucleotides upstream of the 3' splice site. These results suggest that RNA branch point selection is primarily based on a mechanism that measures the distance from the 3' splice site.


Early expression of a malignant phenotype of familial hypertrophic cardiomyopathy associated with a Gly716Arg myosin heavy chain mutation in a Korean family.
The clinical course and prognosis of familial hypertrophic cardiomyopathy (HCM) are different according to the type of mutation in the genes for sarcomere proteins. It has been disputed that a mutation, which occurs at a functionally important region in the sarcomere proteins, may increase the penetrance and expressivity of the disease. We searched for a causative mutation in an HCM family, which is characterized by early expression of clinical phenotype, high incidence of sudden death at young ages, and progressive heart failure in adults. Among the 32 family members in 4 generations, 13 were affected; 4 died suddenly before age 16, 2 children have already had full expression of the cardiac hypertrophy, and other adults have either progressive heart failure or poor left ventricular systolic functions. PCR-SSCP (polymerase chain reaction-single strand confirmation polymorphism) analysis of genomic DNAs isolated from peripheral blood leukocytes of the family members identified a Gly716Arg mutation in the cardiac beta-myosin heavy chain gene, which was cosegregated with the clinical phenotype. The mutation is localized near a functionally important site of the myosin heavy chain, the 2 active thiols, which contribute to the adenosine triphosphatase activity of myosin S1. This family provides further evidence that the mutation, which occurs at a functionally important site of the myosin heavy chain, is associated with the high penetrance and early expression of HCM.


Burnout Subtypes: Psychological Characteristics, Standardized Diagnoses and Symptoms Course to Identify Aftercare Needs.
To better understand individual differences between burnout inpatients and improve individually tailored treatments in a psychiatric hospital, cluster analysis based on a number of self-report measures was used to investigate psychosocial characteristics of 96 participants. Group membership was analyzed regarding associations with standardized measures of psychiatric and personality disorders. Moreover, symptom levels of burnout, depression, and general mental health were used to characterize the groups and to observe differential trajectories at admission, discharge, and follow-up. As in previous research, we identified four subtypes that differed in comorbidity, psychological characteristics and treatment outcome. This calls for tailored interventions for the more vulnerable patients. The replicated and enriched characterization of burnout inpatients can help to optimally meet the differential needs of burnout patients.


Liver mitochondrial function in familial amyloidotic polyneuropathy.
The objective of the present study was to analyze hepatic mitochondrial function in patients with familial amyloidotic polyneuropathy (FAP) undergoing cadaveric donor orthotopic liver transplantation. From February 2005 to May 2007, eight patients with FAP, ranging in age from 34 to 41 years and with Model for End-Stage Liver Disease scores ranging from 24 to 29. Underwent orthotopic transplantation using a liver from a deceased donor by the piggyback method. Immediately before beginning the recipient hepatectomy in a patient with FAP, a biopsy was obtained for analysis of mitochondrial function (FAP group). The control group consisted of 15 patients undergoing hepatic surgery to treat small tumors of the liver. Mitochondrial respiration was determined on the basis of oxygen consumption by energized mitochondria using a polarographic method. The membrane potential of the mitochondria was determined spectrofluorometrically. Data were analyzed statistically by the Mann-Whitney test, with the level of significance set at 5%. State 3 and 4 values, respiratory control ratio, and membrane potential were 47 +/- 8 versus 28 +/- 10 natoms O/min/mg protein (P < .05); 14 +/- 3 vs 17 +/- 7 nat.O/min/mg.prot.mit. (P > .05); 3.6 +/- .5 vs 1.7 +/- 0.7 (P < .05); and 135 +/- 5.2 vs 135 +/- 6 mV (P > .05) for control versus FAP patients, respectively, demonstrating a decreased energy status of the liver in FAP.


Phase II study of oxaliplatin in platinum-resistant and refractory ovarian cancer: a gynecologic group study.
A phase II study was conducted to determine the efficacy of oxaliplatin therapy in patients with platinum-resistant or refractory epithelial ovarian carcinoma. Eligible patients were to receive oxaliplatin 130 mg/m2 intravenously over 2 hours, every 21 days, until progression of disease or adverse effects prohibited further therapy. Of 25 patients entered onto the study, 23 were eligible and assessable. There were no patients with complete response. One patient (4.3%) achieved a partial response, with a response duration of 6.4 months. Nine patients (39.1%) experienced stable disease, with a median duration of 5.6+ months (range, 1.8 to 13.1 months). The most frequently reported drug-related toxicities were hematologic, gastrointestinal, and neurologic. Oxaliplatin as a single agent has minimal activity in patients with platinum-resistant or refractory ovarian cancer at the dosage and schedule tested. However, future studies of oxaliplatin combined with other active agents in women with platinum-naïve or platinum-sensitive epithelial ovarian carcinoma may be indicated.


Clinicopathological significance of oxidative cellular damage in non-alcoholic fatty liver diseases.
Oxidative stress may play an important role in the progression of simple steatosis to non-alcoholic steatohepatitis (NASH). Oxidative stress is generated through multiple sources, including oxidation of free fatty acids, cytochrome P4502E1, iron overload, and necro-inflammatory cytokines including tumor necrosis factor-alpha. Oxidative stress may trigger damage to cellular membranes and nuclear DNA, which results in lipid peroxidation and oxidative DNA damage, respectively. Here, we present our data on intrahepatic localization and clinico-pathological significance of oxidative stress-induced cellular damage in the patients with non-alcoholic fatty liver diseases (NAFLD). Our subjects were 23 patients with non-alcoholic simple fatty liver, 17 with NASH, and 7 with normal liver (control). Hepatic expression of 4-hydroxy-2'-nonenal (HNE) and 8-hydroxydeoxyguanosine (8-OHdG), as reliable markers of lipid peroxidation and oxidative DNA damage, was in situ detected by using commercially available monoclonal antibodies. While no HNE adducts were observed in control livers, they were frequently detected in NAFLD. In NASH, the localization of the HNE adducts was in the cytoplasm of sinusoidal cells and hepatocytes with a predominance in zone 3. The grade of necro-inflammation as well as the stage of fibrosis significantly correlated with the HNE labeling index. With respect to 8-OHdG, although no 8-OHdG expression was observed in normal liver and only a few in non-alcoholic simple fatty liver, 11 of 17 patients with NASH (65%) exhibited nuclear expression of 8-OHdG in hepatocytes and sinusoidal cells in areas of active inflammation. The 8-OHdG index significantly correlated with the grade of necro-inflammation, but not with the stage of fibrosis. Our observations suggest that oxidative cellular damage occurs frequently in livers with NAFLD and may be associated with some clinico-pathological features of NAFLD including liver fibrosis and possibly, hepatocarcinogenesis.


A proteomics approach for identification of single strand DNA-binding proteins involved in transcriptional regulation of mouse mu opioid receptor gene.
The pharmacological actions of morphine and morphine-like drugs such as heroin are mediated primarily through the mu opioid receptor. Previously a single strand DNA element of the mouse mu opioid receptor gene (Oprm1) proximal promoter was found to be important for regulating Oprm1 in neuronal cells. To identify proteins binding to the single strand DNA element as potential regulators for Oprm1, affinity column chromatography with the single strand DNA element was performed using neuroblastoma NS20Y cells followed by two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. We identified five poly(C)-binding proteins: heterogeneous nuclear ribonucleoprotein (hnRNP) K, alpha-complex proteins (alphaCP) alphaCP1, alphaCP2, alphaCP2-KL, and alphaCP3. Binding of these proteins to the single strand DNA element of Oprm1 was sequence-specific as confirmed by supershift assays. In cotransfection studies, hnRNP K, alphaCP1, alphaCP2, and alphaCP2-KL activated the Oprm1 promoter activity, whereas alphaCP3 acted as a repressor. Ectopic expression of hnRNP K, alphaCP1, alphaCP2, and alphaCP2-KL also led to activation of the endogenous Oprm1 transcripts, and alphaCP3 repressed endogenous Oprm1 transcripts. We demonstrate novel roles as transcriptional regulators in Oprm1 regulation for hnRNP K and alphaCP binding to the single strand DNA element.


Using administrative data to predict important health outcomes. Entry to hospital, nursing home, and death.
This paper assesses our ability to use administrative data for developing indicators of health status. Traditionally, measures of health status have been derived from interviews. Here indicators from administrative data and from interviews are compared, i.e., their ability to predict important health outcomes for a large representative sample of elderly residents of Manitoba, Canada. Indicators of health status derived from an administrative data system and from health interviews are shown to provide roughly similar predictions of nursing-home entry. Administrative data provide significantly better predictions of death and future hospital entry than do variables from interview data.


Fate mapping of neural crest cells during eye development using a protein 0 promoter-driven transgenic technique.
To map neural crest cell fate during eye development. Neural crest cells were tracked in developing mouse eyes using a transgene expressing Cre recombinase controlled by the Protein 0 promoter and a Rosa26 Cre-responsive reporter gene that produced beta-galactosidase after Cre-mediated recombination. beta-galactosidase-positive cells were detected in the periocular segment on embryonic day (E) 9.5. Several neural crest cell-derived tissues including corneal stroma, corneal endothelium, iridocorneal angle, ciliary body, primary vitreous and eyelid were strongly stained on E13.5-E18.5. The staining decreased in the corneal stroma after birth, but persisted in the presumptive iridocorneal angle. Protein 0-Cre transgenic mice offer a conditional knock-out strategy to investigate anterior eye segment differentiation.


The proof is in the pudding: children prefer lower fat but higher sugar than do mothers.
Although there are established age-related differences in sweet preferences, it remains unknown whether children differ from mothers in their preference for and perception of fat (creaminess). We examined whether individual differences in sucrose and fat preferences and perception are related to age, genotype and lifestyle. Children 5-10 years-old (n=84) and their mothers (n=67) chose the concentration of sucrose and fat most preferred in pudding and sucrose most preferred in water using identical, two-alternative, forced-choice procedures, and ranked pudding samples for intensity of sweetness and creaminess. Subjects were also weighed and measured for height, as well as genotyped for a sweet-receptor gene (TAS1R3). Children preferred higher concentrations of sucrose in water (P=0.03) and in pudding (P=0.05) and lower concentrations of fat in pudding (P<0.01) than did mothers. Children and mothers were equally able to rank the intensity of different concentrations of fat (P=0.12) but not sucrose in pudding (P=0.01). Obese and lean children and mothers did not differ in preferences, but obese mothers were less able to correctly rank the concentration of fat in pudding than were lean mothers (P=0.03). Mothers who smoked preferred a higher concentration of sucrose than did those who never smoked (P<0.01). Individual differences in sweet preference were associated with genetic variation within the TAS1R3 gene in mothers but not children (P=0.04). Irrespective of genotype, children prefer higher concentrations of sugar but lower concentrations of fat in puddings than do their mothers. Thus, reduced-fat foods may be better accepted by children than adults.


Complete endoscopic closure of gastric defects using a full-thickness tissue plicating device.
Obtaining endolumenal closure of hollow visceral defects may complement conventional, incision-based, surgical alternatives and benefit the experimental field of natural orifice translumenal endoscopic surgery (NOTES). Endoscopic tissue plicating devices (TPD) represent a promising closure technology; however, the long-term integrity of resultant closures is uncertain. Swine (n=10) underwent survival transgastric NOTES peritoneoscopy procedures with TPD gastrotomy closure while device performance and closure integrity were evaluated. Following uncomplicated procedures, no animals revealed leakage on upper gastrointestinal contrast fluoroscopy immediately following closure and on postoperative days 2 and 7. Necropsy performed on the 14th postoperative day revealed a subclinical colonic injury for one animal; the remaining nine animals had no complications. Gastric burst testing revealed the strength of closure was comparable to that of nonsurgical control stomachs (85.1 vs. 85.3 mm Hg, p=0.98). For six of nine (66%) TPD animals, bursting occurred remote to the closure site in nonsurgical tissue, indicating that closure strength equaled that of native tissue. Endoscopic TPD closure of standardized NOTES gastric defects results in strong, leak-proof closure; however, injuries can occur. These findings support evaluation of TPD closure in human trials involving noncontrolled gastric defects.


Symmetry discrimination in patients with retinitis pigmentosa.
To investigate the relative sensory and perceptual contributions to central visual function of patients with retinitis pigmentosa (RP), we tested symmetry discrimination using block patterns with varying types of symmetric organization. Eleven control subjects with normal vision and 11 patients with RP with 20/30 visual acuity or better, viewed patterns presented for 255 msec. The patterns differed in the type of symmetric organization and the subjects were required to identify the type. The control subjects performed significantly better (89.2%) than the patients (74.5%). Four hypotheses to account for these findings were tested and the results were as follows, (1) A reduction in pattern luminance did not change symmetry discrimination performance in the control subjects. (2) Large reductions in pattern contrast did not alter symmetry discrimination in the control subjects. (3) Reductions in stimulus duration, likewise, did not produce similar error patterns in the control subjects as those observed in the patients with RP. (4) Alterations in spatial sampling density did not completely account for the patients' deficits. None of the retinally based explanations alone was sufficient to account for our findings. Additionally, we suggest that alterations of sensory input may affect the perceptual encoding of the relationship among pattern elements.


Analysis of K-ras gene mutations in rare pancreatic and ampullary tumours.
Mutation of the K-ras oncogene is a frequent event in pancreatic ductal carcinogenesis and it is believed to occur at an early stage in the development of pancreatic cancer. However, little is known of the role of K-ras mutations in rare pancreatic epithelial neoplasms, endocrine tumours or other non-epithelial tumours of the pancreas. Furthermore, limited data are available regarding the role of K-ras mutations in the pathogenesis of ampullary tumours. Using single-strand conformation polymorphism (SSCP) and direct sequencing of polymerase chain reaction (PCR)-amplified fragments, we analysed codons 12 and 13 for the presence of oncogenic mutations of the K-ras oncogene. Tissues were obtained from patients undergoing tumour resection for various rare pancreatic or ampullary neoplasms (number of cases in brackets): ampullary adenoma (1), neuro-endocrine tumour (3), malignant fibrous histiocytoma of the pancreas (1), pancreatic cystadenocarcinoma (1), serous cystadenoma (1), and primary and metastatic adenocarcinoma of the ampulla (5) and pancreas (3). K-ras gene mutations at codon 12 were detected in both pancreatic adenocarcinomas and in the metastatic lesion, whereas two ampullary cancers harboured a point mutation at codon 13: GGC-->GGG and GGC-->GGT. None of the other tumours exhibited a K-ras gene mutation at codons 12 or 13. Pancreatic tumours other than ductal adenocarcinoma of the pancreas do not harbour mutations of the K-ras oncogene. In addition, ampullary adenocarcinomas may present with codon 13 mutations; however, these mutations were not associated with amino acid substitution. Therefore, K-ras gene mutations seem to be a specific genetic alteration contributing to the pathogenesis of pancreatic ductal adenocarcinoma.


Response of bacterial community structure to seasonal fluctuation and anthropogenic pollution on coastal water of Alang-Sosiya ship breaking yard, Bhavnagar, India.
Bacterial community structure was analyzed from coastal water of Alang-Sosiya ship breaking yard (ASSBY), world's largest ship breaking yard, near Bhavnagar, using 16S rRNA gene sequencing (cultured dependent and culture independent). In clone libraries, total 2324 clones were retrieved from seven samples (coastal water of ASSBY for three seasons along with one pristine coastal water) which were grouped in 525 operational taxonomic units. Proteobacteria was found to be dominant in all samples. In pristine samples, Gammaproteobacteria was found to be dominant, whereas in polluted samples dominancy of Gammaproteobacteria has shifted to Betaproteobacteria and Epsilonproteobacteria. Richness and diversity indices also indicated that bacterial community in pristine sample was the most diverse followed by summer, monsoon and winter samples. To the best of knowledge, this is the first study describing bacterial community structure from coastal water of ASSBY, and it suggests that seasonal fluctuation and anthropogenic pollutions alters the bacterial community structure.


Density functional calculations for a high energy density compound of formula C6H 6-n (NO 2) n.
A series of polynitroprismanes, C(6)H(6-n )(NO(2))(n) (n = 1-6) intended for use as high energy density compounds (HEDCs) were designed computationally. Their electronic structures, heats of formation, interactions between nitro groups, specific enthalpies of combustion, bond dissociation energies, and explosive performances (detonation velocities and detonation pressures) were calculated using density functional theory (DFT) with the 6-311 G** basis set. The results showed that all of the polynitroprismanes had high positive heats of formation that increased with the number of substitutions for the prismane derivatives, while the specific enthalpy of combustion decreased as the number of nitro groups increased. In addition, the range of enthalpy of combustion reducing is getting smaller. Interactions between ortho (vicinal) groups deviate from the group additivity rule and decrease as the number of nitro groups increases. In terms of thermodynamic stability, all of the polynitroprismanes had higher bond dissociation energies (BDEs) than RDX and HMX. Detonation velocities and detonation pressures were estimated using modified Kamlet-Jacobs equations based on the heat of detonation (Q) and the theoretical density of the molecule (ρ). It was found that ρ, D, and P are strongly linearly related to the number of nitro groups. Taking both their energetic properties and thermal stabilities into account, pentanitroprismane and hexanitroprismane are potential candidate HEDCs.


[Experience with the Sourire Cage for cervical anterior fusion--a clinical study of 113 patients].
The standard treatment for disc diseases of the cervical spine is anterior cervical decompression and fusion (ACDF). For cervical fusion several implants are available. The aim of this study is to examine the clinical and radiographic outcome of patients treated with the Sourire Cage. Between 01. 01. 2008 and 26. 08. 2012 113 patients with degenerative disc diseases of the cervical spine underwent anterior cervical fusion with the Sourire Cage. Clinical and radiological examinations were performed two days after surgery and six weeks, six months and one year after surgery. To assess the patients we used the Japanese Orthopedic Association (JOA) questionnaire. At the one-year follow-up 84 % of the patients had improved. Subsidence was observed in 10 % of them, dislocation was not observed. The results of this study demonstrate that anterior cervical fusion with the Sourire Cage leads to excellent and good clinical outcomes with a low rate of complications.


The Distally Based Posterior Tibial Artery Flap.
Soft tissue defects to the distal leg and hindfoot are challenging with only the smallest defects closed primarily without tissue transposition. These defects to the distal leg and hindfoot can lead to tendon desiccation, damaged neurovascular structures, and exposed joint surfaces. These wounds can be the result of postoperative dehiscence and exposed orthopedic hardware, with high susceptibility to infection. Pedicled fasciocutaneous flaps of the medial leg provide an excellent solution with good outcomes that do not require microanastomosis and have similar outcomes as compared with free flap reconstruction in the lower extremity.


Hemodynamics and prostacyclin release in the early phases of aortic surgery: comparison of transabdominal and retroperitoneal approaches.
Although the retroperitoneal aortic approach (RP) is advocated to reduce myocardial ischemia and cardiac-related death, inadequate physiologic data exist to support this contention. As the aorta is exposed via the transabdominal approach (TA) we noted some patients have manifested reduced systemic vascular resistance (SVR) associated with tachycardia, reduced blood pressure, and facial flushing. To determine whether RP offered physiologic advantages over TA we compared cardiac dynamics and blood levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin, during exposure of the aorta in 52 patients (33 with TA and 19 with RP), comparable in age, cardiac history, medications, and body surface area. Serial measurements of mean arterial pressure, heart rate, wedge pressure, pulmonary artery pressure, cardiac index, and 6-keto-PGF1 alpha were obtained. Results revealed decreased mean arterial pressure and systemic vascular resistance, increased cardiac index and heart rate, and facial flush occurring 10 minutes after the bowel was explored in TA. This was not observed in RP. These hemodynamic alterations correlated in time and magnitude with a fourteen fold increase in 6-keto-PGF1 alpha. These changes in cardiac indexes can produce increased myocardial oxygen consumption with the risk for myocardial ischemia, particularly in patients with coronary artery disease. The absence of this response to bowel exploration in RP may account for some of the observed advantages in "high-risk" aortic reconstruction.


Coping strategies and anxiety in young breast cancer survivors.
We sought to describe coping strategies reported by young breast cancer survivors and evaluate the relationship between utilization of specific coping strategies and anxiety in survivorship. Participants enrolled in The Young Women's Breast Cancer Study, a multi-center, cohort of women diagnosed with breast cancer at age ≤ 40 years, completed surveys that assessed demographics, coping strategies (reported at 6-month post-enrollment and 18-month post-diagnosis), and anxiety (2 years post-diagnosis). We used univariable and multivariable logistic regression to examine the relationship between coping strategies and anxiety. A total of 833 women with stage 0-3 breast cancer were included in the analysis; median age at diagnosis was 37 (range: 17-40) years. Social supports were the most commonly reported coping strategies, with the majority reporting moderate or greater use of emotional support from a partner (90%), parents (78%), other family (79%), and reliance on friends (88%) at both 6 and 18 months. In multivariable analyses, those with moderate or greater reliance on emotional support from other family (odds ratio (OR): 0.37, 95% confidence ratio (CI): 0.22-0.63) at 18 months were less likely to have anxiety at 2 years, while those with moderate or greater reliance on alcohol/drug use (OR: 1.83, 95%CI: 1.12-3.00) and taking care of others (OR: 1.90, 95%CI: 1.04-3.45) to cope were more likely to have anxiety. Young breast cancer survivors rely heavily on support from family and friends. Our findings underscore the importance of considering patients' social networks when developing interventions targeting coping in survivorship. NCT01468246 (first posted November 9, 2011).


Direct formation of the sesquiterpeonid ether liguloxide by a terpene synthase in Senecio scandens.
SsLOS directly catalyzed formation of the sesquiterpenoid ether liguloxide in the medicinal plant Senecio scandens. Terpene synthases determine the diversity of terpene skeletons and corresponding terpenoid natural products. Oxygenated groups introduced in catalysis of terpene synthases are important for solubility, potential bioactivity and further elaboration of terpenoids. Here we identified one terpene synthase, SsLOS, in the Chinese medicinal plant Senecio scandens. SsLOS acted as the sesquiterpene synthase and utilized (E,E)-farnesyl diphosphate as the substrate to produce a blend of sesquiterpenoids. GC-MS analysis and NMR structure identification demonstrated that SsLOS directly produced the sesquiterpenoid ether, liguloxide, as well as its alcoholic isomer, 6-epi-guaia-2(3)-en-11-ol. Homology modeling and site-directed mutagenesis were combined to explore the catalytic mechanism of SsLOS. A few key residues were identified in the active site and hedycaryol was identified as the neutral intermediate of SsLOS catalysis. The plausible catalytic mechanism was proposed as well. Altogether, SsLOS was identified and characterized as the sesquiterpenoid ether synthase, which is the second terpenoid ether synthase after 1,8-cineol synthase, suggesting some insights for the universal mechanism of terpene synthases using the water molecule in the catalytic cavity.


Pre- or postinsult administration of lidocaine or thiopental attenuates cell death in rat hippocampal slice cultures caused by oxygen-glucose deprivation.
Lidocaine and thiopental improve recovery when administrated during hypoxia and ischemia; however, the effect of pre- or postinsult treatment alone is unknown. We applied either lidocaine or thiopental to hippocampal slice cultures from 20-day-old rats either before or after 10 min of oxygen-glucose deprivation (OGD). Propidium iodide (PI) fluorescence was used as an indicator of neuronal death for 7 days after OGD. OGD-induced neuronal death, in both the Cornus Ammonis 1 (CA1) and the dentate gyrus regions, peaked the first day after ischemia. Preinsult administration of either lidocaine (10, 100 microM) or thiopental (250, 600 microM) significantly reduced the damage measured on the first and second days after OGD; these drugs also significantly decreased the summed daily post-OGD PI fluorescence in both regions. Postinsult administration of lidocaine (10, 100 microM) or thiopental (250, 600 microM) significantly decreased the PI fluorescence on the first day after OGD; postinsult administration of these drugs also attenuated the summed daily post-OGD PI. These data indicate that the administration of lidocaine or thiopental either before or directly after OGD reduced neuronal damage in this in vitro model of cerebral ischemia. Postischemic administration is frequently the first opportunity for treatment. Lidocaine or thiopental applied either 10 min before or 10 min directly after oxygen-glucose deprivation reduced neuronal cell death in rat hippocampal slice cultures. Postinsult administration is often the first opportunity for treatment after stroke; lidocaine and thiopental reduced damage caused by oxygen-glucose deprivation, an in vitro model of stroke.


Corneal neovascularization.
The optical clarity of the cornea is essential for maintaining good visual acuity. Corneal neovascularization, which is a major cause of vision loss worldwide, leads to corneal opacification and often contributes to a cycle of chronic inflammation. While numerous factors prevent angiogenesis within the cornea, infection, inflammation, hypoxia, trauma, corneal degeneration, and corneal transplantation can all disrupt these homeostatic safeguards to promote neovascularization. Here, we summarize its etiopathogenesis and discuss the molecular biology of angiogenesis within the cornea. We then review the clinical assessment and diagnostic evaluation of corneal neovascularization. Finally, we describe current and emerging therapies.


Reliability and validity of the Korean version of the Functional Status Score for the ICU after translation and cross-cultural adaptation.
The Functional Status Score for the Intensive Care Unit (FSS-ICU) evaluates the physical function of ICU patients. The objective of the study was to translate and cross-culturally adapt the FSS-ICU into Korean and assess its reliability and validity. An expert committee supervised the forward and backward translation process and the final translated version. Experienced physiotherapists assessed patients (n= 31) from a medical ICU using the Korean version of FSS-ICU. Intra-class correlation coefficients (ICCs) and Bland-Altman's plots were used to evaluate reliability, and Cronbach's alpha for internal consistency. Construct validity was evaluated using Spearman's correlation coefficients. Two physiotherapists in each of the two university hospitals independently assessed 31 medical ICU patients, with a mean FSS-ICU total score of 23 (range: 4-35). The FSS-ICU Korean version demonstrated excellent internal consistency, with Cronbach's alpha of 0.897 for the total FSS-ICU score, and a range of 0.844-0.892 with deletion of each individual activity within the FSS-ICU. Intra-rater and inter-rater reliability were excellent for all of five FSS-ICU activities and the total score, with an ICC range of 0.930-0.993. Bland-Altman's plots revealed a mean difference in FSS-ICU total score of 0.2 (95% limits of agreement: -1.9 to 2.3) between two physiotherapists. The Korean version of FSS-ICU had good convergent and divergent validity with moderate to strong correlation with mobility and muscle strength measures, and poor correlation with unrelated measures. The Korean version of the FSS-ICU showed excellent intra-rater and inter-rater reliability, internal consistency, and construct validity for medical ICU patients. The results of this study, along with prior publications, support that the FSS-ICU Korean version is a valid and reliable assessment tool for the ICU environment.Implications for rehabilitationIntensive care unit patients usually experience decreased muscle strength and physical function.The Korean version of the Functional Status Score for the Intensive Care Unit (FSS-ICU) is suitable for use with Korean speakers and has a valid, reliable measurement tool for physical function of intensive care unit patients.A well-standardized training with videos and written materials is important to ensure correct implementation of the Korean version of the FSS-ICU.


An automatic system for multidimensional integrated protein chromatography.
An automatic system for multidimensional integrated protein chromatography was designed for simultaneous separation of multiple proteins from complex mixtures, such as human plasma and tissue lysates. This computer-controlled system integrates several chromatographic columns that work independently or cooperatively with one another to achieve efficient high throughputs. The pipelines can be automatically switched either to another column or to a collection container for each UV-detected elution fraction. Environmental contamination is avoided due to the closed fluid paths and elimination of manual column change. This novel system was successfully used for simultaneous preparation of five proteins from the precipitate of human plasma fraction IV (fraction IV). The system involved gel filtration, ion exchange, hydrophobic interaction, and heparin affinity chromatography. Human serum albumin (HSA), transferrin (Tf), antithrombin-III (AT-III), alpha 1-antitrypsin (α1-AT), and haptoglobin (Hp) were purified within 3 h. The following recovery and purity were achieved: 95% (RSD, 2.8%) and 95% for HSA, 80% (RSD, 2.0%) and 99% for Tf, 70% (RSD, 2.1%) and 99% for AT-III, 65% (RSD, 2.0%) and 94% for α1-AT, and 50% (RSD, 1.0%) and 90% for Hp. The results demonstrate that this novel multidimensional integrated chromatography system is capable of simultaneously separating multiple protein products from the same raw material with high yield and purity and it has the potential for a wide range of multi-step chromatography separation processes.


The timing of surgical staging has a significant impact on the complications and functional outcomes of adult spinal deformity surgery.
To our knowledge, the effect of the staging regimen on the surgical outcome in patients undergoing combined anterior/posterior surgery for the treatment of spinal deformity has not been previously studied. To compare outcomes of anterior/posterior surgery for adult spinal deformity staged less than 21 days apart versus those 21 or more days apart. A retrospective comparison study. Patients aged 40 years or older who underwent combined anterior/posterior fusions for spinal deformities. Self-reported measures, physiological measures, and functional measures. We retrospectively reviewed prospectively collected data for 63 consecutive patients (50 females and 13 males) older than 40 years who underwent combined anterior/posterior fusions for spinal deformities and who had a minimum of 2-year follow-up. We divided them into those who had surgery staged less than 21 days apart (Group 1, N=29) and those who had surgery staged 21 or more days apart (Group 2, N=34). The groups were not statistically different in age; preoperative American Society of Anesthesiologists, Scoliosis Research Society-22 (SRS-22) patient questionnaire, and Oswestry Disability Index (ODI) scores; number of previous surgeries; number of levels fused; or total operative time. Hotelling t square test and the chi-squared test were used to compare clinical and radiographic parameters, complications, and functional outcomes between groups (significance, p<.05). Compared with Group 1 patients, Group 2 (staged) patients had a lower total estimated blood loss (average, 4.5 L [range, 1.90-8.75 L] vs. 4 L [range, 1.8-10.1 L], respectively), fewer combined hospital days (average, 14 days [range, 7-70 days] vs. 12 days [range, 6-44 days], respectively), and fewer major complications (total, 10 [35%] vs. 6 [18%], respectively). Preoperative SRS-22 and ODI scores were significantly better in Group 2 than in Group 1 at 6 weeks (p<.001) and at final follow-up (p<.001), respectively. For patients who require both anterior and posterior surgery for spinal deformity correction, staging the two procedures 21 or more days apart decreases total perioperative transfusion requirements although significantly improving functional outcomes.


How do they add up? The interaction between the placebo and treatment effect: A systematic review.
The placebo effect and the specific effect are often thought to add up (additive model). Whether additivity holds can dramatically influence the external validity of a trial. This assumption of additivity was tested by Kleijnen et al in 1994 but the data produced since then have not been synthetized. In this review, we aimed to systematically review the literature to determine whether additivity held. We searched Medline and PsychInfo up to 10 January 2019. Studies using the balanced placebo design (BPD), testing two different strengths of placebos, were included. The presence of interaction was evaluated by comparing each group in the BPD with analysis of variance or covariance. Thirty studies were included and the overall risk of bias was high: four found evidence of additivity and 16 studies found evidence of interaction (seven had evidence of positive additivity). Evidence of additivity between placebo and specific features of treatments was rare in included studies. We suggest interventions for placebo-sensitive ailments should be tested in trials designed to take interactions seriously once an exploratory RCTs has proven their efficacy with sufficient internal validity.


Associations between maternal stress during pregnancy and offspring internalizing and externalizing problems in childhood.
Maternal psychological health during pregnancy has been associated with offspring psychopathology. However, it is uncertain whether these associations are mediated by the postpartum depression and related child-rearing factors. Therefore, we examined the associations between prenatal and postnatal factors and internalizing and externalizing behavioral problems in childhood, focusing on maternal psychological health in school-aged children in Korea. The current study included 1,003 children (580 boys, 423 girls, mean age 9.05 ± 0.70 years, age range 8-11 years) recruited from schools in five Korean cities. Children's internalizing and externalizing problems were assessed by the Child Behavior Checklist (CBCL). The parents of the children completed structured questionnaires on perinatal factors. Among 1,003 children, 44 had internalizing problems (IP) and 30 had externalizing problems (EP). When comparing children with IP (n = 44) and without IP (n = 959), severe maternal stress during pregnancy (OR3.36, 95% CI 1.80-6.25) and postpartum depression (OR3.19, 95% CI 1.36-7.53) showed a significant association with the IP. When comparing children with EP (n = 30) and without EP (n = 973), low family income (OR2.19, 95% CI 1.05-4.56), unwanted pregnancy (OR2.76, 95% CI 1.28-5.95) and severe maternal stress during pregnancy (OR2.69, 95% CI 1.29-5.61) with the EP. Only maternal stress during pregnancy was significantly associated with the IP after controlling for postpartum depression and with the EP after controlling for family income and unwanted pregnancy. This study suggests the importance of maternal psychological health during perinatal period on children's mental health. Further prospective studies in a larger sample are required to confirm our findings.


Contemplations on preclinical validation of fluorescence in situ hybridization probe assay for paraffin-embedded tissues in hematologic disorders.
A validation of fluorescence in situ hybridization (FISH) assays for paraffin-embedded tissues (PET) is required before clinical use. Although the FISH probe validation process for hematologic disorders has been described during recent years, none of these descriptions, to our knowledge, address the validation process for paraffin-embedded tissues in detail. We describe an applicable preclinical validation process. The following five-step validation is outlined: (1) pathologist's review of slide; (2) probe validation on metaphases to assess sensitivity and specificity; (3) a pilot study using FISH probes on PET; (4) analytical validation using normal and abnormal PET samples to establish a normal reference range or cutoff; and (5) application of the cutoffs to test samples. Although the procedure focuses on dual-color, dual-fusion FISH assays, the same steps could be used for any type of probe. We have described a preclinical validation for probes on paraffin-embedded tissue.


Morphology of single, physiologically identified retinogeniculate Y-cell axons in the cat following damage to visual cortex at birth.
It has been reported previously that neurons in the dorsal lateral geniculate nucleus (LGN) of cats with neonatal damage to visual cortex (KVC cats) have receptive fields that are abnormally large and that the receptive fields of these neurons sometimes do not appear to conform to the normal retinotopic order in the LGN. A primary aim of this study was to determine if these physiological abnormalities are related to inappropriate patterns of retinogeniculate connections. We therefore have analyzed the terminal arbors of retinogeniculate axons in adult cats that had received a lesion of visual cortex (areas 17, 18, and 19) on the day of birth. Single retinogeniculate axons were characterized physiologically and injected intracellularly with horseradish peroxidase. Consistent with earlier reports that neonatal removal of visual cortex results in a retrograde loss of retinal X-cells, all of the retinogeniculate axons that we recorded were from Y-cells. While the visual responses of these Y-cell axons were normal, the morphology of their terminal arbors in the LGN was abnormal. Retinal Y-cell axons in KVC cats have terminal fields in the A laminae of the LGN that are as large or larger than those of normal Y-cells. However, since the LGN in KVC cats is severely degenerated, single Y-cell arbors occupy a proportional volume of the LGN that is 12 times greater than normal. Thus an early lesion of visual cortex produces a severe mismatch between retinogeniculate axon arbor size and target size. Also, despite the normal size of retinogeniculate axon arbors in KVC cats, the number and density of terminal boutons are greatly decreased. Thus our morphological results suggest that the unusually large receptive fields of LGN cells in KVC cats and the relative lack of retinotopic precision in the LGN are due, at least in part, to anomalies in the relative size and distribution of retinogeniculate axon arbors that develop after neonatal removal of visual cortex.


Platelet-activating factor-mediated contraction of rabbit lung strips: pharmacologic modulation.
Synthetic platelet-activating factor (PAF) (1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, AGEPC) has been shown to induce a slowly developing contraction of rabbit lung parenchymal strips in an isolated organ bath. The spasmogenic effect of AGEPC appeared to be mediated by specific receptors distinct from H1, H2, cholinergic and C5a anaphylatoxin receptors. Prior exposure to AGEPC induced specific desensitization of lung parenchymal strips. Experiments with several pharmacological agents indicated that AGEPC-induced contraction was independent from cyclooxygenase, but was blocked when phospholipase A2 and lipoxygenase were inhibited and when the Ca++ channels were antagonized. Corticosteroids exhibited an inhibitory effect specific for AGEPC. Intracellular levels of cyclic AMP or cyclic GMP seemed to have a modulatory role in AGEPC-induced contraction of rabbit lung parenchymal strips.


Clinical indications and accuracy of gray scale ultrasonography in the patient with suspected biliary tract disease.
One hundred patients with suspected biliary tract disease underwent gray scale cholecystosonography (GSCS) and had diagnostic confirmation by oral cholecystogram (OCG) and/or operation. Ultrasonography demonstrated the gallbladder in 94 of the 100 patients; 2 patients had had previous cholecystectomy and 3 of the 4 remaining patients had documented stones with no confirmation of a nonvisualizing OCG in the other patient. Among the 88 patients with OCG, GSCS findings correlated in 91 per cent (2 per cent false-positive; 7 per cent false-negative). Among the 43 operative patients, GSCS was proven correct in 91 per cent (no false positive; 9 per cent false-negative). Of 12 patients with jaundice GSCS correlated with operative findings in 75 per cent (no false-positive; 25 per cent false-negative). Diagnostic errors occurred in patients with very small biliary calculi, particularly when a single stone was impacted in the cystic duct. Failure to identify the gallbladder with ultrasound signifies probable cholelithiasis in the patient without previous cholecystectomy. On the basis of this experience, we conclude that (1) GSCS is most useful when jaundice or acute illness precludes conventional studies; (2) GSCS provides an inexpensive, quick, accurate means of diagnosing cholelithiasis with a very high specificity (97 per cent) and moderate sensitivity (88 per cent); and (3) GSCS is the optimal diagnostic procedure for evaluating the biliary tract in the acutely ill, jaundiced, vomiting, allergic, and/or pregnant patient.


[Systematic reviews and meta-analysis].
Over the past years, systematic reviews and meta-analyses have led to significant changes in clinical medicine and health policy. To date, they can be viewed as the most objective instruments to answer clinical as well health policy questions. In addition, systematic reviews are an important tool to synthesize the enormous amount of new medical knowledge into a manageable format. Nevertheless, the methodological quality of published systematic reviews and meta-analyses varies and biased results can be misleading. Therefore, it is important for readers of systematic reviews to critically evaluate the underlying methods, to be able to assess the validity of their findings. This manuscript is part of a methods series of the Wiener Medizinische Wochenschrift. It summarizes the methodological hallmarks of systematic reviews and meta-analyses to provide readers with the methodological background necessary to critically evaluate systematic reviews and meta-analyses.


The value of ultrasound and magnetic resonance imaging scoring systems in explaining handgrip strength and functional impairment in rheumatoid arthritis patients: a pilot study.
The goal of this study is to investigate the relationship between joint inflammation and damage of the wrists and hands, measured by semiquantitative ultrasound and magnetic resonance imaging scoring systems, with functional disability and handgrip strength (HGs). Consecutive adult RA patients with active disease, as defined by a Disease Activity Score 28 joints C-reactive protein (DAS28-CRP) > 3.2, underwent a cross-sectional evaluation comprehensive of a clinimetric assessment, an HGs evaluation, an ultrasound assessment aimed at calculating the UltraSound-CLinical ARthritis Activity (US-CLARA), and a magnetic resonance imaging scored according to the modified Simplified Rheumatoid Arthritis Magnetic Resonance Imaging Score (mod SAMIS). The Spearman's rho correlation coefficient was used to test the correlations. Sixty-six patients with RA were investigated (age 55.6 ± 12.2 years). The mod SAMIS total score and the US-CLARA had a weak but significant correlation (rho = 0.377, p = 0.0018). Among the mod SAMIS sub-scores, there was a significant relationship between mod SAMIS bone edema (SAMIS-BME) and US-CLARA (rho = 0.799, p < 0.001) and mod SAMIS synovitis (SAMIS synovitis) and US-CLARA (rho = 0.539, p < 0.001). There were also significant negative relationships between the HGs score and the mod SAMIS total score and US-CLARA (rho = - 0.309, p = 0.011 and rho = - 0.775, p < 0.0001, respectively). BME and synovitis have an influence on the function of the upper extremities. The US-CLARA and the mod SAMIS total score are intriguing options for semiquantitative assessment of joint inflammation and damage in RA.


Insulin status and vascular responses to weight loss in obesity.
The aim of this study was to determine whether the effects of weight loss on arterial function are differentially modified by insulin status. Clinical studies suggest that plasma insulin levels may predict the extent of cardiovascular benefit achieved with weight loss in obese individuals, but mechanisms are currently unknown. We prospectively followed 208 overweight or obese patients (body mass index [BMI] ≥25 kg/m(2)) receiving medical/dietary (48%) or bariatric surgical (52%) weight-loss treatment during a median period of 11.7 months (interquartile range: 4.6 to 13 months). We measured plasma metabolic parameters and vascular endothelial function using ultrasound at baseline and following weight-loss intervention and stratified analyses by median plasma insulin levels. Patients age 45 ± 1 years, with BMI 45 ± 9 kg/m(2), experienced 14 ± 14% weight loss during the study period. In individuals with higher baseline plasma insulin levels (above median >12 μIU/ml; n = 99), ≥10% weight loss (compared with <10%) significantly improved brachial artery macrovascular flow-mediated vasodilation and microvascular reactive hyperemia (p < 0.05 for all). By contrast, vascular function did not change significantly in the lower insulin group (≤12 μIU/ml; n = 109) despite a similar degree of weight loss. In analyses using a 5% weight loss cut point, only microvascular responses improved in the higher insulin group (p = 0.02). Insulin status is an important determinant of the positive effect of weight reduction on vascular function with hyperinsulinemic patients deriving the greatest benefit. Integrated improvement in both microvascular and macrovascular function was associated with ≥10% weight loss. Reversal of insulin resistance and endothelial dysfunction may represent key therapeutic targets for cardiovascular risk reduction in obesity.


Brachytherapy for the treatment of recurrent prostate cancer after radiotherapy or radical prostatectomy.
What's known on the subject? and What does the study add? The curative treatment of prostate cancer includes surgery, external beam radiation or interstitial radiation. However, a high percentage of patients may develop recurrent disease, which is often localised. The possibilities of treatment in these cases, including surgery or adjuvant radiotherapy, are not well defined. Brachytherapy is a well established first-line treatment option. We review and update the use of brachytherapy in the treatment of recurrences post-radiotherapy, brachytherapy or radical prostatectomy as an alternative to surgery and radiotherapy, with a focus on functional and oncological outcomes. Salvage therapeutic options following radical prostatectomy or radiotherapy for patients with local relapse of prostate cancer include radical prostatectomy, radiotherapy, brachytherapy or cryotherapy. Salvage radical prostatectomy following radiotherapy failure is associated with a 5-year PSA relapse-free rate of 30-40%. Biochemical relapse-free survival rates after salvage radiotherapy following radical prostatectomy failure range from 10% to 77% after a follow-up of 22-60 months. A number of studies have evaluated salvage brachytherapy for radiotherapy failure and 5-year biochemical disease-free survival (bDFS) rate results reported are of the order of 20-87%; one study reported a 10-year bDFS rate of 54%. Fewer studies in small numbers of patients and with shorter follow-up have been conducted on brachytherapy for radical prostatectomy failure and bDFS rates reported include 25.8% at a median of 29 months to 70% at a median of 20 months. The side-effects were as expected for brachytherapy. A newer initiative conducted in Spain in a larger series of 42 patients with failure following radical prostatectomy involves brachytherapy with RAPID Strand™(125) I seeds and real-time placement. The 5-year bDFS rate was 88.6% and cancer-specific survival was 97%; complication rates were low. Optimization of salvage brachytherapy is under way and involves accurate placement of seeds, dose optimization and optimal patient selection.


Oral vaccine based on a surface immunogenic protein mixed with alum promotes a decrease in Streptococcus agalactiae vaginal colonization in a mouse model.
The Surface Immunogenic Protein (SIP) of Group B Streptococcus (GBS) had been described as a good target for vaccine development. To date, SIP has been reported as a highly conserved protein, and in a mouse model it induces protection against lethal GBS challenge. Also, similar effects have been described by intranasal immunization with a SIP-based vaccine. In this study, we show the immune response induced by an oral SIP-based vaccine formulated on alum in a mouse model. Our vaccine can reduce vaginal GBS colonization and induce specific SIP-antibodies with opsonophagocytosis activities against GBS. Moreover, we observed the activation of T-cells producing IFN-γ, TNF-α, IL-10, IL-2, and increased expression of the transcription factor T-bet, suggesting a Th1-type humoral response. The oral SIP-based vaccine is a novel alternative in the development of a vaccine against GBS.


Methods taught in dental schools for determining the posterior palatal seal region.
The following conclusions summarize the results of a survey sent to the chairperson of the removable prosthodontic department of 70 dental schools regarding the concepts and techniques taught for developing the posterior palatal seal. A combination of clinical methods was most frequently taught for locating the vibrating line. The phonation of the Ah sound was the most popular single method taught for locating the vibrating line. Seventy-five percent of the dental schools taught that there is one vibrating line per person. The posterior flexion line was related to the distal termination of the maxillary denture by dental schools that teach the concept of two vibrating lines. Most dental schools (80.4%) do not use the fovea palatinae for locating the distal termination of the maxillary denture. Most dental schools (87.5%) teach students to carve the posterior palatal seal on the maxillary master cast. Most dental schools (93.9%) take the compressibility of the palatal tissue into consideration when carving the depth of the posterior palatal seal in the maxillary master cast. The butterfly pattern was most frequently described to carve the posterior palatal seal in the maxillary master cast.


Prevalence of intracranial large artery stenosis and occlusion in patients with acute ischaemic stroke or TIA.
Intracranial large artery stenosis and occlusion disease has been considered to be the cause of 8–10 % of ischaemic strokes in North America, and 30–50 % of strokes and more than 50 % of transient ischaemic attacks in Chinese population. So far we do not know the real prevalence of intracranial disease (ID) and the distribution of its risk factors in European population. We aimed to determine the prevalence and risk factors of ID in a European stroke population with computed tomography angiography (CTA). A retrospective study of consecutive ischaemic patients at the Stroke Unit of Utrecht, The Netherlands, from September 2006 to August 2008 was conducted. We assessed the presence of occlusion and/or stenosis of intracranial Internal Carotid Artery (ICA) and Middle Cerebral Artery on post-contrast 30-mm reconstruction axial CTA images. We analyzed the proportion of patients with ID, and the association of ID with risk factors and stroke subtype. In 220 patients (187 with stroke, 33 with TIA; mean age was 65 years, 57.3 % were male), intracranial stenosis was found in 6.4 % (95 % CI 3.9–10.4), intracranial occlusion in 34.5 % (95 % CI 28.6–41.0), and both occlusion and stenosis in 2.3 % (95 % CI 1.0–5.2). Multivariate analysis showed that the variables independently associated with ID were: extracranial ICA atherosclerosis (OR, 24.64; 95 % CI 6.30–96.38) and stroke subtypes TACS–PACS (OR, 7.61; 95 % CI 3.31–17.49). In conclusion, prevalence of intracranial stenosis in our study may well be consistent with previous observations in European and non-European population. ID may have been an underestimated condition in ischaemic Caucasian population.


Nodular regenerative hyperplasia of the liver.
Nodular regenerative hyperplasia (NRH), characterized by diffuse hepatic micronodular transformation in groups without fibrous septa between the nodules, is a rare benign liver lesion that has many synonyms in previous literature. Pathologic evaluation is the mainstay of accurate diagnosis. Treatment is focused on its underlying conditions and complications of portal hypertension. A 39-year-old man visited our hospital due to right upper quadrant pain and a palpable liver mass. Magnetic resonance examination revealed a slightly hyperintense tumor on T2-weighted images, and focal nodular hyperplasia was diagnosed by the radiologists. Atypical radiologic findings could not yield an accurate diagnosis. Surgical intervention was therefore performed. Pathologic examination of the resected liver tumor confirmed the diagnosis of NRH. We conclude that NRH should be included in the differential diagnosis of benign liver tumor.


Investigation of psychometric properties of the Mindful Eating Questionnaire in Chinese adolescents and young adults using mixed methods.
Overweight and obesity are major public health challenges in China, and increasingly among young people. Valid measures are needed to examine the relationship between eating styles and weight to advance understanding and intervention. Mindful approaches show promise in weight management. This study aimed to investigate the psychometric properties of a Chinese version of Mindful Eating Questionnaire (C-MEQ). Study 1 used a think aloud methodology to examine Chinese young adults' (n = 7) and adolescents' (n = 10) comprehension of C-MEQ items. Findings informed revision of problematic items before a full validation study (Study 2) of the revised C-MEQ (C-MEQ-R) in a sample of 430 Chinese young adults. In Study 1, both groups misinterpreted ten items as asking about noticing about whether behaviour ever occurred rather than noticing experience, indicating the lack of content validity of the C-MEQ. Ten items were rephrased to emphasise mindful (intentional) noticing in the moment. In Study 2, confirmatory factor analysis revealed an inadequate fit to the original MEQ structure. Exploratory Structural Equation Model of the C-MEQ-R revealed five distinct domains. The C-MEQ-R showed better psychometric properties than the C-MEQ, and significant associations with mindfulness, emotional eating, external eating and BMI in expected directions. However, psychometric limitations including low internal reliability, inadequate coherence of the subscales and limited construct validity were identified. These findings contribute to the progress in the measurement of mindful eating by highlighting the weaknesses of the MEQ. Further research is called to adopt and validate alternative mindful eating measurements to assess mindful eating in Chinese adolescents and young adults.


Safety, Feasibility of Controllable Decrease of Vena Cava Pressure by Doraya Catheter in Heart Failure.
Lowering elevated central venous pressure may reduce renal dysfunction in acute heart failure (AHF) patients. The Doraya catheter lowers renal venous pressure by creating a gradient in the inferior vena cava below the renal veins. Here, we present a first-in-human feasibility study of the Doraya catheter performed on 9 AHF patients. We assessed the safety, feasibility, and acute clinical (hemodynamic and renal) effects of transient Doraya catheter deployment when added to the standard diuretic-based regimen in AHF patients with a poor diuretic response. The procedures decreased central venous pressure from 18.4 ± 3.8 mm Hg to 12.4 ± 4.7 mm Hg (P < 0.001) and improved mean diuresis and clinical signs of congestion. No device-related serious adverse events were observed. Thus, Doraya catheter deployment was safe and feasible in AHF patients. (First In Human Study of the Doraya Catheter for the Treatment of AHF Patients; NCT03234647).


Fish oil inhibits development of atherosclerosis in rhesus monkeys.
The effect of feeding fish oil (Menhaden) on the progression of rhesus monkey atherosclerosis was determined by feeding diets containing 2% cholesterol and either 25% coconut oil (Group I), 25% fish oil/coconut oil (1:1) (Group II), or 25% fish oil/coconut oil (3:1) (Group III) for 12 months (n = 8/group). The average serum cholesterol levels were 875 mg/dl for Group I, 463 mg/dl for Group II, and 405 mg/dl for Group III. HDL cholesterol levels were 49 mg/dl for Group I, 29 mg/dl for Group II, and 20 mg/dl for Group III. An average of 79% of the aortic intima was involved with atherosclerosis in Group I, 48% in Group II, and 36% in Group III. The aortas of both fish-oil groups (II or III) contained significantly less cholesterol (total, free, and esterified), as well as less acid lipase, cholesteryl esterase, and ACAT activities when compared to the coconut-oil group (I) (p less than 0.05). Microscopically, the aortic and carotid artery lesions were smaller in cross-sectional area and in thickness, and contained less macrophages in the fish-oil groups (II and III) when compared to the coconut-oil group (I) (p less than 0.05). This protective effect was not consistently enhanced by increasing the proportion of fish oil to 3:1 (Group III) over 1:1 (Group II). The results indicate that fish oil-containing diets reduce serum cholesterol levels and inhibit atherosclerosis even in the face of lowered HDL cholesterol levels when compared to a pure coconut oil/cholesterol diet in rhesus monkeys. Therefore, fish-oil diets exert effective protective control of progression of atherosclerosis during severe atherogenic stimuli.


Comprehensive mass spectrometry for development of proteomic biomarkers of intracranial aneurysms.
Protein biomarkers of intracranial aneurysm (IA) are essential for early detection and prediction of its rupture to facilitate the diagnosis and clinical management of the disease, monitor treatment response and detect recurrence. Here, we developed a comprehensive strategy for IA biomarker discovery by analyzing tissues from an animal model (n = 4) and serum from human patients (n = 60) using isobaric tandem mass tags-based quantitative proteomics. A total of 4811 and 562 proteins were identified from aneurysm tissue and serum samples, respectively. The 223 candidate protein biomarkers were further validated in an independent serum cohort (n = 30) by multiple reaction monitoring analysis. Combined with a logistic regression model, we built a diagnostic classifier P2 (FCN2 & RARRES2) to differentiate IA from healthy controls with accuracy of 93.3%, as well as a diagnostic classifier P7 (ADAM12, APOL3, F9, C3, CEACAM1, ICAM3, KLHDC7A) to classify ruptured IA from unruptured IA with accuracy of 95.0%. Taken together, our results suggest a valuable strategy for biomarker discovery and patient stratification in IA.


Failure of foot salvage in patients with end-stage renal disease after surgical revascularization.
This report ascertained factors responsible for for failure of foot salvage in patients with end-stage renal disease (ESRD) after undergoing infrainguinal bypass for critical ischemia. A retrospective review of 69 distal arterial reconstructions performed in 53 patients with ESRD (hemodialysis [n = 37], kidney transplantation [n = 10], peritoneal dialysis [n = 6]) for foot gangrene (n = 28), nonhealing ulcer (n = 25), or ischemic rest pain (n = 16) was conducted. Endpoints of surgical morbidity, limb loss, and graft patency were correlated with extent of preoperative tissue loss and presence of diabetes mellitus. The 30-day operative mortality rate was 10%, and the patient survival rate at 2 years was 38%. The primary graft patency rate was 96% at 30 days, 72% at 1 year, and 68% at 2 years. Eleven of 22 foot amputations performed during the mean follow-up period of 14 months (range 3 to 96 months) occurred within 2 months of revascularization. Mechanisms responsible for limb loss included graft failure (n = 9), foot ischemia despite a patent bypass (n = 8), and uncontrolled infection (n = 5). Overall, 59% of amputations were performed in limbs with a patent bypass to popliteal or tibial arteries. Healing of forefoot amputations was prolonged, but all limb loss beyond 9 months of revascularization was due to graft failure. The limb salvage rate at 1 year decreased (p = 0.13) from 74% to 51% in patients admitted with gangrene. Only two of seven patients admitted with forefoot gangrene experienced foot salvage. Failure of foot salvage in patients with ESRD and critical ischemia was due to wound healing problems rather than graft thrombosis. Earlier referral for revascularization, before development of extensive tissue ischemia and infection, is recommended. Primary amputation should be considered in patients admitted with forefoot gangrene, particularly if it is complicated by infection.


Bioinformatic analysis of retinal gene function and expression in diabetic rats.
The aim of the present study was to investigate the changes in retinal gene expression at three time points and assess the underlying molecular mechanisms of diabetic retinopathy (DR) in a streptozotocin (STZ)-induced diabetes rat model using bioinformatics analysis. The gene expression profile of GSE28831 was extracted from the Gene Expression Omnibus database and differentially expressed genes (DEGs) were identified at three different time points (1, 4 and 12 weeks) using the limma package in R language. Gene ontology (GO) enrichment analysis of DEGs was performed followed by a principal component and pathway enrichment analysis of the selected DEGs along with protein-protein interaction network construction at the three time points. A total of 402, 105 and 213 DEGs were screened at 1, 4 and 12 weeks, respectively. In addition, the expression of 8 genes was identified to be significantly different at different time points, including cytochrome P450 2B2 (CYP2B2; downregulated gene; P=0.048; at 1 week), mannan binding lectin-associated serine protease-2 (MASP2; downregulated gene; P=0.044), lecithin retinol acyltransferase (LRAT; downregulated gene; P=0.015), retinal pigment epithelium (RPE)-specific protein 65 kDa (RPE65; downregulated gene; P=0.025), 11-cis-retinoldehydrogenase (RDH5; downregulated gene; P=0.04; at 4 weeks), mitogen-activated protein kinase 13 (MAPK13; upregulated gene; P=0.036), LRAT (downregulated gene; P=0.01) and RPE65 (downregulated gene; P=0.009; at 12 weeks). Furthermore, pathway enrichment and GO enrichment analyses revealed that DEGs at 4 weeks were primarily enriched in retinol metabolism and processes associated with visual functions, including 'visual perception' and 'retinol metabolism'. DEGs, including CYP2B2, MASP2, LRAT, RPE65, RDH5 and MAPK13 may be potential targets for the diagnosis and treatment of DR. Thus, the current study demonstrated that abnormal visual functions occur at 4 weeks in STZ-induced diabetic rats. This may provide a scientific basis for the diagnosis and treatment of DR because DEGs may be used to facilitate the development of novel therapeutic strategies to diagnose and treat DR.


DNA methylation signatures to predict the cervicovaginal microbiome status.
The composition of the microbiome plays an important role in human health and disease. Whether there is a direct association between the cervicovaginal microbiome and the host's epigenome is largely unexplored. Here we analyzed a total of 448 cervicovaginal smear samples and studied both the DNA methylome of the host and the microbiome using the Illumina EPIC array and next-generation sequencing, respectively. We found that those CpGs that are hypo-methylated in samples with non-lactobacilli (O-type) dominating communities are strongly associated with gastrointestinal differentiation and that a signature consisting of 819 CpGs was able to discriminate lactobacilli-dominating (L-type) from O-type samples with an area under the receiver operator characteristic curve (AUC) of 0.84 (95% CI = 0.77-0.90) in an independent validation set. The performance found in samples with more than 50% epithelial cells was further improved (AUC 0.87) and in women younger than 50 years of age was even higher (AUC 0.91). In a subset of 96 women, the buccal but not the blood cell DNA showed the same trend as the cervicovaginal samples in discriminating women with L- from O-type cervicovaginal communities. These findings strongly support the view that the epithelial epigenome plays an essential role in hosting specific microbial communities.


Relationship between pharmacodynamic activity and cognitive effects of eptastigmine in patients with Alzheimer's disease. Eptastigmine Study Group.
To assess the safety, tolerability, pharmacodynamics, and preliminary efficacy of eptastigmine, a new long-acting cholinesterase inhibitor, in patients with probable Alzheimer's disease. This was a double-blind, randomized, placebo-controlled, unbalanced parallel-group study. One-hundred and three patients (83 in the eptastigmine group and 20 in the placebo group) were recruited by 10 centers. Patients received 20 mg eptastigmine or placebo for 4 weeks with twice-a-day or three-times-a-day regimens, depending on body weight (< or = 65 kg or > 65 kg, respectively). Patient performance on the Logical Memory Test, Semantic Word Fluency Test, Trail Making Test, Index of Independence in Activities of Daily Living, Instrumental Activities of Daily Living Scales (IADL), and the Physician and Caregiver Clinical Global Impression of Change (CGIC) was assessed at baseline and at the end of treatment. Nine patients, all from the eptastigmine group, did not complete treatment because of uncooperativeness (n = 3), adverse events (n = 3), protocol violations (n = 2), and clinical decline (n = 1). Twenty-five patients receiving eptastigmine (34%) reported adverse events mainly of the cholinergic type. Cholinergic side effects were generally associated with peak red blood cell cholinesterase inhibition exceeding 50% after the first dose, or 70% at steady state. At steady state, average daily acetylcholinesterase inhibition ranged from 13% to 54%. Overall, 34% of patients receiving eptastigmine versus 0% receiving placebo (p = 0.006) improved on the Physician CGIC. This percentage increased to 46% in the subgroup of patients with average daily acetylcholinesterase inhibition ranging from 30% to 35%. Patient performance on the IADL also improved significantly compared with the placebo group (p = 0.019). In the eptastigmine group, performances on all tests and scales improved with an inverted U-shaped relation to average daily acetylcholinesterase inhibition. This study shows that doses of 40 to 60 mg per day of eptastigmine are relatively safe and well tolerated and that moderate acetylcholinesterase inhibition is associated with maximal cognitive efficacy.


Autophagy in multiple myeloma: what makes you stronger can also kill you.
Autophagy, a process for recycling cellular constituents, is normally associated with cell survival and is thought to be beneficial for tumor maintenance. However, in this issue of Cancer Cell, Lamy and colleagues report that multiple myeloma utilizes caspase-10 to restrain autophagy and undergoes autophagic cell death upon its removal or inhibition.


[Catheter ablation of ventricular tachycardias in patients with ischemic cardiomyopathy].
Radiofrequency (RF) ablation is an effective treatment option of scar-related ventricular tachycardias (VT) in patients with ischemic cardiomyopathy. Several studies proved the benefit of VT catheter ablation, which has become routine in most electrophysiology laboratories. This article provides practical instructions to perform a VT catheter ablation. The authors describe conventional and substrate-based mapping and ablation strategies as well as concepts for image integration. This article continues a series of publications created for education in advanced electrophysiology.


Prevelance of Common Aeroallergens in Allergic Rhinitis and its Correlation with Bronchial Asthma: A Study on 798 Patients by Skin Prick Test.
Allergic rhinitis affects 30% of the Indian population (Dey et al. in Int Arch Allergy Immunol 178:60-65, 2019). Patients can be sensitive to single or multiple allergens. Polysensitization is more common (Bousquet et al. in Ann Epidemiol 20:797-803, 2010; Arbes et al. in J Allergy Clin Immunol 116:377-383, 2005). Sensitization to multiple allergens may have a role in the severity and the association of Asthma in such patients. A total of 798 patients with allergic rhinitis (SFAR ≥ 7) were included. Disease severity and associated symptoms were evaluated using questionnaire. Each patient underwent a Skin prick test with an allergen panel of 35 allergens each (Annesi-Maesano et al. in Allergy 57:107-114, 2002) and the results were evaluated to study the association of asthma and severity of Allergic rhinitis. Data consisting of 389 (48.7%) males and 409 (51.3%) females were assessed. A total of 82.2% of the study population of symptomatic patients were sensitized to at least one of the allergens. Seventy patients (8.78%) had associated asthma. Forty-four patients were polysensitized and fifteen were mono sensitized. Among polysensitized patients, 36 patients had sensitization to at least 6 different allergens. Dermatophagoides pteronyssinus was the most common allergen among asthma patients. This study provides a thorough knowledge of locally prevalent aeroallergens which is essential for the prompt diagnosis and treatment of allergic patients. Skin prick test can be a non-invasive vital tool in analyzing patterns of allergen exposure, the prevalence of allergen, sensitizing potential of different allergens in that specific geographic area.


Long noncoding RNA PCAT-1 knockdown prevents the development of ovarian cancer cells via microRNA-124-3p.
Long noncoding RNA prostate cancer-associated transcript 1 (PCAT-1) is overexpressed in human malignancies and its silence abates the exaggeration of cancers. Whereas, the activity of PCAT-1 silence in ovarian cancer (OC) remains elusive. Here, our study was designed to corroborate the function of PCAT-1 silence in cellular activities and the molecular mechanisms. PCAT-1 in human ovarian tumor tissue specimens and cell lines (A2780 and SKOV3) were quantified by real-time quantitative reverse polymerase chain reaction (qRT-PCR). Reinforced silence of PCAT-1 and microRNA (miR)-124-3p was established by transfection and identified by qRT-PCR. The viability, apoptosis as well as migration and invasion were examined. Western blot was exploited for analysis of proteins involved in proliferation, apoptosis, migration and invasion, and signaling transduction. OC tissues showed the accumulation of PCAT-1. Silencing PCAT-1 caused the impediment of proliferation, migration, and invasion with the increase in apoptosis. PCAT-1 knockdown repressed the expression of cyclin D1, CDK6, p53, Bax, cleaved caspase-3, metallopeptidases, and vimentin with the restoration of miR-124-3p. However, the roles of PCAT-1 silence were weakened in the absence of miR-124-3p. PCAT-1 silence caused decrease in Wnt3a, β-catenin, and phosphorylation of protein kinase B and mechanistic target of rapamycin was abolished by miR-124-3p inhibitor. The tumor-suppressive role of PCAT-1 silence was mediated by miR-124-3p.


Immunologic thrombocytopenic purpura in patients at risk for AIDS.
HIV-seropositive homosexuals, narcotic addicts and hemophiliacs develop a new syndrome of immunologic thrombocytopenic purpura (ITP) which is clinically indistinguishable from classic autoimmune thrombocytopenic purpura (ATP) with respect to increased megakaryocytes in the bone marrow, peripheral destruction of antibody-coated platelets, negative serology for SLE, response to treatment with prednisone and/or splenectomy. Eleven of 79 homosexual patients have developed AIDS 2 to 43 months after the diagnosis of ITP (mean, 22 months). The mechanism of the ITP appears to be different in homosexuals and narcotic addicts when compared to classic ATP. Homosexuals and narcotic addicts have markedly elevated platelet-bound IgG and C3C4 (2.5-4-fold ATP levels), PEG-precipitable circulating immune complexes and anti-F(ab')2 antibodies (absent in ATP). There is no inverse relationship between platelet-bound IgG and platelet count and platelet antibody is usually not elutable from washed platelets as is the case with classic ATP. Homosexual patients do not have 7S platelet antibody in their sera as do classic ATP patients, but appear to have immune complex deposition on their platelets, possibly due to the presence of anti-F(ab')2 antibodies. Narcotic addict patients do have detectable 7S platelet antibody but also appear to have immune complex deposition on their platelets, possibly due to anti-F(ab')2 antibodies. The anti-F(ab')2 antibodies are of the IgG class. They react with autologous, homologous patient and healthy control F(ab')2 fragments. Some anti-F(ab')2 antibodies have broad reactivity, others are more limited. It is postulated that some of the anti-F(ab')2 antibodies may be responsible for the thrombocytopenia.


Virulence of Acinetobacter baumannii in proteins moonlighting.
The diverse function of the moonlighting proteins in Acinetobacter baumannii is highly associated with its virulence that had spurred renewed attention in recent years. The existing and newly formed hypothetical moonlighting proteins, evolve without jeopardizing the structural constraints of their original roles. It is yet uncertain and undefined to lucidly describe the functions of the moonlighting proteins in A. baumannii albeit its overwhelming evidences on few proteins. This commentary thus highlights the expression and occurrence of potent moonlighting proteins in A. baumannii, rendering virulence to the strains and the reasons to target the same portraying an active arena of research.


[Injuries to the tibial plateau (author's transl)].
Conservative management of considerably displaced tibial head fractures tends to stretch the ligaments and damage the soft tissue. Plateau steps impair mobility and lead to secondary osteoarthritis. Therefore operative procedures are prefered: A buttressing plate supports the displaced condyle after exposure and immaculate reduction. Impacted fragments call for elevation and underlining by cancellous graft. Postoperatively, early active motion and late weight bearing is the rule. Operative procedures will only produce satisfactory results when performed by an experienced surgeon.


Failure to achieve tight control of plasma cholesterol and apolipoprotein B with intraperitoneal insulin infusion in type 1 diabetes.
The best route of insulin administration by infusion pumps remains a subject of controversy. For that reason plasma lipids and apolipoproteins were compared in three groups of nine patients who had been treated for several months or years with conventional treatment (group I), continuous subcutaneous insulin infusion (CSII, group II) or continuous intraperitoneal insulin infusion (CPII, group III). Plasma cholesterol and apolipoprotein B remained increased on CPII compared with CSII even when similar satisfactory or even tight diabetic control was achieved with both techniques. This study suggests that cholesterol and perhaps apolipoprotein B biosynthesis by the liver is increased in patients treated with CPII compared to those treated with CSII.


Dynamics of antibiotic resistance markers and Escherichia coli invasion in riverine heterotrophic biofilms facing increasing heat and flow stagnation.
As motivation to address environmental dissemination of antimicrobial resistance (AMR) is mounting, there is a need to characterize mechanisms by which AMR can propagate under environmental conditions. Here we investigated the effect of temperature and stagnation on the persistence of wastewater-associated antibiotic resistance markers in riverine biofilms and the invasion success of genetically-tagged Escherichia coli. Biofilms grown on glass slides incubated in-situ downstream of a wastewater treatment plant effluent discharge point were transferred to laboratory-scale flumes fed with filtered river water under potentially stressful temperature and flow conditions: recirculation flow at 20 °C, stagnation at 20 °C, and stagnation at 30 °C. After 14 days, quantitative PCR and amplicon sequencing were used to quantify bacteria, biofilms diversity, resistance markers (sul1, sul2, ermB, tetW, tetM, tetB, blaCTX-M-1, intI1) and E. coli. Resistance markers significantly decreased over time regardless of the treatment applied. Although invading E. coli were initially able to colonize the biofilms, its abundance subsequently declined. Stagnation was associated with a shift in biofilm taxonomic composition, but there was no apparent effect of flow conditions or the simulated river-pool warming (30 °C) on AMR persistence or invasion success of E. coli. Results however indicated that antibiotic resistance markers in the riverine biofilms decreased under the experimental conditions in the absence of exposure to external inputs of antibiotics and AMR.


Speculations on the evolution of the genetic code. II.
An evolutionary scheme is postulated in which a primitive code, involving only guanine and cytosine, would code for glycine (GG), alanine (GC), arginine (CG) and proline (CC). From each of these amino acids and their codons, there evolves a family of related amino acids as the code expands. The four families are: (1) alanine valine, leucine, isoleucine, phenylalanine, tyrosine, methionine and tryptophane; (2) proline, threonine and serine; (3) arginine, lysine, and histidine; (4) glycine, serine cysteine, glutamic acid, glutamine, aspartic acid and asparagine. Except for the glycine relation to glutamic acid and aspartic acid, all amino acids are related by chemical similarities in their side chains. Glycine not having a side chain would permit a more complex set of substitutions.


Generation of prostaglandin E-like material by the guinea-pig trachea contracted by histamine.
Challenges of the superfused (1 ml min-1) trachea with histamine (100-200 mug) result in the release of prostaglandin E-like material (3-25 ng in terms of prostaglandin E2) but no prostaglandin F-like activity has been detected in the superfusate. This release is blocked by indomethacin (1mug ml-1) and then the contractile action of histamine is enhanced. It is concluded that the release of a prostaglandin E-like material by histamine from tracheal smooth muscles is a self-defensive mechanism protecting against the strong constriction of airways. The maximal relaxation of trachea by isoprenaline (50-500 mug) is not accompanied by the release of a prostaglandin-like material.


[Bloom's syndrome. Discussion of the diagnosis concerning two cases of terminal leukemia in a sibship (author's transl)].
Two brothers developed acute leukemia, one at the age of 7 months and the other at the age of 14 months. Both suffered from a staturoponderal retardation and the same malformation syndrome. The karyotype carried out only on the second child revealed breaks and chromatid changes. A diagnosis of Fanconi's anaemia can be discarbed since no blood cytopenia preceded the leukemia. Finally, the diagnosis of Bloom's syndrome prevailed despite the absence of telangiectatic erythema and the atypical chromosomal anomalies.


Unique Pakistani gut microbiota highlights population-specific microbiota signatures of type 2 diabetes mellitus.
Biogeographic variations in the gut microbiota are pivotal to understanding the global pattern of host-microbiota interactions in prevalent lifestyle-related diseases. Pakistani adults, having an exceptionally high prevalence of type 2 diabetes mellitus (T2D), are one of the most understudied populations in microbiota research to date. The aim of the present study is to examine the gut microbiota across individuals from Pakistan and other populations of non-industrialized and industrialized lifestyles with a focus on T2D. The fecal samples from 94 urban-dwelling Pakistani adults with and without T2D were profiled by bacterial 16S ribosomal RNA gene and fungal internal transcribed spacer (ITS) region amplicon sequencing and eubacterial qPCR, and plasma samples quantified for circulating levels of lipopolysaccharide-binding protein (LBP) and the activation ability of Toll-like receptor (TLR)-signaling. Publicly available datasets generated with comparable molecular methods were retrieved for comparative analysis of the bacterial microbiota. Overall, urbanized Pakistanis' gut microbiota was similar to that of transitional or non-industrialized populations, depleted in Akkermansiaceae and enriched in Prevotellaceae (dominated by the non-Westernized clades of Prevotella copri). The relatively high proportion of Atopobiaceae appeared to be a unique characteristic of the Pakistani gut microbiota. The Pakistanis with T2D had elevated levels of LBP and TLR-signaling in circulation as well as gut microbial signatures atypical of other populations, e.g., increased relative abundance of Libanicoccus/Parolsenella, limiting the inter-population extrapolation of gut microbiota-based classifiers for T2D. Taken together, our findings call for a more global representation of understudied populations to extend the applicability of microbiota-based diagnostics and therapeutics.


Adding trans-abdominal elastography to the diagnostic tool for an ileal gastrointestinal stromal tumor: a case report.
Diagnosis of gastrointestinal stromal tumors (GISTs) in the distal small intestine is difficult by endoscopic ultrasound. This is the first reported case of an ileal GIST, which is diagnosed by transabdominal sonography and strain elastography. A 75 y/o woman presented with tarry stool and dizziness. No definite bleeder could be identified by esophagogastroduodenoscopy and colonoscopy. The transabdominal sonography revealed a large heterogeneous tumor involving the muscular layer of the ileum. Strain elastography showed the strain ratio was 6.51. Strain histogram was skewed to the blue side, and mean color value was 230.5, signifying a stiff tumor. GIST was highly suspected. The patient underwent laparoscope-assisted tumor excision and the histological examination confirmed a malignant GIST. The patient was discharged without postoperative event. Transabdominal strain elastography could play a role to discriminate small bowel GISTs and other submucosal tumors, especially in the location with difficulty in endoscopic ultrasound.