Methods to encourage the use of antenatal corticosteroid therapy for fetal maturation: a randomized controlled trial.
Antenatal corticosteroids for fetal maturation have been underused, despite evidence for their benefits in cases of preterm birth. To evaluate dissemination strategies aimed at increasing appropriate use of this therapy. Twenty-seven tertiary care institutions were randomly assigned to either usual dissemination of practice recommendations (n = 14) or usual dissemination plus an active, focused dissemination effort (n = 13). Obstetricians and their preterm delivery cases at participating hospitals. Recommendations by a National Institutes of Health (NIH) Consensus Conference held in late February-early March 1994 were disseminated in early May 1994. Usual dissemination was publication of the recommendations and endorsement by the American College of Obstetricians and Gynecologists. Active dissemination was a year-long educational effort led by an influential physician and a nurse coordinator at each facility, consisting of grand rounds, a chart reminder system, group discussion of case scenarios, monitoring, and feedback. Use or nonuse of antenatal corticosteroids was abstracted from medical records of eligible women delivering at the participating hospitals in the 12 months immediately prior to release of the NIH recommendations (average number of records abstracted, 130) and in the 12 months following their release (average number of records abstracted, 122). Active dissemination significantly increased the odds of corticosteroid use after the conference. Use increased from 33.0% of eligible patients receiving corticosteroids to 57.6%, or by 75% over baseline, in usual dissemination hospitals. Use increased from 32.9% to 68.3%, oran 108% increase, in active dissemination hospitals. Gestational age and maternal diagnosis affected use of the therapy in complex ways. An active, focused dissemination effort increased the effectiveness of usual dissemination methods when combined with key principles to change physician practices.


The effect of zinc on healing of renal damage in rats.
Several studies have previously been performed to promote kidney healing after injuries. Objectives: The aim of this study was to investigate the effect of zinc on renal healing after traumatic injury in rats. Forty healthy female rats were selected and one of their kidneys was incised. Half of the incisions were limited only to the cortex (renal injury type I) and the other ones reached the pelvocalyceal system of the kidney (renal injury type II). All the rats in the zinc treated group (case group) received 36.3 mg zinc sulfate (contained 8.25 mg zinc) orally. After 28 days, the damaged kidneys were removed for histopathological studies. In the rats with type I injury, kidney inflammation of the case group was significantly lower than that of the control group. However, the result was not significant in rats with type II injury. Tissue loss and granulation tissue formation were significantly lower in the case group than the control group in both type I and II kidney injuries. Overall, Zinc can contribute to better healing of the rat's kidneys after a traumatic injury.


Improvement of solvent production from xylose mother liquor by engineering the xylose metabolic pathway in Clostridium acetobutylicum EA 2018.
Xylose mother liquor (XML) is a by-product of xylose production through acid hydrolysis from corncobs, which can be used potentially for alternative fermentation feedstock. Sixteen Clostridia including 13 wild-type, 1 industrial strain, and 2 genetically engineered strains were screened in XML, among which the industrial strain Clostridium acetobutylicum EA 2018 showed the highest titer of solvents (12.7 g/L) among non-genetic populations, whereas only 40% of the xylose was consumed. An engineered strain (2018glcG-TBA) obtained by combination of glcG disruption and expression of the D-xylose proton-symporter, D-xylose isomerase, and xylulokinase was able to completely utilize glucose and L-arabinose, and 88% xylose in XML. The 2018glcG-TBA produced total solvents up to 21 g/L with a 50% enhancement of total solvent yield (0.33 g/g sugar) compared to that of EA 2018 (0.21 g/g sugar) in XML. This XML-based acetone-butanol-ethanol fermentation using recombinant 2018glcG-TBA was estimated to be economically promising for future production of solvents.


The Passovoy defect: further characterization of a hereditary hemorrhagic diathesis.
We studied a coagulation abnormality present in 12 members of five kindreds who bruised easily and bled excessively after minor trauma. Their activated partial thromboplastin times were between 32 and 39 seconds (normal, 22.8 to 28.8 seconds). Prothrombin times, thrombin times, platelet-function tests and the levels of factors XII, XI, IX, VIII, prekallikrein and high-molecular-weight kininogen were normal. Within these kindreds inheritance of prolonged partial thromboplastin times followed an autosomal and probably dominant pattern. The prolonged thromboplastin times were corrected by normal plasma and by normal plasma adsorbed with celite, but there was no mutual correction between plasmas of the patients. These subjects shared a common defect in the intrinsic pathway of coagulation that we designate by the proband's surname, Passovoy.


Selective microvascular procedures in oculoplastic surgery.
The aesthetic and functional reconstruction of the orbital and periorbital anatomy poses a complex challenge to the reconstructive surgeon. Four clinical cases are illustrated regarding the restoration of contour, and coverage of vital structures following tumor resections.


Immunodeficiencies Associated with Abnormal Newborn Screening for T Cell and B Cell Lymphopenia.
Newborn screening for SCID has revealed the association of low T cells with a number of unexpected syndromes associated with low T cells, some of which were not appreciated to have this feature. This review will discuss diagnostic approaches and the features of some of the syndromes likely to be encountered following newborn screening for immune deficiencies.


Antigen-specific HLA-restricted human T-cell lines. II. A GAT-specific T-cell line restricted by a determinant carried by an HLA-DQ molecule.
Human T-cell lines responsive to the polypeptide antigens GAT and (T,G)-A--L were developed. They were specific for the priming antigens and required the participation of accessory cells matched for HLA-linked determinants, as shown in family studies. In panel studies, the ability of accessory cells to present antigen was shown to be associated with HLA-D-region antigens. However, the specificity of these determinants did not fully correspond to any HLA antigens as currently defined. One GAT-specific subline, derived by limiting dilution, utilized a restriction determinant associated with, but distinct from, the DQw3 (MB3) allospecificity. Blocking studies with mouse monoclonal antibodies indicated that this restriction determinant was carried by HLA-DQ molecules. The epitopes recognized in these molecules appear to be distinct from the alloantigenic determinants currently defined by serology.


PEBP4 silencing inhibits hypoxia-induced epithelial-to-mesenchymal transition in prostate cancer cells.
Hypoxia induced epithelial-to-mesenchymal transition (EMT) to facilitate the tumor biology. Phosphatidylethanolamine-binding protein 4 (PEBP4) is a member of the PEBP family and has been reported to be upregulated in various cancer types. The definite function of PEBP4 in regulating the EMT of prostate cancer, however, is still unclear. Here, we examined the functional role of PEBP4 and the underlying molecular mechanisms in hypoxia-induced EMT in prostate cancer cells. Our results showed that PEBP4 mRNA and protein expression was markedly increased in the human prostate cancer tissues and cell lines. Knockdown of PEBP4 significantly inhibited hypoxia-induced migration/invasion and EMT program. Furthermore, knockdown of PEBP4 prevented hypoxia-induced the expression of p-Akt and p-mTOR in prostate cancer cells. Taken together, this study reported here provided evidence that knockdown of PEBP4 inhibited hypoxia-induced EMT in prostate cancer cells. Our study uncovered a novel role for PEBP4 in prostate cancer progression, which might support the potential for PEBP4 targeting in prostate cancer therapy.


Sex steroids and human behavior: prenatal androgen exposure and sex-typical play behavior in children.
Gonadal hormones, particularly androgens, direct certain aspects of brain development and exert permanent influences on sex-typical behavior in nonhuman mammals. Androgens also influence human behavioral development, with the most convincing evidence coming from studies of sex-typical play. Girls exposed to unusually high levels of androgens prenatally, because they have the genetic disorder, congenital adrenal hyperplasia (CAH), show increased preferences for toys and activities usually preferred by boys, and for male playmates, and decreased preferences for toys and activities usually preferred by girls. Normal variability in androgen prenatally also has been related to subsequent sex-typed play behavior in girls, and nonhuman primates have been observed to show sex-typed preferences for human toys. These findings suggest that androgen during early development influences childhood play behavior in humans at least in part by altering brain development.


Pregnancy and delivery in women with Pompe disease.
The obstetric risk in patients with Pompe disease (glycogen storage disease type II), a mainly skeletal muscle disorder, is unknown. The clinical course and the outcome of pregnancy, and the effect of pregnancy on disease manifestations or clinical signs and symptoms in Pompe disease were analyzed retrospectively using a questionnaire. Participating women with Pompe disease were recruited by the German and the UK sections of the International Pompe Association, and by centers associated within the German Pompe Group. The data was compared with information from the German statistical almanac, perinatal registry, and perinatal quality survey. 66 of 136 women responded to the questionnaire (median age: 47 years, range: 18-74). In 10 of 52 women who had been pregnant, the symptoms of Pompe disease were present during pregnancy (n=7 1st, n=1 2nd, n=1 3rd pregnancy). Muscle weakness worsened in 3 women, and first presented in 3 others during the first pregnancy (4.5% each). Respiratory problems deteriorated in 2/10 women during pregnancy. These 10 symptomatic women had 17 pregnancies (15 deliveries, 2 miscarriages, no abortions). The 42 asymptomatic women (63.6%) had 109 pregnancies (72.4% deliveries, 19.3% miscarriages, 7.3% abortions). There were no significant differences between the mean duration of pregnancies or the mean birth weight in symptomatic and asymptomatic women, or compared to the data from the general population. The same was true of pregnancy and delivery complications (including Cesarean section). Our data show that women with Pompe disease do not appear to have an increased risk of pregnancy or delivery complications. However, muscle weakness and respiratory complications might manifest or worsen during pregnancy in some women.


In vitro anticancer activity of Eclipta alba whole plant extract on colon cancer cell HCT-116.
Colon cancer is the third most deadly and one of the most diagnosed diseases in the world. Although routine screening and early detection during last decades has improved the survival, colon cancer still claims hundreds of thousands lives each year worldwide. Surgery and chemotherapy is mainstay of current treatment, nevertheless toxicity associated with this treatment underscores the urgency of demand of a better therapeutics. Close to 50% of current chemotherapeutic drugs are direct or indirect descendants compounds isolated from medicinal plants, which indicate plants are great potential sources of novel therapeutics. In our literature review we found Eclipta alba to posses many pharmacological activities, including those with anticancer potentials. However, no study on anticancer activity of this kind has been reported. Phytochemicals were extracted by maceration method from shade dried whole plant of Eclipta alba using methanol as a solvent. The anticancer effect of extract was investigated on various cancer cell lines like human colorectal carcinoma (HCT-116), human prostate cancer (PC-3), Michigan cancer foundation-breast cancer (MCF-7) and renal cell carcinoma (RCC-45). We have also studied the effects on normal human embryonic lung fibroblast cell (WI-38) using MTT (methyl thiazoldiphenyltetrazolium bromide) assay, clonogenic (colony formation) and migration assay. Finally obtained results were analyzed using ANNOVA and Dunnett's test. Results obtained from MTT assay revealed that the methanolic extract of Eclipta alba carried significant (p < 0.005) specificity against HCT-116 cells as compared to the other cancer cells. This extract also showed minimal or nontoxicity to WI-38 cells. Migration as well as clonogenic assays also confirmed the anticancer potential of the extract against HCT-116 cells. This is a unique finding of its kind because the specific anticancer effect with minimal toxicity on normal cells has not been reported on Eclipta alba extract. Finally this finding opens up a great possibility to develop a novel antitumor drug candidate against deadly colon cancer in the future.


Combining in silico and in vitro experiments to characterize the role of fascicle twist in the Achilles tendon.
The Achilles tendon (AT), the largest tendon in the human body has a unique structural feature, that is the fascicles in the AT display spiral twist. However, their functional and structural roles are still unclear. We used subject-specific computational models and tissue mechanical experiment to quantitatively characterize the role of fascicle twist in the Achilles tendon. Ten subject-specific finite element (FE) models of the Achilles tendon were developed from ultrasound images. Fascicle twist was implemented in these models using the material coordinate system available in our FE framework. Five different angles (0~60°) were implemented and material property optimization was performed for each of them (total 50 sets) using results from uniaxial stretch experiment. We showed that fascicle twist allows for even distribution of stress across the whole tendon, thus improving tissue strength. The predicted rupture load increased up to 40%. A number of connective tissues display similar fascicle twists in their structure. The resulting non-uniform strain distribution has been hypothesized as a primary factor in tissue degeneration and injuries. Therefore, our technique will be used to design biomechanically informed training and rehabilitation protocols for management of connective tissue injuries and degeneration.


Prevalence, risk factor analysis, and hematological findings of hemoplasma infection in domestic cats from Valdivia, Southern Chile.
Four distinct cat hemoplasma species are recognized worldwide. However, this is the first study to investigate the prevalence, risk factors, and hematological findings of hemoplasmas in cats from Chile. Complete blood count and 16S rRNA real-time PCR for cat hemoplasma species were performed in 384 blood samples from domestic cats in Valdivia, Chile. Among the 384 samples the species-specific prevalence was as follows: 'Candidatus Mycoplasma haemominutum' (7.8%), Mycoplasma haemofelis (4.4%), 'Candidatus Mycoplasma turicensis' (1%), 'Ca. M. haemominutum'+M. haemofelis (0.78%), 'Ca. M. haemominutum'+'Ca. M. turicensis' (0.52%), 'Ca. M. haemominutum'+'Candidatus Mycoplasma haematoparvum' (0.26%) and 'Ca. M. haemominutum'+M. haemofelis+'Ca. M. haematoparvum' (0.26%). Male sex, older age, outdoor access, and FIV status were risk factors for hemoplasmosis. Mycoplasma haemofelis-positive cats had higher mean corpuscular volume and monocyte count. Four hemoplasma species circulate in the cat population of Valdivia. 'Candidatus M. turicensis' and 'Ca. M. haematoparvum' have been reported for the first time in Chilean cats.


Validation of the Spanish Acute Cystitis Symptoms Score (ACSS) in native Spanish-speaking women of Europe and Latin America.
The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for clinical diagnostics and patient-reported outcome (PRO), which may assess the symptoms and the effect on the quality of life in women with acute cystitis (AC). The current study aimed to create a validated Spanish version of the ACSS questionnaire. The process of linguistic validation of the Spanish version of the ACSS consisted of the independent forward and backward translations, revision and reconciliation, and cognitive assessment. Clinical evaluation of the study version of the ACSS was carried out in clinics in Spain and Latin America. Statistical tests included the calculation of Cronbach's α, split-half reliability, specificity, sensitivity, diagnostic odds ratio, positive and negative likelihood ratio, and area under the receiver-operating characteristic curve (AUC). The study was performed on 132 patients [age (mean;SD) 45.0;17.8 years] with AC and 55 controls (44.5;12.2 years). Cronbach's α of the ACSS was 0.86, and the split-half reliability was 0.82. The summary scores of the ACSS domains were significantly higher in patients than in controls, 16.0 and 2.0 (p < 0.001), respectively. The predefined cut-off point of ≥6 for a summary score of the "Typical" domain resulted in a specificity of 83.6% and a sensitivity of 99.2% for the Spanish version of the ACSS. AUC was 0.91 [0.85; 0.97]. The validated Spanish ACSS questionnaire evaluates the symptoms and clinical outcomes of patients with AC. It can be used as a patient's self-diagnosis of AC, as a PRO measure tool, and help to rule out other pathologies in patients with voiding syndrome.


[Antibody-mediated proteolysis of myelin-associated proteins as a new mechanism of control over demyelinization processes in multiple sclerosis].
Natural antibodies possessing catalytic activity present a new group of biologically active substances that are found in various autoimmune diseases such as autoimmune thyroiditis, myocarditis, multiple sclerosis, and system lupus erythematosus. Presently, an interconnection between the activity of these antibodies and the extent of organic and tissue lesion in autoaggression have been revealed. Clinical use of catalytic antibodies as a diagnostic criterion to evaluate the severity of disease, a prognostic criterion of the risk of invalidization, and as a pathogenetic basis for medicamentous treatment of autoimmune process is a promising directions of study of the role of catalytic antibodies.


Implementing stepwise solvent elution in sequential injection chromatography for fluorimetric determination of intracellular free amino acids in the microalgae Tetraselmis gracilis.
The concept of sequential injection chromatography (SIC) was exploited to automate the fluorimetric determination of amino acids after pre-column derivatization with o-phthaldialdehyde (OPA) in presence of 2-mercaptoethanol (2MCE) using a reverse phase monolithic C(18) stationary phase. The method is low-priced and based on five steps of isocratic elutions. The first step employs the mixture methanol: tetrahydrofuran: 10 mmol L(-1) phosphate buffer (pH 7.2) at the volumetric ratio of 8:1:91; the other steps use methanol: 10 mmol L(-1) phosphate buffer (pH 7.2) at volumetric ratios of 20:80, 35:65, 50:50 and 65:35. At a flow rate of 10 microL s(-1) a 25 mm long-column was able to separate aspartic acid (Asp), glutamic acid (Glu), asparagine (Asn), serine (Ser), glutamine (Gln), glycine (Gly), threonine (Thr), citruline (Ctr), arginine (Arg), alanine (Ala), tyrosine (Tyr), phenylalanine (Phe), ornithine (Orn) and lysine (Lys) with resolution >1.2 as well as methionine (Met) and valine (Val) with resolution of 0.6. Under these conditions isoleucine (Ile) and leucine (Leu) co-eluted. The entire cycle of amino acids derivatization, chromatographic separation and column conditioning at the end of separation lasted 25 min. At a flow rate of 40 microL s(-1) such time was reduced to 10 min at the cost of resolution worsening for the pairs Ctr/Arg and Orn/Lys. The detection limits varied from 0.092 micromol L(-1) for Tyr to 0.51 micromol L(-1) for Orn. The method was successfully applied to the determination of intracellular free amino acids in the green alga Tetraselmis gracilis during a period of seven days of cultivation. Samples spiked with known amounts of amino acids resulted in recoveries between 94 and 112%.


New hydrolysis products of the beta-lactam antibiotic amoxicillin, their pH-dependent formation and search in municipal wastewater.
Amoxicillin (AMX) is a widespread β-lactam-antibiotic and, together with some of its transformation products (TPs) originating from hydrolysis, a known environmental contaminant. To shed light on the abiotic degradation of AMX and the stability of its known TPs, laboratory hydrolysis experiments of AMX were carried out at pH 3, 7 and 11. Not only the rate of hydrolysis but also the pattern of TPs was strongly pH-dependent. The time courses of the obtained transformation products were analyzed by UPLC-HR-QToF-MS. AMX penicilloic acid (TP 1), AMX 2',5'-diketopiperazine (TP 2), AMX penilloic acid (TP 3) and 3-(4-hydroxyphenyl)pyrazinol (TP 4) were found at neutral pH. Surprisingly, the first three were not stable but transformed into 23 yet unknown TPs within three to four weeks. Seven TPs were tentatively identified, based on their product ion spectra and, where possible, confirmed with reference standards, e.g. penicillamine disulfide, 2-[amino(carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid and dehydrocarboxylated amoxicillin penilloic acid. Analysis of samples from municipal wastewater treatment plants confirmed these findings with TP 1 being the dominant TP in the influent and a shift towards TP 2, TP 3 and TP 4 in the effluents. The lab experiments predicted up to 13 consecutive TPs from TP 1, TP 2 and TP 3 under neutral conditions. Their detection from surface waters will be difficult, because their large number and slow formation kinetics will lead to comparatively low environmental concentrations. Nevertheless the abiotic degradation of TP 1, TP 2 and TP 3 to further TPs needs to be considered in future studies of the environmental fate of amoxicillin.


EUS-guided transrectal drainage of pelvic fluid collections using electrocautery-enhanced lumen-apposing metal stents: a case series.
Pelvic fluid collections (PFCs) are frequent adverse events of abdominal surgery or inflammatory conditions. A percutaneous approach to deep PFCs could be challenging and result in a longer, painful recovery. The transvaginal approach has been considered easy but is limited by the difficulty of leaving a stent in place. The transrectal approach has been described, but issues related to fecal contamination were hypothesized. Data on EUS-guided transrectal drainage (EUS-TRD) with lumen-apposing metal stents (LAMSs) are few and suggest unsatisfactory outcomes. The aim of this study was to evaluate the safety and efficacy of EUS-TRD with LAMSs in patients with PFCs. A retrospective analysis of a prospectively maintained database on therapeutic EUS was conducted. All EUS-TRD procedures were included. Five patients (2 male, age 44-89 years) were included. Four patients had postoperative PFCs, and 1 presented with a pelvic abscess complicating acute diverticulitis. Two of 5 had fecal diversion; the remaining 3 had unaltered large-bowel anatomy. One case had a concomitant abdominal collection, treated with percutaneous drainage in the same session. An electrocautery-enhanced LAMS delivery system (15 × 10 mm) was used in all cases. EUS-TRD was performed with the direct-puncture technique and lasted less than 10 minutes in 4 cases; in the remaining case, needle puncture and LAMS placement over a guidewire was required, and the procedure length was 14 minutes. The clinical success rate was 100%. LAMSs were removed after a median of 14 (range, 12-24) days. One patient reported partial proximal LAMS migration after 24 days (mild adverse event). No PFC recurrence was observed. EUS-TRD with LAMSs is a safe and effective technique for treatment of PFCs. The use of 15- × 10-mm LAMSs allows rapid PFC resolution. EUS-TRD could be performed not only in patients with fecal diversion but also in cases of unaltered anatomy.


The Toxic Element Concentration in Fish Tissues from Saničani Lake, an Urban Environment, in Bosnia and Herzegovina.
Concentrations of toxic elements (lead, cadmium, mercury, and arsenic) were measured in water, sediment, and four commercial fish species (Cyprinus carpio, Hypophthalmichthys molitrix, Silurus glanis, and Esox lucius) and their tissues (muscle, liver, and kidney) from Saničani Lake, Bosnia and Herzegovina. The concentration of toxic elements was measured by atomic absorption spectrometry. Toxic element concentrations were significantly affected by the fish species and tissues sampled. The lead was the most heavily deposited element in lake sediments and waters. The highest concentrations of Pb and Cd were in the kidney in all four fish species. Concentrations of Hg and As were higher in the muscle than in the kidney and liver in all four fish species. The toxic element concentrations in all examined tissues were significantly higher in Silurus glanis and Esox lucius than in the other fish species examined. Concentrations of all tested elements were present in the fish muscle at different levels, but these levels were under the maximum levels allowed by the European Union and FAO/WHO. Accordingly, fish meat from this lake is acceptable for human consumption.


New studies on basil (Ocimum bacilicum L.) seed gum: Part II-Emulsifying and foaming characterization.
BSG is composed of two major fractions with different molecular weight: PER-BSG (5980kgmol(-1)) and SUPER-BSG (1045kgmol(-1)). In the present work, the emulsifying and foaming properties of BSG and its fractions were investigated as a function of molecular weight, chain flexibility and physicochemical features (protein and acid uronic content). BSG prevented creaming of emulsion for 4 weeks. This high stabilization may be related to formation a solid-like structure and viscoelastic film of BSG around oil droplets which protected oil droplets against aggregation. The low molecular weight fraction (SUPER-BSG) created more stable emulsion than high molecular weight fraction (PER-BSG). The foam capacity and stability of albumin solution increased by adding BSG. The highest foam stability was observed at the highest gum concentration (0.3% w/v). Removing protein moieties of BSG led to emulsion and foam stabilization properties of BSG weakened, which presents the importance of protein in emulsifying and foaming properties of BSG.


Differential abundance of IgG antibodies against the spike protein of SARS-CoV-2 and seasonal coronaviruses in patients with fatal COVID-19.
Infection with the novel pandemic SARS-CoV-2 virus has been shown to elicit a cross-reactive immune response that could lead to a back-boost of memory recall to previously encountered seasonal (endemic) coronaviruses (eCoVs). Whether this response is associated with a fatal clinical outcome in patients with severe COVID-19 remains unclear. In a cohort of hospitalized patients, we have previously shown that heterologous immune responses to eCoVs can be detected in severe COVID-19. Here, we report that COVID-19 patients with fatal disease have decreased SARS-CoV-2 neutralizing antibody titers at hospital admission, which correlated with lower SARS-CoV-2 spike-specific IgG and was paralleled by a relative abundance of IgG against spike protein of eCoVs of the genus Betacoronavirus. Additional research is needed to assess if eCoV-specific back-boosted IgG is a bystander phenomenon in severe COVID-19, or a factor that influences the development of an efficient anti-viral immune response.


Prevalence of developmental coordination disorder among mainstream school children in India.
To estimate the prevalence of DCD in children between ages of 6-15 years attending mainstream schools in a school district in southern India using criteria of Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-5). A total of 2282 children, were screened with Kannada version of DCDQ'07. All the children who were identified as probable. DCD cases were defined by using inclusion (Criteria A, B and C) and exclusion criteria (D) of DSM-5 which are ascertained by specific tests. Nineteen (0.8%) children were identified as DCD with girls (1.1%) affected more than boys (0.5%) at confidence interval of 95%. The prevalence of DCD using DSM-5 criteria is found to be 0.8% in Southern India. Girls were twice affected than boys.


Influence of fibrin, fibrinogen and fibrinogen degradation products on cultured endothelial cells.
Thin films of a fibrin-agar mixture induced significant morphological changes in porcine aortic endothelial cells in vitro. The cells became spindle shaped, piled up and consequently the intercellular spaces widened. These morphological changes became more significant with higher concentrations of fibrin. Films of fibrinogen-agar or thrombin-agar mixtures induced no such morphological changes thereby suggesting that fibrin itself injures the endothelial cells. Despite the lack of morphological effects of fibrinogen degradation product D or E on cultured endothelial cells, lower molecular weight fibrinogen degradation products separated by Sephadex G-25 chromatography did induce injury in the endothelial cells. As damage to the endothelium is a key event in initiation of atherosclerosis, fibrinogen and its metabolites probably play important roles.


Nanocomposite packaging regulates extracellular ATP and programed cell death in edible mushroom (Flammulina velutipes).
Our previous study indicated that nanocomposite packaging material (Nano-PM) containing nano-Ag, nano-TiO2, nano-SiO2 and nanoattapulgite alleviated postharvest senescence of Flammulina velutipes by regulating respiration and energy metabolism. In this study, extracellular ATP (eATP) and programmed cell death (PCD) were employed as critical factors to further investigate the senescence mechanism of postharvest F. velutipes. Results demonstrated that Nano-PM delayed apyrase activity decrease and stimulated critical oxidative phosphorylation-related gene expression to inhibit eATP content increase, which is a crucial signaling molecule related to delaying senescence. The regulation of eATP resulted in alleviating PCD including chromosomal concentration, DNA fragmentation, Ca2+ influx, high caspase-1 activity and cytochrome c content and leading to high cell viability. Overall, Nano-PM alleviated PCD and postharvest senescence of F. velutipes by regulating extracellular ATP.


Pregnancy-associated growth factor. I. A proliferative agent which expands adult and cord T4 cells in unfractionated cultures.
Experiments were designed to examine the effects of pregnancy-associated growth factor (PAGF), a substance found in commercial preparations of crude human chorionic gonadotropin (hCG), on unfractionated human cord blood cells (CBC) and adult peripheral blood lymphocytes (PBL) cultured in 5% fetal calf serum (FCS). Comparisons of PAGF-induced [3H]TdR incorporation in nine pairs of simultaneously cultured CBC and PBL with phytohemagglutinin (PHA) and tetanus toxoid (TT) showed that all CBC and PBL responded to PAGF and PHA whereas all PBL and one CBC responded to TT. The rank order of potency for CBC and PBL was PHA greater than PAGF greater than TT. To examine phenotypic changes induced by PAGF, flow cytometry was performed on precultured cells, control cultures, and PAGF-stimulated cultures at 2, 5, 7, and 9 days. The monoclonal antibodies (mAbs) included T3, T4, and T8 (T cells), T9 (transferrin receptor), Tac (IL-2 receptor), 12 (Ia or DR-framework antigen), and T10 (putative activation and/or maturation antigen). PAGF-stimulated cultures had statistically significant increased percentages of T3, T4, T9, T10, and Tac but not T8 when compared to precultured cells and control cultures. PAGF also increased PBL but not CBC Ia. In PAGF-stimulated cultures, CBC had more T3 and T4 cells with increased fluorescence intensity than PBL. Maximal expression of phenotypes usually occurred at Days 7 and 9, 2 days after maximal [3H]TdR incorporation. In comparison to PAGF, PHA-stimulated PBL had earlier expression of these phenotypes but included T8. These data indicate PAGF induces proliferation, activation antigens, and T3 expansion predominantly confined to the T4 subset in both CBC and PBL.


Fabrication of highly fluorinated porphyrin-based covalent organic frameworks decorated Fe3O4 nanospheres for magnetic solid phase extraction of fluoroquinolones.
A highly fluorinated porphyrin-based covalent organic frameworks magnetic adsorbent (FPy-COF@PDA@Fe3O4) was fabricated by using polydopamine (PDA) grafting Fe3O4 nanospheres as magnetic core and FPy-COF as shell for magnetic solid phase extraction (MSPE) of fluoroquinolones (FQs). FPy-COF was constructed by using 5,15-bis(4-aminophenyl)-10,20-bis(perfluorophenyl)porphyrin and 4,4'-biphenyldicarboxaldehyde as two building blocks. PDA as a bridge grafting on the surface of Fe3O4 nanospheres facilitated the growth of FPy-COF. The morphology and structure of FPy-COF@PDA@Fe3O4 adsorbent were characterized in detail. The prepared magnetic adsorbent exhibited good extraction capability to amphiphilic FQs due to their superior chemical affinities such as fluorophilic interaction and hydrogen-bond interaction from nitrogen-rich skeleton. Under the optimized conditions, the MSPE method combined with high performance liquid chromatography with ultraviolet detection (HPLC-UV) was developed to sensitively quantify trace level of six FQs in milk samples. The developed MSPE-HPLC method showed good linearity with wide concentration range, precision, and low limits of detection (S/N = 3) for six FQs as low as 2.3 ngꞏmL-1 in milk. The extraction recoveries of different spiked concentrations were in the range 77.8-110.4% for milk samples with RSD less than 9.7%.


HCV 6a prevalence in Guangdong province had the origin from Vietnam and recent dissemination to other regions of China: phylogeographic analyses.
Recently in China, HCV 6a infection has shown a fast increase among patients and blood donors, possibly due to IDU linked transmission. We recruited 210 drug users in Shanwei city, Guangdong province. Among them, HCV RNA was detected in 150 (71.4%), both E1 and NS5B genes were sequenced in 136, and 6a genotyped in 70. Of the 6a sequences, most were grouped into three clusters while 23% represent emerging strains. For coalescent analysis, additional 6a sequences were determined among 21 blood donors from Vietnam, 22 donors from 12 provinces of China, and 36 IDUs from Liuzhou City in Guangxi Province. Phylogeographic analyses indicated that Vietnam could be the origin of 6a in China. The Guangxi Province, which borders Vietnam, could be the first region to accept 6a for circulation. Migration from Yunnan, which also borders Vietnam, might be equally important, but it was only detected among IDUs in limited regions. From Guangxi, 6a could have further spread to Guangdong, Yunnan, Hainan, and Hubei provinces. However, evidence showed that only in Guangdong has 6a become a local epidemic, making Guangdong the second source region to disseminate 6a to the other 12 provinces. With a rate of 2.737×10⁻³ (95% CI: 1.792×10⁻³ to 3.745×10⁻³), a Bayesian Skyline Plot was portrayed. It revealed an exponential 6a growth during 1994-1998, while before and after 1994-1998 slow 6a growths were maintained. Concurrently, 1994-1998 corresponded to a period when contaminated blood transfusion was common, which caused many people being infected with HIV and HCV, until the Chinese government outlawed the use of paid blood donations in 1998. With an origin from Vietnam, 6a has become a local epidemic in Guangdong Province, where an increasing prevalence has subsequently led to 6a spread to many other regions of China.


Chronic elevation of amyloid precursor protein expression in the neocortex and hippocampus of rats with selective cholinergic lesions.
Overexpression or aberrant processing of the beta-amyloid precursor protein (APP) and loss of cortical cholinergic function represent two hallmark pathological features of Alzheimer's disease, although it is still unclear whether these alterations take place independently or in an inter-related manner. In the present study, the possible relationships between altered APP expression and cholinergic hypofunction in the neocortex and hippocampus were addressed histologically following selective and complete (90-95%) removal of the basal forebrain cholinergic neurons by the 192 IgG-saporin immunotoxin, at a dose (5.0 microg, intraventricularly) producing profound and permanent cognitive deficits. Computer-aided densitometric analyses revealed, at 6 months post-lesion, a virtually complete loss of terminal cholinergic innervation in various neocortical and hippocampal regions (up to 80%), which correlated highly with the marked (up to 71%) increases in APP expression measured in the same territories. The present results indicate that the integrity of ascending basal forebrain cholinergic inputs to the neocortex and hippocampus may be required for the maintenance of physiological levels of APP expression in the same regions, thus providing a novel rationale for interventions aimed at restoring or enhancing cortical cholinergic neurotransmission.


Mutagenicity potential (affect) of new atraumatic restorative treatment (ART) material incorporated with Azadirachta indica (Neem) against Salmonella typhimurium.
The mutagenicity potential of a new atraumatic restorative treatment (ART) material against Salmonella typhimurium without metabolic activity using the Ames test (genotoxicity) was carried out. The potential mutagenicity of new atraumatic restorative treatment materials (ART-I and ART-II) was analyzed using the Ames test. The materials were eluted in dimethyl sulphoxide, 0.9% NaCl solution and sterilized de-ionized water and the aliquots were used after an incubation period of 24 h at 37 °C. Mutagenic effects of the materials were tested on Salmonella typhimurium strains TA 98 and TA 100 using the standard assay, and in absence of S9 fraction from rat liver. No mutagenic effects were detected for these new ART materials on S. typhimurium TA100. The incubated DMSO extract and 0.9% NaCl extract (50 μl/plate) of the ART-I exhibited a weak mutagenic potential on S. typhimurium TA 98. In particular, Aqua extract (50 μl/plate) of ART-II, was associated with a weak mutagenic potential on S. typhimurium TA98. Both ART materials (ART-I and II) exhibited weak mutagenic effects on S. typhimurium TA98 whereas no mutagenic effect was detected on S. typhimurium TA100. ART-II is safer than ART-I.


Maternal exposure to ambient PM2.5 perturbs the metabolic homeostasis of maternal serum and placenta in mice.
Epidemiological and animal studies have shown that maternal fine particulate matters (PM2.5) exposure correlates with various adverse pregnancy outcomes such as low birth weight (LBW) of offspring. However, the underlying biological mechanisms have not been fully understood. In this study, female C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during pregestational and gestational periods, and metabolomics was performed to analyze the metabolic features in maternal serum and placenta by liquid chromatography-mass spectrometry (LC-MS). The partial least squares discriminate analysis (PLS-DA) displayed evident clustering of FA- and CAP-exposed samples for both maternal serum and placenta. In addition, pathway analysis identified that vitamin digestion and absorption was perturbed in maternal serum, while metabolic pathways including arachidonic acid metabolism, serotonergic synapse, 2-oxocarboxylic acid metabolism and cAMP signaling pathway were perturbed in placenta. Further analysis indicated that CAP exposure influenced the nutrient transportation capacity of placenta, by not only changing the ratios of some critical metabolites in placenta to maternal serum but also significantly altering the expressions of nutrition transporters in placenta. These findings reaffirm the importance of protecting women from PM2.5 exposure, and also advance our understanding of the toxic actions of ambient PM2.5.


p97/VCP promotes Cullin-RING-ubiquitin-ligase/proteasome-dependent degradation of IκBα and the preceding liberation of RelA from ubiquitinated IκBα.
Cullin-RING-ubiquitin-ligase (CRL)-dependent ubiquitination of the nuclear factor kappa B (NF-κB) inhibitor IκBα and its subsequent degradation by the proteasome usually precede NF-κB/RelA nuclear activity. Through removal of the CRL-activating modification of their cullin subunit with the ubiquitin (Ub)-like modifier NEDD8, the COP9 signalosome (CSN) opposes CRL Ub-ligase activity. While RelA phosphorylation was observed to mediate NF-κB activation independent of Ub-proteasome-pathway (UPP)-dependent turnover of IκBα in some studies, a strict requirement of the p97/VCP ATPase for both, IκBα degradation and NF-κB activation, was reported in others. In this study, we thus aimed to reconcile the mechanism for tumour necrosis factor (TNF)-induced NF-κB activation. We found that inducible phosphorylation of RelA is accomplished in an IKK-complex-dependent manner within the NF-κB/RelA-IκBα-complex contemporaneous with the phosphorylation of IκBα, and that RelA phosphorylation is not sufficient to dissociate NF-κB/RelA from IκBα. Subsequent to CRL-dependent IκBα ubiquitination functional p97/VCP is essentially required for efficient liberation of (phosphorylated) RelA from IκBα, preceding p97/VCP-promoted timely and efficient degradation of IκBα as well as simultaneous NF-κB/RelA nuclear translocation. Collectively, our data add new facets to the knowledge about maintenance of IκBα and RelA expression, likely depending on p97/VCP-supported scheduled basal NF-κB activity, and the mechanism of TNF-induced NF-κB activation.


Aspects of the usefulness of five marine pollution biomarkers, with emphasis on MN and lipid content.
By using cellular biomarkers, such as the formation of the micronucleus, the morphometric alterations of lipids and the morphometric changes in the lysosomal system, we investigated effects of experimental exposure to phenanthrene, Cu, Cd, and Hg for 15 days in mussels. Concerning micronuclei, the evaluation of the total nuclear abnormalities, instead of the micronucleus only, as a biomarker of marine pollution, indicated more statistically significant differences between the control and the pollutant treated groups. Contrary to the existing knowledge showing that there is an increase in lipid content after pollutant exposure, our results showed that there was a decrease in the amount of lipid, as well as an increase in the number of neutral lipids. Furthermore, although prior studies found that fewer lysosomes formed after pollutant exposure, this was not confirmed by our work, as pollutant treated animals exhibited a decrease in the volume and an increase in the numerical density of lysosomes, compared to control groups.


Chronic HDV (hepatitis delta virus) hepatitis. Intrahepatic expression of delta antigen, histologic activity and outcome of liver disease.
The expression of intrahepatic delta antigen (HDAg) was studied in relation to the morphologic features of HDV hepatitis and the outcome of liver disease. The study was performed in 101 patients followed up for an average of 12 years; one or more liver biopsies were available from each patient, giving a total of 167 specimens. The histologic features were assessed using numerical scores. A significant positive relation was observed between the number of HDAg-positive cells and the extent of portal inflammation (Spearman's rank coefficient 0.75). The highest degree of inflammation and intrahepatic expression of HDAg was found before the elimination of the virus, while the outcome of HDV disease was unrelated to the severity of the initial morphologic lesion. These results suggest that the individual immune response may play an important role in the pathogenesis of HDV hepatitis.


The rabies information system--a model for a common information system in human and veterinary medicine.
An information system is described in the field of rabies, which realizes the integration of information streams from human medicine as well as from veterinary medicine by help of computers. This rabies information system is based on a homogeneous and coordinated system of surveillance in connection with prophylaxis and control of rabies. It includes a modification of the case record, suggested by the WHO-Expert-Committee on Rabies. The aims of this rabies information system are: to make obvious the epizootiological situation with formation and change of foci, to show the epidemiological importance of special animals and to recognize the epidemiological situation. All this has to be fulfilled in an integrated system. Furthermore optimal treatment is guaranteed by express diagnostics and earliest possible special treatment of high-risk groups by the co-operation of human and veterinary medicine. The rabies information system was generally introduced in the GDR in 1970. It has proved to be practicable and effective especially by standardization of diagnostics, recording exposure of the patient, his treatment and partly automated evaluations of situation records and documentation of efficiency.


Scarless excision of an insertion sequence restores capsule production and virulence in Acinetobacter baumannii.
We identify a new mechanism mediating capsule production and virulence in the WHO and CDC priority ESKAPE pathogen Acinetobacter baumannii. Non-capsulated and avirulent bacteria can revert into a capsulated and virulent state upon scarless excision of an ISAba13 insertion sequence under stress conditions. Reversion events fully restore capsule production and in vivo virulence. This increases our knowledge about A. baumannii genome dynamics, and the regulation of capsule production, virulence and resistance.


Does ovarian stimulation affect uterine artery impedance?
We evaluated the effect of induction of ovulation on uterine perfusion. In 42 infertile women transvaginal color Doppler was performed at days 16-21 of a spontaneous ovulatory cycle and prior to embryo transfer in an in vitro fertilization (IVF) cycle. Indication for treatment was mainly tubal or unexplained infertility. Uterine artery pulsatility index was significantly (P < 0.001) lower in IVF than in natural cycles, 3.24 +/- 0.72 2.64 +/- 0.53 (mean +/- SD), with a mean reduction of 18%. The reduction was higher, although not significantly, in the women who conceived (20%) than in those who did not (15%), and in those with a basal PI > 3.0 (20%) as opposed to those with normal values (16%). The percentage reduction correlated with patient age and with estradiol concentration, number of follicles, and oocytes recruited. Induction of superovulation reduces impedance to flow in the uterine circulation. The amplitude of this effect appears to be regulated partially by patient age and by effectiveness of ovarian stimulation.


Paternal bias in parental origin of HRAS mutations in Costello syndrome.
Costello syndrome (CS) is a rare congenital condition caused by heterozygous de novo missense mutations affecting the codon for glycine 12 or 13 of the HRAS gene. We have identified 39 CS patients harboring the p.Gly12Ser mutation (NM_005343.2:c.34 G > A), two patients with c.35G > C mutations resulting in p.Gly12Ala substitutions, and one patient carrying the p.Gly13Cys substitution (c.37G > A). We analyzed the region flanking the mutated sites in 42 probands and 59 parents, and used four polymorphic markers to trace the parental origin of the germline mutations: one highly polymorphic hexanucleotide (GGGCCT) repeat region, defining three alleles with different numbers of repeat units (two, three, or four), and three SNPs. One of the SNPs, rs12628 (c.81T > C), was found in strong linkage disequilibrium with the hexanucleotide repeat region. Out of a total of 24 probands with polymorphic markers, 16 informative families were tested and the paternal origin of the germline mutation was found in 14 CS probands; a distribution that is neither consistent with an equal likelihood of mutations arising in either parent (P = 0.0018), nor with exclusive paternal origin.


Metformin in the management of fibrocystic breast disease: a placebo-controlled randomized clinical trial.
Fibrocystic disease (FCD) of the breast as a very common health problem in women has estrogen-dependent and proliferative features. No effective management strategy has been validated for this disorder, so far. The anti-hyperglycemic agent metformin has both anti-proliferative and estrogen-suppressing effects. Thus, we investigated metformin as a management strategy for FCD. The study was a double-blind placebo-controlled randomized clinical trial. Premenopausal women with FCD according to history, physical exam and ultrasound, who had measurable microcyst clusters on ultrasound (US) were entered the study. Oral placebo and metformin tablets (500 mg) were used twice daily by participants in the intervention and control groups. Size and number of microcyst clusters on US and the subjective pain score were recorded before and after the intervention. 154 participants were randomly allocated into two groups of 77 interventions and 77 controls. The decrease in size of the largest microcyst cluster in each patient and the mean decrease in number of microcyst clusters were not statistically significant (P = 0.310 and P = 0.637, respectively). However, those microcyst clusters which were ≥ 14 mm became significantly smaller after metformin use (P = 0.006). Additionally, in the subset of participants with pain at baseline, a larger proportion in the intervention group experienced at least 50% reduction in pain score (63.8% (30/47) in the intervention vs. 44.2% (19/43) in the placebo groups, P = 0.031). Our study showed that metformin might be effective in the management of FCD. Further studies are proposed for confirmation of this subject.


Periodic and transient motions of large woodpeckers.
Two types of periodic and transient motions of large woodpeckers are considered. A drumming woodpecker may be modeled as a harmonic oscillator with a periodic forcing function. The transient behavior that occurs after the forcing is turned off suggests that the double knocks of Campephilus woodpeckers may be modeled in terms of a harmonic oscillator with an impulsive forcing, and this hypothesis is consistent with audio and video recordings. Wingbeats are another type of periodic and transient motion of large woodpeckers. A model for the flap rate in cruising flight is applied to the Pileated Woodpecker (Dryocopus pileatus) and the Ivory-billed Woodpecker (Campephilus principalis). During a brief transient just after taking off, the wing motion and flap rate of a large woodpecker may not be the same as in cruising flight. These concepts are relevant to videos that contain evidence for the persistence of the Ivory-billed Woodpecker.


Does healthcare regime affiliation influence the clinical outcomes of patients with rheumatoid arthritis?
Adequate control of disease activity in rheumatoid arthritis (RA) depends, to a great extent, on the access to a rheumatologist. This study aimed to compare the disease outcomes of patients with RA, based on their healthcare regime affiliation. A retrospective observational study of Colombian patients with RA in three outpatient services of different regimes: Contributory (CR, workers and their families with a monthly income above a yearly defined threshold, approximately US$ 220, who allocate a percentage of their income to financing the national health fund and to get access to healthcare services), subsidized (SR, a vulnerable population with a monthly income below the threshold, who have access to healthcare through the national health fund; comparable to the USA Medicaid population), and an excellence clinical care center (C3, access to specialized care, regardless of their healthcare affiliation regime). Data were collected from clinical records for 2 years of follow-up and included demographics, lag times between appointments, and time in high disease activity. We used the Mantel-Cox test for the analysis of time to remission/low disease activity. A total of 240 patients were included (80 patients per regime). At the start of follow-up, mean age was 53.7 years; 21.6% of patients were men; 79.6% of patients had established RA; 72.9% of patients had high disease activity. Patients in the CR had longer lag times between scheduled appointments (p < 0.0001). During follow-up, SR had the highest proportion of patients with high disease activity. Survival curve analysis showed no significant difference between SR and CR groups (p = 0.2903), but was significantly different compared with the C3 group (p < 0.0001). Median survival in high disease activity was greater in the SR group (293 days), followed by CR (254 days), and finally by C3 (64 days). Patients that were treated in the excellence clinical care center had better outcomes when compared with other regimes. These data support that healthcare regime may influence disease outcome in patients with RA. Key Points • Prompt access to healthcare in patients with rheumatoid arthritis is pivotal for an adequate control of the disease, for timely adjustment of treatment, and to reduce both the societal burden of the disease and its impact on individual well-being. • As an example of "structural iatrogenesis," healthcare regime affiliation appears to influence disease outcomes in patients with rheumatoid arthritis, in whom differences between regimes are observed. The most vulnerable patients appear to experience the worst outcomes. • Excellence clinical care centers for patients with rheumatoid arthritis should be implemented as an alternative to counteract structural healthcare barriers and as an approach to improve clinical outcomes through a tighter disease control.


Oestrogen and progesterone receptors and their relationship to histological grades of epithelial tumours of the magnum region of the oviduct of the domestic fowl.
Tumours of the proprial tubular glands of the magnum region of the oviduct of the domestic fowl (Gallus domesticus) were found to contain receptors for oestrogen and progesterone. The distribution of the receptors in the cytosol and nucleus of the tumour cells was similar to that of the normal magnum under oestrogen stimulation. Receptor content showed a positive correlation with increasing clinical stage and histological grade, i.e., malignancy and undifferentiation of the tumours. These tumours are unusual for hormonally responsive tumours in that their receptor mechanism remains intact with loss of differentiation.


Interhemispheric communication of visual learning: a developmental study in 3-6-month old infants.
Infants aged 12-26 weeks (3-6 months) were presented with a visual category discrimination learning task (normal vs scrambled faces) in the right or left visual field. Once they had reached the learning criterion, they were tested for transfer to the untrained visual field in order to establish whether visual experience can be communicated to the opposite hemisphere. Transfer of learning was found to occur in infants aged 19-26 weeks but not in younger ones. Neural pathways possibly forming the channels for this communication are discussed.


Involvement of ATP-dependent aminophospholipid translocation in maintaining phospholipid asymmetry in diamide-treated human erythrocytes.
Crosslinking of membrane skeletal proteins such as spectrin by oxidation of their SH-groups can be provoked by treatment of intact erythrocytes with diamide. Shortly after exposure of human erythrocytes to diamide and despite the transverse destabilization of the lipid bilayer that was observed in these cells (Franck, P.F.H., Op den Kamp, J.A.F., Roelofsen, B. and Van Deenen, L.L.M. (1986) Biochim. Biophys. Acta 857, 127-130), no abnormalities could be detected regarding the asymmetric distribution of the phospholipids when probed by either the prothrombinase assay or brief exposure of the cells to a modified phospholipase A2 with enhanced membrane penetrating capacity. This asymmetry appeared to undergo dramatic changes however, when the ATP content of the cytosol had decreased to less than 10% of its original level during prolonged incubation of the treated cells. These observations indicate that the initial maintenance of phospholipid asymmetry in diamide-treated erythrocytes can be solely ascribed to the action of the ATP-dependent aminophospholipid translocase. This view is supported by experiments involving radiolabeled phospholipids of which trace amounts had been inserted into the outer membrane leaflet of diamide-treated red cells and which still showed a preferential translocation of both aminophospholipids in favour of the inner monolayer, be it that the efficiency of the translocase was found to be impaired when compared to control cells.


Cultivable mycobacteria isolated from organs of armadillos uninoculated and inoculated with Mycobacterium leprae.
Mycobacteria were cultivated from 16 out of 32 samples of tissues from armadillos inoculated with Mycobacterium leprae. Three out of 7 samples from non-inoculated armadillos held in captivity were also positive for cultivable mycobacteria. Some isolated strains belonged to the M. avium-intracellulare-scrofulaceum complex, while others were identified as M. gordonae and M. terrae. Unclassified mycobacteria were isolated from M. leprae-inoculated armadillos only. Taxonomic studies confirmed that these new armadillo-derived mycobacteria (ADM) are different from all presently known species of mycobacteria, including M. leprae. The same new species were isolated from different armadillo colonies and were never found in non-inoculated animals. Different factors influence the isolation of these ADM in primary culture. Analysis of some specific markers of these ADM has been suggested in order to quantitatively determine the proportion of these ADM to M. leprae in armadillo tissues. No mycobacteria were cultivated from Nude mouse footpads infected with M. leprae.


The central nervous norepinephrine network links a diminished sense of emotional well-being to an increased body weight.
The neurobiological mechanisms linking obesity to emotional distress remain largely undiscovered. In this pilot study, we combined positron emission tomography, using the norepinephrine transporter (NET) tracer [(11)C]-O-methylreboxetine, with functional connectivity magnetic resonance imaging, the Beck depression inventory (BDI), and the impact of weight on quality of life-Lite questionnaire (IWQOL-Lite), to investigate the role of norepinephrine in the severity of depression (BDI), as well as in the loss of emotional well-being with body weight (IWQOL-Lite). In a small group of lean-to-morbidly obese individuals (n=20), we show that an increased body mass index (BMI) is related to a lowered NET availability within the hypothalamus, known as the brain's homeostatic control site. The hypothalamus displayed a strengthened connectivity in relation to the individual hypothalamic NET availability to the anterior insula/frontal operculum, as well as the medial orbitofrontal cortex, assumed to host the primary and secondary gustatory cortex, respectively (n=19). The resting-state activity in these two regions was correlated positively to the BMI and IWQOL-Lite scores, but not to the BDI, suggesting that the higher the resting-state activity in these regions, and hence the higher the BMI, the stronger the negative impact of the body weight on the individual's emotional well-being was. This pilot study suggests that the loss in emotional well-being with weight is embedded within the central norepinephrine network.


Endothelin ETB1 receptor agonism as a new therapeutic strategy in pulmonary arterial hypertension and chronic heart failure.
Pulmonary arterial hypertension and post-ischemic chronic heart failure are highly prevalent diseases with high morbidity and mortality rates due to chronic vascular injury and extensive remodeling responses at the level of the vessel walls. Endothelins play a central role in this setting, through a complex signaling system that mainly affects endothelial and vascular smooth muscle cells. ETA and ETB2 endothelin receptors are thought to mediate pro-ischemic responses, while ETB1 receptor activity could account for the overall protective effect of ETB signaling in physiology. The pharmacologic modulation of the endothelin system has mainly focused on the dual non-selective blockade of ETA and ETB endothelin receptors or to the selective blockade of ETA-related pathways to date. Good clinical results were achieved in the setting of pulmonary hypertension but no advantage has been demonstrated for heart failure. Restoring and enhancing the physiological protective role of ETB1-signaling with concomitant blockade of ETB2 could possibly improve the efficacy of current therapies in the setting of pulmonary arterial hypertension and post-ischemic chronic heart failure.


Understanding secondary overtriage for neurosurgical patients in a rural tertiary care setting.
Excessive interfacility transfer to a tertiary care facility of minimally injured patients for subspecialty evaluation leads to overuse of resources and is referred to as secondary overtriage (SO). Little is known regarding the epidemiology of SO in rural settings, particularly for patients with a mild head injury who may be safely managed without admission to level I trauma centers. In order to determine the rate of SO for neurosurgical patients with Glasgow Coma Scale (GCS) of 13-15 referred to a rural level 1 trauma center, we conducted a retrospective chart review of 224 patients evaluated for potential transfer to Dartmouth-Hitchcock Medical Center from January 1, 2014 through December 31, 2014. SO was defined as any admission where a patient was transferred from an outside facility, had a length of stay shorter than 48 h, did not require neurosurgical intervention, and was alive at the time of discharge. Of the 224 patients evaluated, 163 patients were transferred. Of the 163 patients included in this study, 43 (26.4%) met criteria for SO, 59 (36.2%) patients met criteria for intervention, and 61 (37.2%) patients met criteria for observation. Approximately a quarter of the total patients who are transferred to a rural level I trauma center for neurosurgical evaluation are minimally injured, do not require neurosurgical intervention, and are discharged within 48 h of presentation. Management at their referring facility with remote neurosurgical consultation is likely safe in this population. Understanding the rate of SO in neurosurgical patients and risk factors present in this group can better guide future transfer policies at rural medical centers.


Photocatalytic oxidation of aqueous ammonia in model gray waters.
This study investigated the TiO2 photocatalytic degradation of aqueous ammonia (NH4+/NH3) in the presence of surfactants and monosaccharides at pH approximately 10.1. Initial rates of NH4+/NH3 photocatalytic degradation decreased by approximately 50-90% in the presence of anionic, cationic, and nonionic surfactants and monosaccharides. Through correlation analysis, we concluded that scavenging of hydroxyl radical (.OH) by the products of surfactant/monosaccharide photocatalytic degradation, including carbonate and formate, could explain approximately 80% of the variance in initial rates of NH4+/NH3 removal in our system. Addition of a supplemental .OH source (H2O2) enhanced the rate of NH4+/NH3 degradation in the presence of the surfactant Brij 23 lauryl ether (Brij 35), further supporting the idea that .OH scavenging is the mechanism by which surfactants and monosaccharides decreased initial rates of NH4+/NH3 photocatalytic degradation. Despite slowed rates of NH4+/NH3 degradation, both surfactants/monosaccharides and NH4+/NH3 were removed by TiO2 photocatalysis, indicating that this process can effectively remove both carbonaceous and nitrogenous biochemical oxygen demand from gray water.


Trending biocontrol strategies against Cronobacter sakazakii: A recent updated review.
Cronobacter sakazakii is an emerging foodborne pathogen, causing life-threatening infections in newborns and premature infants. Cronobacter spp. can survive under difficult processing conditions thereby contaminate the Powdered Infant Formula (PIF) during the manufacturing process. Infantile infections are associated with the consumption of contaminated PIF that was either contaminated intrinsically or extrinsically. This necessitates the development of sustainable strategies to manage the risk of Cronobacter infections. Natural methods of preservation holds promise as a viable alternative strategy to address the critical problem of emerging antimicrobial resistance and also to limit the negative effects of commonly used physico-chemical methods in food processing. The present study reviews the efficacies, potentials and developmental trends of biological antagonists and a combinatorial therapy to eliminate C. sakazakii using in vitro and in vivo methods. The mode of action of each biocontrol method has been discussed comprehensively. Most of these biocontrol agents interfere with the cell membrane integrity and its functions. However, none of the individual methods are able to eliminate the pathogen completely from the model food system i.e. reconstituted PIF. Each of the biological control strategies (agent) has its limitations in terms of their dose and method of application. A synergistic effect has been observed between the biological agent and physico-chemical treatments that may have the potential to ensure pathogen-free foods. Future research studies should evaluate the synergistic activities of these methods for their implication in infant foods as well as to understand the mechanisms of inactivation.


Enhanced Stability of Inactivated Influenza Vaccine Encapsulated in Dissolving Microneedle Patches.
This study tested the hypothesis that encapsulation of influenza vaccine in microneedle patches increases vaccine stability during storage at elevated temperature. Whole inactivated influenza virus vaccine (A/Puerto Rico/8/34) was formulated into dissolving microneedle patches and vaccine stability was evaluated by in vitro and in vivo assays of antigenicity and immunogenicity after storage for up to 3 months at 4, 25, 37 and 45°C. While liquid vaccine completely lost potency as determined by hemagglutination (HA) activity within 1-2 weeks outside of refrigeration, vaccine in microneedle patches lost 40-50% HA activity during or shortly after fabrication, but then had no significant additional loss of activity over 3 months of storage, independent of temperature. This level of stability required reduced humidity by packaging with desiccant, but was not affected by presence of oxygen. This finding was consistent with additional stability assays, including antigenicity of the vaccine measured by ELISA, virus particle morphological structure captured by transmission electron microscopy and protective immune responses by immunization of mice in vivo. These data show that inactivated influenza vaccine encapsulated in dissolving microneedle patches has enhanced stability during extended storage at elevated temperatures.


Risk and reliability analysis for maritime autonomous surface ship: A bibliometric review of literature from 2015 to 2022.
Recently, researchers have shown a soaring interest in maritime autonomous surface ship (MASS). The reliable design and risk evaluation of MASS is crucial in order to support its safe operations. Hence, keeping abreast of emerging trends in developing MASSs safety and reliability-related technologies is necessary and significant. Nevertheless, a comprehensive literature review focused on this realm is currently lacking. On this premises, based on the 118 selected articles (consisting of 79 journal articles and 39 conference papers) between 2015 and 2022, content analyses and science mapping were conducted in this study from the aspects of journal sources, keywords, countries and institutions, authors, and citations of these publications. The bibliometric analysis aims to uncover several characteristics in this area such as the mainstream journals, research trends, knowledge contributors, and their cooperation relationships. Based on this, the research topic analysis was conducted from five facets including mechanical reliability and maintenance, software, hazard assessment, collision avoidance, communication and human element. It is suggested that the Model-Based System Engineering (MBSE) and Function Resonance Analysis Method (FRAM) could be two potential practical methods for future research risk and reliability analysis for MASS. This paper provides insights into the current state-of-the-art of risk and reliability research in MASS, including current research topics, gaps and future directions. It can also serve as a reference for related scholars.


Multi-institutional Survey of Squamous Cell Carcinoma of the External Auditory Canal in Japan.
This study aimed to evaluate the efficacy of chemoradiotherapy (CRT) for patients with advanced cancer of the external auditory canal (EAC) by analyzing the outcome of the patients. This is a multi-institutional retrospective survey, and we reviewed the medical records of the subjects. A total of 181 patients with tumor (T)3 or T4 tumor in 17 institutions were enrolled. Further analysis was performed for 74 patients who underwent CRT under curative intent. Overall 5-year survival rates of the patients who underwent CRT (n = 74) were 54.6%. Those of the patients who underwent CRT with modified TPF (docetaxel, cisplatin [CDDP], and 5-fluorouracil) regimen (n = 50) and CRT with CDDP regimens (n = 24) were 64.4% and 36.7%, respectively. Significant differences were observed between these two groups. Given the tendency that head and neck surgeons prefer CRT for advanced larger cancer of the EAC, CRT for advanced EAC cancer using the modified TPF regimen showed good clinical outcomes. 4 Laryngoscope, 131:E870-E874, 2021.


Inherited ARPC5 mutations cause an actinopathy impairing cell motility and disrupting cytokine signaling.
We describe the first cases of germline biallelic null mutations in ARPC5, part of the Arp2/3 actin nucleator complex, in two unrelated patients presenting with recurrent and severe infections, early-onset autoimmunity, inflammation, and dysmorphisms. This defect compromises multiple cell lineages and functions, and when protein expression is reestablished in-vitro, the Arp2/3 complex conformation and functions are rescued. As part of the pathophysiological evaluation, we also show that interleukin (IL)-6 signaling is distinctively impacted in this syndrome. Disruption of IL-6 classical but not trans-signaling highlights their differential roles in the disease and offers perspectives for therapeutic molecular targets.


Radiation-Induced Damage to Prepubertal Pax7+ Skeletal Muscle Stem Cells Drives Lifelong Deficits in Myofiber Size and Nuclear Number.
During prepubertal development, muscle stem cells (satellite cells, SCs) actively contribute to myofiber growth. Because some SCs are active during this time, they may be particularly susceptible to damage. Using a Small Animal Radiation Research Platform (SARRP), we investigated the effects of local fractionated radiation treatment on prepubertal SCs. Immediately after this regimen, there was a reduction in SC number. Although surviving SCs had deficiencies in function, some myogenic potential remained. Indeed, some muscle regenerative capacity persisted immediately after irradiation. Lastly, we assessed the long-term consequences of radiation-induced SC loss during prepuberty. We observed a reduction of myofiber size and corresponding loss of nuclei in both fast- and slow-contracting muscles 14 months post-irradiation. Notably, prepubertal SC depletion mimicked these lifelong deficits. This work highlights the susceptibility of prepubertal SCs to radiation exposure. We also reveal the importance of prepubertal SC contribution to the lifelong maintenance of skeletal muscle.


CNS-accessible Inhibitor of Glucosylceramide Synthase for Substrate Reduction Therapy of Neuronopathic Gaucher Disease.
Gaucher disease (GD) is caused by a deficiency of glucocerebrosidase and the consequent lysosomal accumulation of unmetabolized glycolipid substrates. Enzyme-replacement therapy adequately manages the visceral manifestations of nonneuronopathic type-1 Gaucher patients, but not the brain disease in neuronopathic types 2 and 3 GD. Substrate reduction therapy through inhibition of glucosylceramide synthase (GCS) has also been shown to effectively treat the visceral disease. Here, we evaluated the efficacy of a novel small molecule inhibitor of GCS with central nervous system (CNS) access (Genz-682452) to treat the brain disease. Treatment of the conduritol β epoxide-induced mouse model of neuronopathic GD with Genz-682452 reduced the accumulation of liver and brain glycolipids (>70% and >20% respectively), extent of gliosis, and severity of ataxia. In the genetic 4L;C* mouse model, Genz-682452 reduced the levels of substrate in the brain by >40%, the extent of gliosis, and paresis. Importantly, Genz-682452-treated 4L;C* mice also exhibited an ~30% increase in lifespan. Together, these data indicate that an orally available antagonist of GCS that has CNS access is effective at attenuating several of the neuropathologic and behavioral manifestations associated with mouse models of neuronopathic GD. Therefore, Genz-682452 holds promise as a potential therapeutic approach for patients with type-3 GD.


Specific determination of bromobenzene metabolites by high-performance liquid chromatography.
A chromatographic method for the quantitative and simultaneous determination of phenolic and mercapturic acid type metabolites of bromobenzene is presented. Acid hydrolysis (1.5 N HCl, 100 degrees C, 10 min) yielded unconjugated bromophenols. After extraction (ethyl acetate, pH 2), evaporation to dryness and dissolution in methanol, samples were analysed by high-performance liquid chromatography (HPLC) with a c18 reverse-phase column and a phosphate buffer (0.1 M,pH 9 + 5 mM tetrabutylammonium dihydrogen phosphate) - acetonitrile gradient with ultraviolet detection (225 nm). Benzylmercapturic acid and o-chlorophenol were used as internal standards. Using this method, it was possible to determine simultaneously o, m- and p-bromophenols together with o-, m- and p-bromophenylmercapturic acids. Additional validation data were obtained by analysis of urine samples from rats treated with bromobenzene. This new method was compared to existing procedures.


Reversible sensorineural hearing loss in a stroke patient.
A case is presented of a patient with lateral pontine stroke which resulted in a moderate unilateral sensorineural hearing loss. ABR, word recognition scores, acoustic reflexes, neurological evaluation, and CT scan were consistent with brain stem lesion. Recovery of hearing, including acoustic reflexes and word recognition ability, occurred 2 months after the stroke.


Posttraumatic stress disorder and somatic complaints: Contrasting Vietnam and OIF/OEF Veterans' experiences.
To replicate and expand upon the relationship of somatic symptoms and posttraumatic stress disorder (PTSD) by comparing symptoms among service eras in US Veterans. Data were collected from 226 Vietnam and 132 Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Veterans who were referred to a Veterans Affairs (VA) hospital PTSD outpatient clinic between 2005 and 2013. Veterans were administered self-report inventories and a clinical interview to measure somatic symptoms and PTSD severity. A subset of Veterans (n=185) screening positive for PTSD were administered the Clinician Administered PTSD Scale (CAPS) to measure PTSD severity. Multiple moderated linear regressions were used to examine the influence of service era on the relationship between somatic and PTSD symptoms. There were no significant differences between service eras in pain severity, pain interference, and total somatic symptoms reported. Vietnam Veterans were more likely to report limb/join pain (p<.05), fainting (p<.01), and shortness of breath (p<.001), whereas OIF/OEF Veterans were more likely to complain of headaches (p<.001). A significant interaction effect occurred between service era and dizziness (p<.05) and chest pain (p<.01), with OIF/OEF Veterans reporting higher levels of these symptoms significantly more likely than Vietnam Veterans to also experience more severe PTSD. Findings are consistent with previous research demonstrating the relationship of somatic symptoms and PTSD across service eras but provide additional data concerning similarities and differences of somatic symptoms between eras. Potential explanations for observed service era differences in somatic symptoms are discussed.


Harpagoside suppresses lipopolysaccharide-induced iNOS and COX-2 expression through inhibition of NF-kappa B activation.
Preparations of Harpagophytum procumbens, known as devil's claw, are used as an adjunctive therapy for the treatment of pain and osteoarthritis. Pharmacological evaluations have proven the effectiveness of this herbal drug as an anti-inflammatory and analgesic agent. The present study has investigated the mechanism of action of harpagoside, one of the major components of Harpagophytum procumbens, using human HepG2 hepatocarcinoma and RAW 264.7 macrophage cell lines. Harpagoside inhibited lipopolysaccharide-induced mRNA levels and protein expression of cyclooxygenase-2 and inducible nitric oxide in HepG2 cells. These inhibitions appeared to correlate with the suppression of NF-kappaB activation by harpagoside, as pre-treating cells with harpagoside blocked the translocation of NF-kappaB into the nuclear compartments and degradation of the inhibitory subunit IkappaB-alpha. Furthermore, harpagoside dose-dependently inhibited LPS-stimulated NF-kappaB promoter activity in a gene reporter assay in RAW 264.7 cells, indicating that harpagoside interfered with the activation of gene transcription. These results suggest that the inhibition of the expression of cyclooxygenase-2 and inducible nitric oxide by harpagoside involves suppression of NF-kappaB activation, thereby inhibiting downstream inflammation and subsequent pain events.


Sphingolipid metabolism in neural cells.
Sphingolipids were discovered more than a century ago in the brain. Cerebrosides and sphingomyelins were named so because they were first isolated from neural tissue. Although glycosphingolipids and especially those containing sialic acid in their oligosaccharide moiety are particularly abundant in the brain, sphingolipids are ubiquitous cellular membrane components. They form cell- and species-specific profiles at the cell surfaces that characteristically change in development, differentiation, and oncogenic transformation, indicating the significance of these lipid molecules for cell-cell and cell-matrix interactions as well as for cell adhesion, modulation of membrane receptors and signal transduction. This review summarizes sphingolipid metabolism with emphasis on aspects particularly relevant in neural cell types, including neurons, oligodendrocytes and neuroblastoma cells. In addition, the reader is briefly introduced into the methodology of lipid evaluation techniques and also into the putative physiological functions of glycosphingolipids and their metabolites in neural tissue.


New species of Euplocania Enderlein (Psocodea: 'Psocoptera': Psocomorpha: Ptiloneuridae) from Colombia.
Seven species of Colombian Euplocania, are here described and illustrated, they increase to 16 the number of species in the genus, eight of which are endemic to Colombia. A new species group is also described.


LuxA gene of light organ symbionts of the bioluminescent fish Acropoma japonicum (Acropomatidae) and Siphamia versicolor (Apogonidae) forms a lineage closely related to that of Photobacterium leiognathi ssp. mandapamensis.
A molecular phylogenetic analysis of luxA gene sequences of light organ symbionts of the fish Acropoma japonicum (Acropomatidae) and Siphamia versicolor (Apogonidae) revealed that the sequences were related to those of Photobacterium leiognathi ssp. mandapamensis, which is not known to occur as a light organ symbiont among bioluminescent P. leiognathi clades. The presence of another lux gene element, luxF, coding for nonfluorescent protein, provided additional support for the identity of the light organ symbionts of the fish. Cladogenesis of the light organ symbiont P. leiognathi may be influenced by the radiation of host fishes.


Cardiac dysautonomia and serotonin plasma levels in Rett syndrome.
In Rett syndrome the autonomic nervous system is abnormal at various levels, from the central to the peripheral nervous system. A role for serotoninergic dysfunction has been suggested. The aim of our study was to evaluate the relation between cardiac dysautonomia (expressed by means of heart rate variability) and plasma serotonin levels in girls affected with Rett syndrome. Heart rate variability and plasma serotonin levels were evaluated in 28 Rett girls aged 1-14 years. A Pearson correlation was used to determine whether there was a relationship between plasma serotonin levels and each heart rate variability parameter. In untreated Rett girls the plasma serotonin levels correlated with the sympathovagal balance, as expressed by the low frequency (LF) to high frequency (HF) ratio (p<0.05). Our results suggest that cardiac dysautonomia could be linked to serotoninergic dysfunction and that treatment with a serotonin analogue could be useful in improving the sympathovagal balance.


Opportunities to investigate the effects of ivermectin mass drug administration on scabies.
The recent article by Mohammed et al. demonstrates an impressive effect of ivermectin mass drug administration for lymphatic filariasis on the burden of scabies. Partnering scabies research within the evaluation and monitoring of Neglected Tropical Disease programmes could potentially increase our understanding of the epidemiology and control of scabies and its important bacterial complications.


Acute poisoning at two hospitals in Kampala-Uganda.
The aim of this study was to characterize acute poisoning cases admitted to two hospitals in Kampala, Uganda. All cases admitted to the two hospitals, from January 2005 to June 2005, were evaluated retrospectively. Data obtained from the hospital medical records included the following: demographic characteristics, toxic agents, length of stay, circumstances of poisoning, and mortality information on the victims. Of the total 276 patients admitted for treatment, whose mean age was 26.6 (+/-12.2) years, 71.0 % were males. The age category of 20-29 years old most affected (42.8%), while only 5.1% of those affected were younger than 13 years old. Toxic agents involved in the incidents were, in descending order, agrochemicals (42.4%), household chemicals (22.1%), carbon monoxide (20.0%), snakebites (14.1%), and food poisoning (1.4%). There was a statistically significant difference with regard to gender, females were more victims of poisoning by snake bites (25.0% vs. 9.7%) and food poisoning (2.5% vs. 1.0%), while males were more affected by carbon monoxide (25.5% vs. 6.3%). Moreover, 61.2% patients spent less than 2 days in hospital, the mean length of stay was 2.1 days, with a range of 1 to 26 days. The overall case fatality rate was 1.4%; of those who died, 75% were males, and the toxic agents responsible for the death were alcohol (50%), carbon monoxide (25%), and organophosphate (25%). Acute poisoning involved more men, who spent more than 2 days being hospitalized, and resulted in a case fatality rate of 1.4% due to alcohol, carbon monoxide, and organophosphates. These findings suggest that further studies are warranted in order to understand the motivation(s) for this emerging problem, and plan appropriate interventions.


Combined mathematical methods in the description of the F(o)F(1)-ATP synthase catalytic cycle.
The FoF1-ATP synthase is one of the key enzymes in supplying energy production in almost all living systems. In this paper, we provide a theoretical description of its catalytic cycle using combined mathematical methods. These methods include Langevin dynamics for the rotation of the central protein core and the Monte-Carlo method to model nucleotide and proton binding. This model is the first in which ATP synthesis and hydrolysis can occur depending on the nucleotide concentration and system conditions. The main advantage of the presented model is the possibility of obtaining results for both single-molecular protein-machines and large ensembles of proteins. The calculated rates are close to the experimentally measured rates for a single enzyme. The model has been formalised as a computer simulation that allows researchers to evaluate ATP production in different types of living cells.


A case-control study of correlation between preoperative serum AFP and recurrence of hepatocellular carcinoma after curative hepatectomy.
The prognostic impact of serum alpha-fetoprotein (AFP) on patients with hepatocellular carcinoma (HCC) undergoing curative resection remains unclear. We conducted a case-control study to investigate it. A total of 196 HCC patients with negative preoperative AFP were admitted and treated by curative liver resection. During the same period, 196 patients with positive preoperative AFP were enrolled to match the TN M stages, Child-Pugh score and HBs-Ag status of the AFP-negative patients. Time to recurrence (TTR) and overall survival (OS) were prospectively studied. Through a median follow-up duration of 5.25 years, we found that the median TTR of patients with negative preoperative AFP was significantly longer than those with positive AFP (17.3 vs. 12.8 months, p=0.001). The median TTRs of AFP-negative and positive patients were 22.1 and 21.0 months (p=0.266), 145 and 7.4 months (p=0.005) and 3.7 and 2.9 months (p=0.197) in TNM stages I, II and IIIa, respectively. The median TTRs of TNM stage II patients with :≤20, 20-400, 400-1000 and >1000 ng/mL preoperative AFP concentration were 14.5, 13.7, 10.7 and 9.6 months (p=0.092), respectively. Preoperative AFP level is an independent prognostic factor affecting postoperative recurrence in HCC patients and correlated with the TTR of TNM II.


[Should we modify our therapeutic behavior as a consequence of the 2009 revision of the ESH/ESC guidelines for the management of arterial hypertension].
The recent publication in November 2009 of the revision of the European guidelines on hypertension management by the European Society of hypertension has aroused great interest. It has included the results of new important studies on hypertension, reinforcing the evidence on which the recommendations of the 2007 ESH/ESC guidelines were based. However, some of the recommendations that were firmly established until now are reconsidered. This dual aspect can generate some relevant doubts in clinical practice, even more so if we consider that some recommendations are opposite to other recently published guidelines. The presentation of a frequently appearing clinical case, as a hypertensive and diabetic female patient >65 years old, provides us the opportunity to analyze and interpret new recommendations, in comparison to the previous ones and to establish the best clinical action approach in the daily practice. In addition to the changes in the management of diabetic patients, some especially relevant aspects of the revised guide are updated, for example, subclinical injury of the target organ and its affect on cardiovascular risk stratification, how to manage those patients with high normal blood pressure values and other cardiovascular risk factors, the "new" blood pressure goals, as well as the objectives and the treatments under specific conditions such as the elderly population and the associated cardiovascular disease.


Challenges and Prospects of Laser Haemorrhoidoplasty in a Low Resource Setting: The LUTH Experience.
Haemorrhoids are the most common condition of the anal canal causing significant disability. Traditional excisional haemorrhoidectomy and its various modifications, while effective, may be attended by severe postoperative pain and other complications. Laser haemorrhoidoplasty is reported to be effective with fewer complications and shorter hospital stay. The aim of this study was to report the outcome of intrahaemorrhoidal coagulation with 1470-nm diode laser at the Lagos University Teaching Hospital. The procedures were performed with a radially emitting laser fibre from Biolitec AG-CeramOptec (Bonn, Germany). The duration of symptoms, grade of the haemorrhoids, duration of the procedures, and postoperative complications were evaluated. Eleven patients had laser haemorrhoidoplasty. There were seven males and four females. The age range was 23-71 years, with a median age of 47 years and an interquartile range (IQR) of 28-57 years. Duration of surgery ranged from 20 to 90 min, with a median of 33 min and IQR of 25-53 min. Postoperative pain was mild in eight patients and moderate in three. Ten patients were discharged as day cases and one 3 days later due to spinal anaesthesia-related headache and acute urinary retention. One patient later had an anal ulcer probably due to too much energy delivered during the procedure, this was managed conservatively. There was no postoperative wound infection, anal incontinence, anal stenosis, subcutaneous abscess, and fistula or recurrence. The advantages of laser haemorrhoidoplasty make it a readily acceptable form of treatment for haemorrhoids in our setting.


Evidence against the mucosal traction theory in cholesteatoma.
To investigate the distribution of ciliated epithelium in the human middle ear and its potential role in the formation of cholesteatoma. Comparative human temporal bone study. We selected temporal bones from 14 donors with a diagnosis of cholesteatoma, 15 with chronic otitis media without retraction pockets, 14 with chronic otitis media with retraction pockets, 14 with cystic fibrosis (CF), and 16 controls. We mapped the distribution of the ciliated cells in the mucosal lining of the middle ear and tympanic membrane using three-dimensional reconstruction analysis, and counted the number of ciliated cells in the middle ear mucosa. Ciliated cells are extremely sparse in the epithelial lining of the lateral surface of the ossicles in the epitympanum and the medial surface of the tympanic membrane. Furthermore, there is a significant decrease in the number of ciliated cells in these areas in temporal bones with cholesteatoma, chronic otitis media, chronic otitis media with retraction pockets, and CF compared to controls. Ciliated cells most commonly are located at the hypotympanum and the Eustachian tube opening but not the tympanic membrane or epitympanum. The paucity of ciliated epithelial cells on the medial side of the tympanic membrane and the lateral surface of the ossicles in the epitympanum in cases with cholesteatoma and/or chronic otitis media do not support the mucosal migration theory of cholesteatoma formation. NA. Laryngoscope, 128:1663-1667, 2018.


Masks, Mingling and Magic: Gibberish Law in the Age of Covid.
The experience of Covid-19 has taught us many things, not least the consequence of what John Milton termed 'gibberish law'. Law drafted amidst the 'throng and noises of irrational men'. The closer purpose of this article is the attempt to regulate 'gatherings' during the coronavirus pandemic, including the re-invention of a bespoke crime of 'mingling'. A jurisprudential curiosity which, it will be suggested, is symptomatic of a broader malaise. An assault on the integrity of the rule of law which is only too familiar; much, it might be said, like the arrival of a pandemic. The first part of the article will revisit three particular gatherings, in part to debunk the myth of the unprecedented. But also to introduce some themes, literal and figurative, of masking and muddle. The conjuring of what Shakespeare called 'rough magic'. The second part of the article will then take a closer look at the jurisprudential consequence of this conjuration. The final part will venture some larger concerns, about the crisis of parliamentary democracy in the 'age of Covid'.


[Disseminated infiltrated cutaneous pruritis].
The diagnosis of scabies is clinically not always simple without the detection of mites. Histology can be difficult, particularly without clinico-pathologic correlation. [corrected] Even after adequate antiscabies treatment the dermatological symptoms and complaints can persist and necessitate an [corrected] intensive follow-up treatment. The case example described here underlines that in consideration of the multifaceted clinical appearance and the sometimes difficult detection of mites, scabies should always be considered as a differential diagnosis in cases of persistent pruritis.


Love Is Not All You Need: Understanding the Association Between Relationship Status and Relationship Dysfunction With Self-Directed Violence in Veterans.
Research indicates that being married is associated with reduced risk of suicide and self-directed violence (SDV) relative to being divorced. Simultaneously, difficulties within relationships predict poorer health outcomes. However, research on relationship status rarely examines relationship functioning, obfuscating the joint contribution of these variables for SDV risk. Veterans (N = 1,049) completed a survey that included assessment of relationship status, relationship functioning, and SDV history. Logistic regression models tested how (a) relationship status, (b) relationship dysfunction, and (c) being divorced compared to being in a low- or high-dysfunction relationship were associated with SDV, controlling for several intrapersonal risk factors. Veterans in a relationship did not differ in SDV history compared to divorced/separated veterans. However, more dysfunction within relationships was associated with greater odds of a history of SDV and suicidal cognitions. Finally, SDV histories were more likely among veterans endorsing high-dysfunction relationships compared with (a) low-dysfunction relationships and (b) divorced veterans. It may be insufficient to only consider relationship status when evaluating interpersonal risk factors for SDV. A single item assessing relationship dysfunction was associated with enacted SDV and suicidal cognitions over and above intrapersonal risk factors. Integrating such single-item measures into clinical practice could improve identification and subsequent tailored intervention for veterans at greater risk for SDV.


Association of non-HDL-C/HDL-C ratio and its dynamic changes with incident type 2 diabetes mellitus: The Rural Chinese Cohort Study.
We aimed to evaluate the association of the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (non-HDL-C/HDL-C) and its dynamic changes with incident type 2 diabetes mellitus (T2DM). A total of 11,487 nondiabetic participants ≥18 years old in rural China were recruited in 2007-2008 and followed up in 2013-2014. A Cox proportional-hazards model was used to assess the risk of incident T2DM by quartiles of baseline non-HDL-C/HDL-C ratio and dynamic absolute and relative changes in non-HDL-C/HDL-C ratio, estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Risk of incident T2DM was increased with quartiles 2, 3, and 4 versus quartile 1 of baseline non-HDL-C/HDL-C ratio (HR 1.46 [95% CI 1.08-1.98], 1.51 [1.12-2.03], and 2.16 [1.62-2.88], Ptrend < 0.001). As compared with stable non-HDL-C/HDL-C ratio during follow-up, an absolute gain in non-HDL-C/HDL-C ratio was associated with increased risk of T2DM (HR 1.67 [95% CI 1.25-2.24] for quartile 3 and 2.00 [1.52-2.61] for quartile 4). A relative increase in non-HDL-C/HDL-C ratio was also associated with increased risk of T2DM (HR 1.56 [95% CI 1.19-2.04] for quartile 3 and 1.97 [1.49-2.60] for quartile 4). Subgroup analyses showed that the association of non-HDL-C/HDL-C ratio with T2DM risk remained consistent. Increased non-HDL-C/HDL-C ratio is associated with increased risk of incident T2DM among rural Chinese adults, so the index may be an important indicator for identifying individuals at T2DM risk.


[Evaluation of leukemogenic and immunogenic properties of leukemic cells modified by neuraminidase of non-cholera Vibrios on the model of Rauscher leukemia].
The leukemogenic activity of modified leukemic cells was studied in experiments on the 385 BALB/c mice with Rauscher leukemia by transplantation of different amount of treated cells. Immunogenicity of modified leukemic cells was estimated under conditions of three-fold immunization of animals 2 days later by the cells dose equal to 1.10(6) which began 24 h after the leukemia transplantation. The effect of immunotherapy of neuraminidase-modified leukemic cells results in elongation of animal lifetime, presence of less pronounced changes in the peripheral blood and spleen as well as in stimulation of cell immunity factors.


A systematic review and meta-analysis of CBT interventions based on the Fennell model of low self-esteem.
Low self-esteem is a feature of several mental health disorders that has been directly treated with Cognitive-Behavioral Therapy (CBT). The aim of our study was to determine the efficacy of interventions for improving low self-esteem in adults by utilizing the model outlined in Fennell (1997; 1998; 1999). A literature search identified 8 studies that met the inclusion criteria of CBT-based interventions for low self-esteem using this model, 7 of which were used in a quantitative synthesis. These studies included weekly group and individual sessions and one-day workshop formats. Summary effect sizes of 1.12 and 0.34 at post-treatment were observed, with low levels of heterogeneity, for weekly sessions and one-day workshops, respectively. Comparable results were found for the reduction of depressive symptoms. Results suggest that CBT-based interventions may be efficacious for treating individuals with low self-esteem, according to changes in self-report measures; however, it is unclear whether these interventions are dissimilar to those aimed at reducing depression.