New chromosomal malformation syndromes. I. Partial monosomy 8p. An attempt to establish a new chromosome deletion syndrome.
A mentally retarded 8-year-old boy with a de novo partial monosomy for the short arm of the No. 8 chromosome is described. Based on G-banding analysis, the patient's karyotype was identified in lymphocytes and skin fibroblasts as 46,XY,del(8) (pter leads to p21:). No chromosomal abnormalities were found in the phenotypically normal mother, father and sister of the propositus. Four further cases described in the literature indicate that partial monosomy of the short arm of the No. 8 chromosome might be associated with a syndrome characterized by the following stigmata: mental retardation, slow growth, high forehead, broad chest, wide-set nipples, pulmonary stenosis with atrial and/or ventricular septal defect, hypoplasia of the genitalia, dermatoglyphic stigmata.


Toward Environmentally Robust Organic Electronics: Approaches and Applications.
Recent interest in flexible electronics has led to a paradigm shift in consumer electronics, and the emergent development of stretchable and wearable electronics is opening a new spectrum of ubiquitous applications for electronics. Organic electronic materials, such as π-conjugated small molecules and polymers, are highly suitable for use in low-cost wearable electronic devices, and their charge-carrier mobilities have now exceeded that of amorphous silicon. However, their commercialization is minimal, mainly because of weaknesses in terms of operational stability, long-term stability under ambient conditions, and chemical stability related to fabrication processes. Recently, however, many attempts have been made to overcome such instabilities of organic electronic materials. Here, an overview is provided of the strategies developed for environmentally robust organic electronics to overcome the detrimental effects of various critical factors such as oxygen, water, chemicals, heat, and light. Additionally, molecular design approaches to π-conjugated small molecules and polymers that are highly stable under ambient and harsh conditions are explored; such materials will circumvent the need for encapsulation and provide a greater degree of freedom using simple solution-based device-fabrication techniques. Applications that are made possible through these strategies are highlighted.


Multiple congenital epulides in a newborn: with special reference to reported cases in Japan.
This report describes a case of multiple epulides which simultaneously occurred on the maxilla and the mandible of a 6-day-old female baby. The clinical findings, diagnostic procedure, surgical treatment, histopathology, and 2-year follow-up of this case are presented. Based on the clinicostatistical and histopathologic investigations with special reference to the pertinent Japanese literature, a possible histogenetic etiology of this entity is discussed. Any odontogenic component might play an important role in the development of this tumor. This case of multiple epulides is considered to be very rare.


Understanding the role of the topology in protein folding by computational inverse folding experiments.
Recent studies suggest that protein folding should be revisited as the emergent property of a complex system and that the nature allows only a very limited number of folds that seem to be strongly influenced by geometrical properties. In this work we explore the principles underlying this new view and show how helical protein conformations can be obtained starting from simple geometric considerations. We generated a large data set of C-alpha traces made of 65 points, by computationally solving a backbone model that takes into account only topological features of the all-alpha proteins; then, we built corresponding tertiary structures, by using the sequences associated to the crystallographic structures of four small globular all-alpha proteins from PDB, and analysed them in terms of structural and energetic properties. In this way we obtained four poorly populated sets of structures that are reasonably similar to the conformational states typical of the experimental PDB structures. These results show that our computational approach can capture the native topology of all-alpha proteins; furthermore, it generates backbone folds without the influence of the side chains and uses the protein sequence to select a specific fold among the generated folds. This agrees with the recent view that the backbone plays an important role in the protein folding process and that the amino acid sequence chooses its own fold within a limited total number of folds.


Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems.
Cardiopulmonary bypass (CPB) is often necessary for congenital cardiac surgery, but CPB can alter drug pharmacokinetic parameters resulting in underdosing. Inadequate plasma levels of antibiotics could lead to postoperative infections with increased morbidity. The influence of pediatric CPB systems on cefazolin and clindamycin plasma levels is not known. We have measured plasma levels of cefazolin and clindamycin in in vitro pediatric CPB systems. We have tested three types of CPB systems. All systems were primed and spiked with clindamycin and cefazolin. Samples were taken at different time points to measure the recovery of cefazolin and clindamycin. Linear mixed model analyses were performed to assess if drug recovery was different between the type of CPB system and sampling time point. The experiments were conducted at a tertiary university hospital. 81 samples were analyzed. There was a significant difference in the recovery over time between CPB systems for cefazolin and clindamycin (P < .001). Cefazolin recovery after 180 minutes was 106% (95% CI: 91-123) for neonatal, 99% (95% CI: 85-115) for infant, and 77% (95% CI: 67-89) for pediatric systems. Clindamycin recovery after 180 minutes was 143% (95% CI: 116-177) for neonatal, 111% (95% CI: 89-137) for infant, and 120% (95% CI: 97-149) for pediatric systems. Clindamycin recovery after 180 minutes compared to the theoretical concentration was 0.4% for neonatal, 1.2% for infants, and 0.6% for pediatric systems. The recovery of cefazolin was high in the neonatal and infant CPB systems and moderate in the pediatric system. We found a large discrepancy between the theoretical and measured concentrations of clindamycin in all tested CPB systems.


Modification of the contractile activity of isolated rat atria by lectin-activated T-lymphocyte subsets.
We had previously shown that human T-lymphocytes (ERFC) that had been activated for a short time with phytohemagglutinin (PHA) produced positive inotropic and chronotropic effects on spontaneously beating rat atria (Sterin-Borda, L., et al., Naunyn Scmiedeberg's Arch. Pharmacol. 324, 58, 1983). In this study, we first prepared T4-rich (T4) and T8-rich (T8) cells from ERFC by selective lysis with OKT4 and OKT8 monoclonal antibodies and rabbit complement. Then, we tested the effect of PHA-stimulated T4 (PHA-T4) and T8 (PHA-T8) on beating rat atria. PHA-T4 cells stimulated the tension and the frequency of contraction of isolated rat atria by a mechanism that involved the generation of the slow reacting substance of anaphylaxis (SRS-A), since both 10(-5) M nordihydroguaiaretic acid (NDGA) and 10(-7) M FPL-55712 were effective inhibitors. On the other hand, PHA-T8 cells decreased the tension of beating atria. Indomethacin (10(-6) M) could not block the depressor effect. Cell-free PHA-T4 supernatants reacted with the heart tissue similarly to whole PHA-T4 cells. Since NDGA or FPL-55712 treated organs did not respond to active PHA-T4 supernatants, the lipoxygenase system of the auricles seems to be required for the reaction and the active metabolites appear to derive mainly from the heart. Our results suggest that PHA-activated "helper/inducer" cells release soluble factors that can in turn trigger the lipoxygenase metabolic pathway of arachidonic acid in the heart, generating the active leukotrienes responsible for the positive inotropic and chronotropic effects.


Metastatic metaplastic carcinoma from a pseudosarcoma (Lane tumor) of the mouth.
A case of polypoid metaplastic carcinoma (Lane tumor) of the mouth is presented. There are well defined zones of transition between the squamous epithelium of the polyp and the stroma. Metastases in the right neck and paratracheal lymph nodes contain areas of cartilaginous and osseous metaplasia as well as squamous epithelial pearls.


Cytogenetic effects of radiotherapy. Breakpoint distribution in induced chromosome aberrations.
A total of 660 breakpoints were identified in the chromosome aberrations detected in lymphocytes from cancer patients after radiotherapy. The results show that chromosomes 1, 3, and 7 were significantly more affected than other chromosomes by ionizing radiation in vivo. Chromosome arms 1p, 1q, 7q, and 11p were also significantly more affected. Some bands also showed a special sensitivity to radiation, and band 1q32 was the most affected. This band is proposed as a "hot point" for the clastogenic effect of ionizing radiation. A significant clustering of breakpoints in G bands was also found, especially at the telomeres, as previously described by other authors. Clustering of breakpoints was also observed in bands where fragile sites, protooncogenes, breakpoints involved in chromosomal cancer rearrangements, and breakpoints involved in chromosomal evolution of the Hominoidea are located.


The epidemiology of multiple sclerosis in Queensland, Australia.
An epidemiological survey of multiple sclerosis (MS) in the State of Queensland was undertaken with its prevalence day being the national census day on June 30th, 1981, 20 years after a regional survey within the State. The relationship between increasing prevalence of MS and increasing south latitude within the State of Queensland which was suggested by the 1961 study was confirmed in the present study. The prevalence rate had increased significantly over the 20-year period between the studies but the State remained a medium frequency zone for MS (prevalence rate between 5 and 29 per 100,000 of population). Although a real increase in disease frequency could not be excluded as a contributing factor to the rise in prevalence, it was most likely due predominantly to an increase in life expectancy amongst the MS population and also in differential migration of a population at a greater risk of developing MS than the indigenous population. The proportions of Australian-born patients who had migrated to Queensland from the higher risk southern regions of Australia or travelled overseas to countries known to be high-risk for MS prior to disease onset, had fallen between the two surveys thus exerting, if anything, a negative influence on the change in prevalence. Analysis of MS prevalence rates amongst migrant populations in Queensland as compared to the more southerly city of Perth in Western Australia, suggested that the risk of acquisition of MS may extend over a wider age range than is generally accepted. Finally, there was an absence of MS cases amongst the Aboriginal population in Queensland but it can only cautiously be concluded from this study that the disease is rare in these peoples.


Treatment of severe acute pancreatitis through retroperitoneal laparoscopic drainage.
A treatment method based on drainage via retroperitoneal laparoscopy was adopted for 15 severe acute pancreatitis (SAP) patients to investigate the feasibility of the method. Ten patients received only drainage via retroperitoneal laparoscopy, four patients received drainage via both retroperitoneal and preperitoneal laparoscopy, and one patient received drainage via conversion to laparotomy. Thirteen patients exhibited a good drainage effect and were successfully cured without any other surgical treatment. Two patients had encapsulated effusions or pancreatic pseudocysts after surgery, but were successfully cured after lavage and B ultrasound-guided percutaneous catheter drainage. SAP treatment via retroperitoneal laparoscopic drainage is an effective surgical method, resulting in minor injury.


Predictors of perinatal outcome in early-onset fetal growth restriction: A study from an emerging economy country.
To identify antenatal predictors of adverse perinatal outcomes in a population of preterm fetuses with early placental insufficiency diagnosed by Doppler abnormalities. In this cross-sectional study of a cohort of singleton pregnant women diagnosed with early placental insufficiency, relationships between perinatal variables (arterial and venous Doppler, gestational age, birth weight, oligohydramnios, estimated fetal weight, and fetal weight z-scores) and major neonatal complications were analyzed by logistic regression. Two hundred sixty-five women were delivered, between 24 and 33 weeks gestation. The overall frequency of intact survival was 57.9% (n = 154). Gestational age thresholds for best prediction of survival was 27 + 6 weeks and for intact survival was 29 + 0 weeks gestation. Fetal weight and absent/reversed ductus venosus a-wave were the main predictors of survival in the regression model. When fetal weight was substituted for fetal weight z-score, ductus venosus abnormal Doppler predicted mortality and absent or reversed umbilical artery diastolic velocities predicted intact survival. This study illustrates the impact of gestational age and fetal weight on perinatal outcomes in early placental insufficiency, with well-defined thresholds. Gestational age and fetal weight, or a combination of fetal weight z-scores and fetal Doppler parameters, were the best predictors of intact survival in our sample.


Stress and ethanol-induced hypothermia.
Three experiments examined the effects of three stressors on the hypothermic response to IP injection of ethanol in rats. Although all three stressors elicited hyperthermia in the absence of ethanol, only electric footshock reduced ethanol hypothermia. Handling/rectal-probing and bright, flashing light enhanced ethanol hypothermia. Type of cage floor (solid vs. grid) affected overall magnitude of ethanol hypothermia, but did not affect handling-induced enhancement of ethanol hypothermia. It is suggested that events which trigger release of endogenous opioids may enhance ethanol hypothermia. This kind of ethanol-stress interaction has important implications for studies of the acute and chronic effects of ethanol, including studies of learned tolerance. It may also have implications for understanding the impact of stress on voluntary consumption of ethanol.


E-cadherin junctions as active mechanical integrators in tissue dynamics.
During epithelial morphogenesis, E-cadherin adhesive junctions play an important part in mechanically coupling the contractile cortices of cells together, thereby distributing the stresses that drive cell rearrangements at both local and tissue levels. Here we discuss the concept that cellular contractility and E-cadherin-based adhesion are functionally integrated by biomechanical feedback pathways that operate on molecular, cellular and tissue scales.


Neurological infections caused by herpes simplex virus in adults.
Over a period of 33 months, 281 neuro-infections were tested for herpes simplex virus. In 26 cases herpes simplex virus was identified as the aetiological agent by isolation of the virus from the cerebrospinal fluid and by serological tests. The illness took the form of severe encephalitis in four cases, less severe encephalitis or meningoencephalitis in 12 cases, aseptic meningitis in seven cases, meningo-encephalitis with radiculitis in one case, ascending radiculomyelitis in one case and radiculitis in one case. The diagnostical and therapeutical problems of herpes simplex neuro-infections are discussed.


Female lordotic behavior mediated by monoamines in male rats.
Direct application of serotonergic of beta-adrenergic receptor blockers to anterior or posterior areas of the hypothalamus induced lordosis in intact estrogen-primed male rats. Such treatment with an alpha-adrenergic blocker or systemic administration of progesterone failed to increase lordosis. Centrally elicited lordosis did not occur without estrogen priming. Anatomical and neurochemical similarity may exist in the brain mechanism mediating lordotic behavior in male and female adult rats.


No evidence for systolic or diastolic left ventricular dysfunction at rest in selected patients with long-term type I diabetes mellitus.
We assessed left ventricular systolic and diastolic function using pulsed-waved Doppler echocardiography in a selected group of 20 patients with insulin-dependent diabetes mellitus (IDDM) (mean age, 35 +/- 8 years; mean diabetes duration, 17 + 7 years). Our patients were free of autonomic neuropathy and major micro- or macrovascular complications and had no evidence of ischemic heart disease or hypertension. The results were compared with those of 20 age- and sex-matched control subjects. We found that left ventricular geometry and mass, systolic function by M-mode and 2D-echocardiography, isovolumetric relaxation time, deceleration time and the PEP/LVET ratio were not significantly different between patients and control subjects. Hemodynamic parameters were also not significantly different except for a slightly higher heart rate in the patient group (75 +/- 11 vs. 68 + 6 bpm, P = 0.019). After correction of A-peak velocities for differences in heart rate, there was no significant difference of Doppler indices of diastolic left ventricular function between patients and control subjects. The absence of significant left ventricular systolic and diastolic dysfunction by Doppler echocardiography in our study patients may be explained by our patient selection. Left ventricular dysfunction in diabetic patients without concomitant hypertensive or ischemic heart disease may only occur in conjunction with microvascular disease in other organ systems, with autonomic neuropathy or with poor metabolic control.


Nitrate removal in iron sulfide-driven autotrophic denitrification biofilter: Biochemical and chemical transformation pathways and its underlying microbial mechanism.
Iron sulfides-based autotrophic denitrification (IAD) is effective for treating nitrate-contaminated wastewater. However, the complex nitrate transformation pathways coupled with sulfur and iron cycles in IADs are still unclear. In this study, two columns (abiotic vs biotic) with iron sulfides (FeS) as the packing materials were constructed and operated continuously. In the abiotic column, FeS chemically reduced nitrate to ammonium under the ambient condition; this chemical reduction reaction pathway was spontaneous and has been overlooked in IAD reactors. In the biotic column (IAD biofilter), the complex nitrogen-transformation network was composed of chemical reduction, autotrophic denitrification, dissimilatory nitrate reduction to ammonium (DNRA) and sulfate reducing ammonium oxidation (Sulfammox). Metagenomic analysis and XPS characterization of the IAD biofilter further validated the roles of functional microbial communities (e.g., Acidovorax, Diaphorobacter, Desulfuromonas) in nitrate reduction process coupled with iron and sulfur cycles. This study gives an in-depth insight into the nitrogen transformations in IAD system and provides fundamental evidence about the underlying microbial mechanism for its further application in biological nitrogen removal.


Pregnancy-associated plasma protein A in a large cohort of Type 1 diabetic patients with and without diabetic nephropathy-a prospective follow--up study.
Pregnancy-associated plasma protein A (PAPP-A) has been implicated in the aetiology of acute coronary syndromes and carotid and peripheral artherosclerosis. Diabetic nephropathy is characterized by increased cardiovascular risk. We investigated the prognostic value of PAPP-A in a large cohort of Type 1 diabetic patients. In a prospective observational follow-up study, 197 Type 1 diabetic patients with diabetic nephropathy and a matched group of 178 patients with normoalbuminuria were followed for 10.1 (0-10.3) years. PAPP-A was determined at baseline. In patients with diabetic nephropathy, plasma PAPP-A was elevated 3.6 (0.4-51.1) mIU/l [median (range)] vs. 2.1 (0.4-46.6) mIU/l in normoalbuminuric patients, P < 0.0001. For acute coronary syndromes, a PAPP-A threshold of 10 mIU/l has been suggested. Thirty-seven patients were above the threshold and of these 13 patients (35%) died, compared with 60 of 338 patients (18%) below the threshold; log rank test P = 0.007. PAPP-A significantly predicted mortality after adjustment for presence of nephropathy; hazard ratio for dying when PAPP-A was above the threshold 2.1 (95% CI 1.13-3.9); P = 0.019. After adjusting for traditional risk factors, the results were attenuated. When only patients with nephropathy were analysed, PAPP-A was significantly predictive of all-cause mortality [P = 0.008; 2.43 (1.26-4.67)] in unadjusted analysis. After adjustment, the predictive value of PAPP-A for all-cause mortality was attenuated (P = 0.064). We find PAPP-A to be associated with increased mortality in Type 1 diabetic patients with nephropathy in unadjusted analysis. After adjustment for traditional risk factors, the prognostic value of PAPP-A was no longer significant.


Site-selective guest inclusion in molecular networks of butadiyne-bridged pyridino and benzeno square macrocycles on a surface.
We present here the formation of a modular 2D molecular network composed of two different types of square-shaped butadiyne-bridged macrocycles, having intrinsic molecular voids, aligned alternately at the solid-liquid interface. Site-selective inclusion of a guest cation took place at every other molecular void in the molecular network with two different recognition sites.


Efficacy of a high bioavailable cetylpyridinium chloride mouthrinse over a 24-hour period: a plaque imaging study.
To evaluate the antiplaque benefits of a 0.07% high bioavailable, alcohol-free cetylpyridium chloride (CPC) rinse used after toothbrushing versus toothbrushing alone. A digital plaque image analysis technique was used to quantify in situ plaque formation in a subject population carrying out modified hygiene using standard fluoridated dentifrice or standard dentifrice augmented with 30 seconds mouthrinsing with an alcohol-free mouthrinse containing 700 ppm CPC. Comparison of plaque formation 24 hours following "last hygiene" revealed that brushing followed by CPC mouthrinse use provided a statistically significant decrease in plaque coverage on teeth averaging 42% as compared with brushing only. Moreover, toothbrushing with a standard dentifrice in the morning resulted in 34% less plaque when subjects used the CPC mouthrinse 24 hours prior to examination. These results support the strong retention and lasting antiplaque efficacy of high bioavailable CPC mouthrinse and suggest that the plaque biofilms formed during CPC use are susceptible to more efficient debridement.


Isolation and culture of hepatic lipocytes, Kupffer cells, and sinusoidal endothelial cells by density gradient centrifugation with Stractan.
A method for isolating purified populations of hepatic lipocytes, Kupffer cells, and sinusoidal endothelial cells suitable for culture, using density gradient centrifugation on the polysaccharide material Stractan is described. A nonparenchymal cell digest of liver from either normal rats or rats treated with modest doses of vitamin A is layered on a discontinuous gradient of 6, 8, 12, ind 20% Stractan; lipocytes are separated efficiently from other nonparenchymal cells and are removed from the top of the gradient. Kupffer cells and sinusoidal endothelial cells, which migrate to denser interfaces in the gradient, are further purified by differential plating and selective trypsinization, respectively. Isolated highly viable lipocytes free of contaminants adhere and spread progressively over several days in primary culture and display both intrinsic vitamin A fluorescence and positive immunostaining for desmin. Lipocytes survive for prolonged periods on plain plastic, and collagen synthesis by these cells remains relatively constant for at least 28 days. Based on serial assay of DNA content, lipocytes in primary culture proliferate, beginning 7 days after plating. Kupffer cells and sinusoidal endothelial cells isolated by Stractan density centrifugation likewise retain their typical morphologic and functional characteristics in culture; the purity of these cell isolates has been confirmed by using specific fluorescent markers. This investigation demonstrates that Stractan density gradient centrifugation is an efficient, sensitive, and reproducible method for isolating pure populations of hepatic nonparenchymal cells.


Structure of the signal recognition particle interacting with the elongation-arrested ribosome.
Cotranslational translocation of proteins across or into membranes is a vital process in all kingdoms of life. It requires that the translating ribosome be targeted to the membrane by the signal recognition particle (SRP), an evolutionarily conserved ribonucleoprotein particle. SRP recognizes signal sequences of nascent protein chains emerging from the ribosome. Subsequent binding of SRP leads to a pause in peptide elongation and to the ribosome docking to the membrane-bound SRP receptor. Here we present the structure of a targeting complex consisting of mammalian SRP bound to an active 80S ribosome carrying a signal sequence. This structure, solved to 12 A by cryo-electron microscopy, enables us to generate a molecular model of SRP in its functional conformation. The model shows how the S domain of SRP contacts the large ribosomal subunit at the nascent chain exit site to bind the signal sequence, and that the Alu domain reaches into the elongation-factor-binding site of the ribosome, explaining its elongation arrest activity.


Epidemiology of brain tumors among adolescents and young adults in Nigeria.
Adolescents and Young Adults (AYA), have distinct endocrine and psychosocial peculiarities. Brain tumors occur less among AYAs, compared to other age groups and with better prognosis. There is however a paucity of literature about brain tumors in AYA in sub-Saharan Africa. We aim to describe the clinical characteristics of brain tumors in AYA across five neurosurgical centers in Nigeria and the associated factors. We report results for older children (10-14 years), adolescents (15-19 years) and young adults (20-24 years). This was a retrospective review of AYA with brain tumors over a 10-year period (2010-2019). Data analysis was by descriptive statistics, Chi square test and multinomial regression at α0.05. There were 104 AYAand the male to female ratio was 1.2:1. Headache (79.8%) and visual symptoms (65.4%) were the most common presenting symptoms. Focal limb weakness (44.1%) occurred less frequently. Median duration of symptoms prior to presentation was 9 months. Glioma was the most common tumor (31, 29.8%) while pituitary adenoma and craniopharyngioma constituted 30.8% of the tumors. Patients with symptom duration of ≤one year were more likely to have infratentorial tumors. There was no significant association between the KPS following intervention and the AYA characteristics. Age group was not significantly associated with any of the presenting symptoms except ataxia, which was significantly higher among the 10 to 14 years group.We have described the epidemiology of brain tumors within AYA in Nigeria and highlighted a need to maximize their care and meet their special needs.


Fatty acids may influence insulin dynamics through modulation of albumin-Zn2+ interactions.
Insulin is stored within the pancreas in an inactive Zn2+ -bound hexameric form prior to release. Similarly, clinical insulins contain Zn2+ and form multimeric complexes. Upon release from the pancreas or upon injection, insulin only becomes active once Zn2+ disengages from the complex. In plasma and other extracellular fluids, the majority of Zn2+ is bound to human serum albumin (HSA), which plays a vital role in controlling insulin pharmacodynamics by enabling removal of Zn2+ . The Zn2+ -binding properties of HSA are attenuated by non-esterified fatty acids (NEFAs) also transported by HSA. Elevated NEFA concentrations are associated with obesity and type 2 diabetes. Here we present the hypothesis that higher NEFA levels in obese and/or diabetic individuals may contribute to insulin resistance and affect therapeutic insulin dose-response profiles, through modulation of HSA/Zn2+ dynamics. We envisage this novel concept to have important implications for personalized treatments and management of diabetes-related conditions in the future.


EUS-guided treatment of gastric fundal varices with combined injection of coils and cyanoacrylate glue: a large U.S. experience over 6 years (with video).
Conventional endoscopic treatment of gastric fundal varices (GFV) with cyanoacrylate (CYA) glue may be complicated by embolization and rebleeding. We evaluated the long-term outcomes of EUS-guided injection of coils and CYA glue for therapy of GFV. A retrospective chart review of patients treated for GFV was performed. The main outcomes measured were hemostasis, obliteration on surveillance EUS, post-treatment bleeding rate, and adverse events. From March 2009 to 2015, 152 patients with GFV were treated. Seven (5%) had active hemorrhage, 105 (69%) had recent bleeding, and 40 (26%) were treated for primary prophylaxis. Treatment was technically successful in 151 patients (>99%). Mean number of coils was 1.4 (range, 1-4 coils), and mean volume of CYA was 2 mL (range, 0.5-6). Follow-up was available for 125 patients with treated GFV (mean, 436 days; range, 30-2043). Among 100 patients with follow-up EUS examinations, complete obliteration (on Doppler study) of GFV was confirmed in 93 (93%). Post-treatment bleeding from obliterated GFV occurred in 3 of 93 patients (3%). Twenty-five patients who had clinical and/or EGD follow-up had 3 post-treatment bleeding episodes after a median follow-up of 324 days (range, 41-486). Among the 40 patients treated for primary prophylaxis, 28 underwent follow-up EUS and 27 (96%) had confirmed obliteration. Mild postprocedure abdominal pain occurred in 4 of 125 patients (3%), and clinical signs of pulmonary embolization were seen in 1 patient (1%). Another 4 of 125 patients (3%) presented with minor delayed upper GI bleeding from coil/glue extrusion. EUS-guided combined coil and CYA glue injection of high-risk GFV appears to be highly effective for hemostasis in active bleeding and primary and secondary bleeding prophylaxis. Once obliteration was achieved, post-treatment bleeding from GFV occurred in only 3% during long-term follow-up. Combination therapy appears safe and may reduce the risk of CYA embolization.


Draft Genome Sequence of Extended-Spectrum Beta-Lactamase-Producing Serratia fonticola BWK15 Isolated from Feces of Anas penelope.
Migratory birds have been postulated as potential vehicles of antibiotic resistance. Here we isolated the extended-spectrum beta-lactamase (ESBL)-producing Serratia fonticola strain BWK15 from the feces of Anas penelope The strain's draft genome sequence indicated that it harbors class A ESBL, class C beta-lactamase, and many multidrug efflux pumps.


Precision and sensitivity of the short-form pediatric enuresis module to assess quality of life (PEMQOL).
To evaluate a derived short-form version of the Pediatric Enuresis Module to assess Quality of Life (PEMQOL) Child and Family Impact Scales, a survey intended for use in clinical practice and research as a means of continuous monitoring of the impacts of enuresis on the child and family. The full-length PEMQOL was completed by parents in two clinical trials (n=143 and n=397, respectively) and for children receiving care at five specialty clinics (n=208). The short-form scales were derived using regression and factor analysis. Multitrait scaling analysis was used to evaluate item internal consistency and discriminant validity. Reliability was estimated using Cronbach's alpha. Clinical validity was computed by comparing the proportion of variance explained by the short-form scales relative to their respective full-length versions. Differences in scores were examined by: (1) less wetting episodes, (2) number of pads used and (3) changes over time. The Child and Family Scales were reduced from 14 to 7 items and 17 to 9 items, respectively. Eighty six percent (median) of items in the Child Scale and 100% in the Family Scale met item level scaling criteria. Median alpha coefficients across seven sub-samples were 0.72 and 0.76, respectively. Relative validity estimates for the Family Scale ranged from 2.66 to 0.87. Findings for the Child Scale were lower and ranged from 0.78 to 0.54.


Congenital absence of pericardium: an unusual cause of atypical angina.
Congenital defects of the pericardium are unusual. Patients may experience exertional chest pain, cardiac arrhythmias, syncope, sudden death, or incarceration of myocardium, or they may be entirely asymptomatic. We describe the case of a symptomatic pericardial herniation diagnosed by echocardiography and confirmed by cineangiography. Successful repair was accomplished using a polytetrafluoroethylene soft-tissue prosthesis.


Analysis on a database of ship accidents in port areas.
In the last 15 years, the number of vessels in the world fleet has grown by around 53% and their gross tonnage has increased by 47%, with a consequent significant increment of marine accidents worldwide. Accident database are the basic resource for risk assessment methods to help decision-makers to enact strategies and undergo hazard and vulnerability mitigation measures. Understanding ship accidents distribution in terms of involved GT, typical age of the affected vessels, category of the ships, as well as distribution of underlying causes and consequences is the first necessary step to improve accident mitigation actions to be implemented for future assessments. In the present work, the results of an analysis on a database of vessel accidents in Mediterranean and worldwide port areas developed within the framework of the project ISY PORT (Integrated SYstem for navigation risk mitigation in PORTs) is herein presented. The distribution of accidents was analyzed in terms of relevant vessel characteristics i.e. Grosse Tonnage (GT), age at the time of the accident, ship's category, causality event, weather conditions and number of fatalities/injuries/lost at sea. The database can be used as a basis for maritime risk assessment methods and for calibration of real-time ship collision avoidance scenarios.


Functional analysis of the 5'-flanking region of the human alanine:glyoxylate aminotransferase gene AGXT.
Primer extension of human liver poly(A)(+) RNA revealed that the main transcription start site of the human alanine:glyoxylate aminotransferase gene (AGXT) is situated near 45 bp upstream from the translation start site. Deletion analysis using the 1203 bp 5'-flanking region of the AGXT gene and a luciferase reporter suggested that the promoter sequence is most likely located 2-325 bp upstream from the translation start site, possibly with enhancer elements 440-700 bp upstream. It was also suggested that the region -2 to -64 is important for the expression of the AGXT gene. The region -2 to -325 has two TATA boxes and some initiator elements.


Influence of dexamethasone on growth and development of rat fetuses: changes in nucleic acids and protein content.
Pregnant rats were treated with dexamethasone in drinking water (10 micrograms/ml) from the 15th to the 22nd day of pregnancy. Dexamethasone significantly reduced the weight of rat fetuses and concentration of DNA, RNA and proteins in fetal adrenal glands, liver, placenta, brain, kidneys, heart, lung, testes and pituitary from the 17th to the 22nd day of pregnancy. These data show that dexamethasone given to pregnant rat may lead to potentially deleterious effects on fetal rat development.


Association of hospital construction with the development of healthcare associated environmental mold infections (HAEMI) in pediatric patients with leukemia.
Healthcare associated mold infections (HAEMI) increase morbidity and mortality in children with leukemia. Excavation adjacent to Children's Medical Center Dallas (CMCD) April 2006-February 2007 provided an opportunity to determine if excavation adjacent to a hospital building is associated with increased risk of developing HAEMI in children receiving intensive chemotherapy for acute leukemia. Children who began receiving intensive chemotherapy for acute leukemia at CMCD from 2004 to 2008 were identified (n = 275). Exposures to the CMCD campus during intensive chemotherapy and duration of neutropenia per exposure were recorded. Proven, probable, or possible invasive fungal disease (IFD) was classified using EORTC/MSG guidelines. Institutional guidelines categorized mold infections as definite or possible HAEMI. A bivariate time-to-event model compared the association of excavation with HAEMI and yeast infections, controlling for neutropenia. There were 7,454 CMCD exposures, 1,007 (13.5%) during excavation. Of 50 cases of IFD, 31 were HAEMI. By time-to-event analysis exposure to the CMCD campus during the excavation period was significantly associated with HAEMI (HR = 2.8, P = 0.01) but not yeast infections (HR = 0.75, P = 0.75). Neutropenia was significantly associated with both HAEMI and yeast infections (P < 0.001). Voriconazole prophylaxis did not prevent HAEMI in 42% of the 14 patients with AML who had been receiving this agent. This study is the first to demonstrate an association between exposure to hospital construction that includes excavation and HAEMI in pediatric oncology patients. Since neutropenic patients need protection from aerosolized fungal spores during visits to expanding medical centers, preventive strategies with adherence monitoring need additional study.


Cleavage orientation and the asymmetric inheritance of Notch1 immunoreactivity in mammalian neurogenesis.
Neurons in the mammalian central nervous system are generated from progenitor cells near the lumen of the neural tube. Time-lapse microscopy of dividing cells in slices of developing cerebral cortex reveals that cleavage orientation predicts the fates of daughter cells. Vertical cleavages produce behaviorally and morphologically identical daughters that resemble precursor cells; these symmetric divisions may serve to expand or maintain the progenitor pool. In contrast, horizontally dividing cells produce basal daughters that behave like young migratory neurons and apical daughters that remain within the proliferative zone. Notch1 immunoreactivity is distributed asymmetrically in mitotic cells, with Notch1 inherited selectively by the basal (neuronal) daughter of horizontal divisions. These results provide cellular and molecular evidence that cortical neurons are generated from asymmetric divisions.


[Fomepizole, ethanol or dialysis in the case of life-threatening ethylenglycol intoxication?]
The EXTRIP (EXtracorporeal Treatments In Poisoning) workgroup is a collaborative international effort of pharmacologists, toxicologists, critical care physicians and nephrologists reviewing all available evidence in extracorporeal procedures for the treatment of intoxications in a standardized way to distill treatment recommendations for the physician at the bedside. The second round of guidelines will include recommendations for ethylenglycol intoxication. The case reported here is of a 60-year old man with a body weight of 65 kg who ingested approximately half a bottle (500 mL) of Aral Antifreeze in a suicidal attempt and presented around 12 h later with severe metabolic acidosis (venous blood gas analysis: pH 7.13; lactate 30 mmol/l, anion gap 23.3 mmol/l). As fomepizole, the inhibitor of the alcohol dehydrogenase, was not readily available, therapy with intermittent hemodialysis was started, as well as ethanol infusion. The first available ethylenglycol concentration before prolonged intermittent hemodialysis was 1230 mg/L. The total removed amount of ethylenglycol during intermittent hemodialysis, as well as following prolonged intermittent renal replacement therapy, was quantified (102 and 65 g). Based on this case report, the new EXRIP recommendations for the role of extracorporeal treatment in the case of ethylenglycol intoxication are discussed.


Laparoscopic resection for gastrointestinal stromal tumors of the stomach.
We reviewed our experience with primary gastrointestinal tumors (GISTs) after surgical treatment. Between 1998 and 2003, 56 patients who underwent surgical treatment for primary GIST of the stomach were enrolled in this study. Statistical analyses of the risk factors for recurrence were assessed. The proportion of cases undergoing laparoscopic surgery was 25 of 56 (44%) in these retrospective data. The site of recurrence was only the liver in all cases. These recurrent cases were defined as high-risk category. Tumors measuring over 2 cm in size tended to recur earlier, namely within 32 months. A statistical analysis showed a statistically significant correlation between the disease progression and the pathological phenotype. This retrospective study has shown that an initial laparoscopic resection of gastric GISTs is feasible even when the tumor size is relatively small (2-5 cm). The pathological phenotype (especially tumor mitosis) directly correlates to the patient's survival even if the resected tumor size was relatively small.


Selection of aroma compounds for the differentiation of wines obtained by fermenting musts with starter cultures of commercial yeast strains.
Nine wines obtained by fermenting Aligoté musts with individual starter cultures of eight Saccharomyces cerevisiae yeast strains and with the indigenous microbiota were compared in terms of their composition in minor volatile aroma compounds. An easy handle methodology Stir-Bar-Sorptive-Adsorption, Gas Chromatography-Mass Spectrometry based, permits the identification of 49 aroma compounds. The rearrangement of these aroma compounds in six chemical families permits the establishment of a finger printing for each wine. Eighteen aroma compounds that exhibit a high differentiation power (p⩽0.05) were selected for chemometric analysis. The Principal Component Analysis carried out with these aroma compounds reveal that the first two principal components explain 53.8% and 17.2% of the total variance, respectively, allowing the establishment of nine different groups, in accordance with the wine types obtained. These results reveal analytical differences among the wines that are not recognized by sensorial analysis.


Radiation therapy in early carcinoma of the true vocal cords (stage I and II).
Seventy-four patients with Stage I and twenty patients with Stage II carcinoma of the true vocal cords received radiation therapy from 1971 to 1983. Sixteen patients had second primary cancers with the most common site being the lung. The patients were treated with 4 MeV linear accelerator X ray or 60Co machine with the average total dose of 6600 rads in 33 fractions, 5 days a week by parallel opposing ports. Local control rate by radiation therapy was 86% in Stage I and 70% in Stage II. Eight of twelve (8 of 12) failures were salvaged by surgery. The actuarial 5-year survival was 92 and 80%. Seventy-six (76%) of patients had good quality of voice after treatment.


Serotyping Plasmodium falciparum from acute human infections using monoclonal antibodies.
Monoclonal antibodies specific for the schizont and merozoite stages of Plasmodium falciparum have been used to demonstrate antigenic differences between parasites obtained from individual patients with acute malaria. Parasites from East Africa are shown to share some strain-specific antigenic determinants with culture-adapted isolates from Africa as well as from Asia and Papua New Guinea.


CD19(+)CD1d(+)CD5(+) B cell frequencies are increased in patients with tuberculosis and suppress Th17 responses.
Although the importance of B cells in the host immune response upon Mycobacterium tuberculosis infection has been recognized, a conclusive role for B cells has yet to be determined. In the present study, we found that primary CD19(+) B cells isolated from patients with tuberculosis significantly inhibited Th17, but not Th1, cell activation. Moreover, the suppressive activity was mediated by a CD19(+)CD1d(+)CD5(+) B cell population. Notably, patients with tuberculosis were found to have significantly higher frequencies of CD19(+)CD1d(+)CD5(+) B cells with stronger suppressive activity than such cells from healthy donors. Furthermore, the frequency of CD19(+)CD1d(+)CD5(+) B cells in peripheral blood was inversely correlated with that of Th17 cells in patients with tuberculosis. This finding that B cells negatively regulate Th17 responses provides a novel mechanism in the regulation of CD4(+) T cell responses-aside from regulatory T cells-during M. tuberculosis infection, which may impact the clinical outcome of tuberculosis.


Melanotic neuroectodermal tumor of the epididymis in infancy: case report and review of the literature.
Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, benign tumor that usually involves the upper or lower jaw, but it may also arise in other sites. We describe a case of MNTI located in the left epididymis of a 6-month-old boy. Left orchiectomy was performed. Immunohistochemical and ultrastructural studies revealed two types of cells: small, poorly differentiated cells that were positive for neuron-specific enolase protein and vimentin, and larger epithelial cells that were positive for melanoma antigen (HMB45) and frequently contained large and elongated melanosomes, similar to those described in retinal pigmented epithelium. At 12 months of follow-up, no recurrences or metastases were seen. Primary involvement of the epididymis has been previously reported in only 16 cases. Immunohistochemical and ultrastructural studies suggest that the neoplasm is of neural crest origin.


Melatonin mitigates aflatoxin B1-induced liver injury via modulation of gut microbiota/intestinal FXR/liver TLR4 signaling axis in mice.
Aflatoxin B1 (AFB1) is a widespread contaminant in foods and feedstuffs, and its target organ is the liver. Melatonin (MT) has been shown to alleviate inflammation in organs and remodel gut microbiota in animals and humans. However, the underlying mechanism by which MT alleviates AFB1-induced liver injury remains unclear. In the present study, MT pretreatment markedly increased the expression of intestinal tight junction proteins (ZO-1, Occludin, and Claudin-1), decreased intestinal permeability, reduced production of gut-derived Lipopolysaccharide (LPS) and remodeled gut microbiota, ultimately alleviated AFB1-induced liver injury in mice. Interestingly, MT pretreatment failed to exert beneficial effects on the intestine and liver in antibiotic-treated mice. Meanwhile, MT pretreatment significantly increased the farnesoid X receptor (FXR) protein expression of ileum, and decreased the TLR4/NF-κB signaling pathway-related messenger RNA (mRNA) and proteins (TLR4, MyD88, p-p65, and p-IκBα) expression in livers of AFB1-exposed mice. Subsequently, pretreatment by Gly-β-MCA, an intestine-selective FXR inhibitor, blocked the alleviating effect of MT on liver injury through increasing the liver-specific expression of TLR4/NF-κB signaling pathway-related mRNA and proteins (TLR4, MyD88, p-p65, and p-IκBα). In conclusion, MT pretreatment ameliorated AFB1-induced liver injury and the potential mechanism may be related to regulate gut microbiota/intestinal FXR/liver TLR4 signaling axis, which provides a strong evidence for the protection of gut-derived liver inflammation.


Effectiveness of lactulose syrup after cardiac surgery.
Dutch cardiac surgery centers lack consistency in management with respect to the prevention of postoperative constipation. Although not based on any evidence, the administration of lactulose syrup is widely used. Because it often causes intestinal discomfort such as abdominal pain, bowel cramps, and feelings of distention, a study was performed in postoperative cardiac surgery patients who were given either standard care (routine administration of lactulose syrup twice daily) or laxative on indication. Postoperative constipation appeared equally frequent in both groups, and patients who received lactulose had more symptoms of intestinal discomfort. Based on these findings, it is safe to abolish the routine management of postoperative laxatives on a cardiac surgery ward.


Plasma N-terminal pro-atrial natriuretic peptide predicts death after premature myocardial infarction, but not as well as radionuclide ejection fraction. A ten-year follow-up study.
To assess N-terminal pro-atrial peptide (N-ANP) as a predictor of total and cardiac death in patients with previous premature myocardial infarction (MI). In this prospective cohort study, we measured plasma N-ANP by ELIZA assays and ejection fraction (EF) by radionuclide ventriculography in a cohort of 247 patients (193 men and 54 women) who had had MI at a relatively young age (males: first MI at age < or =55; females <60). After 10 years 44 patients had died, 36 from cardiac causes. After using a stepwise procedure to adjust for other prognostic factors (i.e. plasma total homocysteine (tHcy), C-reactive protein and age), the relative risk (RR) was 2.00 (95% confidence interval (CI) 1.05-3.80) (p = 0.03) for death of all causes and 2.32 (95% CI 1.19-4.55) (p=0.01) for cardiac death when the top quartile was compared to the three lower quartiles of N-ANP. When radionuclide EF entered the Cox model, N-ANP became insignificant as a predictor of mortality. N-ANP was a significant predictor of total death and cardiac death in young survivors of MI, but radionuclide EF was a more independent prognostic variable.


Glucocorticoid receptor expression in whole blood with preterm infants.
Although glucocorticoid hormones play important roles in fetal development, the expression of their receptors in the whole blood of preterm infants remains unknown. The aim of this study was to investigate the levels of glucocorticoid receptor (GR) α and β in the whole blood of preterm and term infants. The study group consisted of 131 infants, of which 54 (41%) were preterm. Whole blood from preterm and term infants was analyzed by real-time PCR to monitor the levels of each receptor mRNA. GRβ mRNA were detected in 96.6% and GRα mRNA in 100% of participants. The GRα and GRβ isoforms were detected at a ratio of 1:0.0002. GRβ mRNA/GAPDH expression in preterm infants was significantly higher than that in term infants (p=0.002). There was significant correlation between GRα/GRβ ratio and birth weight in preterm infants (rs=0.317, p=0.019), as well as between GRβ/GAPDH expression and birth weight (rs=-0.296, p=0.030). Furthermore, in preterm infants, GRβ/GAPDH expression was higher in those with SGA than in those without SGA (p=0.022). Importantly, in preterm infants, both the expression of GRβ and the GRα/GRβ ratio were associated with birth weight. Further studies with larger populations are necessary to determine the relation between the expression of GR and the clinical relevance of preterm infants.


P-glycoprotein increases the efflux of the androgen dihydrotestosterone and reduces androgen responsive gene activity in prostate tumor cells.
P-glycoprotein (P-gp) is commonly associated with multi-drug resistance (MDR) in cancer cells and the efflux of a broad spectrum of chemicals from the cell, including many chemotherapeutics and certain steroid hormones. The impact of P-gp and mechanisms involved in androgen transport and cellular accumulation within normal and malignant prostate cells remains unclear. Following incubation of LNCaP, PC-3, HeLa, and HeLa FLAG-androgen receptor (AR) cells with (3)H-dihydrotestosterone (DHT) alone and in combination with P-gp inhibitors, PSC-833 and verapamil, we examined the cellular accumulation and efflux of androgens, as well as gene transcriptional response. Our data reveal that the cellular transport and accumulation of DHT is dependent on the expression of functional AR and modulated by P-gp. P-gp over-expression by both transient transfection and aspirin treatment in LNCaP cells showed decreased intracellular DHT accumulation, further suggesting DHT efflux is P-gp regulated. Androgen responsiveness may be modulated by P-gp in prostate cancer cells. The biological consequences of increased P-gp expression are decreased androgen accumulation and a corresponding decrease in androgen-regulated transcriptional activity and PSA gene expression.


Politicizing the Pandemic: A Schemata Analysis of COVID-19 News in Two Selected Newspapers.
This article critically studies coronavirus (COVID-19) pandemic news in the press. The article attempts to study the way the news of COVID-19 is used for political and ideological purposes. In order to achieve the aim, two newspapers namely, The New York Times from the United States of America and Global Times from China are selected. Van Dijk's news schemata framework is used for the analysis of the reports selected from the two newspapers. Van Dijk's news schemata is crucial for the analysis of any news story (report) whether such a news story is taken from a news channel or a newspaper and whether broadcasted or printed. Based on data analysis, the article found out that the news of COVID-19 has been politicized and used for ideological interests. The article recommends that pandemics should not be politicized, instead we should work together to save our lives and live peacefully.


Second-order nonlinear optical responses of carboranyl-substituted indole/indoline derivatives: impact of different substituents.
Carborane has been the subject of great interest over the last decades due to its high structural, chemical, biological stability and diverse applications. In the present work, carboranyl-substituted indole/indoline compounds and their functionalized derivatives have been systematically investigated by density functional theory (DFT) method with the view of assessing their electronic structures and first hyperpolarizabilities. Significantly, the first hyperpolarizabilities can be obviously enhanced by the introduction of a strong electron-withdrawing group for closed-ring forms, while the strong electron-donating group is beneficial for large first hyperpolarizabilities for open-ring forms. It indicates that the NLO properties of these compounds can be enhanced by controlling their relative substituent groups. Furthermore, the time-dependent DFT calculation illustrates that the enhancement of the first hyperpolarizabilities are found due to the obvious charge transfer (CT) transition, and closed-ring forms have a significant difference on the CT patterns versus open-ring ones. Investigation of the structure-property relationship and substituent effects at the molecular level can benefit for further exploration of carboranyl-substituted indole/indoline derivatives with versatile and fascinating NLO properties.


Validation and psychometric evaluation of the Italian version of the Spinal Cord Injury Secondary Conditions Scale.
Validation cross-sectional study. To adapt the Spinal Cord Injury Secondary Conditions Scale (SCI-SCS) to Italian and to assess the validity and reliability of this instrument. Multicentre study in outpatient clinics of three urban spinal units across Italy. After a five-step translation/validation process, the Italian SCI-SCS was administered in a toolset composed of a sociodemographic questionnaire, the Modified Barthel Index, the Short-Form 8, the Patient Health Questionnaire 9, and the General Anxiety Disorder 7. The Italian SCI-SCS construct validity was assessed through exploratory factor analysis (EFA). The internal consistency and test-retest reliability of the instrument were evaluated using Cronbach's α and the intraclass correlation coefficient (ICC) for the total scale and its subscales. Pearson's correlation coefficient with all administered instruments was calculated to evaluate the concurrent validity. One-hundred fifty-six participants were recruited from February to October 2018. EFA suggested a three-factor structure explaining 45% of the total variance. After experts' consideration about the clinical relevance of its components, a final version of the Italian SCI-SCS with four different subscales and 15 items was proposed. The total scale Cronbach's α was 0.73. The ICC agreement for test-retest reliability was 0.91. Correlations of the Italian SCI-SCS with the administered instruments were statistically significant (p < 0.05), highlighting congruent hypothesized relations. Findings of this study provided a first psychometric evaluation of the SCI-SCS. The modified Italian version of this tool may represent a valuable instrument for the longitudinal assessment of the impact of secondary conditions in people with SCI.


[Babinski's legacy].
Joseph Babinski may be considered as a founder of modern neurology. Based upon a strict neurological examination, he was able to clarify a clinical distinction between hysterical and organic symptomatology. Besides his observation on the Sign, which made him world famous, his description of new concepts in cerebellar signs, his studies on reflexes constituted important landmarks in clinical neurology. But he was also a therapist, moving from palliative treatment to give a great impulse in the development of French Neurosurgery.


Oro-dental manifestations in Hallopeau-Siemens-type recessive dystrophic epidermolysis bullosa.
Recessive dystrophic epidermolysis bullosa of Hallopeau-Siemens (RDEB-HS) is a rare genetic disorder characterized by trauma-induced blisters, milia, acral pseudosyndactyly, and scarring. RDEB-HS patients present with a distinct pattern of oral involvement consisting of microstomia, ankyloglossia, vestibule obliteration and dental caries. In this review, we describe the orodental manifestations of RDEB-HS and present our experience in a cohort of six new cases of RDEB-HS in children aged 6-10 years, documenting the presence of microstomia, ankyloglossia and vestibule obliteration in childhood. We also show that compared with unaffected control children, RDEB-HS subjects have a greater risk of developing high caries indices with early onset, both for permanent or deciduous teeth, and a worse oral hygiene index (scored as OHI). Tooth malpositions and the cross-bite relationship between maxilla and mandible could play a major role in promoting these events. We propose that dental management of RDEB-HS subjects should commence as soon as tooth eruption begins.


A recessive PRDM13 mutation results in congenital hypogonadotropic hypogonadism and cerebellar hypoplasia.
The positive regulatory (PR) domain containing 13 (PRDM13) putative chromatin modifier and transcriptional regulator functions downstream of the transcription factor PTF1A, which controls GABAergic fate in the spinal cord and neurogenesis in the hypothalamus. Here, we report a recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia with cerebellar hypoplasia, scoliosis, and delayed puberty with congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed Prdm13/PRDM13 transcripts in the developing hypothalamus and cerebellum in mouse and human. An analysis of hypothalamus and cerebellum development in mice homozygous for a Prdm13 mutant allele revealed a significant reduction in the number of Kisspeptin (Kiss1) neurons in the hypothalamus and PAX2+ progenitors emerging from the cerebellar ventricular zone. The latter was accompanied by ectopic expression of the glutamatergic lineage marker TLX3. Prdm13-deficient mice displayed cerebellar hypoplasia and normal gonadal structure, but delayed pubertal onset. Together, these findings identify PRDM13 as a critical regulator of GABAergic cell fate in the cerebellum and of hypothalamic kisspeptin neuron development, providing a mechanistic explanation for the cooccurrence of CHH and cerebellar hypoplasia in this syndrome. To our knowledge, this is the first evidence linking disrupted PRDM13-mediated regulation of Kiss1 neurons to CHH in humans.


Meta-analysis of correlation between sleep duration and gender difference in adults with type 2 diabetes.
To explore the correlation between sleep duration and type II diabetes in adults. Computer databases searches were carried out through October 1, 2022, including PubMed, Cochrane Library, Embase, and Web of Science. Relevant literature was collected, and the Newcastle-Ottawa Scale (NOS) and extracted data were used to exclude studies and evaluate quality on the basis of inclusion and exclusion criteria. Meta-analysis was conducted using RevMan 5.4.1 software with random/fixed effects models. A total of 5 studies with 74,226 subjects (31,611 in the male study group, 42,615 in the female study group) were included. The meta-analysis revealed that women with long sleep duration (LSD) have a higher risk for developing type II diabetes than men, OR = 0.70; 95% CI 0.59-0.84, Z = 4.00 and P < 0.001. Men with short sleep duration (SSD) tended to have a higher risk in developing type II diabetes than women though the difference between men and women did not reach statistical significance, OR = 1.09, 95% CI 0.73-1.62, Z = 0.42 and P = 0.68. Further subgroup analysis by regional populations suggested that men in Europe and America with SSD had a higher risk of type II diabetes OR = 1.52, 95% CI 1.04-2.21, Z = 2.18 and P = 0.03. Women with LSD may have a higher risk for type II diabetes, and men in Europe and America with SSD may have a higher risk for type II diabetes than men of other regions.


A retrospective molecular analysis of gentamicin resistance in Staphylococcus aureus strains from UK hospitals.
The composite transposon Tn4001 and a related chromosomal Tn4001-like element, encode resistance to the aminoglycosides gentamicin, tobramycin and kanamycin (GmTmKmr) in Australian strains of Staphylococcus aureus. Southern hybridisation analysis of GmTmKmr S. aureus strains isolated from various hospitals in the UK between 1975 and 1985 indicated that they predominantly encoded chromosomal copies of Tn4001 or a Tn4001-like element. However, a strain isolated in 1985 was found to carry Tn4001 on a plasmid related to pSK1, the prototypical multiresistance plasmid commonly detected in S. aureus strains from Australian hospitals.


Effects of mother's imitation on speech sounds in infants with Down syndrome.
The Down syndrome behavioral phenotype includes delays in making speech sounds, production of more non-speech sounds than speech sounds, and contrasting strengths in social development. Within a behavior analytic framework, we conceptualize characteristics of the Down syndrome behavioral phenotype as creating a context for impairments in speech sound development that suggest interventions caregivers can use to improve speech sounds. We examined one intervention, the effects of mother's contingent vocal imitation, on rate of speech and non-speech sound production in infants with Down syndrome using an ABAB design. Mothers responded favorably to learning to imitate their infants' vocalizations and their contingent vocal imitation was associated with increases in infant speech sounds. The increases in infant speech sound suggest the promise of this approach and future research examining variations in contingent vocal imitation and additional outcomes.


Memantine enhances the inhibitory effects of naltrexone on ethanol consumption.
Effects of the opioid receptor antagonist naltrexone (0.1; 0.3; 1.0 mg/kg i.p.) on operant ethanol self-administration alone and in combination with the non-competitive NMDA antagonist memantine (0.5 and 1 mg/kg, i.p.) were studied in rats. Acute administration of naltrexone (0.1; 0.3; 1.0 mg/kg i.p.) inhibited ethanol self-administration in a dose-dependent manner. Memantine (1.0 mg/kg) significantly enhanced the effects of naltrexone at 0.1 mg/kg, failing per se to inhibit ethanol consumption. Thus, low, sub-effective dose of memantine in combination with low doses of naltrexone blocked the reinforcing properties of ethanol in rats. It is suggested that the combination of sub-effective doses of memantine and naltrexone may have therapeutic value in the treatment of alcoholism particularly in a subgroup of alcoholic patients who have high sensitivity to the adverse side effects of naltrexone.


Lesser omental hernia through a defect in the posterior layer of the lesser omentum.
In previously reported cases of lesser omental hernia, a rare clinical presentation, the herniated intestinal tract was passing through both peritoneal layers of the lesser omentum to herniate into the peritoneal cavity or bursa omentalis. Here we present a very rare case of lesser omentum hernia, where the transverse colon entered through only the posterior layer of the lesser omentum to form a hernia between the anterior and posterior layers. A 43-year-old man was admitted to the emergency department with acute abdominal pain. Plain abdominal computed tomography (CT) revealed a change in the caliber of the transverse colon between the stomach and pancreas, forming a closed loop on the cephaloventral side of the stomach. On contrast-enhanced CT images, vessels were observed in the contrast-enhanced lesser omentum surrounding the herniated intestine. The patient was diagnosed with a lesser omental hernia and underwent laparoscopic surgery. Intraoperatively, the transverse colon was covered by the anterior layer of the lesser omentum, and a defect was found in the posterior layer of the lesser omentum on the dorsal side of the stomach. A 2-cm incision was made in the posterior layer of the lesser omentum to widen the small defect. The herniated intestinal section was removed from the hernia sac, and the transverse colon was retained unresected. The postoperative course was uneventful. As illustrated in this first case of a lesser omental hernia forming between the anterior and posterior layers, characteristic CT findings may play an active role in the diagnosis of this rare presentation.


The sustenance of growing and fattening ruminants by intragastric infusion of volatile fatty acid and protein.
A technique is described for feeding young sheep for long periods entirely by the infusion of volatile fatty acids into the rumen and protein and other essential nutrients into the abomasum. When the energy infused was twice the estimated requirement for maintenance, growth rate and nitrogen retention were essentially the same as in normally-fed sheep.


[The nurses involved in therapeutic innovation].
Clinical research nurses (CRNs) play an important role within the teams involved in the fight against cancer and in therapeutic innovation. In the dermatology department of the Gustave-Roussy Institute, patients treated for melanoma and taking part in clinical trials are supported along their care pathway by a CRN who, in addition to her clinical expertise, acts as a link between the different players concerned.


Threat appraisal and negative affect under ambiguity in generalised anxiety disorder.
Generalised anxiety disorder (GAD) is one of the most common anxiety disorders, yet its mechanisms remain poorly understood. In the current study, we assessed threat processing and negative affect under conditions of uncertainty and ambiguity in a sample of treatment-seeking individuals with GAD (n = 34) and in community controls (n = 34). Participants completed a laboratory aversive learning task based on that used by Grupe and Nitschke (2011). A bias in threat expectancy was observed in GAD participants relative to controls for an ambiguous cue that had not been mentioned in the instructions. GAD participants also overestimated the number of times this ambiguous cue had been followed by an aversive outcome, relative to an instructed uncertain cue (50 %). This covariation bias was not observed in controls. GAD participants also reported significantly stronger negative affect towards the ambiguous cue than the uncertain cue, a pattern that was not observed in controls, although the group interaction did not reach significance. These results provide preliminary evidence that ambiguity - rather than uncertainty per se - may be a particularly powerful trigger for biased threat appraisal and negative affect in GAD.


The role of microRNAs in the management of liver cancer.
Four major components of epigenetic regulation are promoter methylation, histone modification, chromatin conformation changes, and altered expression of noncoding RNAs, especially microRNAs (miRNAs). MiRNAs are noncoding RNAs of single-stranded RNA molecules consisting of ∼22 nucleotides that regulate gene expression at the posttranscriptional level. MiRNAs are endogenous and potentially can regulate every aspect of cellular activity, including development and proliferation, differentiation, metabolism, viral infection, epigenetic modulation, apoptotic cell death, and tumor genesis. Recent studies provide evidence that miRNAs are abundant in the liver and affect a diverse spectrum of liver functions. MiRNA expression and deregulation of miRNAs may be a major pathogenetic factor in many liver diseases. Although global downregulation is a common trait in human malignancies, including viral hepatitis, hepatocellular carcinoma, and polycystic liver diseases, specific miRNAs are upregulated in cancer and offer new diagnostic and therapeutic strategies to manage liver diseases. Here, the current status of the role of miRNAs in liver cancer is discussed along with areas for future research.


Rangeability extension of fiber-optic low-coherence measurement based on cascaded multistage fiber delay line.
We demonstrate a simple method to extend the measurable fiber length with a fiber-optic low-coherence technique. This method is based on a cascaded structure of multistage fiber delay line laid in one arm of the low-coherence technique. By choosing different individual stages in the cascaded fiber delay line, the length of the fiber under test can be continuously measured with a different measurement range. The measurement range of 0.81 km and spatial resolution of 60 μm are successfully realized.


The influence of mangrove-derived tannins on intertidal meiobenthos in tropical estuaries.
Mangrove-derived tannins negatively effected laboratory-reared nematode populations and natural communities of meiobenthos in tropical mangrove forests along the northeastern coast of Australia. In the low and mid intertidal zones of five mangrove estuaries, nearly all of the dominant meiofaunal taxa correlated negatively with concentrations of sediment tannins. Only nematodes correlated with low tannin concentrations in the high intertidal zones. The negative exponential equation y=be -mx represented the best-fit for most of the meiofauna-tannin relationships. The mangrove-dwelling nematode, Terschellingia longicaudata did not grow (r=0.001) in the laboratory on fresh, tannin-rich leaves of the red mangrove, Rhizophora stylosa. Population growth of the nematode was significantly greater on fresh, tannin-poor leaves of the grey mangrove, Avicennia marina (r=0.081) with best growth (r=0.112) attained on a diet of tannin-free, mixed cereal. These preliminary field and laboratory results suggest that hydrolyzable tannins leached from mangrove roots and leaf litter are an important factor regulating intertidal meiobenthic communities in tropical mangrove forests along the northeastern Australian coast.


Molecular characterization of Streptococcus agalactiae and Streptococcus dysgalactiae causing bovine mastitis in the southern region of Bangladesh.
This study was conducted to validate polymerase chain reaction (PCR) as a confirmatory diagnostic tool to find out the presence and frequency of Streptococcus agalactiae (S. agalactiae) and Streptococcus dysgalactiae (S. dysgalactiae) in mastitic milk samples obtained from dairy cows in the southern region of Bangladesh. A total of 196 samples of bovine milk were collected from various dairy farms in the Chattogram metropolitan area of the southern part of Bangladesh. DNA extracted from isolates obtained by culturing California mastitis test (CMT)-positive mastitic milk samples (n = 146) on 5% sheep blood agar was used as a template for PCR. Two sets of specific primers based on the 16S rRNA gene were used to discriminate between S. agalactiae and S. dysgalactiae. Four PCR products were subjected to sequencing, followed by phylogenetic analysis. The PCR analyses revealed that out of the 146 CMT-positive milk samples tested, 29 samples were positive for S. agalactiae (19.86%), while 26 samples were positive for S. dysgalactiae (17.81%). Further sequence analysis of the corresponding PCR products and bioinformatics analysis verified the results. The study proves the efficiency of PCR as a useful diagnostic approach to determine the presence and prevalence of S. agalactiae and S. dysgalactiae in mastitic milk samples obtained from dairy cows.


Response of Roses (Rosa hybrida L. 'Herbert Stevens') to Foliar Application of Polyamines on Root Development, Flowering, Photosynthetic Pigments, Antioxidant Enzymes Activity and NPK.
The effect of foliar application of polyamines on roses (Rosa hybrida cv. 'Herbert Stevens') was investigated in a factorial experiment based on a completely randomized design with three replications in a greenhouse. Two factors were applied including polyamine type (putrescine, spermidine, and spermine) and polyamine concentration (0, 1, 2 and 4 mM). The recorded traits included root fresh and dry weight, root length, number of flowers, flower longevity, chlorophyll content, carotenoids, antioxidant enzymes activity (catalase, ascorbate peroxidase and guaiacol peroxidase) and some macronutrients such as nitrogen, phosphorus and potassium. The results showed that among polyamines, putrescine had the greatest effect on root dry weight; spermidine showed the greatest effect on root length, chlorophyll content, plant phosphorus and spermine affected root fresh weight and flower longevity most strongly. Polyamine concentration of 1 mM had the strongest effect on flower longevity, carotenoids, nitrogen and phosphorus content. The highest potassium rate was observed in treatments with the concentration of 4 mM. Polyamine treatments had no significant effect on the number of flowers per plant and antioxidant enzymes.


Corneal-thickness response to ultra-thin Bausch & Lomb Soflens (polymacon) contact lenses.
A study was conducted to test the hypothesis that a more favorable corneal-edema response for hard-to-fit patients might be expected from ultra-thin Bausch & Lomb Soflens (polymacon) contact lenses than from standard-thickness lenses because of the additional oxygen reportedly available to the cornea. Corneal edema was monitored by measuring changes in corneal thickness over 6 hr of lens wear with an electronic pachometry assembly. Statistical analysis showed significantly less edema for a group of hard-to-fit patients wearing ultra-thin lenses than for a group of successful patients fitted with standard-thickness lenses.


Sulfur containing mixed wastes in anaerobic processing by new immobilized synthetic consortia.
Methanogenic biotransformation of unusual substrates (sulfur (S)-containing wastes: non-purified vacuum gas oil, straight-run gasoline fraction (Naphtha), gas condensate, and straight-run diesel fraction) coming from oil industry after their oxidative desulfurization was investigated. Nitrogen-containing wastes (hydrolysates of chicken manure and Chlorella vulgaris biomass) were added as co-substrates to mixture with oil industry wastes. The 100 % conversion of S-organic compounds to inorganic sulfide accumulated in the reaction liquid medium was achieved with simultaneous production of biogas containing high methane percent (greater than 70 %). Polishing of effluents from methane tank was carried out by denitrifying oxidation of ammonium (DEAMOX). The high process efficiency was due to use of original immobilized artificial consortia at the stage of methanogenesis and DEAMOX. This study reveals the real potential in the processing of very complex mixtures of large-scale wastes, usually inhibiting methanogenesis, by developing biocatalysts based on synthetic biology approaches.


A patient registry for cognitive rehabilitation research: a strategy for balancing patients' privacy rights with researchers' need for access.
To describe a consent-based Patient Research Registry designed to improve the quality and efficiency of cognitive rehabilitation research by balancing patients' privacy rights with researchers' need for access to research participants. Description of a protocol for a Patient Research Registry. Three rehabilitation hospitals. Inpatients with stroke or traumatic brain injury (TBI) at the 3 participating hospitals. Not applicable. Percentages of eligible patients with stroke or TBI who consented to be enrolled in the Registry, were subsequently contacted about a study, and ultimately participated in a study. A survey examined satisfaction with the Registry among researchers who used it for recruitment. After 36 months of operation, 58% of patients approached have consented to be in the Registry (N=1256). Eighty-seven percent of those later identified as potential subjects for research studies expressed interest, and 63% eventually participated. Researchers reported satisfaction with the recruitment opportunities afforded by the Registry. The Registry succeeded in identifying eligible patients interested in participating in research studies, while safeguarding their privacy rights. We identify its strengths and limitations and characterize the type of facility that would most profit from adopting this recruitment model.


A case of multisystem inflammatory syndrome in adults following natural infection and subsequent immunization.
Multisystem inflammatory syndrome in adults is a rare and life-threatening complication that follows natural COVID-19 infection and primarily affects young unvaccinated adults. This complication is seldom described following vaccination, which would have important implications for the vaccination timing and platform in this population. COVID-19 vaccines are extremely effective; however, the risk of rare adverse events needs to be balanced with the vaccination benefits.


Osteogenesis from cultured chick periostea has a specific requirement for chloride.
Bone development, like embryonic development in general, depends on a particular internal electrical milieu. Ions are the carriers of currents that maintain this internal environment. In embryonic bone, chloride is a major carrier of such current. To explore the role chloride plays in embryonic bone development we performed several ion-removal experiments, using the chick periosteal osteogenesis (CPO) system as our model. We found that if chloride is reduced in the medium and replaced with a nontoxic anion, alkaline phosphatase (ALP) activity does not rise, nor does osteogenic development occur. However, acid phosphatase (AP) activity is not affected by level of chloride. Experiments using metabolic inhibitors showed that explants cultured in low chloride medium remain viable. Dose-response studies revealed that the response of ALP activity to chloride concentration is sigmoidal, with a [Cl-]0.5 of 45.9 mM. Reciprocal transfers of explants between complete and low chloride medium show that the rise in ALP activity depends on the length of time explants are cultured with chloride. In contrast, such transfer experiments show that osteogenesis requires chloride only during days 2-3 of culture.


Prevalence of Budd-Chiari Syndrome during Pregnancy or Puerperium: A Systematic Review and Meta-Analysis.
Women during pregnancy or puerperium are likely to develop Budd-Chiari syndrome (BCS). However, the reported prevalence of pregnancy-related BCS varied considerably among studies. Our study aims to systematically review this issue. Overall, 817 papers were initially identified via the PubMed, EMBASE, China National Knowledge Infrastructure, and Chinese Scientific and Technological Journal databases. Twenty of them were eligible. The prevalence of pregnancy-related BCS varied from 0% to 21.5%. The pooled prevalence was 6.8% (95% CI: 3.9-10.5%) in all BCS patients, 6.3% (95% CI: 3.8-9.4%) in primary BCS patients, and 13.1% (95% CI: 7.1-20.7%) in female BCS patients. Among them, one study was carried out in Africa with a prevalence of 10.6%; 14 studies in Asian countries with a pooled prevalence of 7.1% (95% CI: 3.1-12.6%); and 5 studies in European countries with a pooled prevalence of 5.0% (95% CI: 3.1-7.3%). The pooled prevalence was 6.7% (95% CI: 2.6-12.3%) in studies published before 2005 and 7.3% (95% CI: 4.2-12.5%) in those published after 2005. In conclusion, pregnancy is a relatively common risk factor for BCS, but there is a huge variation in the prevalence among studies. Physicians should be aware of pregnancy-related BCS.


Immunocytochemical indications for neuronal co-localization of GABA and aspartate in cultured neocortex explants.
The application of postembedding immunocytochemistry on serial semithin plastic sections, revealed the presence of gamma-aminobutyric acid (GABA)-positive and aspartate-positive neurons in cultured neocortex explants. GABA-positive neurons were found in all layers of the cultured cortex, whereas aspartate-positive neurons were mainly restricted to layer 6. Although exact quantification was not carried out because of the variability in aspartate immunoreactivity, colocalization of GABA and aspartate immunoreactivity could unambiguously be observed in a few neurons.


Introduction of a new incentive and target-based contract for family physicians in the UK: good for older patients with diabetes but less good for women?
To determine whether the recording of diabetes-related health indicators has increased and differences diminished between age, gender and deprivation groups, following the introduction of the new General Medical Services contract (nGMS), an incentive- and target-based contract for UK family physicians. A serial cross-sectional study set in 310 primary care practices in Scotland serving a population of 1.5 million registered patients, focussing on diabetic patients. Data were taken immediately before the introduction of the nGMS and after it had been in place for 1 year. One year after the introduction of the nGMS contract, there was a 54.2% relative increase in the number of patients electronically recorded as having diabetes. In addition, measurement of the quality indicators glycated haemoglobin (HbA(1c)), blood pressure, serum creatinine and cholesterol significantly increased (P < 0.05). Women were less likely than men to have HbA(1c)[odds ratio (OR) 0.85, 95% confidence intervals (CI) 0.80-0.91], serum creatinine (OR 0.90, 95% CI 0.84-0.96) and cholesterol recorded (OR 0.83, 95% CI 0.77-0.90) or achieve HbA(1c) (<or= 10.0%; OR 0.87, 95% CI 0.82-0.91) and cholesterol targets (<or= 5.0 mmol/l; OR 0.83, 95%CI 0.77-0.90). The introduction of the nGMS contract was associated with a rise in the recording of patients with diabetes and the recording of diabetes-related quality indicators. However, women have not benefited equally from the nGMS contract. Strategies are needed to further improve the ascertainment of quality measures and care for women with diabetes, to lessen the potential burden of morbidity amongst female patients in the community.


Interferon-beta affects the tryptophan metabolism in multiple sclerosis patients.
Tryptophan and its metabolites are of great interest in understanding the pathogenesis of multiple sclerosis (MS). The total levels of tryptophan and its metabolites, kynurenine and kynurenic acid were determined in plasma by capillary liquid chromatography electrospray ionisation tandem mass spectrometry. This is the first report of the plasma levels of these analytes in healthy controls and relapsing-remitting MS patients receiving long-term and acute interferon-beta (IFN-beta) treatment. Twenty-four hours post-administration increased kynurenine levels (first IFN MS versus healthy, P = 0.042) and kynurenine/tryptophan ratio (K/T; first IFN MS versus healthy, P =0.027; first IFN MS versus long-term IFN MS, P = 0.036) were found. The long-term IFN MS group had higher K/T ratios at 4 and 12 h post-administration (P = 0.015 and 0.009, respectively). The increase of K/T ratio in the first IFN MS group indicate an induction of the enzyme indolamine-2,3-dioxygenase (IDO), as reported earlier in experimental allergic encephalomyelitis. As IDO is participating in both inflammatory and neurodegenerative processes, further knowledge of its involvement in the pathogenesis of MS is of great importance.


The expression of sonic hedgehog in diabetic wounds following treatment with poly(methacrylic acid-co-methyl methacrylate) beads.
The expression of native sonic hedgehog (Shh) was significantly increased in poly(methacrylic acid-co-methyl methacrylate) bead (MAA) treated wounds at day 4 compared to both poly(methyl methacrylate) bead (PMMA) treated and untreated wounds in diabetic db/db mice. MAA beads also increased the expression of the Shh transcription factor Gli3 at day 4. Previously, topical application of MAA beads (45 mol % methacrylic acid) improved wound closure and blood vessel density in excisional wounds in these mice, while PMMA beads did not. Gene expression within the granulation tissue of healing wounds was studied to provide insight into the mechanism of vessel formation and wound healing in the presence of MAA beads. In addition to the increased expression of Shh, MAA-treated wounds had increased expression of osteopontin (OPN), IL-1β and TNF-α, (at day 7) similar to the previously reported MAA response of macrophage-like and endothelial cells in vitro.


Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4'-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80).
The site of action of the antimalarial compound 2-[trans-4-(4'-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80), would appear to be the mitochondrial respiratory chain. Studies reported herein have demonstrated 566C80 to be a potent and selective mitochondrial inhibitor with mitochondria isolated from Plasmodium falciparum and P. yoelii. Selective assay of individual respiratory chain complexes has shown the primary site of action of 566C80 to be the cytochrome bc1 complex (Complex III): supportive evidence from difference spectroscopy indicates the site of inhibition to lie between cytochromes b and c1 of this complex. Using [14C]566C80, evidence is presented which suggests that 566C80 may become irreversibly bound to a polypeptide with an approximate molecular mass of 11,500 Da.


Phase response curves for social entrainment.
Phase shifts in free-running activity rhythms of male golden hamsters, Mesocricetus auratus, often occur when they establish a new territory and home after a cage change. Similar shifts also often occur after pairs of animals interact with each other for half an hour. When these events take place during the middle of the hamsters' subjective day, they produce phase advances: when late in the subjective night, they produce phase delays. Repeated social interactions at the same time of day can entrain activity rhythms in a way consistent with the shape of the phase response curves. Not all individuals become entrained, as is predictable from the modest amplitude of the phase response curve. The effects of social interactions and of other disturbances may be mediated through an oscillator phased by general arousal. The present findings have implications for the interpretation of drug-induced changes in biological rhythms.


Applicant perception of virtual interviews in cardiothoracic surgery: A Thoracic Education Cooperative Group Study.
Cardiothoracic programs used virtual interviews exclusively this year. As programs consider using virtual interviews permanently, our goal was to evaluate the experience of applicants with virtual interviews. All 2020-2021 traditional cardiothoracic fellowship applicants received an anonymous electronic survey after the Match process ended. The survey assessed the number of interviews, strengths, and inadequacies of virtual interviews and factors that affected rank decision. Forty-three percent of applicants responded (60/139). The average number of interviews was 16.0. Eighty percent (48/60) of respondents successfully matched. Eighty-seven percent (52/60) of respondents had a favorable experience with virtual interviews, and 97% (58/60) found them to be convenient. However, only 50% (30/60) were able to evaluate a program fully. Respondents who matched were more likely to have a favorable experience (P = .02), but not more likely to be able to evaluate a program fully (P = .35). The most valued aspect was the informal meet and greet session with fellows (4.2 of 5). The least valued aspect was the program's social media site (2.0 of 5). The factors most frequently used to decide ranking were case numbers by 92% (55/60) and culture/personality by 82% (49/60). Virtual interviews were perceived more favorably compared with last year, but half of applicants were still unable to evaluate a program fully. Fellow interactions were the most popular aspect of virtual interviews. As programs consider using virtual interviews permanently, more exposure to current trainees and a more robust social media/online presence will improve favorability.


[Expression of cMPO in 502 cases of acute myeloid leukemia (AML) and its diagnosis significance in AML subtypes].
To investigate the myeloperoxidase (cMPO) expression pattern by flow cytometry (FCM) in patients with acute myeloid leukemia (AML) and its role in classifying AML. Eight- color multiparametric FCM with CD45/SSC gating was used to determine the cMPO expression in 502 AML patients. The positive rate of cMPO in all patients was 58.0%, in which the proportion of normal positivity, dim positivity and partial positivity was 21.5%, 34.1% and 2.4%, respectively. The remaining case (42.0%) were all negative. In AML with t (15;17)(q22;q12)/PMLRARα, the positive rate was the highest (100%) and the intensity was similar to that of the normal granular leukocytes, followed by AML with t (8;21(q22;q22/RUNX1-RUNX1T1, the positive rate was 91.4% and the intensity was mostly dim. AML with minimal differentiation and acute megakaryoblastic leukemia were all cMPO negative. The positive rates of cMPO in the remaining subtypes were between 22.7% and 76.2%. The positive rate and intensity of cMPO were significantly different among different subtypes of AML.


Spontaneous pulmonary infections in animals affecting studies on comparative lung morphology and function.
Viral, bacterial, and parasitic pulmonary diseases that occur spontaneously in animals used for research can adversely affect the collection and interpretation of data in studies on pulmonary structure and function. Common respiratory infections occurring in a wide range of mammals are summarized, and procedures for detection of spontaneous infectious diseases affecting experimental studies are described.


Preoperative alpha fetoprotein, total bilirubin, fibrinogen, albumin, and lymphocytes predict postoperative survival in hepatocellular carcinoma.
Our study focused on exploring the feasible prognostic laboratory parameters of HCC and establishing a score model to estimate individualized overall survival (OS) in HCC after resection. Four hundred and sixty-one patients with HCC who underwent hepatectomy between January 2010 and December 2017 was enrolled in this investigation. Cox proportional hazards model was conducted to analyze the prognostic value of laboratory parameters. The score model construction was based on the forest plot results. Overall survival was evaluated by Kaplan-Meier method and the log-rank test. The novel score model was validated in an external validation cohort from a different medical institution. We identified that alpha fetoprotein (AFP), total bilirubin (TB), fibrinogen (FIB), albumin (ALB), and lymphocyte (LY) were independent prognostic factors. High AFP, TB, FIB (HR > 1, p < 0.05), and low ALB, LY (HR < 1, p < 0.05) were associated with the survival of HCC. The novel score model of OS based on these five independent prognostic factors achieved high C-index of 0.773 (95% confidence interval [CI]: 0.738-0.808), which was significantly higher than those of the single five independent factors (0.572-0.738). The score model was validated in the external cohort whose C-index was 0.7268 (95% CI: 0.6744-0.7792). The novel score model we established was an easy-to-use tool which could enable individualized estimation of OS in patients with HCC who underwent curative hepatectomy.


A comparative study of single incision versus conventional laparoscopic inguinal hernia repair.
Over the past years, safety and feasibility of conventional laparoscopic inguinal hernia repair was well established. However, conventional laparoscopic hernia repair (CL) usually requires three working ports ranging from 5 to 10 mm, and each increasing port is associated with possible increasing morbidity and pain related to ports. This has led to the development of single incision laparoscopic hernia repair (SIL) which can further reduce the port-related morbidities and improve cosmetic outcomes. The aim of the study was to evaluate the safety and feasibility of SIL using both transabdominal preperitoneal (TAPP) and totally preperitoneal (TEP) approaches and compare the patients' wound satisfaction between the two groups. This is a retrospective review of prospectively collected data. We analyzed the results of patients who underwent either CL or SIL for inguinal hernia between January 2011 and July 2012 in Pamela Youde Nethersole Eastern Hospital. Patients' demographic details, type of hernia, operative time, mesh used, and post-operative complications were compared. A telephone survey was also conducted to evaluate patients' subjective wound satisfaction. In total, 32 SIL and 35 CL procedures were performed in this period. The two groups were matched for age, sex, type of hernia and ASA grading. The mean operative time was significantly shorter in the CL group (52.6 vs. 62.6 min, p = 0.02). All SIL procedures were completed successfully without conversion to CL or open repair and post-operative complications such as wound infection, seroma, recurrence and chronic pain were also comparable between the two groups. As for the telephone survey, SIL groups' wound is less obvious and less detectable by others as compared to CL, but on the whole both groups of patients are very satisfied with the wound outcomes. All the SIL groups would continue with their decision on SIL and 60 % of CL group would choose SIL if they had to go back in time. Our results have shown that in experienced hands, SIL is feasible and as safe as CL. Further randomized trials should be performed to evaluate the clinical application of single incision TEP and TAPP.


Human Pharmacokinetics of the Neuroprotective Agent NBQX.
We studied the pharmacokinetics of the glutamate antagonist NBQX (6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione) in 16 normal male volunteers aged 18--37 years in a double-blind, placebo-controlled design. Intravenous infusions of 0.0075 and 0.03 mg kg(minus sign1) over 30 min were given to six subjects at each dose level (parallel groups). Two subjects at each dose level received placebo. The drug was well tolerated and no clinically significant alterations of cardivascular or renal function or in biochemical and hematological parameters were observed. Mean values of C(max) were 41 and 177 ng ml(minus sign1) at the two-dose levels. Compartmental pharmacokinetic analysis yielded a plasma half-life of 0.75 h, a total plasma clearance of 0.222 L h(minus sign1) kg(minus sign1) and a volume of distribution at steady state of 0.153 L kg(minus sign1). The renal clearance was 0.130 L h(minus sign1) kg(minus sign1) implying tubular secretion of the drug.


Retinal projections to the inferior and medial pulvinar nuclei in the Old-World monkey.
Horseradish peroxidase (HRP) and wheat germ agglutinin conjugated to HRP (WGA-HRP) were used as anterograde tracers to study the macaque monkey retinofugal pathways. Labeled axons were mapped beyond the lateral geniculate nucleus to the inferior (PI) and medial (PM) pulvinar nuclei, where they terminated. Retinofugal fibers project to the medial part of PI, adjacent to the brachium of the superior colliculus. A smaller projection to PM leaves the ventrolateral aspect of the lateral geniculate nucleus and travels parallel to the stria terminalis to reach the dorsal surface of the thalamus and PM. HRP reaction product was bilateral in PI and predominantly contralateral in P)M.


Evaluation of Process Improvement Interventions on Handoff Times between the Emergency Department and Observation Unit.
Mitigating hospital crowding requires judicious use of inpatient resources, making Emergency Department Observation Units (EDOUs) an increasingly vital destination for patients that are not suitable for discharge. Maximizing the utility of the EDOU hinges on efficient patient transfers and safe provider communication, which may be accomplished with asynchronous handoff and an emphasis on pull-through operations. The purpose of this study was to assess the impact of an electronic, asynchronous handoff replacing verbal handoff on transfer times from the Emergency Department (ED) to the EDOU. A retrospective observational study was performed with patients transferred to the EDOU throughout several process improvement measures focused on asynchronous handoff. Multivariable linear regression analysis was used to determine the effect that these process improvements had on the time from EDOU bed assignment to patient transfer. There were 14,996 EDOU stays during the 20-month period included in the analysis. Time from EDOU bed assignment to patient transfer decreased significantly with all three interventions studied. An auto-page to the clinicians notifying them of a ready bed reduced the mean time to transfer by 10.1 min (p < 0.0001), asynchronous nursing handoff reduced it by 3.57 min (p = 0.0299), and asynchronous clinician handoff reduced it by 14.67 min (p < 0.0001). Introducing automatic pages regarding bed status and converting the handoff process from a verbal model to an asynchronous, electronic handoff were effective ways to reduce the time from bed assignment to transfer out of the ED for patients being sent to the EDOU.