Relationship between subjective memory complaint and executive function in a community sample of South Korean elderly.
The aim of this study was to investigate the association between subjective memory complaint (SMC) and executive function in a community sample of South Korean elderly. Data for 1442 non-cognitive impaired elderly individuals aged 65 and over were selected from a nationwide dementia epidemiological study conducted in South Korea. Global cognitive function was assessed by the Korean version of the Mini-Mental State Examination (MMSE-KC). The registration and recall subscales of the MMSE were used for evaluating memory function. Executive function was measured by using the Initiation/Perseveration (IP) subscale of the Korean dementia rating scale (K-DRS). Of the 1442 participants, 1088 were in the normal control group and 354 were in the SMC group. In the SMC group, compared to the normal control group, the proportion of depression was significantly higher, total MMSE scores, delayed recall score and total IP scores were significantly lower, and the mean scores of complex/simple verbal IP, alternating movements, and graphomotor design were lower. In the unadjusted linear regression model, the SMC significantly associated with a lower score of total MMSE-KC, MMSE delayed recall, K-DRS IP, complex/simple verbal IP, alternating movements and graphomotor design. After adjusting for age, gender, education, marital status, alcohol consumption, smoking behaviour, and depression, the SMC were significantly associated with lower total MMSE score, MMSE delayed recall, K-DRS IP, and K-DRS complex/simple verbal IP. In this population-based sample, individuals with SMC had evidence of lower performance on global cognition, memory function, and executive function, especially verbal fluency, after adjusting for demographic variables and depression.


Alveolar bone density and its clinical implication in the placement of dental implants and orthodontic mini-implants.
To assess the bone density in maxilla and mandible in dentate and edentulous patients in Saudi population. This study involved a retrospective analysis of cone beam CT images of 100 patients (50 male and 50 female) who have come to College of Dentistry, University of Dammam, Dammam, Kingdom of Saudi Arabia between January 2014 and 2015. Using the bone density option in the Simplant software, the Hounsfield unit (HU) was calculated at the edentulous sites. While for dentate sites, a region of interest was selected coronally at 3-5 mm to the root apex using I-CAT vision software. The densities of the buccal bone and cancellous bone were measured at interradicular areas of a specific teeth. The highest bone density at the edentulous sites was at the mandibular anterior region (776.5 ± 65.7 HU), followed by the mandibular posterior region (502.2 ± 224.2 HU). Regarding the dentate sites, the highest bone density was at the buccal cortical plate of the lower incisor teeth (937.56 ± 176.92 HU) and the lowest bone density was at the cancellous bone around the posterior maxillary teeth (247.12 ± 46.75 HU). The alveolar bone density at dentate and edentulous sites in our population is generally lower than the norm reference density of other populations, which dictates the need for quantitative assessment of bone density before implants and mini-implants placement.


Distribution of Microorganisms in Cheongyang Red Pepper Sausage and Effect of Central Temperature on Quality Characteristics of Sausage.
The objective of this study was to provide preliminary data for food industry by investigating the distribution of microorganisms in raw materials and sausage examining the effect of heating temperature on sausage quality. Total microbes in sausage ranged 2.21-3.11 Log CFU/g. Bacillus pumilus, B. licheniformis, Staphylococcus saprophyticus, and Enterococcus faecalis were detected on sausage. Total microbes in raw materials was 1.59-7.16 Log CFU/g. Different types of microorganisms were found depending on raw materials, with B. pumilus and B. subtilis were being detected in both raw materials and sausage. Total microbes in sausage after heating was in the range of 1.10-2.22 Log CFU/g, showing the trend of decrease in total microbe with increasing heating temperature, although the decrease was not significant. With increasing heating temperature, pH and hardness were also increased. The yield of sausage manufactured at 85°C was 95.42% while that manufactured at 65°C was 96.67%. Therefore, decreasing heating temperature during sausage production might increase yield and save energy without microbiological effect.


A comparative assessment of KAP regarding tuberculosis and RNTCP among government and private practitioners in District Gwalior, India: an operational research.
Tuberculosis is one of the oldest diseases known to mankind. However, still practitioners are unaware of various facts associated with it. (1) To assess the knowledge, attitude and practices adopted by practitioners of both government and private sectors in diagnosis and management of TB patients. (2) To assess the views of practitioners in strengthening the RNTCP programme. 200 allopathic practitioners from both government and private sectors providing their services in Gwalior District were interviewed using pre-designed pre-tested structured questionnaire. The mean score of knowledge related to tuberculosis and RNTCP was higher among government practitioners (9.8) compared to private practitioners (6.1). All practitioners were having positive attitude towards regular up gradation of knowledge while statistically significant differences were noted on issues related to management of TB patients as per RNTCP guidelines. X-ray was the most preferred modality for diagnosis and follow up among private practitioners compared to sputum examination among government practitioners. Referral of poor and serious patients was also very low among private practitioners. The present study hereby concludes that there is a large gap in Knowledge, Attitude and Practices on TB and RNTCP among the practitioners of both the sectors. There is an urgent need for upgrading the knowledge on various issues and regular Continuing Medical Education (CME) involving various professional bodies.


Schistosoma mansoni: effect of infection on reproduction and gonadal growth in Biomphalaria glabrata.
Sexually mature Biomphalaria glabrata were exposed to 12 miracidia of Schistosoma mansoni, and egg production of snails was monitored over a period of 5 weeks. During the study period, exposed snails grew at approximately the same rate as unexposed controls. Castration, as measured by a reduction in the mean number of eggs laid per snail occurred between 14 and 21 days postexposure (PE). The reduction in fecundity in infected snails coincided with the migration and establishment of daughter sporocysts in the digestive gland and gonad. Enumeration of individual oocytes in longitudinal sections of the ovotestis revealed that uninfected snails contained significantly more oocytes per section than infected snails at 27, 31, and 40 days PE. In addition, the mean area of gonadal sections of control snails increased over the 40-day experimental period, whereas there was no such increase in gonadal area of infected snails. These data suggest that there is an inhibition in gonadal growth in infected snails. When oocyte data were expressed in terms of mean gonadal area, the mean number of oocytes per mm2 of gonad of uninfected and infected snails did not differ significantly over the study period, except at Day 14 PE, when infected snails contained a significantly greater number of oocytes per mm2 of gonad than did uninfected controls. It is hypothesized that daughter sporocysts of S. mansoni are primarily responsible for the inhibition of host reproductive activity, and may be mediating their effects through mechanisms involved in the regulation of gonadal growth.(ABSTRACT TRUNCATED AT 250 WORDS)


Labelling and drug effects in the treatment of neurotic affective disorders: an experimental investigation.
This study investigates the effects of assigned diagnostic labels, with their accompanying predictions of therapeutic response, and prescribed psychotropic drugs. It was thought that such 'labelling' effects might be important in ambiguous situations, such as neurotic anxiety-depressive states, where diagnoses of 'reactive depression' or 'anxiety state' might justifiably be made and treatment with either diazepam or nortriptyline legitimately given. The depression label and its concomitant two-weekly prediction of improvement with antidepressants produced a set towards slower response with higher self-report depression. Nortriptyline produced significantly more improvement in self-report depression than diazepam in the first 2 weeks of treatment. No significant interaction effects were detected between diagnosis or drug. One month after the initial diagnostic evaluation there were no significant effects from either diagnostic label or drug.


Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke.
Upper limb impairment is a common debilitating consequence of ischemic stroke. Physical rehabilitation after stroke enhances neuroplasticity and improves limb function, but does not typically restore normal movement. We have recently developed a novel method that uses vagus nerve stimulation (VNS) paired with forelimb movements to drive specific, long-lasting map plasticity in rat primary motor cortex. Here we report that VNS paired with rehabilitative training can enhance recovery of forelimb force generation following infarction of primary motor cortex in rats. Quantitative measures of forelimb function returned to pre-lesion levels when VNS was delivered during rehab training. Intensive rehab training without VNS failed to restore function back to pre-lesion levels. Animals that received VNS during rehab improved twice as much as rats that received the same rehabilitation without VNS. VNS delivered during physical rehabilitation represents a novel method that may provide long-lasting benefits towards stroke recovery.


Fetuin-A alleviates neuroinflammation against traumatic brain injury-induced microglial necroptosis by regulating Nrf-2/HO-1 pathway.
The microglia-mediated inflammatory response is a vital mechanism of secondary damage following traumatic brain injury (TBI), but the underlying mechanism of microglial activation is unclear. Controlled cortical impact (CCI) was induced in adult male C57BL/6J mice, and glutamate was used to construct a classical in vitro injury model in the primary microglia. Microglial activation was determined by western blot and immunostaining. The inflammatory factors were measured by enzyme-linked immunosorbent assay. The oxidative stress marker and mitochondrial reactive oxygen species (ROS) were measured by immunoblotting and MitoSox Red staining. Transmission electron microscopy was used to observe the typical morphology of necroptotic cells. Our quantitative proteomics identified 2499 proteins; 157 were significantly differentially expressed in brain tissue between the 6 h after CCI (CCI6h) group and sham group, and 109 were significantly differentially expressed between the CCI24h and sham groups. Moreover, compared with the sham group, the terms "acute-phase response", "inflammation", and "protein binding" were significantly enriched in CCI groups. Fetuin-A, a liver-secreted acute-phase glycoprotein, was involved in these biological processes. Using an experimental TBI model, we found that the Fetuin-A level peaked at 6 h and then decreased gradually. Importantly, we showed that administration of Fetuin-A reduced the cortical lesion volume and edema area and inhibited the inflammatory response, which was associated with suppressing microglial necroptosis, thus decreasing microglial activation. Furthermore, administration of Fetuin-A attenuated mitochondrial oxidative stress in glutamate-treated microglial cells, which is a critical mechanism of necroptosis suppression. In addition, we demonstrated that Fetuin-A treatment promoted translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus in vivo; however, the Nrf-2 inhibitor ML385 and si-heme oxygenase-1 (si-HO-1) disrupted the regulation of oxidative stress by Fetuin-A and induced increased ROS levels and necroptosis in glutamate-treated microglial cells. Fetuin-A also protected neurons from adverse factors in vivo and in vitro. Our results demonstrated that Fetuin-A activated Nrf-2/HO-1, suppressed oxidative stress and necroptosis levels, and thereby attenuates the abnormal inflammatory response following TBI. The findings suggest a potential therapeutic strategy for TBI treatment.


Bayliss myogenic response in the isolated ductus arteriosus of guinea-pig and rabbit fetuses.
Isolated ductus arteriosus responds by marked constriction to increases in perfusion pressure. If, however, these increases exceed 90 mm Hg-130 mm Hg, the vessel suddenly dilates and its responsiveness becomes depressed. The importance of these findings in postnatal closure of ductus arteriosus is discussed.


Difficult endotracheal intubation due to a large epiglottic cyst: A case report.
An epiglottic cyst is a type of benign tumor that is formed due to the obstruction of the mucinous duct and the retention of glandular secretion. In such cases, the glottis is not visible as it is covered by the enlarged epiglottic cyst. When conventional anesthesia is administered in such patients, they might have difficulty ventilation since the epiglottic cyst can easily form a flap and move with external pressure changes and can cause the blockage of the glottis due to the loss of consciousness and the relaxation of the throat muscles of the patient. If endotracheal intubation is not initiated and effective ventilation is not established, the patient may suffer from hypoxia and other accidents. A 48-year-old male presented to the otolaryngology department with a foreign body sensation in the throat. A large epiglottic cyst was diagnosed. The patient was planned to undergo epiglottis cystectomy under general anesthesia. After induction of anesthesia, the cyst severely covered the glottis and made endotracheal intubation difficult. The anesthesiologist rapidly adjusted the position of the laryngeal lens; thus, the endotracheal intubation was successful under the visual laryngoscope. The endotracheal intubation was successful under the visual laryngoscope and the operation went well. Patients with epiglottic cysts are more likely to have difficult airways after induction of anesthesia. Anesthesiologists should take preoperative airway assessment seriously, efficiently handle difficult airway and intubation failure, and make quick and correct choices to ensure patient safety.


Restaging transurethral resection of bladder tumor for high-risk stage Ta and T1 bladder cancer.
Bladder cancer is the most common malignancy of the urinary tract. About 75%-85% of patients present with non-muscle-invasive bladder cancer (NMIBC). However, patients with pT1 tumors, as well as all those with high-grade disease, make up a subset with a high-risk of recurrence and disease progression. Although still regarded as the gold standard, clinical evidence from contemporary published series clearly demonstrates that transurethral resection of tumor (TUR) is a procedure far from optimal, highlighting its limitations and the need for further diagnostic accuracy. Routine use of a restaging TUR (re-TUR), supported by the American Urological Association and European Association of Urology guidelines, detects residual tumor in a significant number of cases after initial TUR. It provides a more accurate staging of the disease and, consequently, helps to guide its treatment. Recent years have seen rapid development of novel optical techniques aimed to optimize resection. Routine implementation of these novel techniques in the context of re-TUR is promising and may potentially result in more tumors being identified and completely resected, leading to significantly lower residual tumor rates than with the standard white-light TUR. This article will focus on re-TUR in the management of high-risk NMIBC, with an up-to-date review of the available literature and detailed analysis of the published series.


CT perfusion imaging of the liver and the spleen in patients with cirrhosis: Is there a correlation between perfusion and portal venous hypertension?
To correlate hepatic and splenic CT perfusion parameters with hepatic venous pressure gradient (HVPG) measurements in patients with cirrhosis. Twenty-one patients with cirrhosis (males, 17; females, 4; mean ± SD age, 57 ± 7 years) underwent hepatic and splenic perfusion CT on a 320-detector row volume scanner as well as invasive measurement of HVPG. Different CT perfusion algorithms (maximum slope analysis and Patlak plot) were used to measure hepatic arterial flow (HAF), portal venous flow (PVF), hepatic perfusion index (HPI), splenic arterial flow (SAF), splenic blood volume (SBV) and splenic clearance (SCL). Hepatic and splenic perfusion parameters were correlated with HVPG, and sensitivity and specificity for detection of severe portal hypertension (≥12 mmHg) were calculated. The Spearman correlation coefficient was -0.53 (p < 0.05) between SAF and HVPG, and -0.68 (p < 0.01) between HVPG and SCL. Using a cut-off value of 125 ml/min/100 ml for SCL, sensitivity for detection of a HVPG of ≥12 mmHg was 94%, and specificity 100%. There was no significant correlation between hepatic perfusion parameters and HVPG. CT perfusion in patients with cirrhosis showed a strong correlation between SCL and HVPG and may be used for detection of severe portal hypertension. • SAF and SCL are statistically significantly correlated with HVPG • SCL showed stronger correlation with HVPG than SAF • 125 ml/min/100 ml SCL-cut-off yielded 94 % sensitivity, 100 % specificity for severe PH • HAF, PVF and HPI showed no statistically significant correlation with HVPG.


The flavonoid 6-methoxyflavone allays cisplatin-induced neuropathic allodynia and hypoalgesia.
Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side-effect of several commonly used chemotherapeutic agents (such as cisplatin) that profoundly impairs patient quality of life. Unfortunately, neither prophylactic strategies nor symptomatic treatments have proven useful in this condition. Flavonoids are found ubiquitously in fruits and vegetables and exert a multiplicity of beneficial effects. In this study, the antinociceptive activity of 6-methoxyflavone (6-MF) was investigated and evaluated in comparison with gabapentin in a rat model of CIPN. The effect on motor balance was also assessed using the rotarod and footprint analysis paradigms. 6-MF possessed both peripheral and central antinociceptive activities against tonic and phasic nociceptive stimuli. Cisplatin administration (3.0mg/kg/week, i.p.) for four consecutive weeks generated temporal mechanical allodynia (decreased paw withdrawal threshold; PWT) and thermal hypoalgesia (increased paw thermal threshold; PTT) in the bilateral hindpaws. Daily treatment with 6-MF (25, 50 and 75mg/kg/day, i.p) for four weeks attenuated the cisplatin-induced expression of nocifensive behaviors observed as a significant increase in PWT and alleviation of PTT during the third and fourth weeks of cisplatin administration. Accordingly, daily gabapentin (75mg/kg, i.p) suppressed the expression of CIPN by normalizing the PWT and hotplate response latency. However, these antinociceptive actions were associated with motor impairment exemplified by a significant decrease in rotarod endurance latency and a deficit in the uniformity of step alternation. In contrast, 6-MF was devoid of these adverse side-effects. These findings suggested that 6-MF afforded desirable neuropathic pain alleviating effects in CIPN and it was devoid of gabapentin-like unwanted motor side-effects.


Identification of the primary antimicrobial domains in human neutrophil cathepsin G.
Lysosomal cathepsin G from human neutrophils is a chymotrypsin-like protease which also possesses antimicrobial activity. The antimicrobial activity, however, is independent of protease activity, because treatment of this enzyme with the irreversible serine protease inhibitor diisopropylfluorophosphate has no effect on its antimicrobial action. In this study, we found that digestion of cathepsin G with clostripain caused a loss of proteolytic activity in this neutrophil proteinase. However, bactericidal activity in in vitro assays against Staphylococcus aureus and Neisseria gonorrhoeae was retained. Fractionation of the clostripain-digested cathepsin G mixture yielded two distinct antimicrobial peptides. The sequences of these peptides were IIGGR and HPQYNQR (residues 1-5 and 77-83 in cathepsin G, respectively). Synthetic peptides corresponding to these sequences were also prepared and found to exert broad-spectrum antimicrobial activity in vitro, displaying conditions of temperature- and pH-dependent optima for antimicrobial action resembling that of the full-length enzyme. Depending on the target bacterial strain, these peptides exhibited antimicrobial activity between 5.0 x 10(-5) and 4.0 x 10(-4) M. Significantly, replacement of certain residues within these peptides with either alanine or valine significantly reduced their antibacterial capacities. Our studies suggest that cathepsin G has two antimicrobial sequences, either or both of which may contribute to its bactericidal activity.


Development of a novel matrix-assisted laser desorption/ionization time-of-flight mass spectrum (MALDI-TOF-MS)-based typing method to identify meticillin-resistant Staphylococcus aureus clones.
Mass spectrum analysis enables species- and subspecies-level identification, and can be used as an epidemiological tool in outbreak management. However, its reliability at clonal level has yet to be established. To establish a matrix-assisted laser desorption/ionization time-of-flight mass-spectrum-based method that enables bacterial clone identification with accuracy equivalent to pulsed-field gel electrophoresis/phage open-reading frame typing (PFGE/POT). Meticillin-resistant Staphylococcus aureus (MRSA) was used in this study. Mass spectra were obtained from a standard strain of S. aureus (ATCC29213) and 57 clinically isolated strains, categorized according to POT. Peaks associated with MRSA clone identification (N = 67) were extracted. Based on this peak information, the feasibility of MRSA clone identification was examined by cluster analysis. In addition to the 58 strains used for peak extraction, mass spectrum analysis of 24 clinically isolated outbreak strains revealed that peak data could be used for successful identification of clones. These typing results were fully consistent with the PFGE and POT results. This novel method enables simple and rapid typing with accuracy equivalent to PFGE/POT. This method would be suited to rapid outbreak analysis, offering accurate information to combat infectious diseases.


Association of Household Food Insecurity with Nutritional Status and Mental Health of Pregnant Women in Rural Bangladesh.
Food insecurity may affect women's health; however, pertinent research is scant among pregnant women. This study investigated the association of household food insecurity (HFI) with the nutritional status and mental health of 672 early-gestation (5-16 weeks) pregnant women with a singleton fetus, who participated in the screening activity of a community-based trial (NCT04868669) in Matlab, Bangladesh. Height (cm), weight (kg), body mass index (kg/m2), mid-upper arm circumference (MUAC) (cm), depression, anxiety, and stress were the outcomes studied. HFI was assessed using the Household Food Insecurity Access Scale. Women's depression, anxiety, and stress were assessed using the Depression, Anxiety, and Stress Scales-21. Propensity score matching based weighted multivariable linear and logistic regression were used to evaluate the independent association of HFI with the outcomes. In adjusted models, pregnant women from food-insecure households in rural Matlab were on average 2.0 cm shorter (β = -2.0, 95% CI: -3.3, -0.7), 2.0 kg lighter (β = -2.0, 95% CI: -3.4, -0.7), and had 0.6 cm lower MUAC (β = -0.6, 95% CI: -1.1, -0.1) than their food-secure counterparts. HFI was associated with higher odds of depression (OR = 3.3, 95% CI: 1.8, 5.9), anxiety (OR = 6.1, 95% CI: 3.7, 10.0), and stress (OR = 4.8, 95% CI: 1.6, 14.2) among the women. Public health measures should focus on ensuring proper nutrition during the critical growth periods of life, pregnancy, and external environmental shocks, to mitigate the adverse effects of HFI on women's health.


P311 promotes renal fibrosis via TGFβ1/Smad signaling.
P311, a gene that was identified in 1993, has been found to have diverse biological functions in processes such as cell proliferation, migration and differentiation. However, its role in fibrosis is unknown. We previously observed that P311 is highly expressed in skin hypertrophic scars. In this study, P311 over-expression was detected in a subset of tubular epithelial cells in clinical biopsy specimens of renal fibrosis; this over-expression, was found concurrent with α-smooth muscle actin (α-SMA) and transforming growth factor beta1 (TGFβ1) expression. Subsequently, these results were verified in a mouse experimental renal fibrosis model induced by unilateral ureteral obstruction. The interstitial deposition of collagen, α-SMA and TGF-β1 expression, and macrophage infiltration were dramatically decreased when P311 was knocked out. Moreover, TGFβ/Smad signaling had a critical effect on the promotion of renal fibrosis by P311. In conclusion, this study demonstrate that P311 plays a key role in renal fibrosis via TGFβ1/Smad signaling, which could be a novel target for the management of renal fibrosis.


Prosociality in personality disorders: Status quo and research agenda.
Personality disorders (PDs) are characterized by interpersonal dysfunction and deficits in prosociality are theorized to contribute to this. We review studies linking categorical PDs to prosocial and antagonistic traits and highlight studies that assessed prosocial behavior in PDs via economic games. We structure our review based on the recently proposed affordance framework of prosocial behavior, summarizing the evidence for exploitation, reciprocity, temporal conflict, and dependence under uncertainty as situational affordances that allow the expression of personality in prosocial behavior. We conclude that some of the inconsistencies in the literature may be due to studies focusing on different situational affordances and the reliance on categorical PDs. We suggest a research agenda and a set of testable hypotheses based on maladaptive personality traits included in the newly implemented dimensional PD diagnoses in ICD-11 and DSM-5.


[How has the Covid-19 pandemic questioned the medical power?]
The Covid-19 pandemic marked public opinion by the scale and violence of scientific and medical debates. Patients can sometimes say that they have never seen so many doctors in the papers. Everyone has their own opinion and some use social networks. Yet, despite massive publications on the pandemic, doctors don't always seem to know what to do. While some journalists believe that doctors have found the pandemic an opportunity to assert new medical power through the media, others see medicine as far too limited a science. So how can medical power be re-examined by the action of physicians during this pandemic? The article discusses the classic dimensions of power (politics, judgment, action) to highlight other dimensions of medical power: responsibility, dedication, creativity, and exemplarity.


Hypophosphataemia definitions, incidence and associated outcomes in paediatric intensive care: A retrospective cohort study in post-cardiac surgical patients <2 years of age.
Hypophosphataemia has been linked to higher morbidity and mortality in intensive care but there is inconsistency in the definition of hypophosphataemia for infants and children. We aimed to determine the incidence of hypophosphataemia in a group of at-risk children in paediatric intensive care unit (PICU) and associations with patient characteristics and clinical outcomes using three different hypophosphataemia thresholds. Retrospective cohort study of 205 post-cardiac surgical patients <2 years of age admitted to Starship Child Health PICU, Auckland, New Zealand. Patient demographics and routine daily biochemistry for 14 days after PICU admission were collected. Rates of sepsis, mortality and length of mechanical ventilation were compared between groups with different serum phosphate concentrations. Out of 205 children, 6 (3%), 50 (24%) and 159 (78%) had hypophosphataemia at thresholds of <0.7, <1.0 and <1.4 mmol/L, respectively. There were no differences in gestational age at birth, sex, ethnicity or mortality in those with and without hypophosphataemia at any threshold. Children with a serum phosphate <1.4 mmol/L had more mean (SD) total hours of mechanical ventilation (85.2 (79.6) vs. 54.9 (36.2) h, P = 0.02) and those with mean serum phosphate <1.0 mmol/L had more mean hours of mechanical ventilation (119.4 (102.8) vs. 65.2 (54.8) h, P < 0.0001), episodes of sepsis (14% vs. 5%, P = 0.03) and longer length of stay (6.4 (4.8-20.7) vs. 4.9 (3.9-6.8) days, P = 0.02). Hypophosphataemia is common in this PICU cohort and serum phosphate <1.0 mmol/L is associated with increased morbidity and length of stay.


Autonomic dysfunction in chronic intestinal pseudo-obstruction.
Fifteen tests were used to assess adrenergic, non-vagal cholinergic, and cardiovagal functions in 11 patients with chronic intestinal pseudo-obstruction (CIP). The three aims of this study were: 1) to ascertain the presence of and spectrum of autonomic involvement; 2) to assess the level of autonomic dysfunction; and 3) to compare the results of autonomic function tests with gastrointestinal motility patterns. Gastrointestinal motility displayed a neuropathic pattern in 10 patients. Adrenergic functions were abnormal in nine patients and non-vagal cholinergic functions in 10 patients. Cardiovagal functions were abnormal in only seven patients. The autonomic dysfunction was localized mostly to the postganglionic pathways. One patient, who had a myopathic pattern and muscle degeneration on small bowel biopsy, demonstrated normal responses to autonomic function tests. The patients with neuropathic CIP demonstrated widespread, mostly postganglionic autonomic dysfunction. Neuropathic CIP can occur with or without cardiovagal involvement.


Miscellaneous newly recognized types of CNS tumors in the WHO CNS5 classification (other than gliomas, glioneuronal and embryonal tumors).
In this review, we describe salient features of a few of the newer entities recognized in the fifth edition of World Health Organization (WHO) classification of central nervous system (CNS) tumors. While most of these have been offshoots of the deoxyribonucleic acid (DNA) methylation profiling of CNS tumors with distinct profiling such as desmoplastic myxoid tumor (DMT) of the pineal region, SMARCB1-mutant, these also demonstrate subtle, distinct morphological features, which should be carefully searched for to diagnose them.


Dynamic elution of residual ammonium leaching agent from weathered crust elution-deposited rare earth tailings by magnesium chloride.
The release of residual ammonium (RA) leaching agent from weathered crust elution-deposited rare earth tailings would cause serious environmental pollution, and it was necessary to efficiently remove it from the ore body before the mine closure. In this study, occurrence states of the RA were determined and dynamic elution of RA from rare earth tailings by using magnesium chloride as eluent was investigated. Effects of initial concentration, pH, flow rate, and particle size on the ammonium removal efficiency were investigated, and variations of ammonium occurrence states before and after elution were determined. Lastly, elution mechanism was discussed. Results showed that removal efficiency of RA by magnesium chloride was significantly higher than that by deionized water, and elution efficiency of RA could reach about 95.7% at the optimum laboratory experiment conditions. Energy dispersive spectrometer (EDS) analysis illustrated that the residual ammonium was replaced by Mg2+ during the elution process, and occurrence state experimental results showed that 94.0% of water-soluble and adsorbable ammonium was eluted. The empirical kinetic equation of eluting RA by magnesium chloride was established as 1-2/3α-(1-α)2/3= 0.02*C00.6t. This study provided a valuable method for reducing environmental pollution caused by the release of the residual ammonium from the rare earth tailings.


A Fully Implantable, Programmable and Multimodal Neuroprocessor for Wireless, Cortically Controlled Brain-Machine Interface Applications.
Reliability, scalability and clinical viability are of utmost importance in the design of wireless Brain Machine Interface systems (BMIs). This paper reports on the design and implementation of a neuroprocessor for conditioning raw extracellular neural signals recorded through microelectrode arrays chronically implanted in the brain of awake behaving rats. The neuroprocessor design exploits a sparse representation of the neural signals to combat the limited wireless telemetry bandwidth. We demonstrate a multimodal processing capability (monitoring, compression, and spike sorting) inherent in the neuroprocessor to support a wide range of scenarios in real experimental conditions. A wireless transmission link with rate-dependent compression strategy is shown to preserve information fidelity in the neural data. At 32 channels, the neuroprocessor has been fully implemented on a 5mm×5mm nano-FPGA, and the prototyping resulted in 5.19 mW power consumption, bringing its performance within the power-size constraints for clinical use. The optimal design for compression and sorting performance was evaluated for multiple sampling frequencies, wavelet basis choice and power consumption.


Interaction between membranous EBP50 and myosin 9 as a favorable prognostic factor in ovarian clear cell carcinoma.
Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a scaffold protein that is required for epithelial polarity. Knockout (KO) of membranous EBP50 (Me-EBP50) in ovarian clear cell carcinoma (OCCC) cells induced an epithelial-mesenchymal transition (EMT)-like phenotype, along with decreased proliferation, accelerated migration capability, and induction of cancer stem cell (CSC)-like properties. Shotgun proteomics analysis of proteins that co-immunoprecipitated with EBP50 revealed that Me-EBP50 strongly interacts with myosin 9 (MYH9). Specific inhibition of MYH9 with blebbistatin phenocopied Me-EBP50 KO, and blebbistatin treatment potentiated the effects of Me-EBP50 KO. In OCCC cells from clinical samples, Me-EBP50 and MYH9 were co-localized at the apical plasma membrane. Patients with a combination of Me-EBP50-high and MYH9-high scores had the best prognosis for overall and progression-free survival. Our data suggest that Me-EBP50 has tumor-suppressive effects through the establishment and maintenance of epithelial polarization. By contrast, loss of Me-EBP50 expression induces EMT-like phenotypes, probably due to MYH9 dysfunction; this results in increased cell mobility and enhanced CSC-like properties, which in turn promote OCCC progression.


Long-term pioglitazone treatment enhances lipolysis in rat adipose tissue.
The insulin-sensitizing effects of thiazolidinediones are believed to depend at least in part on reductions in circulating levels of nonesterified fatty acids (NEFA). The mechanisms that mediate the reductions in NEFA are not fully understood and could involve reductions in adipose tissue lipolysis, increases in glyceroneogenesis and NEFA reesterification in triglycerides in adipose tissue and increases in NEFA metabolism by oxidative tissues. In a congenic strain of spontaneously hypertensive rats that fed a high-sucrose diet to promote features of the metabolic syndrome, we studied the effects of chronic pioglitazone treatment over 4 months on adipose tissue lipolysis and NEFA metabolism. We observed significant increases in basal and adrenaline-stimulated NEFA and glycerol release, and near-total suppression of NEFA reesterification in epididymal adipose tissue isolated from rats chronically treated with pioglitazone. However, pioglitazone-treated rats also exhibited significant increases in mitochondrial DNA levels in adipose tissue (3.2-fold increase, P=0.001) and potentially greater sensitivity to the antilipolytic effects of insulin than untreated controls. In addition, chronic pioglitazone treatment was associated with increased palmitate oxidation in soleus muscle, reduced fasting levels of serum NEFA and triglycerides, as well as reduced serum levels of insulin and increased serum levels of adiponectin. Despite suppressing NEFA reesterification and increasing basal and adrenaline-stimulated lipolysis, chronic pioglitazone treatment may decrease circulating NEFA levels in part by increasing adipose tissue sensitivity to the antilipolytic effects of insulin and by enhancing NEFA oxidation in skeletal muscle.


Structures and biological functions of IL-31 and IL-31 receptors.
Interleukin-31, produced mainly by activated CD4(+) T cells, is a newly discovered member of the gp130/IL-6 cytokine family. Unlike all the other family members, IL-31 does not engage gp130. Its receptor heterodimer consists of a unique gp130-like receptor chain IL-31RA, and the receptor subunit OSMRbeta that is shared with another family member oncostatin M (OSM). Binding of IL-31 to its receptor activates Jak/STAT, PI3K/AKT and MAPK pathways. IL-31 acts on a broad range of immune- and non-immune cells and therefore possesses potential pleiotropic physiological functions, including regulating hematopoiesis and immune response, causing inflammatory bowel disease, airway hypersensitivity and dermatitis. This review summarizes the recent findings on the biological characterization and physiological roles of IL-31 and its receptors.


Influence of cooking method on arsenic retention in cooked rice related to dietary exposure.
Arsenic concentration in raw rice is not only the determinant in actual dietary exposure. Though there have been many reports on arsenic content in raw rice and different tissues of rice plant, little is known about arsenic content retained in cooked rice after being cooked following the traditional cooking methods employed by the people of arsenic epidemic areas. A field level experiment was conducted in Bangladesh to investigate the influence of cooking methods on arsenic retention in cooked rice. Rice samples were collected directly from a severely arsenic affected area and also from an unaffected area, to compare the results. Rice was cooked according to the traditional methods employed by the population of subjected areas. Arsenic concentrations were 0.40+/-0.03 and 0.58+/-0.12 mg/kg in parboiled rice of arsenic affected area, cooked with excess water and 1.35+/-0.04 and 1.59+/-0.07 mg/kg in gruel for BRRI dhan28 and BRRI hybrid dhan1, respectively. In non-parboiled rice, arsenic concentrations were 0.39+/-0.04 and 0.44+/-0.03 mg/kg in rice cooked with excess water and 1.62+/-0.07 and 1.74+/-0.05 mg/kg in gruel for BRRI dhan28 and BRRI hybrid dhan1, respectively. Total arsenic content in rice, cooked with limited water (therefore gruel was absorbed completely by rice) were 0.89+/-0.07 and 1.08+/-0.06 mg/kg (parboiled) and 0.75+/-0.04 and 1.09+/-0.06 mg/kg (non-parboiled) for BRRI dhan28 and BRRI hybrid dhan1, respectively. Water used for cooking rice contained 0.13 and 0.01 mg of As/l for contaminated and non-contaminated areas, respectively. Arsenic concentrations in cooked parboiled and non-parboiled rice and gruel of non-contaminated area were significantly lower (p<0.01) than that of contaminated area. The results imply that cooking of arsenic contaminated rice with arsenic contaminated water increases its concentration in cooked rice.


Group separation of free and conjugated bile acids by pre-packed anion-exchange cartridges.
A rapid and simple procedure for the group separation of the major free and conjugated bile acids of man is described. After initial extraction with Bond Elut C18 cartridges, the analytes are fractionated into the unconjugated, glycine- and taurine-conjugated forms using disposable Bond Elut SAX columns and methanol-acetate buffer eluents. The method is found to be accurate and reproducible and to afford complete resolution between fractions. Free and conjugated bile acids present in human bile and gastric juice are assayed by high-performance liquid chromatography, after extraction and group separation according to the described procedure.


Further studies of the mixed acetals of nucleosides.
We reported in 1988 on a new nucleoside modification reaction: the exocyclic amino groups of (d)adenosine and (d)cytidine react rapidly at ambient temperature with acetaldehyde and alcohols to give stable mixed acetals (N-ethylethoxy-acetal). NH2 + O = CH(CH3) + ROH-->NH-CH(CH3)-O-R + H2O. Here we report in detail on the occurrence of this reaction in very dilute aqueous solution (ie under biological conditions), on its mechanism and kinetics, on the mixed acetal formation with other aldehydes and other nucleic acid components, and on the question of whether these adducts are mutagenic.


[Use of Tc-99m sulfur microcolloid for lymphoscintigraphy of neoplasms of the lymphatic system].
The usefulness of examination of lymphatic nodes with Technetium labelled microcolloid for assessment of lymphatic nodes in patients with non Hodgkin's lymphomas and Hodgkin's disease is discussed. Examination has been applied in 60 cases. The criteria of performance of the examinations in physiologic and pathologic conditions are described, together with comparison with other methods of examination. In the own material significant concordance of lymphoscintigraphic examinations with lymphography and CT has been found, whereas fairly big discrepancies resulted when lymphoscintigraphic and USG examination have been compared.


Suppression of tumor growth by intra-muscular transfer of naked DNA encoding adrenomedullin antagonist.
We have recently reported that the intra-tumoral injection of adrenomedullin (AM) antagonist (AMA; AM (22-52)) peptides significantly reduced the in vivo growth of a pancreatic cancer cell line in severely combined immunodeficient (SCID) mice. In the present study, we examined the effects of intra-tumoral and intra-muscular transfers of naked DNA encoding AMA on the in vivo growth of cancer cell lines. We demonstrate that these treatments induce the regression of a pancreatic cancer cell line and a breast cancer cell line inoculated in SCID mice. Furthermore, CD31-positive cells disappear completely from tumor tissues, following treatment, indicating that neo-vascularization is entirely inhibited. These results suggest that the intra-tumoral or intra-muscular transfer of naked DNA encoding AMA might be a promising alternative modality for treating human cancers.


Sesquiterpene Cyclisations Catalysed inside the Resorcinarene Capsule and Application in the Short Synthesis of Isolongifolene and Isolongifolenone.
Terpenes constitute the largest class of natural products and serve as an important source for medicinal treatments. Despite constant progress in chemical synthesis, the construction of complex polycyclic sesqui- and diterpene scaffolds remains challenging. Natural cyclase enzymes, however, are able to form the whole variety of terpene structures from just a handful of linear precursors. Man-made catalysts able to mimic such natural enzymes are lacking. Here, we describe the examples of sesquiterpene cyclisations inside an enzyme-mimicking supramolecular catalyst. This strategy allowed the formation of the tricyclic sesquiterpene isolongifolene in only four steps. The mechanism of the catalysed cyclisation reaction was elucidated using 13C-labelling studies and DFT calculations.


Use of HPLC- and GC-QTOF to determine hydrophilic and lipophilic phenols in mango fruit (Mangifera indica L.) and its by-products.
Mango industry processing generates high quantities of mango by-products such as peels and seeds (35%-60% of the fruit). Indeed, it is known that mango and its by-products contain different families of bioactive compounds that possess several health benefits. Thus, the aim of this study has been the determination of different families of phenolic derivatives (free and bound phenolic compounds and alk(en)ylresorcinols (ARs)) in mango edible part and its by-products (peel, seed and seed husk) from three different cultivars. This is the first study that evaluates the phenolic compounds and ARs in the four fractions of mango of three different cultivars. Special attention has been paid to the determination of anthocyanins and ARs, because these families of compounds had not been studied in depth in mango. In fact, petunidin rutinoside-(p-coumaric acid) gallate was found in mango pulp, peel, seed and seed husk of the three cultivars and, it had never been described in mango before. It is also important to highlight that this is the first time that the identification and quantification of ARs have been performed in mango seed and seed husk; besides, four and five out of eleven alk(en)ylresorcinols detected in peel and pulp, respectively, were identified for the first time in these mango fractions. Furthermore, antioxidant activity was measured by ABTS and FRAP assays. Seed free and bound phenolic extracts showed the highest antioxidant capacity.


[Analysis of Clinical Characteristics in 595 Patients with Herb-induced Liver Injury].
To observe clinical characteristics of herb-induced liver injury (HILI). General conditions, medical history, clinical manifestations, biochemical indices, prognosis, and Roussed Uclaf Causality Assessment Method (RUCAM) scores were retrospectively analyzed in 595 inpatients at 302 Military Hospital between January 2009 and January 2014. There were 423 cases (accounting for 71.1%) were females with multiple onset age ranging 41 to 50 years old. The median time from starting Chinese herbs to the occurrence of liver injury (LI) was 30 days (15-75 days), and 511 cases (85.9%) were classified as hepatocellular injury. Chinese herbs inducing HILI were mainly used for skin disease (102 cases, 17.1%), osteoarticular disease (57 cases, 9.6%), and gastrointestinal disease (49 cases, 8.2%), covering 207 kinds of Chinese patent medicines. Polygonum multiflorum, Psoralea corylifolia, and Corydalis ambigua were often seen in Chinese prescriptions. In RUCAM scoring, 451 HILI patients (accounting for 74.1%) were very possibly associated with Chinese herbs. Liver failure occurred in 47 HILI patients (accounting for 7.9%), cirrhosis in 45 patients (accounting for 7.6%), chronic HILI in 80 patients (accounting for 13.4%), 27 (4.5%) died, and only 2 (0.3%) underwent liver transplantation. Chinese herbs could cause LI or even death. Attention should be paid to herbal hepatotoxicity and improving monitoring system of HILI.


Independent and incremental prognostic value of endogenous ouabain in idiopathic dilated cardiomyopathy.
Increased circulating levels of endogenous ouabain (EO) have been observed in some heart failure patients, but their long term clinical significance is unknown. This study investigated the prognostic value of EO for worsening heart failure among 140 optimally treated patients (age 50+/-14 years; 104 male; NYHA class 1.9+/-0.7) with idiopathic dilated cardiomyopathy. Plasma EO was determined by RIA and by liquid chromatography mass spectrometry, values were linearly correlated (r = 0.89) in regression analysis. During follow-up (13+/-5 months), heart failure progression was defined as worsening clinical condition leading to one or more of the following: sustained increase in conventional therapies, hospitalization, cardiac transplant, or death. NYHA functional class, age, LVEF, peak VO2 and plasma levels of EO were predictive for heart failure progression. Heart failure worsened 1.5 fold (HR: 1.005; 95% CI: 1.001-1.007; p<0.01) for each 100 pmol/L increase in plasma EO. Moreover, those patients with higher plasma EO values had an odds ratio of 5.417 (95% CI: 2.044-14.355; p<0.001) for heart failure progression. Following multivariate analysis, LVEF, NYHA class and plasma EO remained significantly linked with clinical events. This study provides the first evidence that circulating EO is a novel, independent and incremental marker that predicts the progression of heart failure.


Intercalator conjugates of pyrimidine locked nucleic acid-modified triplex-forming oligonucleotides: improving DNA binding properties and reaching cellular activities.
Triplex-forming oligonucleotides (TFOs) are powerful tools to interfere sequence-specifically with DNA-associated biological functions. (A/T,G)-containing TFOs are more commonly used in cells than (T,C)-containing TFOs, especially C-rich sequences; indeed the low intracellular stability of the non-covalent pyrimidine triplexes make the latter less active. In this work we studied the possibility to enhance DNA binding of (T,C)-containing TFOs, aiming to reach cellular activities; to this end, we used locked nucleic acid-modified TFOs (TFO/LNAs) in association with 5'-conjugation of an intercalating agent, an acridine derivative. In vitro a stable triplex was formed with the TFO-acridine conjugate: by SPR measurements at 37 degrees C and neutral pH, the dissociation equilibrium constant was found in the nanomolar range and the triplex half-life approximately 10 h (50-fold longer compared with the unconjugated TFO/LNA). Moreover to further understand DNA binding of (T,C)-containing TFO/LNAs, hybridization studies were performed at different pH values: triplex stabilization associated with pH decrease was mainly due to a slower dissociation process. Finally, biological activity of pyrimidine TFO/LNAs was evaluated in a cellular context: it occurred at concentrations approximately 0.1 microM for acridine-conjugated TFO/LNA (or approximately 2 microM for the unconjugated TFO/LNA) whereas the corresponding phosphodiester TFO was inactive, and it was demonstrated to be triplex-mediated.


T helper cell lines that augment in vivo cytotoxic T-cell responses to minor alloantigens.
We have investigated the ability of long-term cultured T helper (Th) cell lines to help an in vivo cytotoxic T lymphocyte (CTL) response to non-H-2 alloantigens (minor antigens). Th cell lines specific for various single or undefined minor antigens were selected by regular restimulation with antigen in vitro. They were antigen specific and H-2 restricted in proliferation assays and were found to be able to help primary CTL responses to multiple minor antigens and secondary CTL responses to single minor antigens. Although the Th were antigen specific they did not determine the specificity of the CTL. Th cells were both necessary and limiting for an effective CTL response indicating that "helper-independent" CTL are not in themselves sufficient to generate a strong in vivo response. Under conditions where a CTL response was clearly H-2 restricted, Th cells were not. Thus, the Th cells appeared to be activated by reprocessed antigen rather than antigen on the surface of the injected antigenic cells even though the CTL themselves reacted directly to the injected antigen.


The role of regulatory T cells in allergy.
Atopic diseases are characterized by Th2 and IgE responses to common environmental and food antigens. In vivo, IgE production depends on interactions between allergen-specific B lymphocytes and Th2 lymphocytes. IgE levels are extremely low in normal individuals, suggesting that IgE production is under strong regulation. One of the reasons behind the lack of atopy in healthy individuals is the activity of regulatory T cells, which prevent naïve T helper cell precursors from acquiring a differentiated Th2 phenotype. In addition to naturally occurring regulatory T cells, atopy can be prevented by allergen-specific tolerant/regulatory cells induced through mucosal stimulation, and by mechanisms that directly suppress Iepsilon sterile transcript production on activated B lymphocytes. This article reviews the recent progress on thymic-derived as well as peripherally induced regulatory T cells as they relate to atopy. The latter discussion also includes regulatory T cells that arise through immunotherapy.


Phase II multi-institutional prospective trial of nab-paclitaxel as second-line chemotherapy for advanced gastric cancer refractory to fluoropyrimidine with modified dose reduction criteria (CCOG1303).
The aim of this study was to explore the efficacy and safety of nab-paclitaxel as second-line chemotherapy for advanced gastric cancer with modified dose reduction criteria by which the doses were manipulated earlier. Gastric cancer patients who developed progression during the fluoropyrimidine-containing first-line chemotherapy were assigned to receive nab-paclitaxel (260 mg/m2) by triweekly administration. Dose reduction was regulated according to predefined toxicity criteria which included neutropenia less than 1000/mm3 and/or peripheral sensory neuropathy of grade 2 or more. The primary endpoint was progression-free survival. A total of 50 patients were enrolled, 47 of whom were eligible for efficacy analyses. The median number of treatment cycles and relative dose intensity given per patient was four (range 1-25), and 90% (range 60-100). Of total administration throughout the trial of 280 cycles, dose reduction was required in 50 cycles. The median progression-free survival was 3.5 months (95% confidence interval 2.5-4.4) that met the primary endpoint. The median overall survival was 9.0 months (95% confidence interval 6.8-11.8), overall response rate was 16% (95% confidence interval 2-30), and disease control rate was 72% (95% confidence interval 54-90). The median time to treatment failure was 3.5 months (95% confidence interval 2.5-4.4). Adverse events of grade 3 or worse included neutropenia in 49%, and peripheral sensory neuropathy in 11%. Febrile neutropenia occurred only in one patient (2%). The modified dose reduction criteria for triweekly administration of nab-paclitaxel resulted in decreased incidence of severe peripheral sensory neuropathy without decline in efficacy.


High-dose intravenous immunoglobulin therapy for eosinophilic granulomatosis with polyangiitis.
Regulatory T (Treg) cells are implicated in the development and progression of eosinophilic granulomatosis with polyangiitis (EGPA). We previously showed beneficial effects of intravenous immunoglobulin (IVIG) therapy combined with corticosteroid and immunosuppressant treatment on clinical symptoms, including mononeuritis multiplex and cardiac dysfunction, and Treg cell frequency, during EGPA. Whether the timing of administration (during initial treatment or at relapse after remission) or previous treatment affects the clinical and immunologic efficacy of IVIG is unknown. We evaluated whether the frequency of Treg cells varied depending on when IVIG was provided relative to the start of conventional therapy for EGPA. The patient population for this retrospective analysis comprised 17 patients with severe mononeuritis multiplex or heart failure whose EGPA did not respond to corticosteroids combined with immunosuppressant therapy. Ten patients first received IVIG during initial treatment, whereas the remaining 7 patients first received IVIG on relapse after remission. We measured the percentage of Treg cells, defined as FOXP3(+)CD4(+) T cells, present before the first round of IVIG and at 1 month after the last IVIG treatment. FOXP3(+)CD4(+) T cells were increased in patients who required only a single course of IVIG to achieve remission compared with those who needed two or more courses. The dosage of prednisolone at initial IVIG was inversely correlated with the ratio of the number of FOXP3(+)CD4(+) T cells before IVIG and that at 1 month thereafter. Patients with severe EGPA who receive IVIG after nonresponse to high-dose prednisolone during initial treatment may need multiple courses of IVIG to achieve remission. An increase in the frequency of Treg cells after IVIG may predict the need for additional IVIG in EGPA.


Epileptiform lesions in rat hippocampus and acquisition of two-way avoidance.
Three experiments were conducted to examine the effects on the acquisition of two-way active avoidance of implantation into the hippocampus of rats of two substances (aluminum hydroxide, penicillin) known to produce epileptogenic electrical discharges. In Experiment 1 bilateral deposits of aluminum hydroxide (ALOH) were placed in the hippocampus and the effects of this manipulation were compared to the effects of bilateral hippocampal aspiration. Sufficient postoperative time (130 days) was allowed such that epileptogenic discharges developed in the ALOH-implanted rats. Both bilateral hippocampal-ALOH deposits and bilateral hippocampal aspiration resulted in facilitated acquisition of the two-way avoidance. The results of Experiment 2 replicated this observation, but also indicated that bilateral hippocampal deposits of penicillin did not cause detectable effects on acquisition of the avoidance. Epileptiform activity produced by the penicillin was observed to disappear by postoperative Day 4. In Experiment 3 unilateral hippocampal aspiration was combined with contralateral implants of either ALOH or penicillin and avoidance training was begun 13 days postoperatively. Epileptiform activity was not observed in the ALOH-implanted rats and disappeared by postoperative Day 4 in the penicillin implanted rats. No significant changes were observed in the rate of acquisition of two-way active avoidance as a result of the manipulations done in Experiment 3. It is concluded that epileptiform discharge initiated focally within the hippocampus produces effects on the acquisition of two-way active avoidance which are similar to the effects produced by bilateral ablation.


Crystal structure and Hirshfeld surface analysis of 2,2'-[(3,5-di-tert-butyl-4-hy-droxy-phen-yl)methanedi-yl]bis-(3-hy-droxy-5,5-di-methyl-cyclo-hex-2-en-1-one).
In the title compound, C31H44O5, mol-ecules are connected by O-H⋯O and C-H⋯O hydrogen bonds, forming hydrogen-bonded zigzag chains running along the b axis and parallel to the (001) plane. The mol-ecular packing is stabilized by van der Waals inter-actions between these chains along the a and c axes. The inter-molecular inter-actions in the crystal structure were qu-anti-fied and analysed using Hirshfeld surface analysis.


Watermelon and ragweed share allergens.
A biotin-avidin amplified ELISA was used to measure antigen-specific IgE for ragweed, representative members of the gourd family (watermelon, cantaloupe, honeydew melon, zucchini, and cucumber), and banana in the sera of 192 allergic patients, each with an IgE greater than or equal to 180 microns/ml. Sixty-three percent (120/192) of the sera contained antiragweed IgE, and of these patients, 28% to 50% contained IgE specific for any single gourd family member. In contrast, no greater than 11% of the sera positive for a given gourd or banana were negative for ragweed. Correlations between ragweed and gourd-specific IgE levels were significant (p less than 0.001), and correlation coefficients between any two gourds exceeded 0.79. In an ELISA system, the extracts of watermelon and ragweed inhibited each other in a dose-dependent manner; the resulting nonparallel inhibition curves indicate that some, but not all, of the allergens in the two extracts are cross-reactive. Isoelectric focusing of watermelon and ragweed extracts in narrow range gel (pH 4 to 6) followed by immunoblotting demonstrated six watermelon allergen bands with isoelectric points identical to those of ragweed allergens. Several remaining bands in the two extracts had differing isoelectric points, however. Six of 26 patients interviewed with watermelon-specific IgE reported developing oropharyngeal symptoms (itching and/or swelling of the lips, tongue, or throat) after ingesting at least one of the study foods, whereas only one of 25 patients interviewed without detectable watermelon-specific IgE reported similar symptoms (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


A patient with neuropathy and ataxia: what do I have to consider?
An increasing number of peripheral neuro(no)pathies are identified as involving other components of the neurological system, particularly those that further impair balance. Here we aim to outline an evidence-based approach to the diagnosis of patients who present with a somatosensory disorder which also involves at least one other area of neurological impairment such as the vestibular, auditory, or cerebellar systems. Detailed objective investigation of patients who present with sensory impairment, particularly where the degree of imbalance is greater than would be expected, aids the accurate diagnosis of genetic, autoimmune, metabolic, and toxic neurological disease. Diagnosis and management of complex somatosensory disorders benefit from investigation which extends beyond the presenting sensory impairment.


Blood products and liver transplantation: A strategy to balance optimal preparation with effective blood stewardship.
Unanticipated transfusion requirements during liver transplantation can delay lifesaving intraoperative resuscitation and strain blood bank resources. Risk-stratified preoperative blood preparation can mitigate these deleterious outcomes. A two-tiered blood preparation protocol for liver transplantation was retrospectively evaluated. Eleven binary variables served as criteria for high-risk (HR) allocation. Primary outcomes included red blood cell (RBC), plasma (FFP), and platelet (Plt) utilization. Secondary outcomes included product under- and overpreparation. Contingency tables for transfusion requirements above the population means were generated using 15 clinical variables. Modified protocols were developed and retrospectively optimized using the study population. Of 225 recipients, 102 received HR preoperative orders, which correlated to higher intraoperative transfusion requirements. However, univariate analysis identified only two statistical risk factors per product: Hgb ≤7.8 g/dl (p < .001) and MELD ≥38 (p = .035) for RBCs, Hgb ≤7.8 g/dl (p = .002) and acute alcoholic hepatitis (p = 0.015) for FFP, and Hgb ≤7.8 g/dl (p = .001) and normothermic liver preservation (p = .037) for Plts. Based on these findings, we developed modified protocols for individual products, which were evaluated retrospectively for their effectiveness at reducing under-preparatory events while limiting product overpreparation. Cohort statistics were used to define the preparation strategy for each protocol. Retrospective comparative analysis demonstrated the superiority of the modified protocols by improving the under-preparation rate from 24% to <10% for each product, which required a 1.56-fold and 1.44-fold increase in RBC and FFP overpreparation, respectively. Importantly, there was no difference in Plt overpreparation. We report translatable data-driven blood bank preparation protocols for liver transplantation.


Exploration of the nutrition knowledge among general population: multi-national study in Arab countries.
Knowing what to eat and realizing the significance of healthful eating habits are among the important steps to promoting eating behavior. The current study aims to assess the nutrition knowledge (NK) among a convenient sample in four different countries, determine the association between different demographic factors and NK, and investigate the need for future interventions on nutrition in the four selected countries. A cross-sectional multi-national survey study among a convenient sample of 8,191 subjects from Egypt, Syria, Saudi Arabia, and Jordan who undertook surveys between January 2019 and January 2020. A pre-tested interview questionnaire was utilized for data collection from study participants. It included three sections: i) Sociodemographic characteristics:. ii). Section two included twenty-one questions related to NK.. iii). Section three included one question about NK sources. About three-quarters showed inadequate nutrition knowledge (73.1%). Youth (15-24 yrs.) were more dependent on social media, with 87% using it as a primary source of NK, while adults (≥ 25 yrs.) demonstrated that 43% of them used social media. In contrast, TV was more prominent among them, with participants' characteristics such as living with parents, body mass index, and country of residence showing no association with NK. However, female sex, education, and reading nutrition articles are significantly correlated with adequate knowledge (p < 0.001). Significant predictors of satisfactory knowledge were age, sex, education, living with parents, and reading nutrition articles. The study revealed low levels of NK indicating an urgent need to implement educational programs to promote nutrition knowledge. As NK is a modifiable determinant of diet intake and can positively impact the need for developing strategies in counselling and raising awareness among the general population to improve their health status.


Simultaneous Estimation of Azimuth and Elevation Angles Using a Decision Tree-Based Method.
This study addresses the problem of accurately predicting azimuth and elevation angles of signals impinging on an antenna array employing Machine Learning (ML). Using the information obtained at a receiving system when a transmitter's signal hits it, a Decision Tree (DT) model is trained to estimate azimuth and elevation angles simultaneously. Simulation results demonstrate the robustness of the proposed DT-based method, showcasing its ability to predict the Direction of Arrival (DOA) in diverse conditions beyond the ones present in the training dataset, i.e., the results display the model's generalization capability. Additionally, the comparative analysis reveals that DT-based DOA estimation outperforms the state-of-the-art MUltiple SIgnal Classification (MUSIC) algorithm. Our results demonstrate an average reduction of over 90% in the prediction error and 50% in the prediction time achieved by our proposal when compared to the MUSIC algorithm. These results establish DTs as competitive alternatives for DOA estimation in signal reception systems.


Intestinal protozoa are hypothesized to stimulate immunosurveillance against colon cancer.
Colon cancer in humans results in considerable morbidity and mortality throughout most of the world. During the twentieth century, there was a rapid rise in colon cancer within modernizing countries that has not been adequately explained, although the role of diet has been widely explored. Previously, we showed that the presence of the endemic Eimeria spp. protozoan in intestinal tissues is associated with regions of low tumorigenesis in the large and small bovine intestine and that an Eimeria surface protein is a potent activator of dendritic cells and a useful immunomodulator, with anti-cancer and anti-viral properties. Therefore, we hypothesize that the persistent presence of such an intestinal protozoan enhances immunosurveillance by elevating the intestinal alert status and that the loss of these organisms could lead to a higher incidence of colon cancer. Preliminary support of this hypothesis derives from the observations that domestic animals, known to maintain this protozoan, have very low colon cancer incidence. We propose that this also may occur in human populations that use human excrement (night soil) as a fertilizer, a practice that serves to complete the life cycle of this type of microbe. We examine some evidence for this hypothesis in Japan's mortality patterns, where we show that colon cancer increased after the cessation of night soil use, but before the change to a western diet. We conclude that this hypothesis, a variation of the hygiene hypothesis, is worth further consideration and continued elaboration.


Reconstructive surgery and patients with spinal cord injury: Perioperative considerations for the plastic surgeon.
Patients with spinal cord injury (SCI) requiring reconstructive surgery, particularly for pressure ulcers, are ubiquitous in Plastic and Reconstructive Surgery practices. Much of the current literature focuses on operative techniques, antibiotic indications, sitting protocols, and dressing and bedding choices. This paper reviews normal neuroanatomy, outlines changes in neurophysiology observed in spinal cord injury, and addresses concepts related to perioperative care that are highly relevant but often under-emphasised. Vascular disturbances such as autonomic dysreflexia and orthostatic hypotension are dangerous phenomena occurring in this patient population that, if not properly recognised and treated, may result in complications such as haematoma, flap loss, inadequate tissue perfusion, and death. The management of spasticity, deep venous thrombosis, and perioperative pain are also relevant and discussed in this paper. A basic understanding of these concepts is essential for the Plastic Surgeon involved in the care of patients with SCI and pressure ulcers, particularly before and after debridement or reconstruction.


Equivalence of Generic Glatiramer Acetate in Multiple Sclerosis: A Randomized Clinical Trial.
The patents for the first approved treatments for relapsing-remitting multiple sclerosis are expiring, creating the opportunity to develop generic alternatives. To evaluate in the Glatiramer Acetate Clinical Trial to Assess Equivalence With Copaxone (GATE) study whether generic glatiramer acetate (hereafter generic drug) is equivalent to the originator brand glatiramer acetate (hereafter brand drug) product, as measured by imaging and clinical end points, safety, and tolerability. Randomized, multicenter, double-blind, active and placebo-controlled phase 3 trial. The setting included academic medical centers and clinical practices. Participants were patients with relapsing-remitting multiple sclerosis 18 to 55 years old with at least 1 relapse in the prior year and 1 to 15 gadolinium-enhancing brain magnetic resonance imaging lesions. They were randomized between December 7, 2011, and March 21, 2013. The last participant completed follow-up December 2, 2013. Participants were randomized 4.3:4.3:1 to receive generic glatiramer acetate (20 mg), brand glatiramer acetate (20 mg), or placebo by daily subcutaneous injection for 9 months. The primary end point was the total number of gadolinium-enhancing lesions during months 7, 8, and 9. Additional end points included other magnetic resonance imaging parameters, annualized relapse rate, and Expanded Disability Status Scale score. Safety and tolerability were assessed by monitoring adverse events, injection site reactions, and laboratory test results. In total, 794 participants were randomized and treated with generic drug (n = 353), brand drug (n = 357), or placebo (n = 84). The estimated mean numbers of gadolinium-enhancing lesions with generic drug and brand drug were lower than with placebo (ratio, 0.488; 95% CI, 0.365-0.651; P < 001), confirming study sensitivity. For gadolinium-enhancing lesions, the estimated ratio of generic drug to brand drug was 1.095 (95% CI, 0.883-1.360), which was within the predefined equivalence margin of 0.727 to 1.375. The incidence, spectrum, and severity of reported adverse events, including injection site reactions, were similar in the generic drug and brand drug groups. As treatment for relapsing-remitting multiple sclerosis, glatiramer acetate generic drug and brand drug had equivalent efficacy, safety, and tolerability. clinicaltrials.gov Identifier: NCT01489254.


Effect of plasma sprayed flyash based composite coatings on corrosion resistance.
With the aim of exploring the possibility of achieving a low-cost thermal spray coating to prevent wear, erosion and corrosion. In the current study, flyash-Al2O3 and flyash-SiC composite coatings were effectively created using the air plasma spray process on substrates of Al6061 alloy. NiCr material is used as the bond coat to improve the bond strength between the coat and the substrate. Taguchi's DoE method is applied to for spray process parameters optimization. In addition, the developed coating is subjected to microstructure analysis and long-term immersion corrosion testing (1 year) in an aqueous environment to assess corrosion properties. The results revealed that the over a certain test period, the developed flyash-SiC coating has greater corrosion resistance than the uncoated and flyash-Al2O3 coated Al6061. It is noticed that the corrosion resistance of the flyash-Al2O3 coating shifts to a negative value with respect to the uncoated substrate. The uncoated sample is extensively pitted and locally corroded, as shown by the SEM image of the corroded surface. Flyash-corroded Al2O3's surface exhibits extensive degradation in the form of peeling, breaking, and cracking of the splats. With flyash-SiC composite coating a very minor corrosion splat deterioration is seen.


Head Trauma.
Head trauma is a common cause of significant morbidity and mortality in dogs and cats. Traumatic brain injury may occur after head trauma. Understanding the pathophysiology of primary and secondary injury after head trauma is essential for management. This article reviews the pathophysiology of head trauma, patient assessment and diagnostics, and treatment recommendations.


Two-stage liver transplant for ruptured hepatic adenoma: A case report.
Only one case of liver transplantation for hepatic adenoma has previously been reported for patients with rupture and uncontrolled hemorrhage. We present the case of a massive ruptured hepatic adenoma with persistent hemorrhagic shock and toxic liver syndrome which resulted in a two-stage liver transplantation. This is the first case of a two-stage liver transplantation performed for a ruptured hepatic adenoma. A 23 years old African American female with a history of pre-diabetes and oral contraceptive presented to an outside facility complaining of right-sided chest pain and emesis for one day. She was found to be in hemorrhagic shock due to a massive ruptured hepatic hepatic adenoma. She underwent repeated embolizations with interventional radiology with ongoing hemorrhage and the development of renal failure, hepatic failure, and hemodynamic instability, known as toxic liver syndrome. In the setting of uncontrolled hemorrhage and toxic liver syndrome, a hepatectomy with porto-caval anastomosis was performed with liver transplantation 15 h later. She tolerated the anhepatic stage well, and has done well over one year later. When toxic liver syndrome is recognized, liver transplantation with or without hepatectomy should be considered before the patient becomes unstable.


GATA2 co-opts TGFβ1/SMAD4 oncogenic signaling and inherited variants at 6q22 to modulate prostate cancer progression.
Aberrant somatic genomic alteration including copy number amplification is a hallmark of cancer genomes. We previously profiled genomic landscapes of prostate cancer (PCa), yet the underlying causal genes with prognostic potential has not been defined. It remains unclear how a somatic genomic event cooperates with inherited germline variants contribute to cancer predisposition and progression. We applied integrated genomic and clinical data, experimental models and bioinformatic analysis to identify GATA2 as a highly prevalent metastasis-associated genomic amplification in PCa. Biological roles of GATA2 in PCa metastasis was determined in vitro and in vivo. Global chromatin co-occupancy and co-regulation of GATA2 and SMAD4 was investigated by coimmunoprecipitation, ChIP-seq and RNA-seq assays. Tumor cellular assays, qRT-PCR, western blot, ChIP, luciferase assays and CRISPR-Cas9 editing methods were performed to mechanistically understand the cooperation of GATA2 with SMAD4 in promoting TGFβ1 and AR signaling and mediating inherited PCa risk and progression. In this study, by integrated genomics and experimental analysis, we identified GATA2 as a prevalent metastasis-associated genomic amplification to transcriptionally augment its own expression in PCa. Functional experiments demonstrated that GATA2 physically interacted and cooperated with SMAD4 for genome-wide chromatin co-occupancy and co-regulation of PCa genes and metastasis pathways like TGFβ signaling. Mechanistically, GATA2 was cooperative with SMAD4 to enhance TGFβ and AR signaling pathways, and activated the expression of TGFβ1 via directly binding to a distal enhancer of TGFβ1. Strinkingly, GATA2 and SMAD4 globally mediated inherited PCa risk and formed a transcriptional complex with HOXB13 at the PCa risk-associated rs339331/6q22 enhancer, leading to increased expression of the PCa susceptibility gene RFX6. Our study prioritizes causal genomic amplification genes with prognostic values in PCa and reveals the pivotal roles of GATA2 in transcriptionally activating the expression of its own and TGFβ1, thereby co-opting to TGFβ1/SMAD4 signaling and RFX6 at 6q22 to modulate PCa predisposition and progression.


Cardiac tamponade during transesophageal echocardiography in a patient with infective endocarditis.
An 81-year-old man with a history of diabetes mellitus and end-stage renal disease was admitted because of infective endocarditis. During transesophageal echocardiography (TEE), pericardial effusion rapidly increased and led to cardiac tamponade. Despite intensive therapy, the patient did not recover. Autopsy showed hemopericardium, ruptured sinus of Valsalva, and vegetation on the aortic valve. Our case suggests that cardiac tamponade due to the rupture of a sinus of Valsalva can occur in patients with aortic valve endocarditis complicated by perivalvular abscess. Therefore, we must be aware of this devastating complication and take preventive measures when performing TEE in such patients.


Considerations and adaptions to the modulated arc total body irradiation technique: dosimetry description.
Total body irradiation (TBI) is a complex treatment technique, which has been slow to transition to a three-dimensional (3D) planning approach. There is limited literature available providing a detailed description on methods to plan TBI on a 3D planning system. 3D planning using the modulated arc TBI (MATBI) technique is a complex process involving a significant number of quality assurance processes and scripts, due to more than 40 treatment beams and two patient positions. This article will focus on the workflow and technical planning aspects of our institution's MATBI technique and identify reasons for modifications made to the developing institution's original MATBI approach. Included is a description of specific simulation equipment, detailed explanation of the four-stage computing process including the role of scripting to standardise and streamline what is otherwise a complex number of steps. The information provided is specific to one centre's approach but shows the fundamental planning process and demonstrates a streamlined method, which can be adapted to other planning systems. Overall, the ability to accurately represent the TBI technique in 3D on a planning system will be shown.


Comparative genomics analysis of the metallomes.
Biological trace metals are needed in small quantities, but used by all living organisms. They are employed in key cellular functions in a variety of biological processes, resulting in the various degree of dependence of organisms on metals. Most effort in the field has been placed on experimental studies of metal utilization pathways and metal-dependent proteins. On the other hand, systemic level analyses of metalloproteomes (or metallomes) have been limited for most metals. In this chapter, we focus on the recent advances in comparative genomics, which provides many insights into evolution and function of metal utilization. These studies suggested that iron and zinc are widely used in biology (presumably by all organisms), whereas some other metals such as copper, molybdenum, nickel, and cobalt, show scattered occurrence in various groups of organisms. For these metals, most user proteins are well characterized and their dependence on a specific element is evolutionarily conserved. We also discuss evolutionary dynamics of the dependence of user proteins on different metals. Overall, comparative genomics analysis of metallomes provides a foundation for the systemic level understanding of metal utilization as well as for investigating the general features, functions, and evolutionary dynamics of metal use in the three domains of life.


Transmission of human mitochondrial DNA along the paternal lineage in transmitochondrial mice.
Previously we obtained heteroplasmic mice carrying murine and human mitochondrial DNA (mtDNA). Even the fourth generation of such mice had human mtDNA in their organs, hence, they were used to study the possibility of paternal mtDNA transmission. A lineage was obtained in which human mtDNA was transmitted by males to the progeny in four successive generations. This is the first observation of such a continuous paternal transmission of mtDNA. Persistence of paternal mtDNA in several successive generations of animals suggests that mechanisms aimed at elimination of paternally inherited mtDNA species are not as strict as has been postulated.


Association of Neck Circumference with Obesity in Female College Students.
Obesity levels have been dramatically increased in the United Arab Emirates over the last few years. High levels of body Mass Index, waist circumference, and percent of total body fat as a measure of obesity have found to be related to cardiovascular risk factors and other diseases. Neck circumference is a new tool that has been linked to obesity. However, no studies in UAE have been conducted yet. The purpose of this study was to measure the obesity levels in a college population and to correlate them with NC and other anthropometrical indexes. Two hundred forty three (243) female students aged 18-25 were conveniently selected to participate in the study. Anthropometrical indexes were obtained from all subjects e after fasting. The prevalence of overweight and obesity together was found to be 28.4 % (n = 69). Pearson correlation showed that WC, NC and BF (%) were significantly positively related to obesity, (r = 0.790; r = 0.758; r = 0.767, p < 0.001), respectively. In multiple regression analysis, only NC (Beta: 1.627, 95 %CI: 0.370, 2.846, p < 0.001) and WC (Beta: 0.464, 95 %CI: 0.135, 0.664, p < 0.001) were found to be independently associated with obesity. NC was found to be independently associated with obesity levels in Emirati college students.


Encephalitogenic activity of guinea pig myelin basic protein in the SJL mouse.
GPBP was shown to be encephalitogenic in SJL mice by direct challenge and in experiments in which an adoptive transfer system was employed. The three fragments obtained by treating GPBP with pepsin were assessed in the same manner. The encephalitogenic activity resided in the C terminal half of the molecule (residues 89-169). LNC also proliferated to the same fragment in vitro. Fragments 1-37, and, to a lesser extent, 44-48 stimulated sensitized LNC to proliferate but did not induce disease.


Transcriptional regulation of the AP-2alpha promoter by BTEB-1 and AP-2rep, a novel wt-1/egr-related zinc finger repressor.
AP-2 transcription factors have been suggested to exert key regulatory functions in vertebrate embryonic development, in tumorigenicity of various cancer cell types, and in controlling cell cycle and apoptotic effector genes. In this study, we investigated transcriptional regulation of the AP-2alpha gene promoter mediated by an autoregulatory element (referred to as A32) with a core consensus AP-2 binding site at position -336 relative to the mRNA initiation site. AP-2 and multiple different nuclear proteins in HeLa and Neuro2A cell extracts form specific bandshifts with the A32 element. By screening a mouse brain cDNA expression library, we isolated two different cDNAs encoding the transcription factor BTEB-1 and a novel zinc finger protein, AP-2rep. AP-2rep reveals a modular structure with homology to transcription factors of the wt-1/egr-1-family. AP-2rep, BTEB-1, and AP-2 interact in a mutually exclusive manner with overlapping binding sites in the A32 element. Transfection studies revealed that BTEB-1 is a strong activator of AP-2alpha promoter activity, whereas cotransfected AP-2alpha resulted in moderate autoactivation of promoter activity. In contrast, AP-2rep confers strong transcriptional repression to the AP-2alpha gene, and we observed an excellent correlation between induction of AP-2rep mRNA expression and downregulation of AP-2alpha mRNA during development of the kidney. In summary, we have identified multiple transcription factors and cloned from an expression library a novel zinc finger silencing factor, AP-2rep, mediating positive and negative regulation of AP-2alpha expression through a set of overlapping cis-regulatory promoter elements.


Use of signal detection theory in examining the results of a contrast examination: a case study using the lymphangiogram.
The receiver operating characteristic curve is an unbiased technique useful for quantitating the extent to which varying modalities differ in their ability to identify pathological processes. It was applied specifically to a radiographic contrast examination--the evaluation of the lymphangiogram in patients with Hodgkin's disease.


[Length of stay of hernia patients: an international comparison].
A comparison of four community hospitals in four countries (U.S.A., Sweden, U.K., Switzerland) shows important differences regarding the average length of stay in these four countries. The mean stay for the diagnosis of inguinal hernia in Switzerland is about twice as high as in the other countries. Explanations for such variations lie with the shape of the system of care rather than with the medical needs of different populations.


Widely tunable Tm-doped mode-locked all-fiber laser.
We demonstrated a widely tunable Tm-doped mode-locked all-fiber laser, with the widest tunable range of 136 nm, from 1842 to 1978 nm. Nonlinear polarization evolution (NPE) technique is employed to enable mode-locking and the wavelength-tunable operation. The widely tunable range attributes to the NPE-induced transmission modulation and bidirectional pumping mechanism. Such kind of tunable mode-locked laser can find various applications in optical communications, spectroscopy, time-resolved measurement, and among others.


Heteroepitaxial diamond growth on 4H-SiC using microwave plasma chemical vapor deposition.
Deposition of heteroepitaxial diamond via microwave chemical vapor deposition has been performed on a 4H-SiC substrate using bias enhanced nucleation followed by a growth step. In future work, the diamond film will serve as a protective layer for an alpha particle sensor designed to function in an electrorefiner during pyroprocessing of spent fuel. The diamond deposition on the 4H-SiC substrate was carried out using a methane-hydrogen gas mixture with varying gas flow rates. The nucleation step was conducted for 30 minutes and provided sufficient nucleation sites to grow a diamond film on various locations on the substrate. The resulting diamond film was characterized using Raman spectroscopy exhibiting the strong Raman peak at 1332 cm-1. Scanning electron microscopy was used to observe the surface morphology and the average grain size of the diamond film was observed to be on the order of ∼2-3 μm.


The apoptosome: heart and soul of the cell death machine.
Apoptosis is a fundamental biologic process by which metazoan cells orchestrate their own self-demise. Genetic analyses of the nematode C elegans identified three core components of the suicide apparatus which include CED-3, CED-4, and CED-9. An analogous set of core constituents exists in mammalian cells and includes caspase-9, Apaf-1, and bcl-2/xL, respectively. CED-3 and CED-4, along with their mammalian counterparts, function to kill cells, whereas CED-9 and its mammalian equivalents protect cells from death. These central components biochemically intermingle in a ternary complex recently dubbed the "apoptosome." The C elegans protein EGL-1 and its mammalian counterparts, pro-apoptotic members of the bcl-2 family, induce cell death by disrupting apoptosome interactions. Thus, EGL-1 may represent a primordial signal integrator for the apoptosome. Various biochemical processes including oligomerization, adenosine triphosphate ATP/dATP binding, and cytochrome c interaction play a role in regulating the ternary death complex. Recent studies suggest that cell death receptors, such as CD95, may amplify their suicide signal by activating the apoptosome. These mutual associations by core components of the suicide apparatus provide a molecular framework in which diverse death signals likely interface. Understanding the apoptosome and its cellular connections will facilitate the design of novel therapeutic strategies for cancer and other disease states in which apoptosis plays a pivotal role.


Exosomes from CIITA-transfected CT26 cells enhance anti- tumor effects.
To study anti-tumor effects of exosomes from class II transactivator (CIITA) gene transfected CT26 cells. In this study, we established an MHC class II molecule-expressing murine colon cancer cell line (CT26-CIITA) by transduction of the CIITA gene. Immune effects in vitro and tumor protective results in vivo were tested and monitored. Exosomes from CT26-CIITA cells were found to contain a high level of MHC class II protein. When loaded on dendritic cells (DCs), exosomes from CT26-CIITA cells significantly increased expression of MHC class II molecules, CD86 and CD80, as compared to exosomes from CT26 cells. In vitro assays using co-culture of immunized splenocytes and exosome-loaded DCs demonstrated that CIITA- Exo enhanced splenocyte proliferation and IFN-γ production of CD4+T cells, while inhibiting IL-10 secretion. In addition, compared to exosomes from CT26 cells, CT26-CIITA-derived exosomes induced higher TNF-α and IL-12 mRNA levels. A mouse tumour preventive model showed that CT26-CIITA derived exosomes significantly inhibited tumour growth in a dose-dependent manner and significantly prolonged the survival time of tumour- bearing mice. Our findings indicate that CT26-CIITA-released exosomes are more efficient to induce anti-tumour immune responses, suggesting a potential role of MHC class II-containing tumour exosomes as cancer vaccine candidates.


Catching flame retardants and pesticides in silicone wristbands: Evidence of exposure to current and legacy pollutants in Uruguayan children.
Children are exposed to many potentially toxic compounds in their daily lives and are vulnerable to the harmful effects. To date, very few non-invasive methods are available to quantify children's exposure to environmental chemicals. Due to their ease of implementation, silicone wristbands have emerged as passive samplers to study personal environmental exposures and have the potential to greatly increase our knowledge of chemical exposures in vulnerable population groups. Nevertheless, there is a limited number of studies monitoring children's exposures via silicone wristbands. In this study, we implemented this sampling technique in ongoing research activities in Montevideo, Uruguay which aim to monitor chemical exposures in a cohort of elementary school children. The silicone wristbands were worn by 24 children for 7 days; they were quantitatively analyzed using gas chromatography with tandem mass spectrometry for 45 chemical pollutants, including polychlorinated biphenyls (PCBs), pesticides, polybrominated diphenyl ethers (PBDEs), organophosphorus flame retardants (OPFRs), and novel halogenated flame-retardant chemicals (NHFRs). All classes of chemicals, except NHFRs, were identified in the passive samplers. The average number of analytes detected in each wristband was 13 ±3. OPFRs were consistently the most abundant class of analytes detected. Median concentrations of ΣOPFRs, ΣPBDEs, ΣPCBs, and dichlorodiphenyltrichloroethane (DDT) and its metabolites (dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD)) were 1020, 3.00, 0.52 and 3.79 ng/g wristband, respectively. Two major findings result from this research; differences in trends of two OPFRs (TCPP and TDCPP) are observed between studies in Uruguay and the United States, and the detection of DDT, a chemical banned in several countries, suggests that children's exposure profiles in these settings may differ from other parts of the world. This was the first study to examine children's exposome in South America using silicone wristbands and clearly points to a need for further studies.


New endomyocardial biopsy catheter for the left ventricle.
A new biopsy catheter specifically made for left ventricular endomyocardial biopsy is described. The biopsy catheter is equipped with a device enabling one to bend the tip at will by rotating a knob on the operating handle. The rate of success in obtaining left ventricular biopsy specimens was very high (100%) and there were no serious complications in a group of 10 dogs and in five patients with cardiomyopathy.


Peptides: new signalling molecules in plants.
For many years, our insight into intercellular signalling in plants was based upon our knowledge of the so-called five classical plant hormones--auxin, cytokinin, ethylene, gibberellin and abscisic acid. However, biochemical and genetic studies have identified peptides that play crucial roles in plant growth and development, including defence mechanisms in response to wounding by pests, the control of cell division and expansion, and pollen self-incompatibility. Genome sequencing has revealed many predicted peptide-encoding genes and possible receptors, and a major challenge of the post-genomics era is to determine the function of these molecules.


Eye signs for the neurologist in the Intensive Care Unit.
The eyes are a window to the brain' is a maxim that holds true especially in the intensive care setting. Recognising specific eye signs aids rapid decision-making regarding diagnosis or prognosis. Eye signs play a pivotal role in intensive care for the neurologist. Eye signs have long been considered the best clinical clue for assessment of a comatose patient. In critically ill patients, the recognition of brainstem involvement hinges primarily on eye signs. The ability to recognise and interpret these signs goes a long way towards ensuring proper care of neurological illness in intensive care units. In this article we enumerate the various signs to be assessed in the ocular and periocular structures. We look at the various types of nystagmus and abnormal eye movements which help to localise lesions in the brainstem. This will aid better diagnosis and prognostication. We categorise eye signs as Category 1 or 2 according to whether they are periorbital and ocular signs or oculomotor abnormalities. Category 2 signs are further sub-classified into Category 2a - common and Category 2b - uncommon. Clinical anatomical correlation of specific signs such as ocular dipping has yet to be elucidated. Research that looks into specific eye signs may help with better anatomic correlation and localisation of lesions.


Versatility of uniplanar prearthoplastic distraction osteogenesis in the correction of post-ankylosis facial deformities-a report of five different cases.
Unilateral or bilateral ankylosis can lead to severe micrognathia and facial deformity that requires multiple, often, staged surgical corrections. To date, there is no ideal treatment modality that satisfactorily corrects the complex anatomy, restores the ramal height, and corrects the micrognathia and microgenia. Distraction osteogenesis has been acclaimed as a successful modality for the treatment of such deformities. It is a cost-effective approach with low morbidity and less relapse thus providing better functional and esthetic outcomes. It allows the surgeon to correct the deformity in various planes by using various devices by changing osteotomy designs and vectors, with simultaneous hard tissue and soft tissue reconstruction. Here, we present a series of five cases where different types of distraction osteogenesis were combined with various other procedures to correct post-ankylotic facial asymmetry. In one case, simultaneous maxillo-mandibular distraction [Molina's technique] was used. All patients showed significant improvement in function and esthetics. Outcome assessment was made using clinical photographs and radiographs. Pre-arthroplastic distraction osteogenesis is a versatile cost effective approach that can be customized for every patient based on their needs.