Simultaneous P and N removal in a sequencing batch biofilm reactor: insights from reactor- and microscale investigations.
A sequencing batch biofilm reactor (SBBR) with well established enhanced biological phosphate removal (EBPR) was subjected to higher ammonium concentrations to stimulate and eventually implement simultaneous nitrification. Changes of activity and populations were investigated by a combination of online monitoring, microsensor measurements and fluorescence in situ hybridisation (FISH) of biofilm sections. Nitrification and nitrifying bacteria were always restricted to the periodically oxic biofilm surface. Both, activity and population size increased significantly with higher ammonium concentrations. Nitrification always showed a delay after the onset of aeration, most likely due to competition for oxygen by coexisting P accumulating and other heterotrophic bacteria during the initial aeration phase. This view is also supported by comparing oxygen penetration and oxygen uptake rates under low and high ammonium conditions. Therefore, simultaneous nitrification and phosphorus removal in a P removing SBBR appears to be only possible with a sufficiently long oxic period to ensure oxygen availability for nitrifiers.


Whole genome scanning of a Mediterranean basin hotspot collection provides new insights into olive tree biodiversity and biology.
Olive tree (Olea europaea L. subsp. europaea var. europaea) is one of the most important species of the Mediterranean region and one of the most ancient species domesticated. The availability of whole genome assemblies and annotations of olive tree cultivars and oleaster (O. europaea subsp. europaea var. sylvestris) has contributed to a better understanding of genetic and genomic differences between olive tree cultivars. However, compared to other plant species there is still a lack of genomic resources for olive tree populations that span the entire Mediterranean region. In the present study we developed the most complete genomic variation map and the most comprehensive catalog/resource of molecular variation to date for 89 olive tree genotypes originating from the entire Mediterranean basin, revealing the genetic diversity of this commercially significant crop tree and explaining the divergence/similarity among different variants. Additionally, the monumental ancient tree 'Throuba Naxos' was studied to characterize the potential origin or routes of olive tree domestication. Several candidate genes known to be associated with key agronomic traits, including olive oil quality and fruit yield, were uncovered by a selective sweep scan to be under selection pressure on all olive tree chromosomes. To further exploit the genomic and phenotypic resources obtained from the current work, genome-wide association analyses were performed for 23 morphological and two agronomic traits. Significant associations were detected for eight traits that provide valuable candidates for fruit tree breeding and for deeper understanding of olive tree biology.


Primary malignancy after primary female breast cancer in the South of the Netherlands, 1972-2001.
To assess the risk of second primary cancers among women with previous breast cancer and calculate the excess burden of second cancer in the population. A population-based longitudinal study was conducted using the Eindhoven cancer registry data on 9919 breast cancer patients diagnosed in the period 1972-2000 and followed until 2001. Standardised incidence ratios (SIR) and absolute excess risks (AER) were calculated. In total, 1298 (13%) women developed a second primary cancer. The risk of overall second cancer was higher among breast cancer patients compared to the general population (SIR: 2.8; 95% CI: 2.6-2.9), with an AER of 115 second cancers for every 10,000 breast cancer patients per year. High SIR and AER were observed for breast cancer (SIR: 4.1; 95% CI: 3.8-4.4; AER: 64/10,000 patients/year) and ovarian cancer (SIR: 2.0; 95% CI: 1.5-2.7; AER: 4.5/10,000 patients/year). Our recent data show that women with previous breast cancer have an elevated risk of developing a second cancer compared to the general population. Excess burden for the population is especially high for second cancers of the breast, ovary and colon. Screening may only be justified for breast, ovary and colon cancer in certain groups of patients.


Pyruvate kinase from Lactobacillus bulgaricus: possible regulation by competition between strong and weak effectors.
The pyruvate kinase from Lactobacillus bulgaricus has been purified to homogeneity. The native enzyme is composed of four probably identical subunits of relative molecular mass M(r) 72,000 +/- 4,000. The unique N-terminal amino acid sequence is homologous to those of other pyruvate kinases, especially of type I and II enzymes from Escherichia coli. The saturation of the pyruvate kinase from Lactobacillus bulgaricus is hyperbolic for ADP and cooperative for the other substrate phospho-enol-pyruvate. The enzyme is strongly activated by glucose-6-phosphate, ribose-5-phosphate, and fructose-6-phosphate, which increase the affinity for phospho-enol-pyruvate. These activators seem to stabilize the same state of the enzyme, since their maximum activations are not additive, but their partial activations can be cumulated. Pyruvate kinase is also weakly activated by AMP and inhibited by fructose-1,6-bisphosphate. However, both AMP and fructose-1,6-bisphosphate act as strong inhibitors in the presence of a strong activator, because these weak effectors suppress the activation by glucose-6-phosphate, ribose-5-phosphate, or fructose-6-phosphate. This mutual exclusion of strong and weak effectors, which appears as an original regulatory mechanism, could reflect either the binding of different effectors to different interacting sites or their competition for a unique polyvalent regulatory site in the pyruvate kinase from Lactobacillus bulgaricus.


Refractive Changes Associated with Diabetes Mellitus.
Diabetes mellitus is the most prevalent endocrinedisease in developed countries. In people with diabetes in addition to visionloss caused by diabetic retinopathy transient visual disturbances may occurfrequently caused by refractive changes. These changes in refraction are associated with variations in blood glucose levelsbut the underlying mechanism is still not fully understood. A systematic reviewwith a comprehensive literature search was performed in order to clarify the underlyingmechanisms regarding the connection of glycaemic control and refractive shift. Some studies have shown that increasedblood sugar leads to a myopic shift whilst others demonstrated that this changeis in a hyperopic direction. Changes in visual acuity in patients with diabetescould be an indicator of inadequate metabolic control or even the first sign ofdiabetes mellitus. This reviewgives a brief overview of current research regarding potential mechanisms ofglycemic control influence on refractive error. The aim isto emphasizethe importance ofunderstanding the relationship ofblood glucose concentration and refractive changes as one of thecommon but overlooked diabetic complications.


Consent in medical decision making: the role of communication.
Informed participation in medical decisions is important because it demonstrates respect for the ethical principle of individual autonomy and increases the likelihood of reaching therapeutic goals. Twenty hospitalized patients were randomly selected and observed for six and a half hours to assess the degree to which informed participation was possible with diagnostic and therapeutic procedures. Resident physicians and patients were then interviewed about the rationale, benefit, risk, and alternative for each observed procedure. Commonly observed activities were injecting and giving oral medications, and performing invasive diagnostic procedures. Clinicians' communication involved rationale (43%) more often than benefits (34%), risks (14%), and alternatives (12%). Communication was similar when the procedures proposed were important and risky. Residents' and patients' interviews demonstrated limited congruence in shared understanding of rationale (57%), benefit (45%), risk (19%), and alternatives (25%). These results suggest that clinicians selectively impart information essential for informed patient participation, and highlight areas of clinician-patient communication in need of attention.


Ketamine reduces aversion in rodent pain models by suppressing hyperactivity of the anterior cingulate cortex.
Chronic pain is known to induce an amplified aversive reaction to peripheral nociceptive inputs. This enhanced affective response constitutes a key pathologic feature of chronic pain syndromes such as fibromyalgia. However, the neural mechanisms that underlie this important aspect of pain processing remain poorly understood, hindering the development of treatments. Here, we show that a single dose of ketamine can produce a persistent reduction in the aversive response to noxious stimuli in rodent chronic pain models, long after the termination of its anti-nociceptive effects. Furthermore, we demonstrated that this anti-aversive property is mediated by prolonged suppression of the hyperactivity of neurons in the anterior cingulate cortex (ACC), a brain region well known to regulate pain affect. Therefore, our results indicate that it is feasible to dissociate the affective from the sensory component of pain, and demonstrate the potential for low-dose ketamine to be an important therapy for chronic pain syndromes.


The role of bone marrow evaluation in the staging of patients with otherwise localized, low-risk neuroblastoma.
Bone marrow aspirations and biopsies are standard staging procedures for neuroblastoma because the tumor frequently metastasizes to the bone marrow. The presence of bone marrow metastases indicates stage 4 or 4S neuroblastoma by International Neuroblastoma Staging System (INSS) criteria; these stages are also associated with other metastatic sites of disease. We questioned whether bone marrow studies changed the staging or treatment of children with localized, completely resected tumors if there was no other evidence of metastatic spread. If stage of disease rarely changed with bone marrow results, it might be possible to avoid this procedure in a subset of patients with neuroblastoma. The staging studies of patients with INSS stage 1 (n = 29), 4 (n = 60), and 4S (n = 13) neuroblastoma from two institutions were reviewed. There were no patients upstaged from stage 1 to 4 or 4S by bone marrow metastases alone. Fifty-nine of 60 stage 4 patients had other sites of metastases on imaging studies, the remaining patient had an unresectable primary tumor and marrow disease. All subjects with stage 4S disease had liver metastases. Bone marrow studies did not contribute data that changed the stage of patients who had surgically resectable tumors and no evidence of metastatic spread on imaging studies. When present, metastatic spread to the marrow was associated with advanced local tumors or other sites of metastatic disease. Given the relatively small size of our study population, further studies are warranted that investigate the utility of bone marrow studies for patients who otherwise have INSS stage 1 neuroblastoma.


The increased cost of complications in children with status asthmaticus.
Status asthmaticus is one of the most common causes of admission to a pediatric intensive care unit (PICU). There is little published data, however, examining the complications associated with the treatment of status asthmaticus in children in the PICU. Our hypothesis was that children experiencing a complication would have an increased duration of hospitalization for status asthmaticus. We performed a retrospective review of the complication profile and hospital course of all children admitted to a PICU with status asthmaticus over a 9 years period. Twenty-two (8%) of the 293 children admitted to the ICU with status asthmaticus experienced one or more complications during their treatment. The most common complications were aspiration pneumonia, ventilator-associated pneumonia, pneumomediastinum, pneumothorax, and rhabdomyolysis. Intubated children were significantly more likely than non-intubated children to experience a complication (RR 15.3; 95% CI 6.7-35). Fifteen (42%) of the 36 intubated children experienced a complication. Intubated children experiencing a complication had significantly longer duration of mechanical ventilation (163 +/- 169 hr vs. 66 +/- 65 hr, P = 0.03), ICU length of stay (237 +/- 180 hr vs. 124 +/- 86 hr, P = 0.02) and hospital charges (US dollars 117,184 +/- 111,191 vs. US dollars 38,788 +/- 27,784; P = 0.001) than intubated children not experiencing a complication. In this review, complications were associated with increased morbidity and duration of hospitalization in children with status asthmaticus, particularly in those intubated as part of their therapy. This suggests that intubation and mechanical ventilation itself may increase the risk of developing a complication in this population.


Dietary supplementation of ginger and turmeric improves reproductive function in hypertensive male rats.
Ginger [Zingiber officinale Roscoe (Zingiberaceae)] and turmeric [Curcuma longa Linn (Zingiberaceae)] rhizomes have been reportedly used in folk medicine for the treatment of hypertension. However, the prevention of its complication such as male infertility remains unexplored. Hence, the aim of the present study was to investigate the preventive effects of ginger and turmeric rhizomes on some biomarkers of male reproductive function in L-NAME-induced hypertensive rats. Male Wistar rats were divided into seven groups (n = 10): normotensive control rats; induced (L-NAME hypertensive) rats; hypertensive rats treated with atenolol (10 mg/kg/day); normotensive and hypertensive rats treated with 4% supplementation of turmeric or ginger, respectively. After 14 days of pre-treatment, the animals were induced with hypertension by oral administration of L-NAME (40 mg/kg/day). The results revealed significant decrease in serum total testosterone and epididymal sperm progressive motility without affecting sperm viability in hypertensive rats. Moreover, increased oxidative stress in the testes and epididymides of hypertensive rats was evidenced by significant decrease in total and non-protein thiol levels, glutathione S-transferase (GST) activity with concomitant increase in 2',7'-dichlorofluorescein (DFCH) oxidation and thiobarbituric acid reactive substances (TBARS) production. Similarly, decreased testicular and epididymal NO level with concomitant elevation in arginase activity was observed in hypertensive rats. However, dietary supplementation with turmeric or ginger efficiently prevented these alterations in biomarkers of reproductive function in hypertensive rats. The inhibition of arginase activity and increase in NO and testosterone levels by both rhizomes could suggest possible mechanism of action for the prevention of male infertility in hypertension. Therefore, both rhizomes could be harnessed as functional foods to prevent hypertension-mediated male reproductive dysfunction.


Fulminant hepatitis. A presentation of Wilson's disease.
A boy, 10 years of age, was admitted to the hospital with rapid onset of hepatic failure and died within three weeks. Laboratory and pathological data were consistent with Wilson's disease. We discuss the importance of Wilson's disease in the differential diagnosis of acute liver failure.


Assessing pollution in the Danube River near Novi Sad (Serbia) using several biomarkers in sterlet (Acipenser ruthenus L.).
The response of wild fish to pollutants was studied in sterlet (Acipenser ruthenus L.) collected in 2001 and 2002 at two sampling sites in the Danube River near Novi Sad (Serbia): in the vicinity of the oil refinery and at the Danube-Begec, remote from the oil refinery and considered a reference site. The following biomarkers were measured in sterlet collected from these two sites: the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), and glutathione S-transferase and the induction of CYP1A1 in liver and the activities of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase in serum. The results demonstrated increase in the activity of SOD and GSH-Px in sterlet collected from the Danube-oil refinery (DOR) compared to that from the reference site, while no differences were found in other enzymes. In conclusion, the overall results suggest that an alteration in the activity of SOD and GSH-Px during the observed period reflects the presence of certain prooxidative compounds that can lead to oxidative stress in the liver of sterlet at the DOR site.


Metabolic syndrome in healthy obese, overweight, and normal weight individuals: the Atherosclerosis Risk in Communities Study.
There is recent interest in characterizing the subset of obese (OB) individuals who have healthy metabolic profiles yet only two studies have examined this group prospectively but not in racially diverse populations. We analyzed factors associated with the prevalence and incidence of metabolic syndrome (MetSyn) among individuals grouped by BMI categories in a multi-center, community-based cohort of 14,663 African-American and white men and women aged 45-64 years at recruitment in 1987-1989, the Atherosclerosis Risk in Communities (ARIC) Study. Logistic and proportional hazards regression were utilized to estimate odds ratios (ORs) for the prevalence and hazard ratios (HRs) for incidence of MetSyn with 95% confidence intervals (CIs). At visit 1, MetSyn was positively associated with age, female gender, African-American race, and inversely related to education, associations being more pronounced among normal weight (NW) subjects. Among those without MetSyn at visit 1, OB subjects were more likely to develop MetSyn compared with NW (HR (95% CI): 4.53 (4.09-5.01)). Several factors were associated with incident MetSyn among NW, including older age (per year: 1.05 (1.03-1.06)), female gender (vs. male: 1.29 (1.10-1.52)), heavy alcohol intake (vs. never: 0.75 (0.59-0.94)), and physical activity (tertile 3 vs. tertile 1: 0.71 (0.58-0.86)) but not OB. Weight gain (>5%) was also more highly associated with MetSyn in NW (1.61 (1.28-2.02)) compared with OB (1.01 (0.85-1.20)). We conclude that lifestyle factors may play a stronger role in the development of MetSyn in NW individuals compared with OB and that metabolically healthy obesity may not be a stable condition.


Effect of lipoxygenase inhibitors on Ca2(+)-induced constriction of the rabbit ear artery.
1. The effects of nafazatrom, nordihydroguaiaretic acid (NDGA) and quercetin on Ca2(+)-induced vasoconstriction were studied in isolated rabbit ear arteries. 2. The arteries were perfused with Ca2(+)-free and high K+ (75 mM) Krebs bicarbonate buffer. Constriction of the artery was induced by addition of Ca2+ (1.5 mM) to the perfusion fluid. 3. Indomethacin (1 microM) did not alter the response to Ca2+. 4. Nafazatrom (2 or 5 microM) produced a concentration-dependent inhibition of the constrictor response to Ca2+ ranging from 4 to 23% after 1 hr of perfusion and 26 to 62% after 3 hr. 5. Similar effects were obtained with NDGA and quercetin (0.5 and 1 microM). 6. The inhibitory effects of nafazatrom and quercetin were antagonized by Ca2+ (2.5 mM) or Bay K 8644 (1 microM), a calcium channel activator. 7. Ca2(+)-induced contractions recovered within 30 min after discontinuation of perfusion with quercetin, whereas nafazatrom and NDGA had longer durations of action. 8. These results suggest that inhibitors of lipoxygenase antagonized Ca2(+)-induced vasoconstriction and that products of lipoxygenase metabolism may facilitate Ca2+ entry into vascular smooth muscle cells.


Incidence of traumatic brain injuries in head-injured children with seizures.
Incidence and short-term outcomes of clinically important traumatic brain injury (ciTBI) in head-injured children presenting to ED with post-traumatic seizure (PTS) is not described in current literature. Planned secondary analysis of a prospective observational study undertaken in 10 Australasian Paediatric Research in Emergency Departments International Collaborative (PREDICT) network EDs between 2011 and 2014 of head-injured children <18 years with and without PTS. Clinical predictors and outcomes were analysed by attributable risk (AR), risk ratios (RR) and 95% confidence interval (CI), including the association with Glasgow Coma Scale (GCS) scores. Of 20 137 head injuries, 336 (1.7%) had PTS with median age of 4.8 years. Initial GCS was 15 in 268/336 (79.8%, AR -16.1 [95% CI -20.4 to -11.8]), 14 in 24/336 (7.1%, AR 4.4 [95% CI 1.6-7.2]) and ≤13 in 44/336 (13.1%, AR 11.7 [95% CI 8.1-15.3]) in comparison with those without PTS, respectively. The ciTBI rate was 34 (10.1%) with PTS versus 219 (1.1%) without PTS (AR 9.0 [95% CI 5.8-12.2]) with 5/268 (1.9%), 6/24 (25.0%) and 23/44 (52.3%) with GCS 15, 14 and ≤13, respectively. In PTS, rates of admission ≥2 nights (34 [10.1%] AR 9.0 [95% CI 5.8-12.3]), intubation >24 h (9 [2.7%] AR 2.5 [95% CI 0.8-4.2]) and neurosurgery (8 [2.4%] AR 2.0 [95% CI 0.4-3.7]), were higher than those without PTS. Children with PTS and GCS 15 or 14 had no neurosurgery, intubations or death, with two deaths in children with PTS and GCS ≤13. PTS was uncommon in head-injured children presenting to the ED but associated with an increased risk of ciTBI in those with reduced GCS on arrival.


Ischemic Stroke in Patients With Malignancy.
Approximately one-quarter to one-third of patients with ischemic stroke have an embolic stroke of undetermined source (ESUS). An estimated 5% to 10% of patients with ESUS have an active cancer diagnosis. Presence of cancer potentially increases the risk of acute ischemic stroke through various mechanisms such as cancer-related hypercoagulability, intracranial tumors leading to an arterial compression, or intracardiac tumors leading to cardioembolism. Certain cancer therapeutics can also contribute to risk of ischemic stroke. Multiple vascular lesions involving bilateral anterior and posterior circulations, high plasma D-dimer levels, and elevated inflammatory markers might suggest cancer-related ischemic stroke. Patients with ischemic stroke related to malignancy are also at higher risk of stroke recurrence, early neurologic deterioration, and mortality. Cancer screening in acute ischemic stroke patients can be considered when no other etiology for stroke can be established and clinical history such as tobacco use, unexplained constitutional symptoms such as fever or night sweats, or unexplained weight loss suggests an underlying malignancy. Selection of antithrombotics for secondary stroke prevention remains controversial as clinical trial data for use of antiplatelet therapy vs anticoagulation in ESUS and cancer patients is limited. Future clinical trials should specifically focus on patients with ischemic stroke related to malignancy are needed to guide appropriate therapeutic agent selection.


Substance P stimulates the release of Met5-enkephalin-Arg6-Phe7 and Met5-enkephalin from rat spinal cord.
Substance P (10(-6) M) injected in the fluid perfusing the subarachnoidal spaces of the spinal cord can release met5-enkephalin (YGGFM) and met5-enkephalin-Arg6-Phe7 (YGGFMRF) from spinal cord. This effect is Ca2+ dependent and can be blocked by the substance P antagonist, D-pro2, -D Trp7,9-substance P. The release of YGGFM and YGGFMRF was not observed when substance P was replaced by substance P1-9. These results suggest that substance P receptors are involved in triggering the release of enkephalins.


Acute pulmonary toxicity to nitrofurantoin.
Nitrofurantoin is a widely prescribed antibiotic used for the treatment of urinary tract infections. In some patients it can produce an acute pulmonary reaction ranging from mild dyspnea to noncardiogenic pulmonary edema. Symptoms include fever, dyspnea, chills, cough, and chest pain. Physical examination generally reveals an acutely ill, extremely apprehensive patient in varying degrees of respiratory distress. Fever is usually present and there is an increase in heart rate and respiratory rate. Cyanosis, rales, and a maculopapular rash are common findings. Laboratory studies typically demonstrate a leukocytosis with eosinophilia, varying degrees of hypoxia and hypocapnia, and a mild to moderate elevation of the erythrocyte sedimentation rate. The chest x-ray study may be normal but more often demonstrates bilateral lower lobe interstitial infiltrates frequently accompanied by pleural effusions. Treatment in the majority of cases requires only stopping the drug, but steroids, bronchodilators, or antihistamines may be used in selected cases. Once the diagnosis is made and the drug withdrawn, prognosis for full recovery is excellent.


Skeletal phenotypes in adult patients with osteogenesis imperfecta-correlations with COL1A1/COL1A2 genotype and collagen structure.
Osteogenesis imperfecta (OI) is characterized by a high fracture rate and great heterogeneity. This cross-sectional study presents skeletal investigations and protein analyses in 85 adult OI patients. We find significant differences in bone mass, architecture, and fracture rate that correlate well with the underlying biochemical and molecular abnormalities. OI is a hereditary disease characterized by compromised connective tissue predominantly caused by mutations in collagen type 1 (COL-1) encoding genes. Widespread symptoms reflect the ubiquity of COL-1 throughout the body. The purpose of this study was to improve our understanding of clinical manifestations by investigating anthropometry and skeletal phenotypes (DXA, HRpQCT) in an adult OI population and compare the findings to underlying COL-1 genotype and structure. The study comprised 85 OI patients aged 45 (19-78) years, Sillence type I (n = 58), III (n = 12), and IV (n = 15). All patients underwent DXA, HRpQCT, spine X-ray, biochemical testing, and anthropometry. COL1A1 and COL1A2 were sequenced and 68 OI causing mutations identified (46 in COL1A1, 22 in COL1A2). Analysis of COL-1 structure (quantitative/qualitative defect) by SDS-PAGE was performed in a subset (n = 67). A qualitative collagen defect predisposed to a more severe phenotype with reduced aBMD, more fractures, and affected anthropometry compared to patients with a quantitative COL-1 defect (p < 0.05). HRpQCT revealed significant differences between patients with OI type I and IV. Patients with type I had lower vBMD (p < 0.005), thinner cortexes (p < 0.001), and reduced trabecular number (p < 0.005) compared to patients with type IV indicating that HRpQCT may distinguish type I from type IV better than DXA. The defective collagen in patients with OI has pronounced effects on the skeleton. The classical OI types based on the clinical classification show profound differences in bone mass and architecture and the differences correlate well with the underlying biochemical and molecular collagen abnormalities.


The relationship between menopausal hormone therapy and keratinocyte carcinoma: A review.
Keratinocyte carcinoma (KC) is the most common malignancy in the United States. The two most common forms of KC are basal cell carcinoma and squamous cell carcinoma (SCC), which account for 80% and 20% of cases, respectively. There are many well-established risk factors for KC, but a more controversial risk factor for KC development is menopausal hormone therapy (MHT). This review synthesizes existing information on this topic and identifies knowledge gaps for future study. A systematic review of the literature using the Medical Subject Headings terms "menopausal hormone therapy; skin neoplasms" was conducted in the PubMed database from March 19, 2018 to April 1, 2018. This yielded 168 articles, case reports, and reviews, which were further refined for inclusion during the development of this manuscript. Additional articles were identified from cited references. Four studies pertaining to this topic were identified. The results were evaluated in the context of these studies' strengths and weaknesses. MHT contributes to an increased risk of basal cell carcinoma in Caucasian subjects and may make these tumors histologically more aggressive. There is not enough evidence to make a conclusion with regard to a potential relationship between MHT and SCC. However, one study suggested an increased risk of SCC with MHT use and another demonstrated a temporal association with prolonged MHT use and increased risk of SCC development. Ever users of MHT should be screened more frequently for KC. This issue is of importance to dermatologists because patients who receive earlier diagnoses of KC will have a better opportunity to pursue treatment.


Home range and activity patterns of male red deer (Cervus elaphus L.) in the alps.
From 1978 to 1981 in the Bavarian Alps (Southern West Germany) the home range and activity patterns of nine male red deer have been studied using radio-telemetry. The home range patterns definetely change with age. Younger stags first follow the patterns of their mothers, then often emigrate from these home ranges and establish new ones elsewhere. Except for the change in range at about 21/2 years of age, these patterns seem to be very constant in both spatial as well as seasonal position and the size of the home ranges. Winter and rutting ranges are relatively small, averaging 113 ha and 134 ha, respectively, whereas the mean size of the home ranges used from spring to autumn amounts to some 386 ha. Just as do the home range patterns, so also do activity patterns exhibit a marked annual cycle. The daily sum total of activity varies from about 9 h in winter to some 15 h in summer. The daily distribution of activity reveals a typical bimodal 24-h rhythm which in the course of the year also shows modifications according to the seasonally varying LD-ratio. In the discussion, earlier results on female red deer are compared to those of this study. Notable differences between sexes occur in the home range patterns and the annual cycle of daily activity.


Metabolic activation of mutagenic N-hydroxyarylamines by O-acetyltransferase in Salmonella typhimurium TA98.
A new enzymatic activation of mutagenic N-hydroxyarylamines is described. An acetyl-CoA dependent enzyme that can activate 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1) to a reactive species capable of binding to nucleic acid was found in a cell-free extract of Salmonella typhimurium TA98 but not in that of TA98/1,8-DNP6, which shows low sensitivity to the mutagenic activity of N-OH-Glu-P-1. The enzyme was partially purified by streptomycin treatment, ammonium sulfate precipitation, DEAE-cellulose chromatography, and gel filtration chromatography of Sephadex G-150. Its molecular weight was estimated to be approximately 48,000. The directly mutagenic N-hydroxyarylamines, such as N-OH-Glu-P-1, 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-OH-Trp-P-2), and N-hydroxy-2-aminofluorene (N-OH-AF), were transformed to reactive derivatives by partially purified enzyme in the presence of acetyl-CoA. The Km value for acetyl-CoA was calculated to be 3.3 microM. No acetyl residue, however, was incorporated into nucleic acid adducts. The enzymatic product of N-OH-Glu-P-1 bound most efficiently to polyguanylic acid among four polynucleotides. The enzyme did not show the N,O-acetyltransfer activity of N-hydroxyacetylaminofluorene (N-OH-AAF). These results indicate that the enzymatic product of N-hydroxyarylamine is N-acetoxyarylamine, and that this enzyme can be called acetyl-CoA:N-hydroxyarylamine O-acetyltransferase. O-Acetyltransferase activity was inhibited by SH-blocking agents, several phenolic compounds, such as pentachlorophenol and 1-nitro-2-naphthol, and an antibiotic thiolactomycin. S. typhimurium mutation studies suggested that the O-acetyltransferase functions as an enzyme activating certain N-hydroxyarylamines within bacterial cells and is involved in the formation of mutants.


Coastal survey data for Perranporth Beach and Start Bay in southwest England (2006-2021).
Records of beach morphologic change and concurrent hydrodynamic forcing are needed to understand how coastlines in different environments change over time. This submission contains data for the period 2006 to 2021, for two contrasting macrotidal environments in southwest England: (i) cross-shore dominated, dissipative, sandy Perranporth Beach, Cornwall; and (ii) longshore-dominated, reflective gravel beaches within Start Bay, Devon. Data comprise monthly to annual beach profile surveys, annual merged topo-bathymetries, in addition to observed and numerically modelled wave and water levels. These data provide a valuable resource for modelling the behaviour of coastal types not covered by other currently available datasets.


Beliefs and perceptions of patient safety event reporting in a Canadian Emergency Department: a qualitative study.
Patient safety events (PSEs) are unwanted or unexpected events that occur during medical care. High cognitive loads and frequent interruptions make emergency departments (EDs) uniquely error prone environments. Yet, frontline clinicians rarely report PSEs using incident reporting systems. The incidence, severity, and preventability of PSEs thus remain poorly understood, and contributing factors are understudied. We sought to understand ED staff beliefs and perceptions about their PSE reporting system and what features they believe are important in such a system. We conducted a qualitative study among healthcare providers working in the ED and departmental leadership. We recruited participants via email and held a series of interviews, focus groups, and participatory workshops. We iteratively analyzed the data using the constant comparative method and used thematic analysis to establish themes. 50 participants attended at least one focus group, interview, or workshop. Participants perceived that PSE reporting through formal channels in the ED was challenging. Clinicians had an inherent desire to report PSEs and do so through numerous informal channels, yet underreported in formal reporting systems. The current PSE reporting system did not meet frontline staff needs and was viewed as ineffective in improving care quality and safety. We identified three key features for an improved PSE reporting system: (1) clear definitions; (2) transparency; and (3) simplicity. In this study, we have identified ideal features for PSE reporting processes to meet the needs of both frontline staff and departmental leadership based on perceptions of current PSE reporting practices. Improved PSE reporting processes have the potential to increase PSE reporting in the ED overall, increasing the availability of information about PSEs to support quality improvement and improve patient safety.


Fludarabine, cytarabine, and mitoxantrone (FLAM) for the treatment of relapsed and refractory adult acute lymphoblastic leukemia. A phase study by the Polish Adult Leukemia Group (PALG).
Outcome of adults with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission (CR) or who relapse soon after initial response is poor. The goal of this phase II study by the Polish Adult Leukemia Group (PALG) was to evaluate safety and efficacy of a new salvage regimen (FLAM) consisting of sequential fludarabine, cytarabine, and mitoxantrone. Fifty patients were included with primary (n = 13) or secondary (n = 5) refractoriness, early (<12 months) first relapse (n = 15), first relapse after hematopoietic cell transplantation (HCT) regardless CR duration (n = 13), and second or subsequent relapse (n = 4). Median age was 31(18-60) years, 28% of patients were bcr/abl-positive. CR rate equaled 50% and was significantly higher for patients in whom FLAM was administered as a second-line therapy compared to those more heavily pre-treated (66 vs 13%, p = 0.02). Seventeen patients had leukemia regrowth after initial cytoreduction, whereas, eight patients died in aplasia. The incidence of early death was higher in patients aged > or =40 years compared to the younger subgroup (33 vs 8%, p=0.03). Septic infections were the most frequent severe complication. At 3 years, the probability of disease-free survival for patients who achieved CR equaled 16%. Seven patients underwent allogeneic HCT. FLAM regimen is feasible for relapsed and refractory adults with ALL and could be recommended in particular for younger patients as a second-line treatment. However, as the remission duration is short, allogeneic HCT (alloHCT) should be considered as soon as possible.


Differences in pathological characteristics and prognosis of clinical A2 prostatic cancer from A1 and B disease.
A retrospective study was done of 53 cases of clinical stages A1 to B2 prostatic carcinomas staged by pelvic lymphadenectomy. The study compared the histologic differentiation, degree of lymphocytic infiltration, incidence of lymph node metastases and type of cellular response of clinical stage A2 to stages A1 and B disease. The available data pertaining to the incidence and survival of patients with stage A2 prostatic carcinoma were analyzed. Our study indicates that 1 of every 3 unsuspected carcinomas is of clinical stage A2. The stage A2 tumors are diffused, with a higher degree of undifferentiation and a higher incidence of lymph node metastases than tumors classified clinically as stages A1 and B1. Also the survival of patients with clinical stage A2 tumors is lower than the survival of patients with clinical stage B1 disease. Clinical stage A2 tumors are more advanced biologically than clinical stage B1 tumors.


COVID-19 vaccine hesitancy among older adult Thai Muslim people: A case-control study.
The highest death toll during the COVID-19 pandemic in Thailand was among unvaccinated older adults. Deaths among older adults in Narathiwat Province were related to a lower COVID-19 vaccination rate. This study explored the factors influencing COVID-19 vaccination hesitancy in a Muslim community with low vaccination rates. A case-control study was conducted with participants assigned to the unvaccinated "case" group and the vaccinated "control" group. The sample was Thai older adults who practiced Islam and lived in Narathiwat Province. Purposive sampling was conducted by selecting a case house and finding the control around the case house in a 1:2 ratio. This study included 141 participants with a median age of 67 years (interquartile range [IQR], 8). More than 80% of both groups were retired and lived with their extended relatives. More participants in the vaccinated group believed that vaccines could prevent death from COVID-19 than in the unvaccinated group. In the multivariable analysis, factors related to the low perceived importance of the COVID-19 vaccination (odds ratio [OR] = 2.63) and a lack of vaccine recommendation from religious leaders (OR = 4.67) significantly influenced COVID-19 vaccination refusal. The COVID-19 guidance from religious leaders and the perceived importance of COVID-19 vaccination influence vaccination uptake among Muslim older adults in Thailand.


Impact of the method and success of pharyngeal reconstruction on the outcome of treating laryngeal and hypopharyngeal cancers with pharyngolaryngectomy: A national analysis.
Surgical treatment of cancers that arise from or invade the hypopharynx presents major reconstructive challenges. Reconstructive failure exposes the airway and neck vessels to digestive contents. We performed a national N = near-all analysis of the administrative dataset to identify pharyngolaryngectomies in England between 2002 and 2012. Information about morbidity, pharyngeal closure method and post-operative complications was derived. There were 1589 predominantly male (78%) patients whose mean age at surgery was 62 years. The commonest morbidities were hypertension (24%) and ischemic heart disease (11%). For 232 (15%) patients, pharyngolaryngectomy was performed during an emergency admission. The pharynx was closed primarily in 551 patients, with skin or muscle free or pedicled flaps in 755 patients and with jejunum and gastric pull-up in 123 and 160 patients, respectively. In-hospital mortality rate was 6% and was significantly higher in the gastric pull-up group (11%). Reconstructive failure had an odds ratio of 6.2 [95% confidence interval (CI) 2.4-16.1] for in-hospital death. The five-year survival was 57% and age, morbidities, emergency surgery, gastric pull-up, major acute cardiovascular events, renal failure and reconstructive failure independently worsened prognosis. Patients who underwent pharyngeal reconstruction with radial forearm or anterolateral thigh flaps had lower mortality rates than patients who had jejunum flap reconstruction (hazard ratio = 1.50 [95% CI 1.03-2.19]) or gastric pull-up (hazard ratio = 1.92 [95% CI 1.32-2.80]). Pharyngolaryngectomy carries a high degree of risk of morbidity and mortality. Reconstructive failure worsens short- and long-term prognosis, and the use of cutaneous free flaps appears to improve survival.


Teratoid Wilms' tumor of kidney with neural tissue predominant: Case report with review of literature.
Wilms' tumor is most common pediatric renal tumor. Teratoid Wilms' tumor is a variant of Wilms' tumor, in which heterologous tissue predominates. Most commonly, epithelial and mesenchymal tissue present as heterologous component. Biological behavior of this tumor is very different from usual Wilms' tumor. They do not respond to chemotherapy and radiotherapy. We are presenting another case of teratoid Wilms' tumor in a 4-year female child with a review of literature.


Repeated measures of Heparin-binding protein (HBP) and procalcitonin during septic shock: biomarker kinetics and association with cardiovascular organ dysfunction.
Heparin-binding protein (HBP) is a neutrophil-derived pro-inflammatory protein, an inducer of endothelial dysfunction and vascular permeability and a promising prognostic biomarker in sepsis. This exploratory study aims to describe the kinetics of plasma HBP during septic shock and investigate an association between repeated measures of HBP concentration and cardiovascular organ dysfunction severity. We included patients at or above 18 years with suspected septic shock on admission to the intensive care unit (ICU) during 2014 and 2016 to 2018. Plasma samples were collected from ICU admission and every 4 h for 72 h or until death or ICU discharge and batch analysed for HBP. Mean arterial blood pressure (MAP) and noradrenaline dose (NA dose) were recorded at each sampling time point, and systemic vascular resistance index (SVRI) was recorded when available from non-invasive monitoring. The association between HBP, NA dose, MAP and SVRI was assessed respectively using mixed-effects linear regression models. Procalcitonin (PCT) was used as a comparator. A total of 24 patients were included. The kinetics of plasma HBP was highly variable over time, with occasional >2-fold increases and decreases in between 4-h measurements. Every 100 ng/mL increase in HBP corresponded to a 30% increase in NA dose in a crude model (95% CI 3 to 60%, p = 0.03, nobs = 340), a 1.4-mmHg decrease in MAP in an adjusted model (95% CI - 1 to - 2.3 mmHg, p = 0.04) or a 99 dyne s cm-5 m-2 decrease in SVRI in another adjusted model (95% CI - 36 to - 162, p = 0.002, npat = 13). PCT had a stronger association to NA dose than HBP in a crude model but was not significantly associated to NA dose, MAP or SVRI in any time-adjusted model. Plasma HBP displayed a highly variable kinetic pattern during septic shock and was significantly associated to cardiovascular organ dysfunction severity over time.


Voxel-wise analysis of diffusion tensor MRI improves the confidence of diagnosis of corticobasal degeneration non-invasively.
Corticobasal degeneration (CBD) presents with symptoms that often overlap with other neurological conditions. In many cases, diagnosis, prognosis and consequent clinical management remain uncertain. Structural and functional asymmetric brain changes represent the most consistent imaging findings that may assist in CBD diagnosis. Diffusion Tensor MRI (DT-MRI) is a quantitative technique that allows microscopic tissue abnormalities to be non-invasively assessed in vivo. A single case of clinically suspected CBD with symmetric diffuse brain atrophy on conventional-MRI scans was studied using DT-MRI by voxel-wise comparison with eight healthy subjects. The lateralized distribution of DT-MRI abnormalities was consistent with clinical features providing a substantial support to the diagnosis.


Exploring circannual rhythms and chronotype effect in patients with Obsessive-Compulsive Tic Disorder (OCTD): A pilot study.
The aim of this study was to test, through a chronobiologic approach, the existence of a significant circannual rhythm of tics and obsessive-compulsive symptoms in patients with Obsessive-Compulsive Tic Disorder (OCTD). The chronotype effect on tics and OC symptoms during seasons was also studied. Patients with a diagnosis of OCTD (N = 37; mean age = 18.78 ± 8.61) underwent four clinical evaluations: Winter (WIN), Spring (SPR), Summer (SUM) and Autumn (AUT). Tics were evaluated through Yale Global Tic Severity Scale (YGTSS) and OC symptoms through Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Patients' chronotype was assessed by the Horne-Ostberg morningness-eveningness questionnaire (MEQ), which categorizes subjects according to the individuals'chronotype, being morning-type, evening-type, and neither-type. A statistically significant circannual rhythm was observed for OC symptoms (p = 0.007), with the acrophase occurring between AUT and WIN. Y-BOCS differed along the year (p = 0.0003 and η2p = 0.40) with lower results in SUM compared to WIN (p < 0.05) and AUT (p < 0.01). Tics displayed no circannual rhythm and YGTSS scores were comparable among seasons. Patients were classified as 15 morning-types (40.5%) 15 neither-types (40.5%) and 7 evening-types (19.0%). YGTSS data were similar for all chronotypes while Y-BOCS results were greater during SUM in evening-types than morning-type patients (p < 0.05; 15.7 ± 5.2 vs 3.4 ± 6.0). It is essential to investigate the existence of tics and OC symptoms circannual rhythms over the course of more than one year with a larger sample. OC symptoms displayed a significant circannual rhythm and were influenced by patients' chronotype. On the contrary, tics resulted similar among seasons and chronotypes.


FDG-PET scans in patients with Kraepelinian and non-Kraepelinian schizophrenia.
We recruited 14 unmedicated patients with Kraepelinian schizophrenia (12 men and 2 women; mean age = 47 years old), 27 non-Kraepelinian patients (21 men and 6 women; mean age = 36.4 years old) and a group of 56 age- and sex-matched healthy volunteers. FDG positron emission tomography and MRI scans were coregistered for both voxel-by-voxel statistical mapping and stereotaxic regions of interest analysis. While both Kraepelinian and non-Kraepelinian patients showed equally lower uptake than healthy volunteers in the frontal lobe, the temporal lobes (Brodmann areas 20 and 21) showed significantly greater decreases in Kraepelinian than in non-Kraepelinian patients. Kraepelinian patients had lower FDG uptake in parietal regions 39 and 40, especially in the right hemisphere, while non-Kraepelinian patients had similar reductions in the left. Only non-Kraepelinian patients had lower caudate FDG uptake than healthy volunteers. While both patient groups had lower uptake than healthy volunteers in the medial dorsal nucleus of the thalamus, Kraepelinian patients alone had higher uptake in the ventral nuclei of the thalamus. Kraepelinian patients also showed higher metabolic rates in white matter. Our results are consistent with other studies indicating that Kraepelinian schizophrenia is a subgroup of schizophrenia, characterized by temporal and right parietal deficits and normal rather than reduced caudate uptake. It suggests that Kraepelinian schizophrenia may be more primarily characterized by FDG uptake decreased in both the frontal and temporal lobes, while non-Kraepelinian schizophrenia may have deficits more limited to the frontal lobe. This is consistent with some neuropsychological and prognosis reports of disordered sensory information processing in Kraepelinian schizophrenia in addition to deficits in frontal lobe executive functions shared with the non-Kraepelinian subtype.


Room-temperature storage of microalgae in water-in-oil emulsions: influence of solid particle type and concentration in the oil phase.
Water-in-oil emulsions containing silica nanoparticles (Aerosil R974) have the potential to stabilize microalgae for long-term storage. Studies were completed to determine if smectite clays could be used as an alternative to Aerosil R974. Emulsions were prepared with Aerosil R974, and hectorite and bentonite clays in the continuous phase and Chlorella sorokiniana was added to the aqueous phase to monitor the effects of solid particles on emulsion stability. Biological stability (cell viability) was determined using cell density measurements, and physical stability was measured from water droplet size distributions obtained by light scattering measurements and by examining phase separation over time. Measurements were also made to determine the effects of particles in the oil phase on emulsion viscosity. Particle concentrations greater than 0.25 wt% in the oil phase were required for maintaining physical stability. In emulsions containing 1 wt% solid particles and microalgae, biological stability of cells could be sustained for 340 days, regardless of particle type. At 1 wt% particles in the oil phase, apparent viscosity was 165% greater for samples containing hectorite and bentonite clays compared to samples containing Aerosil R974. The higher viscosity would need to be considered in large-scale production of emulsions for commercial application.


Non-invasive prenatal diagnosis and screening for monogenic disorders.
Cell-free fetal DNA (cffDNA) can be detected in the maternal circulation from 4 weeks gestation, and is present with cell-free maternal DNA at a level of between 5 % and 20 %. Cell-free DNA (cfDNA) can be extracted from a maternal blood sample and, although it is not possible to separate the fetal from the maternal cfDNA, it has enabled non-invasive prenatal diagnosis (NIPD) without the associated miscarriage risk that accompanies invasive testing. NIPD for monogenic diseases was first reported in 2000 and since then there have been many proof of principle studies showing how analysis of cfDNA can provide a definitive diagnosis early in pregnancy for a wide range of single gene diseases. Testing for a number of these diseases has been available in the UK National Health Service (NHS) since 2012. This review highlights the main techniques that are being used for NIPD and discusses the technical limitations of the methods, as well as the advances that are being made to overcome some of the issues. NIPD is technologically challenging for a number of reasons. Firstly, because it requires the detection of low level fetal variants in a high maternal background. For de novo and paternally-inherited variants this has been achieved through the use of techniques such as next-generation sequencing (NGS) and digital PCR to detect variants in the cffDNA that are not present in the maternal cfDNA. However, for maternally-inherited variants this is much more challenging and relies on dosage-based techniques to detect small differences in the levels of mutant and wild-type alleles. Alongside the technical advances that are making NIPD more widely available in both the public healthcare and commercial settings, it is crucial that we continue to monitor the social and ethical impact to ensure that patients are being offered safe and accurate testing.


Development of a Core-Shell Heterojunction TiO2 /SrTiO3 Electrolyte with Improved Ionic Conductivity.
The front cover artwork is provided by Prof. Faze Wang's group at the Southeast University. The built-in electric field created by the semiconductor heterostructure confines the proton transport on the surface layer of the nanocomposite core-shell heterostructure imparting faster ion transport and lower activation energy. Read the full text of the Research Article at 10.1002/cphc.202200170.


Assessment of the genotoxic effects of methyl chloride in human lymphoblasts.
The activity of methyl chloride was measured in 4 genotoxicity assays. In an established human lymphoblast line, a 3-h treatment with 0-5% methyl chloride resulted in a dose-related increase in mutant fraction at the thymidine kinase locus and induction of sister-chromatid exchange. No increase in DNA damage, as measured by alkaline elution, was detected in the lymphoblasts at concentrations of methyl chloride shown to be mutagenic. Also, a concentration-related increase in 8-azaguanine-resistant fraction in Salmonella typhimurium was observed following a 3-h treatment with atmospheres containing 0-20% methyl chloride. Thus, methyl chloride is a weak, direct-acting mutagen for bacteria and human cells in culture.


Polycystic ovary syndrome and obesity do not affect vascular parameters related to early atherosclerosis in young women without glucose metabolism disturbances, arterial hypertension and severe abnormalities of lipid profile.
The aim of this study was to evaluate the influence of polycystic ovary syndrome (PCOS) and obesity on vascular parameters related to early atherosclerosis (VP-EA) [brachial flow-mediated dilation (FMD), carotid intima-media thickness (CIMT) and carotid arterial compliance (CAC)] in women with minor cardiovascular risk factors (CVRFs). Twenty-five young women with PCOS and 23 eumenorrheic women matched for body mass index (BMI) were studied. The women were subdivided according to BMI and PCOS status, and comparisons were done between PCOS and Control group, regardless of BMI, and between Obese and Lean group, regardless of the presence of PCOS. Insulin resistance was higher in PCOS-group than in control-group and in obese-group than in lean-group. The median of all VP-EA evaluated were similar between PCOS-group and Control-group [FMD: 6.6 versus 8.4% (p = NS); CIMT: 48.0 versus 47.0 mm.10-2 (p = NS); CAC: 6.2 versus 5.6N-1.m4.10-10 (p = NS)] and between obese-group and lean-group [FMD: 7.8 versus 6.6% (p = NS); CIMT: 48.0 versus 47.0 mm.10-2 (p = NS); CAC: 5.7 versus 6.3N-1.m4.10-10 (p = NS)]. These results suggest that PCOS and obesity do not affect VP-EA in women with minor CVRFs.


The absence of type II collagen and changes in proteoglycan structure of hyaline cartilage in a case of Langer-Saldino achondrogenesis.
Structural analysis of hyaline cartilage extracellular matrix components from the ribs and knee joint of a stillborn female with type II achondrogenesis was carried out. The absence of type II collagen, a decrease in the amount of proteoglycans (PG), and structural changes in PG, namely, increased electrophoretic mobility of PG, lower relative content of chondroitin 4-sulfate (Ch4-S), lower molecular weight and decreased total chondroitin sulfate (ChS) sulfation, were detected. Increased amounts of type I and type III collagens, atypical for hyaline cartilage, were revealed. Among the link proteins (LPs), a large protein with a mol. wt. of 48 kDa was predominant. Molecular and cellular mechanisms of the pathogenesis of achondrogenesis ("chondrogenesis imperfecta") are discussed. The data obtained suggest that the primary defect in type II achondrogenesis involves ChS or type II collagen synthesis.


Metabolomics-based component profiling of hard and semi-hard natural cheeses with gas chromatography/time-of-flight-mass spectrometry, and its application to sensory predictive modeling.
Gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS) was used to analyze hydrophilic low molecular weight components, including amino acids, fatty acids, amines, organic acids, and saccharides, in cheese, and the sensometric application for practical metabolomic studies in the food industry is described. Derivatization of target analytes was conducted prior to the GC/TOF-MS analysis. Data on 13 cheeses, six Cheddar cheeses, six Gouda cheeses and one Parmigiano-Reggiano cheese, were analyzed by multivariate analysis. The uniqueness of the Parmigiano-Reggiano cheese metabolome was revealed. Principal component analysis (PCA) showed no grouping of the Cheddar cheeses and Gouda cheeses according to production method or country of origin. The PCA loading plot confirms that many amino acids contribute positively to PC1, suggesting that PC1 is closely related to degradation of proteins, and that lactic acid contributed positively to PC2, whereas glycerol contributed negatively to PC2, suggesting that factors regarding degradation of carbohydrates and fats were expressed in PC2. Partial least squares (PLS) regression models were constructed to predict the relationship between the metabolite profile and two sensory attributes, "Rich flavor" and "Sour flavor", which were related to maturation. The compounds that play an important role in constructing each sensory prediction model were identified as 12 amino acids and lactose for "Rich flavor", and 4-aminobutyric acid, ornithine, succinic acid, lactic acid, proline and lactose for "Sour flavor". The present study revealed that metabolomics-based component profiling, focusing on hydrophilic low molecular weight components, was able to predict the sensory characteristics related to ripening.


Enteral nutrition for severe malnutrition Crohn's disease patient: Case report.
Crohn's disease (CD) is a chronic systemic inflammatory disease with indefinite remission and relapse cycles, which can result in a high incidence rate of malnutrition. There has been increasing clinical interest in enteral nutrition (EN) as an adjunct treatment for CD. This report aims to present a case of a severely malnourished CD patient given EN support in combination with conventional infliximab (IFX) treatment. A 42-year-old CD patient with severe malnutrition. She once weighted 27.5 kg (BMI 11.4 kg/m) with hyponatremia, which may cause sudden death at any time. In this study, the diagnosis of CD made by our gastroenterologist was based on integrating patient symptoms, radiologic findings, and biopsy results. The patient had no differential diagnosis. The patient received EN support and actively followed up for more than 2 years. The patient also received IFX treatment and four surgeries on an as-needed basis to manage her symptoms. The patient's inflammation and symptoms were finally improved by a combination of enteral nutrition and IFX, and her body weight increased to 44 kg. The jejunal feeding tube was the starting point of her weight gain and inflammation reduction, which allowed her adequate energy. EN may be a potential complementary therapeutic strategy to manage clinical symptoms of CD and improve severe malnutrition.


Prospects of epileptogenesis prevention.
Epilepsy is a common neurologic disease, affecting about 1-2% of the population. In around 30% of patients with epilepsy, their seizures are not satisfactorily controlled and drug-resistant epilepsy constitutes a real therapeutic challenge. Consequently, there are efforts aimed at the inhibition of epileptogenesis, a process of converting a normal into an epileptic brain. Data on this problem have been mainly obtained in post-status epilepticus rodent models in which spontaneous seizure activity and behavioral disturbances develop over time. Among antiepileptic drugs, diazepam at high dose of 20mg/kg given during status epilepticus, significantly inhibited the development of spontaneous seizures and also, a strong neuroprotective effect was evident. Also gabapentin and valproate (over a period of 40 days) proved effective in the inhibition of spontaneous seizure activity and reduction of behavioral deficit. However, there are also data that valproate (over 28 days) significantly improved the behavioral performance without affecting the occurrence of spontaneous seizures. A number of antiepileptic drugs, carbamazepine, lamotrigine, levetiracetam, phenobarbital, and topiramate were completely ineffective. Among non-antiepileptic drugs, some promise show rapamycin, losartan and combinations of anti-inflammatory drugs, targeting different inflammatory pathways. Inhibition of epileptogenesis may become a valuable therapeutic approach provided that there are reliable markers of this process. Actually, such markers begin to emerge.


Structure of the human immune interferon gene.
Sequence determination of cloned cDNAs and genes of the three classes of interferon (IFN-alpha, -beta and -gamma) has revealed more than a dozen members of the human IFN-alpha gene family and a single gene for IFN-beta. These genes are found on chromosome 9 and contain no introns. We recently reported that the 146-amino acid sequence of mature IFN-gamma deduced from the nucleotide sequence of a cloned cDNA was quite unrelated to those of the other IFNs, and that the gene for IFN-gamma contains at least one intron. We now describe the isolation, characterization and DNA sequence of the human IFN-gamma gene. It contains three introns, a repetitive DNA element, and is not highly polymorphic. All our evidence to date and the present data suggest that this is the only gene for IFN-gamma and that the resolution of IFN-gamma into two components is probably the result of post-translational processing of the protein.


c-myc and c-Ha-ras cellular oncogenes and human papillomaviruses in benign and malignant cutaneous lesions.
To analyze the role of human papillomavirus (HPV) infection and c-myc and c-Ha-ras oncogene activation in cutaneous and mucosal lesions, serial frozen sections of 47 lesions from grafted recipients and 10 biopsies from non-immunosuppressed patients were examined. HeLa, CaSki, MCF7, Colo 320 and 3T3 cells, which contain various copy numbers of HPV DNA and/or c-myc gene, were used as controls. HPV, myc and ras oncogene DNAs were not detected in normal epithelia by in situ hybridization with biotinylated DNA probes. The amplification of ras oncogene was detected in 20/57 lesions. The amplification of myc oncogene was found in 14/57 lesions, 13 of which showed both myc and ras gene amplification. c-myc and/or c-Ha-ras DNA was more frequently amplified in cutaneous squamous cell carcinomas (8/14 cases) and anogenital papillomas (4/6 cases), than in common and plantar warts (3/14 cases) or actinic keratoses (2/10 cases). HPV DNA was detected in 26/57 biopsies. Oncogene amplification was codetected with HPV DNA in 10/26 lesions, each of them containing at least one potentially oncogenic HPV type (5,16 and/or 18). The amplification was also found in 11/31 cases in the absence of HPV DNA. No significant difference was observed in the detection of HPV or oncogene DNA between the lesions of transplant recipients and those of the non-immunosuppressed population. Viral antigen was detected in 17/55 lesions by indirect immunofluorescence; 5 of the positive biopsies showed ras oncogene amplification. Myc and ras p21 oncoproteins were respectively localized in the nuclei and on the membrane of epithelial cells by indirect immunofluorescence. A good correlation was observed between the amplification of oncogenes and the expression of oncoproteins. Our results favor the hypothesis of a cooperation between HPV infection and myc and ras oncogene activation in skin carcinogenesis.


Feeding time strategies of the fringe-toed lizard, Uma inornata, during breeding and non-breeding seasons.
I examined the foraging behavior during the breeding and non-breeding seasons, May and July 1986, of the fringe-toed lizard Uma inornata (Iguanidae). During the breeding season males differ from females in their diet and in their foraging time strategy, males exhibiting time minimization and females energy maximization. In May, plant associated foods were selectively eaten. Males concentrated on flowers, a readily available quick energy food, which reduced foraging time and increased time for reproductive activities. Time budgets indicate that males spend over twice as much time in the open and in movement in May than do females. Females at this time restrict their activities to the cover of perennial bushes, and feed primarily on plant foods (flowers and arthropods). Energy maximization appears to be maintained by both sexes in the non-breeding season when food resources diminished to one-half of those in the breeding season. The lizards were less selective in their July feeding habits, broadening their diets to include ground-dwelling arthropods and foliage. Predation by these lizards follows a wait-ambush mode of foraging.


Prostanoid receptors mediating contraction in rat, macaque and human bladder smooth muscle in vitro.
Selective prostaglandin EP1 antagonists have been suggested for the treatment of bladder dysfunction. This study assessed the contractile prostanoid receptor subtypes in human and non-human bladder in vitro. Classical tissue bath studies were conducted using bladder strips exposed to prostanoid agonists and antagonists. Prostaglandin E2 (PGE2) contracted rat, macaque and human bladder smooth muscle strips (pEC50 7.91±0.06 (n=7), 6.40±0.13 (n=7), and 6.07±0.11 (n=5), respectively). The EP1 receptor antagonist, PF2907617 (300nM), caused a rightward shift of the PGE2 concentration-response curve in the rat bladder only (pKB 8.40±0.15, n=3). PGE2 responses in rat and macaque bladders, but not human, were antagonised by the EP3 antagonist CJ24979 (1µM). Sulprostone, a mixed EP1/EP3/FP receptor agonist, induced potent contractions of rat bladder muscle (pEC50 7.94±0.31, n=6). The FP receptor agonist, prostaglandin F2α (PGF2α), induced bladder contraction in all species tested, but with a lower potency in rat. The selective FP receptor agonist latanoprost caused potent contractions of macaque and human bladder strips only. SQ29548, a selective TP antagonist, and GW848687X, a mixed EP1/TP antagonist caused rightward shifts of the concentration-response curves to the selective TP agonist, U46619 (pKB estimates 8.53±0.07 and 7.56±0.06, n=3, respectively). Responses to U46619 were absent in rat preparations. These data suggest significant species differences exist in bladder contractile prostanoid receptor subtypes. We conclude that the EP1 subtype does not represent the best approach to the clinical treatment of bladder disorders targeting inhibition of smooth muscle contraction.


Isoarecolone-induced enhancement of delayed matching to sample performance in monkeys: role of nicotinic receptors.
Nicotine enhances memory performance in young and aged monkeys performing a version of the delayed matching to sample (DMTS) task. However, the beneficial actions of nicotine are often limited by debilitating side effects. Isoarecolone is a piperidine derivative with nicotine-like activity, but having a slightly different profile of behavioral actions in rodents. In young monkeys, isoarecolone produced a dose-dependent enhancement of the DMTS task on the same day of testing, with a trend towards enhanced performance in animals tested 24 h after administration. Isoarecolone was about 1500-fold less potent than nicotine in enhancing DMTS performance. The ability of isoarecolone to enhance DMTS performance was well correlated with its ability to interact with cortical nicotinic receptors in vitro.


Financial inclusion and households' choice of solid waste disposal in Ghana.
As the amount of solid waste generated by households in Ghana continues to grow, policy makers are preoccupied with finding better means of managing these solid wastes. To this end, a number of studies have been conducted on the factors that determine the choice of solid waste disposal method among households in Ghana. Notwithstanding, while financial inclusion is deemed as an effective tool for improved solid waste management, none of these studies paid attention to it. This study therefore, investigates the effect of financial inclusion on the choice of solid waste disposal method among households in Ghana. The study uses data from the Ghana Living Standards Survey round 7 (GLSS7). The multinomial probit regression is used as the empirical estimation technique. Our results show that financial inclusion increases the likelihood of households opting for the collection method of solid waste disposal relative to burning, public dumping and indiscriminate disposal of solid waste. Financial inclusion enables households to opt for a healthy solid waste disposal method (collection method), hence, in policy makers' attempts to improve solid waste disposal, paying attention to financial inclusion can be a very useful strategy.


5-HT2 receptor regulation of extracellular GABA levels in the prefrontal cortex.
Monoamines, including both dopamine and serotonin, synapse onto prefrontal cortical interneurons. Dopamine has been shown to activate these GABAergic interneurons, but there are no direct data on the effects of serotonin on GABA release in the prefrontal cortex. We, therefore, examined the effects of the 5-HT2a/c agonist 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI) on extracellular GABA levels in the prefrontal cortex of the rat. Local infusions of DOI dose-dependently increased cortical extracellular GABA levels. In addition, systemic DOI administration resulted in Fos protein expression in glutamic acid decarboxylase67-immunoreactive interneurons of the prefrontal cortex. These data indicate that serotonin, operating through a 5-HT2 receptor, acutely activates GABAergic interneurons in the prefrontal cortex. These data further suggest that there may be convergent regulation of interneurons by dopamine and serotonin in the prefrontal cortex.


Designer receptor inhibition suggests mechanism for monkey Theory of Mind.
Theory of Mind (ToM) is a critical component of human social cognition that has not been found reliably in other primates, especially monkeys. Hayashi et al. (Cell Reports, 30, 4433-4444, 2020) used newly developed behavioral techniques to detect evidence for ToM in Japanese macaque monkeys and employed sophisticated neurobiological manipulations to implicate the medial prefrontal cortex is this capacity.


Bedtime procrastination in the relationship between self-control and depressive symptoms in medical students: From the perspective of sex differences.
Depressive symptoms typically exhibit sex differences among medical students and are associated with bedtime procrastination (BP) and self-control. However, it remains unclear whether sex differences exist in the relationship between these variables. A cross-sectional observational study was conducted among 402 medical students from a public university in China. Students' depressive symptoms, BP, and trait self-control were assessed using the Chinese version of the Beck Depression Inventory (BDI)-II, the Bedtime Procrastination Scale, and the Self-control Scale, respectively. Applying a BDI cutoff value of 14, 364 valid participants were divided into non-depressed (<14) and depressed (≥14) groups. Binary logistic regression revealed that BP was an independent predictor of the prevalence of depressive symptoms in women only. Hierarchical regression showed that high BP levels were independently positively correlated to more depressive symptoms only in non-depressed women. In contrast, low self-control levels were independently negatively correlated to more depressive symptoms in non-depressed and depressed female students. Furthermore, structural equation modeling reflected the mediating role of BP between self-control and depressive symptoms in the non-depressed female group only. Sex differences exist in the effect of BP on depressive symptoms as well as the relationship between self-control and depressive symptoms among Chinese medical students. As a moderator, sex regulates the mediating effect of BP on the relationship between self-control and depressive symptoms in the non-depressed group. These findings provide a sex-specific perspective for targeted prevention and intervention of depressive symptoms among high-risk medical students, especially during the non-depressed period.


Feto-maternal cholesterol transport regulated by β-Klotho-FGF15 axis is essential for fetal growth.
β-Klotho (β-KL) is indispensable to regulate lipid, glucose, and energy metabolism in adult animals. β-KL is highly expressed in the yolk sac, but its role in the developmental stages has not been established. We hypothesized that β-KL is required for metabolic regulation in the embryo and aimed to clarify the role of β-KL during development. Here, we show that β-KL regulates feto-maternal cholesterol transport through the yolk sac by mediating FGF 15 signaling, and also that impairment of the β-KL-FGF15 axis causes fetal growth restriction (FGR). Embryos of β- kl knockout (β-kl-/-) mice were morphologically normal but exhibited FGR before placental maturation. The body weight of β-kl-/- mice remained lower after birth. β-KL deletion reduced cholesterol supply from the maternal blood and led to lipid shortage in the embryos. These phenotypes were similar to those of embryos lacking FGF15, indicating that β-KL-FGF15 axis is essential for growth and lipid regulation in the embryonic stages. Our findings suggest that lipid abnormalities in early gestation provoke FGR, leading to reduced body size in later life.


Pathogenesis of bone loss in heart transplant candidates and recipients.
Heart transplantation (HTX) is associated with decreased bone mineral density and changes in bone metabolism. We conducted this study to evaluate the pathophysiology of bone metabolism in HTX candidates and recipients. Thirty-six HTX recipients were compared with 36 HTX candidates concerning biochemical parameters of bone metabolism and bone mineral density. Osteocalcin, bone-specific alkaline phosphatase, cross-linked-N-telopeptide of type I collagen, estradiol, serum creatinine, and blood urea nitrogen concentrations were significantly higher, whereas the calcium-creatinine ratio, thyrotropin, thyroxine, and bone mineral density were significantly lower in HTX recipients than in HTX candidates. Compared with a control group, HTX candidates had decreased renal function and increased bone resorption, whereas HTX recipients additionally had increased alkaline phosphatase and osteocalcin levels. In HTX recipients, we found positive correlations between creatinine clearance and bone mineral density; daily and cumulative cortisone doses were not associated with bone mineral density. In HTX candidates, disturbances in bone metabolism with increased bone resorption may be caused partly by existing low-grade renal insufficiency, regular intake of loop diuretics, and restriction of mobility. In HTX recipients, immunosuppressive therapy-glucocorticoids and cyclosporine-seem to be responsible for changes in bone metabolism.


The results of stent graft versus medication therapy for chronic type B dissection.
This prospective multicenter comparative study examined early and midterm results of medication and stent-graft therapies on chronic type B aortic dissection in China. The study consisted of 303 consecutive patients with chronic type B aortic dissection from four centers in China from January 2007 to December 2010 who were prospectively enrolled and treated by either optimal medical therapy (OMT) or thoracic endovascular aorta repair (TEVAR). Of the patients, 219 were male and 84 were female (average age, 53.6 ± 20.3 years; range, 29-81 years). Baseline diameter of the thoracic aorta was 41.2 (19.1) mm (mean [standard deviation]), and dissection extended beyond the celiac axis in 87.1% of cases. In total, there were 208 patients in the TEVAR group and 95 patients in the OMT group. Procedural success was 100%, and no deaths occurred during index hospitalization in the two groups. In the TEVAR group, two patients (0.9%) suffered from retrograde type A dissection, and two (0.9%) suffered from paraplegia or paraparesis. For in-hospital outcome, multivariate analysis revealed that age >75 years and American Society of Anesthesiologists class greater than III were independent predictors of major early adverse events. Average follow-up time for hospital survivors was 28.5 ± 16.3 months (range, 1.0-58 months). In the OMT group, five patients died from rupture of an enlarged false lumen, and six patients died suddenly of unknown reasons. Fourteen cases required crossover to TEVAR (n = 12) or surgical conversion (n = 2). In the TEVAR group, nine patients required reintervention or surgical conversion, and one died of postoperative multi-organ failure. One patient died of delayed retrograde type A dissection, and four died suddenly of unknown reasons. The Kaplan-Meier analysis of survival probability at 2 and 4 years was 87.5% and 82.7% with TEVAR, respectively, and 77.5% and 69.1% with OMT, respectively (P = .0678, log-rank test). The estimated cumulative freedom from aorta-related death at 2 and 4 years was 91.6% and 88.1% with TEVAR, respectively, and 82.8% and 73.8% with OMT, respectively (P = .0392, log-rank test). The thoracic aorta diameter decreased from 42.4 (23.1) mm to 37.3 (12.8) mm in the TEVAR group and increased from 40.7 (18.6) mm to 48.1 (17.3) mm in the OMT group. This was the first prospective multicenter comparative study on the treatment of type B aortic dissection in China. TEVAR had a significantly lower aorta-related mortality compared with OMT but failed to improve overall survival rate or lower the aorta-related adverse event rate.


A chimeric ribozyme in clostridium difficile combines features of group I introns and insertion elements.
CdlSt1, a DNA insertion of 1975 bp, was identified within tcdA-C34, the enterotoxin gene of the Clostridium difficile isolate C34. Located in the catalytic domain A1-C34, Cd/St1 combines features of two genetic elements. Within the first 434 nt structures characteristic for group I introns were found; encoding the two transposase-like proteins tlpA and tlpB nucleotides 435-1975 represent the remainder of a IS605-like insertion element. We show that the entire CdlSt1 is accurately spliced from tcdA-C34 primary transcripts and that purified TcdA-C34 toxin is of regular size and catalytic activity. A search for CdlSt1-related sequences demonstrates that the element is widespread in toxinogenic and non-toxinogenic C. difficile strains, indicating the mobility of CdlSt1. In strain C34, we characterize 10 CdlSt1 variants; all are highly homologous to CdlSt1 (> 93% identity), integrated in bacterial open reading frames (ORFs), show the typical composite structure of CdlSt1 and are precisely spliced from their primary transcripts. CdlSt1-like chimeric ribozymes appear to combine the invasiveness of an insertion element with the splicing ability of a group I intron, rendering transposition harmless for the interrupted gene.


Part C early intervention utilization in preterm infants: Opportunity for referral from a NICU follow-up clinic.
Early Intervention (EI) services promote development for preterm infants. In the state of Illinois, Child and Family Connections (CFC) is the intake agency that determines qualification for EI services. In Illinois, all extremely low birth weight (ELBW) infants are eligible for and referred to CFC at discharge from the Neonatal Intensive Care Unit (NICU). This study investigated: (1) patterns of CFC and EI enrollment, and; (2) predictors of CFC enrollment, need for CFC referral, and high EI therapy use among preterm infants seen in a NICU follow-up clinic. 405 preterm infants, including 169 ELBW infants, were seen in a NICU follow-up clinic at 4-, 8- and 20-months corrected age. CFC/EI data were collected at each visit. Multiple regression analyses adjusted for the effect of medical, sociodemographic and neurodevelopmental risk factors on CFC/EI outcome. Despite the high rate of EI utilization and routine care by primary pediatricians, up to 28% of ELBW infants required a CFC referral from a NICU follow-up clinic. Medical and neurodevelopmental risk factors were associated with CFC enrollment while medical, sociodemographic and neurodevelopmental risk factors were associated with need for CFC referral. NICU follow-up clinics facilitate appropriate CFC/EI services for preterm infants.


Relationship between patient sex and anatomical sites of extrapulmonary tuberculosis in Mali.
Contribution of host factors in mediating susceptibility to extrapulmonary tuberculosis is not well understood. To examine the influence of patient sex on anatomical localization of extrapulmonary tuberculosis. We conducted a retrospective cross-sectional study in Mali, West Africa. Hospital records of 1,304 suspected cases of extrapulmonary tuberculosis, available in TB Registry of a tertiary tuberculosis referral center from 2019 to 2021, were examined. A total of 1,012 (77.6%) were confirmed to have extrapulmonary tuberculosis with a male to female ratio of 1.59:1. Four clinical forms of EPTB predominated, namely pleural (40.4%), osteoarticular (29.8%), lymph node (12.5%), and abdominal TB (10.3%). We found sex-based differences in anatomical localization of extrapulmonary tuberculosis, with males more likely than females to have pleural TB (OR: 1.51; 95% CI [1.16 to 1.98]). Conversely, being male was associated with 43% and 41% lower odds of having lymph node and abdominal TB, respectively (OR: 0.57 and 0.59). Anatomical sites of extrapulmonary tuberculosis differ by sex with pleural TB being associated with male sex while lymph node and abdominal TB are predominately associated with female sex. Future studies are warranted to understand the role of sex in mediating anatomical site preference of tuberculosis.


Gastrointestinal invasion by herpes simplex virus type 1 inoculated cutaneously into the immunosuppressed mice.
The pathogenesis of infection in mice with herpes simplex virus type 1 (HSV-1) strain 7401H was studied. Mice immunosuppressed by intraperitoneal injection of cyclophosphamide were inoculated cutaneously into the flank with the virus and developed severe zosteriform skin lesions. All of them died within 2 weeks after the infection, while most of the normal mice survived the viral infection with healing of the lesions. In the gastrointestinal tract of the immunosuppressed mice, macroscopic abnormalities were frequently observed, and infectious viruses were detected on days 7 to 9. The viruses were also detectable in the dorsal root ganglia and the spinal cord of thoracolumbar area on days 5 to 7, and in the celiac plexus on day 7. However, no viruses were detected in the blood. Immunohistological examination of the gastrointestinal tract revealed that the viral antigens were localized in Auerbach's myenteric plexus. These results suggest that HSV-1 inoculated into the flank skin invaded the gastrointestinal tract via the nervous system, which gastrointestinal involvement might possibly have caused the death of the mice.


The effect of recombinant factor VIIa (NovoSeven) in healthy volunteers receiving acenocoumarol to an International Normalized Ratio above 2.0.
Vitamin K antagonists are most commonly used in long-term thrombosis prophylaxis and the use in patients with cardiovascular disease seems to be increasing. By interfering with the normal hemostatic mechanism, an increased risk of bleeding will arise and administration of human plasma or prothrombin complex concentrates may be necessary. It can be difficult to normalize hemostasis using plasma and prothrombin complex concentrates, because these may be associated with thromboembolic side-effects. The level of factor VII, one of the vitamin-K-dependent coagulation factors, decreases during oral anticoagulant therapy and the administration of recombinant factor VIIa normalizes the prolonged prothrombin time in warfarin-treated rats. After administration of acenocoumarol (International Normalized Ratio > 2), decreased levels of factor X and factor IX (19-46%), protein C (2-20%) and factor VII (4-17%) were found in 28 healthy volunteers. After one dose of recombinant factor VIIa (5, 10, 20, 40, 80, 120, 160, 240, or 320 microg/kg) the International Normalized Ratio and prothrombin time normalized, which may imply an effect on bleeding in individuals receiving oral anticoagulant therapy. The lowest dose (5 microg/kg) normalized the International Normalized Ratio for 12 h and doses > 120 microg/kg normalized it for 24 h. Fragment 1+2 stayed within its normal range in all dose groups, indicating that no systemic coagulation occurred.


The effect of ultrasonic irradiation on the crystallinity of nano-hydroxyapatite produced via the wet chemical method.
Nanohydroxyapatite (nHAp) powders were produced via aqueous precipitation by adopting four different experimental conditions, assisted or non-assisted by ultrasound irradiation (UI). The nHAp powders were characterized by X-ray diffraction, energy-dispersive X-ray fluorescence, Raman and attenuated total reflection Fourier transform infrared spectroscopies, which showed typical surface chemical compositions of nHAp. Analysis found strong connections between UI and the crystallization process, crystal growth properties, as well as correlations between calcination and substitution reactions.


A Simple Method for Closure of Urethrocutaneous Fistula after Tubularized Incised Plate Repair: Preliminary Results.
Urethrocutaneous fistula (UCF) is the most prevalent complication after hypospadias repair surgery. Many methods have been developed for UCF correction, and the best technique for UCF repair is determined based on the size, location, and number of fistulas, as well as the status of the surrounding skin. In this study, we introduced and evaluated a simple method for UCF correction after tubularized incised plate (TIP) repair. This clinical study was conducted on children with UCFs ≤ 4 mm that developed after TIP surgery for hypospadias repair. The skin was incised around the fistula and the tract was released from the surrounding tissues and the dartos fascia, then ligated with 5 - 0 polydioxanone (PDS) sutures. The dartos fascia, as the second layer, was covered on the fistula tract with PDS thread (gauge 5 - 0) by the continuous suture method. The skin was closed with 6 - 0 Vicryl sutures. After six months of follow-up, surgical outcomes were evaluated based on fistula relapse and other complications. After six months, relapse occurred in only one patient, a six-year-old boy with a single 4-mm distal opening, who had undergone no previous fistula repairs. Therefore, in 97.5% of the cases, relapse was non-existent. Other complications, such as urethral stenosis, intraurethral obstruction, and epidermal inclusion cysts, were not seen in the other patients during the six-month follow-up period. This repair method, which is simple, rapid, and easily learned, is highly applicable, with a high success rate for the closure of UCFs measuring up to 4 mm in any location.


Functional characterization of lipase in the pathogenesis of Staphylococcus aureus.
During infection, Staphylococcus aureus produces multiple enzymes that enable it to invade and destroy host tissues and metastasize to other sites. One such enzyme, lipase, has been recognized for its relationship in the virulence of S. aureus. However, a direct involvement of lipase in the pathogenesis of S. aureus remains to be demonstrated. Our prior study indicated that anti-lipase serum inhibits biofilm formation in S. aureus clinical strains. The aim of this study was to further characterize the roles of lipase in the pathogenesis in S. aureus. We found that deletion of the lipase-coding gene reduced biofilm formation relative to the wild-type strain. This was shown by culture in 96-well plates coated with collagen to resemble the in vivo infection process. Intraperitoneal inoculation of mice with a lipase mutant strain showed defective formation of peritoneal abscesses, and bacterial loads in different organs were much lower compared with the wild-type. Importantly, active immunization with recombinant lipase protected mice against a lethal challenge with S. aureus. Altogether, our data provide evidence that S. aureus lipase plays important roles in the pathogenesis of S. aureus.


Sleep duration is a potential risk factor for newly diagnosed type 2 diabetes mellitus.
U-shaped patterns have been observed for the relationship between sleep duration and diabetes. In addition, prediabetes is associated with the risk of cardiovascular diseases and diabetes. However, there are few studies investigating the relationship between sleep duration and prediabetes/newly diagnosed diabetes. The aim of this study is to examine the relationship between sleep duration and prediabetes/newly diagnosed diabetes in a Taiwanese population. After excluding the subjects with a high risk of obstructive sleep apnea, those with a positive history of diabetes, or those taking hypnotic drugs, a total of 3470 adults were recruited from a health checkup center. Each subject completed a self-administrated structured questionnaire on sleep duration and lifestyle factors. Prediabetes/diabetes was defined following the definition of the American Diabetes Association. Subjects with different sleep durations were classified into short (<6.0 hours), normal (6.0∼8.49 hours), and long sleepers (≥8.5 hours). The proportion of subjects with normal glucose tolerance, prediabetes, and newly diagnosed diabetes was 71.9%, 22.9%, and 5.2%, respectively. There were significant differences in age, sex, weight, education level, body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, alcohol and coffee drinking habits, family history of diabetes, and sleep duration among the 3 glycemic groups. In multinomial regression, both short and long sleepers had a higher risk of newly diagnosed diabetes; and the odds ratio were 1.55 (95% confidence interval, 1.07-2.24) and 2.83 (1.19-6.73), respectively. However, sleep duration was not found to relate to prediabetes. In conclusion, both short and long sleep durations were independently associated with newly diagnosed diabetes, but not with prediabetes.


Comparing Intradermal Sterile Water with Intravenous Morphine in Reducing Pain in Patients with Renal Colic: A Double-Blind Randomized Clinical Trial.
The present study was conducted to investigate the effect of intradermal administration of sterile water compared to intravenous morphine on patients with renal colic. This double-blind, randomized clinical trial study was conducted in 2017 to compare the therapeutic effects of intradermal sterile water with those of intravenous morphine on patients with renal colic presenting to the emergency departments (ED) of Imam Khomeini and Golestan Hospitals in Ahvaz, Iran. The first group received 0.5 ml of intradermal sterile water, and the second group 0.1mg/kg of intravenous morphine plus 0.5 ml of intradermal sterile water in the most painful area or the center of the painful area in the flank. The pain severity was measured using a visual analogue scale (VAS), and the medication side-effects were recorded at the beginning of the study and minutes 15, 30,45 and 60. A total of 94 patients were studied in two groups. The mean severity of pain was 2.97 ± 1.51 in the sterile water group and 2.34 ± 1.89 in the morphine group at minute 30 (P=0.042), 2.58 ± 1.43 in the sterile water group and 1 ± 1.23 in the morphine group at minute 45 (P<0.001), and 1.89 ± 1.7 in the sterile water group and 0.52 ± 0.79 in the morphine group at minute 60 (P<0.001). Morphine reduces pain faster and more effectively than intradermal sterile water; nevertheless, treatment with intradermal sterile water can be used as an appropriate surrogate or adjunct therapy for pain control, particularly in special patients or in case of medication scarcity.


'Syntactic Perturbation' During Production Activates the Right IFG, but not Broca's Area or the ATL.
Research on the neural organization of syntax - the core structure-building component of language - has focused on Broca's area and the anterior temporal lobe (ATL) as the chief candidates for syntactic processing. However, these proposals have received considerable challenges. In order to better understand the neural basis of syntactic processing, we performed a functional magnetic resonance imaging experiment using a constrained sentence production task. We examined the BOLD response to sentence production for active and passive sentences, unstructured word lists, and syntactic perturbation. Perturbation involved cued restructuring of the planned syntax of a sentence mid utterance. Perturbation was designed to capture the effects of syntactic violations previously studied in sentence comprehension. Our experiment showed that Broca's area and the ATL did not exhibit response profiles consistent with syntactic operations - we found no increase of activation in these areas for sentences > lists or for perturbation. Syntactic perturbation activated a cortical-subcortical network including robust activation of the right inferior frontal gyrus (RIFG). This network is similar to one previously shown to be involved in motor response inhibition. We hypothesize that RIFG activation in our study and in previous studies of sentence comprehension is due to an inhibition mechanism that may facilitate efficient syntactic restructuring.


Inhibitory role of focal adhesion kinase on anoikis in the lung cancer cell A549.
Resistance to anoikis is a characteristic of malignant cells with increased tumorigenesis and metastasis. Altered FAK activity has been strongly implicated in the development, growth, progression, and metastasis of human cancers, but the mechanism of FAK in regulating anoikis is unknown. In this study, the resistance anoikis role of FAK and its downstream mediators was evaluated in the human lung cancer cell line A549. It has been shown that down regulation of FAK stimulates the apoptosis of cells and the down-regulation of p-ERK, p-PI3K, p-Src, and p-p38. Furthermore, in detached A549 cells, increased FAK phosphorylations (Tyr397, Tyr861, Tyr925) were detected in a time-dependent manner, and the specific inhibitors of MEK1, PI3K, and Src (PD98059, LY294002, and PP2) partly abolished the resistance to the anoikis characteristic of cancer cells. Altogether, our data suggested that Src is involved in the progress of detachment-induced FAK activation in lung tumor cells. PI3K/AKT, MAPK-ERK, and perhaps MAPK-p38 but not MAPK-JNK, appear to be the key downstream effectors of FAK in mediating cell survival. The increased FAK activity upon cell detachment may contribute to the metastasis potential of malignant tumors.


Coherent confinement of plasmonic field in quantum dot-metallic nanoparticle molecules.
Interaction of a hybrid system consisting of a semiconductor quantum dot and a metallic nanoparticle (MNP) with a laser beam can replace the intrinsic plasmonic field of the MNP with a coherently normalized field (coherent-plasmonic or CP field). In this paper we show how quantum coherence effects in such a hybrid system can form a coherent barrier (quantum cage) that spatially confines the CP field. This allows us to coherently control the modal volume of this field, making it significantly smaller or larger than that of the intrinsic plasmonic field of the MNP. We investigate the spatial profiles of the CP field and discuss how the field barrier depends on the collective states of the hybrid system.


Phytochemical Investigation on Volatile Compositions and Methoxylated Flavonoids of Agrostis gigantea Roth.
In this study, methoxylated flavonoids and volatile constitutions of Agrostis gigantea Roth (Poaceae) were investigated for the first time. The flavonoids were identified by spectroscopic methods (1H-NMR, 13C-NMR, COSY, NOSEY, TCOSY, and HMBC). The volatile constitutions of aerial parts and seeds were analyzed by gas chromatography-mass spectrometry (GC-MS). Two methoxylated flavonoids, luteolin 5-methyl ether (1), and cirsilineol (2) were isolated from the aerial parts of this plant. According to the GC-MS data the main constitutions of these volatile oils belong to the simple phenolic category which include coniferyl alcohol (18.80%) and eugenol (12.19%) in aerial parts and seeds, respectively. By using the computer- aided molecular modeling approaches, the binding affinity of these compounds was predicted in the catalytic domains of aryl hydrocarbon receptor (AhR). These two isolated flavonoids were investigated in-vitro for their inhibitory activity on 4T1 breast carcinoma cells. It was predicted that these compounds could be well-matched in aryl hydrocarbon receptor (3H82) active site, but based on the in-vitro assay, the IC50 values on cytotoxicity were 428.24 ±3.21 and 412.7±3.02 μg/mL for luteolin 5-methyl ether and cirsilineol, respectively. Thus, it can be concluded that these flavonoids exhibit low cytotoxicity against 4T1 breast carcinoma cell line.


Association of central obesity and insulin resistance with high prevalence of diabetes and cardiovascular disease in an elderly population with low fat intake and lower than normal prevalence of obesity: the Indian paradox.
To test the hypothesis that high prevalences of cardiovascular disease and diabetes in urban population of India are manifestations of insulin-resistance syndrome. Cross-sectional surveys were conducted in 20 streets in the city of Moradabad and in two villages. There were 566 subjects (255 rural and 311 urban) aged 60-84 years. All subjects were divided on the basis of their insensitivity to insulin into groups with mild, moderate and high insensitivity to insulin and data from both sexes were pooled for analysis. Overall increases in the prevalences of coronary disease, diabetes, hypertension, central obesity and associated disturbances were observed with increasing insensitivity to insulin and the trend was more significant among urban than it was among rural subjects. Multivariate logistic regression analysis revealed a significant positive association of level of insulin insensitivity with the age-adjusted prevalences of coronary disease, hypertension, diabetes, hypertriglyceridaemia, intolerance of glucose and central obesity among urban subjects. We observed a significant inverse association between insensitivity to insulin and physical activity both for rural and for urban subjects and between insensitivity to insulin and high-density lipoprotein cholesterol level for urban subjects. For rural subjects, we found significant associations of sensitivity to insulin with coronary artery disease and intolerance of glucose without significant associations with other risk factors. Insensitivity to insulin was significantly associated with risks of cardiovascular disease and diabetes, despite there being a low prevalence of obesity (9.0%) among urban subjects. Hypertension, diabetes, hypertriglyceridaemia, intolerance of glucose and central obesity were significantly associated with insensitivity to insulin and coronary disease for urban but not for rural people.