Comparing narrative storytelling ability in individuals with autism and fetal alcohol spectrum disorders.
Narrative discourse, or storytelling, is used in daily conversation and requires higher-level language and social communication skills that are not always captured by standardised assessments of language. Many autistic individuals and individuals with fetal alcohol spectrum disorders (FASD) have difficulties with both social communication and language skills, and narrative discourse analysis offers an ecologically relevant approach to assessing those challenges. This study investigated narrative discourse in individuals with autism and FASD, as well as an age- and sex-matched comparison group. Narratives from 45 adolescents and adults, 11 with autism, 11 with FASD and 23 age- and sex-matched comparison participants were elicited using a wordless storybook. They were then transcribed orthographically, formatted to the Systematic Analyses of Language Transcript (SALT) convention and scored based on the SALT Narrative Scoring Scheme (NSS), a standardised language analysis protocol. In addition to the NSS total score, which assesses the overall structure and cohesion of the narratives produced, local and global measures of language ability were also employed. The local language measures included the number of mental state and temporal relation terms produced, while the global language measures included mean length of utterance, total different words, total words, total utterances, rate of speech, the number of mazes (e.g., repetitions, 'um', 'uh' or self-corrections) per total word and the NSS total score. Using the SALT Language Sample Analysis tool, our results revealed that on global language measures, group differences were found on rate of speech, number of mazes per total words and the description of conflict/resolution in the narratives produced. The autism group produced significantly more mazes per total word and scored higher on the NSS conflict/resolution category score compared to the FASD and comparison groups. Both the autism and FASD groups spoke at a lower rate than the comparison group. On local language measures of narrative production, all groups were comparable, on average. While many aspects of narrative discourse in the autism and FASD groups were similar to each other and to the comparison group, we observed group differences on global measures of narrative production and significant individual variability within groups, suggesting that narrative abilities considered at an individual level may provide important clinical information for intervention planning. Future research should also consider additional variables that influence narrative discourse, such as motivation, distractibility or decision-making of individual participants. What is already known on the subject Narrative discourse, or storytelling, is used in daily conversational interactions and reveals higher-level language skills that may not be well captured by standardised assessments of language. Many autistic individuals and individuals with fetal alcohol spectrum disorders (FASD) show difficulty with pragmatic and expressive language skills. What this paper adds to existing knowledge We found that many aspects of the narratives produced by the adolescents/young adults in the autism and FASD groups were comparable to each other and to the neurotypical group. However, the groups differed on three global measures of narrative production: rate of speech, number of mazes per total words and the description of conflict/resolution in the narratives produced. Also, significant variability was observed within groups, suggesting that narrative abilities should be considered at an individual level as opposed to their clinical groups. What are the potential or actual clinical implications of this work? This study showed that narrative discourse is an appropriate task that can be added to routine clinical assessments of language abilities in autistic adolescents/young adults as well as those with FASD or typical development and has the potential to reveal higher-level, real-world language skills. An important clinical implication of this study is that narrative language abilities should be considered at an individual level and individual-tailored interventions based on ability level due to the variability observed across individuals.


[The value of ultrasound-guided cyto-biopsy in the study of livers with abnormal ultrasonograms].
This retrospective study considers the diagnostic reliability of 97 cyto-biopsies performed with a fine needle and guided by ultrasonography in 92 patients with one or several suspicious liver lesions. The results of the cyto-biopsy were compared with the final diagnosis obtained by histological examination or by the evolution. In 65 confirmed malignant tumors, fine needle biopsy was concordant in 54 cases. The sensitivity of this method in the diagnosis of malignant liver lesions was 83% with a specificity of 93%. In 54 malignant cytologies, the differentiation between primary or secondary lesions was possible in 31 cases (57%). In 32 confirmed benign lesions, fine needle biopsy was concordant in 30 cases. This study confirms the advantage of cyto-biopsy guided by ultrasonography in the positive and etiological diagnosis of malignant liver tumors.


The insulin resistance syndrome: mechanisms of clustering of cardiovascular risk.
For more than a decade, insulin resistance has been proposed as the key linking factor for the metabolic syndrome disease cluster of glucose intolerance, hypertension, dyslipidemia, obesity, and cardiovascular disease. Although most of the epidemiological, experimental, and clinical evidence still support the role of insulin resistance as an important component of this multifaceted syndrome, there is evidence amassing that a neurohormonal mechanism, including an endocrine role for adipocytes, probably plays a more fundamental role. This is supported by the strong associations between obesity, especially central adiposity, and all components of the metabolic syndrome, in contrast to the inconsistent relationships between blood pressure and markers of insulin resistance. However, much of the effect of visceral fat on cardiovascular risk factors is mediated through the metabolic actions of free fatty acids (FFA) on insulin resistance, thus resolving any obesity versus insulin resistance controversy. In addition to the roles of obesity and FFA in the development of insulin resistance syndrome, the high prevalence rates of this disease cluster among subjects from low socioeconomic groups as well as from developing countries have led to alternative hypotheses to better our understanding of the contributory roles of socioeconomic, in utero, and genetic factors in this syndrome. More recently, the pathogenetic roles of iron overload and liver dysfunction have also been re-examined. In this article, the various hypotheses which have been put forward to explain the diverse clinical manifestations of the metabolic or insulin resistance syndrome are summarized and put into perspective. While there is clinical and experimental evidence to support many of these independent pathways, alternative statistical methods such as factor analysis or structural equation modeling may be needed to unravel the complex nature of these interacting pathways. Finally, these hypotheses, if proven, will add new dimensions to our current strategies and emphasize the need to focus on behavioral and socioeconomic interventions in addition to the use of pharmacological therapy in our attempt to control this epidemic disease of modern societies.


[Bartter's syndrome and tubular functional disturbances].
A 5-year-old boy is presented who exhibited the classical symptoms of the syndrome described by BARTTER et al. in 1962: growth retardation, hypokalemic alkalosis, hyperplasia of the juxtaglomerular apparatus with normotensive hyperreninism-hyperaldosteronism, polydipsia with impaired renal concentration ability resistant to pitressin. In addition, the patient showed the typical proximal tubular defects of the Fanconi syndrome: hyperphosphaturia with hypophosphatemic ricktts, generalized hyperaminoaciduria, proteinuria and glucosuria. In the cases of Bartter's syndrome described to date, no uniform pathogenetic mechanism could be identified. Proximal tubular salt wasting generally is assumed to be the primary defect. The studies carried out in this case support this hypothesis and indicate that the complete clinical picture of Bartter's syndrome may occur within the framework of multiple proximal tubular defects.


Withaferin A, a novel compound of Indian ginseng (Withania somnifera), ameliorates Cerulein-induced acute pancreatitis: Possible role of oxidative stress and inflammation.
Acute pancreatitis is an inflammatory disorder of the pancreas that may precipitate due to various reasons such as chronic alcoholism, gall stone obstruction, and life style. Current treatment options offer limited efficacy, as they provide only symptomatic relief. This study is an attempt to study the effects of Withaferin A (WFA) against Cerulein-induced acute pancreatitis in mice. Animals were pretreated with WFA via intraperitoneal route, for 7 days. Plasma amylase and lipase, tissue malondialdehyde (MDA), and glutathione were evaluated for all groups. Western blot analysis; haematoxylin and eosin staining of the liver, lung, and pancreas; immunohistochemistry for nitrotyrosine; and myeloperoxidase activity were performed. Haematoxylin and eosin stained sections significantly revealed the altered architecture and thereby damage in the pancreas, lungs, and liver that has been low in treatment groups. Increased myeloperoxidase and nitrotyrosine have also been reduced upon treatment with WFA. Increased levels of MDA, NO, and expression of myeloperoxidase and nitrotyrosine in the parameters estimated add evidence to the role of oxidative stress and inflammation in acute pancreatitis. WFA evidently altered these conditions upon pretreatment. Our study shows that this novel steroidal compound has potent anti-inflammatory property. Natural compounds can therefore be good remedies against many diseases if incorporated in routine diet as dietary supplement.


The establishment of an anaesthetist-managed intraoperative neurophysiological monitoring service and initial outcome data.
Neurophysiological monitoring has been recommended to reduce the risk of neurological damage during a wide variety of surgeries. While the concept of an anaesthesia-led intraoperative neurophysiological monitoring (IONM) service is not new, the quality of this service provision has not been studied. In this article, we present our experience with the establishment of this service, and the results of our audit of 302 cases monitored over the initial four years. Our results identified that an anaesthesia-led IONM service was able to achieve a reliable signal in 95.4% of cases and capture significant alerts in 15.6% of these cases with sensitivity, specificity, false positive and negative rates consistent with published data. Our results indicate an anaesthesia-led IONM service is effective in identifying patients at an increased risk of an adverse outcome.


Liver transplantation for hepatocellular carcinoma: Hangzhou experiences.
Liver transplantation (LT) has been the treatment of choice for patients with hepatocellular carcinoma (HCC). This study was designed to summarize our experience in LT for HCC patients and establish a new set of criteria for patient selection and prognosis prediction. Data of 195 patients with HCC were retrospectively analyzed and various clinical and pathological factors for survival and tumor-free survival were examined by univariate and multivariate analyses. Macrovascular invasion, preoperative serum alpha fetoprotein (AFP) level, tumor size, multifocality, histopathologic grading, distribution, and cirrhosis background were significant factors for survival and tumor-free survival by univariate analysis. Multivariate analysis identified macrovascular invasion, tumor size, preoperative AFP level, and histopathologic grading were prognostic factors independently associated with patient survival or tumor-free survival (RR=1.688-2.779, P=0.000-0.034). Based on the prognostic stratification of different risk groups of patients without macrovascular invasion, Hangzhou criteria was established, containing one of the two following items: (a) Total tumor diameter less than or equal to 8 cm; (b) total tumor diameter more than 8 cm, with histopathologic grade I or II and preoperative AFP level less than or equal to 400 ng/mL, simultaneously. The difference between survival curves of patients fulfilling Milan criteria (n=72) and patients fulfilling Hangzhou criteria (n=99) did not achieve statistical significance (5-year survival rates: 78.3% vs. 72.3%, P>0.05). Of the patients exceeding Milan criteria (n=123), those who fulfilled Hangzhou criteria (n=26) also had better prognosis than the others (n=97) (P=0.000). The results of this study show a reliable and feasible candidates selection and prognostic criteria of LT in HCC patients.


Zonisamide concentrations during pregnancy.
To describe a series of serum concentrations of zonisamide in a pregnant woman. A 30-year-old woman with primary generalized tonic-clonic seizures and myoclonic jerks was taking zonisamide 200 mg daily as her sole antiepileptic agent when she conceived. She continued on zonisamide throughout her pregnancy. The zonisamide concentrations ranged between 7.5 microg/mL and 17 microg/mL during pregnancy, with the exception of a 4.4-microg/mL concentration at 27 weeks postconception. Following this lower concentration, the zonisamide dose was increased to 300 mg/day at week 29. She had an uneventful pregnancy, with only occasional myoclonic jerks, and delivered at 41 weeks. At 42 weeks, while taking zonisamide 300 mg/day, her concentration was 20.8 microg/mL. A single report from Japan reviewed 26 cases of prenatal exposure to zonisamide. Twenty-two offspring were exposed to zonisamide monotherapy; 4 were exposed to polytherapy. During the first trimester, 2 pregnant women on zonisamide and at least one other antiepileptic medication had serum concentrations of 6.1 microg/mL and 6.2 microg/mL; 2 of the infants had teratogenic effects. Teratogenicity has also been reported in animals. There are no other published data regarding zonisamide concentrations during pregnancy. The change in zonisamide serum concentrations in a pregnant woman suggests an increase in clearance at the end of the second trimester.


Adherence to varenicline and associated smoking cessation in a community-based patient setting.
Varenicline, a selective α4β2 nicotinic acetylcholine receptor partial agonist, is a pharmacotherapy indicated for smoking cessation treatment. To our knowledge, no studies have described varenicline treatment adherence and efficacy from real-world treatment patterns in a U.S. primary care setting. To estimate adherence to varenicline prescription orders and subsequent quit rates among smokers in a primary care setting. In this retrospective cohort study, eligible patients were enrolled with Geisinger Health Plan, had an initial varenicline prescription written by a Geisinger provider between January 1, 2006, and December 31, 2009, and had a follow-up clinic visit within the subsequent 12 months. Adherence was derived from linking electronic prescriptions with adjudicated pharmacy claims. Smoking status was collected at each health care encounter. Of the 1,477 eligible patients, 823 (55.7%) were primary nonadherent, having failed to initiate on the prescribed varenicline therapy. Of the remaining 654 patients, 359 (54.9%) were adherent, having completed a full 12-week course of therapy, and 295 (45.1%) were partially adherent, having initiated but not completed the full course of therapy. A total of 521 patients (35.3%) ceased smoking during the 12-month follow-up period: 182 (50.7%) of the adherent cohort, 82 (27.8%) of the partially adherent population, and 257 (31.2%) of the nonadherent cohort. No significant difference was found in quit rates between the partially adherent and nonadherent patient cohorts (adjusted HR 0.88 [95% CI=0.69-1.13]). However, patients adherent to the varenicline regimen were almost twice as likely to succeed in quitting smoking compared with completely nonadherent patients (HR 1.93 [95% CI=1.59-2.33]). Smoking cessation occurred more often among individuals adherent to varenicline therapy; however, medication nonadherence was common. After prescribing varenicline, clinicians and payers could consider active patient follow-up to maximize adherence and optimize treatment outcomes.


N-myc regulates growth and fiber cell differentiation in lens development.
Myc proto-oncogenes regulate diverse cellular processes during development, but their roles during morphogenesis of specific tissues are not fully understood. We found that c-myc regulates cell proliferation in mouse lens development and previous genome-wide studies suggested functional roles for N-myc in developing lens. Here, we examined the role of N-myc in mouse lens development. Genetic inactivation of N-myc in the surface ectoderm or lens vesicle impaired eye and lens growth, while "late" inactivation in lens fibers had no effect. Unexpectedly, defective growth of N-myc-deficient lenses was not associated with alterations in lens progenitor cell proliferation or survival. Notably, N-myc-deficient lens exhibited a delay in degradation of DNA in terminally differentiating lens fiber cells. RNA-sequencing analysis of N-myc-deficient lenses identified a cohort of down-regulated genes associated with fiber cell differentiation that included DNaseIIβ. Further, an integrated analysis of differentially expressed genes in N-myc-deficient lens using normal lens expression patterns of iSyTE, N-myc-binding motif analysis and molecular interaction data from the String database led to the derivation of an N-myc-based gene regulatory network in the lens. Finally, analysis of N-myc and c-myc double-deficient lens demonstrated that these Myc genes cooperate to drive lens growth prior to lens vesicle stage. Together, these findings provide evidence for exclusive and cooperative functions of Myc transcription factors in mouse lens development and identify novel mechanisms by which N-myc regulates cell differentiation during eye morphogenesis.


Prediction of preeclampsia in primigravida in late first trimester using serum placental growth factor alone and by combination model.
We investigated a placental growth factor alone and combined clinical (mean arterial pressure, MAP), biophysical (uterine artery pulsability index, PI) and biochemical (placental growth factor, PLGF) model for predicting preeclampsia in late first trimester. The inclusion criteria was primigravida (<40 years) attending their first hospital visit with singleton pregnancy at 11-14 weeks of gestation. Of the enrolled and followed 291 subjects, 35 (12%) later developed PE (5.8%)/GH (6.2%). An equal number of randomised women with normotensive non-proteinuric course were considered as reference group. For preeclampsia, PLGF alone had detection rate of 40% and 51% with 5% and 10% FPR, respectively. On addition of MAP, the AUC improved to 0.937 for PE. Further, addition of mean PI slightly improved AUC to 0.965. This signifies that a model with all three markers had better prediction of preeclampsia rather than PLGF alone. Impact statement In view of high morbidity and mortality due to hypertensive disorders in pregnancy, there has been extensive research for developing markers to detect/screen the condition in early pregnancy. Several such markers have been tested in their individual capacities and in combination during early pregnancy. Most of these studies have originated from high income countries and focussed mainly on the second trimester of pregnancy. We investigated a placental growth factor alone and combined clinical (mean arterial pressure, MAP), biophysical (uterine artery pulsability index, PI) and biochemical (placental growth factor, PLGF) model for predicting preeclampsia in the first trimester in primigravida (<40 years). A nested case control model was used for our study. For preeclampsia, PLGF alone had detection rate of 40% and 51% with 5% and 10% FPR, respectively. On addition of MAP, the AUC improved to 0.937 for PE. Further, addition of mean PI slightly improved AUC to 0.965. The present study has been done in an Indian subcontinent setting (where maternal mortality related to preeclampsia are even higher) where very limited studies are available for the role of either PLGF or in combinations for prediction of preeclampsia. Our research pointed shows better predictability for PE when a combination of markers is used especially in low-risk nulligravida. These are easy, cheap and non-invasive measurements that can be taken in all women at their first routine antenatal visit.


Phosphatidylinositol synthesis and exchange of the inositol head are catalysed by the single phosphatidylinositol synthase 1 from Arabidopsis.
In order to study some of its enzymatic properties, phosphatidylinositol synthase 1 (AtPIS1) from the plant Arabidopsis thaliana was expressed in Escherichia coli, a host naturally devoid of phosphatidylinositol (PtdIns). In the context of the bacterial membrane and in addition to de novo synthesis, the plant enzyme is capable of catalysing the exchange of the inositol polar head for another inositol. Our data clearly show that the CDP-diacylglycerol-independent exchange reaction can occur using endogenous PtdIns molecular species or PtdIns molecular species from soybean added exogenously. Exchange has been observed in the absence of cytidine monophosphate (CMP), but is greatly enhanced in the presence of 4 microm CMP. Our data also show that AtPIS1 catalyses the removal of the polar head in the presence of much higher concentrations of CMP, in a manner that suggests a reverse of synthesis. All of the PtdIns metabolizing activities require free manganese ions. EDTA, in the presence of low Mn2+ concentrations, also has an enhancing effect.


[Lewy bodies, a misleading marker for Parkinson's disease?].
The Lewy body, an eosinophilic inclusion around 10 microns in diameter, is localised in the neuronal perikaryon. Its dense core is surrounded by a clear halo, which is lacking in the so-called "cortical Lewy bodies". Numerous proteins have been identified in Lewy bodies, among which the three neurofilament isoforms, ubiquitin and proteasome subunits. More recently, alpha-synuclein--a pre-synaptic protein--has been found to be the essential constituent of the Lewy body. Alpha-synuclein antibody has greatly increased the sensitivity of the neuropathological examination: it has emphasized the frequency of "Lewy neurites" (accumulation of alpha--synuclein in neuronal processes) and has shown the importance of extra-nigral pathology. Lewy bodies and neurites are indeed to be found in many areas of the central and peripheral nervous system: stellate ganglia, cardiac and enteric plexus, pigmented nuclei of the brainstem, basal nucleus of Meynert, amygdala, limbic nuclei of the thalamus, parahippocampal and cingulate gyri, insula and isocortex. Lewy body diseases include at least three clinical syndromes: 1) idiopathic Parkinson disease in which the brainstem bears the brunt of the pathology 2) Parkinson disease dementia in which Lewy lesions are found in the brainstem and are also abundant in the isocortex. A large number of senile plaques is frequently associated. 3) In dementia with Lewy bodies, the same lesions are observed but the cognitive deficit occurs first or shortly (less than one year) after the motor symptoms.


Review of Mental Health Response to COVID-19, China.
Public mental health response to coronavirus disease is essential. After reviewing systemic and local efforts in China, we found efficient coordination and human resources. We recommend better symptom assessment, monitoring of organizations, and basic needs protection. This recommendation can inform how other countries can overcome mental health challenges during this pandemic.


Effects of fetal calf serum and disruption of cadherin function on the formation of bile canaliculi between hepatocytes.
The polarization of hepatocytes to form a connected network of bile canaliculi (BC) is necessary for the function of the liver. Hepatocyte polarization may be controlled by soluble factors and/or physical interactions between cells. Monolayer cultures of embryonic chicken hepatocytes in DMEM supplemented with ornithine, dexamethasone, and insulin express BC-specific antigens for at least 7 days. However, BC-specific antigen expression is lost within 3 days of culture initiation in DMEM containing 10% fetal calf serum. The dedifferentiating effects of fetal calf serum (FCS) can be reversed. Furthermore, cultures in medium containing ornithine, dexamethasone, insulin, and 10% FCS appear identical to cultures grown in 10% FCS alone. Thus FCS contains a soluble inhibitor of hepatocyte polarization. Aggregate cultures grown in suspension maintain hepatocyte polarization for 10-12 days. This may be due to the increased cell-cell contact between hepatocytes in aggregate culture or to more normal contact with the extracellular matrix. We have evaluated the role of cadherin-mediated interactions on hepatocyte polarization. Anti-E-cadherin Fab' fragments disrupted the formation of long networks of BC in monolayer cultures but did not stop polarized expression of BC-specific antigens. The BC antigens in anti-E-cadherin-treated cells were concentrated in small areas between cells and were present at lower levels uniformly on the cell surface. These results indicate that E-cadherin is required for the formation of extended BC networks, but that other factors are responsible for maintaining the synthesis and localization of BC-specific antigens.


Bowel ischaemia and cocaine consumption; case study and review of the literature.
Amongst others, cocaine consumption has a detrimental effect in the vascular supply to the mesenteric area causing abdominal ischemic changes. Early recognition of these changes and adequate treatment are essential to avoid serious complications and possible death of the patient from sepsis. In this case study, the subject is a 40-years-old gentleman presenting with acute abdominal pain due to multiple ischemic changes in both small bowel and sigmoid loops. The patient required emergency surgical intervention consisting of bowel resection and anastomosis. The pathologic analysis of the segment showed transmural necrosis and necrotizing phlebitis caused by the ingestion of drugs or toxic agents. The patient later confirmed the habitual consumption of cocaine. The increase in cocaine consumption and other recreational toxins substructed from erythroyilon coca alkaloids amongst young people have generated a large number of admissions to Hospital Accident and Emergency Departments with patients complaining of acute abdominal pain. In many of these cases, surgical intervention is required and in some cases patients will sadly die without a proper diagnosis. Some of the most common effects of cocaine and its compounds includes; hollow viscus perforation, gastro-intestinal bleed, and other vascular problems such as enteritis and ischemic colitis. It appears clear that there is a great need for an advance history taking of these patients and their habit to cocaine and other drugs together with a urine test for drug screening. These together with a suspicion of a non- occlusive ischemic bowel caused by the effects of cocaine in young adults with no cardiac risk factors will guide clinicians and establish, and plan the correct treatment for these categories of patients.


Effect of remifentanil on pre-osteoclast cell differentiation in vitro.
The structure and function of bone tissue is maintained through a constant remodeling process, which is maintained by the balance between osteoblasts and osteoclasts. The failure of bone remodeling can lead to pathological conditions of bone structure and function. Remifentanil is currently used as a narcotic analgesic agent in general anesthesia and sedation. However, the effect of remifentanil on osteoclasts has not been studied. Therefore, we investigated the effect of remifentanil on pre-osteoclast (pre-OCs) differentiation and the mechanism of osteoclast differentiation in the absence of specific stimulus. Pre-OCs were obtained by culturing bone marrow-derived macrophages (BMMs) in osteoclastogenic medium for 2 days and then treated with various concentration of remifentanil. The mRNA expression of NFATc1 and c-fos was examined by using real-time PCR. We also examined the effect of remifentanil on the osteoclast-specific genes TRAP, cathepsin K, calcitonin receptor, and DC-STAMP. Finally, we examined the influence of remifentanil on the migration of pre-OCs by using the Boyden chamber assay. Remifentanil increased pre-OC differentiation and osteoclast size, but did not affect the mRNA expression of NFATc1 and c-fos or significantly affect the expression of TRAP, cathepsin K, calcitonin receptor, and DC-STAMP. However, remifentanil increased the migration of pre-OCs. This study suggested that remifentanil promotes the differentiation of pre-OCs and induces maturation, such as increasing osteoclast size. In addition, the increase in osteoclast size was mediated by the enhancement of pre-OC migration and cell fusion.


Challenges of diabetes care in India: Results from a Family Cohort Study.
Diabetes is a significant public health concern in India, with Kerala being labeled as the diabetes capital of the country. The study aims to evaluate the prevalence, treatment, and management of diabetes to examine the unmet need for care to propose cost-effective strategies. A cross-sectional study was conducted on a geographically defined cohort population in Ernakulam. This paper presents diabetes data of adults ≥30 years enrolled from the community cohort. The interviews were conducted with 997 participants at their residence. Random blood glucose was assessed for each participant using a finger prick test. The overall prevalence of diabetes was 30.1%, of which 4.1% of participants had undiagnosed diabetes. Among those with diabetes, 86.3% were aware of their diagnosis; among those aware, 86.5% were on treatment. Among those on treatment for diabetes, 54% achieved controlled blood sugar. The challenge in diabetes management is controlling the blood glucose levels of people who adhere to treatment. Younger employed females from lower-income quartiles have the highest risk. The study also raises questions about quality and strategies for medication compliance. The findings inspire future research on care needs, policies, and program responses to reduce the diabetes disease burden.


[Pharmacoeconomics - Challenges for Health Professionals].
Over the last 30 years, medical expenditure has increased throughout the world. The main reasons estimated to lay behind it include aging, ever more chronic diseases and new emerging diseases, new drugs, expanded indications of current drugs, and development of pharmaceutical industry. A challenge for healthcare professionals is to sustain current quality of care and enable medical innovations while attempting to contain costs. The overall goal is to demonstrate the pharmacoeconomic value, i.e. a balance of economic, humanistic and clinical outcomes.


Comparative analysis of the Squamosa Promoter Binding-Like (SPL) gene family in Nicotiana benthamiana and Nicotiana tabacum.
SQUAMOSA PROMOTER BINDING-LIKE (SPL) proteins constitute a large family of transcription factors known to play key roles in growth and developmental processes, including juvenile-to-adult and vegetative-to-reproductive phase transitions. This makes SPLs interesting targets for precision breeding in plants of the Nicotiana genus used as e.g. recombinant biofactories. We report the identification of 49 SPL genes in Nicotiana tabacum cv. K326 and 43 SPL genes in Nicotiana benthamiana LAB strain, which were classified into eight phylogenetic groups according to the SPL classification in Arabidopsis. Exon-intron gene structure and DNA-binding domains were highly conserved between homeologues and orthologues. Thirty of the NbSPL genes and 33 of the NtSPL genes were found to be possible targets of microRNA 156. The expression of SPL genes in leaves was analysed by RNA-seq at three different stages, revealing that genes not under miR156 control were in general constitutively expressed at high levels, whereas miR156-regulated genes showed lower expression, often developmentally regulated. We selected the N. benthamiana SPL13_1a gene as target for a CRISPR/Cas9 knock-out experiment. We show here that a full knock-out in this single gene leads to a significant delay in flowering time, a trait that could be exploited to increase biomass for recombinant protein production.


Galactosamine inhibition of protein synthesis in Bacteroides thetaiotaomicron.
Galactosamine does not support growth of Bacteroides thetaiotaomicron. Despite this, galactosamine was more effective than utilizable carbohydrates such as glucose in preventing synthesis of the inducible enzymes alpha-glucosidase and chondroitin lyase. Galactosamine also stopped overall protein synthesis. By contrast glucose and other utilizable carbohydrates increased the rate of protein synthesis. Addition of glucose to bacteria which had been treated with galactosamine restored the ability of the bacteria to synthesize protein and to produce inducible enzymes. Moreover, when B. thetaiotaomicron was incubated with [1-14C]galactosamine for 30 min at 37 degrees C, about one-third of the label which was taken up by the cells comigrated with glucosamine-6-phosphate on a thin-layer chromatogram. Thus galactosamine appears to be phosphorylated by the bacteria. After 2 h incubation of the bacteria with [1-14C]galactosamine, there was a significant increase in the amount of label which could be extracted from acidified extracellular fluid with diethyl ether. This indicates that galactosamine can be metabolized to the level of volatile fatty acids. The rate of uptake of galactosamine and the amount of labeled fatty acids produced from galactosamine were both much lower than the values obtained when glucosamine was the substrate. Thus, although some metabolism of galactosamine occurs, the rate is apparently too slow to enable galactosamine to support growth of B. thetaiotaomicron.


Food insecurity in people living with obesity: Improving sustainable and healthier food choices in the retail food environment-the FIO Food project.
At both UK and global level, dietary consumption patterns need to change to address environmental, health and inequality challenges. Despite considerable policy interventions, the prevalence of overweight and obesity in the United Kingdom has continued to rise with obesity now a leading cause of mortality and morbidity. Obesity prevalence is greater among those on lower incomes and the current UK food system, including government policy, does not effectively address this. Current behavioural approaches, without the support of structural changes in the system, may even widen the inequalities gap. Hence, using behavioural insights from those living with obesity and food insecurity, the project will explore potential avenues that can be applied in the food system to promote healthier choices in the food retail environment. The National Food Strategy report recommends that the UK food system should ensure "safe, healthy, affordable food; regardless of where people live or how much they earn". However, the association between food insecurity and the development of obesity is not well understood in relation to purchasing behaviours in the UK retail food environment, nor is the potential effectiveness of interventions that seek to prevent and reduce the impact of diet-induced health harms. The FIO Food (Food insecurity in people living with obesity - improving sustainable and healthier food choices in the retail food environment) project provides a novel and multi-disciplinary collaborative approach with co-development at the heart to address these challenges. Using four interlinked work packages, the FIO Food project will combine our knowledge of large-scale population data with an understanding of lived experiences of food shopping for people living with obesity and food insecurity, to develop solutions to support more sustainable and healthier food choices in the UK retail food environment.


CD147-induced cell proliferation is associated with Smad4 signal inhibition.
CD147 is a multifunctional trans-membrane glycoprotein, which is highly expressed in many cancers. However, the mechanism by which CD147 modulates cell proliferation is not fully understood. The aim of this study is to investigate the role of CD147 in cell proliferation associated with the TGF-β/Smad4 signaling pathway. Here, we used cell viability and clone formation assays in LNCaP prostate cancer cells to demonstrate that CD147 promotes cell proliferation. The luciferase assay and western blotting show that silencing CD147 using shRNA enhances transcription and expression of p21WAF1. Using immunofluorescence and nuclear-cytoplasmic separation, we show that this is primarily attributed to transport of Smad4 from the cytoplasm to nucleus. Other assays (GST pull-down, co-immunoprecipitation and immunofluorescence) demonstrate that Smad4 is a new interaction partner of CD147, with the Smad4 MH2 domain and CD147 intracellular domain (CD147-ICD) being involved in the interaction. Furthermore, we report that a phosphoserine (pSer) in CD147 (pSer252) is responsible for this interaction and inhibition of the Smad4/p21WAF1 signal that promotes cell proliferation. Our results provide a novel molecular mechanism for CD147-induced cell proliferation associated with Smad4 signal inhibition.


Biochemical and other markers of colon cancer.
Advances in the understanding of biochemical and molecular processes associated with cellular growth and differentiation, as well as colonic carcinogenesis hold promise for the development of new diagnostic and therapeutic modalities for this disease. Altered glycosylation of cell surface and secreted glycoconjugates appear to be useful markers in differentiating normal from malignant colonic tissue. New information regarding deletion and inappropriate expression of several blood group-related carbohydrate antigens as well as the synthesis of unique cancer-related carbohydrate structures has been derived from the use of monoclonal antibody technology, and may lead to more sensitive and specific screening tests and targeted therapies. Several glycoprotein markers for colon cancer have been studied whose diagnostic accuracy may surpass the limited sensitivity and specificity of traditional markers such as CEA. Colorectal cancers contain numerous quantitative and qualitative differences in metabolic and synthetic enzyme activities compared with normal colonic mucosa, which may be of potential importance in designing chemotherapeutic regimens or for following disease activity. Other cancer-associated markers, such as increases in orthinine decarboxylase activity and crypt cell labeling reflect abnormal proliferative activity and may be correlated with premalignant states. Studies of protooncogene expression and certain chromosomal deletions will provide insight into mechanisms of carcinogenesis and may also serve to define high-risk individuals. It is likely that as the biochemical and molecular mechanisms underlying malignancy are further delineated, cancer-associated markers will be defined that will improve diagnostic and more importantly, therapeutic efficacy.


The diagnostic value of hyperostosis in midline subfrontal meningioma.
Roentgenologic analysis of 66 patients with proved midline subfrontal meningioma indicates a very high incidence of hyperostosis. A total of 63 patients (95%) showed varying degrees of hyperostosis involving the cribiform plate, planum sphenoidale, or tuberculum sellae (including the chiasmatic sulcus). The planum sphenoidale is the most common site of hyperostosis (59%). In 19 cases (29%), the region of hyperostosis did not correspond to the site of tumor attachment. Mild or localized hyperostosis may be apparent only on tomograms. Small "blistering" and "saw-tooth-like" osteoma formation are reliable early signs of midline subfrontal meningioma; conversely, midline subfrontal meningioma can be virtually ruled out if hyperostosis is absent.


Outcome comparison of partial and full component revision TKA.
We compare the clinical and radiographic results of partial-component versus full-component revision total knee arthroplasty. A retrospective review was used to identify patients who had partial revision total knee arthroplasty. Only isolated femoral or tibial revisions were included. From 1986 to 2000, 448 revision total knee arthroplasties were done. Seventy-seven partial revisions were done. Three were excluded for a diagnosis of infection. The average followup was 63 months. The average Knee Society score for full component revisions was 85 compared with 79 for partial revisions. This difference was significant (p = 0.0001). The average Knee Society score for those patients who had a full revision for instability was 85 compared with 63 for partial revision (p = 0.0001). The average Knee Society score for those patients who had a full revision for wear-related problems was 88 compared with 78 for partial revisions (p = 0.03). Although the advantages of partial revision in hip replacement are well-documented, the efficacy of this treatment strategy has not been established in revision total knee arthroplasty. Care should be taken when considering partial revision for instability or wear-related problems. Therapeutic study, Level III (retrospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.


Nursing faculty teaching a module in clinical skills to medical students: a Lebanese experience.
Nursing faculty teaching medical students a module in clinical skills is a relatively new trend. Collaboration in education among medical and nursing professions can improve students' performance in clinical skills and consequently positively impact the quality of care delivery. In 2011, the Faculty of Medicine in collaboration with the Faculty of Health Sciences at the University of Balamand, Beirut, Lebanon, launched a module in clinical skills as part of clinical skills teaching to first-year medical students. The module is prepared and delivered by nursing faculty in a laboratory setting. It consists of informative lectures as well as hands-on clinical practice. The clinical competencies taught are hand-washing, medication administration, intravenous initiation and removal, and nasogastric tube insertion and removal. Around sixty-five medical students attend this module every year. A Likert scale-based questionnaire is used to evaluate their experience. Medical students agree that the module provides adequate opportunities to enhance clinical skills and knowledge and favor cross-professional education between nursing and medical disciplines. Most of the respondents report that this experience prepares them better for clinical rotations while increasing their confidence and decreasing anxiety level. Medical students highly appreciate the nursing faculties' expertise and perceive them as knowledgeable and resourceful. Nursing faculty participating in medical students' skills teaching is well perceived, has a positive impact, and shows nurses are proficient teachers to medical students. Cross professional education is an attractive model when it comes to teaching clinical skills in medical school.


Role of Langerhans cells, Ki-67 protein and apoptosis in acquired cholesteatoma: prospective clinical study.
To investigate the role of Langerhans cells in the pathogenesis and clinical picture of middle-ear cholesteatoma. The study included 40 patients operated upon for a diagnosis of chronic otitis due to acquired cholesteatoma. A closed surgical technique was used in 20 per cent of patients and an open technique in 80 per cent. Langerhans cells were more densely accumulated in cholesteatoma epithelium, compared with external ear canal skin (p < 0.001). Staining for Ki-67 protein was greater in cholesteatoma epithelium (p < 0.001) and Apo2.7 protein staining (indicating apoptosis) was more prominent (p < 0.001), compared with ear canal skin. Regarding significant relationships between clinical and pathological findings, staining for Ki-67 (p = 0.046) and Apo2.7 (p = 0.037) was more prominent in patients undergoing open versus closed surgery. Using cell proliferation and apoptosis markers, a dense Langerhans cell infiltration was found to occur as a host response to middle-ear cholesteatoma.


The effect of glyceraldehyde on red cells. Haemoglobin status, oxidative metabolism and glycolysis.
Glyceraldehyde induces changes in the flux of glucose oxidised through the hexose monophosphate pathway, the concentrations of intermediates in the Embden-Meyerhoff pathway, the oxidative status of haemoglobin and levels of reduced and oxidised pyridine nucleotides and glutathione in red cells. Glyceraldehyde autoxidises in the cellular incubations, consuming oxygen and producing glyoxalase I- and II-reactive materials. Major fates of glyceraldehyde in red cells appear to be: (i) adduct formation with reduced glutathione and cellular protein; (ii) autoxidation and reaction with oxyhaemoglobin and pyridine nucleotides, and (iii) phosphorylation of D-glyceraldehyde and entry into the glycolytic pathway as glyceraldehyde 3-phosphate. The production of glycerol from glyceraldehyde by red cell L-hexonate dehydrogenase appears not to be a major reaction of glyceraldehyde in red cells. These results indicate that high concentrations of glyceraldehyde (1-50 mM) may induce oxidative stress in red cells by virtue of the spontaneous autoxidation of glyceraldehyde, forming hydrogen peroxide and alpha-ketoaldehydes (glyoxalase substrates). The implications of glyceraldehyde-induced oxidative stress for the in vitro anti-sickling effect of DL-glyceraldehyde and for the polyol pathway metabolism of glyceraldehyde are discussed.


Disparate estimates of hypertension control from ambulatory and clinic blood pressure measurements in hypertensive kidney disease.
Ambulatory blood pressure (ABP) monitoring provides unique information about day-night patterns of blood pressure (BP). The objectives of this article were to describe ABP patterns in African Americans with hypertensive kidney disease, to examine the joint distribution of clinic BP and ABP, and to determine associations of hypertensive target organ damage with clinic BP and ABP. This study is a cross-sectional analysis of baseline data from the African American Study of Kidney Disease Cohort Study. Masked hypertension was defined by elevated daytime (>or= 135/85 mm Hg) or elevated nighttime (>or= 120/70 mm Hg) ABP in those with controlled clinic BP (<140/90 mm Hg); nondipping was defined by a <or= 10% decrease in mean nighttime systolic BP; reverse dipping was defined by a higher nighttime than daytime systolic BP. Of the 617 participants (mean age: 60.2 years; 62% male; mean estimated glomerular filtration rate: 43.8 mL/min per 1.73 m(2)) with both clinic BP and ABP, 498 participants (80%) had a nondipping or reverse dipping profile. Of the 377 participants with controlled clinic BP (61%), 70% had masked hypertension. Compared with those with controlled clinic BP or white-coat hypertension, target organ damage (proteinuria and left ventricular hypertrophy) was more common in those with elevated nighttime BP, masked hypertension, or sustained hypertension. In conclusion, clinic BP provides an incomplete and potentially misleading assessment of the severity of hypertension in African Americans with hypertensive kidney disease, in large part because of increased nighttime BP. Whether lowering nighttime BP improves clinical outcomes is unknown but should be tested given the substantial burden of BP-related morbidity in this population.


The exploration of macrocycles for drug discovery--an underexploited structural class.
Macrocyclic natural products have evolved to fulfil numerous biochemical functions, and their profound pharmacological properties have led to their development as drugs. A macrocycle provides diverse functionality and stereochemical complexity in a conformationally pre-organized ring structure. This can result in high affinity and selectivity for protein targets, while preserving sufficient bioavailability to reach intracellular locations. Despite these valuable characteristics, and the proven success of more than 100 marketed macrocycle drugs derived from natural products, this structural class has been poorly explored within drug discovery. This is in part due to concerns about synthetic intractability and non-drug-like properties. This Review describes the growing body of data in favour of macrocyclic therapeutics, and demonstrates that this class of compounds can be both fully drug-like in its properties and readily prepared owing to recent advances in synthetic medicinal chemistry.


[Liposomes--therapeutic progress and technological problems].
Liposomes represent globular vesicles composed of an aqueous core and one or several phospholipid bilayers. They can encapsulate hydrophilic or lipophilic drugs used in therapy and diagnostic imaging. Liposomes provide protection of the active substances, sustained or controlled release and also targeted delivery of drugs to specific cells, tissues, organs. Easy oxydation of phosphatidylcholin (lecithin)--the main membrane component--is the limitation of the introduction of liposomes to the medicinal practice in a broader scale. Unsatisfying chemical stability of lecithin has an unfavourable influence on drug and liposome stability. Liposomes decompose during storage and leakage of the encapsulated drug occurs. A review of advantages of application of liposomes in medicine and methods of increasing their stability was presented.


The role of iron in metal-metal interactions in hard tissues of roe deer (Capreolus capreolus L.).
The toxicity of heavy metals in humans and animals has been attributed to their potential for accumulation in solid tissues and interference with other vitally important elements present in the body. We have devised this study to determine the content of some metals in bone and to determine with the Statistica Neural Networks program whether the content of one metal has any effect on the content of other metals. Our material consisted of mandibles obtained from deer aged 2 to 6 years. Using a dental drill, pulverized bone was obtained for measurements of calcium, copper, and zinc with atomic absorption spectrometry and magnesium, chromium, manganese, and iron with inductively coupled plasma atomic emission spectometry. Statistical analysis was performed with the Statistica software and its Statistica Neural Network program. We found that the concentration in bone of one metal affects the concentrations of other metals. Iron seems to play a special role in the accumulation of other metals by bone. The use of artificial neural networks was helpful in identifying candidate elements (like iron) which are active in controlling concentrations of other metals in bone.


Patient access to healthcare services and optimisation of self-management for ethnic minority populations living with diabetes: a systematic review.
A higher risk of diabetes mellitus in South Asian and Black African populations combined with lower reported access and self-management-related health outcomes informed the aims of this study. Our aims were to synthesise and evaluate evidence relating to patient self-management and access to healthcare services for ethnic minority groups living with diabetes. A comprehensive search strategy was developed capturing a full range of study types from 1995-2010, including relevant hand-searched literature pre-dating 1995. Systematic database searches of MEDLINE, Cochrane, DARE, HTA and NHSEED, the British Nursing Index, CAB abstracts, EMBASE, Global Health, Health Management Information Consortium and PsychInfo were conducted, yielding 21,288 abstracts. Following search strategy refinement and the application of review eligibility criteria; 11 randomised controlled trials (RCTs), 18 qualitative studies and 18 quantitative studies were evaluated and principal results extracted. Results suggest that self-management practices are in need of targeted intervention in terms of patients' knowledge and understanding of their illness, inadequacy of information and language and communication difficulties arising from cultural differences. Access to health-care is similarly hindered by a lack of cultural sensitivity in service provision and under use of clinic-based interpreters and community-based services. Recommendations for practice and subsequent intervention primarily rest at the service level but key barriers at patient and provider levels are also identified.


Factors affecting profitability for craniotomy.
The authors studied factors influencing hospital profitability after craniotomy in patients who underwent craniotomy coded as diagnosis-related group (DRG) 1 (17 years of age with nontraumatic disease without complication) and who met their hospital's craniotomy pathway criteria and had a hospital length of stay 4 days or less during a 20-month period. Data in all patients meeting these criteria (76 cases) were collected and collated from various hospital databases. Twenty-one cases were profitable and 55 were not. Variables traditionally influencing cost of care, such as surgeon, procedure, length of operation, and pharmacy use had no significant effect on whether a patient was profitable. The most important influence on profitability was the individual payor. Cases in which care was reimbursed under the prospective payment system based on DRGs were nearly always profitable whereas those covered by per diem plans were nearly always nonprofitable. 1) Hospital information systems should be customized to deliver consolidated data for timely analysis of cost of care for individual patients. This information may be useful in negotiating profitable contracts. 2) A clinical pathway was successful in reducing the difference in cost of care between profitable and nonprofitable postcraniotomy cases. 3) In today's health care environment both cost containment and revenue assume importance in determining profitability.


Choledochoduodenostomy an important surgical tool in the management of common bile duct stones. A review of 126 cases.
Of 2,000 patients who underwent cholecystectomy between 1965-1984, 457 had their common bile ducts explored and of these 126 had choledochoduodenostomies. There were 70 women and 56 men and a third were over 70 years old. Forty-three also had acute cholecystitis or pancreatitis, and 73 had an increased serum concentration of bilirubin. Of the 126, 103 had stones in the common duct, and 16 had benign strictures of the sphincter of Oddi. Morbidity included wound infections in 18 (14%) and bile discharge from the drain for over 14 days in four (3%). Five patients died (4%), and they were all over 70 years old. Ninety-seven of 103 patients followed-up over 1-19 years were symptom free (94%). Two patients required re-operation for a narrow anastomosis. Three patients developed a "sump" syndrome; two were treated with antibiotics, and the third responded to endoscopic sphincterotomy. Choledochoduodenostomies should be considered during operation for benign biliary disease, when stones or a stricture in the common bile duct are anticipated.


Logistics of performing an ophthalmic assessment in elderly inpatients.
To assess the feasibility of performing an ophthalmic assessment on elderly inpatients, we examined 48 patients over 75 years of age who were consecutively admitted to an acute elderly-care ward. Difficulties were encountered in 35 patients (73%). By employing simple methods to overcome these problems, useful information was obtained in all cases and the time taken to complete the examination ranged from six to 20 minutes (mean 7.5 minutes). Doctors looking after elderly patients should be encouraged to assess visual function and must not be deterred by anticipated logistical difficulties.


Diagnosis and treatment of connective tissue disease-associated interstitial lung disease.
Interstitial lung disease (ILD) is one of the most serious pulmonary complications associated with connective tissue diseases (CTDs), resulting in significant morbidity and mortality. Although the various CTDs associated with ILD often are considered together because of their shared autoimmune nature, there are substantial differences in the clinical presentations and management of ILD in each specific CTD. This heterogeneity and the cross-disciplinary nature of care have complicated the conduct of prospective multicenter treatment trials and hindered our understanding of the development of ILD in patients with CTD. In this update, we present new information regarding the diagnosis and treatment of patients with ILD secondary to systemic sclerosis, rheumatoid arthritis, dermatomyositis and polymyositis, and Sjögren syndrome. We review information on risk factors for the development of ILD in the setting of CTD. Diagnostic criteria for CTD are presented as well as elements of the clinical evaluation that increase suspicion for CTD-ILD. We review the use of medications in the treatment of CTD-ILD. Although a large, randomized study has examined the impact of immunosuppressive therapy for ILD secondary to systemic sclerosis, additional studies are needed to determine optimal treatment strategies for each distinct form of CTD-ILD. Finally, we review new information regarding the subgroup of patients with ILD who meet some, but not all, diagnostic criteria for a CTD. A careful and systematic approach to diagnosis in patients with ILD may reveal an unrecognized CTD or evidence of autoimmunity in those previously believed to have idiopathic ILD.


Structure-Property Relationships of Amine-rich and Membrane-Disruptive Poly(oxonorbornene)-Coated Gold Nanoparticles.
The article describes the interactions between poly (oxonorbornenes) (PONs)-coated gold nanoparticles (AuNPs) with phospholipid vesicles and shows that the strength of these interactions strongly depends on the molecular structure of PONs, specifically their amine/alkyl side chain ratio. PONs, which are a recently introduced class of cationic polyelectrolytes, can be systematically varied to control the amine/alkyl ratio and to explore how the chemical character of cationic polyelectrolytes affects their interactions and the interactions of their nanoparticle conjugates with model membranes. Our study shows that increasing the amine/alkyl ratio by copolymerization of diamine and 1:1 amine/butyl oxonorbornene monomers impacts the availability of PONs amine/ammonium functional groups to interact with phospholipid membranes, the PONs surface coverage on AuNPs, and the membrane disruption activity of free PONs and PONs-AuNPs. The study makes use of transmission electron microscopy, UV-vis spectroscopy, dynamic light scattering, thermogravimetric analysis, fluorescamine assay, ζ-potential measurements, and X-ray photoelectron spectroscopy measurements to characterize the PONs-AuNPs' size, size distribution, aggregation state, surface charge, and PONs surface coverage. The study also makes use of real-time fluorescence measurements of fluorescent liposomes before and during exposure to free PONs and PONs-AuNPs to determine the membrane disruption activity of free PONs and PONs-AuNPs. As commonly observed with cationic polyelectrolytes, both free PONs and PONs-AuNPs display significant membrane disruption activity. Under conditions where the amine/alkyl ratio in PONs maximizes PONs surface coverage, the membrane disruption activity of PONs-AuNPs is about 10-fold higher than the membrane disruption activity of the same free PONs. This is attributed to the increased local concentration of ammonium ions when PONs-AuNPs interact with the liposome membranes. In contrast, the hydrophobicity of amine-rich PONs, which are made for example from diamine oxonorbornene monomers, is significantly reduced. This leads to a significant reduction of PON surface coverage on AuNPs and in turn to a significant decrease in membrane disruption.


[Treatment of shoulder dislocation and the prevention of its recurrence].
Shoulder dislocation is a frequent pathology with a high level of recurrences especially in young patients. One week immobilization in a Dessault dressing is sufficient if it is followed by free mobilization avoiding external rotation and abduction. A 6 weeks rehabilitation program seems to prevent recurrences.


The experience of delayed health care access during the COVID 19 pandemic in Australian women: A mixed methods exploration.
Delayed health care access is a potential collateral effect of pandemic conditions, health rationing strategies and social distancing responses. We investigated experiences of delayed health care access in Australian women during COVID-19. A mixed methods study used quantitative and free-text data from the Australian Longitudinal Study on Women's Health COVID-19 survey 4 (health care access or delay). Logistic regression models were used to estimate factors associated with delaying access to general practitioners (GPs), specialists and allied health services. Free-text comments were analysed thematically, employing a process of constant comparison. COVID-19 survey 4 was completed by 8,200 women and 2,727 provided free-text comments. Of the women who needed the health service, 25% (1,268/5,071) delayed seeing their GP, 23.6% (570/1,695) delayed seeing a specialist and 45% (791/1,757) delayed use of an allied health service. Younger age was most significantly associated with delaying attendance. Women born 1989-95 were significantly more likely to delay compared to women born 1946-51 (OR (95% CI): GP = 0.28 (0.22, 0.35)); Specialist = 0.65 (0.45, 0.92; Allied Health = 0.59 (0.42, 0.82)). Women born 1973-78 were also likely to delay GP visits (0.69, (0.58, 0.83)). Four qualitative themes emerged including: (1) Challenges negotiating care during a pandemic; (2) Ongoing uncertainty towards accessing health care when a specialist delays an appointment; (3) Accessing health care (or not) using Telehealth and (4) Managing complex care needs. COVID-19 has had a significant effect on access to health care. Women delayed seeking help for cancer screening, mental health, and other health conditions involving chronic and complex needs for health and social care. While there is a need to rationalise and optimise health access during a pandemic, our outcomes suggest a need for public health campaigns that clarify how to access care, engage with telehealth and respond to missed appointments.


Loss to Follow-Up and Re-Engagement in HIV Pre-Exposure Prophylaxis Care in the United States, 2013-2019.
Retention in HIV pre-exposure prophylaxis (PrEP) care is critical for effective PrEP implementation. Few studies have reported long-term lost to follow-up (LTFU) and re-engagement in PrEP care in the United States. Medical record data for all cisgender patients presenting to the major Rhode Island PrEP clinic from 2013 to 2019 were included. LTFU was defined as no PrEP follow-up appointment within 98 days. Re-engagement in care was defined as individuals who were ever LTFU and later attended a follow-up appointment. Recurrent event survival analysis was performed to explore factors associated with PrEP retention over time. Of 654 PrEP patients, the median age was 31 years old [interquartile range (IQR): 25, 43]. The majority were male (96%), White (64%), non-Hispanic (82%), and insured (97%). Overall, 72% patients were ever LTFU and 27% of those ever LTFU re-engaged in care. Female patients were 1.37 times [crude hazard ratio (cHR): 1.37; 95% confidence interval (CI): 0.86-2.18] more likely to be LTFU than male patients, and a 1-year increase in age was associated with a 1% lower hazard of being LTFU (cHR: 0.99; CI: 0.98-0.99). Being either heterosexual (aHR: 2.25, 95% (CI): 1.70-2.99] or bisexual (aHR: 2.35, 95% CI: 1.15-4.82) was associated with a higher hazard of loss to follow-up compared with having same-sex partners only. The majority of PrEP users were LTFU, especially at the first 6 months of PrEP initiation. Although a significant number were re-engaged in care, targeted interventions are needed to improve retention in PrEP care. This study characterized the natural projection of loss to follow-up and re-engagement in HIV PrEP care using a longitudinal clinic cohort data and explored associated factors for guiding future interventions to improve retention in PrEP care.


Prolongation of growth by treatment of 11-hydroxylase deficiency with depot-leuprolide, growth hormone, and hydrocortisone.
A 4-10/12 year-old boy presented with tall stature and advanced secondary sexual characteristics. His bone age was 13 years giving him a height prediction of 147 cm. An initial 11-deoxycortisol level of 13,770 ng/dl and associated hypertension suggested the diagnosis of 11-hydroxylase deficiency, which was confirmed by dexamethasone suppression and genotyping. Treatment strategy was based on the premise that known hypothalamic priming resulting in early pubertal development could be averted by delaying puberty with leuprolide; also that effects of hydrocortisone and leuprolide on attenuating growth could be counteracted by growth hormone. The combined treatment resulted in a final height at age 12 years which was 25.4 cm greater than predicted, and bone density above average. We conclude that delaying puberty until an appropriate age, offsetting growth suppression, and improving bone mineralization can be effectively achieved using glucocorticoids, leuprolide and growth hormone in patients with 11-hydroxylase deficiency.


The effect of neonatal nerve injury on the expression of heat shock proteins in developing rat motoneurones.
The expression of the heat shock proteins hsp27 and hsp70 was examined in the spinal cord and sciatic nerves of developing rats. Using immunohistochemistry, we found that hsp27 is present in many motoneurones at birth. With development, the intensity of staining increases, reaching adult levels by 21 days, when all sciatic motoneurones express hsp27. In the sciatic nerve, hsp27 is strongly expressed throughout postnatal development. In contrast, hsp70 immunoreactivity in motoneurones and the sciatic nerve is weak at birth and does not change with development. The expression of heat shock proteins has been shown to increase in cells under conditions of stress, where they have beneficial effects on cell survival. The effect of neonatal nerve injury on hsp27 and hsp70 expression was also examined in this study. Four days after injury, staining for hsp27 increases in motoneurones, whereas hsp70 does not change. However, there is a significant increase in hsp70 staining in glial cells surrounding the injured motor pool, predominantly in astrocytes. Since neonatal nerve injury induces apoptotic motoneurone death, we also studied the co-expression of hsp27 with markers of apoptosis. No hsp27-positive motoneurones were found to be apoptotic, as assessed by both TUNEL and caspase-3 immunoreactivity. Therefore, it is possible that the upregulation of hsp27 observed in injured motoneurones may play a role in protecting motoneurones from apoptotic cell death following nerve injury.


Risk factors of readmission and the impact of outpatient management in heart failure patients: A national study in Japan.
Heart failure is a significant disease, and its high readmission rate is a big concern. We must identify readmission risk factors and optimize outpatient management to prevent them. This study aims to investigate the readmission risk factors, including outpatient management represented by the number of outpatient visits, and to identify the factors related to frequent outpatient visits. We used the diagnosis-procedure-combination database between April 2016 and March 2022. Based on the number of outpatient visits within 60 days after discharge, we categorized patients into <1 visits/month, (1<, ≦2) visits/month, and <2 visits/month and observed the occurrence of 60 days readmission. We performed multiple logistic regression analyses to reveal the readmission risk factors and the association between the number of outpatient visits and readmission. As a subgroup analysis, we conducted the same research in the low- and high-readmission risk groups. We compared medical contents between (1<, ≦2) visits/month and <2 visits/month. We analysed 101 239 patients and identified the following factors as a risk of readmission: older age (P < 0.001), female (P = 0.009), longer length-of-hospital-stay (P < 0.001), artificial ventilator (P < 0.001), tolvaptan (P < 0.001), top 50% dosage of loop diuretics (P = 0.036), bottom 50% dosage of class III antiarrhythmic agents (P < 0.001), hypertension (P = 0.005), atrial fibrillation (P < 0.001), dilated cardiomyopathy (P < 0.001), valvular disease (P = 0.021), myocardial infarction (P < 0.001), diabetes (P < 0.001), and renal disease (P < 0.001). We revealed that the risk of readmission increases in <2 visits/month compared to (1<, ≦2) visits/month (P < 0.001), whereas the risk of readmission decreases in ≦1 visits/month compared with (1<, ≦2) visits/month (P < 0.001). In the subgroup analysis, we found the possibility that some risk factors are specific to the subgroup. We identified that the following factors were related to frequent outpatient visits: older age (P < 0.001), home medical care (P = 0.007), tolvaptan (P < 0.001), top 50% dosage of loop diuretics (P < 0.001), diabetes (P < 0.001), renal disease (P = 0.009), 0-2 weeks follow-up (P < 0.001), 2-4 weeks follow-up (P < 0.001), cardiac rehabilitation (P < 0.001), and echocardiography (P < 0.001). This study comprehensively identified risk factors for readmission and found outpatient visit is personalized by readmission risk. There is still room to optimize outpatient management. We suggest optimizing outpatient management according to our identified characteristics.


Dysfunction of Kidney Endothelium after Ischemia/Reperfusion and Its Prevention by Mitochondria-Targeted Antioxidant.
One of the most important pathological consequences of renal ischemia/reperfusion (I/R) is kidney malfunctioning. I/R leads to oxidative stress, which affects not only nephron cells but also cells of the vascular wall, especially endothelium, resulting in its damage. Assessment of endothelial damage, its role in pathological changes in organ functioning, and approaches to normalization of endothelial and renal functions are vital problems that need to be resolved. The goal of this study was to examine functional and morphological impairments occurring in the endothelium of renal vessels after I/R and to explore the possibility of alleviation of the severity of these changes using mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decylrhodamine 19 (SkQR1). Here we demonstrate that 40-min ischemia with 10-min reperfusion results in a profound change in the structure of endothelial cells mitochondria, accompanied by vasoconstriction of renal blood vessels, reduced renal blood flow, and increased number of endothelial cells circulating in the blood. Permeability of the kidney vascular wall increased 48 h after I/R. Injection of SkQR1 improves recovery of renal blood flow and reduces vascular resistance of the kidney in the first minutes of reperfusion; it also reduces the severity of renal insufficiency and normalizes permeability of renal endothelium 48 h after I/R. In in vitro experiments, SkQR1 provided protection of endothelial cells from death provoked by oxygen-glucose deprivation. On the other hand, an inhibitor of NO-synthases, L-nitroarginine, abolished the positive effects of SkQR1 on hemodynamics and protection from renal failure. Thus, dysfunction and death of endothelial cells play an important role in the development of reperfusion injury of renal tissues. Our results indicate that the major pathogenic factors in the endothelial damage are oxidative stress and mitochondrial damage within endothelial cells, while mitochondria-targeted antioxidants could be an effective tool for the protection of tissue from negative effects of ischemia.


Organ transplantation and gut microbiota: current reviews and future challenges.
Organ transplantation is often the only effective treatment for patients with end-stage diseases, such as heart, liver, kidney and small bowel failure and is carried out frequently worldwide. Still the post-transplantation complications remain health- and life-threatening outcome that needed to be resolved. With the rapid development of molecular technologies in recent years, more and more researchers realize that the gut microbiota may play a critical role in human diseases. The intestinal microbiome has been proved to provide a lot of functions to the host, such as digesting food, modulating metabolism, promoting angiogenesis and regulating the immune system. Several studies have investigated the alteration of intestinal microbiota in post-transplantation patients and observed significant changes in the intestinal microbiome compared to the pre-transplant condition. Due to the abovementioned features that the gut microbiota may be used in the prognosis of clinical outcome of organ transplantation. In addition, the FMT (fecal microbiota transplantation), probiotics and prebiotics as the newest therapy methods, effectiveness of which has been verified in some diseases, such as Clostridium difficile infection, inflammatory bowel disease and other chronic disorders, might be used as the prognosis tool in organ transplantation as well. The purpose of this present review is to elucidate the relationship between gut microbiota and organ transplantation as well as the potential use of new therapies like fecal microbiota transplantation, probiotic and prebiotic administration after the transplantation, and provide some ideas for future researches in field of organ transplantation.


Teratogenicity of antiepileptic drugs.
We review data on the comparative teratogenicity of antiepileptic drugs (AEDs), focusing on major congenital malformations (MCMs), intrauterine growth restriction, impaired cognitive development, and behavioral adverse effects following prenatal exposure. Prospective registries and meta-analyses have better defined the risk of MCMs in offspring exposed to individual AEDs at different dose levels. Valproate is the drug with the highest risk, whereas prevalence of MCMs is lowest with lamotrigine, levetiracetam, and oxcarbazepine. For valproate, phenobarbital, phenytoin, carbamazepine, and lamotrigine, the risk of MCMs is dose-dependent. Prenatal exposure to valproate has also been confirmed to cause an increased risk of cognitive impairments and autistic traits. In a population-based study, the risk of AED-induced autistic traits was attenuated by periconceptional folate supplementation. The risk of adverse fetal effects differs in relation to the type of AED and for some AEDs also the daily dose. Although for MCMs the risk is primarily associated with the first trimester of gestation, influences on cognitive and behavioral development could extend throughout pregnancy. Available information now permits a more rational AED selection in women of childbearing potential, and evidence-based counseling on optimization of AED treatment before conception.


Update on RefSeq microbial genomes resources.
NCBI RefSeq genome collection http://www.ncbi.nlm.nih.gov/genome represents all three major domains of life: Eukarya, Bacteria and Archaea as well as Viruses. Prokaryotic genome sequences are the most rapidly growing part of the collection. During the year of 2014 more than 10,000 microbial genome assemblies have been publicly released bringing the total number of prokaryotic genomes close to 30,000. We continue to improve the quality and usability of the microbial genome resources by providing easy access to the data and the results of the pre-computed analysis, and improving analysis and visualization tools. A number of improvements have been incorporated into the Prokaryotic Genome Annotation Pipeline. Several new features have been added to RefSeq prokaryotic genomes data processing pipeline including the calculation of genome groups (clades) and the optimization of protein clusters generation using pan-genome approach.


Lateral calcaneal artery island flaps.
A robust, arterially based, innervated island flap of thin skin has been successfully used in nine patients to repair defects around the ankle and heel. Based on the lateral calcaneal artery, the flap gives excellent, well-bedded cover in a short operation with insignificant donor site problems.


Analysis of the patient experience measure.
Assessing the patient experience has been a component of national health care policy for years in various forms, and it is now incorporated into many areas affecting physician practice. This review will focus on the origin and importance of this measure and address its critiques. The evolution of the measure as it progressed from patient satisfaction to patient experience and the rationale behind this shift will be detailed, the thought process behind the measure as an indicator of a culture of patient-centeredness and quality rather than as strictly a score will be reviewed, and the various motivators for physicians to improve patient experience will be divided into extrinsic and intrinsic and discussed.


Middle ear cavity and ear canal pressure-driven stapes velocity responses in human cadaveric temporal bones.
Drive pressure to stapes velocity (V(st)) transfer function measurements are collected and compared for human cadaveric temporal bones with the drive pressure alternately on the ear canal (EC) and middle ear cavity (MEC) sides of the tympanic membrane (TM), in order to predict the performance of proposed middle-ear implantable acoustic hearing aids, as well as provide additional data for examining human middle ear mechanics. The chief finding is that, in terms of the V(st) response, MEC stimulation performs at least as well as EC stimulation below 8 kHz, provided that the EC is unplugged. Plugging the EC causes a reduced response for MEC drive below 2 kHz, due to a corresponding reduction of the pressure difference between the two sides of the TM. Between 8 and 11 kHz, the MEC drive transfer functions feature an approximately 17 dB drop in magnitude below the EC drive case, the cause of which remains unknown. The EC drive transfer functions reported here feature significantly less magnitude roll-off above 1 kHz than previous studies [with a slope of -2.3 vs -6.7 dB/octave for Aibara et al., Hear. Res. 152, 100-109 (2001)], and significantly more phase group delay (134 vs 62 micros for Aibara et al.).


Multiple primary malignancies involving lung cancer.
The incidence of multiple primary malignancies (MPM) has increased sharply in recent decades. However, the clinical characteristics and prognosis of MPM patients involving lung cancer were not fully elucidated. This retrospective study was designed to explore the clinical characteristics and prognosis of MPM patients involving lung cancer in the People's Republic of China. Of 5405 lung cancer cases diagnosed at the Guangdong Lung Cancer Institute between 2005 and 2013, we analyzed 185 patients (3.4 %) with MPM involving lung cancer. Among 185 patients with MPM involving lung cancer, 10 (5.4 %)had three malignancies and 175 (94.6 %) had two malignancies. 10 patients with three malignancies were excluded from the analysis to avoid misunderstanding. Of 175 accompanying malignancies, 64 (36.6 %) were synchronous MPM patients and 111 (63.4 %) were metachronous MPM patients; 49 (28.0 %) were lung cancer first MPM patients and 126 (72.0 %) were other cancer first MPM patients. The most frequent accompanying malignancy was colon cancer (25/175), followed by rectal cancer (18/175), esophageal cancer (17/175), and thyroid cancer (13/175). Metachronous MPM patients showed significantly better overall survival (OS) than synchronous MPM, with a median OS of 72.8 (range 12.2-391.0) and 12.9 (range 0.8-86.3)months, respectively (P < 0.001). Cox regression analysis revealed that time of occurrence and stage were independent factors for OS. Colorectal cancer, esophageal cancer, and thyroid cancer were the tumors that most frequently accompanying lung cancer. Metachronous MPM patients showed significantly better OS compared with synchronous MPM patients.


Tuning gene expression to changing environments: from rapid responses to evolutionary adaptation.
Organisms are constantly exposed to a wide range of environmental changes, including both short-term changes during their lifetime and longer-term changes across generations. Stress-related gene expression programmes, characterized by distinct transcriptional mechanisms and high levels of noise in their expression patterns, need to be balanced with growth-related gene expression programmes. A range of recent studies give fascinating insight into cellular strategies for keeping gene expression in tune with physiological needs dictated by the environment, promoting adaptation to both short- and long-term environmental changes. Not only do organisms show great resilience to external challenges, but emerging data suggest that they also exploit these challenges to fuel phenotypic variation and evolutionary innovation.


Effect of phlorotannins on melanosis and quality changes of Pacific white shrimp (Litopenaeus vannamei) during iced storage.
Effect of phlorotannins (PT) treatments on the ployhenoloxidase (PPO) activity and quality changes of Pacific white shrimp during a 16-day period of storage in ice were studied. Among seaweeds, Sargassum tenerimum had the highest amount of PT (10.00 mg phloroglucinol/g), PPO inhibitory activity (71.94%) and therefore selected for PT extraction. The shrimp treated with 5% PT (w/v) showed the least melanosis score, pH, TVB-N values and lipid oxidation among all treatments throughout the iced storage. Lower counts of mesophilic and psychrotrophic bacteria (1-2 log CFU/g) were obtained with 5% PT treatment compared to the control at the last day of storage (P < 0.05). Sensory evaluation proved that 5% PT treatment could cause a 4-days increase in the shelf-life of shrimp compared to the control, PT1% and PT2% treatments. Therefore, 5% phlorotannins from S. tenerimum could be used as a safe melanosis inhibitor for the treatment of shrimp.


Accelerated Cine Cardiac MRI Using Deep Learning-Based Reconstruction: A Systematic Evaluation.
Breath-holding (BH) for cine balanced steady state free precession (bSSFP) imaging is challenging for patients with impaired BH capacity. Deep learning-based reconstruction (DLR) of undersampled k-space promises to shorten BHs while preserving image quality and accuracy of ventricular assessment. To perform a systematic evaluation of DLR of cine bSSFP images from undersampled k-space over a range of acceleration factors. Retrospective. Fifteen pectus excavatum patients (mean age 16.8 ± 5.4 years, 20% female) with normal cardiac anatomy and function and 12-second BH capability. 1.5-T, cine bSSFP. Retrospective DLR was conducted by applying compressed sensitivity encoding (C-SENSE) acceleration to systematically undersample fully sampled k-space cine bSSFP acquisition data over an acceleration/undersampling factor (R) considering a range of 2 to 8. Quality imperceptibility (QI) measures, including structural similarity index measure, were calculated using images reconstructed from fully sampled k-space as a reference. Image quality, including contrast and edge definition, was evaluated for diagnostic adequacy by three readers with varying levels of experience in cardiac MRI (>4 years, >18 years, and 1 year). Automated DL-based biventricular segmentation was performed commercially available software by cardiac radiologists with more than 4 years of experience. Tukey box plots, linear mixed effects model, analysis of variance (ANOVA), weighted kappa, Kruskal-Wallis test, and Wilcoxon signed-rank test were employed as appropriate. A P-value <0.05 was considered statistically significant. There was a significant decrease in the QI values and edge definition scores as R increased. Diagnostically adequate image quality was observed up to R = 5. The effect of R on all biventricular volumetric indices was non-significant (P = 0.447). The biventricular volumetric indices obtained from the reconstruction of fully sampled cine bSSFP acquisitions and DLR of the same k-space data undersampled by C-SENSE up to R = 5 may be comparable. 3 TECHNICAL EFFICACY: Stage 1.


[Cartilage-perichondrium autografting for the repair articular cartilage defects of finger: a report of 11 cases].
To study the clinical effects of self-invented cartilage-perichondrium autografting for the repair of articular cartilage defects, so as to reconstruct the joint surface. Among total 11 patients with hand injuries from Oct. 2005 to Oct. 2009, 7 patients were male and 4 patients were female, ranging in age from 17 to 50 years, with an average of 29 years. All the patients had serious injuries of finger joint and were treated with cartilage-perichondrium autografting. After the operation, function exercises were performed, and composite scores of joints at hand were used to evaluate therapeutic effects. All the patients were followed-up from 1 to 4 years with an average of 24 months. The operation of all the patients were successful, and there were no infection. The mean score was (41.0 +/- 0.63) in 2 years after operation. Eight patients got an excellent result (> 38 scores), 2 good (from 35 to 38 scores) and 1 bad (< 30 scores). The cartilage-perichondrium autografting method is effective to reconstruct the defects of articular cartilage, and decrease the disablement rate of hand injuries.


Influence of hormonal extracts on hens producing eggs with non-calcified or partially calcified shells and factors associated with this condition.
1. Daily injection of hypothalameal extract (HE) and adenohypophyseal extract (AE) into hens aged 56 or 67 weeks for 14 d did not significantly influence the production of shell-less (SL) or ultra-thin-shell (UTS) eggs. 2. The injection of HE significantly increased hard-shell (HS) egg production in the younger hens. 3. Neither AE nor HE affected egg weight, serum calcium, gain in body weight or food consumption. 4. In a third experiment hens selected for poor egg production laid at a rate of 58% of which 36% were SL, 29% UTS and 35% HS eggs. Whereas the production rate of the good layers was 65% of which 1-4% were SL and 1-4% were UTS eggs. 5. Specific gravity of HS eggs, serum calcium, weight of ovary, oviduct, or adenohypophysis did not differ between good and poor layers. 6. Since SL and UTS eggs are easily overlooked the decrease in egg production with age may be as great as indicated by normal production records; the problem may be concerned more with the mechanism of shell formation.


Light output function and assembly of the time-of-flight enhanced diagnostics neutron spectrometer plastic scintillators for background reduction by double kinematic selection at EAST.
The 2.5 MeV neutron spectrometer TOFED (Time-Of-Flight Enhanced Diagnostics) has been constructed to perform advanced neutron emission spectroscopy diagnosis of deuterium plasmas on EAST. The instrument has a double-ring structure which, in combination with pulse shape digitization, allows for a dual kinematic selection in the time-of-flight/recoil proton energy (tof/Ep) space, thus improving the spectrometer capability to resolve fast ion signatures in the neutron spectrum, in principle up to a factor ≈100. The identification and separation of features from the energetic ions in the neutron spectrum depends on the detailed knowledge of the instrument response function, both in terms of the light output function of the scintillators and the effect of undesired multiple neutron scatterings in the instrument. This work presents the determination of the light output function of the TOFED plastic scintillator detectors and their geometrical assembly. Results from dedicated experiments with γ-ray sources and quasi-monoenergetic neutron beams are presented. Implications on the instrument capability to perform background suppression based on double kinematic selection are discussed.


The effect of monoamine oxidase and catechol O-methyltransferase inhibitors on the accumulation and metabolism of [l-3H] norepinephrine by the adventitia and media of rabbit aorta.
The effects of catechol O-methyltransferase (COMT) and monoamine oxidase (MAO) inhibitors on the accumulation and metabolism of [l-3H] norepinephrine ([l-3H]NE) were studied in the isolated adventitia and media of rabbit aorta. The COMT inhibitors produced a greater inhibition of O-methylation in the isolated media than in the isolated adventitia. In addition, exposure to these drugs was associated with an increased level of [l-3H]NE and increased formation of the catechol deaminated metabolites by the isolated media but not by the isolated adventitia. The effects of these drugs on the balance of the oxidized vs. reduced forms of the deaminated metabolites was interpreted to mean that 3-methoxy-4-hydroxyphenylethylglycol is formed from normetanephrine rather than from 3,4-dihydroxyphenylethylglycol whereas 3-methoxy-4-hydroxymandelic acid is formed from 3,4-dihydroxymandelic acid. 3,4-Dihydroxyphenylethylglycol does not seem to serve as a substrate for 3-methoxy-4-hydroxyphenylethylglycol becuase it rapidly passes out of the tissue after it is formed. Parglyline and iproniazid markedly decreased deamination of [l-3H]NE and increased the tissue level of [l-3H]NE. However, these drugs produced little if any compensatory increase in O-methylation of [l-3H]NE. The effects of these drugs are compatible with the hypothesis that adrenergic nerves contain MAO and vascular smooth muscle contains MAO and COMT. Harmaline seemed to block both MAO and COMT. Based on the effects of clorgyline and deprenyl and the other MAO inhibitors tested, the isolated adventitia seems to contain primarily type A MAO and the isolated media seems to contain primarily type B MAO.


Characterization of mixing in shaker table containers.
Mixing in shaker table beakers is studied using dye dispersion to measure mixing times. Experimental conditions range from the laminar regime into the turbulent mixing. Different flow patterns occurring in the beakers are reported for the mixing. The transition Reynolds number is determined. Rotational speed of the table, volume of material to be mixed, and viscosity of the material are studied as to their effects on mixing time. A graphical mixing time correlation is provided which is useful for the translation of mixing from laboratory scale to pilot scale.


Levetiracetam in porphyric status epilepticus: a case report.
Status epilepticus in patients with acute intermittent porphyria (AIP) are difficult to treat. In this report the author describes a patient with AIP and status epilepticus who was successfully treated with a combination of intravenous magnesium and levetiracetam. This case and the limited experience reported in the literature show that it is probably safe to administer levetiracetam in patients with AIP; however, its role in the treatment of status epilepticus deserves further evaluation.


Complications of intestinal intubation; with report of two cases of unusual complication.
Many complications may arise from the use of intubation in treatment of intestinal obstruction. They are readily subject to classification and can be prevented by proper precautions. Two illustrative case reports of unusual complications are presented.


Colitis of Behçet's syndrome.
A 25-year-old previously healthy man developed complete Behçet's syndrome during five weeks. His main complaint was diarrhea with blood. Ulcers resembling aphthous ulcers of the mouth were revealed in the transverse, left and sigmoid colon by X-ray and sigmoidoscopy. Prednisone therapy was initiated and resulted in complete clinical restitution within three weeks.


Structural basis for LeishIF4E-1 modulation by an interacting protein in the human parasite Leishmania major.
Leishmania parasites are unicellular pathogens that are transmitted to humans through the bite of infected sandflies. Most of the regulation of their gene expression occurs post-transcriptionally, and the different patterns of gene expression required throughout the parasites' life cycle are regulated at the level of translation. Here, we report the X-ray crystal structure of the Leishmania cap-binding isoform 1, LeishIF4E-1, bound to a protein fragment of previously unknown function, Leish4E-IP1, that binds tightly to LeishIF4E-1. The molecular structure, coupled to NMR spectroscopy experiments and in vitro cap-binding assays, reveal that Leish4E-IP1 allosterically destabilizes the binding of LeishIF4E-1 to the 5' mRNA cap. We propose mechanisms through which Leish4E-IP1-mediated LeishIF4E-1 inhibition could regulate translation initiation in the human parasite.


Sleep Quality Assessment of Adolescents Residing in an Urban Resettlement Colony, New Delhi, India.
Sleep is essential for physical and psychological development of children as well as adolescents. Poor sleep has been noted to lead to poor diet, obesity, stunted growth, mental health issues, and substance abuse. Despite the knowledge regarding the importance of sufficient sleep, the prevalence of insufficient sleep has been noted to increase among children and adolescents. The aim of the study was to determine the prevalence of poor sleep quality among adolescents of an urban resettlement colony and to evaluate the association of poor sleep quality with the correlates. A community-based cross-sectional study was conducted including 620 adolescents aged 10-19 years, in an Urban Resettlement Colony, Dakshinpuri Extension, New Delhi. A self-reported interview was conducted with the pretested, semi-structured interview schedule. The interview focused on sociodemographic variable, sleep quality using Pittsburgh sleep quality index, Perceived stress scale, screen time, and anthropometric measurements. The mean of Pittsburgh sleep quality index total score was 2.3 (standard deviation = 1.9). Among the adolescents, 7.3% of them were found to be poor sleepers. Poor sleep quality was observed to be higher during school days as compared to vacation (9.3%, 6.5%, respectively). Adolescents of age group equal to and > 15 years have higher odds of having poor sleep quality than those younger than 15 years of age (odds ratio = 4.9; 95% confidence interval: 2.2, 10.8). Significant difference in sleep duration was noted among adolescents of age ≥15 years as compared to the younger group in the present study.


A Severe Diabetic Foot Ulcer With Intermediate Cuneiform Displacement and Multidrug-Resistant Pseudomonas aeruginosa Infection: A Rare Case Report.
Diabetic foot ulcer (DFU) is considered as one of the most serious and prevailing complications of diabetes mellitus, while it is the major cause of amputations in diabetic patients. Herein, we reported an acquired severe traumatic DFU with an intermediate cuneiform hairline fracture and displacement in a 55-year old male (Grade IV of Wagner classification; Grade III of IWGDF classification). The Pseudomonas aeruginosa was identified in pus culture. Data of antibiotic susceptibility testing indicated that the isolates of Pseudomonas aeruginosa were multi-drug resistant. Routine debridement, clearing displaced intermediate cuneiform and drainage were performed to facilitate the outflow of pus and pressure mitigation. Dressing with Prontosan solution and gel was applied to the wound, and meropenem was systemically administrated in addition to effective glycemic control. The DFU has been fully healed after ~40-day treatment. For this case, clearing the displaced and fractured intermediate cuneiform is essential for the heal of the DFU in addition to the common strategy for DFU treatment, i.e., the combination of debridement, pressure mitigation, wound dressing with Prontosan, antibiotic selection and effective glycemic control. This case report might have value for the treatment of complex DFU with bone fracture and displacement, reducing the risk of amputation.


Mechanism of Inactivation of Ornithine Aminotransferase by (1S,3S)-3-Amino-4-(hexafluoropropan-2-ylidenyl)cyclopentane-1-carboxylic Acid.
The inhibition of ornithine aminotransferase (OAT), a pyridoxal 5'-phosphate-dependent enzyme, has been implicated as a treatment for hepatocellular carcinoma (HCC), the most common form of liver cancer, for which there is no effective treatment. From a previous evaluation of our aminotransferase inhibitors, (1S,3S)-3-amino-4-(perfluoropropan-2-ylidene)cyclopentane-1-carboxylic acid hydrochloride (1) was found to be a selective and potent inactivator of human OAT (hOAT), which inhibited the growth of HCC in athymic mice implanted with human-derived HCC, even at a dose of 0.1 mg/kg. Currently, investigational new drug (IND)-enabling studies with 1 are underway. The inactivation mechanism of 1, however, has proved to be elusive. Here we propose three possible mechanisms, based on mechanisms of known aminotransferase inactivators: Michael addition, enamine addition, and fluoride ion elimination followed by conjugate addition. On the basis of crystallography and intact protein mass spectrometry, it was determined that 1 inactivates hOAT through fluoride ion elimination to an activated 1,1'-difluoroolefin, followed by conjugate addition and hydrolysis. This result was confirmed with additional studies, including the detection of the cofactor structure by mass spectrometry and through the identification of turnover metabolites. On the basis of this inactivation mechanism and to provide further evidence for the mechanism, analogues of 1 (19, 20) were designed, synthesized, and demonstrated to have the predicted selective inactivation mechanism. These analogues highlight the importance of the trifluoromethyl group and provide a basis for future inactivator design.