Medial Pontomedullary Stroke Mimicking Severe Bell's Palsy: A Case Report.
Patients with acute unilateral upper and lower facial palsy frequently present to the emergency department fearing they have had a stroke, but many cases are benign Bell's palsy. We present a rare case of a medial pontomedullary junction stroke causing upper and lower hemifacial paralysis associated with severe dysphagia and contralateral face and arm numbness. Although rare, pontine infarct must be considered in patients who present with both upper and lower facial weakness. Unusual neurologic symptoms (namely diplopia, vertigo, or dysphagia) and signs (namely gaze palsy, nystagmus, or contralateral motor or sensory deficits) should prompt evaluation for stroke.


Changing psychosocial morbidity in people aging with spinal cord injury.
to examine how scores on measures of stress, life satisfaction, depression, and psychological well-being relate to perceived quality of life among people with longstanding spinal cord injuries. 189 members of a British population-based study of outcomes after spinal cord injury were evaluated at three-year intervals from 1990 to 1999. Participants rated their quality of life at each interval, and completed various psychosocial measures. Scores and results were analyzed to identify changes over time and correlations with perceived quality of life. Self-ratings of quality of life were high and relatively stable over the duration of the longitudinal study. There were strong concurrent relationships between perceived quality of life and psychosocial outcomes. Across time periods, the outcomes studied did not seem to strongly predict later quality of life, but earlier perceived quality of life did predict later stress, depression, and psychological well-being. Perceived quality of life among this group of individual with long duration spinal cord injuries was high and relatively stable over time. Significant relationships identified between earlier quality of life and later perceived stress, depression, and well-being suggest that quality of life, typically thought of as a key outcome may itself be a predictor of other outcomes.


Improving resilience against natural gastrointestinal nematode infections in browsing kids during the dry season in tropical Mexico.
The objective was to determine the effect of supplementary feeding on the resilience and resistance of Criollo kids against natural gastrointestinal nematode (GIN) infections, when browsing native vegetation during the dry season in tropical Mexico. Thirty-three two-month-old Criollo kids, raised nematode free, were included at weaning in a 20-week trial. The kids were placed into four groups. Two groups of eight kids were offered 100g/day soybean and sorghum meal (26%:74% respectively fresh basis) (treated/supplemented (T-S) and infected/supplemented (I-S)). Two groups remained with no supplement for the duration of the trial (infected/non-supplemented (I-NS) (n=9) and treated/non-supplemented (T-NS) (n=8)). Kids in groups T-S and T-NS were drenched with 0.2mg of moxidectin/kg body weight orally (Cydectin, Fort Dodge) every 28 days. Groups I-S and I-NS were naturally infected with GIN. The animals browsed native vegetation for an average of 7h/day together with a herd of 120 naturally infected adult goats. Cumulative live weight gain (CLWG), packed cell volume (PCV), haemoglobin (Hb), total plasma protein and plasma albumin were recorded every 14 days as measurements of resilience. Resistance parameters (faecal egg counts (FEC) and peripheral eosinophil counts (PEC)) were also measured. Bulk faecal cultures were made for each group every 28 days. Every month a new pair of initially worm-free tracer kids assessed the infectivity of the vegetation browsed by the animals. Tracer kids and faecal cultures showed that kids faced low mixed infections (Haemonchus contortus, Trichostrongylus colubriformis and Oesophagostomum columbianum). Under conditions of scarce vegetation, such as those in the present study, supplemented groups (I-S and T-S) had higher growth rates compared to the non-supplemented groups independently of the control of GIN infection with anthelmintic (AH) treatment (P<0.001). Supplementary feeding did not affect FEC or PEC. In the absence of supplementation, lack of AH treatment may lead to outbreaks of clinical nematodosis. The supplementary feeding was economically feasible.


Effectiveness of 1, 2, and 3 Doses of Human Papillomavirus Vaccine Against High-Grade Cervical Lesions Positive for Human Papillomavirus 16 or 18.
Before 2016, human papillomavirus (HPV) vaccination was recommended on a 3-dose schedule. However, many vaccine-eligible US females received fewer than 3 doses, which provided an opportunity to evaluate the real-world vaccine effectiveness (VE) of 1, 2, and 3 doses. We analyzed data on cervical intraepithelial neoplasia (CIN) grades 2-3 and adenocarcinoma in situ (designated CIN2+) from the HPV Vaccine Impact Monitoring Project (HPV-IMPACT; 2008-2014). Archived tissue from CIN2+ lesions was tested for 37 types of HPV. Women were classified by number of doses received ≥24 months before CIN2+ detection. Using a test-negative design, VE was estimated as 1 minus the adjusted odds ratio from a logistic regression model that compared vaccination history for women whose lesions tested positive for HPV-16/18 (vaccine-type cases) with that for women who had all other CIN2+ lesions (controls). Among 3,300 women with available data on CIN2+, typing results, and vaccine history, 1,561 (47%) were HPV-16/18-positive, 136 (4%) received 1 dose of HPV vaccine, 108 (3%) received 2 doses, and 325 (10%) received 3 doses. Adjusted odds ratios for vaccination with 1, 2, and 3 doses were 0.53 (95% confidence interval (CI): 0.37, 0.76; VE = 47%), 0.45 (95% CI: 0.30, 0.69; VE = 55%), and 0.26 (95% CI: 0.20, 0.35; VE = 74%), respectively. We found significant VE against vaccine-type CIN2+ after 3 doses of HPV vaccine and lower but significant VE with 1 or 2 doses.


Effect of dithiothreitol of the reaction of renin and angiotensinogen.
Effects of several sulfhydryl reagents on the reaction of renin and angiotensinogen were investigated by measuring the production of angiotensin I. Renin and angiotensinogen were prepared from the kidneys of dogs and from plasma of nephrectomized dogs, respectively. The amount of angiotensin I generated was increased with application of dithiothreitol, dithioerythritol and 2,3-mercapto-1-propanol. The greatest enhancement of the generation of angiotensin I was observed with dithiothreitol. Dithiothreitol had no influence on renin activity, on radioimmunoassay for angiotensin I and the recovery of synthetic angiotensin I from the incubation medium. When heterologous angiotensinogen was used, a great enhancement of generation of angiotensin I was observed. Dithiothreitol did not accelerate the reaction following replacement of the natural substrate, angiotensinogen, with the synthetic tetradecapeptide as substrate. It is postulated that dithiothreitol augments angiotensin I generation by acting on the angiotensinogen and not on the renin.


ICS-SUFU standard: Theory, terms, and recommendations for pressure-flow studies performance, analysis, and reporting. Part 2: Analysis of PFS, reporting, and diagnosis.
The Working Group (WG), initiated by the International Continence Society (ICS) Standardisation Steering Committee and supported by the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction, has revised the ICS Standard for pressure-flow studies of 1997. Based on the ICS standard for developing evidence-based standards, the WG developed this new ICS standard in the period from May 2020 to December 2022. A draft was posted on the ICS website in December 2022 to facilitate public discussion and the comments received have been incorporated into this final release. The WG has recommended analysis principles for the diagnosis of voiding dysfunction for adult men and women without relevant neurological abnormalities. New standard terms and parameters for objective and continuous grading of urethral resistance (UR), bladder outflow obstruction (BOO) and detrusor voiding contraction (DVC) are introduced in this part 2 of the standard. The WG has summarized the theory and recommendations for the practice of pressure-flow study (PFS) for patients in part 1. A pressure-flow plot is recommended for the diagnosis of every patient, in addition to time-based graphs. Voided percentage and post void residual volume should always be included in PFS analysis and diagnosis. Only parameters that represent the ratio or subtraction of pressure and synchronous flow are recommended to quantify UR and only parameters that combine pressure and flow in a product or sum are recommended to quantify DVC. The ICS BOO index and the ICS detrusor contraction index are introduced in this part 2 as the standard. The WG has suggested clinical PFS dysfunction classes for male and female patients. A pressure-flow scatter graph including every patient's pdet at maximum flow (pdetQmax ) with maximum flow rate (Qmax ) point should be included in all scientific reports considering voiding dysfunction. PFS is the gold standard used to objectively assess voiding function. Quantifying the dysfunction and grading of abnormalities are standardized for adult males and females.


Measurement of the secondary structure of adsorbed protein by circular dichroism. 1. Measurements of the helix content of adsorbed melittin.
A new circular dichroism (CD) technique is presented which quantifies, in situ, the changes in protein and peptide secondary structure upon adsorption at the quartz/liquid interface. Far-UV CD spectra of adsorbed proteins were recorded from several quartz interfaces contained in a specially constructed cell. Adsorbed, oriented alpha-helical spectra were recorded from hydrophilic and hydrophobic quartz using the bee venom peptide, melittin, which can be induced into an alpha-helical, tetrameric conformation in solution. The hydrophobic quartz provides a model system for oil-in-water emulsions and cell membranes. Surface concentrations were determined by radio-counting and were dependent on the nature of the surface. The characterization of these spectra has been partly achieved using far-UV CD spectra obtained from melittin adsorbed onto hydrophilic colloidal silica particles, where orientation effects are eliminated. Analysis of these spectra reveals considerable denaturation of the helical structures upon adsorption. Surface concentrations from the silica were determined from adsorption isotherms. The surface orientation of adsorbed melittin was dependent on the state of aggregation and hence degree of helicity of the molecule. These results support a model for the mode of action of melittin in lysing membranes.


Assessment of various psychopharmacological combinations in the treatment of presenile and senile primary degenerative dementia.
The effects of various psychopharmacological combinations were used in a sample of 90 patient fulfilling the DMS-III criteria for presenile or senile primary degenerative dementia divided into 3 equal subgroups. Regardless of the drug combination used, an improvement of verbal test performances was noticed.


An immunohistochemical study of myelin proteins during remyelination in the central nervous system.
The process of remyelination in the superior cerebellar peduncles of mice following demyelination with Cuprizone was studied immunohistochemically using antisera to myelin basic protein (MBP) and myelin-associated glycoprotein (MAG). Demyelination occurred after formation of myelinic vacuoles and resulted in almost complete loss of demonstrable MBP and MAG from the peduncle. Prior to the onset of remyelination, oligodendrocytes with cytoplasmic staining for both proteins appeared in the peduncle. These cells were then associated with remyelinating axons. The axons were remyelinated in clusters until the MBP and the MAG in the whole peduncle were reconstituted, although the axon sheaths were thinner than those in normal animals. The results show that the immunohistochemical distribution of MBP and MAG in remyelinating axons resembles that in normal axons, and that the expression of myelin proteins in oligodendrocytes during remyelination reverts to that seen during normal development.


Endothelin and 5-hydroxytryptamine on rat pulmonary artery in pulmonary hypertension.
Contractile responses to endothelin, 5-hydroxytryptamine (5-HT), noradrenaline and potassium were obtained on isolated preparations of pulmonary artery from rats made pulmonary hypertensive by an injection of monocrotaline (105 mg/kg s.c.) 4 weeks previously. When compared with data obtained in control rats, the potencies (negative log EC50 values) for 5-HT, noradrenaline and potassium were increased (30, 3- and 3-fold, respectively), and the maximum contractions (mN/mm2) to endothelin, noradrenaline and potassium were reduced (65, 40 and 45% reduction). These changes were not seen 2 weeks after injection of monocrotaline, before pulmonary hypertension developed, or in preparations of aorta. It is concluded that monocrotaline-induced pulmonary hypertension affects pulmonary vascular responsiveness to spasmogens differentially. The comparative importance of endothelin and 5-HT as pulmonary vasoconstrictors may change in monocrotaline-induced pulmonary hypertension, there being an increase in responsiveness to 5-HT and a decrease in responsiveness to endothelin.


For children leaving the emergency department before being seen by a physician, counseling from nurses decreases return visits.
Nurses counsel the parents of patients leaving without being seen by a physician (LWBS) about common childhood illnesses. This strategy's impact is not known. To assess the impact of nurse counseling on ED return visits and outcomes for children who LWBS. This retrospective cohort study used the computerized database of a tertiary care pediatric ED. Participants were all triaged children who LWBS between April 1st 2008 and March 31st 2009. Parents who notified nurses of their intention to leave received information and counseling on when to return. This counseling's occurence was this study's exposure of interest. The control group included patients who LWBS without notification and thus were not counseled. The primary outcome was a return visit to the ED within 48h. Triage level and referral status were used as severity indicators. To demonstrate a 2% difference in return visits (α value 0.05, power 80%), 3213 participants were needed per group. During the study period, 60,525 patients consulted the ED and 10,323 LWBS; of these, 4639 (45%) received nurse counseling and 5684 (65%) did not. There was a 2.0% (95% CI 1.0, 3.0) decrease in ED return visit proportions between groups. On multiple logistic regression, the counseled group was less likely to return to the ED within 48h. This study suggests that, of patients who LWBS, those who receive counseling by a nurse have less return visits in the following 48h.


Expression analysis of wound healing genes in human periapical granulomas of progressive and stable nature.
Wound healing process involves the activation of extracellular matrix components, remodeling enzymes, cellular adhesion molecules, growth factors, cytokines and chemokines genes. However, the molecular patterns underlying the healing process at the periapical environment remain unclear. Here we hypothesized that endodontic infection might result in an imbalance in the expression of wound healing genes involved in the pathogenesis of periapical lesions. Furthermore, we suggest that differential expression of wound healing markers in active and latent granulomas could account for different clinical outcomes for such lesions. Study samples consisted of 93 periapical granulomas collected after endodontic surgeries and 24 healthy periodontal ligament tissues collected from premolars extracted for orthodontic purposes as control samples. Of these, 10 periapical granulomas and 5 healthy periapical tissues were used for expression analysis of 84 wound healing genes by using a pathway-specific real-time polymerase chain reaction array. The remaining 83 granulomas and all 24 control specimens were used to validate the obtained array data by real-time polymerase chain reaction. Observed variations in expression of wound healing genes were analyzed according to the classification of periapical granulomas as active/progressive versus inactive/stable (as determined by receptor activator for nuclear factor kappa B ligand/osteoprotegerin expression ratio). We observed a marked increase of 5-fold or greater in SERPINE1, TIMP1, COL1A1, COL5A1, VTN, CTGF, FGF7, TGFB1, TNF, CXCL11, ITGA4, and ITGA5 genes in the periapical granulomas when compared with control samples. SERPINE1, TIMP1, COL1A1, TGFB1, and ITGA4 mRNA expression was significantly higher in inactive compared with active periapical granulomas (P < .001), whereas TNF and CXCL11 mRNA expression was higher in active lesions (P < .001). The identification of novel gene targets that curb the progression status of periapical lesions might contribute to a more accurate diagnosis and lead to treatment modalities more conducive to endodontic success.


Measuring Quality of Care for Ischemic Stroke Treated With Acute Reperfusion Therapy in Japan - The Close The Gap-Stroke.
In Japan there is no consensus on how to efficiently measure quality indicators (QIs), defined as a standard of care, for acute ischemic stroke (AIS). Using information from a health insurance claims database and electronic medical records, we evaluated the feasibility and validity of measuring QIs for AIS patients who received intravenous recombinant tissue plasminogen activator (IV rt-PA) or endovascular therapy (EVT).Methods and Results:AIS patients receiving rt-PA or EVT between 2013 and 2015 were identified. We selected 17 AIS QI measures for primary stroke centers (PSCs) and 8 for comprehensive stroke centers (CSCs). Defined QIs were calculated for each hospital and then averaged. In total, the data of 8,206 patients (rt-PA 83.7%, EVT 34.9%) from 172 hospitals were obtained. Median National Institute of Health Stroke Scale score at admission was 14, and 37.7% of the patients were functionally independent at discharge. All target QIs were successfully measured with fewer missing values, and the accuracy of preset data was about 90%. Adherence rates were low (<50%) in 5 QI measures among PSCs, including door-to-needle time ≤1 h, and in 1 QI measure among CSCs (door-to-brain and vascular imaging time ≤30 min). Measuring QIs for AIS by this novel approach was feasible and reliable in the provision of a national benchmark.


[The determination of trypsin activity in duodenal fluid with N alpha-(p-toluenesulfonyl)-L-arginine-p-nitranilide (L-TAPA)].
The conditions are optimized for the determination of trypsin activity in duodenal juice at 37 degrees C using L-TAPA as a substrate ("Bio-La-Test Trypsin", Lachema, CSSR). Most of the directions of the kit could be accepted, but optimal pH was 0.4 units below that described there. This method allows a highly specific, sensitive, and sufficiently precise determination of trypsin activity in duodenal juice.


Toxicity and biogas production potential of refinery waste sludge for anaerobic digestion.
Two waste streams from an oil refinery wastewater treatment system, float from a dissolved air flotation unit (DAF sludge) and waste activated sludge (WAS), were investigated to determine toxicity and biogas production potential for anaerobic digestion through batch testing methods. Ozonation as a pretreatment was investigated to observe the impacts of waste solubilization on both toxicity and biodegradability. Anaerobic toxicity assays resulted in no detectible inhibition from WAS, neither with nor without ozonation. Untreated DAF sludge exhibited inhibition that amplified with the increases in DAF sludge inclusion. Ozone treatment effectively reduces this inhibition. The biodegradability of WAS, measured by biochemical methane potential tests, doubled with low dose ozonation. DAF sludge biodegradability was negligible prior to treatment and was successfully enhanced through ozonation.


Recruitment of epitope-specific T cell clones with a low-avidity threshold supports efficacy against mutational escape upon re-infection.
Repetitive pathogen exposure leads to the dominant outgrowth of T cell clones with high T cell receptor (TCR) affinity to the relevant pathogen-associated antigens. However, low-affinity clones are also known to expand and form immunological memory. While these low-affinity clones contribute less immunity to the original pathogen, their role in protection against pathogens harboring immune escape mutations remains unclear. Based on identification of the TCR repertoire and functionality landscape of naive epitope-specific CD8+ T cells, we reconstructed defined repertoires that could be followed as polyclonal populations during immune responses in vivo. We found that selective clonal expansion is governed by clear TCR avidity thresholds. Simultaneously, initial recruitment of broad TCR repertoires provided a polyclonal niche from which flexible secondary responses to mutant epitopes could be recalled. Elucidating how T cell responses develop "from scratch" is informative for the development of enhanced immunotherapies and vaccines.


False aneurysm of the common femoral artery secondary to migration of a threaded acetabular component. A case report and review of the literature.
A 66-year-old woman with severe rheumatoid arthritis had revision of a protrusio acetabuli component with a threaded socket. Subsequent anteromedial migration of the socket and thread laceration of the common femoral artery resulted in a pseudoaneurysm and massive pelvic erosion seven months later. Vascular reconstruction and excisional arthroplasty were necessary. Later, gracilis and gluteal muscle flaps were swung to fill the resultant pelvic cavity. The hip was nonreconstructable. Ten months later the wound healed and the patient was ambulating in a walker. This represents a previously unreported cause of vascular injury complicating total hip arthroplasty (THA). A comprehensive review of the English and European literature illustrates the various mechanisms of vascular trauma in this setting and provides a rational basis for prevention.


Social media and orthodontics: A mixed-methods analysis of orthodontic-related posts on Twitter and Instagram.
In modern health care, social media has become an important tool for both patients and professionals. On platforms like Twitter and Instagram, patients can express their experiences, attitudes, and emotions regarding their orthodontic treatment or the available treatment options. This study aimed to investigate orthodontic-related social media use by analyzing the contents of posts made by patients and/or peers and exploring potential differences of users' attitudes on Twitter and Instagram. During a 30-day period, we collected 361 orthodontic-related posts-153 from Twitter and 208 from Instagram-using the same search strategy on both platforms. A mixed-methods approach was applied. First, all posts were structured according to a qualitative content analysis. Subsequently, quantitative analysis was performed to detect potential differences between posts on Twitter and Instagram. The following main themes were identified: "Getting braces" and "Getting braces removed," "Limitations due to braces," "Seeking information," and "Comedy." In addition to this classification, all posts were categorized as positive, negative, or neutral. Pictures and emoticons were frequently used to express experiences, attitudes, and emotions regarding orthodontic appliances. There were significant differences between posts on Twitter and those on Instagram; that is, the latter contained more posts that were categorized as positive. To date, only a few studies addressed the role of social media for orthodontic patients. This study provided insights into the experiences, attitudes, and emotions of patients and their peers regarding orthodontics and helped to reveal the potential impact of social media use on the field of orthodontics. Attention must be paid to the functional differences between Twitter and Instagram because these might lead patients to express themselves in specific ways.


Homophily in the career mobility of China's political elite.
We argue that leadership promotion in China's political elite relies on homophily for signals of trustworthiness and future cooperative behavior more than on economic performance. We first point to the limitation of the economic performance argument from within the framework of China's specific M-form state structure, and then we proffer a sociological explanation for why higher-level elites in China rely on homophilous associations in recruiting middle-level elites to the top positions of state. Using a unique dataset covering China's provincial leaders from 1979 to 2011, we develop a homophily index focusing on joint origin, joint education and joint work experience. We trace personal similarities in these respects between provincial leaders and members of China's supreme decision-making body, the Politbureau's Standing Committee. We then provide robust evidence confirming the persisting impact of homophilous associations on promotion patterns in post-reform China.


Tissue-Specific Features of Innate Lymphoid Cells.
Although the function of the circulating immune cell compartment has been studied in detail for decades, limitations in terms of access and cell yields from peripheral tissues have restricted our understanding of tissue-based immunity, particularly in humans. Recent advances in high-throughput protein analyses, transcriptional profiling, and epigenetics have partially overcome these obstacles. Innate lymphoid cells (ILCs) are predominantly tissue-resident, and accumulating data indicate that they have significant tissue-specific functions. We summarize current knowledge of ILC phenotypes in various tissues in mice and humans, aiming to clarify ILC immunity in distinct anatomical locations.


Influence of surgical margin width on survival rate after resection of intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.
Hepatectomy is the best treatment for patients with intrahepatic cholangiocarcinoma (ICC) at present, but there has been controversy about the width of surgical margins. In this study, we systematically investigated the effects of different surgical margin widths on the prognosis of patients with ICC undergoing hepatectomy. Systematic review and meta-analysis. PubMed, Embase and Web of Science databases were systematically searched from inception to June 2022. Cohort studies reported in English with patients who underwent negative marginal (R0) resection were included. The effects of surgical margin width on overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) in patients with ICC were assessed. Two investigators independently conducted literature screening and data extraction. Risk of bias was assessed using funnel plots and quality was assessed by the Newcastle-Ottawa Scale. Forest plots of HRs and their 95% CIs for outcome indicators were plotted. Heterogeneity was assessed and determined quantitatively using I2, and the stability of the study results was evaluated using sensitivity analysis. Analyses were performed using Stata software. Nine studies were included. With the wide margin group (≥10 mm) as the control, pooled HR of OS in the narrow margin group (<10 mm) was 1.54 (95% CI 1.34 to 1.77). HRs of OS in three subgroups where the margin was less than 5 mm ranged from 5 mm to 9 mm, or was less than 10 mm in length were 1.88 (1.45 to 2.42), 1.33 (1.03 to 1.72) and 1.49 (1.20 to 1.84), respectively. Pooled HR of DFS in the narrow margin group (<10 mm) was 1.51 (1.14 to 2.00). Pooled HR of RFS in the narrow margin group (<10 mm) was 1.35 (1.19 to 1.54). HRs of RFS in three subgroups where the margin was less than 5 mm ranged from 5 mm to 9 mm, or was less than 10 mm in length were 1.38 (1.07 to 1.78), 1.39 (1.11 to 1.74) and 1.30 (1.06 to 1.60), respectively. Neither lymph node lesions (HR 1.44, 95% CI 1.22 to 1.70) nor lymph node invasion (2.14, 1.39 to 3.28) was favourable for postoperative OS in patients with ICC. Lymph node metastasis (1.31, 1.09 to 1.57) was unfavourable for RFS in patients with ICC. Patients with ICC who underwent curative hepatectomy with a negative margin ≥10 mm may have a long-term survival advantage, but lymph node dissection also needs to be considered. In addition, tumour-related pathological features need to be explored to see if they affect the surgical outcome of R0 margins.


Cosmetic Labiaplasty in an Adolescent Population.
Labiaplasty (defined as the surgical reduction of the labia minora) is the most common procedure under the umbrella of female genital cosmetic surgery with the prevalence increasing over the past 10-15 years. However, the concept of labial hypertrophy holds an arbitrary definition, with no research into labial size undertaken within the pediatric and adolescent populations. Under the tenets of medical ethics there is acceptance of the need to avoid harm and so, for reasons to be outlined, performance of labiaplasty in children and adolescents should be avoided. This Mini-Review does not extend to pathological conditions that affect the labia minora.


Epimerization of 3-hydroxyacyl-CoA esters in rat liver. Involvement of two 2-enoyl-CoA hydratases.
Interconversion of D- and L-isomers of 3-hydroxy-decanoyl-CoA was catalyzed by rat liver homogenate. Cation exchange chromatography followed by ammonium sulfate precipitation and PBE-94 chromatofocusing column was used to separate the peroxisomal bifunctional protein, the classic 2-enoyl-CoA hydratase (crotonase), and a novel 2-enoyl-CoA hydratase. Epimerization activity was lost during the last purification step. None of the above proteins was capable of catalyzing the epimerization by itself, but reconstitution was achieved by recombining crotonase and the novel 2-enoyl-CoA hydratase. Since hydration by the latter enzyme follows a different stereochemical course from that with crotonase, these two hydratases are distinguished as 2-enoyl-CoA hydratase 1 (crotonase) and 2-enoyl-CoA hydratase 2 (the novel hydratase). The data strongly suggested that epimerization in the rat liver proceeds via dehydration-hydration catalyzed by the two different hydratases. The intermediate of this two step mechanism appears to be trans-2-enoyl-CoA.


Dynamic evaluation of anterior dental alignment in a sample of 8- to 11-year-old children.
To describe perceptions related to different anterior dental alignments in a sample of 106 children aged between 8- and 11-years-old. We employed dynamic media (videos) showing a smile in four different arrangements (ideal incisal occlusion - N, median diastema - D, incisal crowding - A, protruding incisors - P), with and without general contextual attractiveness. The perception is the same both for the whole face and for the frontal smile alone and there are no significant differences between the answers from male and female interviews. Smiles with normal alignment gain higher scores for esthetics and are associated with more positive qualities. In contrast, smiles with proclined and crowded teeth obtain lower scores. Analysis of the results showed that there are no significant differences between perceptions, sensations and judgments related to smiles presented either as part of the whole face or in only the lower facial third: general facial attractiveness does not influence evaluations of the smile. The study confirms the general tendency to award higher scores to smiles with normal alignment.


Heart rate variability and the prone position under general versus spinal anesthesia.
To evaluate heart rate (HR) variability in the prone position with power spectral heart rate (PSHR) analysis during spinal and general anesthesia. Prospective, clinical evaluation of HR variability in the prone position. Tertiary care teaching hospital. 20 healthy, ASA physical status I and II patients scheduled for elective lumbar spine surgery in the prone position. Anesthetic technique was either a standard general anesthetic or spinal anesthetic, based on the preference of the patient. Power spectral heart rate, HR, and blood pressure (BP) readings were determined prior to anesthetic intervention and as soon as a stable PSHR reading was available in the prone position. Heart rate and BP were recorded at baseline prior to anesthesia and at the time of stable PSHR data in the prone position. Power spectral heart rate data included low-frequency activity (LFa), high-frequency activity (HFa), and the ratio (LFa/HFa). Spinal anesthesia level was recorded by thoracic dermatome at complete onset. Data were collected from 20 patients; 12 patients chose spinal anesthesia and 8 chose general anesthesia. The prone position resulted in significant increase in HR in the spinal group and significant decrease in BP in the general anesthesia group. Low-frequency activity and LFa/HFa ratio were unchanged in the spinal anesthesia group and were significantly decreased in the general anesthesia group. Spinal level was T8.7. The association of less change in LFa activity and preservation of BP on assumption of the prone position in patients during low spinal anesthesia suggests better preservation of autonomic nervous system compensatory mechanisms during low spinal anesthesia than with general anesthesia.


A systems approach to management training for mental health professionals.
As an example of progress, a program is described, undertaken, by the New York School of Psychiatry, to train and educate psychiatrists and related professional groups in management and administration.


Mechanomics analysis of hESCs under combined mechanical shear, stretch, and compression.
Human embryonic stem cells (hESCs) can differentiate to three germ layers within biochemical and biomechanical niches. The complicated mechanical environments in vivo could have diverse effects on the fate decision and biological functions of hESCs. To globally screen mechanosensitive molecules, three typical types of mechanical stimuli, i.e., tensile stretch, shear flow, and mechanical compression, were applied in respective parameter sets of loading pattern, amplitude, frequency, and/or duration, and then, iTRAQ proteomics test was used for identifying and quantifying differentially expressed proteins in hESCs. Bioinformatics analysis identified 37, 41, and 23 proteins under stretch pattern, frequency, and duration, 13, 18, and 41 proteins under shear pattern, amplitude, and duration, and 4, 0, and 183 proteins under compression amplitude, frequency, and duration, respectively, where distinct parameters yielded the differentially weighted preferences under each stimulus. Ten mechanosensitive proteins were commonly shared between two of three mechanical stimuli, together with numerous proteins identified under single stimulus. More importantly, functional GSEA and WGCNA analyses elaborated the variations of the screened proteins with loading parameters. Common functions in protein synthesis and modification were identified among three stimuli, and specific functions were observed in skin development under stretch alone. In conclusion, mechanomics analysis is indispensable to map actual mechanosensitive proteins under physiologically mimicking mechanical environment, and sheds light on understanding the core hub proteins in mechanobiology.


IgA-Mediated Killing of Tumor Cells by Neutrophils Is Enhanced by CD47-SIRPα Checkpoint Inhibition.
Therapeutic monoclonal antibodies (mAb), directed toward either tumor antigens or inhibitory checkpoints on immune cells, are effective in cancer therapy. Increasing evidence suggests that the therapeutic efficacy of these tumor antigen-targeting mAbs is mediated-at least partially-by myeloid effector cells, which are controlled by the innate immune-checkpoint interaction between CD47 and SIRPα. We and others have previously demonstrated that inhibiting CD47-SIRPα interactions can substantially potentiate antibody-dependent cellular phagocytosis and cytotoxicity of tumor cells by IgG antibodies both in vivo and in vitro IgA antibodies are superior in killing cancer cells by neutrophils compared with IgG antibodies with the same variable regions, but the impact of CD47-SIRPα on IgA-mediated killing has not been investigated. Here, we show that checkpoint inhibition of CD47-SIRPα interactions further enhances destruction of IgA antibody-opsonized cancer cells by human neutrophils. This was shown for multiple tumor types and IgA antibodies against different antigens, i.e., HER2/neu and EGFR. Consequently, combining IgA antibodies against HER2/neu or EGFR with SIRPα inhibition proved to be effective in eradicating cancer cells in vivo In a syngeneic in vivo model, the eradication of cancer cells was predominantly mediated by granulocytes, which were actively recruited to the tumor site by SIRPα blockade. We conclude that IgA-mediated tumor cell destruction can be further enhanced by CD47-SIRPα checkpoint inhibition. These findings provide a basis for targeting CD47-SIRPα interactions in combination with IgA therapeutic antibodies to improve their potential clinical efficacy in tumor patients.


Update on avian influenza in Europe.
This article has been prepared by Helen Roberts and colleagues from Defra's International Disease Monitoring Team with Jane Clark, Richard Irvine and Ian Brown of the APHA.


A new approach for pudendal nerve exposure and its clinical significance.
Analgesia of the pudendal nerve is used in patients undergoing gynecologic, obstetric and penile surgery. Stimulation techniques are used to determine the functions of the nerve. In these interventions, different landmarks are used to describe the localization of this nerve. Although some authors use perineal approaches, others prefer a transvaginal (rectal in males) approach. Knowledge regarding the anatomy of the pudendal nerve and its blockade allows an easy approach to the clinical problems like perineal neuralgia, neurogenic bladder dysfunction and penile implant operations. However, in the descriptions of these different approaches, there is no clear information regarding the depth of the nerve and the branches of the pudendal nerve that are blocked. The aim of the present study was to determine the depth and location of the pudendal nerve and, thus, describe certain and easily identified surface landmarks for clinical use. According to our examinations, the distance between the ischial tuberosity and the coccyx (the base of a triangle defined by the ischial tuberosity, coccyx and ischial spine) was 8.62 +/- 0.92 cm (range 6.74-9.77 cm). The distance between the ischial tuberosity and the ischial spine was 5.23 +/- 0.33 cm (range 4.76-5.81 cm) and the distance from the ischial spine to the coccyx was 5.42 +/- 0.52 cm (range 4.02-6.32 cm). Because the pudendal nerve intersected the distance between the posterior superior iliac spine and the ischial tuberosity, the distance between these two landmarks was also measured and found to be 13.31 +/- 0.91 cm (range 10.58-15.13 cm); the depth of the nerve was 4.14 +/- 0.83 cm (range 3.13-5.25 cm).


[Filariasis in Gabon: treatment with mebendazole of filariasis due to M. perstans and Loa loa].
Mebendazole (Vermox 500) in long duration treatment 2 g/day for 3 to 4 weeks, is sometimes indicated in therapy of Loa Loa filariasis but remains the only active therapy on M. perstans filariasis. The perfect product tolerance and efficacy allow large indication in treatment of this last filariasis, the most often found in Gabon (Central Africa).


Effects of depolarization evoked Na+ influx on intracellular Na+ concentration at neurosecretory nerve endings.
Electrophysiological measurements of voltage-dependent Na+ influx using patch-clamp methodology were combined with optical monitoring of the free intracellular Na+ concentration in isolated rat neurohypophysial nerve endings to determine the relationship between Na+ influx generated by repetitive stimulation and change in [Na+]i. Application of step depolarizations under voltage-clamp-evoked tetrodotoxin-sensitive inward currents that were dependent upon extracellular Na+ and that exhibited rapid activation and inactivation properties. These characteristics substantiated the evoked current as a voltage-dependent Na+ current. Application of stimulus trains consisting of step depolarizations that mimick in frequency and duration those of action potentials were found to result in increases in [Na+]i. The induced change in [Na+]i was found to be related to the frequency and period of stimulation. Changes in [Na+]i were greatest at frequencies of 40 Hz and gave maximal changes with 30 s of continuous stimulation of approximately 2.4 mM. Sodium influx expressed as a molar quantity resulted in a nearly directly proportional increase in [Na+]i during the initial period of stimulation at low Na+ loads. When expressed as a charge density (pC/microm2) Na+ influx was found to increase with smaller diameter nerve endings as did the rate of change in [Na+]i in response to applied repetitive step depolarizations. Repetitive step depolarizations which simulate impulse activity that invade neuroendocrine nerve endings in vivo in response to physiological demand for hormone secretion resulted in an increased [Na+]i. It is postulated that this increased [Na+]i may provide a modulatory influence on the secretory response indirectly via alteration of intracellular calcium regulation or, perhaps, via a direct action on the secretory mechanism.


Implementation of an Online Intraoperative Assessment of Technical Performance for Surgical Trainees.
Assessment of surgical resident technical performance is an integral component of any surgical training program. Timely assessment delivered in a structured format is a critical step to enhance technical skills, but residents often report that the quality and quantity of timely feedback received is lacking. Moreover, the absence of written feedback with specificity can allow residents to seemingly progress in their operative milestones as a junior resident, but struggle as they progress into their postgraduate year 3 and above. We therefore designed and implemented a web-based intraoperative assessment tool and corresponding summary "dashboard" to facilitate real-time assessment and documentation of technical performance. A web form was designed leveraging a cloud computing platform and implementing a modified Ottawa Surgical Competency Operating Room Evaluation instrument; this included additional, procedure-specific criteria for select operations. A link to this was provided to residents via email and to all surgical faculty as a Quick Response code. Residents open and complete a portion of the form on a smartphone, then relinquish the device to an attending surgeon who then completes and submits the assessment. The data are then transferred to a secure web-based reporting interface; each resident (together with a faculty advisor) can then access and review all completed assessments. The Assessment form was activated in June 2021 and formally introduced to all residents in July 2021, with residents required to complete at least one assessment per month. Residents with less predictable access to operative procedures (night float or Intensive Care Unit) were exempted from the requirement on those months. To date a total of 559 assessments have been completed for operations performed by 56 trainees, supervised by 122 surgical faculty and senior trainees. The mean number of procedures assessed per resident was 10.0 and the mean number per assessor was 4.6. Resident initiation of Intraoperative Assessments has increased since the tool was introduced and scores for technical and nontechnical performance reliably differentiate residents by seniority. This novel system demonstrates that an online, resident-initiated technical assessment tool is feasible to implement and scale. This model's requirement that the attending enter performance ratings into the trainee's electronic device ensures that feedback is delivered directly to the trainee. Whether this aspect of our assessment ensures more direct and specific (and therefore potentially actionable) feedback is a focus for future study. Our use of commercial cloud computing services should permit cost-effective adoption of similar systems at other training programs.


Atomic force microscopy for revealing micro/nanoscale mechanics in tumor metastasis: from single cells to microenvironmental cues.
Mechanics are intrinsic properties which appears throughout the formation, development, and aging processes of biological systems. Mechanics have been shown to play important roles in regulating the development and metastasis of tumors, and understanding tumor mechanics has emerged as a promising way to reveal the underlying mechanisms guiding tumor behaviors. In particular, tumors are highly complex diseases associated with multifaceted factors, including alterations in cancerous cells, tissues, and organs as well as microenvironmental cues, indicating that investigating tumor mechanics on multiple levels is significantly helpful for comprehensively understanding the effects of mechanics on tumor progression. Recently, diverse techniques have been developed for probing the mechanics of tumors, among which atomic force microscopy (AFM) has appeared as an excellent platform enabling simultaneously characterizing the structures and mechanical properties of living biological systems ranging from individual molecules and cells to tissue samples with unprecedented spatiotemporal resolution, offering novel possibilities for understanding tumor physics and contributing much to the studies of cancer. In this review, we survey the recent progress that has been achieved with the use of AFM for revealing micro/nanoscale mechanics in tumor development and metastasis. Challenges and future progress are also discussed.


A Change in the Use of Regulatory Criteria for Assessing Potential Impacts of Sound on Fishes.
The National Marine Fisheries Service (NMFS) currently uses interim criteria developed on the US West Coast to assess the potential onset of peak and cumulative effects of noise on fishes. Analyses performed for this project provided adequate support for the NMFS to use the peak criterion (i.e., area ensonified by 206 dB re 1 μPa peak sound pressure level [SPL(peak)]) for estimating the incidental take of Hudson River sturgeon. Application of the peak criterion (rather than the cumulative criterion) could have implications for future construction projects because estimates of take using SPL(peak) will generally be considerably lower than estimates of take based on the cumulative sound exposure level.


DANGER Signals Activate G -Protein Receptor Kinases Suppressing Neutrophil Function and Predisposing to Infection After Tissue Trauma.
Injured tissue predisposes the subject to local and systemic infection. We studied injury-induced immune dysfunction seeking novel means to reverse such predisposition. Injury mobilizes primitive "DANGER signals" [danger-associated molecular patterns (DAMPs)] activating innate immunocyte (neutrophils, PMN) signaling and function. Mitochondrial formyl peptides activate G -protein coupled receptors (GPCR) like formyl peptide receptor-1. Mitochondrial DNA and heme activate toll-like receptors (TLR9 and TLR2/4). GPCR kinases (GRKs) can regulate GPCR activation. We studied human and mouse PMN signaling elicited by mitochondrial DAMPs (GPCR surface expression; protein phosphorylation, or acetylation; Ca 2+ flux) and antimicrobial functions [cytoskeletal reorganization, chemotaxis (CTX), phagocytosis, bacterial killing] in cellular systems and clinical injury samples. Predicted rescue therapies were assessed in cell systems and mouse injury-dependent pneumonia models. Mitochondrial formyl peptides activate GRK2, internalizing GPCRs and suppressing CTX. Mitochondrial DNA suppresses CTX, phagocytosis, and killing through TLR9 through a novel noncanonical mechanism that lacks GPCR endocytosis. Heme also activates GRK2. GRK2 inhibitors like paroxetine restore functions. GRK2 activation through TLR9 prevented actin reorganization, implicating histone deacetylases (HDACs). Actin polymerization, CTX, bacterial phagocytosis, and killing were also rescued, therefore, by the HDAC inhibitor valproate. Trauma repository PMN showed GRK2 activation and cortactin deacetylation, which varied with severity and was most marked in patients developing infections. Either GRK2 or HDAC inhibition prevented loss of mouse lung bacterial clearance, but only the combination rescued clearance when given postinjury. Tissue injury-derived DAMPs suppress antimicrobial immunity through canonical GRK2 activation and a novel TLR-activated GRK2-pathway impairing cytoskeletal organization. Simultaneous GRK2/HDAC inhibition rescues susceptibility to infection after tissue injury.


Developing information literacy skills in pre-registration nurses: an experimental study of teaching methods.
To compare the effectiveness of an online information literacy tutorial with a face-to-face session for teaching information literacy skills to nurses. Randomised control trial. Seventy-seven first year undergraduate pre-registration diploma nursing students. Online in-house information literacy tutorial One hour face-to-face session, covering the same material as the intervention, delivered by the nursing subject librarian. Search histories were scored using a validated checklist covering keyword selection, boolean operators, truncation and synonyms. Skills retention was measured at 1 month using the same checklist. Inferential statistics were used to compare search skills within and between groups pre and post-session. The searching skills of first year pre-registration nursing students improve following information literacy sessions (p<0.001), and remain unchanged 1 month later, regardless of teaching method. The two methods produce a comparable improvement (p=0.263). There is no improvement or degradation of skills 1 month post-session for either method (p=0.216). Nurses Information literacy skills improve after both face-to-face and online instruction. There is no skills degradation at 1 month post-intervention for either method.


Retinoprotective effect of Epithalon in campbell rats of various ages.
We studied the retinoprotective effect of Epithalon administered to the offspring of Campbell rats during postnatal ontogeny and to mothers before mating and during pregnancy. After this treatment the morphological structure and functional activity of the retina were preserved for a longer period compared to control rats (by 2 times) and to the animals receiving the peptide only during postnatal ontogeny (by 30%).


Hematological changes during androgen deprivation therapy.
Androgen deprivation therapy (ADT) has been associated with a plethora of adverse effects, consistent with the androgen dependency of multiple reproductive and somatic tissues. One such tissue is the hemopoietic system, and one of the most predictable consequences of ADT is the development of anemia. Although anemia caused by ADT is rarely severe, ADT is often given to frail, elderly men with increased susceptibility to anemia due to multiple other causes. ADT-associated anemia may contribute to fatigue and reduced quality of life (QoL) in such men, although this requires further study. While anemia is an independent risk factor of mortality in men with prostate cancer, it is not known whether treatment of ADT-associated anemia alters clinically important outcomes, or whether treatment affects mortality. Awareness of the phenomenon of ADT-induced anemia should avoid unnecessary work-up in mild cases of normocytic normochromic anemia. However, assessment and treatment of more severe anemia may be required. This should be determined on an individual basis. In contrast to the well-described actions of ADT on erythropoiesis, its effect on other hemopoietic lineages has been less well elucidated. While preclinical studies have found roles for androgens in maturation and differentiated function of neutrophils, lymphocytes and platelets, the implications of these findings for men with prostate cancer receiving ADT require further studies.


Toolbox of assessment tools of technical skills in otolaryngology-head and neck surgery: A systematic review.
To support the development of programs of assessment of technical skills in the operating room (OR), we systematically reviewed the literature to identify assessment tools specific to otolaryngology-head and neck surgery (OTL-HNS) core procedures and summarized their characteristics. We systematically searched Embase, MEDLINE, PubMed, and Cochrane to identify and report on assessment tools that can be used to assess residents' technical surgical skills in the operating room for OTL-HNS core procedures. Of the 736 unique titles retrieved, 16 articles met inclusion criteria, covering 11 different procedures (in otology, rhinology, laryngology, head and neck, and general otolaryngology). The tools were composed of a task-specific checklist and/or global rating scale and were developed in the OR, on human cadavers, or in a simulation setting. Our study reports on published tools for assessing technical skills for OTL-HNS residents during core procedures conducted in the OR. These assessment tools could facilitate the provision of timely feedback to trainees including specific goals for improvement. However, the paucity of publications suggests little agreement on how to best perform work-based direct-observation assessment for core surgical procedures in OTL-HNS. The sparsity of tools specific to OTL-HNS may become a barrier to a fluid transition to competency-based medical education. Laryngoscope, 128:1571-1575, 2018.


A particle concentration fluorescence immunoassay for prostaglandin D synthase in the rat central nervous system.
A solid phase, particle concentration fluorescence immunoassay (PCFIA) was developed for the measurement of prostaglandin (PG) D synthase in the 100,000g supernatant of various regions of the rat central nervous system. In this assay, the enzyme (in the range of 1-25 micrograms protein of brain supernatant or 1-100 ng of the purified enzyme) is attached to submicrometer carboxypolystyrene beads coated with polyclonal anti-rat brain PGD synthase IgG. The total particle-bound enzyme is assayed with fluorescein isothiocyanate (FITC)-conjugated monoclonal anti-PGD synthase IgG after incubation for 1 h. The optimum assay condition was obtained when carboxyl particles coated with ca. 500 micrograms/ml of polyclonal IgG at pH 5.0 and 5 micrograms/ml of FITC-IgG were used. No significant fluorescence was observed when FITC conjugates or carboxyl particles were prepared using IgG from nonimmunized rabbits. Heat treatment of the brain supernatant decreased the specific binding of the enzyme in parallel with the loss of enzyme activity, indicating that the denatured enzyme is not recognized by this assay method. The PGD synthase immunoreactivity was widely distributed in the brain regions and was highest in the paraflocculus. Although slight discrepancy was observed between the concentration by PCFIA and the enzyme activity measured by using [14C]PGH2 in some brain regions, there is a considerable correlation (0.727) between the values by both methods in the same brain regions. The PCFIA now developed showed higher sensitivity (around 10 times), greater reliability, and larger number of samples measurable at once than the radio-TLC assay using [14C]PGH2. This method could provide valuable information concerning the regulatory mechanisms of PGD synthase.


Induction of malignant nasal cavity tumours in Wistar rats fed Chinese salted fish.
Epidemiological evidence has implicated Chinese salted fish as a human nasopharyngeal carcinogen. In the present study, 221 Wistar-Kyoto rats aged 21 days were randomly assigned to one of three experimental groups. Rats in group 1 (high dose group) were fed a powder diet of one part Chinese salted fish to three parts certified rat chow during the first 18 months. Similarly, rats in group 2 (low dose group) were fed a powder diet of one part salted fish to five parts rat chow for 18 months. Rats in group 3 were given rat chow only throughout the 3-year experiment. Four malignant tumours of the nasal cavity were observed among rats fed the experimental diets (three and one respectively in the high and low dose groups). No comparable tumours were observed in controls, compatible with the historical control rate of zero. Our results, therefore, further strengthen the hypothesis that Chinese salted fish is a human nasopharyngeal carcinogen; they also establish Wistar rats as a viable animal model for carcinogenicity studies of this food in the laboratory.


Effects of X-irradiation at different times during development on the yield of somatic mutations in melanocytes of the mouse.
The effect of 2.0 Gy X-irradiation at different times during foetal and early post-natal development on the resultant somatic mutation frequency was investigated by scoring for changes in follicular melanocyte morphology (nucleofugal vs. nucleopetal) in mice heterozygous for the recessive coat colour mutations dilute (d) and leaden (ln). Two peaks were observed following X-irradiation on days 12.5 and 17.5 post coitus (p.c.). The biomodal character of the mutation frequency with time of X-irradiation may be related to changes in the dynamics of the melanocyte population with foetal age. Nonetheless, the results validate the treatment time used in the pilot study (Searle and Stephenson, 1982) as the most sensitive to the induction of somatic mutations within the follicular melanocyte population.


Mechanical and oral antibiotics bowel preparation for elective rectal cancer surgery: A propensity score matching analysis using a nationwide inpatient database in Japan.
The best bowel preparation method for rectal surgery remains controversial. In this study we compared the efficacy and safety of mechanical bowel preparation (MBP) alone and MOABP (MBP combined with oral antibiotic bowel preparation [OABP]) for rectal cancer surgery. In this retrospective study we analyzed data from the Japanese Diagnosis Procedure Combination (DPC) database on 37 291 patients who had undergone low anterior resection for rectal cancer from 2014 to 2017. Propensity score matching analysis was used to compare postoperative outcomes between MBP alone and MOABP. A total of 37 291 patients were divided into four groups: MBP alone: 77.7%, no bowel preparation (NBP): 16.9%, MOABP: 4.7%, and OABP alone: 0.7%. In propensity score matching analysis with 1756 pairs, anastomotic leakage (4.84% vs 7.86%, P < 0.001), small bowel obstruction (1.54% vs 3.08%, P = 0.002) and reoperation (3.76% vs 5.98%, P = 0.002) were less in the MOABP group than in the MBP group. The mean duration of postoperative antibiotics medication was shorter in the MOABP group (5.2 d vs 7.5 d, P < 0.001) than in the MBP group. There was no significant difference between the two groups in the incidence of Clostridium difficile (CD) colitis (0.40% vs 0.68%, P = 0.250) and methicillin-resistant Staphylococcus aureus (MRSA) colitis (0.11% vs 0.17%, P = 0.654). There was no significant difference in in-hospital mortality between the two groups (0.00% vs 0.11% respectively, P = 0.157). MOABP for rectal surgery is associated with a decreased incidence of postoperative complications without increasing the incidence of CD colitis and MRSA colitis.


[Prevalence of blindness among adults aged 50 years or above in Shunyi county of Beijing].
To estimate the prevalence of blindness among older adults aged >or= 50 years in Shunyi county of Beijing, China. Cluster sampling was used in randomly selecting individuals aged >or= 50 years in 28 villages in Shunyi county in fall, 1996. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. 5,555 individuals were enumerated. The response rate was 91.5%. In this population, the prevalence of blindness was 1.7% defined as pinhole visual acuity < 0.05 in both eyes; or 2.8% were blind, defined as presenting visual acuity < 6/60 in both eyes. Blindness was associated with older age and female gender. The principal cause of blindness in eyes was cataract. The prevalence of blindness was decreased 35.8% after ten year active eye-care program in the survey area. However, cataract blindness continues as a significant problem among elderly, especially females, in this population sample of rural area.


Effects and mechanisms of constructed wetlands with different substrates on N2O emission in wastewater treatment.
Nitrous oxide (N2O) emissions from constructed wetlands (CWs) are accompanying problems and have attracted much attention in recent years. CWs filled with different substrates (gravel, biochar, zeolite, and pyrite) were constructed to investigate the nitrogen removal performance and N2O emissions, which named C-CWs, B-CWs, Z-CWs, and P-CWs, respectively. C-CWs showed the poorest nitrogen removal performance in all CWs. Although B-CWs exhibited the highest fluxes of N2O emissions, the percentage of N2O emissions in nitrogen removal (0.15%) was smaller than that of C-CWs (0.18%). In addition, microbiological analysis showed that compared with C-CWs, CWs filled with biochar, zeolite, and pyrite had higher abundance of nitrifying and denitrifying microorganisms and lower abundance of N2O producing bacteria. In conclusion, biochar, zeolite, and pyrite were more favorable kinds of substrate than the conventional substrates of gravel for the nitrogen removal and reduction of N2O emissions from CWs.


KISS--a new approach to self-controlled e-learning of selected chapters in Medical Engineering and other fields at bachelor and master course level.
Modern life style requires new methods for individual lifelong learning, based on access at every time and from every place. This fundamental requirement is provided by the Internet. The Internet technology promises an increasing potential in the future for e-learning or tele-learning. Some special requirements are password-controlled access, applicability of most commercially available PCs and laptops equipped with standard software (Microsoft Internet Explorer 6.0), central evaluation of the students' performance, inclusion of an examination part, provision of a picture gallery and a comprehensive glossary accessible in the learning mode. The KISS-shell has been developed based on the Oracle 10g application server in combination with a relational data base (Oracle 8i) on the server side and a web browser based interface using JavaScript for user control of data input on the client side (Kontrolliertes Intelligentes Selbstgesteuertes Studium, KISS). The first tutorial application has been realized with a chapter about cardiac pacemakers. The weight of that chapter (or module) is about 2 ECTS (i.e. the equivalent of 30 working hours; European Credit Transfer System, ECTS). The internal structure of the chapter is organized in sequential mode. It consists of five main sections. Each of those five sections is subdivided into five subsections of comparable length. Progression from one subsection to the next is possible only after successfully passing through the respective examination. The whole learning programme with the pacemaker chapter has been evaluated by 10 students. The system will be presented together with first experiences including the evaluation results. Until now the program has not been used for training purposes.


PREVALENCE OF SELF-MEDICATION FOR DYSPEPTIC SYMPTOMS IN PRIMARY CARE: A BRAZILIAN SURVEY.
Dyspeptic symptoms are among the eight symptoms that most lead to the use of self-medication globally. The aim of the present study was to evaluate the frequency of use and profile of the population doing self-medication to control dyspeptic symptoms in a capital from South Brazil. Application of a survey consisting of topics regarding individual's socio-cultural data, self-reported comorbidities, use of self-medication in the 15 days prior to the interview and information on the use of this medication. Statistical analysis was performed on the data collected to determine the prevalence of self-medication for dyspeptic symptoms (SMDS) and to establish correlations with independent factors, such as gender, age, body mass index (BMI), education, family income and self-reported comorbidities. A total of 719 individuals from the public health system were interviewed. Overall, 67.7% were female, 65.3% had a BMI greater than 25; 28.4% presented with self-reported hypertension, 21.4% with depression and 13.8% with diabetes. The prevalence of self-medication to control digestive symptoms in this population was 28.7% (95%CI: 25.3-32), 91.8% (n=189) due to complaints of dyspeptic origin. Proton pump inhibitors were the most used class of medication (67%), followed by antacids (15%). There was a relationship between SMDS and age >38 years (OR=1.734, 95%CI: 1.177-2.580, P=0.001), BMI >26 (OR=1.660, 95%CI: 1.166-2.362, P<0.001) and self-reported depression (OR=1.471, 95%CI: 0.983-2.201, P=0.04). There was a higher prevalence of the use of self-medication to control dyspeptic symptoms in relation to previous data from the literature. Age >38 years, BMI >26 and self-reported depression were associated with SMDS.


Armc8 regulates the invasive ability of hepatocellular carcinoma through E-cadherin/catenin complex.
Armc8 (armadillo-repeat-containing protein 8) was proved to promote disruption of E-cadherin complex through regulating α-catenin degradation. In this study, we investigated Armc8 expression in hepatocellular carcinoma using immunohistochemistry (IHC). The positive rate of Armc8 expression in hepatocellular carcinoma was 53.9 % and higher than that in normal hepatic tissues (9.2 %) (p < 0.05). Clinicopathological analysis shows that Armc8 expression in hepatocellular carcinoma was significantly associated with larger tumor size (≥5 cm), multiple tumor numbers, higher pathological grade (media and poor), advanced TNM stages (II/III), and advanced BCLC stages (B/C). Western blot study also detected higher Armc8 expression in hepatocellular carcinoma cells including HepG2, HCC97L, and SMMC-7721 than in human hepatic cell Bel-7402. We further use specific small interfering RNAs (siRNAs) to knock down Armc8 expression in HepG2 cells and found that knockdown of Armc8 expression significantly inhibited the invasive ability of HepG2 cells. Downregulation of Armc8 expression significantly upregulated α-catenin, β-catenin, and E-cadherin expression in HepG2 cells. Immunofluorescent study shows that knockdown of Armc8 expression restored E-cadherin expression in membrane of HepG2 cells. These results indicate that Armc8 may be a potential cancer marker in hepatocellular carcinoma and may regulate cancer invasion through E-cadherin/catenin complex.


High-resolution imaging of O2 dynamics and metal solubilization in the rhizosphere of the hyperaccumulator Leersia hexandra Swartz.
The mobilization of trace metals in the rhizosphere can be affected by the redox potential, which is closely related to the O2 dynamics. This study examined the distributions of O2 and trace metals in the rhizosphere of the subaquatic hyperaccumulator Leersia hexandra Swartz under chromium (Cr) stress using planar optodes and the diffusive gradients in thin films technique coupled with laser ablation inductively coupled plasma mass spectrometry. The O2 concentrations and oxidized areas in the rhizosphere significantly increased with increases in the light intensity, air humidity, and atmospheric CO2 concentrations (p < 0.05). The O2 concentration first increased with increasing ambient temperatures, then decreased when the temperature increased from 25 to 32 ℃. The O2 concentration in the rhizosphere was significantly decreased under Cr stress (p < 0.05), with a prolonged response time to the altered ambient temperature. Cr stress led to decreased mobilities of As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Sb, V, W, and Zn in the rhizosphere, which were negatively correlated with the concentrations of O2. These results provide new insights into the role of changes in the O2 concentration induced by the roots of hyperaccumulator plants in controlling the mobility of trace metals in soils.


Convenient synthesis of (+)-valiolamine and (-)-1-epi-valiolamine from (-)-vibo-quercitol.
Convenient and practical synthesis of (+)-valiolamine and (-)-1-epi-valiolamine from (-)-vibo-quercitol, 1-deoxy-L-myo-inositol, readily obtained by bioconversion of myo-inositol, is described.


Hyper-Ia antigen expression on B cells from B6-lpr/lpr mice correlates with manifestations of the autoimmune state.
To investigate the state of activation of B cells from mice with the lpr gene defect, membrane Ia antigen (mIa) expression was analyzed on B cells from B6-lpr/lpr (lpr) and control B6- +/-/+/- mice. B cells from lpr mice exhibited marked increases in levels of mIa as determined by flow cytometry using a monoclonal anti-I-Ab,d reagent. This increase, which was progressive with age, suggests that phenotypic alteration of B-cell mIa expression is a consequence of lpr gene action. Since B-cell activation manifest by elevated mIa expression may promote productive interactions with helper T cells, these observations suggest an important role for B-cell abnormalities in the etiology of lpr-induced autoimmune disease.


Analgesic and anti-ulcerogenic effects of a polar extract from leaves of Vernonia condensata.
An aqueous crude extract and a polar fraction derived from this extract were prepared from leaves of Vernonia condensata Baker and assessed in standard rodent models of algesia and ulcerogenesis. Oral pretreatment with the lyophilized crude extract (200 mg/kg) significantly reduced mouse writhing counts caused by the i.p. injection of increasing concentrations (0.6-1.2%) of acetic acid (0.1 ml/10 g). In doses ranging from 50 to 400 mg/kg, the crude extract inhibited dose-dependently mouse writhing induced by acetic acid (0.6%) (ED50 = 241 mg/kg) and also markedly increased the sleeping time induced by thiopental. The polar fraction, prepared by washing out the crude extract with chloroform, did not alter sleeping time but kept the analgesic activity (ED50 = 154 mg/kg), indicating that these effects are indeed dissociated. In contrast, the tail flick response in the immersion test was not modified by the crude extract or the polar fraction. The relative potency with which polar fraction and non-steroidal anti-inflammatory drugs inhibited mouse writhing caused by acetic acid in mice was indomethacin >> dypirone > polar fraction > aspirin. Furthermore, the combined polar fraction/aspirin or polar fraction/indomethacin treatments presented a marked synergistic effect, in contrast to what was observed when submaximal doses of indomethacin and aspirin were coadministered, suggesting that polar fraction and aspirin like drugs may have complementary analgesic actions. Finally, despite being able to potentiate the analgesic effect of indomethacin in mouse writhing caused by acetic acid, the pretreatment with the polar fraction (200 mg/kg, oral) significantly prevented indomethacin-induced ulcers in rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Development and validation of a nanometer manipulation and measurement system for biomechanical testing of single macro-molecules.
A biomechanical testing system for single macro-molecules has been developed using optical tweezers. To achieve nanometer manipulation and measurement, a piezo-stage and an interferometer were adopted. A systematic calibration was then performed on the displacement resolution. The piezo-stage has a noise level around 1 nm standard deviation, and the interferometer has a noise level of less than 5 nm standard deviation. The results revealed that the system has a nanometer resolution which is sufficient for the measurement of deformation and stiffness of single macro-molecules.


Polycyclic aromatic hydrocarbons in weathered bottom ash from incineration of municipal solid waste.
Polycyclic aromatic hydrocarbons (PAHs) were analysed in weathered bottom ash from different municipal solid waste incinerators. The sum of the 16 "USEPA" PAHs was found to vary from 480 to 3590 microg/kg. The amounts of carcinogenic PAHs were between 89 and 438 microg/kg ash. The maximum levels of carcinogenic PAHs exceed the Swedish generic guidelines for sensitive land use. The results showed that the amount of PAHs in fresh and weathered bottom ash are similar, indicating that the PAHs are strongly bound to the ash and only limited amounts are released to the surroundings.


Efficacy and safety of a premixed versus a basal-plus insulin regimen as intensification for type 2 diabetes by timing of the main meal.
To describe the efficacy and safety of premixed insulin lispro protamine suspension 75%/insulin lispro solution 25% (LM25) twice daily (bid) versus basal insulin glargine plus prandial insulin lispro (IGL), both once daily, according to main meal timing. Data were obtained post hoc from a 24 week, randomized, open-label study comparing LM25 and IGL as insulin intensification in patients with type 2 diabetes inadequately controlled with once daily basal insulin glargine plus metformin and/or pioglitazone (ClinicalTrials.gov identifier: NCT01175824). Patients administered LM25 bid before breakfast and the evening meal, insulin glargine at bedtime and insulin lispro before the day's main meal (meal with the highest 2 hour postprandial glucose level during screening). Patients were grouped by main meal. Changes in glycosylated hemoglobin (HbA1c) and bodyweight were summarized using likelihood-based mixed models; hypoglycemia incidence was compared between treatments using Fisher's exact test. Overall, 476 patients (LM25, n = 236; IGL, n = 240) were randomized. In all main meal groups, with both insulin regimens, mean HbA1c significantly decreased from baseline to 24 weeks (p < 0.0001). Patients whose main meal was in the evening had a greater bodyweight increase with LM25 than with IGL (p = 0.015), and a smaller proportion of these patients experienced total (p = 0.027) and nocturnal (p = 0.006) hypoglycemia with LM25 compared with IGL. Patients whose main meal was lunch experienced more nocturnal hypoglycemia with LM25 than with IGL (p = 0.030). Study limitations include that this was a post hoc analysis and no assessments ensured that: SMBG results determined timing of the main meal, each patient's main meal remained unchanged throughout the study, or patients administered insulin lispro with that meal. Glycemic control improved in patients receiving either LM25 or IGL, irrespective of main meal timing. Both regimens can be used in patients with inadequate glycemic control who are in need of insulin intensification.


Preparation of human Melanocortin-4 receptor agonist libraries: linear peptides X-Y-DPhe7-Arg8-Trp(or 2-Nal)9-Z-NH2.
Two libraries of hMC4R agonists, X-Y-DPhe(7)-Arg(8)-2-Nal(9)-Z-NH(2) and X-Y-DPhe(7)-Arg(8)-Trp(9)-Z-NH(2), totaling 185 peptides were prepared using Irori radiofrequency tagging technology and Argonaut Quest 210 Synthesizer, where X stands for N-caps, Y for His(6) surrogates and Z for Gly(10) surrogates. As a result of this study, His-modified pentapeptides with Trp were found to be more hMC4R potent than the corresponding 2-Nal analogs, novel N-caps and Gly surrogates were identified and 19 new peptides which are potent hMC4R agonists (EC(50) 1-15nM) and selective against hMC1R were discovered.


Lack of sequence homology between the nucleic acids of Rauscher leukaemia virus and polyoma virus Y8e produced simultaneously in a continuous mouse cell line.
In a continuous cell line (Y8e) from spleen and thymus cells of mice, infected with RLV, the presence of both RLV and polyoma virus Y8e in a single cell could be demonstrated by electron microscopy. A comparison of the nucleic acids of RLV and polyoma virus from Y8e cells by two molecular hybridization methods showed lack of sequence homology between the viral nucleic acids.


Association of lower limb cutaneous sensitivity with gait speed in the elderly: the health ABC study.
To examine the association of fast-adapting receptor-mediated vibrotactile sensitivity and slow-adapting receptor-mediated pressure sensitivity with self-selected usual gait speed and gait speed over a challenging narrow (20 cm wide) course. Participants from the population-based older cohort of the Health ABC study were included (n = 1721; age: 76.4 +/- 2.8 yrs). Usual gait speed over 6 m and gait speed over a 6-m narrow course were measured. Vibration perception threshold (100 Hz) was measured on the plantar surface, and monofilament testing (1.4 and 10 g) was performed on the dorsum of the great toe. Covariates including knee extensor torque, standing balance, visual acuity and contrast sensitivity, knee pain, depressive symptoms, high fasting glucose levels, and peripheral arterial disease were evaluated. Vibrotactile and monofilament sensitivity were significantly worse in slower gait speed groups in both walking conditions (P < 0.001 to P = 0.015). Adjusting for covariates, vibrotactile (P < 0.001) but not monofilament sensitivity (P = 0.655) was independently associated with self-selected normal gait speed. Neither sensory function was associated with narrow-base gait speed. In the elderly, poor lower limb vibrotactile sensitivity measured on the plantar surface of the great toe, but not the pressure sensitivity as measured by monofilament testing on the dorsum of the great toe, is independently associated with slower self-selected normal gait speed. Narrow-based walking seems to depend on other neuromuscular mechanisms.


A quantitative definition of scaphoid union: determining the inter-rater reliability of two techniques.
Despite extensive literature supporting the use of computerized tomography (CT) scans in evaluating scaphoid fractures, there has not been a consensus on the methodology for defining and quantifying union. The purpose of this study was to test the inter-observer reliability of two methods of quantifying scaphoid union. The CT scans of 50 non-operatively treated scaphoid fractures were reviewed by four blinded observers. Each was asked to classify union into one of three categories, united, partially united, or tenuously united, based on their general impression. Each reviewer then carefully analyzed each CT slice and quantified union based on two methods, the mean percentage union and the weighted mean percentage union. The estimated percentage of scaphoid union for each scan was recorded, and inter-observer reliability for both methods was assessed using a Bland-Altman plot to calculate the 95% limits of agreement. Kappa statistic was used to measure the degree of agreement for the categorical assessment of union. There was very little difference in the percentage of union calculated between the two methods (mean difference between the two methods was 1.2 ± 4.1%), with each reviewer demonstrating excellent agreement between the two methods based on the Bland-Altman plot. The kappa score indicated very good agreement (Κ = 0.80) between the consultant hand surgeon and the musculoskeletal radiologist, and good agreement (Κ = 0.62) between the consultant hand surgeon and the hand fellow for the categorical assessment of union. This study describes two methods of quantifying and defining scaphoid union, both with a high inter-rater reliability. This indicates that either method can be reliably used, making it an important tool for both for clinical use and research purposes in future studies of scaphoid fractures, particularly those which are using union or time to union as their endpoint. Diagnostic, level III.


Expression of the L-type pyruvate kinase gene and the hepatocyte nuclear factor 4 transcription factor in exocrine and endocrine pancreas.
The L-pyruvate kinase (L-PK) gene is slightly active in normal and tumoral endocrine pancreatic tissues while, in vivo, this gene is not transcribed in the exocrine pancreas. Nevertheless, the L-PK gene is re-expressed at a very low level in cultured 266.6 cells derived from an exocrine pancreas carcinoma. The L-PK gene is early activated in endodermal tissues, e.g. yolk sac and primitive intestine; it remains transcribed in fetal pancreas. In adult, L-PK gene expression is restricted to some endocrine cells. Hepatocyte nuclear factor (HNF) 1 and HNF4 are the main tissue-restricted transcription factors involved in tissue-specific expression of the L-PK gene. HNF1 concentration is similar in liver and all pancreatic cells. HNF4 concentration is high in liver, much lower in islets of Langerhans, endocrine pancreatic tumors, and cultured insulinoma cells, and is scarcely detectable in adult exocrine pancreas. This distribution of HNF4 parallels the expression of the L-PK gene. In vivo footprinting experiments show that the HNF1 binding site is similarly occupied in both adult liver and adult pancreas, in which this gene is practically inactive. In this latter tissue, however, the HNF4 binding site is differently occupied with respect to the liver. Since the chromatin structure remains open around the L-PK promoter in pancreas, the L-PK gene can probably be re-expressed under certain circumstances, for instance in cancerous pancreatic cells.


Unconscious priming by color and form: different processes and levels.
Using a metacontrast masking paradigm, prior studies have shown (a) that a target's color information and form information, can be processed without awareness and (b) that unconscious color processing occurs at early, wavelength-dependent levels in the cortical information processing hierarchy. Here we used a combination of paracontrast and metacontrast masking techniques to explore unconscious color and form priming effects produced by blue, green, and neutral stimuli. We found that color priming in normal observers is significantly reduced when an additional paracontrast mask precedes the target at optimal masking SOAs. However, no reduction of form-priming effects was obtained at similar optimal paracontrast SOAs. We conclude that unconscious color priming depends on an early, wavelength- or stimulus-dependent response of color neurons located at early cortical levels whereas unconscious form priming occurs at later levels.


Proofreading, NTPases and translation: successful increase in specificity.
The discussion of proofreading started in the April issue of TIBS is completed by treating the two branched Michaelis-Menten enzymes that can proofread. The conditions required for proofreading can be seen to determine the expression of proofreading in its biological settings. There are surely instances of proofreading as yet unrecognized.


A silent gigantic solitary fibrous tumor of the pleura: case report.
Solitary fibrous tumor of the pleura is a rare mesenchymal tumor, representing less than 5% of all neoplasms associated with the pleura. A 57-year-old man had general malaise without chest symptoms for 1 month. A chest roentgenogram and computed tomography showed a giant mass in the left thorax. Although the tumor compressed the descending aorta and other mediastinal structures strongly, thereby shifting them to the right side, the patient had no symptoms except malaise. The tumor was successfully resected via two separate thoracotomies. The tumor was measured (20 cm × 19 cm × 15 cm) and weighed (2150 g). The tumor was histologically and immunohistochemically diagnosed as benign. Although SFT is benign, a long follow-up period is essential as even patients with complete resection are at risk of recurrence many years after surgery.


Nepafenac-associated corneal melt.
We describe a patient with systemic graft-versus-host disease who developed a nonhealing epithelial defect after cataract surgery that healed on cessation of a topical nonsteroidal antiinflammatory drug (NSAID) (ketorolac). The patient developed a central corneal perforation in the fellow eye while on a new NSAID formulation (nepafenac) after routine cataract surgery. Our case suggests that new topical NSAIDs may be similar to older NSAID formulations in promoting corneal melting in patients predisposed to poor epithelialization and corneal wound healing.


A Novel Surgical Technique for Posterior Glottic Stenosis Using a Silastic Implant.
To introduce a novel surgical technique for the management of posterior glottic stenosis (PGS). Literature review (PubMed 1973-2020) and case example of a patient treated with novel technique by principal investigator (R.T.S.) RESULTS: Numerous techniques for the treatment of PGS have had varying success. Our patient, a 67-year-old male with a 2-year history of posterior glottic stenosis secondary to multiple, prolonged intubations previously had been treated with several surgical and medical interventions. Three weeks following an additional endotracheal intubation, he presented to our office with PGS recurrence, exhibiting hoarseness, and shortness of breath with any physical activity. He was treated with a silastic sheet placed through a tunnel in the stenosis and sutured posteriorly as a stent. The stent was removed 3 weeks later and the remaining stenosis was divided, successfully treating our patient's PGS with long-term improvement in both respiratory and voice complaints. This led to the design of a stent to be used for this purpose. This new surgical technique addresses a complex clinical problem and provides otolaryngologists with a minimally invasive option for the surgical treatment of PGS that offers advantages over existing techniques. The two-stage procedure should reduce the risk of recurrence, but more experience is needed. This novel implant may be a valuable tool in the treatment of select patients with mild-moderate PGS.


Evidence for the presence of phosphoriboisomerase and ribulose-1,5-diphosphate carboxylase in extracts of Desulfovibrio vulgaris.
Cell extracts of Desulfovibrio vulgaris were found to incorporate 14CO2 into acid-stable products when ribose-5-phosphate or ribulose-1,5-diphosphate was used as a substrate. This CO2 fixation required adenosine triphosphate and produced 3-phosphoglyceric acid as one of the products. The assimilation of CO2 by pentose phosphates was unrelated to the pyruvate-CO2 exchange reaction. The pyruvate-CO2 exchange did not require adenosine triphosphate, did not produce phosphorylated compounds, and, unlike the pentose phosphate system, required an acidic protein fraction for activity.


HSP70 inhibits stress-induced cardiomyocyte apoptosis by competitively binding to FAF1.
Stress-induced cardiomyocyte apoptosis plays an important role in the pathogenesis of a variety of cardiovascular diseases. Our early studies showed that HSP70 effectively inhibited apoptosis, but the underlying mechanism remained unclear. Fas-associated factor 1 (FAF1) is a member of the Fas death-inducing signaling complex (Fas-DISC) that acts upstream of caspase-8. We investigated the interactions among FAF1, HSP70, and FAS in stressed cardiomyocytes to elucidate the protective mechanism of HSP70. FAS and caspase-3/8 activity was higher in cardiomyocytes undergoing stress-induced apoptosis in restraint-stressed rats compared with cardiomyocytes in non-stressed rats, which indicated that the Fas signaling pathway was activated after restraint stress. Geranylgeranylacetone (GGA) induced an increase in HSP70 expression, which reduced stress-induced apoptosis. Additionally, overexpression of HSP70 via transfection with the pEGFP-rHSP70 plasmid attenuated norepinephrine (NE)-induced apoptosis. FAF1 expression increased during stress-induced apoptosis, and overexpression of FAF1 exacerbated NE-induced apoptosis. We also found that HSP70 interacted with FAF1. Overexpression of HSP70 inhibited the binding of FAF1 to FAS in H9C2 cells, which indicated that HSP70 suppressed NE-induced apoptosis by competitively binding to FAF1. An N-terminal deletion mutant of HSP70 (HSP70-△N) was unable to interact with FAF1. After HSP70-△N was transfected into H9C2 cells, the cells were unable to attenuate the NE-induced increases in caspase-8 and apoptosis. These results indicate that the 1-120 sequence of HSP70 binds to FAF1, which alters the interactions between FAS and FAF1 and inhibits the activation of the Fas signaling pathway and apoptosis.


The External Validation of the Nursing Homes Short Depression Inventory in Older Adults with Major Neurocognitive Disorders in Long-Term Care Centers.
Depression is often difficult to detect in long-term care (LTC) patients with major neurocognitive disorders (MNCD), and an observer-rated screening scale could facilitate assessments. This study aimed to establish the external validity and reliability of the Nursing Homes Short Depression Inventory (NH-SDI) in LTC patients with MNCD and to compare its estimates to the Cornell Scale for Depression in Dementia (CSDD), the most used scale for depression in MNCD. A focus discussion group of experts assessed the content validity of the NH-SDI. Then, a convenience sample of 93 LTC patients with MNCD was observer-rated by trained nurses with the NH-SDI and CSDD. For 57 patients, a medical assessment of depression was obtained, and screening accuracy estimates were generated. The prevalence of depression was 8.8% as per reference standard. NH-SDI's content validity was judged acceptable with minor item wording modifications and specifications. The NH-SDI (cut-off ≥3) achieved 100% (95% confidence interval [CI]: 46-100%) sensitivity, 83% (95% CI: 69-91%) specificity, and 36% (95% CI: 14-64%) positive predictive value (PPV). The CSDD (cut-off ≥3) achieved 100% (95% CI: 46-100%) sensitivity, 75% (95% CI: 61-86%) specificity, and 28% (95% CI: 11-54%) PPV. No significant differences in areas under the receiver operating characteristic curve were found between scales. The NH-SDI and CSDD were highly correlated (rs = 0.913; p < 0.001) and reliable (ICC = 0.77; p < 0.001). The NH-SDI appears valid and reliable in LTC patients with MNCD and quicker than the CSDD to rule out depression in a busy or short-staffed setting.


Synthesis of α-Chiral Butyrolactones by Highly Stereoselective Radical Transfer or Sequential Asymmetric Alkylations: Concise Preparation of Leupyrrin Moieties.
Inspired by the bioactive natural metabolites leupyrrin A1 and B1 , two novel stereoselective methods for the highly concise synthesis of densely substituted α-chiral butyrolactones are reported. The first approach relies on an innovative three-step Ti(III) -catalyzed radical reaction that proceeds with excellent chemo-, regio-, and stereoselectivity. The alternative route utilizes sequential asymmetric alkylations and enables asymmetric synthesis of the authentic α-tetrasubstituted butyrolactone motif of the leupyrrins in only four steps from commercially available substrates.


BRAIN FUNCTION ALTERATIONS IN PATIENTS WITH DIABETIC NEPHROPATHY COMPLICATED BY RETINOPATHY UNDER RESTING STATE CONDITIONS ASSESSED BY VOXEL-MIRRORED HOMOTOPIC CONNECTIVITY.
Objective: The voxel-mirrored homologous connection (VHMC) technique was applied to detect resting brain function alterations in patients with diabetic nephropathy and retinopathy (DNR), and their relationships with clinical manifestations in the kidneys and eyes are discussed. Methods: Twenty-two patients with DNR and 22 healthy controls (HCs) similarly matched in age, sex, and educational background were recruited. Resting-state functional magnetic resonance imaging scans were performed for all subjects. Retinal fundus photography and renal biopsy were employed to observe the clinical features of the kidney and retina. Pearson correlation analysis was used to analyze the relationship between clinical manifestations and experimental results. Results: Compared with the HCs, patients with DNR showed decreased mean VMHC values in the bilateral middle temporal gyrus, bilateral middle occipital gyrus (BMOG), and bilateral medial frontal gyrus. The receiver operating characteristic curve analysis of each brain region confirmed that the accuracy of the area under the curve was excellent. The results showed that the average VHMC value of BMOG signals was positively correlated with the urinary protein to creatinine ratio in female subjects (r = 0.626; P<.05). Nonetheless, no such correlation was noted among the male subjects. Conclusion: There were significant changes in brain function in DNR patients compared to the control group. Changes in the central nervous system in patients with DNR were mainly due to the dual negative effects of kidney function and diabetes mellitus. Abbreviations: ACR = albumin/creatinine ratio; BMFG = bilateral medial frontal gyrus; BMOG = bilateral middle occipital gyrus; BMTG = bilateral middle temporal gyrus; DN = diabetic nephropathy; DNR = diabetic nephropathy complicated by retinopathy; DR = diabetic retinopathy; fMRI = functional magnetic resonance imaging; HC = healthy control; MRI = magnetic resonance imaging; PCR = protein to creatinine ratio; ROC = receiver operating characteristic; VHMC = voxel-mirrored homologous connection.


Different effects of taproot and fibrous root crops on pore structure and microbial network in reclaimed soil.
Understanding the effects of plant roots on the pore structure and microbial community of soil is crucial to recovery and improve soil productivity in mining areas. This study aims to assess the impact of taproot (TR) and fibrous root (FR) crops on the physicochemical properties, pore structure, and microbial communities and networks in reclaimed mine soil. Results showed that reclamation positively influenced pore structure and microbial diversity. Tillage with TR and FR crops significantly increased porosity, total pore volume, and area of mining soil (p < 0.05). Compared with TR, FR produced more macropores, mesopores, and micropores. In addition, the module group, average degree, density, and connectivity of microbial network in FR cultivated soil were higher than those in TR cultivated soil. The microbial network map showed that FR had more keystone taxa than TR, and mainly consisted of Acidobacteria and Proteobacteria. In the FR microbial network, Rhizobiales, Betaproteobacteria, and Acidobacteria_Gp11 play critical roles as module hubs and Noviherbaspirillum and Zavarzinella as connectors. Furthermore, most of the key microbes were significantly correlated (p < 0.05) with the total pore area and probably tended to live in pores >75 μm and 0.1-5 μm in size. Therefore, FR crops were more effective than TR crops in improving pore structure and enhancing the development of microbial network in reclaimed soil.


Pilot randomized controlled trial of a complex intervention for diabetes self-management supported by volunteers, technology, and interprofessional primary health care teams.
Most health care for people with diabetes occurs in family practice, yet balancing the time and resources to help these patients can be difficult. An intervention empowering patients, leveraging community resources, and assisting self-management could benefit patients and providers. Thus, the feasibility and potential for effectiveness of "Health Teams Advancing Patient Experience, Strengthening Quality through Health Connectors for Diabetes Management" (Health TAPESTRY-HC-DM) as an approach supporting diabetes self-management was explored to inform development of a future large-scale trial. Four-month pilot randomized controlled trial (RCT), sequential explanatory qualitative component. Participants-patients of an interprofessional primary care team-were over age 18 years, diagnosed with diabetes and hypertension, and had Internet access and one of the following: uncontrolled HbA1c, recent diabetes diagnosis, end-stage/secondary organ damage, or provider referral. The Health TAPESTRY-HC-DM intervention focused on patient health goals/needs, integrating community volunteers, eHealth technologies, interprofessional primary care teams, and system navigation. Pilot outcomes included process measures (recruitment, retention, program participation), perceived program feasibility, benefits and areas for improvement, and risks or safety issues. The primary trial outcome was self-efficacy for managing diabetes. There were a number of secondary trial outcomes. Of 425 eligible patients invited, 50 signed consent (11.8%) and 35 completed the program (15 intervention, 20 control). Volunteers (n = 20) met 28 clients in 234 client encounters (home visits, phone calls, electronic messages); 27 reports were sent to the interprofessional team. At 4 months, controlling for baseline, most outcomes were better in the intervention compared to control group; physical activity notably better. The most common goal domains set were physical activity, diet/nutrition, and social connection. Clients felt the biggest impact was motivation toward goal achievement. They struggled with some of the technologies. Several participants perceived that the program was not a good fit, mostly those that felt they were already well-managing their diabetes. Health TAPESTRY-HC-DM was feasible; a large-scale randomized controlled trial seems possible. However, further attention needs to be paid to improving recruitment and retention. The intervention was well received, though was a better fit for some participants than others. ClinicalTrials.gov, NCT02715791. Registered 22 March 2016-retrospectively registered.


The leukemia inhibitory factor receptor (LIFR) gene is located within a cluster of cytokine receptor loci on mouse chromosome 15 and human chromosome 5p12-p13.
The leukemia inhibitory factor receptor (LIFR) gene was localized to human chromosome 5p12-p13 by somatic cell hybrid analysis. Interspecific backcross analysis revealed that the murine locus was on chromosome 15 in a region of homology with human chromosome 5p. In both human and mouse genomes, the LIFR locus was linked to the genes encoding the receptors for interleukin-7, prolactin, and growth hormone.


Temporomandibular joint destruction in mucolipidosis type III necessitating gastrostomy insertion.
Mucolipidosis III is a genetically heterogeneous lysosomal disorder characterised by progressive symptoms and signs, the commonest being skeletal pain due to bony destruction. We describe a patient who developed severe destruction of the temporomandibular joints leading to difficulties with speech and feeding, necessitating gastrostomy insertion. Temporomandibular joint involvement has not been previously reported in mucolipidosis III.