Validation of a Deep Learning Algorithm for Diabetic Retinopathy.
Background:To validate our deep learning algorithm (DLA) to read diabetic retinopathy (DR) retinographies.Introduction:Currently DR detection is made by retinography; due to its increasing diabetes mellitus incidence we need to find systems that help us to screen DR.Materials and Methods:The DLA was built and trained using 88,702 images from EyePACS, 1,748 from Messidor-2, and 19,230 from our own population. For validation a total of 38,339 retinographies from 17,669 patients (obtained from our DR screening databases) were read by a DLA and compared by four senior retina ophthalmologists for detecting any-DR and referable-DR. We determined the values of Cohen's weighted Kappa (CWK) index, sensitivity (S), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV), and errors type I and II.Results:The results of the DLA to detect any-DR were: CWK = 0.886 ± 0.004 (95% confidence interval [CI] 0.879-0.894), S = 0.967%, SP = 0.976%, PPV = 0.836%, and NPV = 0.996%. The error type I = 0.024, and the error type II = 0.004. Likewise, the referable-DR results were: CWK = 0.809 (95% CI 0.798-0.819), S = 0.998, SP = 0.968, PPV = 0.701, NPV = 0.928, error type I = 0.032, and error type II = 0.001.Discussion:Our DLA can be used as a high confidence diagnostic tool to help in DR screening, especially when it might be difficult for ophthalmologists or other professionals to identify. It can identify patients with any-DR and those that should be referred.Conclusions:The DLA can be valid to aid in screening of DR.


Electrochemical behaviour of isatin at a glassy carbon electrode.
The electrochemical behavior of isatin--a molecule with a broad range of applications in synthetic, biological and clinical activity--has been investigated over a wide pH range at a glassy carbon electrode (GCE) using cyclic, square wave and differential pulse voltammetry. The oxidation of isatin is an irreversible process, pH dependent and occurs with the formation of a main oxidation product that strongly adsorbs on the electrode surface. The reduction of isatin is also a pH dependent irreversible process. Cyclic voltammograms show two consecutive charge transfer reactions. The diffusion coefficient of isatin was calculated in pH 7.0 phosphate buffer to be D(0)=4.9 x 10(-7) cm2 s(-1). The limit of detection obtained in a solution of pH 7.0 phosphate buffer was LOD=0.194 microM, based on three times the noise level.


Best laid plans: pre- and postpartum comparison of self and spouse in primiparous Lamaze couples who share delivery and those who do not.
This study investigated pre- and postpartum attitudes toward self, spouse, and the ideal of 47 primiparous couples who chose the psychoprophylactic (Lamaze) method of childbirth, 34 who were able to share the delivery as planned (Y/Y) and 13 who were blocked from doing so because of complications, necessitating cesarean section (Y/N). Osgood Semantic Differential ratings revealed that both Y/N men and women perceived self- and various ideal concepts lower pre- and postnatally than did Y/Y subjects. Both groups of women showed statistically significant increases pre-post in activity for several concepts, and Y/N women also showed increases in potency for the ideal woman. Y/N husbands showed no statistically significant pre-post gains, while Y/Y husbands widened a statistically significant gain pre-post on the activity dimension for self. Implications for nursing practice and for further research are discussed.


Correctional mental health services in New York: then and now.
This article chronicles the legislation, litigation, and the agency initiatives which have shaped the New York State correctional mental health system into what it is today. An historical perspective provides a context and framework for the examination of the current and future salient issues and challenges in providing a comprehensive range of mental health services in a correctional setting. The Central New York Psychiatric Center organization, which is comprised of a 206 bed maximum-security forensic hospital and a community support network of 23 prison-based mental health units was established in 1977. This article takes an in-depth look at the organization's 25-year growth and development, the implementation and outcome of some innovative treatment programs, and the unique partnership between the New York State Office of Mental Health (OMH) and the New York State Department of Correctional Services (DOCS).


Neuropeptide Y modulates growth hormone but not luteinizing hormone secretion from prepuberal gilt anterior pituitary cells in culture.
Pituitary cells, from seven 160- to 170-day-old pigs, were studied in primary culture to determine the affects NPY on LH and GH secretion at the level of the pituitary. On day 4 of culture, medium was discarded, plates were rinsed twice with serum-free medium and cells were cultured in 1 ml fresh medium without serum and challenged individually with 10(-10), 10(-8) or 10(-6) M [Ala(15)]-h growth hormone-releasing factor-(1-29)NH(2) (GRF); 10(-9), 10(-8) or 10(-7) M GnRH or 10(-9), 10(-8), 10(-7) or 10(-6) M NPY individually or in combinations with 10(-9) or 10(-8) M GnRH or 10(-8) or 10(-6)M GRF. Cells were exposed to treatment for 4 h at which time medium was harvested and quantified for LH and GH. Basal LH secretion (control; n = 7 pituitaries) was 12 +/- 6 ng/well. Relative to control at 4 h, 10(-9), 10(-8) and 10(-7) M GnRH increased (P < 0.01) LH secretion by 169, 176 and 197%, respectively. Neuropeptide-Y did not alter (P > 0.4) basal LH secretion nor 10(-8) M GnRH-induced increase in LH secretion but 10(-9) M GnRH-stimulated LH secretion was reduced by NPY and was not different from control or GnRH alone. Basal GH secretion (control; n = 7 pituitaries) was 56 +/- 12 ng/well. Relative to control at 4 h, 10(-10), 10(-8) and 10(-6) M GRF increased GH secretion by 111%, 125% (P < 0.01) and 150% (P < 0.01), respectively. Only 10(-6) M (134%) and 10(-7) M (125%) NPY increased (P < 0.04) basal GH secretion. Addition of 10(-9), 10(-8) and 10(-7) M NPY in combination with 10(-8) M GRF suppressed (P < 0.04) GRF-stimulated GH secretion. However, 10(-9) M NPY enhanced (P < 0.06) the GH response to 10(-6) M GRF. These results demonstrate that NPY may directly modulate GH secretion at the level of the pituitary gland.


Ambient PM2.5 and its components associated with 10-year atherosclerotic cardiovascular disease risk in Chinese adults.
Exposure to particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) may increase the risk of 10-year atherosclerotic cardiovascular disease (ASCVD) risk. While PM2.5 is comprised of various components, the evidence on the correlation of its components with 10-year ASCVD risk and which component contributes most remains limited. Data were derived from the baseline assessments of China Multi-Ethnic Cohort (CMEC). In total, 69,722 individuals aged 35-74 years were included into this study. The annual average concentration of PM2.5 and its components (black carbon, ammonium, nitrate, sulfate, organic matter, soil particles, and sea salt) were estimated by satellite remote sensing and chemical transport models. The ASCVD risk of individuals was calculated by the equations from the China-PAR Project (prediction for ASCVD risk in China). The relationship between single exposure to PM2.5 and its components and predicted 10-year ASCVD risk was assessed using the logistic regression model. The effect of joint exposure was estimated, and the most significant contributor was identified using the weighted quantile sum approach. Totally 69,722 participants were included, of which 95.8 % and 4.2 % had low and high 10-year ASCVD risk, respectively. Per standard deviation increases in the 3-year average concentration of PM2.5 mass (odds ratio [OR] 1.23, 95 % confidence interval [CI]: 1.12-1.35), black carbon (1.21, 1.11-1.33), ammonium (1.21, 1.10-1.32), nitrate (1.25, 1.14-1.38), organic matter (1.29, 1.18-1.42), sulfate (1.17, 1.07-1.28), and soil particles (1.15, 1.04-1.26) were related to high 10-year ASCVD risk. The overall effect (1.19, 1.11-1.28) of the PM2.5 components was positively associated with 10-year ASCVD risk, and organic matter had the most contribution to this relationship. Female participants were more significantly impacted by PM2.5, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles compared to others. Long-term exposure to PM2.5 mass, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles were positively associated with high 10-year ASCVD risk, while sea salt exhibited a protective effect. Moreover, the organic matter might take primary responsibility for the relationship between PM2.5 and 10-year ASCVD risk. Females were more susceptible to the adverse effect.


Skeletal muscle mass and sarcopenia can be determined with 1.5-T and 3-T neck MRI scans, in the event that no neck CT scan is performed.
Cross-sectional area (CSA) measurements of the neck musculature at the level of third cervical vertebra (C3) on CT scans are used to diagnose radiological sarcopenia, which is related to multiple adverse outcomes in head and neck cancer (HNC) patients. Alternatively, these assessments are performed with neck MRI, which has not been validated so far. For that, the objective was to evaluate whether skeletal muscle mass and sarcopenia can be assessed on neck MRI scans. HNC patients were included between November 2014 and November 2018 from a prospective data-biobank. CSAs of the neck musculature at the C3 level were measured on CT (n = 125) and MRI neck scans (n = 92 on 1.5-T, n = 33 on 3-T). Measurements were converted into skeletal muscle index (SMI), and sarcopenia was defined (SMI < 43.2 cm2/m2). Pearson correlation coefficients, Bland-Altman plots, McNemar test, Cohen's kappa coefficients, and interclass correlation coefficients (ICCs) were estimated. CT and MRI correlated highly on CSA and SMI (r = 0.958-0.998, p < 0.001). The Bland-Altman plots showed a nihil mean ΔSMI (- 0.13-0.44 cm2/m2). There was no significant difference between CT and MRI in diagnosing sarcopenia (McNemar, p = 0.5-1.0). Agreement on sarcopenia diagnosis was good with κ = 0.956-0.978 and κ = 0.870-0.933, for 1.5-T and 3-T respectively. Observer ICCs in MRI were excellent. In general, T2-weighted images had the best correlation and agreement with CT. Skeletal muscle mass and sarcopenia can interchangeably be assessed on CT and 1.5-T and 3-T MRI neck scans. This allows future clinical outcome assessment during treatment irrespective of used modality. • Screening for low amount of skeletal muscle mass is usually measured on neck CT scans and is highly clinical relevant as it is related to multiple adverse outcomes in head and neck cancer patients. • We found that skeletal muscle mass and sarcopenia determined on CT and 1.5-T and 3-T MRI neck scans at the C3 level can be used interchangeably. • When CT imaging of the neck is missing for skeletal muscle mass analysis, patients can be assessed with 1.5-T or 3-T neck MRIs.


Giant aneurysms of the posterior fossa suspected as neoplasms on computed tomography.
Giant intracranial aneurysms of the vertebral and basilar artery can be mistakenly diagnosed as neoplasms of the posterior fossa on the basis of their clinical presentation and CT findings. The following report of three cases of tumorous aneurysms emphasizes the complementary value of angiography and computed tomography for the localization and correct diagnosis of space-occupying lesions of the posterior fossa.


Pleiotropy and heterogeneity in the expression of atherogenic lipoproteins: the IRAS Family Study.
Dyslipidemia is an important determinant of coronary disease. Phenotypic correlations between atherogenic lipids are well established, but the contribution of common genetic influences is less clear. This study investigates the pair-wise genetic (rhog) and environmental (rhoe) correlations between apoB, LDL-C, HDL-C, and triglyceride (Tg) from Hispanic and African American families of the IRAS Family Study. Heritability estimates (ĥ2) indicate significant genetic effects on apoB (ĥ2=0.46+/-0.05), LDL-C (ĥ2=0.40+/-0.05), HDL-C (ĥ2=0.47+/-0.05), and Tg (ĥ2=0.35+/-0.05) (all p<0.001). Genetic and environmental correlations were strong for apoB-LDL-C (rhog=0.87, rhoe=0.84), apoB-Tg (rhog=0.38, rhoe=0.65), and HDL-C-Tg (rhog=-0.42, rhoe=-0.46). Environmental correlations were strong for apoB-HDL-C (rhoe=-0.40), LDL-C-HDL-C (rhoe=-0.24), and Tg-LDL-C (rhoe=0.33) with weak genetic correlations for these pairs (rhog=-0.09, 0.10, 0.09 respectively). These results suggest multiple pathways leading to atherogenic dyslipidemia. There are common genetic and environmental influences contributing to variations in apoB and LDL-C as well as apoB and Tg. In addition, the inverse relation between Tg and HDL-C appears to have both genetic and environmental basis. Identifying genes involved in atherogenic dyslipidemia will require careful dissection of the genetic architecture of these pathways.


Paludiculture as a sustainable land use alternative for tropical peatlands: A review.
Peatlands cover approximately 4.2 million km2 of terrestrial land surface and store up to 700 Pg of terrestrial carbon. Preserving the carbon stocks in peatland is therefore crucial for climate change mitigation. Under natural conditions, peatland carbon storage is maintained by moist peat conditions, which decreases decomposition and encourages peat formation. However, conversion of peatlands to drainage-based agriculture in the form of industrial plantations and smallholder farming has resulted in globally significant greenhouse gas emissions. Paludiculture, loosely conceptualized as biomass production on wet peatlands with the potential to maintain carbon storage, is proposed as a sustainable, non-drainage-based agriculture alternative for peatland use. However, while the concept of paludiculture was developed in temperate ecoregions, its application in the tropics is poorly understood. In this review, we examine common definitions of paludiculture used in literature to derive key themes and future directions. We found three common themes: ecosystem services benefits of paludiculture, hydrological conditions of peatlands, and vegetation selection for planting. Ambiguities surrounding these themes have led to questions on whether paludiculture applications are sustainable in the context of carbon sequestration in peat soil. This review aims to evaluate and advance current understanding of paludiculture in the context of tropical peatlands, which is especially pertinent given expanding agriculture development into Central Africa and South America, where large reserves of peatlands were recently discovered.


Dinucleophilic Reactivity of Isocyanoacetate: Base-Catalyzed One-Pot Access to 4-Azafluorenes and 4-Azafluorenones.
A base-catalyzed double annulation of isocyanoacetates with various enynones has been developed for the expeditious synthesis of 4-azafluorene and 4-azafluorenone derivatives. Against the well-known 1,3-dipolar reactivities, the active methylene and isocyano groups of isocyanoacetate serve as nucleophiles in this domino transformation.


The regulatory strength: how to be precise about regulation and homeostasis.
The concepts of regulation and homeostasis are of frequent use but lack a single universally accepted definition. Here we propose a definition of the regulatory strength and homeostatic strength, which allow to assess the importance of a regulatory pathway in a quantitative fashion.


Prevalence of Childhood Obesity in an Affluent School in Telangana Using the Recent IAP Growth Chart: A Pilot Study.
To study the prevalence of obesity in children in an affluent school in Hyderabad, Telangana, using the recent Indian Academy of Paediatrics (IAP) growth charts and to compare the same with the Centre for Disease Control and Prevention (CDC) charts. A cross-sectional study was conducted in an affluent school of Hyderabad in January 2018. After getting appropriate permission, anthropometry measurements of the school children were done. The data were collected from students of Classes 4-10. Each class had three sections. Each section had around 25-30 students. Body mass index (BMI), calculated as weight (kg)/height2 (m2) was used to classify the participants using age- and gender-specific cut-points as per CDC growth charts and the recent IAP charts. A total of 544 students were studied. About 52% were boys (n = 288) and 48% were girls (n = 256). Using the IAP charts, 24.6% were obese and 35.8% were overweight. Using the CDC criteria, the prevalence of obesity and overweight was 15.4% and 26.1%, respectively. The mean BMI in the obese group was 25.6 ± 3.5 kg/m2 and in the overweight group was 21.1 ± 1.9 kg/m2. The prevalence of obesity and overweight was more in girls (obesity 32.8% versus 17.3% and overweight 44.5% versus 28.1%, respectively). The highest prevalence of childhood obesity was seen in the 8-10 years age group. Our study reflects the increased prevalence of obesity and overweight in the adolescent age group, using the recent IAP criteria.


How expert surgeons review robotic videos: A grounded theory study.
Surgical video review has been shown to improve technical skill in novice surgeons; however, to date, there are no studies examining the use of video review by experts. This study sought to understand the process expert robotic surgeons use when they review their surgical videos. In this qualitative pilot study, eight expert robotic colorectal surgeons individually participated in semi-structured interviews and video elicitation sessions. Grounded theory was used to develop a process model on how expert surgeons review their robotic videos. The participants identified four categories of video review: critical incidents, unique cases, new techniques/procedures, and routine cases. They ask themselves questions with the primary goal of improving surgical technical skills. Surgeons compare their performance to benchmark videos and share videos for teaching and collaboration. Expert robotic surgeons use video review for self-reflection and self-assessment. They recognize that improving surgical skills requires a growth mindset. These findings may contribute to the surgical education of novices.


Craft, money and mercy: an apothecary's self-portrait in sixteenth-century Bologna.
The apothecary occupied a liminal position in early modern society between profit and healing. Finding ways to distance their public image from trade was a common problem for apothecaries across Europe. This article uses the case of a Bolognese apothecary, Filippo Pastarino, to address the question of how early modern apothecaries chose to represent themselves to political authorities and to the wider public. 'Mercy', alongside 'craft', was a pillar of apothecaries' social identity. By contrast, no matter how central financial transactions ('money') were to their activity, apothecaries did not want to be perceived as merchants. Thus, the assistance and advice apothecaries provided to patients and customers resulted as central aspects of their social role. In this context, Bolognese apothecaries aimed to defend their current status, which had been challenged by naturalist Ulysses Aldrovandi, city authorities and local monasteries. However, Pastarino's claims can also be seen as antecedents to the self-legitimizing strategy that seventeenth-century artisans deployed when faced with the need to enhance their new status as natural philosophers. The present study attributes a name, a date of birth and a shop to Filippo Pastarino, revising previous interpretations. More broadly, by focusing on how these artisans defended their position in the city it enriches our understanding of the self-representation of apothecaries.


Characterization of tumour mutation burden in patients with non-small cell lung cancer and interstitial lung disease.
The efficacy expectation of immune checkpoint inhibitors against NSCLC in patients with ILD seems to be high because these populations are supposed to have high TMB. However, information about the characterization of TMB in patients with NSCLC and ILD is limited. Therefore, this study aimed to evaluate TMB in samples of NSCLC with ILD and clarify factors that influence TMB values. The medical records of patients with NSCLC who underwent thoracic surgery at our institution between January 2014 and January 2017 were retrospectively reviewed. Whole-exome sequencing with an Ion Proton system and gene expression profiling of fresh surgical specimens were performed. Among 367 patients with NSCLC, 62 (16.9%) were diagnosed with ILD. All samples were collected from primary tumours with a median TMB of approximately 2.1 (range: 0.1-64.4) mutation/Mb. Among 81 squamous cell carcinomas, we compared 27 tumours with concomitant ILD and 54 tumours without ILD. Univariate analyses revealed that tumours with concomitant ILD showed lower TMB values than those without ILD. Multivariate analysis revealed that concomitant ILD was significantly associated with low TMB values. Conversely, no difference was noted in the TMB value of adenocarcinoma between patients with and without ILD. Squamous cell carcinoma and adenocarcinoma with ILD do not have high TMB values. Therefore, considering the risk of severe pneumonitis, immune checkpoint inhibitors should not be used routinely against patients with NSCLC and ILD based on the expectation of high TMB values.


Studies on the F-actin.tropomyosin.troponin complex. III. Effects of troponin components and calcium ion on the binding affinity between tropomyosin and F-actin.
We studied the effects of the troponin components TN-T, TN-I and TN-C, and of Ca2+ concentration on the dissociation temperature of the F-actin.tropomyosin complex. Troponin components and their complexes increased the dissociation temperature in the following sequence of effectiveness: TN-C(+/- Ca2+) less than TN-I less than TN-I.TN-C(+/-Ca2+) less than TN-T.TN-C(+/- Ca2+) less than TN-T.TN-C(--Ca2+) approximately TN-T less than TN-T.TN-I.TN-C(+Ca2+) less than TN-T.TN-I.TN-C(--Ca2+) approximately TN-T.TN-I; TN-C has no effect. The effect of TN-I is small. TN-T is the most important component for increasing the dissociation temperature. The shifting by Ca2+ of the dissociation temperature to lower values is only seen when both TN-T and TN-C are present.


Regression of low-grade gastric mucosa-associated lymphoid tissue lymphoma after eradication of Helicobacter pylori: possible association with p16 hypermethylation.
Many reports have stated that the cure of Helicobacter pylori infection can induce a complete remission of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Although p16 hypermethylation was frequently found in MALT lymphoma, the association between this finding and the remission of MALT lymphoma has not been clarified. We performed a prospective study to evaluate the outcome of patients with low-grade gastric MALT lymphoma and the expression of p16 hypermethylation. We prospectively enrolled 20 patients with H. pylori-positive low-grade gastric MALT lymphoma (stage I E1). After the eradication of H. pylori, the patients were regularly followed-up with endoscopic and histological assessment. The methylation-specific polymerase chain reaction (PCR) (MSP) method was used for the serial detection of p16 hypermethylation. Eighteen patients (90%) achieved complete remission, with a median duration of 15.7 months. The initial detection rate of p16 hypermethylation was 58% (7 of the 12 patients in whom p16 hypermethylation was evaluated successfully). In a serial investigation, 3 patients who were followed-up for a median 28 months showed that the p16 hypermethylation had disappeared. Complete remission of low-grade gastric MALT lymphoma after the eradication of H. pylori infection can be maintained for more than 1 year. Further studies are warranted to investigate the role of p16 hypermethylation in the pathogenesis of gastric MALT lymphoma.


Pharmacokinetics of Antiretroviral Drugs in Older People Living with HIV: A Systematic Review.
The life expectancy of people living with HIV (PLWHIV) has significantly improved in recent decades, mostly due to antiretroviral (ARV) therapy. Aging can affect the pharmacokinetics of drugs and, as a consequence, increase the risk of drug interactions and toxicity that may impact treatment. The aim of this study was to carry out a systematic review of the literature on the effect of aging on ARV pharmacokinetics. Searches were performed in the BVS, EMBASE and PUBMED databases until November 2022. All studies available in English, Spanish and Portuguese investigating the pharmacokinetics of ARV approved by the US Food and Drug Administration (FDA) from 2005 to 2020 were selected. Peer-reviewed publications were included if they met all criteria: adults (≥ 18 years of age) living with or without HIV; report any pharmacokinetic parameter or plasma concentration of at least one of the following ARVs: tenofovir alafenamide fumarate (TAF); doravirine (DOR), rilpivirine (RIL) and etravirine (ETR); darunavir (DRV), tipranavir (TPV) and fostemsavir (FTR); dolutegravir (DTG), raltegravir (RAL), bictegravir (BIC) and elvitegravir (EVG); maraviroc (MVC); ibalizumab (IBA); cobicistat (COBI). Pharmacokinetic parameters were reported stratified per age group: young adults (aged 18-49 years) or older (age ≥ 50 years) and all studies were evaluated for quality. The review protocol was registered in the PROSPERO database (registration number CRD42021236432). Among 97 studies included, 20 reported pharmacokinetic evaluation in older individuals (age ≥ 50 years). Twenty five percent of the articles were phase I randomized clinical trials with HIV-negative participants and non-compartmental pharmacokinetic analysis presenting the parameters area under the curve (AUC) and peak drug concentration (Cmax). Seven age-stratified studies evaluated BIC, ETR, DRV, DTG, DOR and RAL. We found publications with discordant results for ETR and DTG pharmacokinetics in different age groups. DRV exposure was highly variable but modestly increased in aging PLWHIV. In contrast, no influence of age on BIC, DOR and RAL exposure was observed. A variability in pharmacokinetic parameters could be observed for the other ARVs (TAF and MVC) in different age groups. Exposure to DRV increases modestly with age, while exposure to BIC, DOR and RAL appears to be unaffected by age. As the available evidence to confirm a potential effect of aging on ARV pharmacokinetics is limited, further studies are necessary.


Postmortem Antigen-Detecting Rapid Diagnostic Tests to Predict Infectivity of SARS-CoV-2-Associated Deaths.
We investigated the infectivity of 128 severe acute respiratory disease coronavirus 2-associated deaths and evaluated predictive values of standard diagnostic procedures. Maintained infectivity (20%) did not correlate with viral RNA loads but correlated well with anti-S antibody levels. Sensitivity >90% for antigen-detecting rapid diagnostic tests supports their usefulness for assessment.


Distinction between normal and epileptic rhythms in rodent sensorimotor cortex.
Characteristics of spontaneous spindling in electrocorticograms from awake rodents are described. Comparisons are made between this spontaneous activity and epileptic activity generated in the sensorimotor cortex.


The use of sialodochoplasty in the treatment of benign inflammatory obstructive submandibular gland disease.
One of the most common causes of submandibular gland enlargement is benign inflammatory disease. The usual cause is ductal outflow obstruction due to either a calculus or stenosis allowing stasis and retrograde movement of the saliva into the acinar structures leading to an inflammatory response and gland enlargement. Faced with a submandibular mass, a work-up that will rule out neoplastic causes of submandibular enlargement is instituted. This includes clinical assessment, probing of the gland, radiocontrast sialography, and CT scanning. The treatment should reflect the obstructive nature of the disease. Plastic reconstruction of the duct allows the removal of calculi, shortening of the duct, and enlargement of the outflow opening preventing recurrence and allowing healing of the gland. The procedure is performed intraorally as an outpatient, does not disrupt oral functioning, or subject the patient to the risks of gland removal or loss of that organ's function. Our experience with 27 patients over a 7-year period is presented with a detailed description of the technique and an analysis of the results. The procedure was successful in 22 of the 27 patients.


SARS-CoV-2 Circulation in the School Setting: A Systematic Review and Meta-Analysis.
The contribution of children to viral spread in schools is still debated. We conducted a systematic review and meta-analysis of studies to investigate SARS-CoV-2 transmission in the school setting. Literature searches on 15 May 2021 yielded a total of 1088 publications, including screening, contact tracing, and seroprevalence studies. MOOSE guidelines were followed, and data were analyzed using random-effects models. From screening studies involving more than 120,000 subjects, we estimated 0.31% (95% confidence interval (CI) 0.05-0.81) SARS-CoV-2 point prevalence in schools. Contact tracing studies, involving a total of 112,622 contacts of children and adults, showed that onward viral transmission was limited (2.54%, 95% CI 0.76-5.31). Young index cases were found to be 74% significantly less likely than adults to favor viral spread (odds ratio (OR) 0.26, 95% CI 0.11-0.63) and less susceptible to infection (OR 0.60; 95% CI 0.25-1.47). Lastly, from seroprevalence studies, with a total of 17,879 subjects involved, we estimated that children were 43% significantly less likely than adults to test positive for antibodies (OR 0.57, 95% CI 0.49-0.68). These findings may not applied to the Omicron phase, we further planned a randomized controlled trial to verify these results.


Selective versus strategic control against Rhipicephalus microplus in cattle: A comparative analysis of efficacy, animal health, productivity, cost, and resistance management.
This study compared selective control versus strategic control against Rhipicephalus (Boophilus) microplus, under conditions of a real dairy farm. Strategic control requires that all animals be treated with acaricide at regular pre-determined intervals. Selective control only requires treatment of infested animals and only when they are at or above a pre-determined threshold. Tick counts on animals and in pasture were performed and the susceptibility of tick populations to the different treatment methods was evaluated at the beginning and end of the study using the Larval Packet Test, Larval Immersion Test, and Adult Immersion Test. Over the four years of the study strategic control was more advantageous than the selective control as the group experienced lower tick burden on animals and in pasture, absence of skin lesions and myiases, lower operating costs, treatments concentrated in fewer months of the year and lower resistance pressure.


Artificial intelligence in radiology - beyond the black box.
Artificial intelligence is playing an increasingly important role in radiology. However, more and more often it is no longer possible to reconstruct decisions, especially in the case of new and powerful methods from the field of deep learning. The resulting models fulfill their function without the users being able to understand the internal processes and are used as so-called black boxes. Especially in sensitive areas such as medicine, the explainability of decisions is of paramount importance in order to verify their correctness and to be able to evaluate alternatives. For this reason, there is active research going on to elucidate these black boxes. This review paper presents different approaches for explainable artificial intelligence with their advantages and disadvantages. Examples are used to illustrate the introduced methods. This study is intended to enable the reader to better assess the limitations of the corresponding explanations when meeting them in practice and strengthen the integration of such solutions in new research projects. Besides methods to analyze black-box models for explainability, interpretable models offer an interesting alternative. Here, explainability is part of the process and the learned model knowledge can be verified with expert knowledge. · The use of artificial intelligence in radiology offers many possibilities to provide safer and more efficient medical care. This includes, but is not limited to support during image acquisition and processing or for diagnosis.. · Complex models can achieve high accuracy, but make it difficult to understand data processing.. · If the explainability is already taken into account during the planning of the model, methods can be developed that are powerful and interpretable at the same time.. · Gallée L, Kniesel H, Ropinski T et al. Artificial intelligence in radiology - beyond the black box. Fortschr Röntgenstr 2023; 195: 797 - 803.


Home enteral nutrition via gastrostomy in advanced head and neck cancer patients.
We investigated whether home enteral feeding via a tube gastrostomy would enable patients with advanced malignant disease, who were unable to maintain themselves nutritionally via the oral route, to be independent of the hospital setting. Thirty-nine patients with advanced upper gastrointestinal and head and neck cancer had a tube gastrostomy placed. Before discharge, the patient was trained in the care and use of the gastrostomy feeding tube. Ten patients died of their disease before they could be discharged. During the 6-month period before gastrostomy insertion, the mean weight loss of the remaining 29 patients was 12.8%, and the mean body weight was less than 90% of ideal body weight. Prior to operation, the mean serum albumin and total lymphocyte count were 3.7 g/L and 1,087/mL, respectively. At discharge the mean caloric intake was 1.48 times resting energy expenditure. Home enteral nutrition was provided for a median of 94 days and resulted in stabilization of nutritional indices. During their median survival of 176 days, the 29 patients were admitted a total of 52 times. Twenty-eight percent of the patients were never re-admitted after gastrostomy and were adequately maintained at home, whereas 24% needed to be re-admitted once. Only 48% were re-admitted twice to assist in their nutritional management. Twenty patients received temporary home nursing services to aid in their transition. Four patients eventually resumed oral intake, and their feeding gastrostomies were removed.(ABSTRACT TRUNCATED AT 250 WORDS)


Detection of Phenolic and Flavonoid Compounds Using High Performance Thin Layer Chromatography (HPTLC).
High performance thin layer chromatography (HPTLC) is a sophisticated instrumental technique based on the full capabilities of thin layerchromatography. The advantages of automation, scanning, full optimization, selective detection principle, minimum sample preparation,hyphenation, etc., enable it to be a powerful analytical tool for chromatographic information of complex mixtures of inorganic, organic andbiomolecules which are characterized in this chapter.


ErbB receptor tyrosine kinase family expression levels in urothelial bladder carcinoma.
ErbB receptor tyrosine kinases family plays an important role in cell cycle regulation. Overexpression of ErbB receptors has been described in several solid tumors. The aim of this study was to investigate the levels of ErbB1, ErbB2, ErbB3, and ErbB4 expression in bladder cancer. Urinary bladder tumor samples were obtained from 33 bladder cancers and 7 non-cancerous bladder biopsies. The levels of ErbB1, ErbB2, ErbB3, and ErbB4 genes expression in bladder cancer were determined by real-time PCR. The presence of protein was confirmed by immunostaining. Expression of ErbB1, ErbB2, ErbB3, and ErbB4 genes increased 0.67, 4.72, 2.89, and 2.65-fold, respectively, in bladder tumors as compared with normal tissue. There was a significant difference between immunostaining results of ErbB4 protein in bladder tumors and normal bladder tissue (P<0.01). The present data suggest that ErbB2, ErbB3, and ErbB4 genes may have a role in bladder cancer tumorigenesis.


Perfluoroheptanoic acid induces Leydig cell hyperplasia but inhibits spermatogenesis in rats after pubertal exposure.
Perfluoroheptanoic acid (PFHpA) is a short-chain alternative to long-chain perfluoroalkyl substances, which have been reported to possess reproductive toxicity. However, it is unclear whether PFHpA affects Leydig cell development during puberty. The 35-day-old Sprague Dawley male rats were exposed to PFHpA by gavage with 0 (corn oil), 10, 50, and 100 mg/kg/day for 21 days. PFHpA did not affect the body weight of rats, but it reduced testis weight, relative testis weight, and epididymis weight at 100 mg/kg. It significantly increased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels at a dose of 100 mg/kg without affecting serum estradiol levels. PFHpA suppressed sperm production at a dose of 100 mg/kg. PFHpA induced Leydig cell hyperplasia (increased number of CYP11A1-positive Leydig cells) at a dose of 100 mg/kg, but down-regulated the expression of Cyp11a1, Hsd3b1, and Cyp17a1 in individual Leydig cell pe se and up-regulated the expression of Fshr in the Sertoli cell pe se. PFHpA did not affect the number of HSD11B1 (a biomarker for more mature Leydig cells) positive Leydig cells and SOX9 positive Sertoli cells. PFHpA increased BCL2, and the phosphorylation of AKT1, AKT2, ERK1/2, and JNK, but decreased BAX levels. However, it had no effect on SIRT1 and PGC-1α levels. In conclusion, PFHpA induces Leydig cell hyperplasia due to the increase in the secretion of luteinizing hormone through negative feedback after down-regulating the expression of steroidogenic enzymes and inhibiting testosterone production in individual Leydig cells. This proliferation may be mediated by increasing BCL2 and phosphorylation of AKT, ERK1/2, and JNK, and decreasing BAX level.


Triple emergencies: Hyperosmolar hyperglycemic state, venous thromboembolism, and huge free-floating right heart thrombus successfully managed with anticoagulation.
A 57-year-old man, with type 2 diabetes mellitus, was admitted with a hyperosmolar hyperglycemic state, who developed in-hospital venous thromboembolism with huge free-floating right heart thrombus, and there is no available optimal treatment option for the huge free-floating right heart thrombus, except anticoagulation with warfarin and low molecular weight heparin with successful outcome.


Death rate in a small air-lift loop reactor of vero cells grown on solid microcarriers and in macroporous microcarriers.
The death rate of Vero cells grown on Cytodex-3 microcarriers was studied as a function of the gas flow rate in a small air-lift loop reactor. The death rate may be described by first-order death-rate kinetics. The first-order death-rate constant as calculated from the decrease in viable cells, the increase in dead cells and the increase in LDH activity is linear proportional to the gas flow rate, with a specific hypothetical killing volume in which all cells are killed of about 2·10(-3) m(3) liquid per m(3) of air bubbles. In addition, an experiment was conducted in the same air-lift reactor with Vero cells grown inside porous Asahi microcarriers. The specific hypothetical killing volume calculated from this experiment has a value of 3·10(-4) m(3) liquid per m(3) of air bubbles, which shows that the porous microcarriers were at least in part able to protect the cells against the detrimental hydrodynamic forces generated by the bubbles.


Allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning regimen in children: a single-center experience.
This single-center retrospective study reported the outcome of 19 children treated with a reduced-intensity conditioning (RIC) regimen prior to allogeneic stem cell transplantation (allo-SCT), for hematologic malignancies (n = 17), bone marrow failure (n = 1), and neuroblastoma (n = 1). Children were ineligible for standard myeloablative conditioning because of severe comorbidities (n = 9), a previous auto or allo-SCT (n = 7) or a prior history of extensive chemotherapy (n = 3). All patients underwent a fludarabine-based RIC regimen, and received grafts from matched-related donors (n = 5), match-unrelated donors (n = 6), or unrelated cord blood (UCB, n = 8). In this series, two patients treated with UCB failed to engraft and 63% achieved full donor chimerism at day 100 after allo-SCT. With a median follow-up of 537 d (range, 115-4136), treatment-related mortality was 16% and overall survival was 47%. The principal cause of death was disease relapse (n = 7). Acute graft versus host disease (GVHD) occurred in 53% of patients, while only 10% developed extensive chronic GVHD. Overall, results from this series suggest that RIC allo-SCT can be a valid alternative treatment option in unfit children with malignant hematological diseases. Prospective studies are needed to enlarge pediatric experience in this domain and better identify those children more suitable for a RIC allo-SCT approach.


Serum lipid physiology and the influence of glaucoma medications.
Understanding the effect of serum lipid levels on risk factors for coronary heart disease and how they are influenced by medical therapy may lead to overall better care of the glaucoma patient. Elevated low-density lipoprotein and total cholesterol levels are major risk factors for heart disease. In contrast, high-density lipoprotein (HDL) is protective for heart disease. beta-adrenergic blockers, a class of medicines used to treat glaucoma, may influence serum lipid levels. Oral nonselective beta-adrenergic blockers reduce HDL cholesterol by 19% and increase triglycerides by 20-40%. Furthermore, topical nonselective beta-adrenergic blockers also decrease serum HDL and worsen the total cholesterol/HDL ratio. However, beta-blockers with intrinsic sympathomimetic activity appear to be lipid neutral. At present, there is no clear clinical evidence to indicate that changes in serum lipids with use of topical beta-adrenergic blockers significantly affect the clinical course of the patient. Little information is available for other classes of medicines used topically to treat glaucoma. However, oral preparations of prostaglandins, alpha-adrenergic agonists, angiotensin-converting enzyme inhibitors, and calcium channel blockers do not adversely affect serum lipid levels. Further study is required on newer glaucoma preparations to determine their specific actions on lipid levels. Additionally, further work is required to understand the significance of not only the adverse effect of beta-adrenergic blockers on lipid levels, but their overall effect on long-term cardiac morbidity and mortality.


Barriers in education and professional development of Belgian medical imaging technologists and nurses working in radiotherapy: A qualitative study.
Radiotherapy (RT) professionals are not officially recognised or have formal education in many countries, with RT being often a very short component of a broader programme. This study aims to investigate Belgian stakeholders' perpectives regarding existing barriers and solutions for the education and professional development of Radiation therapists (RTT) which regroups medical imaging technologists (MIT) and nurses working in RT. Nine experts with vast experience in RT were invited to be interviewed; eight participated (4 heads of the RT departments, 2 school representatives, 2 national society's representatives). A semi-structured questionnaire was used. The first two authors open-coded all interviews using thematic analysis. Five themes and eleven sub-themes were drawn from the analysis. Belgian MIT and nurses in RT perform the same roles, but have different educational backgrounds. The barriers in education and professional development are related to law, education landscape, economics, social-cultural context, politics and professional identity. The main difference between the French and Dutch-speaking parts of the country were at the education level. The proposed solutions included modifying the legislative framework surrounding the RTT profession, setting up financial support, formalizing the educational requirements and increasing professional awareness. Future strategies might include the development of advanced roles and responsibilities. Current law, educational landscape and lack of economic support were the main barriers identified. Except for the educational background, no fundamental differences were found between nurses and MIT in the French and Dutch-speaking parts. Perspectives for both professional groups are linked to future legislative and financial actions, the stakeholders involved and a clear strategic vision. In the upcoming years, increased responsibilities and the creation of a master's degree should be foreseen. Regulation of RTT profession and education and an increase in RT-specific training must be implemented in Belgium to ensure professional development and optimized treatment delivery.


The production and characterisation of an immobilised chaperonin system.
Here we report a method of immobilising the chaperonins GroEL and GroES to a glass matrix. The immobilised chaperone system has been used to successfully refold target proteins denatured by guanidine hydrochloride and produce substantially higher levels of active protein than occur on dilution into aqueous solution alone. The chaperone system has been shown to refold proteins from each of the three categories of GroEL substrate. The refolding of the enzyme glycerol dehydrogenase from Bacillus stearothermophilus shows a two-fold increase in activity in the presence of immobilised GroEL compared to that in free solution. The lactate dehydrogenase from B. stearothermophilus also shows a two-fold higher yield of activity in the presence of the immobilised GroEL and ATP. The presence of immobilised GroEL in the absence of ATP arrests the refolding of LDH. The enzyme citrate synthetase from porcine heart demonstrates a three-fold increase in activity when refolded in the presence of immobilised GroEL, ATP and free GroES. Similar results are obtained in the presence of free GroEL, immobilised GroES and ATP. The matrix-bound chaperone can be removed from the refolding mixture by centrifugation, producing a reusable system that can be easily isolated and purified from the refolded substrate.


Efficacy of methods of intercostal nerve blockade for pain relief after thoracotomy.
Intercostal nerve blockade for postthoracotomy pain relief can be accomplished by continuous infusion of local anesthetics through a catheter in the subpleural space or through an interpleural catheter, by cryoanalgesia, and by a direct intercostal nerve block. A systematic review of randomized studies indicates that an extrapleural infusion is at least as effective as an epidural and significantly better than narcotics alone. The other techniques of intercostal blockade do not offer an advantage over narcotics alone.


Ambiquitous behavior of rabbit liver lactate dehydrogenase.
Rabbit liver mitochondrial fraction shows lactate dehydrogenase activity. The enzyme can be released from particles by increasing the pH and the ionic strength of the medium. There is a narrow range of pH (6.8-7.4) and ionic strength (20-50 mM NaCl) in which the solubilization sharply increases. It has been shown that divalent anions (SO4(2-) and cations (Mg2+, Ca2+) are highly effective specific solubilizing agents. NADH (1.5 mM) and ATP (1.0 mM) were effective in solubilizing 50% of the enzyme bound, whereas the same concentrations of the analogs NAD+ and ADP had little effect. Cytosolic lactate dehydrogenase bound to the mitochondrial fraction and a saturation of particles by enzyme was observed in all experiments performed. The in vitro binding requires a short period of incubation between the enzyme and particles and the binding is independent of the temperature in the 0-37 degrees C range. Binding was prevented by 0.15 M NaCl. The bound enzyme is approximately 20% less active than the soluble one. The results described give support to the proposal that rabbit liver lactate dehydrogenase has an ambiquitous behavior, like other glycolytic enzymes, which have not a fixed intracellular localization.


Contraception in hereditary angioedema.
To report a case of successful use of a transdermal contraceptive in a patient with hereditary angioedema. Case report. University medical center. A patient who had used oral contraceptives contracted SC and submucosal tumefaction every 1 or 2 months. She was diagnosed with type I hereditary angioedema. It was determined that she was complement C4 deficient and C1-inhibitor quantitative deficient but functional C1-inhibitor normal. After she was diagnosed, the use of oral contraceptives was contraindicated. Oral contraceptives were suspended, and a hormonal transdermal contraceptive was started. The absence of symptoms after 26 months using a transdermal contraceptive. After 26 months of using this treatment, the patient has not experienced any symptoms of the hereditary angioedema. The use of hormonal contraceptives transdermally can be an alternative in patients with hereditary angioedema.


Global Threats to Child Safety.
Children have rights, as enumerated in the Declaration of the Rights of the Child, and need protection from violence, exploitation, and abuse. Global threats to child safety exist. These threats include lack of basic needs (food, clean water, sanitation), maltreatment, abandonment, child labor, child marriage, female genital mutilation, child trafficking, disasters, and armed conflicts/wars. Recent disasters and armed conflicts have led to a record number of displaced people especially children and their families. Strategies and specific programs can be developed and implemented for eliminating threats to the safety of children.


Effects of a urolith prevention diet on urine compositions of glycosaminoglycans, Tamm-Horsfall glycoprotein, and nephrocalcin in cats with calcium oxalate urolithiasis.
To evaluate urine concentrations of glycosaminoglycans, Tamm-Horsfall glycoprotein, and nephrocalcin in cats fed a diet formulated to prevent calcium oxalate uroliths. 10 cats with calcium oxalate urolithiasis. In a previous study conducted in accordance with a balanced crossover design, cats were sequentially fed 2 diets (the diet each cat was consuming prior to urolith detection and a diet formulated to prevent calcium oxalate uroliths). Each diet was fed for 8 weeks. At the end of each 8-week period, a 72-hour urine sample was collected. Concentrations of glycosaminoglycans, Tamm-Horsfall glycoprotein, and the 4 isoforms of nephrocalcin in urine samples collected during that previous study were measured in the study reported here. RESULTS; Diet had no effect on the quantity of Tamm-Horsfall glycoprotein and nephrocalcin in urine. However, the urine concentration of glycosaminoglycans was significantly higher during consumption of the urolith prevention diet. Feeding a urolith prevention diet increased the urine concentration of glycosaminoglycans, which are glycoprotein inhibitors of growth and aggregation of calcium oxalate crystals.


Functional characterization of evolutionarily conserved DNA regions in forkhead box f1 gene locus.
The Forkhead Box f1 (Foxf1) transcription factor (previously known as HFH-8 or Freac-1) is expressed in the septum transversum and splanchnic (visceral) mesoderm and is required for proper development of gut-derived organs. Sequence comparisons of mouse and human Foxf1 genes have revealed highly conserved DNA sequences located within the -5.3-kb Foxf1 promoter region and the 400-nucleotide regulatory element located 1 kb 3' to the Foxf1 gene (3'RE). To examine their transcriptional activity during mouse embryonic development, we generated transgenic mice in which the expression of the beta-galactosidase transgene was controlled by the -2.7-kb Foxf1 promoter region, the -5.3-kb Foxf1 promoter region, or the -5.3-kb Foxf1 promoter region fused to the 3'RE. The -5.3-kb Foxf1 promoter sequences induced appropriate transgene expression in the midgut and developing intestine, whereas the -2.7-kb Foxf1 promoter region was transcriptionally inactive. Addition of 3'RE to the -5.3-kb Foxf1 promoter restored proper transgene expression in the foregut, liver, and lung mesenchyme and prevented ectopic transgene expression in the developing nervous system. Cotransfection studies demonstrated that FoxA2 protein bound to the 3'RE region (+4506/+4529 bp) and was sufficient to inhibit expression of the -5.3-kb Foxf1 promoter. Furthermore, C/EBPbeta and HNF-6 proteins bound to the 3'RE region (+4647/+4694 bp) and provided synergistic transcriptional activation of the -5.3-kb Foxf1 promoter in cotransfection assays. These studies demonstrated that the conserved Foxf1 3'RE region is essential for proper tissue-specific regulation of the Foxf1 promoter region during mouse embryogenesis.


Did the adoption of accelerated partial-breast irradiation reduce the noncompliance with adjuvant radiation in lumpectomy patients?
The underutilization of radiation therapy after breast-conserving surgery in early-stage breast cancer patients has been attributed to the inconvenience and potential side effects of whole-breast radiation treatment regimens. Accelerated partial-breast irradiation (APBI) involves twice-daily treatments more than 4 to 5 days, which could potentially improve convenience and adherence for women undergoing treatment. We studied local therapies in about one-third of a million female breast cancer patients who were diagnosed between January 2000 and June 2011. We found that the use of APBI brachytherapy increased rapidly from .2% in 2000 to about 3.1% in 2008 and leveled off after 2009. The increased use of APBI did not reduce the percentage of early-stage breast cancer patients who improperly forego radiation (about 14% over the whole study period). Noncompliance with adjuvant radiation is still common when shortened radiation therapy becomes increasingly accessible.


Protein-oxidized phospholipid interactions in cellular signaling for cell death: from biophysics to clinical correlations.
Oxidative stress is associated with several major ailments. However, it is only recently that the developments in our molecular level understanding of the consequences of oxidative stress in modifying the chemical structures of biomolecules, lipids in particular, are beginning to open new emerging insights into the significance of oxidative stress in providing mechanistic insights into the etiologies of these diseases. In this brief review we will first discuss the role of lipid oxidation in controlling the membrane binding of cytochrome c, a key protein in the control of apoptosis. We then present an overview of the impact of oxidized phospholipids on the biophysical properties of lipid bilayers and continue to discuss, how these altered properties can account for the observed enhancement of formation of intermediate state oligomers by cytotoxic amyloid forming peptides associated with pathological conditions as well as host defense peptides of innate immunity. In the third part, we will discuss how the targeting of oxidized phospholipids by i) pathology associated peptides and ii) host defense peptides can readily explain the observed clinical correlations associating Alzheimer's and Parkinson's diseases with increased risk for type 2 diabetes and age-related macular degeneration, and the apparent protective effect of Alzheimer's and Parkinson's diseases from some cancers, as well as the inverse, apparent protection by cancer from Alzheimer's and Parkinson's diseases. This article is part of a Special Issue entitled: Oxidized phospholipids-Their properties and interactions with proteins.


Functional imaging and neural information coding.
Measuring functional magnetic resonance imaging (fMRI) responses to parametric stimulus variations in imaging experiments can elucidate how sensory information is represented in the brain. However, a potential limitation of this approach is that fMRI responses reflect only a regional average of neuronal activity. For this reason stimulus-induced changes in fMRI signal may not always reflect how sensory information is encoded by neuronal population activity. We investigate the potential problems induced by the finite spatial resolution of the fMRI signal by combining the principles of Information Theory with a computational model of neuronal activity based on known tuning properties of sensory cortex and assuming a linear spike rate to fMRI signal relationship. We found that the relationship between neuronal information and fMRI signal is highly nonlinear. It follows that the brain voxel experiencing the largest fMRI signal change is not necessarily the voxel encoding the most sensory information. Results also show that functional imaging data can be better interpreted in terms of neural information processing if the fMRI data and some knowledge about the tuning properties of the underlying neuronal populations are incorporated into a computational model. We discuss how imaging techniques themselves may provide an estimation of neuronal tuning properties.


The Caenorhabditis elegans Eph receptor activates NCK and N-WASP, and inhibits Ena/VASP to regulate growth cone dynamics during axon guidance.
The Eph receptor tyrosine kinases (RTKs) are regulators of cell migration and axon guidance. However, our understanding of the molecular mechanisms by which Eph RTKs regulate these processes is still incomplete. To understand how Eph receptors regulate axon guidance in Caenorhabditis elegans, we screened for suppressors of axon guidance defects caused by a hyperactive VAB-1/Eph RTK. We identified NCK-1 and WSP-1/N-WASP as downstream effectors of VAB-1. Furthermore, VAB-1, NCK-1, and WSP-1 can form a complex in vitro. We also report that NCK-1 can physically bind UNC-34/Enabled (Ena), and suggest that VAB-1 inhibits the NCK-1/UNC-34 complex and negatively regulates UNC-34. Our results provide a model of the molecular events that allow the VAB-1 RTK to regulate actin dynamics for axon guidance. We suggest that VAB-1/Eph RTK can stop axonal outgrowth by inhibiting filopodia formation at the growth cone by activating Arp2/3 through a VAB-1/NCK-1/WSP-1 complex and by inhibiting UNC-34/Ena activity.


How learning preferences and teaching styles influence effectiveness of surgical educators.
Effective surgical educators have specific attributes and learner-relationships. Our aim was to determine how intrinsic learning preferences and teaching styles affect surgical educator effectiveness. We determined i) learning preferences ii) teaching styles and iii) self-assessment of teaching skills for all general surgery attendings. All general surgical residents in our program completed teaching evaluations of attendings. Multimodal was the most common learning preference (20/28). Although the multimodal learning preference appears to be associated with more effective educators than kinesthetic learning preferences, the difference was not statistically significant (80.0% versus 66.7%, p = 0.43). Attendings with Teaching Style 5 were more likely to have a lower "professional attitude towards residents" score on SETQ assessment by residents (OR 0.33 (0.11, 0.96), p = 0.04). Attendings rated their own "communication of goals" (p < 0.001), "evaluation of residents" (p = 0.04) and "overall teaching performance" (p = 0.01) per STEQ domains as significantly lower than the resident's assessment of these cofactors. Identification of factors intrinsic to surgical educators with high effectiveness is important for faculty development. Completion of a teaching style self-assessment by attendings could improve effectiveness.


Screening for hereditary hemochromatosis: a clinical practice guideline from the American College of Physicians.
Hereditary hemochromatosis is a genetic disorder of iron metabolism. Diagnosis of hereditary hemochromatosis is usually based on a combination of various genetic or phenotypic criteria. Decisions regarding screening are difficult because of the variable penetrance of mutations of the HFE gene and the absence of any definitive trials addressing the benefits and risks of therapeutic phlebotomy in asymptomatic patients or those with only laboratory abnormalities. The purpose of this guideline is to increase physician awareness of hereditary hemochromatosis, particularly the variable penetrance of genetic mutations; aid in case finding; and explain the role of genetic testing. This guideline provides recommendations based on a review of evidence in the accompanying background paper by Schmitt and colleagues. The target audience for this guideline is internists and other primary care physicians. The target patient population is all persons who have a probability or susceptibility of developing hereditary hemochromatosis, including the relatives of individuals who already have the disease.


Transient photovoltages in purple membrane multilayers. Charge displacement in bacteriorhodopsin and its photointermediates.
The photovoltaic properties of bacteriorhodopsin molecules and their photochemical intermediates have been investigated in an experimental cell consisting of multilayered films of highly oriented, dry fragments of purple membrane and lipid sandwiched between two metal (Pd) electrodes. The electrical time constant of these sandwich cells containing between 5 and 30 layers is less than 10(-5) S. Bright illumination of these cells with actinic flashes of approximately 1 ms duration generates transient photovoltages. These photovoltages, which make the extracellular surface of purple membrane positive with respect to the intracellular surface, follow the time course of the flash with no detectable latency. The amplitude of the photovoltages increases linearly with light intensity and their action spectrum matches the absorption spectrum of the light-adapted state of bacteriorhodopsin, BR570. In these dry multilayer cells, the slow photointermediates of bacteriorhodopsin, M412, N520 and O640 are long lived. Illumination of the sandwich cells with long duration (200 ms) pulses of light results, therefore, in the formation of photomixtures containing all these slow photointermediates. Flash illumination of the sandwich cells immediately following the conditioning pulse produces photovoltages whose action spectra match the absorption spectra of the M412 and N520 photointermediates. The M412 photovoltages, like the BR570 photovoltages, follow the time course of the actinic flash with no detectable latency and increase in amplitude linearly with light intensity. But, unlike the BR570 photovoltage, the M412, N520 and O640 photovoltages make the extracellular surface of purple membrane negative with respect to the intracellular surface. Through the of their specific photovoltaic signals, M412 and N520 are shown to be kinetically distinct photointermediates of bacteriorhodopsin. Detection of fast photovoltages with these characteristics in the absence of any ionic solution, and in parallel with spectrophotometric changes, suggest that they arise from charge displacements in the bacteriorhodopsin molecules and their photointermediates as they undergo photochemical conversion in response to the absorption of photons.


Large voltage-induced coercivity change in Pt/Co/CoO/amorphous TiOx structure and heavy metal insertion effect.
There is urgent need for spintronics materials exhibiting a large voltage modulation effect to fulfill the great demand for high-speed, low-power-consumption information processing systems. Fcc-Co (111)-based systems are a promising option for research on the voltage effect, on account of their large perpendicular magnetic anisotropy (PMA) and high degree of freedom in structure. Aiming to observe a large voltage effect in a fcc-Co (111)-based system at room temperature, we investigated the voltage-induced coercivity (Hc) change of perpendicularly magnetized Pt/heavy metal/Co/CoO/amorphous TiOx structures. The thin CoO layer in the structure was the result of the surface oxidation of Co. We observed a large voltage-induced Hc change of 20.2 mT by applying 2 V (0.32 V/nm) to a sample without heavy metal insertion, and an Hc change of 15.4 mT by applying 1.8 V (0.29 V/nm) to an Ir-inserted sample. The relative thick Co thickness, Co surface oxidation, and large dielectric constant of TiOx layer could be related to the large voltage-induced Hc change. Furthermore, we demonstrated the separate adjustment of Hc and a voltage-induced Hc change by utilizing both upper and lower interfaces of Co.


Acute Abdomen Is a Rare Presentation of COVID-19 in the Absence of Respiratory Manifestations: A Case Report.
Mild gastrointestinal symptoms and mild abdominal pain often occur in association with COVID-19. However, acute abdomen and severe abdominal pain warranting urgent surgical treatment are rare. Here we present the case of a 40-year-old man who presented with the clinical picture of a perforated duodenal ulcer. He was eventually found to have COVID-19 and was treated conservatively. In this report, we discuss his course of treatment and review the relevant literature.


Production of tumor necrosis factor, interleukin 1, and interferon-gamma by peripheral blood mononuclear cells from patients with primary biliary cirrhosis.
Since patients with primary biliary cirrhosis (PBC) have evidence of abnormal function of the immune system, we evaluated production of various cytokines by peripheral blood mononuclear cells (PBMCs) and monocytes from patients with this disease, using an enzyme-linked immunosorbent assay. The mean amounts of production of tumor necrosis factor alpha(TNF alpha), interleukin 1 beta (IL1 beta), and interferon-gamma (IFN-gamma) by PBMCs from patients with PBC tended to be increased in cultures in the presence of stimulating agents in comparison with controls, but there was no significant difference because of a wide scatter of results. Monocytes from PBC patients also tended to produce higher amounts of TNF alpha and IL1 beta than control monocytes did, although the percentage of monocytes in PBMCs was similar in PBC and controls. A significant correlation was found between TNF alpha production and IL1 beta production in PBC patients. The number of TNF alpha or IFN-gamma positive infiltrating mononuclear cells detected by immunohistochemical staining in liver biopsy sections correlated with the production of these cytokines by PBMCs in vitro. However, cytokine production did not correlate with serum biochemical or hepatic histologic findings, except for serum alkaline phosphatase values. In patients with type B chronic active hepatitis, IL1 beta and IFN-gamma production was similar to controls, while TNF alpha production tended to be enhanced. Thus the cytokines studied here may play some role in the pathogenesis of PBC.


Isolated limb perfusion and external beam radiotherapy for soft tissue sarcomas of the extremity: long-term effects on normal tissue according to the LENT-SOMA scoring system.
With the combined treatment procedure of isolated limb perfusion (ILP), delayed surgical resection and external beam radiotherapy (EBRT) for locally advanced soft tissue sarcomas (STS) of the extremities, limb salvage rates of more than 80% can be achieved. However, long-term damage to the healthy surrounding tissue cannot be prevented. We studied the late effects on the normal tissue using the LENT-SOMA scoring system. A total of 32 patients-median age 47 (range 14-71) years-were treated for a locally advanced STS with ILP, surgical resection and often adjuvant 60-70 Gy EBRT. After a median follow-up of 88 (range 17-159) months, the patients were scored, using the LENT-SOMA scales, for the following late tissue damage: muscle/soft tissue, peripheral nerves, skin/subcutaneous tissue and vessels. According to the individual SOM parameters of the LENT-SOMA scales, 20 patients (63%) scored grade-3 toxicity on one or more separate items, reflecting severe symptoms with a negative impact on daily activities. Of these patients, 3 (9%) even scored grade-4 toxicity on some of the parameters, denoting irreversible functional damage necessitating major therapeutic intervention. In evaluating long-term morbidity after a combined treatment procedure for STS of the extremity, using modified LENT-SOMA scores, two-thirds of patients were found to have experienced serious late toxic effects.


Bone marrow-derived mesenchymal stem cells (JR-031) for steroid-refractory grade III or IV acute graft-versus-host disease: a phase II/III study.
Following a phase I/II study using mesenchymal stem cells (MSCs; JR-031) for steroid-refractory grade II or III acute graft-versus-host disease (aGVHD), a phase II/III study using the cells focused on steroid-refractory grade III or IV aGVHD was conducted. The number of infused MSCs and the number of MSC infusions were the same as the phase I/II study. No additional immunosuppressant was given for steroid-refractory aGVHD during the course of MSC infusions. Twenty-five patients (grade III, 22 patients and grade IV, 3 patients) were enrolled in this study. At 4 weeks after the first MSC infusions, six (24 %) and nine patients (36 %) achieved a complete response (CR) and partial response (PR), respectively. Durable CR by 24 weeks, which was the primary end-point, was obtained in 12 of 25 patients (48 %). At 52 weeks, 12 patients (48 %) treated with MSCs only (six patients) and MSCs plus additional treatments (six patients) were alive in CR. The survival was significantly better in patients showing overall response (OR; CR+PR) than in those showing no OR at 4 weeks. Adverse effects commonly associated with MSC infusions were not observed. Taken together, our two clinical trials suggest JR-031 to be effective for steroid-refractory aGVHD.


Clinical trials and promising preclinical applications of CRISPR/Cas gene editing.
Treatment of genetic disorders by genomic manipulation has been the unreachable goal of researchers for many decades. Although our understanding of the genetic basis of genetic diseases has advanced tremendously in the last few decades, the tools developed for genomic editing were not efficient and practical for their use in the clinical setting until now. The recent advancements in the research of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas) systems offered an easy and efficient way to edit the genome and accelerated the research on their potential use in the treatment of genetic disorders. In this review, we summarize the clinical trials that evaluate the CRISPR/Cas systems for treating different genetic diseases and highlight promising preclinical research on CRISPR/Cas mediated treatment of a great diversity of genetic disorders. Ultimately, we discuss the future of CRISPR/Cas mediated genome editing in genetic diseases.


Asymmetric friction of nonmotor MAPs can lead to their directional motion in active microtubule networks.
Diverse cellular processes require microtubules to be organized into distinct structures, such as asters or bundles. Within these dynamic motifs, microtubule-associated proteins (MAPs) are frequently under load, but how force modulates these proteins' function is poorly understood. Here, we combine optical trapping with TIRF-based microscopy to measure the force dependence of microtubule interaction for three nonmotor MAPs (NuMA, PRC1, and EB1) required for cell division. We find that frictional forces increase nonlinearly with MAP velocity across microtubules and depend on filament polarity, with NuMA's friction being lower when moving toward minus ends, EB1's lower toward plus ends, and PRC1's exhibiting no directional preference. Mathematical models predict, and experiments confirm, that MAPs with asymmetric friction can move directionally within actively moving microtubule pairs they crosslink. Our findings reveal how nonmotor MAPs can generate frictional resistance in dynamic cytoskeletal networks via micromechanical adaptations whose anisotropy may be optimized for MAP localization and function within cellular structures.


Human subthalamic nucleus: evaluation with high-resolution MR imaging at 3.0 T.
The purpose of this study was to compare the visibility of the normal subthalamic nucleus (STN) between fast spin-echo T2-weighted (FSE T2-W) images and fast short inversion time inversion-recovery (FSTIR) images, and to assess the age-related changes of the STN at 3.0 T. We evaluated high-resolution FSE T2-W and FSTIR images in 24 neurologically normal subjects. Using both sequences, we assessed the visibility of the margins of the STN, and calculated the difference in signal intensity between the STN and structures adjacent to the STN. Then, to assess the age-related changes of the STN, we calculated the contrast-to-noise ratio between the STN and the white matter, and measured the position, length, and height of the STN. All data were statistically evaluated. The visibility of the lower margin of the STN was significantly better on the FSTIR images than on the FSE T2-W images (P = 0.0001), while the visibility of other margins was significantly better on the FSE T2-W images than on the FSTIR mages (P = 0.002). The difference in signal intensity between the STN and substantia nigra was significantly greater on the FSTIR images than on the FSE T2-W images (P < 0.0001). The distance from the midline to the lateral border of the STN increased with age (FSE T2-W images: left r = 0.4916, P = 0.015; right r = 0.4442, P = 0.030). The combined reading of both FSE T2-W and FSTIR images at 3 T will improve the identification of the STN. The age-related positional change of the STN should be considered in target determination for deep brain stimulation procedures.


Tort versus no-fault: compensation and injury prevention.
The tort system, as a means of compensating the victims of injury, no longer fulfills the purpose for which it was intended. The attempt to achieve a fair and rational method of compensation, especially in the areas of medical malpractice and products liability, has been displaced by a form of litigation lottery which permits attorney's fees to divert great amounts of money from victims in needs. A reform of this system is much in need and long overdue. Following a discussion of these and other problems with the tort system, this paper will present a method for ensuring the prompt settlement of most personal injury claims through payment of the victim's net economic losses. The parallels to no-fault auto insurance and workers' compensation are examined and attention is given to the likely impact of this proposal on the conduct of potential injurers and victims.


Recombinant human erythropoietin: implications for nephrology.
The pathophysiology of the anemia of chronic renal failure (CRF), erythropoietin physiology, the characteristics of recombinant human erythropoietin, and the results of nearly 2 years of therapy with this product in hemodialysis patients are detailed in this review. This anemia is primarily an endocrine deficiency state corrected by the hormone erythropoietin. Correction of the anemia eliminates transfusions and their associated risks, improves physical endurance, and results in healthier patients beginning dialysis. Adequate support services will be necessary to maximize patient rehabilitation and employment potential. Further research is needed to better understand erythropoietin physiology and metabolism, and the impact of uremia on end organ function in the absence of anemia.


Interictal sleep recordings during presurgical evaluation: Bidirectional perspectives on sleep related network functioning.
Sleep recordings are an integral part of presurgical evaluation in drug-resistant focal epilepsy. Physiological network functioning is substantially different between wakefulness and sleep and thus may add further complexity to the task of determining the epileptogenic zone (EZ). A thorough understanding of changes in epileptic networks in relation to sleep is therefore essential in order to fully appreciate the added value of sleep recordings. Furthermore, shared expertise in epilepsy and sleep is beneficial for both domains, as intracerebral EEG during presurgical evaluation offers a unique window into physiological networks and their interaction during sleep. This review intends to delineate the way in which sleep modifies interictal epileptic discharges (IEDs), and to summarize which sleep state is the most appropriate for aiding in discerning the EZ. Two approaches will be reviewed. First, classical scalp electroencephalography (EEG) recordings help to localize the EZ, especially during rapid-eye-movement (REM) sleep. REM sleep tends to narrow the field size of IEDs, and thus helps to target the core of the EZ. Second, automated analysis of intracerebral recordings can make use of both IEDs and sleep-related oscillations in combination. Notably, high frequency oscillations and directed connectivity measures can be assessed in a single sleep cycle and are valuable tools to probe epileptogenicity. In this approach, which exploits increased network interactions during sleep, non-REM-sleep is the most suitable sleep stage to extract multiple features of local and distributed neuronal activity in order to predict the EZ. The added value of intracerebral recordings is perfectly bidirectional. From a sleep perspective, invasive EEG recordings are a unique opportunity to unravel local sleep-related network function of superficial and deeply situated brain structures. Intracerebral EEG has thus allowed the dissection of sleep features and oscillations and their anatomical sources. A multicenter effort led by the Montreal Neurological Institute resulted in a detailed open-access atlas on normative EEG activity during sleep (https://mni-open-ieegatlas.research.mcgill.ca/). It contributed to our understanding that the human brain does not sleep uniformly but that specifically deep structures have distinct signatures that are discernable from the rest of the brain. Also, this research direction allowed us to gain insights into our understanding of the important neurocognitive functions of sleep. Finally, this review provides a clinical outlook on the benefit of genuine sleep recordings, i.e. recordings with additional sleep sensors, concomitant to presurgical evaluation, in order to fully discern common sleep disorders as a frequent comorbidity of epilepsy. In conclusion, shared expertise in sleep and epilepsy is of mutual added value for improving the management of patients with epilepsy.


'Survival gene' Bcl-xl potentiates DNA-raised antitumor immunity.
T-cell priming is strongly affected by the longevity of antigen-bearing dendritic cells (DCs), which are typically short-lived in lymphoid tissues. 'Survival gene' Bcl-xl is critical for the lifespan of DCs in vivo. Here, we showed that in vivo coadministration of Bcl-xl under control of the DC-specific promoter (CD11c-Bcl-xl) and TRP2hsp70 DNA prolonged T-cell stimulation by DCs and augmented TRP2-specific-IFN-gamma-producing CD8+ T-cell responses. Consistent with these findings, enhanced protection and significant therapeutic immunity to B16 melanoma was generated by this coimmunization strategy, which also augmented therapeutic immunity to GL-26 tumor. In this B16 melanoma model, results from animal experiments with depletion of immune cells indicate that CD8+ T cells and NK cells are important in the antitumor immunity induced by this coimmunization strategy. These observations suggest that 'survival gene' Bcl-xl potentiates the magnitude of antigen-specific-CD8+ T-cell responses and the efficacy of antitumor immunity induced by DNA vaccine, and is relevant for the design of in vivo targeted DC-based vaccine strategies to improve immunity against cancer.


A novel technique for removal of permanent pacemaker leads.
We removed from 4 patients pacemaker leads that had migrated or become infected. Case 1: A 62-year-old man developed uncontrollable infection of the pacing leads. Case 2: A 78-year-old man, whose infected pacemaker was removed, had a second one implanted in the contralateral side; the pacing lead infection from the first procedure, however, was uncontrollable. Case 3: A 56-year-old woman presented with dyspnea and hepatomegaly subsequent to the second implantation of a pacemaker; the pacing leads from the first procedure caused severe stenosis in both the superior and inferior vena cavae. Case 4: A 60-year-old woman had a ruptured and migrated pacing lead in the right ventricle. We operated using a cardiopulmonary bypass and a specially designed plastic tube for removal of the leads. Although Case 2 required reconstruction of the vena cavae, all patients recovered. When removal of pacing leads is necessary, it should be done as soon as possible with cardiopulmonary bypass.


Expression of poriferasterol monoglucoside associated with differentiation of Physarum polycephalum.
A glycolipid which was expressed during a differentiation from haploid myxoamoebae to diploid plasmodia of a true slime mold, Physarum polycephalum, has been examined. In the amoeboid stage, cells did not contain this glycolipid, but after conjugation of the haploid cells, this substance appeared and increased in its amount. From structural studies of the purified glycolipid, it has been identified as poriferasterol monoglucoside.


A quantitative electron microscope study of cerebellar axon terminals on the magnocellular red nucleus neurons in the cat.
In the red nucleus (RN) of the cat, the bouton covering ratio (BCR: the ratio of whole somatic surface length and that covered with axon terminals) and the density of axon terminals in contact with somatic profiles (DAST: the number of axosomatic terminals per micron of somatic surface membrane) were calculated in each neuronal somatic profile over 60 micron in diameter. The mean BCR was 61.4 +/- 1.43 (S.E. M.)%. The mean DAST of axosomatic terminals filled with spherical synaptic vesicles (S-terminals) was 27.7 +/- 0.95, and that of terminals with pleomorphic and/or flattened vesicles (F-terminals) was 10.3 +/- 1.12. Subsequently, sequential changes of the BCR and DAST of intact terminals were examined in the RN deafferented from the cerebellorubral fibers. The mean BCR and DAST were decreased most markedly during the survival period of 4-7 days; thus decrease was chiefly due to degeneration of S-terminals (BCR: 16.7 +/- 1.17 %, DAST of S-terminals: 7.1 +/- 1.12, DAST of F-terminals: 5.8 +/- 1.22). In the RN 11-63 days after the operation, both the BCR and DAST tended to re-increase slightly and the majority of the re-increased terminals appeared to be F-terminals. Possible meanings of this re-increase of axosomatic terminals are discussed.


Three Cases of KCNT1 Mutations: Malignant Migrating Partial Seizures in Infancy with Massive Systemic to Pulmonary Collateral Arteries.
KCNT1 mutations are gain-of-function mutations in potassium channels resulting in severe infantile epilepsy. Herein we describe 3 infants with malignant migrating partial seizures with KCNT1 mutations accompanied by massive systemic to pulmonary collateral arteries with life-threatening hemoptysis and heart failure.


Modification of a glnB-like gene product by photosynthetic electron transport in the cyanobacterium Synechococcus 6301.
Covalent modification of a 13 kDa soluble-phase protein occurs during adaptation of cells of the cyanobacterium Synechococcus 6301 (mutant AN112) to light specifically absorbed by photosystem II. This adaptation is accompanied by functional changes indicative of altered excitation energy distribution between the photosystems. The 13 kDa protein is identified by solid-phase N-terminal sequencing as a protein related to PII, the glnB gene product of E. coli. In E. coli, the PII protein undergoes uridylylation and acts as a regular of glutamine synthetase at both the post-translational and transcriptional levels. The implications of modification of a transcriptional regulator by photosynthetic electron transport are discussed.


Ouabain-induced cell swelling in rabbit cortical collecting tubule: NaCl transport by principal cells.
Ouabain had no effect on the volume of intercalated cells of DOCA-stimulated rabbit cortical collecting tubules, but caused principal cells to swell rapidly at an initial rate of 67%/min. Principal cells swelled 133% then activated regulatory volume decrease mechanisms and shrank at an initial rate of -3%/min to a new volume 13% above control. The initial rate of ouabain swelling was completely inhibited by perfusate Na+ removal or reduced 95% by luminal addition of 10(-5) M amiloride. Luminal, peritubular, or bilateral Cl- removal each caused cell shrinkages of 10% and reduced the rate of ouabain swelling by 70, 85, and 99%, respectively. The presence of an apical Cl- transport step in principal cells was confirmed by increasing luminal K+ from 5 to 53 mM, which caused cell swelling of 22%. This volume increase was completely blocked by luminal Cl- removal, but was unaffected by peritubular Cl- substitution. Perfusion of CCT with 0.1 mM acetazolomide, 0.1 mM DPC or 0.5 mM SITS caused principal cell shrinkages of 7-9% and reduced the rate of ouabain swelling by 60, 70, and 40%, respectively. The initial rate of ouabain swelling was inhibited 70% by bilateral CO2/HCO3 removal and 50% by whole animal acid loading. Taken together these results demonstrate that ouabain swelling is due to cellular NaCl accumulation and that Na+ enters the cell primarily through apical Na+ channels. Cellular Cl- entry occurs at least partially through the apical membrane and may be mediated by a Cl-/HCO3- exchanger. Brief (45-90 sec) exposure of principal cells to ouabain is associated with a rapid inhibition of Na+ and/or Cl- entry steps, whereas long-term (greater than 5 min) ouabain exposure completely blocks one or both of these transport pathways.


Post-insertion Posterior Single-implant Occlusion Changes at Different Intervals: A T-Scan Computerized Occlusal Analysis.
The aim of this prospective cohort study was to evaluate the postinsertion posterior single-implant occlusion changes at 3- and 6-month intervals using T-Scan computerized occlusal analysis. A total of 21 patients received single implant, opposed by natural dentition, in posterior regions of the maxilla or mandible (13 premolar, 8 molar) and were finally restored with cemented-retained metal-ceramic crowns. The occlusal contacts were equilibrated according to the implant-protective occlusion concept to develop light contact with heavy occlusion and no contact with light occlusion in maximum inter-cuspation. The percentage of force applied to the implant crowns (POFI) and contralateral teeth (POFT) was evaluated using T-Scan computerized occlusal analysis at prosthesis insertion, 3- and 6-month follow-up appointments. The data were statistically analyzed using Friedman test and Wilcoxon post hoc test (α = 0.05). The POFI values at the 6- and 3-month follow-up appointments were significantly higher than those at prostheses insertion (p = 0.001 and p = 0.005 respectively). In addition, there were significant differences between the POFI at 3- and 6-month follow-up (p = 0.020). However, the POFT values at 3- and 6-month follow-up appointments were significantly lower than those at baseline (p < 0.001). The intensity of occlusal contacts of implant-supported prostheses opposed by natural dentition gradually increased after prosthesis insertion. Placement of single posterior implant-supported restoration decreased the percentage of occlusal force applied to contralateral arch. A periodic occlusal adjustment of implant-supported prostheses is necessary to prevent potential overloading from the movement of opposing natural dentition.


The transverse forked flap in columella reconstruction.
A single-staged transverse forked flap in columella reconstruction is described. This can be either unilateral or bilateral and an example of each is presented.


A polymorphism in the complement component C1qA correlates with prolonged response following rituximab therapy of follicular lymphoma.
Complement may play a role in the clinical response to rituximab and other monoclonal antibody-based therapies of cancer. The purpose of this study was to explore the relationship between the C1qA([276]) polymorphism and the clinical response to rituximab in patients with follicular lymphoma. Genotyping for C1qA([276A/G]) was done in 133 subjects with follicular lymphoma treated with single-agent rituximab, and correlation with clinical response was done using Cox regression analysis. Prolonged remission was observed among subjects that responded clinically to rituximab therapy and were carriers of the A allele compared with homozygous G subjects. Homozygous G subjects had a time to progression of 282 days, whereas A-allele carriers had a time to progression of 708 days [hazard ratio, (HR), 2.5; 95% confidence interval (95% CI), 2.0-3.1; P = 0.02]. Among subjects who achieved complete remission, homozygous G subjects had a time to progression of 250 days, whereas A-allele carriers had a time to progression of 1,118 days (HR, 4.5; 95% CI, 4.1-4.8, P = 0.04). The difference persisted after controlling for CD32 and CD16 polymorphisms. In patients who responded to rituximab used as first-line agent, a linear trend was observed among the C1qA([276]) genotypes, with homozygous A subjects achieving complete response at a higher rate compared with heterozygous or homozygous G subjects. Our findings indicate that polymorphisms in the C1qA gene may affect the clinical response and duration of response to rituximab therapy of follicular lymphoma. These results could have direct implications on designing antibodies with improved efficiency and enhance our understanding of the role of complement in monoclonal antibody therapy.


SurgiNet: Pyramid Attention Aggregation and Class-wise Self-Distillation for Surgical Instrument Segmentation.
Surgical instrument segmentation plays a promising role in robot-assisted surgery. However, illumination issues often appear in surgical scenes, altering the color and texture of surgical instruments. Changes in visual features make surgical instrument segmentation difficult. To address illumination issues, the SurgiNet is proposed to learn pyramid attention features. The double attention module is designed to capture the semantic dependencies between locations and channels. Based on semantic dependencies, the semantic features in the disturbed area can be inferred for addressing illumination issues. Pyramid attention is aggregated to capture multi-scale features and make predictions more accurate. To perform model compression, class-wise self-distillation is proposed to enhance the representation learning of the network, which performs feature distillation within the class to eliminate interference from other classes. Top-down and multi-stage knowledge distillation is designed to distill class probability maps. By inter-layer supervision, high-level probability maps are applied to calibrate the probability distribution of low-level probability maps. Since class-wise distillation enhances the self-learning of the network, the network can get excellent performance with a lightweight backbone. The proposed network achieves the state-of-the-art performance of 89.14% mIoU on CataIS with only 1.66 GFlops and 2.05 M parameters. It also takes first place on EndoVis 2017 with 66.30% mIoU.


Integrative p53, micro-RNA and Cathepsin Protease Co-Regulatory Expression Networks in Cancer.
As the direct regulatory role of p53 and some of its isoform proteins are becoming established in modulating gene expression in cancer research, another aspect of this mode of gene regulation that has captured significant interest over the years is the mechanistic interplay between p53 and micro-RNA transcriptional regulation. The input of this into modulating gene expression for some of the cathepsin family members has been viewed as carrying noticeable importance based on their biological effects during normal cellular homeostasis and cancer progression. While this area is still in its infancy in relation to general cathepsin gene regulation, we review the current p53-regulated micro-RNAs that are generating significant interest through their regulation of cathepsin proteases, thereby strengthening the link between activated p53 forms and cathepsin gene regulation. Additionally, we extend our understanding of this developing relationship to how such micro-RNAs are being utilized as diagnostic or prognostic tools and highlight their future uses in conjunction with cathepsin gene expression as potential biomarkers within a clinical setting.


Ammon's horn commissural responses in young rabbits.
Different responses evoked by stimulation of contralateral hippocampus at various levels are examined in new-born rabbits up to 1 month of age. Commissural fibres coming from the CA3-CA4 reach the contralateral regio superior (CA1) essentially at the st. oriens levels. CA1 responses elicited by stimulation of the contralateral CA1 in the st. oriens (commissural CA3 fibres) or in the st. radiatum (Schaffer's collaterals) are present at any age. For the regio inferior (CA3-CA4), the distribution of commissural fibres is more diffuse. Before 5--6 days, CA3-CA4 fields do not respond to a contralateral stimulation and do not give contralateral responses, showing that fibres and cells are not yet organized.


What can long-lived mutants tell us about mechanisms causing aging and lifespan variation in natural environments?
Long-lived mutants of model organisms have brought remarkable progress in our understanding of aging mechanisms. However, long-lived mutants are usually maintained in optimal standardized laboratory environments (SLEs), and it is not obvious to what extent insights from long-lived mutants in SLEs can be generalized to more natural environments. To address this question, we reviewed experiments that compared the fitness and lifespan advantage of long-lived mutants relative to wild type controls in SLEs and more challenging environments in various model organisms such as yeast Saccharomyces cerevisiae, the nematode worm Caenorhabditis elegans, the fruitfly Drosophila melanogaster and the mouse Mus musculus. In competition experiments over multiple generations, the long-lived mutants had a lower fitness relative to wild type controls, and this disadvantage was the clearest when the environment included natural challenges such as limited food (N=6 studies). It is well known that most long-lived mutants have impaired reproduction, which provides one reason for the fitness disadvantage. However, based on 12 experiments, we found that the lifespan advantage of long-lived mutants is diminished in more challenging environments, often to the extent that the wild type controls outlive the long-lived mutants. Thus, it appears that information on aging mechanisms obtained from long-lived mutants in SLEs may be specific to such environments, because those same mechanisms do not extend lifespan in more natural environments. This suggests that different mechanisms cause variation in aging and lifespan in SLEs compared to natural populations.


Temporomandibular joint disorder determined by Fonseca anamnestic index and associated factors in 18- to 27-year-old university students.
The aim of this study was to investigate temporomandibular disorder (TMD) and associated risk factors. This study was conducted using 212 university students. Based on the Fonseca anamnestic index, the population was divided into two groups: those with TMD and those without TMD. The two groups were compared in terms of global body posture, craniohorizontal and craniovertebral angles, neck and temporomandibular joint range of motion, stress level, and sleep quality. Stress level, sleep quality, and left cervical rotation were found to have statistical differences between the groups (p = 0.00, 0.00, and 0.046, respectively). Sleep quality and stress level were found to be important risk factors for the presence of TMD (p = 0.017 and 0.00, respectively). In the prevention and treatment of TMD, a holistic approach that evaluates mechanical factors and psychosocial factors should be adopted.


Effects of lower alcohols on nanocomposite particles for inhalation prepared using O/W emulsion.
Inhalable nanocomposite particles using O/W emulsions were studied. The effect of the composition of the dispersed phase on the nanoparticles in the nanocomposite particles was reported, however, the effect on the inhalation characteristics of nanocomposite particles has not been investigated. The aim of this study was to study the effects of lower alcohols in the dispersed phase of O/W emulsions on inhalable nanocomposite particles. Nanocomposite particles were prepared using a spray dryer from O/W emulsion. A mixed solution of dichloromethane and lower alcohols in which rifampicin (RFP) and poly(L-lactide-co-glycolide) were dissolved was used as a dispersed phase, and an aqueous solution in which arginine and leucine were dissolved was used as a continuous phase. We succeeded in preparing non-spherical nanocomposite particles with an average diameter of 9.01-10.91 μm. The results of the fine particle fraction (FPF) measurement showed that the higher the hydrophobicity of the lower alcohol mixed in the dispersed phase, the higher the FPF value. The FPF value of the nanocomposite particles was significantly increased by using ethanol and 1-propanol. The results were revealed that mixing 1-propanol with the dispersed phase increased the amount of RFP delivered to the lungs.