Deep learning algorithms for automated detection of Crohn's disease ulcers by video capsule endoscopy.
The aim of our study was to develop and evaluate a deep learning algorithm for the automated detection of small-bowel ulcers in Crohn's disease (CD) on capsule endoscopy (CE) images of individual patients. We retrospectively collected CE images of known CD patients and control subjects. Each image was labeled by an expert gastroenterologist as either normal mucosa or containing mucosal ulcers. A convolutional neural network was trained to classify images into either normal mucosa or mucosal ulcers. First, we trained the network on 5-fold randomly split images (each fold with 80% training images and 20% images testing). We then conducted 10 experiments in which images from n - 1 patients were used to train a network and images from a different individual patient were used to test the network. Results of the networks were compared for randomly split images and for individual patients. Area under the curves (AUCs) and accuracies were computed for each individual network. Overall, our dataset included 17,640 CE images from 49 patients: 7391 images with mucosal ulcers and 10,249 images of normal mucosa. For randomly split images results were excellent, with AUCs of .99 and accuracies ranging from 95.4% to 96.7%. For individual patient-level experiments, the AUCs were also excellent (.94-.99). Deep learning technology provides accurate and fast automated detection of mucosal ulcers on CE images. Individual patient-level analysis provided high and consistent diagnostic accuracy with shortened reading time; in the future, deep learning algorithms may augment and facilitate CE reading.


Aetiological factors in the genesis of pregnancy hydronephrosis.
In order to identify possible aetiological factors in the genesis of physiological hydronephrosis in pregnancy, the degree of pelvic-calyceal dilatation in 90 asymptomatic pregnant women was correlated with levels of plasma oestradiol, progesterone, 24-hour urinary oestriol, the site of the placenta, birthweight of the fetus, and pelvic inlet measurements. A grading system based on maximum calyceal diameter was used; 90% of the patients were found to have at least mild dilatation on the right side. No correlation was demonstrated between the degree of hydronephrosis and the levels of oestradiol, progesterone and 24-hour urinary oestriol excretion. The birth-weight of the fetus and its relationship with the pelvic inlet measurements also did not correlate with the occurrence of hydronephrotic changes in the kidneys. The only significant positive finding was a higher incidence of moderate and severe hydronephrosis occurring in patients with a right-sided placenta than compared with the left (x2 = 4.77; p less than 0.05), although the sensitivity and specificity in predicting hydronephrosis from a right-sided placenta is low (53% and 66% respectively). Our results support the hypothesis of a mechanical aetiology in the genesis of pregnancy hydronephrosis, where vascular compression on the ureters may be an important contributory factor. Our study has also shown that urinary tract infection and reduction of creatinine clearance were not more common in patients with moderate or severe pelvic-calyceal dilatation.


Increased processing of APLP2 and APP with concomitant formation of APP intracellular domains in BDNF and retinoic acid-differentiated human neuroblastoma cells.
The amyloid precursor protein (APP) belongs to a conserved gene family, also including the amyloid precursor-like proteins, APLP1 and APLP2. We have previously shown that all members of the APP protein family are up-regulated upon retinoic acid (RA)-induced neuronal differentiation of SH-SY5Y neuroblastoma cells. Here, we demonstrate that RA also affects the processing of APLP2 and APP, as shown by increased shedding of both sAPLP2 and sAPPalpha, as well as elevated levels of the APP intracellular domains (AICDs). Brain-derived neurotrophic factor (BDNF) has been reported to induce APP promoter activity and RA induces expression of the tyrosine kinase receptor B (TrkB) in neuroblastoma cells. We show that the increase in shedding of both APLP2 and APP in response to RA is not mediated through the TrkB receptor. However, BDNF concomitant with RA increased the expression of APP even further. In addition, the secretion of sAPLP2 and sAPPalpha as well as the levels of AICDs were increased in response to BDNF. In contrast, the levels of membrane-bound APP C-terminal fragment C99 significantly decreased. Our results suggest that RA and BDNF shifts APP processing towards the alpha-secretase pathway. In addition, we show that RA and BDNF regulate N-linked glycosylation of APLP1.


Impulse Noise Removal from Medical Images by Two Stage Quaternion Vector Median Filter.
This paper presents a two-stage impulse noise removal filter from medical images. Quaternion is used to represent differences of two pixels. The pixels are sorted and assigned a rank based on the aggregated sum of pixel differences with other pixels inside the filtering window. The central pixel is considered as corrupted by an impulse if its rank is bigger than a predefined rank and the minimum difference between it and other pixels in the four edge direction inside the window is larger than a predefined threshold. The noisy pixel is replaced by output of vector median filter implemented using quaternion. For color images, both intensity and chromaticity components are used. Quaternion processes color images as single unit rather than as separated color channels. This preserves the correlation and three dimensional vector natures of the color channels. For grayscale medical images, the same algorithm is implemented by using the intensity difference between two pixels. Experimental results show improved performance of the proposed filter in suppressing the impulse noise while retaining the original image details comparing against other well-known filters.


Single dual-trained surgeon for breast care leads to higher reconstruction rates after mastectomy.
Breast reconstruction improves the quality of life for mastectomy patients but is underutilized in the United States. This study investigated reconstruction rates for a dual-trained oncologic plastic surgeon to explore how provider-based factors influence reconstruction. We evaluated consecutive mastectomy patients treated at the University of California, San Diego Medical Center between 2009 and 2012. We identified mastectomy patients based on Current Procedural Terminology codes and evaluated them for patient- and disease-specific variables. We evaluated reconstruction rates for the traditional team model of collaborating plastic and oncologic surgeons versus a single surgeon, dual trained in surgical breast oncology and plastic surgery. A multivariate regression analysis was then used to identify the significant predictors of reconstruction. Mastectomy was performed in 344 patients. The surgeon group was a significant predictor of postmastectomy reconstruction (p < 0.05). The traditional team of oncologic and plastic surgeons reconstructed 93 (63.3 %) of 147 mastectomy patients, whereas the single dual-trained surgeon reconstructed 140 (71.1 %) of 197 mastectomy patients. Race and insurance status did not influence the receipt of reconstruction in our single-surgeon model, however, patients of older age [odds ratio (OR) 0.93, confidence interval (CI) 0.89-0.98, p < 0.01], higher body mass index (OR 0.89, CI 0.82-0.97, p < 0.01), or more advanced disease (p < 0.01) were less likely to undergo reconstruction. A single dual-trained surgeon for breast care influences reconstruction rates. A dual-trained surgeon increases the likelihood of reconstruction and obtains rates higher than previously reported. This may reflect the comprehensive care provided by a multidisciplinary-trained professional. A single surgeon providing care in oncology and reconstruction represents a comprehensive approach to breast care and demonstrates a relationship between provider practice and breast reconstruction.


Sensing cellular biochemistry with fluorescent chemical-genetic hybrids.
Fluorescent biosensors are powerful tools for the detection of biochemical events inside cells with high spatiotemporal resolution. Biosensors based on fluorescent proteins often suffer from issues with photostability and brightness. On the other hand, hybrid, chemical-genetic systems present unique opportunities to combine the strengths of synthetic, organic chemistry with biological macromolecules to generate exquisitely tailored semisynthetic sensors.


Drug Repurposing: Escitalopram attenuates acute lung injury by inhibiting the SIK2/ HDAC4/ NF-κB signaling cascade.
Acute lung injury (ALI) is a significant cause of morbidity and mortality worldwide. To search for a new treatment for acute lung injury, we investigated the effect of escitalopram on lipopolysaccharide (LPS)-induced ALI. Our results showed that escitalopram inhibited salt-inducible kinase 2 (SIK2) activity (IC50 = 6.36 ± 0.93 μM) and triggered histone deacetylase 4 (HDAC4) dephosphorylation. Following its dephosphorylation, HDAC4 translocated into the nucleus, promoted deacetylation and cytoplasmic shuttling of p65, thus inhibited LPS-induced pro-inflammatory cytokine production. Moreover, escitalopram markedly ameliorated the inflammatory responses, reduced neutrophils infiltration and attenuated LPS-induced pulmonary injury in mice. Taken together, we identified a previously unexplored role for escitalopram in SIK2/HDAC4/NF-κB pathway, therefore escitalopram may be considered as a new treatment for ALI.


Factors determining the optimal body site and method for obtaining punch biopsies of human skin as a tissue in which to assess pharmacodynamic and pharmacokinetic endpoints in drug development studies.
There are potential advantages to detecting pharmacodynamic (PD) and pharmacokinetic (PK) endpoints in a tissue-based compartment such as the skin during the development of molecularly targeted drugs. We explored regional differences between inner arm, inner thigh, lower back and buttocks in 12 healthy male Caucasian volunteers in the tolerability of skin biopsy procedures; the Ki67 proliferation index; the frequency of detecting hair follicles and sweat glands; and the percentage of melanocytes. We also explored the amounts of tissue and protein obtained, and two separate methods of splitting biopsies for processing in mutually exclusive media. Biopsies from all body sites were well tolerated. The subjective ranking order was inner arm > buttocks = back > thigh. There were no statistically significant differences in the Ki67 labelling index (P > 0.05). The frequency of detecting sweat glands was the same in all body sites, but the frequency of detecting hair follicles was higher in back and buttock, compared to arm and thigh. The percentage of melanocytes was significantly lower in the buttocks compared to the back and thigh (P < 0.05), but not compared to the arm (P = 0.07). A 4-mm punch biopsy yielded a mean of 16.8 mg of tissue (range: 9-28 mg) and 160 microg of protein (range: 80-270 microg). In vivo sample splitting, by following a 2-mm punch with a 4-mm overpunch, had a shorter time from devascularisation to immersion into processing medium than ex vivo dissection of a 4-mm sample, which may be of importance to the assessment of labile endpoints. We conclude that multiple punch biopsies of the skin are feasible, with the buttocks representing the studied body site with the optimal balance between tolerability, hair follicle density and melanocyte density for obtaining tissue in which to assess PD and PK endpoints during drug development studies.


Impact of variation in reagent combinations for one-stage clotting assay on assay discrepancy in nonsevere haemophilia A.
Factor VIII activity (FVIII:C) is measured by one-stage clotting assay (OSA) or chromogenic substrate assay (CSA). Significant differences in FVIII:C between OSA (FVIII:C1st ) and CSA (FVIII:CChr ) are described as assay discrepancy in nonsevere haemophilia A (HA). A large number of reagent combinations (APTT reagent and FVIII-deficient plasma) are used for OSA, but the impact of variations in reagent combinations on assay discrepancy has not been fully characterized. To clarify the variations in FVIII:C1st /FVIII:CChr ratios according to OSA reagent combination in HA subjects with/without assay discrepancy. Thirty-nine patients previously diagnosed with nonsevere HA were enrolled, and their FVIII genes were investigated and FVIII:C levels were assessed by a single CSA reagent and 11 OSA reagent combinations. Receiver operating characteristic (ROC) curve analysis was used to predict possible cut-off values of the FVIII:C1st /FVIII:CChr ratio to define FVIII assay discrepancy for each reagent combination. Patients were categorized into nondiscrepant (n = 25), discrepant (n = 5) and unclassified (n = 9) groups according to their genotypes and information in the database. The FVIII:C1st /FVIII:CChr ratio in nondiscrepant HA varied widely, depending on the APTT reagents and FVIII-deficient plasma used. The ratio in discrepant HA patients differed with respect to their genotype and the reagent combination used. ROC curve analyses revealed that cut-off values to distinguish the assay discrepancy differed depending on the reagents used, but revealed two novel genotype variants, p.Cys573Gly and p.Gly582Arg, associated with FVIII assay discrepancy. Our findings showed that the FVIII:C1st /FVIII:CChr ratio is dependent on the reagent combination used for OSA.


Difference in kinetics between the distal and proximal parts of the canine parietal cell mass in response to histamine.
Dogs provided with one denervated gastric pouch in the distal part of the corpus fundus and another of equal size in the proximal part, were studied during histamine stimulation. Dose-response curves were determined for acid output and mucosal blood flow, which was measured with the Neutral Red technique. Maximum acid output was significantly higher for the distal (mean 234.0 mumol min-1) than for the proximal pouch (120.0 mumol min-1). ED50 for acid output was significantly higher for the distal (105.0 micrograms kg-1 h-1 of histamine) than for the proximal pouch (57.0 micrograms kg-1 h-1). ED50 for blood flow did not differ significantly between the distal (40.5 micrograms kg-1 h-1) and the proximal pouch (29.0 micrograms kg-1 h-1). For both pouches ED50 for blood flow was significantly lower than that for simultaneous acid output. This indicated that the rise in blood flow precedes that in acid output. Regression analysis showed a significantly higher ratio between maximum mucosal blood flow and maximum acid output for the distal (0.30 ml mumol-1) than for the proximal pouch (0.15 ml mumol-1). The finding that ED50 for acid output in response to histamine was lower for the proximal pouch is contrary to earlier results obtained with pentagastrin, which showed that ED50 was lower for the distal pouch. There is no valid explanation for these differences in ED50 between the pouches, but a difference at receptor level could be hypothesized. The difference in maximum acid output between the two pouches is explained by the known difference between distal and proximal parts in volume fraction of the parietal cells. The possibility that these differences in acid production depend on dissimilarities in mucosal blood flow can be excluded.


Surgery of the dilated aortic root and ascending aorta in pediatric patients: techniques and results.
Dilatation of the aortic root is a well-known cardiovascular manifestation in children and adult patients with connective tissue disease (e.g. Marfan syndrome). Dilatation of the ascending aorta is extremely rare and may be associated with bicuspid aortic valve. This report evaluates the incidence of dilatative aortic root and ascending aortic pathology in patients younger than 18 years and analyzes the results obtained after repair and replacement strategies. Between 1/1995 and 12/2002, a total of 752 operations on the thoracic aorta were performed in adult and pediatric patients. We present our experience with a group of 26 patients <18 years of age, who required isolated surgery of the aortic root and/or ascending aorta because of a dilatative lesion. Fifteen patients had isolated aortic root dilatation (13 of them suffered from Marfan syndrome), eight patients presented with an idiopathic dilatation of the ascending aorta and three patients had dilatation in association with a bicuspid aortic valve. Mean age was 10 +/- 4.8 years (4-18 years). Repair of the aortic root with preservation of the aortic valve (Yacoub, David or selective sinus repair) was performed in nine patients, replacement using a homograft was performed in five patients, composite graft with mechanical prosthesis in two patients, with biological prosthesis in one patient and Ross operation was performed in one case. Isolated supracoronary graft replacement was performed in eight patients. Two patients died during hospitalization: a 10-year old girl developed respiratory failure on the 2nd postoperative day and autopsy revealed Ehlers-Danlos syndrome with a massive intrapulmonary emphysema. A 14-year-old Marfan patient with severely depressed preoperative LV function died from low cardiac output following composite-graft, mitral and tricuspid valve repair. One patient required aortic valve replacement 7 days after an aortic valve sparing root repair. There was no additional perioperative morbidity. In the long-term, two patients died from rupture of the thoracic aorta, both following minor non-cardiovascular surgical procedures. Both had normal sized descending and abdominal aorta. Repair of the aortic root and/or ascending aorta in children and adolescent patients can be performed with acceptable early and late results. While the presence of severe comorbidity may adversely affect early outcome, long-term survival was mainly determined by rupture of the descending aorta.


An Ethenoadenine FAD Analog Accelerates UV Dimer Repair by DNA Photolyase.
Reduced anionic flavin adenine dinucleotide (FADH- ) is the critical cofactor in DNA photolyase (PL) for the repair of cyclobutane pyrimidine dimers (CPD) in UV-damaged DNA. The initial step involves photoinduced electron transfer from *FADH- to the CPD. The adenine (Ade) moiety is nearly stacked with the flavin ring, an unusual conformation compared to other FAD-dependent proteins. The role of this proximity has not been unequivocally elucidated. Some studies suggest that Ade is a radical intermediate, but others conclude that Ade modulates the electron transfer rate constant (kET ) through superexchange. No study has succeeded in removing or modifying this Ade to test these hypotheses. Here, FAD analogs containing either an ethano- or etheno-bridged Ade between the AN1 and AN6 atoms (e-FAD and ε-FAD, respectively) were used to reconstitute apo-PL, giving e-PL and ε-PL respectively. The reconstitution yield of e-PL was very poor, suggesting that the hydrophobicity of the ethano group prevented its uptake, while ε-PL showed 50% reconstitution yield. The substrate binding constants for ε-PL and rPL were identical. ε-PL showed a 15% higher steady-state repair yield compared to FAD-reconstituted photolyase (rPL). The acceleration of repair in ε-PL is discussed in terms of an ε-Ade radical intermediate vs superexchange mechanism.


The epidemiology of postnatal depression in Ethiopia: a systematic review and meta-analysis.
Postnatal depression is among the common mental health problems that occur during the postnatal period. However, it is left undiagnosed in low- and middle-income countries including Ethiopia. Therefore, this systematic review and meta-analysis aimed to systematically summarize the available evidence on the epidemiology of postnatal depression in Ethiopia and suggest recommendations for future clinical practice. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed to conduct this systematic review and meta-analysis. We searched PubMed, SCOPUS, EMBASE and Google Scholar databases for the relevant articles that assessed the prevalence of postnatal depression in Ethiopia. We used a random-effect model to conduct a meta-analysis. We conducted a subgroup and sensitivity analysis to explore the source of heterogeneity. Cochrane Q- and the I2-test were used to check the heterogeneity of the included studies. The presence of publication bias was also checked by visual inspection of symmetry and Egger's test. The pooled estimated prevalence of postnatal depression in Ethiopia was 20.1% (95% CI 12.7-30.2). The pooled prevalence of postnatal depression in the studies that were conducted in community settings and used the Patient Health Questionnaire to assess postnatal depression [16.6% (95% CI 8.90-28.99)] was lower than the prevalence in studies based in institutions and that used the Edinburgh Postnatal Depression Scale [23.2% (95% CI 14.50-28.5)]. Further, in a leave-one-out sensitivity analysis the prevalence of postnatal depression ranges between 15.4% and 25.4%. Unplanned pregnancy [AOR = 3.46, 95% CI (2.37-5.04)], age between 15-24 years [AOR = 1.72, 95% CI (1.11-2.68)], marital problems [AOR = 3.07, 95% CI (2.36-3.99)], experiencing the death of infant [AOR = 3.41, 95% CI (1.91-6.09)] and history of substance use [AOR = 3.47, 95% CI (2.17-5.56)] were associated with the increased odds of postnatal depression in Ethiopia. The prevalence of postnatal depression in Ethiopia was high. Therefore, the concerned body should give due attention to improve reproductive health services through early detection of risk factors of postnatal depression.


Calcitonin gene-related peptide immunoreactive sensory DRG neurons innervating the cervical facet joints in rats.
The rat C5/6 facet joint is innervated multisegmentally from the C3 to the T3 dorsal root ganglia. Sensory fibers from the C3, C4, and C7-T3 dorsal root ganglia were reported to be innervated nonsegmentally through the paravertebral sympathetic trunks, while those from the C5 and C6 dorsal root ganglia were reported to segmentally innervate the C5/6 facet joint. The presence of calcitonin gene-related peptide-immunoreactive nerve fibers has been proved in the facet joints, but their ratios have not been studied. Fluoro-gold-labeled neurons innervating the C5/6 facet joint were distributed throughout the dorsal root ganglia from the C3 to T3 levels. Of the fluoro-gold-labeled neurons, the ratios of calcitonin gene-related peptide-immunoreactive C3, C4, C45 C6, C7, C8, T1, T2, and T3 dorsal root ganglion neurons were 30%, 22%, 43%, 47%, 21%, 19%, 25%, 36%, and 40%, respectively. The ratios of calcitonin gene-related peptide-immunoreactive neurons in the C5 and C6 dorsal root ganglia were significantly higher than those in the C3, C4, C7, and C8 dorsal root ganglia. In the physiological condition in rats, the neurons of the C5 and C6 dorsal root ganglia may have a more significant role in pain sensation of the facets than other dorsal root ganglion neurons.


Endoscopic transumbilical subglandular augmentation mammaplasty.
This technique has provoked many controversial comments. With modification and adequate clinician training and experience, however, the results can improve, and complications can be minimized. The author's complications occurred in the early stages of the use of this method; as experience was gained, they decreased. Furthermore, fewer and less severe complications occurred when the techniques were modified, including using instrument dissection before tissue expansion, better patient selection, early massage, and more frequent postoperative follow-up visits. In addition, this method leaves no scar at the breast and allows a quicker recovery. Most patients who underwent this procedure have been pleased with their results. Transumbilical endoscopic bilateral augmentation mammaplasty is an attractive alternative technique, and with careful patient selection, operative modification, and technical expertise, results can be achieved comparable with an open subglandular augmentation.


Predictors of operative difficulty in robotic low anterior resection for rectal cancer.
This study evaluates the relationship of tumour and anatomical features with operative difficulty in robotic low anterior resection performed by four experienced surgeons in a high-volume colorectal cancer practice. Data from 382 patients who underwent robotic low anterior resection by four expert surgeons between January 2016 and June 2019 were included in the analysis. Operating time was used as a measure of operative difficulty. Univariate and multivariate mixed models were used to identify associations between baseline characteristics and operating time, with surgeon as a random effect, thereby controlling for variability in surgeon speed and proficiency. In an exploratory analysis, operative difficulty was defined as conversion to laparotomy, a positive margin or an incomplete mesorectum. Median operating time was 4.28 h (range 1.95-11.33 h) but varied by surgeon from 3.45 h (1.95-6.10 h) to 5.93 h (3.33-11.33 h) (P < 0.001). Predictors of longer operating time in multivariate analysis were male sex, higher body mass index, neoadjuvant radiotherapy, low tumour height, greater sacral height and larger mesorectal area at the S5 vertebral level. Conversion occurred in two cases (0.5%), and incomplete mesorectum and positive margins were found in nine (2.4%) and 19 (5.0%) patients, respectively. Neoadjuvant radiotherapy and larger pelvic outlet were the only characteristics associated with the exploratory measure of difficulty. Predicting operative difficulty based on easy to identify, preoperative radiological and clinical variables is feasible in robotic anterior resection.


Molecular characterization, by digital PCR analysis of four HMBS gene mutations affecting the ubiquitous isoform of Porphobilinogen Deaminase (PBGD) in patients with Acute Intermittent Porphyria (AIP).
Genetic variants in promoters and alternative-splicing lesions require to be experimentally tested in order to validate them as causatives of a disease. The digital PCR (dPCR) approach, which is an alternative to the classical qPCR, is an innovative and a more sensitive method for the detection and quantification of nucleic acids. In the present study, we identified four HMBS gene mutations affecting the ubiquitous isoform of porphobilinogen deaminase (PBGD) and established a dPCR protocol which would be able to detect the different transcripts of this gene. With the application of this method, we were able to characterize the functional roles of these four genetic variants, demonstrating that all these mutations were causatives of the non-erythroid variant of the acute intermittent porphyria (AIP) disease.


Key components of an effective mentoring relationship: a qualitative study.
Despite the recognized importance of mentoring, little is known about specific mentoring behaviors that result in positive outcomes. To identify key components of an effective mentoring relationship identified by protégés-mentor dyads in an academic setting. In this qualitative study, purposive sampling resulted in geographic diversity and representation of a range of academic disciplines. Participants were from 12 universities in three regions of the U.S. (South, n=5; Northeast, n=4; Midwest, n=2) and Puerto Rico (n=1). Academic disciplines included natural sciences (51%), nursing/health sciences (31%), engineering (8%), and technology (1%). Twelve workshops using the Technology of Participation method were held with 117 mentor-protégé dyads. Consensus was reached regarding the key components of an effective mentoring relationship. Conventional content analysis, in which coding categories were informed by the literature and derived directly from the data, was employed. Eight themes described key components of an effective mentoring relationship: (1) open communication and accessibility; (2) goals and challenges; (3) passion and inspiration; (4) caring personal relationship; (5) mutual respect and trust; (6) exchange of knowledge; (7) independence and collaboration; and (8) role modeling. Described within each theme are specific mentor-protégé behaviors and interactions, identified needs of both protégé and mentor in the relationship, and desirable personal qualities of mentor and protégé. Findings can inform a dialog between existing nurse mentor-protégé dyads as well as student nurses and faculty members considering a mentoring relationship. Nurse educators can evaluate and modify their mentoring behaviors as needed, thereby strengthening the mentor-protégé relationship to ensure positive outcomes of the learning process.


Penetrating multichannel stimulation and recording electrodes in auditory prosthesis research.
Microelectrode arrays offer the auditory systems physiologists many opportunities through a number of electrode technologies. In particular, silicon substrate electrode arrays offer a large design space including choice of layout plan, range of surface areas for active sites, a choice of site materials and high spatial resolution. Further, most designs can double as recording and stimulation electrodes in the same preparation. Scala tympani auditory prosthesis research has been aided by mapping electrodes in the cortex and the inferior colliculus to assess the CNS responses to peripheral stimulation. More recently silicon stimulation electrodes placed in the auditory nerve, cochlear nucleus and the inferior colliculus have advanced the exploration of alternative stimulation sites for auditory prostheses. Multiplication of results from experimental effort by simultaneously stimulating several locations, or by acquiring several streams of data synchronized to the same stimulation event, is a commonly sought after advantage. Examples of inherently multichannel functions which are not possible with single electrode sites include (1) current steering resulting in more focused stimulation, (2) improved signal-to-noise ratio (SNR) for recording when noise and/or neural signals appear on more than one site and (3) current source density (CSD) measurements. Still more powerful are methods that exploit closely-spaced recording and stimulation sites to improve detailed interrogation of the surrounding neural domain. Here, we discuss thin-film recording/stimulation arrays on silicon substrates. These electrode arrays have been shown to be valuable because of their precision coupled with reproducibility in an ever expanding design space. The shape of the electrode substrate can be customized to accommodate use in cortical, deep and peripheral neural structures while flexible cables, fluid delivery and novel coatings have been added to broaden their application. The use of iridium oxide as the neural interface site material has increased the efficiency of charge transfer for stimulation and lowered impedance for recording electrodes.


A Detailed Analysis of Mandibular Angle Fractures: Epidemiology, Patterns, Treatments, and Outcomes.
The purpose was to analyze mandibular angle fractures by examining epidemiologic trends and mechanisms of injury and to determine whether a statistically meaningful relation existed between certain treatment modalities and patient outcomes. A retrospective chart analysis was performed, and data were limited to 1 operator. Treatment variables were methods of fixation, postoperative intermaxillary fixation (IMF), and retention versus extraction of teeth in the line of fracture. Outcomes were rates of postoperative infection, fracture healing, and overall patient comfort. Analysis was performed using the Fisher exact test, Wald test, and χ(2) test, with a P value less than .05 considered significant. One hundred three patients were included in this study. The mean age was 30.4 years, most patients were men, and most injuries occurred during physical altercations and on the left side of the face. The most common concomitant fracture was of the contralateral parasymphysis. A statistically meaningful relation was noted between methods of fixation and healing and overall patient comfort, with the Champy technique and reconstruction plate being associated with the highest rates of bony union and patient comfort. No statistically relevant correlation was found between methods of fixation and rates of infection. There was no statistically relevant link for extraction versus retention of healthy teeth in the line of fracture or use of IMF with patient comfort, postoperative infection, or fracture healing. Although the Champy technique and reconstruction plates were associated with better postoperative outcomes, such as patient comfort and fracture healing, these should not be used interchangeably. IMF and extraction versus retention of teeth in the line of fracture did not influence any of the outcomes.


[Changes in ultrastructure and bone morphogenetic protein expression in reconstructed mandibular condylar cartilage under continuous mandibular advancement in adult rats].
This study investigated the reconstructed mandibular condylar cartilage and the ultrastructural variations in mandibular condylar cartilage in adult rats as a result of mandibular advancement. Thirty 9-week-old male Sprague-Dawley rats were randomly divided into experimental and control groups. Rats in the experimental group were subjected to mandibular advancement. Rats were sacrificed on days 3, 7, 14, 21, 30. Sections were cut from condyles, and bone morphogenetic protein-2 (BMP-2) expression in condylar cartilage was examined through immunohistochemical analysis. Condylar cartilage samples were harvested, and ultrastructural changes in these samples were observed under Micro-CT and transmission electron microscope. Compared with the control group, the experimental group obviously displayed cartilage hyperplasia in the middle and rear of the condyle. Moreover, the number of BMP-2-positive cells in condylar cartilage and the gray value gradually increased in the experimental group on day 7 of the intervention. Ultrastructural changes, such as karyopyknosis, reduced microfilaments around the nucleus, reduction in size or even disappearance of lipid droplets, swelling of endoplasmic reticulum compartments, broadened and increased extracellular matrix, were observed in the condylar hypertrophic chondrocytes. Micro-CT revealed that the trabecula and the newly formed bone gradually thickened. Hypertrophic remodeling of the condylar cartilage and high BMP-2 expression are observed in adult rats as a result of continuous mandibular advancement.


Canonical Wnt pathway signaling suppresses VCAM-1 expression by marrow stromal and hematopoietic cells.
The Wnt family may contribute to hematopoietic stem cell (HSC) maintenance in bone marrow, but many questions remain concerning mechanisms. Vascular cell adhesion molecule-1 (VCAM-1) is expressed in cellular compartments of the bone marrow and might contribute to the HSC niche, but mechanisms concerning its constitutive expression are largely unknown. We now explore the influence of Wnt signaling on cellular adhesion molecule expression by bone marrow stromal and hematopoietic cells. Recombinant Wnt ligands, retroviral Wnt transductions and cocultures with Wnt-secreting cells were used to analyze the effect of Wnt on adhesion molecule expression by stromal and hematopoietic cells. In vivo experiments were also done to assess the ability of Wnt3a-induced, VCAM-1 deficient hematopoietic cells to engraft bone marrow. We now report that the beta-catenin-dependent canonical Wnt signaling pathway negatively regulates VCAM-1 expression on two types of bone marrow cells. Wnt pathway inhibitors, Axin (intracellular) or Dickkopf-1 (extracellular) blocked the regulation of VCAM-1 by diffusible Wnt3a. Interestingly, lipopolysaccharide restored a substantial degree of VCAM-1 expression, suggesting functional cross-talk between Wnt and TLR4 signaling pathways. Decreasing VCAM-1 on HSC-enriched Lin(-) Sca-1(+) c-Kit(Hi) Thy1.1(Lo) cells by exposure to Wnt3a did not prevent their successful transplantation. Our results suggest that cells comprising and residing in the HSC niche can respond to Wnt ligands and extinguish VCAM-1. This response may be important for export of hematopoietic cells. Given the known contribution of VCAM-1 to inflammation, this may represent a new avenue for therapeutic intervention.


Differentiation of muscle fiber types in the chicken hindlimb.
The differentiation of myotubes into fiber types was studied by examining the ATPase staining characteristics of chicken embryo thigh muscles. Two distinct fiber types, designated type IEMB and IIEMB, could be distinguished as early as stage 29. Paralysis of the embryo with d-tubocurarine prevented the differentiation of type IEMB but not type IIEMB characteristics. The two embryonic fiber types differed from each other, and mature type I and II fibers, in the acid and alkali labilities of their ATPases. Myotubes which were type IEMB at stage 29 matured into type I fibers, whereas those which were type IIEMB predominantly but not exclusively developed into type II fibers. The process of maturation involved sequential changes in the staining characteristics of the myotubes. Thus, the ultimate fiber type of a myotube can be detected long before it expresses its mature characteristics.


Infections in inflammatory bowel disease patients on immunomodulator and biologic therapy are not associated with high serum drug levels.
Inflammatory bowel disease (IBD) therapies now utilise higher doses of immunomodulatory and biologic therapies, predisposing patients to an increased risk of infections. We aimed to determine whether infections were associated with high anti-tumour necrosis factor (TNF) drug levels in IBD and to quantify the risk and consequences of infections. Two retrospective studies were performed, a descriptive cohort study and a matched case-control study. For the matched case-control study, cases of infection occurring on anti-TNF agents were matched in a 1:2 ratio to controls of anti-TNF treated patients without infections. In the descriptive study, 76 infections occurred in 60 patients, including 49 bacterial, 24 viral, four fungal and four parasitic. Of these, 61 (80.3%) were on biologics, 49 (64.5%) on immunomodulators and 11 (14.5%) on corticosteroids. Thirty-four (44.7%) were on combination therapy, 27 (35.5%) on biologic monotherapy and 15 (19.7%) on immunomodulator monotherapy. Median anti-TNF drug levels in infection cases were 3.9 μg/mL for infliximab and 6.0 μg/mL for adalimumab. In the case-control study, 32 cases of infection in 27 anti-TNF treated patients were matched with 64 anti-TNF treated controls without infections. Among infection cases, 59.5% were on combination therapy versus 40.6% on biologic monotherapy (P = 0.59). Median drug levels for cases and controls respectively were 3.9 μg/mL versus 5.5 μg/mL for infliximab (P = 0.72) and 6.0 μg/mL versus 9.9 μg/mL for adalimumab (P = 0.34). Infections in patients with IBD were common, and the risk was highest with combination therapy. Infections were not associated with high serum anti-TNF levels.


Medulla oblongata volume as a promising predictor of survival in amyotrophic lateral sclerosis.
Unconventional magnetic resonance imaging studies of the brainstem have recently acquired a growing interest in amyotrophic lateral sclerosis (ALS) pathology since they provide a unique opportunity to evaluate motor tract degeneration and bulbar lower motor neuron involvement. The aim of this study was to investigate the role of brainstem structures as accurate biomarkers of disease severity and predictors of survival. A total of 60 ALS patients and 30 healthy controls subjects (CS) were recruited in this study. Patients were divided in two subgroups according to the onset of the disease: 42 spinal (S-ALS) and 18 bulbar (B-ALS). All subjects underwent 3D-structural MRI. Brainstem volume both of the entire cohort of ALS patients and S-ALS and B-ALS onset were compared with those of CS. In addition the two ALS subgroups were tested for differences in brainstem volumes. Volumetric, vertex-wise, and voxel-based approaches were implemented to assess correlations between MR structural features and clinical characteristics expressed as ALSFRS-r and its bulbar (ALSFSR-r-B) and spinal subscores (ALSFSR-r-S). ROC curves were performed to test the accuracy of midbrain, pons, and medulla oblongata volumes able to discriminate patients dichotomized into long and short survivors by using Two-Steps cluster analysis. Univariate and multivariate survival analyses were carried out to test the prognostic role of brainstem structures' volume, trichotomized by applying a k-means clustering algorithm. Both the entire cohort of ALS patients and B-ALS and S-ALS showed significant lower volumes of both medulla oblongata and pons compared to CS. Furthermore, B-ALS showed a significant lower volume of medulla oblongata, compared to S-ALS. Lower score of ALSFRS-r correlated to atrophy in the anterior compartment of midbrain, pons, and medulla oblongata, as well as in the posterior portion of only this latter region. ALSFSR-r-S positively correlated with shape deformation and density reduction of the anterior portion of the entire brainstem, along the corticospinal tracts. ALSFSR-r-B instead showed a positive correlation with shape deformation of the floor of the fourth ventricle in the medulla oblongata and the crus cerebri in the midbrain. Only medulla oblongata volume demonstrated a significant accuracy to discriminate long and short survivors ALS patients (ROC AUC 0.76, p < 0.001). Univariate and multivariate analysis confirmed the survival predictive role of the medulla oblongata (log rank test p: 0.003). Our findings suggest that brainstem volume may reflect the impairment of corticospinal and corticobulbar tracts as well as lower bulbar motor neurons. Furthermore, medulla oblongata could be used as an early predictor of survival in ALS patients.


Assessment of eHealth literacy to reduce financial toxicity and improve shared decision-making in cancer patients: A cross-sectional study.
This study aimed to investigate the associations between eHealth literacy, preferences for financial decision-making, and financial toxicity (FT) in a sample of Chinese cancer patients. Eligible cancer patients were invited to participate in a cross-sectional survey from January to April 2021. Three measures (eHealth literacy scale, control preference scale, and COST) were used to analyze patients' eHealth literacy, decisional preferences, and FT, respectively. Wilcoxon signed-rank test and Kruskal-Wallis H test assessed the differences between population subgroups. Binary logistic and multivariate linear regression models were used to assess the relationships between eHealth literacy, decisional preferences, and FT. A total of 590 cancer patients completed the questionnaire. We found that high FT was associated with poor ECOG performance, severe cancer stage, and longer cancer duration. Patients who preferred to adopt collaborative attitude toward decision-making showed a significantly higher eHealth literacy. However, there was an inverse relationship between eHealth literacy and a patient-driven attitude toward decision-making in female cancer patients. Regression analysis indicated that patients who were highly educated and actively employed might report a higher eHealth literacy. A significant relationship was found between high eHealth literacy and low FT. However, this relationship became insignificant when the background characteristics of cancer patients were taken into account. A relationship between enhanced eHealth literacy, preference for collaborative decision-making, and low risk of FT is identified. Interventions to improve patients' ability to use quality and reliable web-based information on cancer care should be encouraged.


Evolution of human emotion: a view through fear.
Basic tendencies to detect and respond to significant events are present in the simplest single cell organisms and persist throughout all invertebrates and vertebrates. Within vertebrates, the overall brain plan is highly conserved, though differences in size and complexity also exist. The forebrain differs the most between mammals and other vertebrates. The classic notion that the evolution of mammals led to radical changes such that new forebrain structures (limbic system and neocortex) were added has not held up nor has the idea that so-called limbic areas are primarily involved in emotion. Modern efforts have focused on specific emotion systems, like the fear or defense system, rather than on the search for a general purpose emotion systems. Such studies have found that fear circuits are conserved in mammals, including humans. Animal work has been especially successful in determining how the brain detects and responds to danger. Caution should be exercised when attempting to discuss other aspects of emotion, namely subjective feelings, in animals since there are no scientific ways of verifying and measuring such states except in humans.


[Carcinoma of the nasopharynx in the young subjects. Clinical, pathological and ultrastructural study of 50 cases in Eastern Algeria (author's transl)].
Africa, and in particular North Africa, is a site of high prevalence of carcinoma of the nasopharynx in the young subject. There is a marked male predominance and a clear peak of incidence between 15 and 25 years. The presenting feature is usually rapidly growing cervical lymphadenopathy. The diagnosis is based upon histological examination of these nodes. It is a squamous carcinoma, usually highly undifferentiated and difficult to identify. However, for the experienced observer, the special appearance of tumour proliferation makes it possible to localise the primary tumour in the epi-pharyngeal region. Current work is aimed at research into a possible genetic predisposition and the relationship which the carcinoma may have with the Epstein-Barr virus.


Identification and characterization of a novel fibril forming peptide in fungal starch binding domain.
Scanty information is available regarding the chemical basis for structural alterations of the carbohydrate-binding modules (CBMs). The N-terminal starch binding domain (SBD) of Rhizopus oryzae glucoamylase (GA) forms fibrils under thermal stress, presenting an unusual conformational change from immunoglobulin-like to beta-sheet-rich structure. Site-directed mutagenesis revealed that the C-terminal Lys of SBD played a crucial role in the fibril formation. The synthetic peptide (DNNNSANYQVSTSK) representing the C-terminal 14 amino acid residues of SBD was further demonstrated to act as a fibril-forming segment, in which terminal charges and an internal NNNxxNYQ motif were key fibril-forming determinants. The formation of fibril structure in a fungal SBD, caused by its chemical and biophysical requirements, was demonstrated for the first time.


A novel NFIA gene nonsense mutation in a Chinese patient with macrocephaly, corpus callosum hypoplasia, developmental delay, and dysmorphic features.
NFIA gene (OMIM*600727) has been shown to be associated with a syndrome of central nervous system malformations (corpus callosum and ventriculomegaly) with or without urinary tract defects(BRMUTD) (OMIM#613735) with a low incidence. METHODS AND RESULTS: We presented the clinical data of a 3-month-old Chinese infant with clinical features such as thin corpus callosum, ventriculomegaly, development delay, and dysmorphic features (macrocephaly, hypertelorism, slightly pointed chin, broad forehead, and large ears). Genomic DNA was extracted for Trio Whole Exome Sequencing. Preliminary genetic tests revealed one de novo heterozygous nonsense mutation c.220 C>T (p.Arg74Ter) of the NFIA gene (NM_005595). Genetic DNA sequencing is a crucial method for diagnosing BRMUTD. This approach enriches the genotype and spectrum of BRMUTD syndrome and the outcome of the patient.


The lumi-aggregometer: a new instrument for simultaneous measurement of secretion and aggregation by platelets.
We have developed a new instrument that simultaneously monitors aggregation and secretion of ATP from the same sample of platelets. Aggregation is determined by the usual turbidimetric method; secretion of ATP is followed by measuring luminescence from the firefly luciferase system at right angles to the aggregometer light path. Data are recorded on a two-pen strip chart recorder and reveal the temporal relations between the two platelet responses.


HLA-DQ8 is a predisposing molecule for detergent enzyme subtilisin BPN'-induced hypersensitivity.
Several million individuals are exposed to agents in the workplace associated with atopy and asthma. Detergent enzymes have been implicated in occupationally induced hypersensitivity. However, the genetic susceptibility and T cell responses to detergent enzymes are undefined. We generated and used HLA-DQ6, -DQ8, -DR2, -DR3, and -DR4 transgenic mice to examine the immune and inflammatory components involved in the response to the detergent enzyme subtilisin BPN'. Based on in vitro and in vivo studies, for the first time, we present evidence that DQ8 is a strong susceptibility marker for BPN'-induced hypersensitivity. Only DQ8 mice showed consistent T cell responses to five immunodominant regions of BPN' comprising peptides #14 to 16, 36-37, 42-43, 62-63, and 80-81. The DQ8 mice also developed allergic eosinophilic inflammatory reactions in the airways following intranasal instillations of this enzyme. The DQ8 mice also responded to BPN' with a significant IgG1 and IgE production. We propose that the HLA Class II tg mice are useful for understanding allergenic responses to enzymes in humans, screening of allergenic and immunogenic properties of detergent enzymes, and for the development of modified enzymes to maintain efficient detergent qualities without allergic properties.


Exploring the learning curve for minimally invasive sutureless aortic valve replacement.
The study objective was to assess the learning process and quality of care of right minithoracotomy aortic valve replacement with a sutureless bioprosthesis at a single institution. We performed an analysis of the first 300 consecutive patients (aged 76 ± 6 years; logistic European System for Cardiac Operative Risk Evaluation 9 ± 6) who underwent sutureless valve implantation via a right minithoracotomy by 6 surgeons at the G. Pasquinucci Heart Hospital between 2011 and 2015. The learning curve was analyzed by dividing the study population into tertiles of 100 patients each. Departmental and individual learning curves were calculated using sequential probability cumulative sum failure analysis. Quality indicators were 2 composite end points reflecting the technical success and 30-day complications. The overall mortality was 0.7% (2 patients). No significant differences were noted in terms of mortality and complications between tertiles. The sutureless valve was implanted successfully in 99% of patients (298/300). Cumulative sum analysis failed to identify any significant learning effects for technical success. Nevertheless, surgeons A, B, and C had a small initial learning curve, and surgeons D, E, and F did not, reflecting a trend toward a positive effect of cumulative institutional experience on the individual learning curve. The 30-day complications analysis revealed a cluster of failures at the beginning of the experience. This cluster prompted an internal audit and modification of the patients' selection process. Consecutively, the procedure returned in control. Right minithoracotomy sutureless valve implantation can be performed safely without learning curve effects. Cumulative sum analysis is a valuable tool to describe and monitor the learning process. The analysis can identify periods of less than expected performance and alert the team to react.


The role of GABAA and GABAB receptors in presynaptic inhibition of Ia EPSPs in cat spinal motoneurones.
1. The role of GABAA and GABAB receptors in presynaptic inhibition was studied by examining the effect of local application of antagonists by ionophoresis during intracellular recording of presynaptic inhibition of compound and unitary group Ia afferent excitatory postsynaptic potentials (EPSPs) in gastrocnemius motoneurones. 2. Ionophoresis of the GABAA antagonist bicuculline methochloride (BMC) was found to block presynaptic inhibition of both compound and unitary EPSPs by up to 85%. BMC also substantially reduced, and occasionally abolished, the late part of the inhibitory postsynaptic potential (IPSP) evoked in motoneurones by the conditioning stimulation. The early part of this IPSP was found to be sensitive to ionophoresis of strychnine hydrochloride. 3. Ionophoresis of 2-OH-saclofen caused a reduction in presynaptic inhibition of compound EPSPs by 5-25% but had no effect on the IPSP evoked in motoneurones by the conditioning stimulation. 4. Ionophoresis of the GABAB antagonist (-)-baclofen reduced the amplitude of unconditioned EPSPs; however it had little effect on presynaptic inhibition. 5. It was concluded that at the Ia afferent-motoneurone synapse presynaptic inhibition is mediated primarily through the activation of GABAA receptors. The activation of GABAB receptors appears to play only a minor role in presynaptic inhibition at this synapse. This contrasts with the relative ease with which (-)-baclofen can reduce transmitter release from Ia afferent terminals and suggests that the receptors activated by (-)-baclofen are predominantly extrasynaptic.


Reduced pupillary light reflexes in diabetic autonomic neuropathy.
Infrared television pupillometry was performed in 71 healthy and 66 insulin-treated diabetic subjects. Resting pupil diameter and the amplitude of the reflex response to standard light flashes were measured in background darkness. In the healthy subjects with small pupils (less than 6 mm) the size of the light reflex was found to depend on the diameter of the pupil in darkness, the former decreasing by 0.55 mm/mm decrease in diameter. A positive correlation was also found in the diabetic subjects with small pupils but the reflexes were much smaller for a given resting diameter than in healthy subjects. The majority of the diabetic patients with small pupils had autonomic neuropathy. It is suggested that impaired pupillary dilatation in diabetic subjects is due to a sympathetic neuropathy and the small light reflex response in some patients is due to parasympathetic dysfunction in addition.


Influence of healing time on the outcomes of alveolar ridge preservation using a collagenated bovine bone xenograft: A randomized clinical trial.
To evaluate the healing outcomes in non-molar post-extraction sockets filled with deproteinized bovine bone mineral with collagen (DBBM-C) as a function of time. Patients in need of non-molar tooth extraction were randomly allocated into one of three groups according to the total healing time (A-3 months; B-6 months; C-9 months). The effect of alveolar ridge preservation (ARP) therapy via socket filling using DBBM-C and socket sealing with a porcine collagen matrix (CM) was assessed based on a panel of clinical, digital, histomorphometric, implant-related, and patient-reported outcomes. A total of 42 patients completed the study (n = 14 in each group). Histomorphometric analysis of bone core biopsies obtained at the time of implant placement showed a continuous increase in the proportion of mineralized tissue with respect to non-mineralized tissue, and a decrease in the proportion of remaining xenograft material over time. All volumetric bone and soft tissue contour assessments revealed a dimensional reduction of the alveolar ridge overtime affecting mainly the facial aspect. Linear regression analyses indicated that baseline buccal bone thickness is a strong predictor of bone and soft tissue modelling. Ancillary bone augmentation at the time of implant placement was needed in 16.7% of the sites (A:2; B:1; C:4). Patient-reported discomfort and wound healing index scores progressively decreased over time and was similar across groups. Healing time influences the proportion of tissue compartments in non-molar post-extraction sites filled with DBBM-C and sealed with a CM. A variable degree of alveolar ridge atrophy, affecting mainly the facial aspect, occurs even after performing ARP therapy. These changes are more pronounced in sites exhibiting thin facial bone (≤1 mm) at baseline (Clinicaltrials.gov NCT03659617).


Resisting temptation: effects of exposure to a forbidden food on eating behaviour.
The study tests existing evidence on the paradoxical effects of exposure to a forbidden snack. Sixty-eight females were assigned randomly to one of two conditions: a temptation group, who were given the instruction to abstain from a favourite snack for 24h while being exposed to it, or a control group, who were given no specific instructions. A further distinction was made between high-restraint/high-disinhibition (n=21), high-restraint/low-disinhibition (n=20) and low-restraint participants (n=27) based on DEBQ subscale scores. After exposure to the foods, all participants were given free access to the food. Participants ate more of the snack after abstinence with exposure. The high-restraint/high-disinhibition group in particular displayed a substantial disinhibition effect. Results indicate that prohibition with exposure may backfire and increase the risk of loss of control over eating behaviour, particularly in at-risk groups of disinhibited restrained eaters.


Upregulated vimentin suggests new areas of neurodegeneration in a model of an alcohol use disorder.
Excessive alcohol intake, characteristic of an alcohol use disorder (AUD), results in neurodegeneration as well as cognitive deficits that may recover in abstinence. Neurodegeneration in psychiatric disorders such as AUDs is due to various effects on tissue integrity. Several groups report that alcohol-induced neurodegeneration and recovery include a role for adult neurogenesis. Therefore, the initial purpose of this study was to investigate the effect of alcohol on the temporal profile of neural progenitor cells using the radial glia marker, vimentin, in a model of an AUD. However, striking vimentin expression throughout corticolimbic regions led, instead, to the discovery of a significant gliosis response in this model. Adult male rats were subjected to a 4-day binge model of an AUD and brains harvested for immunohistochemistry at 0, 2, 4, 7, 14, and 28 days following the last dose of ethanol. A prominent increase in vimentin immunoreactivity was apparent at 4 and 7 days post binge that returned to control levels by 14 days in the corticolimbic regions examined. Vimentin-positive cells co-labeled with glial fibrillary acidic protein (GFAP), which suggested that cells were reactive astrocytes. A second experiment supported that increased vimentin was not primarily due to alcohol withdrawal seizures and is more likely due to alcohol-induced cell death. As this gliosis was remarkably distinct in regions where cell death had not previously been reported in this model, adjacent tissue sections were processed for FluoroJade B staining for cell death. FluoroJade B-positive cells were evident immediately following the last ethanol dose as expected, but were significantly elevated in the hippocampal dentate gyrus and CA3 regions and corticolimbic regions from 2 to 7 days post binge. Intriguingly, vimentin labeling of astrogliosis is more widespread than FluoroJade B labeling of cell death, which suggests that 4-day binge ethanol consumption is more damaging than originally realized.


Receptor-mediated degradation and internalization of insulin in the adenocarcinoma cell line HT-29 from human colon.
In the adenocarcinoma cell line HT-29 receptor-bound insulin is substrate for a proteolytic process leading to the release of about half of the cell-associated [125I]monoiodoinsulin in the form of [125I]iodide and [125I]monoiodotyrosine. Classical lysosomal inhibitors (NH+4, methylamine, leupeptin) did not inhibit this proteolysis. Inhibitors of membrane traffic (chloroquine and monensin) and of metabolism (CN-) inhibited the fractional receptor-mediated degradation. The former led to an increased cell-associated 125I activity whereas the latter reduced the uptake. Sulphydryl reagents inhibited the receptor-mediated degradation. The data are not compatible with a quantitatively major role of lysosomes in the receptor-mediated insulin degradation. However, since the process requires energy it is suggested that the receptor-mediated degradation takes place in vesicles other than secondary lysosomes. The responsible enzyme(s) may belong to the thiol group of proteases. Both insulin and the insulin receptor are internalized as a consequence of incubation of HT-29 cells with insulin.


Brain glucocorticoid receptors and their role in behavioural teratogenicity of synthetic glucocorticoids.
The distribution of glucocorticoid receptors (GR) in rat brain during development (postnatal days 3-16) was investigated and the prevalence of GR number was found in the cerebellum, the fastest growing part of perinatal brain. Dexamethasone (D) administration (0.04-3 mg . kg-1 s.c.) in 7-day-old rats induced dose-dependent depletion of brain cytosol GR with a 70% depletion after the smallest dose. Long-term effects of this GR mediated insult (D 1.0 and 0.2 mg . kg-1 s.c.) manifested themselves in adult rats as structural and biochemical brain deviations (especially in the cerebellum and hippocampus), behavioural abnormalities and reproduction disturbances. These sequels were detectable after D doses equal to clinical dosage in obstetrics and neonatology (0.2-0.6 mg . kg-1).


Host-Guest Assembly of a Molecular Reporter with Chiral Cyanohydrins for Assignment of Absolute Stereochemistry.
The absolute stereochemistry of cyanohydrins, derived from ketones and aldehydes, is obtained routinely, in a microscale and derivatization-free manner, upon their complexation with Zn-MAPOL, a zincated porphyrin host with a binding pocket comprised of a biphenol core. The host-guest complex leads to observable exciton-coupled circular dichroism (ECCD), the sign of which is easily correlated to the absolute stereochemistry of the bound cyanohydrin. A working model, based on the ECCD signal of cyanohydrins with known configuration, is proposed.


Injection administration of mangosteen, Garcinia mangostana, husk extract enhances physiological and immune-neuroendocrinological regulation of Macrobrachiumrosenbergii.
The study aimed to investigate the effects of injecting mangosteen husk hot-water extracts (MHE) on immune and physiological factors in Macrobrachium rosenbergii. Different doses of MHE (10, 20, and 40 μg prawn-1) were injected into the prawns, and various immune and physiological parameters were evaluated. The results revealed that higher doses of MHE (20 and 40 μg prawn-1) led to significant increases in immune parameters, improved phagocytic activity, and clearance efficiency. However, certain parameters, such as phenoloxidase activity per granulocyte, plasma glucose, and lactate levels were decreased after injection. Moreover, prawns injected with MHE and subjected to hypothermal stress exhibited changes in haemolymph dopamine and norepinephrine. Prawns injected with MHE for 7 days showed increased survival rates when challenged with Lactococcus garvieae. The relative survival percentages were 11.8%, 46.6%, and 47.1% for MHE doses of 10, 20, and 40 μg prawn-1 injection, respectively, indicating enhanced resistance to the pathogen. In conclusion, injecting MHE can act as an immunostimulant and physiological and neuroendocrine regulator for prawns, enhancing their resistance to L. garvieae.


Filter columns for preparation of leukocyte-poor blood for transfusion.
Filter columns (Imugard filters) packed with cotton wool prepared from Gossypium barbadense cotton removed 95--100% of leukocytes from packed red cell suspensions. Recovery of red cells was about 95%. The efficacy was similar for ACD and heparinized blood. Blood was filtered below 10 degrees C within 30 min under pressures of less than 0.2 kg/cm2. The shape and functions of the red cells were not altered by filtration. No pyrogenic or toxic substances, and little particulate matter were eluted from the filters.


High yield and ultrafast sources of electrically triggered entangled-photon pairs based on strain-tunable quantum dots.
Triggered sources of entangled photon pairs are key components in most quantum communication protocols. For practical quantum applications, electrical triggering would allow the realization of compact and deterministic sources of entangled photons. Entangled-light-emitting-diodes based on semiconductor quantum dots are among the most promising sources that can potentially address this task. However, entangled-light-emitting-diodes are plagued by a source of randomness, which results in a very low probability of finding quantum dots with sufficiently small fine structure splitting for entangled-photon generation (∼10(-2)). Here we introduce strain-tunable entangled-light-emitting-diodes that exploit piezoelectric-induced strains to tune quantum dots for entangled-photon generation. We demonstrate that up to 30% of the quantum dots in strain-tunable entangled-light-emitting-diodes emit polarization-entangled photons. An entanglement fidelity as high as 0.83 is achieved with fast temporal post selection. Driven at high speed, that is 400 MHz, strain-tunable entangled-light-emitting-diodes emerge as promising devices for high data-rate quantum applications.


Sample extensiveness in qualitative nutrition education research.
Extensiveness represents the amount of information gathered in qualitative research. This study examined sample extensiveness in qualitative nutrition education research. Retrospective analysis was performed on articles published in the Journal of Nutrition Education (JNE) from 1969 to 1999 (Volumes 1 to 31). Content analysis was used to code articles and the studies they reported as units of analysis. Articles were coded to determine whether they included one or more studies using qualitative research and, if so, the types of qualitative studies performed, the sample extensiveness of each study, and mention of sample extensiveness limitations in the article. The statistics used were univariate (counts, percentages, means, medians, modes, ranges) and bivariate (chi-square, correlations). Of the published JNE articles, 71 (8%) used qualitative methods, and most (85%) qualitative articles were published in the 1990s. Some (19%) of these articles reported using multiple qualitative methods. The 30 studies using individual interviews interviewed an average of 45 people (range 15-155). The 38 studies using group interviews averaged 15 groups (range 1-180) and 141 people (range 9-900). Ten studies used observation/fieldwork, and eight used other types of qualitative research, with mixed [corrected] patterns of sample extensiveness in those studies. Few articles made specific statements about limitations based on sample extensiveness. Sample extensiveness in qualitative research in JNE varied considerably. Future qualitative research would benefit from more explicit attention to sample extensiveness.


[Quantitative concepts in the evaluation of diagnostic tests with reference to their suitability in diagnosis and therapy].
In the paper the necessity of quantitative data describing the efficiency of diagnostic and therapeutic measures is pointed out. Possible parameters of diagnostic (or therapeutic) effectiveness are indication lists, decision trees (diagnostic strategies), sensitivity, specificity, accuracy, predictive value and ROC-characteristics. These quantities and the mathematical relations between them are described. For chest x-ray screening the sensitivity is 0.84, specificity 0.90 and the respective predictive values are only 0.34% for Ca and 0.13% for tuberculosis.


Shift in vacuolar to cytosolic regime of infecting Salmonella from a dual proteome perspective.
By applying dual proteome profiling to Salmonella enterica serovar Typhimurium (S. Typhimurium) encounters with its epithelial host (here, S. Typhimurium infected human HeLa cells), a detailed interdependent and holistic proteomic perspective on host-pathogen interactions over the time course of infection was obtained. Data-independent acquisition (DIA)-based proteomics was found to outperform data-dependent acquisition (DDA) workflows, especially in identifying the downregulated bacterial proteome response during infection progression by permitting quantification of low abundant bacterial proteins at early times of infection when bacterial infection load is low. S. Typhimurium invasion and replication specific proteomic signatures in epithelial cells revealed interdependent host/pathogen specific responses besides pointing to putative novel infection markers and signalling responses, including regulated host proteins associated with Salmonella-modified membranes.


Low-Voltage Intrinsically Stretchable Organic Transistor Amplifiers for Ultrasensitive Electrophysiological Signal Detection.
Stretchability is a prerequisite for electronic skin devices. However, state-of-the-art stretchable thin-film transistors do not possess sufficiently low operating voltages and good stability, significantly limiting their use in real-world biomedical applications. Herein, a van der Waals-controlling elastomer/carbon quantum dot interfacial polarization methodology is proposed to form a hybrid polymer dielectric with 620% tensile strain and large-area film uniformity (>A4 paper size). Using the hybrid polymer dielectrics, the prepared intrinsically stretchable organic thin-film transistors demonstrate a low operating voltage below 5 V, 100% strain tolerance, and excellent operational stability, as well as a high on-current/off-current ratio of 105 and a steep subthreshold slope of 500 mV dec-1 . Based on this device technology, an amplifier with a high gain of 90 V V-1 among the highest values of reported stretchable transistors is realized. This amplifier is at the first time applied to detect human electrophysical signals with an output signal amplitude of over 0.2 V, which even outperforms other types of the state-of-the-art organic amplifiers for human electrophysiology monitoring. This stretchable device technology sufficiently meets the safety and portability requirements of wearable biomedical applications, opening a new opportunity to e-skin with signal control and amplification capabilities.


Influence of the -675 4G/5G dimorphism of the plasminogen activator inhibitor 1 promoter on thrombotic risk in patients with factor V Leiden.
Elevated plasminogen activator inhibitor 1 (PAI-1) levels are associated with venous thromboembolism, although their significance is unclear. PAI-1 levels are influenced by a PAI-1 promoter dimorphism (4G/5G), the 4G allele being associated with increased PAI-1 activity. We investigated whether the 4G allele influenced thrombotic risk by studying 99 symptomatic factor V (FV) Leiden heterozygotes and 99 healthy subjects. The 4G allele was more prevalent among cases than among healthy subjects (chi2 = 8.00, P = 0.005) and the odds ratio (OR) for thrombosis associated with either heterozygosity or homozygosity for the 4G allele was 2.43 (P = 0. 011). We conclude that carriership of the 4G allele was more prevalent in patients who already carried factor V Leiden than in control subjects without factor V Leiden.


Interferon-gamma gene and protein are spontaneously expressed by the porcine trophectoderm early in gestation.
The nature and the source of the antiviral activity found in the reproductive tract of pregnant gilts early in gestation were analyzed. Two antigenically distinct antiviral activities were found in uterine flushings and in supernatants of conceptus-conditioned culture medium between days 12 and 20 of gestation, using Madin Darby bovine kidney cells and vesicular stomatitis virus as a challenge in the antiviral bioassay. One component was antigenically identified as interferon-gamma (IFN-gamma). Northern blot analysis of conceptus poly(A)+ RNA with a human IFN-gamma cDNA probe revealed two mRNA of 1.3 and 1.4 kb. In addition, immunoprecipitation of metabolically labeled conceptus secretory proteins with an antiserum raised against purified porcine rIFN-gamma resulted in four bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with molecular mass 18.5 to 24.5 kDa. Pre-electrophoresis incubation of the immunoprecipitate with glycopeptidase F, which removes N-linked carbohydrates, yielded a single band of 16.5 kDa. Finally, staining of ultrathin sections by indirect immunofluorescence using the same antiserum to rIFN-gamma revealed that all cells of extra-embryonic trophectoderm contained intensely fluorescent granules in their apical cytoplasm. Neither endoderm nor embryonic cells stained positive. These results clearly show that IFN-gamma, known so far as a T or NK cell-derived lymphokine, is spontaneously and intensively secreted by the porcine trophectoderm, an embryonic tissue not related to the hematopoietic lineage. They also suggest that the implanting conceptus, at least in the porcine species, could play an active role in immune interactions with the mother.


Vitamin D and cardiovascular disease will it live up to its hype?
Substantial evidence suggests that a large portion of the population have suboptimal levels of vitamin D, which may adversely affect the cardiovascular (CV) system, including increasing levels of parathyroid hormone, activating the renin-angiotensin-aldosterone system, and increasing insulin resistance, thus leading to hypertension and left ventricular hypertrophy, metabolic syndrome/diabetes mellitus, systemic inflammation, and increased risk of atherosclerosis and CV disease events. We review the evidence that vitamin D deficiency is associated with incident CV disease events, as well as evidence that vitamin D supplementation is associated with reduction in CV diseases. Although the current evidence has created substantial hype, randomized controlled trials are needed to determine whether routine vitamin D assessment and supplementation will improve CV outcomes.


Response and recovery of Nile tilapia exposed to diesel oil - Behavioral, hemato-biochemical and morphological changes of erythrocytes.
Pollution caused by petroleum oil in several manners is becoming a threat to aquatic ecosystem. Hence, we carried out an experiment to investigate how diesel oil affects biota behavior, physiological attributes and how they recover by using Nile tilapia (Oreochromis niloticus) as a model organism. Nile tilapia of two different treatment groups were exposed to 0.1 mL/L and 0.5 mL/L diesel oil for 7 days. Then both groups were kept in completely diesel oil-free water for 14 days. A control group was maintained throughout the experimental period. We examined the behavioral attributes, hemato-biochemical parameters: hemoglobin (Hb), red blood cell (RBC), white blood cell (WBC) and glucose (Glu), and morphological changes of erythrocytes after diesel exposure and at the end of recovery phase. Our results revealed that there were abnormalities in behavior and significant changes in Hb, RBC, WBC and Glu level in both of the treatment group after 7 days of exposure. Frequencies of erythrocytic cellular abnormalities (ECAs), for example, twin, spindle, elongated, tear drop and erythrocytic nuclear abnormalities (ENAs) like notch nuclei, karyopyknosis, nuclear bud and nuclear bridge were prominent in both groups. However, the amount of anomalies was higher in most if not all the cases in 0.5 mL/L treatment group. Nile tilapia of both groups were quick to recover but the 0.1 mL/L group showed profound recovery than the 0.5 mL/L group. However, in the cases of ECAs and ENAs, recovery of the 0.5 mL/L group was insignificant. Hence, our experimental study concluded that the higher the exposure to diesel oil, higher incidences of major health problems are recorded, seriously piercing the healing system of Nile tilapia.


Anaphylaxis after Hymenoptera stings in three patients with urticaria pigmentosa.
Three patients with urticaria pigmentosa are reported who developed symptoms of anaphylaxis after Hymenoptera stings. Serum IgE antibodies to various Hymenoptera venoms could not be detected in any of the patients. Skin tests were completely negative in one patient, and borderline reactions with honeybee and yellow jacket venom, respectively, were found in the other two. Peripheral blood leukocytes of these latter two patients did not release significant amounts of histamine after exposure to the respective venoms. In patients with mastocytosis, anaphylaxis after insect stings may not be IgE-mediated but due to mediator release by the pharmacologic action of histamine liberators normally present in Hymenoptera venoms.


Acetabular cup placement and offset control in robotic total hip arthroplasty performed through the modified anterolateral approach.
The modified anterolateral approach (Röttinger) for total hip arthroplasty (THA) offers great advantages over conventional approaches, especially concerning early postoperative symptoms, which are mild and well tolerated by patients. Robotic-assisted implantation might facilitate rapid adoption of the modified anterolateral approach without exposing surgeons to risks encountered during the learning curve. This study posits that the use of robotic assistance in conjunction with the modified anterolateral approach for total hip arthroplasty (THA) can provide a substantial enhancement in the accuracy of cup placement in comparison to manual surgery. Thirty-two robotic-assisted THAs met the inclusion criteria and were matched to 32 conventional cases. Acetabular cup inclination, anteversion, limb-length discrepancy, and acetabular offset were assessed using certified planning software by two independent observers using pre- and postoperative anterior-posterior radiographs. Data was analyzed for normal distribution. Chi2 test was used to determine whether implanted acetabular cups that were within Lewinnek's safe zones were influenced by type of implantation. Effect size estimates and statistical power analysis were also performed to appreciate the appropriateness of the chosen sample size. Robotic-assisted implantation was found to significantly improve acetabular cup placement in terms of inclination (p < 0.001) but not anteversion (p = 0.783). Although mean postoperative limb-length discrepancy and mean acetabular offset did not differ between groups, a significantly smaller variance was found in the robotic-assisted group (p < 0.001) and (p = 0.04), respectively. There were no significant differences between the two groups in terms of consistently implanting the acetabular cup within the Lewinnek safe zones p = 0.641 for anteversion and p = 0.230 for inclination, respectively. Our results show that although robotic-assisted acetabular cup implantation performed through the modified anterolateral approach did not significantly differ from conventional implantation, it did offer increased accuracy in cup positioning, acetabular bone preservation, and limb-length restoration.


Obesity and sleep mismatch between weekends and weekdays in the Korean population according to working status.
To investigate whether sleep mismatch between weekends and weekdays is correlated with obesity according to working status and sex in the Korean population. This study was conducted using data from the Korea National Health and Nutritional Examination Survey (KNHANES) in 2016. A total of 5,684 subjects (2,453 men and 3,231 women) were divided into subgroups according to age, sex and working status. Sleep mismatch was defined as the difference in sleep duration between weekdays and weekends. In this study, multivariable logistic regression analysis was applied to obtain odds ratios (ORs) for obesity in those with sleep mismatch ≥ 90 min when referenced to those with sleep mismatch < 90 min. In the working group, adjusted ORs for obesity were mostly less than 1, but they were not statistically significant among any age or sex groups. However, for the non-working group, men over 60 years of age with sleep mismatch ≥ 90 min showed significantly increased ORs when referenced to those with sleep mismatch < 90 min in every model; the OR in model 4 was 2.89. Women over 60 years of age with sleep mismatch ≥ 90 min also showed higher ORs but they were not statistically significant. Men who are not working and over 60 years of age in Korea may be at increased risk of obesity if their sleep mismatch is ≥ 90 min. Therefore, it might be possible to lower the prevalence of obesity in the elderly population by correcting sleep irregularity or through reemployment.


[Epidural anesthesia using local anesthetics and clopheline in geriatric urology].
Study of pharmacokinetics of lidocaine, trimecaine, and clofelin demonstrated rapid resorption of these drugs in the postoperative period. Comparison of two methods of epidural anesthesia in high-risk patients (ASA 3) subjected to urologic surgery showed the objective advantages of adrenergic regional anesthesia, ensuring the stability of vital functions during surgery and allowing operations in awaken patients with adequate spontaneous respiration.


Sexual and site differences in calcium consumption by the Malabar Giant Squirrel Ratufa indica.
The calcium ingestion of Malabar Giant Squirrels Ratufa indica (Sciuridae) was examined at two sites, Magod and Bhimashankar, in western India. In females at Magod a positive correlation was found between rates of calcium ingestion from food resources and the contribution of those resources to the daily diet. This relationship was true for all females at Magod irre-spective of their reproductive condition. This relationship was neither significant for males at the same site nor for both sexes at Bhimashankar. A differential requirement for calcium between the sexes and the occurrence of higher rates of calcium ingestion or the probable presence of more easily digestible calcium at Bhimashankar are postulated to explain the observed phenomenon. Mature leaves and bark appear to be reliable sources of calcium at these sites.


Piracetam prevents memory deficit induced by postnatal propofol exposure in mice.
Postnatal propofol exposure impairs hippocampal synaptic development and memory. However, the effective agent to alleviate the impairments was not verified. In this study, piracetam, a positive allosteric modulator of AMPA receptor was administered following a seven-day propofol regime. Two months after propofol administration, hippocampal long-term potentiation (LTP) and long-term memory decreased, while intraperitoneal injection of piracetam at doses of 100mg/kg and 50mg/kg following last propofol exposure reversed the impairments of memory and LTP. Mechanically, piracetam reversed propofol exposure-induced decrease of BDNF and phosphorylation of mTor. Similar as piracetam, BDNF supplementary also ameliorated propofol-induced abnormalities of synaptic plasticity-related protein expressions, hippocampal LTP and long-term memory. These results suggest that piracetam prevents detrimental effects of propofol, likely via activating BDNF synthesis.


Interzonal transcallosal connections of the auditory and parietal cortex.
Transcallosal evoked potentials arising in the parietal region in response to stimulation of the auditory cortex of the opposite hemisphere were investigated in acute experiments on cats immobilized by tubocurarine. Interzonal transcallosal responses were recorded over the whole surface of the parietal cortex and were of two types: positive-negative and negative-positive. Positive-negative EP have a longer response latency and a greater total amplitude of both components. Negative-positive EP disappeared after division of the corpus callosum, whereas positive-negative responses were not significantly changed. Interzonal transcallosal potentials were characterized by the presence of functional interhemispheric asymmetry of individual shape. The right hemisphere was dominant with respect to average amplitude of the negative phase in negative-positive responses. The amplitude of the early positive component was greater in the right hemisphere in males and in the left hemisphere in females. The late negative wave in animals of both sexes was greater in the right hemisphere. Late components of the EP had a significantly shorter peak latency in the dominant hemisphere. Characteristics of generation and interhemispheric asymmetry of auditory-parietal transcallosal responses are discussed and compared with visual-parietal responses.


[Our experience in reconstructive surgery in glottic cancers].
A retrospective study was carried out in 58 patients operated between 1978 and 1983 for cancer of larynx of glottic origin and mainly T1 and T2. Functional results were always of good quality, and the recurrence rate significantly lowered by the use of the Majer-Piquet or C.H.E.P. procedure when compared with results after thyroidectomy. A simplified technique is proposed.


Preparation of TiO2-supported twinned gold nanoparticles by CO treatment and their CO oxidation activity.
We found that twinned gold nanoparticles (T-AuNPs) are generated at a high probability by CO treatment of TiO2-supported Au(iii) at room temperature. Because of the formation of T-AuNPs, the Au/TiO2 prepared by the CO treatment showed higher catalytic activity for CO oxidation than Au/TiO2 prepared by conventional H2 treatment.


Dopaminergic and serotonergic alterations in the rat brain during ethanol withdrawal: association with behavioral signs.
Changes in dopaminergic and serotonergic levels and metabolites in cerebral cortex, corpus striatum and hippocampus were investigated during the first 6-h of withdrawal in ethanol-dependent Wistar rats. Ethanol was given by a liquid diet for 21 days. The concentration of ethanol was 7.2% (v/v) for the last 15 days of the exposure. After 2, 4 and 6 h of ethanol withdrawal, and after audiogenic stimulus (100 dB for 60 s) at 6 h of ethanol withdrawal, various brain regions were assayed for levels of dopamine (DA), DOPAC, HVA, serotonin (5-HT) and 5-HIAA. Behavioral signs of ethanol withdrawal and blood ethanol levels were also evaluated in other parallel groups of ethanol-dependent rats. Significant decreases in 5-HT levels and significant increases in HVA levels in striatum were found during the first 6 h of ethanol withdrawal and after the audiogenic seizures. In hippocampus, 5-HIAA levels were significantly reduced after 2 h of ethanol withdrawal and after the audiogenic seizures. 5-HIAA levels significantly increased after 2 h of ethanol withdrawal in cerebral cortex. Significant increases in both DA and 5-HT levels were also found in cerebral cortex after the audiogenic seizures. The results suggest that the levels of DA, 5-HT and their metabolites are altered by ethanol withdrawal. Furthermore, this may suggest that DA and 5-HT may be involved in the first 6 h of ethanol withdrawal syndrome in rats.


Transformation of LMTK- cells with purified HLA class I genes. II. Serologic characterization of HLA-A3 and CW3 molecules.
The expression of two different HLA class I genes was observed after transformation of LMTK- cells. The corresponding class I molecules reacted differentially with monomorphic monoclonal antibodies (m.Ab). Absorption and elution studies of the human alloantibodies reacting with the transformed cells and cellular radioimmunoassay of these cells with polymorphic m.Ab resulted in the identification of HLA-A3 and CW3 molecules. These transformed cells were used to immunize C3H mice and induce the production of xenogeneic antisera, which, following absorption, showed polymorphic reactivity with human cells, suggesting that some of these sera could be used as typing reagents.


A basic experimental approach in perspective of pineal and melatonin involvement in photoperiod-induced alteration of spermatogenesis in toad (Bufo melanostictus).
Blinding decreases spermatogenesis along with Leydig cell degeneration in toad. Pinealectomy decreases spermatogenesis with an increase in Leydig cell activity. Melatonin decreases spermatogenesis as well the Leyding cells. Possibly pineal and melatonin possess an inverse relationship with light and inhibit testis.


Daily practices in chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma: METESTOMAC French prospective cohort.
Around 50% of gastric cancers are diagnosed at an advanced stage. Several chemotherapy regimens are now internationally validated. Few data are available on the routine daily management of advanced gastric or gastroesophageal junction cancers. We aimed to describe chemotherapy practices, tolerance, and efficacy overall survival (OS) and Progression free survival (PFS) in a prospective French cohort. Patients starting palliative chemotherapy were prospectively enrolled in 49 French centres. The primary objective was to report and describe patients' characteristics and treatment strategies. Secondary objectives were OS, PFS, objective response rate, adverse events rate, performance status deterioration during the chemotherapy. A total of 182 patients were included; 179 were analysed. Most patients received platinium-based chemotherapy as the first treatment and FOLFIRI as second; 62.0% of patients received a second line, and 32.4% a third line. More than two thirds of Her2-positive patients were first treated with trastuzumab. The FOLFIRI regimen was the most frequently used second-line therapy. Median OS was 13.3 months, similar whatever the chemotherapy or combinations used in the first line. One- and 2-year OS increased with the number of chemotherapy lines received, from respectively 24.7% and 5.7% (1 line), to 46.9% and 12.4% (2 lines) and 88.1% and 29.9% (3 or more lines) (p < 0.0001). Our study showed that treatment strategies in France are based on a succession of doublets, making it possible to offer a second and third line of treatment more often. This treatment strategy must be taken into account for future trials with immunotherapy combinations.


New insights into the roles of oligodendrocytes regulation in ischemic stroke recovery.
Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, are integral to axonal integrity and function. Hypoxia-ischemia episodes can cause severe damage to these vulnerable cells through excitotoxicity, oxidative stress, inflammation, and mitochondrial dysfunction, leading to axonal dystrophy, neuronal dysfunction, and neurological impairments. OLs damage can result in demyelination and myelination disorders, severely impacting axonal function, structure, metabolism, and survival. Adult-onset stroke, periventricular leukomalacia, and post-stroke cognitive impairment primarily target OLs, making them a critical therapeutic target. Therapeutic strategies targeting OLs, myelin, and their receptors should be given more emphasis to attenuate ischemia injury and establish functional recovery after stroke. This review summarizes recent advances on the function of OLs in ischemic injury, as well as the present and emerging principles that serve as the foundation for protective strategies against OLs deaths.


Mortality and causes of death in the aged with organic brain symptoms.
By various mental status rating methods, 363 aged residents at a nursing home (aged 80 years on the average) were previously evaluated with regard to chronic brain syndrome (CBS), and now at two and four years thereafter, the relation between mortality and the degree of CBS was statistically tested. The results showed that the severer the CBS, the higher the mortality, with significant difference. In 136 autopsy cases, the primary cause of death was investigated. The results showed no significant difference in the cause of death, either between dementia and non-dementia groups or between groups of mild, moderate and severe CBS.


Complete remission after neoadjuvant chemoradiation in a stage IV vulvar cancer patient.
Surgery is the standard in the management of vulvar cancer. Several studies assessed the feasibility of radiochemotherapy as definitive therapy and/or neoadjuvant procedure in order to limit the extent of surgery. Combined radiochemotherapy is associated with considerable toxicity. The authors report on a modified neoadjuvant radiochemotherapy schedule which is isoeffective to the GOG (Gynecologic Oncology Group) protocol, but associated with less therapy-related toxicity. A 36-year-old woman with stage IV vulvar cancer and long-distance rectal infiltration is reported. Laparoscopic pretherapeutic staging confirmed pelvic and paraaortic lymph node metastases. The patient received a neoadjuvant radiochemotherapy. After complete remission, a simple vulvectomy carried out 3 months later showed no evidence of tumor. Up to now, there is no evidence of tumor progression or recurrence. Preoperative conventionally fractionated simultaneous radiochemotherapy seems to be a feasible and safe treatment option for patients with locally advanced vulvar cancer in order to avoid exenterative surgery.


Fractionation of phosphorus biowastes: characterisation and environmental risk.
Phosphorus (P) fertilizer is essential for food production and is a limiting factor in crop yields. However, the role of P in the eutrophication of surface water has long been recognised. During recent years, the input of P from agriculture to surface waters has increased and has been the focus for strategies aimed at mitigating diffuse P losses. As not all forms of P have the same availability, it is important to know the main forms of phosphorus in biowastes, and hence to develop fractionation schemes. The standards, measurements, and testing (SMT) procedure for phosphorus fractionation in freshwater sediments, developed within the framework of the Standards, Measurements, and Testing Program of the European Commission, was applied to 15 biowastes used frequently in agriculture, to obtain total P, inorganic and organic P, apatite P, and non-apatite inorganic P. The Hedley method was applied to determine the water-soluble phosphorus (WSP) in all the biowastes. In addition, the aluminium, calcium, and iron concentrations were quantified and related to the WSP. The results confirm the applicability of the SMT protocol to all kinds of waste usually applied in agriculture. The SMT protocol revealed the existence of large amounts of inorganic P and non-apatite inorganic P, the most-available forms of P for all the biowastes. The comparison of the data for total P (SMT protocol) and WSP (Huang protocol) does not show a good linear relationship between these parameters. Instead, the relationship between [aluminium+calcium+iron] and WSP is a better indication of the availability of P.


Novel aspects of enteric serotonergic signaling in health and brain-gut disease.
Gastrointestinal (GI) comorbidities are common in individuals with mood and behavioral dysfunction. Similarly, patients with GI problems more commonly suffer from co-morbid psychiatric diagnoses. Although the central and enteric nervous systems (CNS and ENS, respectively) have largely been studied separately, there is emerging interest in factors that may contribute to disease states involving both systems. There is strong evidence to suggest that serotonin may be an important contributor to these brain-gut conditions. Serotonin has long been recognized for its critical functions in CNS development and function. The majority of the body's serotonin, however, is produced in the GI tract, where it plays key roles in ENS development and function. Further understanding of the specific impact that enteric serotonin has on brain-gut disease may lay the foundation for the creation of novel therapeutic targets. This review summarizes the current data focusing on the important roles that serotonin plays in ENS development and motility, with a focus on novel aspects of serotonergic signaling in medical conditions in which CNS and ENS co-morbidities are common, including autism spectrum disorders and depression.


Advancing injury and violence prevention through data science.
The volume of new data that is created each year relevant to injury and violence prevention continues to grow. Furthermore, the variety and complexity of the types of useful data has also progressed beyond traditional, structured data. In order to more effectively advance injury research and prevention efforts, the adoption of data science tools, methods, and techniques, such as natural language processing and machine learning, by the field of injury and violence prevention is imperative. The Centers for Disease Control and Prevention's (CDC) National Center for Injury Prevention and Control has conducted numerous data science pilot projects and recently developed a Data Science Strategy. This strategy includes goals on expanding the availability of more timely data systems, improving rapid identification of health threats and responses, increasing access to accurate health information and preventing misinformation, improving data linkages, expanding data visualization efforts, and increasing efficiency of analytic and scientific processes for injury and violence, among others. To achieve these goals, CDC is expanding its data science capacity in the areas of internal workforce, partnerships, and information technology infrastructure. Practical Application: These efforts will expand the use of data science approaches to improve how CDC and the field address ongoing injury and violence priorities and challenges.