Direct coronal CT scanning for the body.
A direct coronal CT scanning technique for the trunk, named "Quasi-Coronal" CT, is presented and its usefulness demonstrated with clinical examples. Patients are placed in the lateral position on a wide plate laid on the scanner bed and instructed to assume various special postures. An important concept of this technique is to obtain the tomograms in which target organs with predominant longitudinal orientation are directly imaged in the coronal plane. An analysis of artifacts due to "Out of Field" objects is presented. When properly performed, "Quasi-Coronal" CT can provide useful additional information, despite having some limitations.


Listeriosis as an obstetric complication in an immunocompromised patient.
We have reported a case of maternal death associated with Listeria monocytogenes septicemia in a woman who was being treated with immunosuppressive drugs for lupus nephritis. This report, coupled with a previous case of L monocytogenes sepsis in a pregnant patient with AIDS, emphasizes that L monocytogenes infection may be an important, unrecognized pathogen in pregnant women with impaired immunity.


Diagnostic accuracy of anti-keratin antibody for rheumatoid arthritis: a meta-analysis.
Anti-keratin antibody (AKA) is a serum antibody for patients with rheumatoid arthritis (RA), and it has a high specificity. Diagnostic role of AKA in RA was evaluated in this study. PubMed, EMBASE, and Web of Science were searched to acquire eligible studies. Articles published before 15 March 2018 were considered to be included. Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the risk of bias and application concern of the included articles. Pooled analysis of diagnostic indicators of AKA for RA was conducted by using a random effects model. Subgroup analysis was employed to explore the potential influencing factors. RevMan 5.3, Stata 11.0, and Meta-DiSc 1.4 software were used in this study. A total of 15 studies (2350 positive and 2067 negative participants) were included. The pooled sensitivity was 0.46 (95% CI 0.44-0.48), pooled specificity was 0.94 (95% CI 0.93-0.95), and pooled diagnostic odds ratio was 15.86 (95% CI 9.48-26.52). In addition, the area under the curve was 0.7194. The current evidence indicated that AKA has high diagnostic specificity in RA and may be useful for RA diagnostic application in clinic.


Does noninvasive ventilation work in ARDS? A case report and review of the current literature.
The role of noninvasive positive pressure ventilation (NIPPV) in adult respiratory distress syndrome (ARDS) is controversial, in contrast to its well established benefits in other types of respiratory failure, especially acute exacerbations of chronic obstructive pulmonary disease and cardiogenic pulmonary oedema. We report a case of ARDS caused by Mycoplasma pneumoniae in a 70 year old man, treated with NIPPV in addition to standard medical therapy and analyse current evidence regarding the role of NIPPV in patients with ARDS.


Strengthening the Canadian alcohol advertising regulatory system.
Research evidence points to harmful effects from alcohol advertising among children and youth. In particular, exposure to alcohol advertising has been associated with adolescents drinking both earlier and heavier. Although current federal and provincial guidelines have addressed advertising practices to prevent underage drinking, practice has not been supported by existing policy. While protective measures such as social marketing campaigns have the potential for counteracting the effects from alcohol advertising, the effectiveness of such measures can be easily drowned out with increasing advertising activities from the alcohol industry, especially without effective regulation. Research reviewed by the European Focus on Alcohol Safe Environment (FASE) Project has identified a set of key elements that are necessary to make alcohol advertising policy measures effective at protecting children and youth from the harmful effects of alcohol marketing. Using these key elements as an evaluation framework, there are critical components in the Canadian alcohol advertising regulatory system that clearly require strengthening. To protect impressionable children and youth against the harmful effects of alcohol advertising, 13 recommendations to strengthen current alcohol advertising regulations in Canada are provided for Canadian policy-makers, advertising standard agencies, and public health groups.


Treatment of intracranial ependymomas of children: review of a 15-year experience.
There are still major controversies in the optimal management of children with intracranial ependymomas. To assess the impact of tumor site, histology, and treatment, the outcome of children treated at the Institut Gustave Roussy was reviewed retrospectively. Between 1975 and 1989, 80 children aged 4 months to 15.8 years were seen at the Institut Gustave Roussy for postoperative management of an intracranial ependymoma. Location of tumor was infratentorial in 63 cases and supratentorial in 17. Surgical treatment consisted of complete resection in 38, incomplete resection in 38 and biopsy only in 4. Postoperative irradiation was done in 65 patients and chemotherapy in 33. Surviving patients have been followed from 12-197 months with a median of 54 months. The 5-year actuarial survival and event-free survival are 56% and 38%, respectively. Thirty-four patients relapsed from 3-72 months after diagnosis (median 25 months). In 20 patients, the only site of failure was the original tumor site. Three patients failed locally and at distance, while 10 others failed only at distance. Survival at 5 years was significantly better for patients who had complete resection of the tumor (75% vs. 41%, p = 0.001) and for those who received radiation therapy (63% vs. 23%, p = 0.003). Event-free survival at 5 years was superior in patients with complete resection of the tumor (51% vs. 26%, p = 0.002) and in patients who received radiation therapy (45% vs. 0%, p < 0.001). Sex and tumor site had no impact on survival or event-free survival. There was no difference in survival, event-free survival, or pattern of failure between patients treated with local field, whole brain or craniospinal irradiation, while severe longterm sequelae were noted predominantly in the latter two groups. Considering that failures were predominantly local and that there was no apparent benefit from prophylactic irradiation, we recommend local field irradiation with doses above 50.0 Gy for all children with intracranial ependymomas, without meningeal dissemination at diagnosis. Special considerations are necessary for children < 3 years of age.


Bifidobacterium infantis and 2'-fucosyllactose supplementation in early life may have potential long-term benefits on gut microbiota, intestinal development, and immune function in mice.
The health benefits of nutritional interventions targeting the gut microbiota in early life are transient, such as probiotics, prebiotics, and synbiotics. This study sought to determine whether supplementation with Bifidobacterium infantis 79 (B79), 2'-fucosyllactose (2'-FL), or both (B79+2'FL) would lead to persistent health benefits in neonatal BALB/c mice. We found that at postnatal day (PND) 21, Ki67 and MUC2 expression increased, while total serum IgE content decreased in the B79, 2'-FL, and B79+2'-FL groups. The gut microbiota structure and composition altered as well. The levels of propionic acid, sIgA, and IL-10 increased in the 2'-FL group. Moreover, butyric acid content increased, while IL-6, IL-12p40, and tumor necrosis factor-α decreased in the B79+2'-FL group. At PND 56, Ki67 and MUC2 expression increased, whereas the gut microbiota remained altered in all 3 groups. The serum total IgG level increased only in the B79+2'-FL group. In conclusion, our study suggests that early-life supplementation with B79, 2'-FL, or their combination persistently alters the gut microbiome and promotes intestinal development; the immunomodulatory capacity of B79 and 2'-FL occurs during weaning, and their combination may persist into adulthood.


Statistical prediction of immunity to placental malaria based on multi-assay antibody data for malarial antigens.
Plasmodium falciparum infections are especially severe in pregnant women because infected erythrocytes (IE) express VAR2CSA, a ligand that binds to placental trophoblasts, causing IE to accumulate in the placenta. Resulting inflammation and pathology increases a woman's risk of anemia, miscarriage, premature deliveries, and having low birthweight (LBW) babies. Antibodies (Ab) to VAR2CSA reduce placental parasitaemia and improve pregnancy outcomes. Currently, no single assay is able to predict if a woman has adequate immunity to prevent placental malaria (PM). This study measured Ab levels to 28 malarial antigens and used the data to develop statistical models for predicting if a woman has sufficient immunity to prevent PM. Archival plasma samples from 1377 women were screened in a bead-based multiplex assay for Ab to 17 VAR2CSA-associated antigens (full length VAR2CSA (FV2), DBL 1-6 of the FCR3, 3D7 and 7G8 lines, ID1-ID2a (FCR3 and 3D7) and 11 antigens that have been reported to be associated with immunity to P. falciparum (AMA-1, CSP, EBA-175, LSA1, MSP1, MSP2, MSP3, MSP11, Pf41, Pf70 and RESA)). Ab levels along with clinical variables (age, gravidity) were used in the following seven statistical approaches: logistic regression full model, logistic regression reduced model, recursive partitioning, random forests, linear discriminant analysis, quadratic discriminant analysis, and support vector machine. The best and simplest model proved to be the logistic regression reduced model. AMA-1, MSP2, EBA-175, Pf41, and MSP11 were found to be the top five most important predictors for the PM status based on overall prediction performance. Not surprising, significant differences were observed between PM positive (PM+) and PM negative (PM-) groups for Ab levels to the majority of malaria antigens. Individually though, these malarial antigens did not achieve reasonably high performances in terms of predicting the PM status. Utilizing multiple antigens in predictive models considerably improved discrimination power compared to individual assays. Among seven different classifiers considered, the reduced logistic regression model produces the best overall predictive performance.


The role of mRNA stability in airway remodelling.
As a consequence of long-term exposure to inflammatory mediators, the airways of asthmatics become remodelled. Airway fibrosis becomes apparent, with thickening of the lamina recticularis and increased interstitial matrix deposition being typical features of an asthmatic airway. Mucus hypersecretion occurs, airway smooth muscle mass is increased and neovascularization is evident in the subepithelial mucosa. As development of a remodelled airway is correlated with deterioration of lung function in asthmatics, there is an urgent need for therapies that reduce airway inflammation and reverse structural changes in a remodelled airway. However, in order to design efficacious anti-remodelling agents we first need a greater understanding of the molecular mechanism/s underlying the development of airway remodelling. To date, however, most studies have primarily focused on the transcriptional regulation of genes that promote airway remodelling. Post-transcriptional mechanisms, such as control of mRNA stability, remain largely unexplored. Levels of cellular mRNA transcripts are regulated by controlling the rate at which the mRNA decays, thus investigation into the mechanisms underlying mRNA stability in asthma are of critical importance. Therefore, this review will present an overview of the control of mRNA stability and examine how mRNA stability may play a role in the development of airway remodelling in asthma.


Pretreatment MR-Based Radiomics Signature as Potential Imaging Biomarker for Assessing the Expression of Topoisomerase II alpha (TOPO-IIα) in Rectal Cancer.
Rectal cancer (RC) is one of the most common cancers throughout the world. Chemotherapy or neoadjuvant chemotherapy play an important role in the treatment of advanced RC. Whether to add topoisomerase inhibitor to individualized chemotherapy is a puzzling question for clinicians. To investigate whether pretreatment MR-based radiomics signature can assess the expression of topoisomerase II alpha (TOPO-IIα) in RC. Retrospective. In all, 122 patients with RC. Field Strength/Sequence: Pretreatment 3.0T; T2 WI turbo spin echo (TSE) sequence. A training group (n = 85) and a test group (n = 37) with pathologically confirmed RC. Patients underwent TOPO-IIα expression. A total of 180 radiomics features were extracted from oblique axial T2 WI TSE images of the entire primary tumor. The least absolute shrinkage and selection operator (LASSO) regression model was used to reduce the dimension of the data and select the features. The assessment models were established by multivariable logistic regression analysis. The performance of the model was assessed by the receiver operating characteristic (ROC) curve, nomogram, and calibration. The radiomics signature, which consisted of 10 selected optimal features, was significantly associated with TOPO-IIα expression (P < 0.01 for both training and test groups). The area under the curve (AUC), the sensitivity, and the specificity for assessing TOPO-IIα expression, were 0.859, 0.872, and 0.739, respectively, in the training group, while they were 0.762, 0.941, and 0.600 in the test group. The nomogram model of the radiomics signature (Rad-score) had good calibration. Calibration curves were plotted to assess the calibration of the radiomics nomogram that was accompanied with the Hosmer-Lemeshow test (P = 0.52). The proposed pretreatment MR-based radiomics signature was associated with TOPO-IIα expression. A radiomics nomogram might be helpful in the individualized assessment of TOPO-IIα expression in patients with RC. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1881-1889.


Development and Validation of the Beliefs About Revenge Pornography Questionnaire.
The non-consensual sharing of private sexual images (so-called 'revenge pornography') has become an increasingly prominent topic in social and legislative discussions about sexual crime but has received relatively little attention within psychological research. Here, we leveraged existing theorizing in the area of sexual offending proclivity to systematically develop and validate a measure of beliefs about this type of offending. There is currently a lack of validated assessment tools in this area, and these are important to better understand the role of offense-supportive cognition in predicting both proclivity of these offenses and judgements of both victims and perpetrators. Using an international community sample (N = 511) we found our 'Beliefs about Revenge Pornography Questionnaire (BRPQ)' to be comprised of four underpinning domains: 'Victims as Promiscuous', 'Victim Harm', 'Avoiding Vulnerable Behaviors' and 'Offense Minimization'. Concurrent validity is demonstrated through relationships with trait empathy, belief in a just world, dark personality traits and rape myth acceptance. Randomly dividing the sample, we also show that the BRPQ was associated with both proclivity (n = 227) and social judgements of this type of offending (n = 232). Implications and future directions are discussed. An open-access preprint is available at https://psyarxiv.com/6qr7t/.


Predicting weighted unobserved nodes in a regulatory network using answer set programming.
The impact of a perturbation, over-expression, or repression of a key node on an organism, can be modelled based on a regulatory and/or metabolic network. Integration of these two networks could improve our global understanding of biological mechanisms triggered by a perturbation. This study focuses on improving the modelling of the regulatory network to facilitate a possible integration with the metabolic network. Previously proposed methods that study this problem fail to deal with a real-size regulatory network, computing predictions sensitive to perturbation and quantifying the predicted species behaviour more finely. To address previously mentioned limitations, we develop a new method based on Answer Set Programming, MajS. It takes a regulatory network and a discrete partial set of observations as input. MajS tests the consistency between the input data, proposes minimal repairs on the network to establish consistency, and finally computes weighted and signed predictions over the network species. We tested MajS by comparing the HIF-1 signalling pathway with two gene-expression datasets. Our results show that MajS can predict 100% of unobserved species. When comparing MajS with two similar (discrete and quantitative) tools, we observed that compared with the discrete tool, MajS proposes a better coverage of the unobserved species, is more sensitive to system perturbations, and proposes predictions closer to real data. Compared to the quantitative tool, MajS provides more refined discrete predictions that agree with the dynamic proposed by the quantitative tool. MajS is a new method to test the consistency between a regulatory network and a dataset that provides computational predictions on unobserved network species. It provides fine-grained discrete predictions by outputting the weight of the predicted sign as a piece of additional information. MajS' output, thanks to its weight, could easily be integrated with metabolic network modelling.


Evaluating the extent to which homeostatic plasticity learns to compute prediction errors in unstructured neuronal networks.
The brain is believed to operate in part by making predictions about sensory stimuli and encoding deviations from these predictions in the activity of "prediction error neurons." This principle defines the widely influential theory of predictive coding. The precise circuitry and plasticity mechanisms through which animals learn to compute and update their predictions are unknown. Homeostatic inhibitory synaptic plasticity is a promising mechanism for training neuronal networks to perform predictive coding. Homeostatic plasticity causes neurons to maintain a steady, baseline firing rate in response to inputs that closely match the inputs on which a network was trained, but firing rates can deviate away from this baseline in response to stimuli that are mismatched from training. We combine computer simulations and mathematical analysis systematically to test the extent to which randomly connected, unstructured networks compute prediction errors after training with homeostatic inhibitory synaptic plasticity. We find that homeostatic plasticity alone is sufficient for computing prediction errors for trivial time-constant stimuli, but not for more realistic time-varying stimuli. We use a mean-field theory of plastic networks to explain our findings and characterize the assumptions under which they apply.


Obscure gastrointestinal bleeding localization using preoperative super-selective mesenteric angiography and intraoperative methylene blue injection: A case report and literature review.
Currently available diagnostic tests for localizing the source of gastrointestinal bleeding include esophagogastroduodenoscopy, colonoscopy, push enteroscopy, video capsule endoscopy, deep enteroscopy, nuclear scan, angiography, radiographic contrast studies of the small bowel, intraoperative enteroscopy, and computed tomography scanning. Despite these diagnostic modalities obscure gastrointestinal bleeding (OGIB) can be difficult to localize, making surgical intervention challenging. We report the case of a 78-year-old patient who presented with OGIB, melena and passing bright red blood per rectum, with a hemoglobin of 4.8 g/dl requiring multiple blood transfusions. Initially the source of the bleeding was difficult to identify. Eventually, a preoperative superior mesenteric angiogram was performed, identifying an arteriovenous malformation (AVM) within the small bowel as the source of OGIB. Intraoperative methylene blue was then injected through the previously placed angiogram catheter to further localize the bowel segment with the lesion. Despite multiple diagnostic modalities, OGIB, especially originating in the small bowel, is challenging to localize, making surgical intervention difficult. Methylene blue is frequently used intraoperatively to properly identify anatomic landmarks. In cases of OGIB, superselective mesenteric angiography (SSMA) with intraoperative methylene blue injection can be used as an adjunct to routine diagnostic modalities to guide surgical interventions for controlling hemorrhage and for limiting the extent of bowel resection.


MO19390 (SAiL): bleeding events in a phase IV study of first-line bevacizumab with chemotherapy in patients with advanced non-squamous NSCLC.
The clinical benefit and safety profile associated with first-line bevacizumab with doublet chemotherapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC) was established in two large phase III studies, E4599 and AVAiL. SAiL, a single-arm phase IV study, was conducted to evaluate bevacizumab with a range of first-line chemotherapy regimens in a routine oncology practice setting. This analysis of the SAiL data was undertaken to specifically evaluate bleeding adverse events (AEs) in this study, and to explore potential associations between bleeding and baseline patient and disease characteristics. In total, 2212 patients were evaluated. Bleeding AEs (any grade) occurred in 38.2% of patients (grade ≥ 3 bleeding AEs: 3.6%). Grade ≥ 3 pulmonary hemorrhage and central nervous system bleeding events were observed in 0.7% and 0.1% of patients, respectively. The incidence of grade ≥ 3 bleeding AEs was comparable across patient subgroups defined by central tumor location, tumor cavitation, histology, concomitant anticoagulation therapy and age. The majority (88.6%) of bleeding events resolved or improved, 10.2% persisted and 1.3% led to death; 10.2% of bleeding events required bevacizumab interruption or discontinuation. This analysis from the SAiL trial reaffirms a comparable incidence of clinically significant bleeding associated with first-line bevacizumab and chemotherapy as previous phase III studies in NSCLC patients despite less stringent first-line selection criteria. Grade ≥ 3 bleeding appears to be comparable when analyzed for patient and tumor characteristics, including tumor cavitation and concomitant anticoagulation therapy. Most bleeding events resolved or improved, and interruption/discontinuation of bevacizumab was infrequent in a standard oncology practice setting.


The usefulness of cross-sectional Doppler flow imaging in the detection of small ventricular septal defects with left-to-right shunt.
Small ventricular septal defects (VSDs) with left to right (L-R) shunt have been difficult to diagnose with conventional ultrasound techniques. Using the cross-sectional Doppler flow imaging system, additional information can be obtained. In a group of 60 patients with a clinical diagnosis of VSD with L-R shunt, the new technique proved valuable, especially in detecting muscular and apical VSDs.


Studies on new process procedures in plasma fractionation on an industrial scale. IV. Comparison of two semipermeable membrane systems for the concentration of albumin solutions.
Two semipermeable membrane systems for the production of salt-poor, concentrated human albumin preparations for clinical use are compared. A very efficient method, on an industrial scale, is obtained by the combination of gel filtration and ultrafiltration.


Prevalence, awareness, treatment and control of hypertension in Turkey (the PatenT study) in 2003.
To determine the distribution of blood pressure (BP) and prevalence, awareness, treatment and control of hypertension in Turkey (PatenT). A population-based cross-sectional epidemiology survey was carried out in 2003. Twenty-six cities from seven geographical provinces of Turkey, with proportional representation of urban and rural populations. A two-stage stratified sampling method was used to select a sample of the adult population over 18 years of age. The total number of participants was 4910. Data collection and BP measurements were conducted by specifically trained physicians in the households of the participants. The mean systolic and diastolic BP levels, distribution of blood pressure, prevalence of hypertension (mean systolic BP>or=140 mmHg or mean diastolic BP>or=90 mmHg, or previously diagnosed and/or taking antihypertensive drugs), awareness, treatment and control of hypertension were assessed. The overall age-adjusted and sex-adjusted prevalence of hypertension in Turkey was 31.8%, and it was higher in women than in men (36.1 versus 27.5%, P<0.001). In the whole group, 32.2% had never had their BP measured. Overall, 40.7% of those with hypertension were aware of their diagnosis, only 31.1% were receiving pharmacologic treatment and only 8.1% had their BP under control. The subjects who were aware and treated had a control ratio of 20.7%. PatenT data indicate that hypertension is a highly prevalent but inadequately managed health problem in Turkey. There is an urgent need for population-based strategies to improve the prevention, early detection and control of hypertension.


Determination of furan levels in commercial orange juice products and its correlation to the sensory and quality characteristics.
The objective of current study was to determine the furan levels in commercial orange juices (OJs) and relate to the sensory and quality characteristics of OJs. The factors among sensory and quality characteristics that showed high correlation to furan were identified. The furan levels found in 18 commercial OJs ranged from 0.59 to 27.39ng/mL. Freshly-squeezed type OJs (n=4) had significantly lower furan levels (4.68ng/mL) than other OJs treated with heat processing (p<0.05). Vitamin C content, specifically, dehydroascorbic acid showed higher correlation to the furan level in OJs (r=0.833). A descriptive sensory analysis result revealed the different flavor profile of commercial OJs according to the processing method and added ingredient in OJs. Current approach of using sensory analysis for prediction of furan level in food products can be applied to future studies in many other food commodities.


Seasonal patterns of daily net photosynthesis, transpiration and net primary productivity of Juncus roemerianus and Spartina alterniflora in a Georgia salt marsh.
Studies of the seasonal CO2 and water vapor exchange patterns of Juncus roemerianus and Spartina alterniflora were conducted in an undisturbed marsh community on Sapelo Island, Georgia. Daily patterns of net photosynthesis, transpiration, leaf diffusive conductance and water-use efficiency in response to ambient conditions were monitored on intact, in situ plants. Net primary productivity was calculated from the daytime CO2 fixation totals, nighttime CO2 loss, leaf standing stock and aboveground to belowground biomass ratios for each plant type.The tall form of S. alterniflora had higher rates of photosynthesis and higher water-use efficiency values which, in conjunction with low respiratory losses and large leaf standing crop, results in high values of net primary productivity. The environmental factors in the marsh which permit these physiological responses occur in less than 10% of the marsh. Overall, the physiological capabilities of the short form of S. alterniflora were reduced in comparison to the tall form, but the combination of environmental factors which determine the physiological responses of this form occur in a much greater portion of the marsh, and the short form of S. alterniflora dominates the Sapelo Island marshes.The response patterns of the C3 species, J. roemerianus, differed somewhat from the height forms of S. alterniflora. A large, seasonally constant leaf standing crop coupled with moderate rates of photosynthesis resulted in a net primary productivity value which was between the tall and short height forms of S. alterniflora. However, as with the tall S. alterniflora, the environmental conditions under which this high productivity and high water loss rate can be sustained are restricted to specific regions of the environmental gradient in the marsh.


Portal tumor thrombus secondary to gastric carcinoma: report of a case with an emphasis on color Doppler ultrasound findings.
We report the case of a 67-year-old woman with portal tumor thrombus (PTT) associated with gastric carcinoma. Abdominal ultrasound (US) revealed a marked thickening of the gastric wall and a mass lesion in the splenic vein. Color Doppler US showed the intraportal mass to be blood flow-poor and revealed a gastroepiploic vein extending from the splenic hilum to the portal confluence, passing behind the peritoneum. These findings corresponded well with gastric carcinoma with PTT. Endoscopy confirmed the presence of an advanced type II carcinoma predominantly located in the upper body, which yielded histological results consistent with a well-differentiated adenocarcinoma. The patient's general condition deteriorated rapidly, and she died 2 months later. To the best of our knowledge, this is the first report describing the presence of a large gastroepiploic vein secondary to gastric carcinoma-associated PTT.


Food selection by western gorillas (G.g. gorilla) in relation to food chemistry.
Samples of stems, leaves, shoots and fruit (N=36) from lowland, African rain forest are analyzed for nutrients, digestibility and digestion-inhibiting substances. Plants from which the samples are drawn are all important in the diet of western gorillas, large generalist herbivores in coastal Cameroon. Many of the plants are common in the early succession following disturbance to the forest. Analysis of food chemistry in relation to food preference indicates that lignin, digestibility and crude protein are the most significant factors in food selection for western gorillas at this site. Food chemistry of western gorillas is compared to food chemistry of mountain gorillas in the montane forest of East Africa. Foliage consumed by western gorillas contains more condensed tannin than does foliage consumed by mountain gorillas. The greater content of condensed tannin in the leaves consumed by western gorillas is related to the greater representation of woody plants in the western diet.


Effects of fructose and glucose preloads on subsequent food intake.
To determine how the nutrient content of one eating event might affect amount consumed at the next, we evaluated whether equicaloric fructose and glucose preloads differentially influence subsequent food intake. Subjects consumed 50 g of glucose or fructose in 500 ml of water or water alone and were given a "buffet" containing a variety of foods two and a quarter hours later. Subjects in glucose conditions ate, on the average, 252 X 7 calories more than subjects in the water condition, who in turn ate, on the average, 225 X 9 calories more than subjects in the fructose condition. The fructose and glucose preloads did not differentially affect the amount eaten of different types of nutrients (carbohydrate, fat and protein). This study, employing several sensory and cognitive controls, suggests that type of nutrient ingested, in and of itself, plays a role in determining subsequent intake for humans. The data are discussed in terms of possible physiological mechanisms that might account for these effects.


Environmental sustainability assessment of tropical dairy buffalo farming vis-a-vis sustainable feed replacement strategy.
Feeding management in dairy animals is crucial for ensuring optimal production apart from making the farming as a whole, a more sustainable activity. In our study we evaluated the production and environmental effects of two different feeding regimens i.e., one dominated by traditional cottonseed meal (CSM) and other with coated urea (slow release urea - SRU) as a replacement for CSM on dairy buffalo production. The SRU at 2% level was evaluated by conducting two different trials using twelve lactating Murrah buffaloes and four adult Murrah buffalo bulls. Neither diet nor dry period management showed any substantial effect on milk components, intakes, nutrients' digestibility coefficients, and nutritive values. The SRU diet revealed increased (P < 0.01) rumen pH, ammonia nitrogen, volatile fatty acids, and microbial nitrogen yield, which were interacted with time of post-prandial sampling. The dynamics of nitrogen metabolism revealed unaltered N-based parameters, except for degradable-N intake and serum urea-N at 3 hr post-feeding. The CSM replacements did not influence (P > 0.05) the residual feed intake, but led to an enhanced milk retention efficiency of nitrogen, calcium, and phosphorus contents, thus reducing their impact on soil pollution and eutrophication of water bodies. Despite an unaltered (P > 0.05) enteric methane emission, SRU diets achieved in decreasing manure methane and nitrous oxide emission. Furthermore, the virtual water flow and lifecycle assessment revealed a water sparing effect and low carbon foot print per unit milk production. In summary, the CSM replacements with SRU could achieve an economical and eco-friendly production system from animal nutrition perspective.


Pseudoepitheliomatous, keratotic, micaceous balanitis. A clinical lesion with two histologic subsets: hyperplastic dystrophy and verrucous carcinoma.
A 58-year-old man presented with a 4-year history of a slowly enlarging, hyperkeratotic plaque on his glans penis that was compatible with a clinical diagnosis of pseudoepitheliomatous, keratotic, micaceous balanitis. The lesion had been treated unsuccessfully on three occasions with superficial shave excisional biopsies. Complete surgical excision produced excellent cosmetic and functional results with no evidence of recurrence at 3- and 6-month follow-up. A diagnosis of verrucous carcinoma was made on histologic examination of the excised material. Pseudoepitheliomatous, keratotic, micaceous balanitis is a distinctive clinical entity that represents a histologic spectrum ranging from hypertrophic-hyperplastic penile dystrophy to verrucous carcinoma.


Facultative monophagy as a consequence of prior feeding experience: behavioral and physiological specialization in Colias philodice larvae.
Although newly-emerged Colias philodice readily accept Medicago sativa, Melilotus alba, and Coronilla varia, fifth instar larvae reared on any single plant species display a highly significant induced feeding preference for their rearing host. Forced host-switching reveals that fifth instar relative growth rate (RGR) on M. sativa and M. alba is significantly reduced by prior feeding on either alternative host. Moreover, regardless of rearing diet, switching to a novel host during the fifth instar results in reduced RGR, relative consumption rate (RCR), efficiency of conversion of digested food (ECD), and pupal weight. These results support the hypothesis that induction of feeding preference is an adaptive response that predisposes larvae to feed on the plant species they are most capable of utilizing for growth.


Analysis of the relationship between short tandem repeats and lactation performance of Xinjiang Holstein cows.
Microsatellite markers, also known as short tandem repeats (STRs), are important for marker-assisted selection to detect genetic polymorphism, and they are uniformly distributed in eukaryotic genomes. To analyze the relationship between microsatellite loci and lactation traits of Holstein cows in Xinjiang, 175 lactating cows with similar birth dates, the same parity, and similar calving dates were selected, and 10 STR loci closely linked to quantitative trait loci were used to analyze the correlation between each STR locus and four lactation traits (daily milk yield, milk fat percentage, milk protein percentage, and lactose percentage). All loci showed different degrees of genetic polymorphism. The average values of observed alleles, effective alleles, expected heterozygosity, observed heterozygosity, and polymorphic information content of the 10 STR loci were 10, 3.11, 0.62, 0.64, and 0.58, respectively. Chi-square and G-square tests showed that all populations of loci were in accordance with the Hardy-Weinberg equilibrium. Analysis of the correlation between STR locus genotype and lactation performance in the whole lactation period showed three loci (namely, BM143, BM415, and BP7) with no significant correlation with all lactation traits, two loci (BM302 and UWCA9) related to milk yield, three loci (BM103, BM302, and BM6425) related to milk fat percentage, two loci (BM302 and BM6425) related to milk protein percentage, and three loci (BM1443, BM302, and BMS1943) related to lactose percentage. The microsatellite loci selected in this study showed rich polymorphism in the experimental dairy cow population and were related to the lactation traits, which can be used for the evaluation of genetic resources and early breeding and improvement of Holstein dairy cows in Xinjiang.


Compatibility of various materials with oral tissues. I: The components in composite restorations.
The basic ingredients in composite restorative materials include: monomers, polymerization stabilizers, color stabilizers, polymerization initiators, polymerization accelerators, inorganic reinforcing fillers, and coupling agents. Typical members of each category are discussed.


Effectiveness of Montelukast on asthma control in infants: methodology of a French claims data study.
This pilot study, conducted on a 1/97th representative sample of French claims data, prepared a project to assess the effectiveness of Montelukast (MTL-4) as add-on therapy for asthma in infants (6-24 months) compared to inhaled corticosteroids (ICS), based on real-world data. Due to the very recent opening of French claims data for effectiveness research, and the complex structure of this data source, we first tested the feasibility of identifying infants with asthma and outcome criteria, and the ability to perform relevant comparisons. We identified a cohort of infants with uncontrolled asthma and receiving ≥2 consecutive dispensations of any respiratory drug (R03 ATC classification) during a 6-month period. Uncontrolled asthma was identified either from exacerbations or from markers of acute loss of asthma control; date of occurrence of an event (exacerbation and/or acute loss of asthma control) was defined as index date. The study groups comprised infants receiving MTL-4 +/- ICS (MTL-4 group) or ICS without MTL-4 (ICS group) at index date. These two groups were matched on gender, age, quarter of index date, therapy before index date, past asthma-related hospitalization (ever), and were followed for 6 months. The outcome was the rate of infants with uncontrolled asthma, defined as above. This pilot cohort study included 1,149 infants with asthma (mean age 14.1 months, 64% boys). Of these, 51 and 768 were assigned to the MTL-4 and ICS groups, respectively. Uncontrolled asthma occurred in 78.8% and 78.4% of infants in these groups, respectively (oral corticosteroids were dispensed to 49% and 61%, respectively). Assessment of uncontrolled asthma, exposure to MTL-4 and ICS, and occurrence of outcomes were achieved. For the development of matching criteria, we defined a new marker of severity (therapeutic typologies). These data support the feasibility of the final project, to be conducted on claims data from the whole French population. We also showed that, with appropriate methodology and by using valid criteria, French claims data are an adequate resource for conducting comparative effectiveness studies in pediatric asthma. Finally, the algorithm used to identify infants with asthma could be applied to other studies using claims data.


Disorders of nucleotide excision repair.
Deficient repair of ubiquitous errors in the genome risks faulty transcription or replication. Its direct and indirect phenotypic consequences are rare, complex, dementing, lethal disorders of children with inadequately understood overlapping genotypes and variable severity. Mutations of CSA or CSB responsible for impaired transcription-coupled repair cause Cockayne syndrome (CS). Its characteristics are (1) profound growth deficiency affecting all tissues, including the brain, (2) premature aging marked by cachexia, vascular disease, exocrine deficiency, and osteopenia, but not cancer, and (3) a selective degenerative disorder of central and peripheral myelin and by neuronal loss in the retina and inner ear, and in the cerebellum and basal ganglia where it is associated with calcification. Xeroderma pigmentosum (XP) can arise from mutations of at least eight genes involved in global genomic repair. Severe XPA and XPC cause innumerable carcinomas and melanomas in light-exposed eyes and skin, and enhanced risk of visceral cancers. XPA and XPD and others can cause childhood XP neurological disease with widespread neuronal loss, axonal sensorimotor neuropathy, and dwarfing. Four genes, including XPD, can cause trichothiodystrophy (TTD) with sulfur-deficient, brittle, tiger-tail hair, and growth and developmental inadequacy. CSB or XPD can cause the severe congenital cerebro-oculofacioskeletal (COFS) CS-like syndrome with joint contractures, cataracts, and early death. Three XP genes can also cause XP/CS complex. Much more needs to be learned about these and other disorders of DNA repair to enable prevention and treatment.


Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases.
There are 17 crystal structures of nucleoside monophosphate kinases known. As expected for kinases, they show large conformational changes upon binding of substrates. These are concentrated in two chain segments, or domains, of 30 and 38 residues that are involved in binding of the substrates N1TP and N2MP (nucleoside tri- and monophosphates with bases N1 and N2), respectively. After aligning the 17 structures on the main parts of their polypeptide chains, two domains in various conformational states were revealed. These states were caused by bound substrate (or analogues) and by crystal-packing forces, and ranged between a 'closed' conformation and a less well defined 'open' conformation. The structures were visually sorted yielding an approximately evenly spaced series of domain states that outlines the closing motions when the substrates bind. The packing forces in the crystals are weak, leaving the natural domain trajectories essentially intact. Packing is necessary, however, to produce stable intermediates. The ordered experimental structures were then recorded as still pictures of a movie and animated to represent the motions of the molecule during a catalytic cycle. The motions were smoothed out by adding interpolated structures to the observed ones. The resulting movies are available through the World Wide Web (http:@bio5.chemie.uni-freiburg.de/ak movie.html). Given the proliferating number of homologous proteins known to exist in different conformational states, it is becoming possible to outline the motions of chain segments and combine them into a movie, which can then represent protein action much more effectively than static pictures alone are able to do.


[A new classification of pancreatic cancer to guide operative decisions and the comparison with the TNM stage].
Despite the worldwide application of various terminological and classification systems used for pancreatic cancer, such as UICC classification and JPS classification based on the TNM system, however, little information on their use in operative decision-making is available. A new classification system according to the relationship with the tumor and key vasculature around the pancreas is described, and the pancreatic carcinomas are divided into eight types to provide operative decisions for different types of pancreatic cancer. Furthermore, the relationship between the classification system and TNM system is discussed. The new classification is the first time to discuss the classification for the operative decisions for the pancreatic cancer and this formalized type of approach may provide the best chance of achieving R0 resection and providing improved safety results.


Analysis of risk factors for nosocomial sepsis in surgical patients.
This study aimed to identify patients at high risk for developing sepsis following surgery according to criteria determined by the American College of Chest Physicians and the Society of Critical Care Medicine Consensus Conference on sepsis. A prospective case-control study was performed in surgical patients in a tertiary care centre over 1 year. Patients were identified by a daily prospective surveillance. Controls were selected randomly from the daily list of surgical inpatients. Data were collected prospectively. Crude and adjusted odds ratios (ORs) and their 95 per cent confidence intervals were computed using logistic regression analysis. During follow-up, 99 cases and 99 controls were identified. The main risk factors for sepsis found in the multivariate analysis were coma within 48 h before sepsis (OR 13.5, 95 per cent confidence interval 3.6-50.8), low serum albumin level at admission (OR 15.8, 5.4-46.4), two or more intrinsic co-morbidities (OR 11.8, 2.8-49.4) and parenteral nutrition (OR 5.1, 1.5-17.1). Emergency surgery (OR 3.0, 1.4-6.4), abdominal surgery (OR 2.6, 1.0-6.8) and number of surgical interventions (OR 2.5, 1. 1-6.1) were the variables related to surgery that significantly increased the risk of sepsis. Both the study on the Efficacy of Nosocomial Infection Control (SENIC) and the National Nosocomial Infections Surveillance indices showed a statistically significant trend with sepsis. Patient-related factors appear to represent the greatest risk for developing postoperative nosocomial sepsis, rather than factors associated with the surgery.


Misguided good intentions.
A 3-day-old infant unexpectedly developed cardiopulmonary arrest at home. A resuscitation process was initiated and the infant was transported to a nearby community hospital where a highly respected senior pediatrician assumed responsibility for the prolonged resuscitation. Following cessation of aggressive support measures, the infant resumed gasping/respiratory efforts. The pediatrician admitted to occluding the infant's nose and mouth just before death. Several of the important medical issues and ethical distinctions are discussed.


Conformation of actin subunits at the barbed and pointed ends of F-actin with and without capping proteins.
Advances in cryo-electron microscopy have made possible the determination of structures of the barbed and pointed ends of F-actin, both in the absence and the presence of capping proteins that block subunit exchange. The conformation of the two exposed protomers at the barbed end resembles the "flat" conformation of protomers in the middle of F-actin. The barbed end changes little upon binding of CapZ, which in turn undergoes a major conformational change. At the pointed end, however, protomers have the "twisted" conformation characteristic of G-actin, whereas tropomodulin binding forces a flat conformation upon the second subunit. The structures provide a mechanistic understanding for the asymmetric addition/dissociation of actin subunits at the ends of F-actin and open the way to future studies of other regulators of filament end dynamics.


Retrospective blood lead assessment from archived clotted erythrocyte fraction in a cohort of lead-exposed mother-child dyads.
Exposure to lead (Pb) is linked to a host of adverse health effects. Recent revelations of unmonitored exposures to hazardous levels of lead as seen in the Flint Water Crisis have manifested a need for evaluating biological samples, other than regularly prepared whole blood, for biomonitoring of lead exposure. Here, we present a method utilizing clotted erythrocyte fraction samples, which are commonly archived along with serum (or plasma) in biorepositories, to predict whole blood lead levels to allow for retrospective assessments of environmental exposure to lead. Whole blood and clotted erythrocyte fraction samples were collected from 91 participants in the Airborne Exposure to Semivolatile Organic Pollutants (AESOP) cohort study of mother-child dyads. Clotted erythrocyte fraction samples were prepared either using microwave assisted acid digestion or alkaline dilution and subsequently analyzed for lead using Inductively-couple plasma-mass spectrometry (ICP-MS). Simultaneously withdrawn whole blood samples were also analyzed. A strong linear relationship was observed between lead in whole blood and clotted erythrocyte fraction with Pearson correlation coefficients (r) of 0.90, and 0.89 (p < 0.001) for acid digestion and alkaline dilution, respectively. Slopes and intercepts from simple linear regression models of the two clotted erythrocyte fraction methods were not found to be significantly different (p > 0.05) when compared to the standard blood lead assay method. Modeled blood lead predicted from clotted erythrocyte fraction was evaluated at a test threshold of 3 μg/dL was found to have diagnostic sensitivity of 88% and specificity of 100%. Results from this study demonstrate clotted erythrocyte fraction samples are a viable alternative biological sample for retrospective public health surveillance of environmental exposure to lead.


Prediction of HIV-1 protease cleavage site from octapeptide sequence information using selected classifiers and hybrid descriptors.
In most parts of the world, especially in underdeveloped countries, acquired immunodeficiency syndrome (AIDS) still remains a major cause of death, disability, and unfavorable economic outcomes. This has necessitated intensive research to develop effective therapeutic agents for the treatment of human immunodeficiency virus (HIV) infection, which is responsible for AIDS. Peptide cleavage by HIV-1 protease is an essential step in the replication of HIV-1. Thus, correct and timely prediction of the cleavage site of HIV-1 protease can significantly speed up and optimize the drug discovery process of novel HIV-1 protease inhibitors. In this work, we built and compared the performance of selected machine learning models for the prediction of HIV-1 protease cleavage site utilizing a hybrid of octapeptide sequence information comprising bond composition, amino acid binary profile (AABP), and physicochemical properties as numerical descriptors serving as input variables for some selected machine learning algorithms. Our work differs from antecedent studies exploring the same subject in the combination of octapeptide descriptors and method used. Instead of using various subsets of the dataset for training and testing the models, we combined the dataset, applied a 3-way data split, and then used a "stratified" 10-fold cross-validation technique alongside the testing set to evaluate the models. Among the 8 models evaluated in the "stratified" 10-fold CV experiment, logistic regression, multi-layer perceptron classifier, linear discriminant analysis, gradient boosting classifier, Naive Bayes classifier, and decision tree classifier with AUC, F-score, and B. Acc. scores in the ranges of 0.91-0.96, 0.81-0.88, and 80.1-86.4%, respectively, have the closest predictive performance to the state-of-the-art model (AUC 0.96, F-score 0.80 and B. Acc. ~ 80.0%). Whereas, the perceptron classifier and the K-nearest neighbors had statistically lower performance (AUC 0.77-0.82, F-score 0.53-0.69, and B. Acc. 60.0-68.5%) at p < 0.05. On the other hand, logistic regression, and multi-layer perceptron classifier (AUC of 0.97, F-score > 0.89, and B. Acc. > 90.0%) had the best performance on further evaluation on the testing set, though linear discriminant analysis, gradient boosting classifier, and Naive Bayes classifier equally performed well (AUC > 0.94, F-score > 0.87, and B. Acc. > 86.0%). Logistic regression and multi-layer perceptron classifiers have comparable predictive performances to the state-of-the-art model when octapeptide sequence descriptors consisting of AABP, bond composition and standard physicochemical properties are used as input variables. In our future work, we hope to develop a standalone software for HIV-1 protease cleavage site prediction utilizing the linear regression algorithm and the aforementioned octapeptide sequence descriptors.


Cortical modulation of the nucleus of the optic tract in the rabbit.
We analyzed in rabbits the relationships between the temporooccipital nystagmogenic cortex (NGC)--the region sited at the border between cortical areas 17, 21, and 22--and the nucleus of the optic tract (NOT). Two experimental approaches were used: (a) eye movement analysis before and after electrolytic lesion of the NOT region provided an indication of the importance of the NOT for the interaction between the ocular nystagmus elicited by natural optokinetic stimulation (OKN) and the nystagmus evoked by electrical stimulation of the nystagmogenic area; (b) NOT direction-selective and velocity-sensitive units were tested with single shock or repetitive electrical stimulation of the nystagmogenic region. Single-shock stimulation evoked single or multiple spikes in 50% of NOT units analyzed and repetitive stimuli induced prolonged facilitation and inhibitory rebounds in 70% of the units tested. Comparison of orthodromic activation latencies of the NOT cells (3.2 and 6.1 ms) after cortical stimulation and of antidromic activation latencies of cortical nystagmogenic units (2.6 ms) after NOT shocks, suggested monosynaptic as well as polysynaptic connections between the temporooccipital cortex and the NOT. The existence of such cortical-NOT linkage indicates that the NOT is intercalated between the cortex and the oculomotor centers and represents the most probable site of interaction of the cortical nystagmus pathway with the optokinetic reflex arc.


Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma arginine and citrulline levels-a pilot randomized trial.
Deficiencies of citrulline and arginine have been associated with adverse outcomes in preterm-infants and data regarding enteral supplementation in preterm infants is limited. This randomized -trial [NCT03649932] included 42 preterm infants (gestational age ≤33 weeks) randomized to receive enteral L-citrulline in low (100 mg/kg/day), medium (200 mg/kg/day) and high-dose (300 mg/kg/day) groups for 7 days. Plasma citrulline and arginine levels were obtained pre-and-post supplementation and efficacy was determined by a significant increase in levels after supplementation. A p < 0.05 was considered significant. Safety monitoring included blood-pressure-monitoring as well as complications and death during hospitalization. A total of 40/42 (95%) of the recruits completed the 7-day supplementation with no adverse events. Plasma-citrulline levels increased significantly in all three groups while plasma-arginine levels increased significantly in the high-dose group. Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma citrulline and arginine levels. NCT03649932 https://clinicaltrials.gov/ct2/show/NCT03649932 .


The role of task demands in racial face encoding.
People more accurately remember faces of their own racial group compared to faces of other racial groups; this phenomenon is called the other-race effect. To date, numerous researchers have devoted themselves to exploring the reasons for this other-race effect, and they have posited several theoretical explanations. One integrated explanation is the categorization-individuation model, which addresses two primary ways (categorization and individuation) of racial face processing and emphasizes the emergence of these two ways during the encoding stage. Learning-recognition and racial categorization tasks are two classical tasks used to explore racial face processing. Event-related potentials can facilitate investigation of the encoding differences of own- and other-race faces under these two typical task demands. Unfortunately, to date, results have been mixed. In the current study, we investigated whether categorization and individuation differ for own- and other-race faces during the encoding stage by using racial categorization and learning-recognition tasks. We found that task demands not only influence the encoding of racial faces, but also have a more profound effect in the encoding stage of recognition tasks for other-race faces. More specifically, own-race faces demonstrate deeper structural encoding than other-race faces, with less attentional involvement. Moreover, recognitions tasks might ask for more individual-level encoding, requiring more attentional resources in the early stage that may be maintained until relatively late stages. Our results provide some evidence concerning task selection for future racial face studies and establish a groundwork for a unified interpretation of racial face encoding.


Communicating exophthalmos: a sign of bilateral orbital roof defects.
The term communicating exophthalmos is suggested for a condition where manual retropulsion of one eye results in proptosis of the other eye. This sign was observed in a patient with bilateral pulsating exophthalmos. The pulsating exophthalmos was ascribed to orbital roof defects in combination with post-traumatic hydrocephalus. It was controlled by a shunting procedure.


Surface electromyogram and muscle ultrasonography for detection of muscle fasciculations in pediatric peripheral neuropathy.
A 12-year-old girl presented with talipes equinus of both legs, attenuation of upper and lower limb tendon reflexes, thermal hyperalgesia, and reduction of vibratory sensation. On clinical examination, muscle twitches of fingers of both hands, as well as the abductor halluces and the dorsal interossei muscles of the right foot were observed. Nerve conduction velocity was significantly declined in the upper and lower extremities. Needle electromyography (EMG) was not performed; however, ultrasonography revealed repetitive, semi-regular muscle twitches lasting 0.2-0.4s, concomitant with muscle discharges on surface EMG in the right foot muscles. These findings were compatible with contraction fasciculation in muscles under chronic reinnervation. Nerve and muscle biopsies were suggestive of chronic motor, sensory, and autonomic neuropathy. This is the first case of pediatric peripheral neuropathy where muscle fasciculation was noninvasively identified by simultaneous surface EMG and ultrasonography.


MiRNAs as molecular biomarkers in stage II egyptian colorectal cancer patients.
To assess the role of aberrant miRNAs expressions in stage II CRC patients from Egypt. Tumor tissue samples were obtained from 124 CRC stage II patients compared to 100 healthy controls for assessing miRNAs expression using; 1) a cataloged 84-miRNAs PCR array panel, and 2) another five miRNAs (miR-21, miR-137, miR-145, miR-320 and miR-498) that have been reported in previous studies to have a role in CRC, by quantitative real time PCR (qPCR). The results were correlated to patients' characteristics, response to treatment and survival. There were 17 out of 84 miRNAs differentially expressed in the CRC patients. Twenty six miRNAs were significantly differentially expressed in the female CRC patients, while 16 miRNAs were significantly differentially expressed in the male CRC patients. Only, five miRNAs (miR-21, Let-7a-5p, miR-100-5p, miR-200c-3p and miR-23b-3p) were significantly common deregulated in CRC patients regardless gender. miR-21 was overexpressed in 48.4% of the patients and it was significantly downregulated in females and over expressed in males. In univariate analysis; performance status, over-expression of miR-21 and miR-498 and reduced miR-137, miR-145, and miR-320 associated significantly with reduced DFS and OS whereas in multivariate analysis; miR-498 and miR-320 were independent prognostic factors for DFS and miR-21 was independent prognostic factors for OS. miRNAs expression differs significantly between male and female stage II CRC patients, miR-21, Let-7a-5p, miR-100-5p, miR-200c-3p and miR-23b-3p could be used as common diagnostic biomarkers for CRC. On the other hand, a three miRNAs panel (miR-21, miR-498 and miR-320) can predict recurrence and survival in those patients.


Health-promotion behaviors and psychological distress in cancer survivors.
To determine whether cancer survivors engage in health-promotion behaviors, to evaluate the extent of their experience of psychological distress, and to investigate the relationship between the practice of health-promotion behaviors and psychological distress. Cross-sectional secondary data analysis. A national, face-to-face interview conducted by personnel of the U.S. Census Bureau using a random sampling of American adults. 1,784 survey respondents who reported a previous cancer diagnosis. Data from the 2009 National Health Interview Survey were used to examine the prevalence of smoking, physical inactivity, alcohol use, and reports of psychosocial distress. Interviews pertained to the amount and distribution of illness, its effects in terms of disability and chronic impairments, and the kinds of health services people receive. Age, current smoking prevalence, alcohol consumption, physical activity, and the experience of feeling hopelessness, sadness, and anxiety. Cancer survivors continue to smoke at a rate similar to the national average. Overall, most respondents reported no symptoms of psychological distress. However, age appears to play a major role, showing significant differences in the prevalence of current smoking, participation in physical activity, alcohol use, and reported level of distress. This study provides estimates of the prevalence of health-promotion behaviors and experience of psychological distress among American cancer survivors. The results reveal opportunities for interventions among cancer survivors. Nurses should be proactive in providing guidance to survivors regarding the adoption of healthy lifestyle behaviors. Those who encounter younger cancer survivors need to be alert to the higher potential for distress in that population, perform appropriate screenings, and be prepared to offer guidance, supportive care, and referrals for psychological care if needed.


Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma.
Circulating nucleic acids have been shown to have potential as non-invasive diagnostic markers in cancer. We therefore investigated whether microRNAs also have diagnostic utility by comparing levels of tumour-associated MIRN155 (miR-155), MIRN210 (miR-210) and MIRN21 (miR-21) in serum from diffuse large B-cell lymphoma (DLBCL) patients (n = 60) with healthy controls (n = 43). Levels were higher in patient than control sera (P = 0.009, 0.02 and 0.04 respectively). Moreover, high MIRN21 expression was associated with relapse-free survival (P = 0.05). This is the first description of circulating microRNAs and suggests that microRNAs have potential as non-invasive diagnostic markers for DLBCL and possibly other cancers.


Revision of the structure assigned to the antibiotic BU-4664L from Micromonopora.
The structure assigned to the antitumor antibiotic BU-4664L from Micromonospora sp. was revised to 5,10-dihydro-4,6,8-trihydroxy-10-(3,7,11-trimethyl-trans-2,trans-6,10-dodecatrienyl)-11H-dibenzo[b,e] [1,4]-diazepin-11-one based on the NMR analysis.


Understanding the biology and advent of physics of cancer with perspicacity in current treatment therapy.
Cancer has become a key healthcare problem worldwide. The background of cancer research has brought the advent of cross-disciplinary collaborations that has enabled us to get an idea of the disease mechanisms at spatial and temporal scales. Understanding the combination of biology and physics of cancer presents a promising field of research with apprehensions in better clarity over both cellular and molecular mechanisms impacting cancer therapy. Investigation of cancer biology has provided a wealth of knowledge on cancer initiation and propagation and has provided newer treatment strategies in the fight against cancer. Understanding the physics of cancer provides wonderful set of equations that take advantage of mechanisms of force production, propagation by the cancer cells and mechanical properties of the tumor tissue. The spatial tissue arrangement in which the tumor growth occurs can be better understood with biophysics. Thus, the combination of biology and physics of cancer contributes crucially in impacting the correct treatment of cancer. The present review is aimed at providing an overview of regulatory networks, regulation of cell division and differentiation, the signal transduction pathways and integration of all sciences including physics, biology, and medicine which is very well needed to tackle the war against cancer and thus influence cancer therapy. These circuits will help us understand whether the therapy will work wonders or cause failure. As cancer is much more than a genetic disease, more insights into the malignancy with physical approaches are designed to use cancer therapy effectively.


Non-coding RNAs in marine Synechococcus and their regulation under environmentally relevant stress conditions.
Regulatory small RNAs (sRNAs) have crucial roles in the adaptive responses of bacteria to changes in the environment. Thus far, potential regulatory RNAs have been studied mainly in marine picocyanobacteria in genetically intractable Prochlorococcus, rendering their molecular analysis difficult. Synechococcus sp. WH7803 is a model cyanobacterium, representative of the picocyanobacteria from the mesotrophic areas of the ocean. Similar to the closely related Prochlorococcus it possesses a relatively streamlined genome and a small number of genes, but is genetically tractable. Here, a comparative genome analysis was performed for this and four additional marine Synechococcus to identify the suite of possible sRNAs and other RNA elements. Based on the prediction and on complementary microarray profiling, we have identified several known as well as 32 novel sRNAs. Some sRNAs overlap adjacent coding regions, for instance for the central photosynthetic gene psbA. Several of these novel sRNAs responded specifically to environmentally relevant stress conditions. Among them are six sRNAs changing their accumulation level under cold stress, six responding to high light and two to iron limitation. Target predictions suggested genes encoding components of the light-harvesting apparatus as targets of sRNAs originating from genomic islands and that one of the iron-regulated sRNAs might be a functional homolog of RyhB. These data suggest that marine Synechococcus mount adaptive responses to these different stresses involving regulatory sRNAs.


Quantitative analysis of cathepsin L mRNA and protein expression during oral cancer progression.
Although an important risk factor for oral cancer is the presence of epithelial dysplasia, most of these lesions will not progress to malignancy. Presently, for the individual patient with dysplasia, there are few reliable markers that may indicate the likelihood of progression to oral cancer. Cathepsin L is a lysosomal protease that degrades extracellular matrix material. Because cathepsin L is frequently overexpressed in oral squamous cell carcinoma (SCC) we hypothesized that it is also overexpressed in oral premalignancy and that premalignant lesions that progressed to oral cancer expressed higher levels of cathepsin L than those premalignant lesions that did not. In this retrospective pilot study we examined changes in cathepsin L expression at the mRNA level using quantitative TaqMan RT-PCR and at the protein level by immunohistochemistry in 33 routinely processed oral dysplastic lesions and 14 SCCs obtained from 33 patients. Sixteen of the dysplastic lesions progressed to oral SCC and 17 did not after several years of follow-up. Cathepsin L mRNA was overexpressed in 16/33 (48%) dysplastic lesions and in 9/14 (64%) oral SCC. Cathepsin L protein was also overexpressed in a large proportion of dysplasias and cancers. Overexpression was independent of dysplasia grade and identified in both those patients who progressed to oral SCC and in those who did not. Levels of cathepsin L mRNA and protein did not differ significantly in the progressing versus non-progressing dysplasias (P=0.27). However, cathepsin L mRNA and protein were significantly lower in the non-progressing dysplasias when compared to the oral cancers (P=0.03) but not in the progressing dysplasias suggesting a trend for dysplasias with overexpressed cathepsin L to be more likely to progress to oral cancer.


Mimicking normal tissue architecture and perturbation in cancer with engineered micro-epidermis.
Correct tissue architecture is essential for normal physiology, yet there have been few attempts to recreate tissues using micro-patterning. We have used polymer brush micro-engineering to generate a stratified micro-epidermis with fewer than 10 human keratinocytes. Epidermal stem cells are captured on 100 μm diameter circular collagen-coated disks. Within 24 h they assemble a stratified micro-tissue, in which differentiated cells have a central suprabasal location. For rings with a non-adhesive centre of up to 40 μm diameter, cell-cell and cell-matrix adhesive interactions together result in correct micro-epidermis assembly. Assembly requires actin polymerization, adherens junctions and desmosomes, but not myosin II-mediated contractility nor coordinated cell movement. Squamous cell carcinoma cells on micro-patterned rings exhibit disturbed architecture that correlates with the characteristics of the original tumours. The micro-epidermis we have generated provides a new platform for screening drugs that modulate tissue assembly, quantifying tissue stratification and investigating the properties of tumour cells.


Analyzing Spatial Transcriptomics Data Using Giotto.
Spatial transcriptomic technologies have been developed rapidly in recent years. The addition of spatial context to expression data holds the potential to revolutionize many fields in biology. However, the lack of computational tools remains a bottleneck that is preventing the broader utilization of these technologies. Recently, we have developed Giotto as a comprehensive, generally applicable, and user-friendly toolbox for spatial transcriptomic data analysis and visualization. Giotto implements a rich set of algorithms to enable robust spatial data analysis. To help users get familiar with the Giotto environment and apply it effectively in analyzing new datasets, we will describe the detailed protocols for applying Giotto without any advanced programming skills. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Getting Giotto set up for use Basic Protocol 2: Pre-processing Basic Protocol 3: Clustering and cell-type identification Basic Protocol 4: Cell-type enrichment and deconvolution analyses Basic Protocol 5: Spatial structure analysis tools Basic Protocol 6: Spatial domain detection by using a hidden Markov random field model Support Protocol 1: Spatial proximity-associated cell-cell interactions Support Protocol 2: Assembly of a registered 3D Giotto object from 2D slices.


Health and Social Care (Community Health and Standards) Bill.
A Bill going through Parliament will allow yet more people access to patients' medical records: the following are the relevant sections.


Auditory Discrimination of Natural and High-Pass Filtered Bark Vocalizations in a California Sea Lion (Zalophus californianus).
A California sea lion performed a psychophysical auditory discrimination task with a set of six stimuli: three barks recorded from conspecific males and high-pass filtered versions of the barks that removed the majority of energy at fundamental frequencies. Discrimination performance and subject reaction times (RTs) suggested that the vocalizations were all perceived as fairly dissimilar. This preliminary study hints that low-frequency components are a salient part of the California sea lion bark despite elevation of this species' aerial hearing thresholds and the potential for elevated environmental noise levels at frequencies below 1 kHz.


Lack of correlation between mdr-1 expression and volume-activation of cloride-currents in rat colon cancer cells.
Correlation between expression of the mdr-1 genes (a and b) at the mRNA and protein level and volume-activation of chloride-channels was studied in rat colon cancer CC531 cells by means of RT-PCR, Western blotting and patch clamp, respectively. Three different kinds of cell lines were used: CC531-PAR, CC531-COL and CC531-REV. At the mRNA level, the parental cell line CC531-PAR showed significantly less mdr-1a expression in comparison with CC531-COL, a drug-resistant cell line induced from the parental CC531 cells by growth in the presence of colchicin. The third cell line, CC531-REV, was a spontaneous revertant of the drug-resistant cell line to a drug-sensitive one, but with a maintained level of mdr-1a mRNA. In none of the three cell lines, mdr-1b mRNA could be detected. At the protein level, a clear difference in mdr1 expression between CC531-PAR/REV and CC531-COL was observed. Although the amount of mdr-1a mRNA detected in CC531-REV was comparable to that found in CC531-COL, the amount of mdr-1 encoded protein in CC531-REV was remarkably reduced. In all three cell types, cell swelling activated chloride-currents which could be blocked by NPPB.(ABSTRACT TRUNCATED AT 250 WORDS)


Herpes simplex virus type 2 myelitis mimicking ICU-acquired weakness as a complication of meningococcal meningitis: A case report.
Herpes simplex virus 2 (HSV-2) is a well-known cause of neurological complications. This case study describes the first reported case of reactivated HSV-2 myelitis, which was induced by immunosuppression due to sepsis. During the treatment of meningococcal meningitis, the patient developed quadriparesis and was later diagnosed as HSV-2 myelitis, mimicking ICU-acquired weakness. The case emphasizes the importance of excluding viral myelitis before making the diagnosis of ICU-acquired weakness.


Effects of misalignment during corneal topography.
To evaluate consequences of misalignment during corneal topography. Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada. Twenty-nine healthy subjects were enrolled in a study of 2 types of misalignment during Orbscan topography acquisition. The first was rotation, which was defined as angular deviation of the subject's visual axis away from the central fixation target, and the second was translation, defined as off-center displacement of the joined half slits on the computer screen during alignment by the technician. The effect of vertical and horizontal misalignments, by rotation or translation, was assessed. Study parameters included simulated keratometries (SimKs), mean corneal power (mean power), and corneal apex (R) and the asphericity factor (Q) values. Inferior-superior (I-S) and temporal-nasal (T-N) indices were calculated. Differences in parameter values between aligned and misaligned positions were studied. A mathematical model was also developed to simulate rotational and translational misalignment and consolidate clinical experimentation. The mean SimK values were slightly but significantly affected by rotation. The I-S value increased significantly with downward rotation and decreased with upward rotation of the eye, while T-N values increased significantly with temporal rotation and decreased with nasal rotation. The R and Q values increased with rotation. Overall, the topography parameters were minimally affected by translation. Comparable results were obtained with the theoretical model. Rotational misalignment of the eye during acquisition influenced topography more than the translational misalignment during focusing by the technician. Rotational misalignment induced corneal asymmetry on elevation and curvature maps as well as pseudokeratoconus patterns.


Grafting of neural stem and progenitor cells to the hippocampus of young, irradiated mice causes gliosis and disrupts the granule cell layer.
Ionizing radiation persistently reduces the pool of neural stem and progenitor cells (NSPCs) in the dentate gyrus (DG) of the hippocampus, which may explain some of the learning deficits observed in patients treated with radiotherapy, particularly pediatric patients. A single dose of 8 Gy irradiation (IR) was administered to the brains of postnatal day 14 (P14) C57BL/6 mice and 1.0 × 10(5) bromodeoxyuridine-labeled, syngeneic NSPCs were injected into the hippocampus 1 day, 1 week or 6 weeks after IR. Cell survival and phenotype were evaluated 5 weeks after grafting. When grafted 1 day post-IR, survival and neuronal differentiation of the transplanted NSPCs were lower in irradiated brains, whereas the survival and cell fate of grafted cells were not significantly different between irradiated and control brains when transplantation was performed 1 or 6 weeks after IR. A young recipient brain favored neuronal development of grafted cells, whereas the older recipient brains displayed an increasing number of cells developing into astrocytes or unidentified cells. Injection of NSPCs, but not vehicle, induced astrogliosis and reduced thickness of the dorsal blade of the GCL after 5 months. In summary, we demonstrate that age and interval between IR and grafting can affect survival and differentiation of grafted NSPCs. The observed long-term gliosis and degeneration warrant caution in the context of NSPC grafting for therapeutical purposes.


Vibrational study of the metal-adsorbate interaction of phenylacetic acid and alpha-phenylglycine on silver surfaces.
Raman and SERS spectra of phenylacetic acid and alpha-phenylglycine on silver sols have been recorded at several concentrations and pH values. The alpha-phenylglycine has been also studied in D(2)O. The respective vibrational assignments have been proposed and the analysis of the SERS spectra has made it possible to conclude that phenylacetic acid links to the metal through its carboxylate group only, while alpha-phenylglycine links also through its amino group. In both cases the aromatic ring seems to be almost perpendicular to the metal surface. On the other hand, the contribution of the charge transfer (CT) mechanism to the enhancement of the SERS spectra has been calculated as well and it is found to be very important in both molecules. The band most enhanced by this mechanism is that of vibration 8a, mainly in alpha-phenylglycine.


Opiate participation in thyroid hormone regulation in domestic fowl.
Administration of morphine sulfate (at 5 and 50 mg/kg) to immature domestic fowl lowered the circulating thyroxine (T4) concentration in a dose- and time-dependent manner. The inhibitory effect of morphine on T4 secretion was mediated via opiate receptors, since it was completely blocked in the presence of naloxone (50 mg/kg). The possibility that T4 secretion may be under tonic opioid inhibition was suggested by a stimulatory effect of naloxone on plasma T4 concentrations. Morphine sulfate (50 mg/kg) enhanced plasma triiodothyronine concentrations, an effect that was completely suppressed in the presence of naloxone. These results demonstrate differential effects of opiates on T4 and T3 concentrations and suggest that opiates tonically inhibit T4 release and accelerate its rate of peripheral monodeiodination.


Anomalously high aggregation level of the polyene antibiotic amphotericin B in acidic medium: implications for the biological action.
Amphotericin B (AmB) is a polyene antibiotic used to treat deep-seated mycoses. Both the therapeutic action and the toxic side effects of this drug are dependent on its molecular organization. AmB appears as a zwitterion at neutral pH owing to NH(3)(+) and COO(-) groups. The results obtained with electronic absorption, fluorescence, resonance light scattering and infrared absorption spectroscopic analyses show that in the aqueous medium at pH above 10 AmB appears in the monomeric form owing to the negative net electric charge of the molecule. On the contrary, anomalously high aggregation level has been observed at pH below 2, despite the positive net electric charge. The effect is interpreted in terms of the permanent polarization of the polyene chain at low pH, associated with relative rotational freedom of the charged mycosamine fragment of the molecule. The pH-dependent aggregation of AmB is discussed in aspect of pharmacological action of the drug.


Subclinical articular involvement in primary Sjögren's syndrome assessed by ultrasonography and its negative association with anti-centromere antibody.
To evaluate the subclinical articular involvement in patients with primary Sjögren's syndrome (pSS) using musculoskeletal ultrasound (MSUS), and to correlate the findings with laboratory results and clinical manifestations. Forty-eight consecutive patients with pSS were enrolled. The bilateral metacarpophalangeal, proximal interphalangeal, and interphalangeal joints were examined using MSUS, and the synovial hypertrophy and power Doppler signal were recorded for each joint using semi-quantitative scores (0 = normal, 1 = mild change compared with undamaged joint, 2 = moderate change, and 3 = severe change). Mild or moderate synovial hypertrophy was found in 151 (15.7%) and 2 (0.2%) out of 960 hand joints, respectively, and power Doppler signals were present in 19 (2.0%) of the 960 joints. While anti-centromere antibody (ACA) was found in 10 patients (20.8%), none of the patients with MSUS-confirmed synovitis was positive for ACA. No other autoantibodies, laboratory tests, or clinical manifestations correlated with MSUS-confirmed synovitis. MSUS is useful for detecting subclinical synovitis in pSS patients. MSUS showed that ACA-positive pSS patients had a low prevalence of synovitis.


A single-cloning-step procedure for the generation of RNAi plasmids producing long stem-loop RNA.
RNA interference (RNAi), used as a tool, has revolutionized the studies of gene function. Long stem-loop dsRNA has been proven the most effective trigger for down-regulating target transcripts in RNAi-positive trypanosomatid parasites. Here we describe a protocol for constructing plasmids that produce long stem-loops by using a single cloning step. Inverted repeats are first obtained by self-ligation of PCR products that contain a randomized segment at one of their ends and then inserted in a plasmid vector. The random sequences create the loop (or "stuffer") of the hairpin. This methodology was tested in Leishmania (Viannia) braziliensis to constitutively knock down the mRNAs for the well-studied paraflagellar rod protein 1 and 2 (PFR1 and PFR2) genes and revealed that mRNA cleavage products are unusually stable in these parasites. The protocol is suitable for any plasmid (for constitutive or inducible expression) and for any organism in which long stem-loops can be used to elicit RNAi.


Nanobody-peptide-conjugate (NPC) for passive immunotherapy against SARS-CoV-2 variants of concern (VoC): a prospective pan-coronavirus therapeutics.
The COVID-19 crisis, incited by the zoonotic SARS-CoV-2 virus, has quickly escalated into a catastrophic public health issue and a grave threat to humankind owing to the advent of mutant viruses. Multiple pharmaceutical therapies or biologics envision stopping the virus from spreading further; however, WHO has voiced concerns about the variants of concern (VoCs) inability to respond. Nanobodies are a new class of antibody mimics with binding affinity and specificity similar to classical mAbs, as well as the privileges of a small molecular weight, ease of entry into solid tissues, and binding cryptic epitopes of the antigen. Herein, we investigated multiple putative anti-SARS-CoV-2 nanobodies targeting the Receptor binding domain of the WHO-listed SARS-CoV-2 variants of concern using a comprehensive computational immunoinformatics methodology. With affinity maturation via alanine scanning mutagenesis, we remodeled an ultrapotent nanobody with substantial breadth and potency, exhibiting pico-molar binding affinities against all the VoCs. An antiviral peptide with specificity for ACE-2 receptors was affixed to make it multispecific and discourage viral entry. Collectively, we constructed a broad-spectrum therapeutic biparatopic nanobody-peptide conjugate (NPC) extending coverage to SARS-CoV-2 VoCs RBDs. We PEGylated the biparatopic construct with 20kD maleimide-terminated PEG (MAL-(PEG)n-OMe) to improve its clinical efficacy limiting rapid renal clearance, and performed in silico cloning to facilitate future experimental studies. Our findings suggest that combining biparatopic nanobody conjugate with standard treatment may be a promising bivariate tool for combating viral entry during COVID-19 illness.


Influence of academic stress and season on 24-hour mean concentrations of ACTH, cortisol, and beta-endorphin.
We investigated the influence of a common stressful event, i.e., academic examinations, on the 24-h mean concentration of adrenocorticotropic hormone (ACTH), cortisol, and/or beta-endorphin. In addition, we evaluated the effect of season on the endocrine response to this stressor. We studied medical students (n = 55), screened for a variety of health and life style factors, from three consecutive medical school classes 1 month before, during, and 2 weeks following examinations. Hourly blood samples were obtained from an indwelling catheter and two serum pools were made (0800-2200h = day and 2300-0700h = night). Examinations produced a significant (p < .001) increase in perceived stress scores. In addition, we found a significant (p < .001) effect of examination stress on the increase in mean daytime but not nocturnal ACTH levels during autumn, but not during the spring. In contrast, the examination stress did not significantly affect day or night mean cortisol levels from baseline to examination week. We further divided the students by whether their perceived stress scores increased during examination week and fell during recovery (Group 1) or whether their perceived stress scores did not follow the expected pattern (Group 2). We found that in the Group 1 students who perceived the most stress, cortisol levels significantly increased (p < .001) from baseline to examination. Therefore, the nature of the stressor and the state of the responder were of equal importance in the observed cortisol response during examinations among these students. Further, academic stress had no significant effect on beta-endorphin levels. Finally, we found that the mean day and night ACTH levels were higher (p < .001) in the spring than in the fall; a seasonal influence on cortisol and beta-endorphin concentrations, however, was not observed. In summary, we have demonstrated that stress associated with the taking of examinations produces a dissociation among mean 24-h levels of ACTH, cortisol, and beta-endorphin. In addition, daytime cortisol levels increased during examinations only in the group of students whose perceived stress scores increased. Further, a seasonal influence on ACTH secretion was suggested by these results with higher levels observed in the spring than in the fall.


Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival.
To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. Analysis of new data from a previously published prospective investigation. Electrophysiology laboratory of a major referral hospital. 43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular arrhythmias.


Intradermal skin test with mRNA vaccines as a surrogate marker of T cell immunity in immunocompromised patients.
Intradermal skin test (IDT) with mRNA vaccines may represent a simple, reliable, and affordable tool to measure T cell response in immunocompromised patients who failed to mount serological responses following vaccination with mRNA covid-19 vaccines. We compared anti-SARS-CoV-2 antibodies and cellular responses in vaccinated immunocompromised patients (n = 58), healthy seronegative naive controls (NC, n = 8), and healthy seropositive vaccinated controls (VC, n = 32) by Luminex, spike-induced IFN-γ Elispot and an IDT. A skin biopsy 24 h after IDT and single-cell RNAseq was performed in three vaccinated volunteers. Twenty-five percent of seronegative NC had a positive Elispot (2/8) and IDT (1/4), compared to 95% (20/21) and 93% (28/30) in seropositive VC, respectively. Single-cell RNAseq data in the skin of VC showed a predominant mixed population of effector helper and cytotoxic T cells. The TCR repertoire revealed 18/1064 clonotypes with known specificities against SARS-CoV-2, among which six were spike-specific. Seronegative immunocompromised patients with positive Elispot and IDT were in 83% (5/6) treated with B cell-depleting reagents, while those with negative IDT were all transplant recipients. Our results indicate that delayed local reaction to IDT reflects vaccine-induced T-cell immunity opening new perspectives to monitor seronegative patients and elderly populations with waning immunity.


Brain and spinal cord affected by amyotrophic lateral sclerosis induce differential growth factors expression in rat mesenchymal and neural stem cells.
Stem cell research raises hopes for incurable neurodegenerative diseases. In amyotrophic lateral sclerosis (ALS), affecting the motoneurones of the central nervous system (CNS), stem cell-based therapy aims to replace dying host motoneurones by transplantation of cells in disease-affected regions. Moreover, transplanted stem cells can serve as a source of trophic factors providing neuroprotection, slowing down neuronal degeneration and disease progression. To determine the profile of seven trophic factors expressed by mesenchymal stem cells (MSC) and neural stem cells (NSC) upon stimulation with CNS protein extracts from SOD1-linked ALS rat model. Culture of rat MSC, NSC and fibroblasts were incubated with brain and spinal cord extracts from SOD1(G93A) transgenic rats and mRNA expression of seven growth factors was measured by quantitative PCR. MSC, NSC and fibroblasts exhibited different expression patterns. Nerve growth factor and brain-derived neurotropic factor were significantly upregulated in both NSC and MSC cultures upon stimulation with SOD1(G93A) CNS extracts. Fibroblast growth factor 2, insulin-like growth factor and glial-derived neurotropic factor were upregulated in NSC, while the same factors were downregulated in MSC. Vascular endothelial growth factor A upregulation was restricted to MSC and fibroblasts. Surprisingly, SOD1(G93A) spinal cord, but not the brain extract, upregulated brain-derived neurotropic factor in MSC and glial-derived neurotropic factor in NSC. These results suggest that inherent characteristics of different stem cell populations define their healing potential and raise the concept of ALS environment in stem cell transplantation.


A computer system for neurosurgical patient monitoring.
The variables monitored in intensive care units are generally late indicators of neurologic deterioration. A system based on a LINC-8 computer was therefore developed for on-line monitoring of evoked potentials, electroencephalography (EEG), and transcranial and transthoracic impedances as well as conventional parameters. Somatosensory evoked potentials are recorded at either 30 min or 1 h intervals. One minute epochs of EEG are analyzed every 10 min using a peak-detection algorithm. Impedances and conventional parameters are also monitored at 10 min intervals. In a study of 50 patients, the technical feasibility of this type of monitoring with a small laboratory computer has been demonstrated. In some instances, evoked potentials and EEG show changes prior to detectable neurologic changes. The study suggests that this type of monitoring can provide a valuable adjunct for evaluation of physiologic function in neurosurgical intensive care.


Hematopoietic growth factors (BPA and Epo) induce the expressions of c-myc and c-fos proto-oncogenes in normal human erythroid progenitors.
We investigated serial expressions of eight proto-oncogenes during in-vitro differentiation of normal human burst-forming unit, erythroid (BFU-E), and found that c-myc and c-fos are expressed in progenies of BFU-E. The expressions of the two proto-oncogenes correlated to the replating efficiency and adversely to erythroid differentiation. The absence of hematopoietic growth factors decreased the expressions, but the addition of erythropoietin together with burst promoting activity induced a re-expression of the c-myc and c-fos after 2 h of incubation. These observations suggest that the c-myc and c-fos proto-oncogenes have a physiological role in the proliferation of erythroid progenitors and that activations of the two proto-oncogenes are early cellular events after the stimulation by hematopoietic growth factors.


A "Congenitally Adapted" TFCC Tear in Radial Longitudinal Deficiency: Case Report and Review of Literature.
We present a case of chronic wrist pain in a 14-year-old child with mild radial longitudinal deficiency and radiographic carpal collapse due to the absence of the scaphoid. Wrist arthroscopy demonstrated synovitis and a tear to the TFCC, which would be called "degenerative," according to the Palmer classification. This was debrided, and the patient is still asymptomatic at long-term follow-up. Review of the literature found one paper with a similar observation in a 17-year-old adolescent. We propose that paediatric "degenerative" tears ought to be called "congenitally adapted" tears.


Cognitive decline in late-life schizophrenia: a longitudinal study of geriatric chronically hospitalized patients.
Geriatric schizophrenic patients with a chronic course of institutionalization manifest cognitive and functional impairments that implicate decline at some time point after the onset of illness. The rate of change in cognitive and functional status in these patients has not yet been identified with a longitudinal study. Three hundred and twenty-six schizophrenic patients entered a 30-month follow-up study with two separate assessments of the patients. Overall functional and cognitive status was indexed with the Clinical Dementia Rating (CDR). Survival analysis was used to examine changes in cognitive and functional status, including worsening for the less impaired patients and improvements on the part of more impaired patients. Approximately 30% of the patients who had baseline scores in the less impaired range manifested a worsening of their CDR ratings to a score of 2.0 (moderate) or more severe, whereas only 7% of the sample with lower scores at baseline appeared to improve in their functioning. Several characteristics of the patients at baseline assessment predicted increased risk for cognitive and functional decline, including lower levels of education, older age, and more severe positive symptoms. Cognitive and functional decline can be detected in a short-term follow-up in a subset of geriatric long-stay patients with schizophrenia. This decline appears distributed across patients and not due to the presence of progressive degenerative dementing conditions. Later research will have to identify the causes of this decline, possibly on the basis of the risk factors identified in this study.


Cultivation of Borrelia burgdorferi from the blood of two patients with erythema migrans lesions lacking extracutaneous signs and symptoms of Lyme disease.
We recently demonstrated that cultivation of Borrelia burgdorferi from skin biopsy specimens obtained from erythema migrans lesions was an efficacious procedure to confirm the diagnosis of Lyme disease. Our purpose was to investigate the efficacy of our microbiologic technique on blood samples obtained from patients with Lyme disease and erythema migrans. Whole blood samples were obtained from 52 patients with erythema migrans and early localized or early disseminated Lyme disease and placed into polystyrene tubes containing 6 ml of modified Barbour-Stoenner-Kelly medium, processed, and examined for B. burgdorferi by dark-field microscopy. B. burgdorferi was cultured from the blood of two of our 52 patients (4%). Clinically, both of these patients were considered to have early localized Lyme disease. The culture of B. burgdorferi from the blood of patients with early Lyme disease does not appear to be an efficacious procedure to confirm the diagnosis of Lyme disease. However, the demonstration of spirochetemia in patients with erythema migrans without any extracutaneous evidence of disseminated illness does have therapeutic significance.