Households' access to an improved latrine and its associated factors among households of sanitation marketing products users and non-users, Northeast Amhara, Ethiopia.
Sanitation marketing is an approach to increase access to the improved latrine on a large scale which helps households to promote proper utilization of sanitary facilities. It helps to close the huge sanitation access gap in developing countries like Ethiopia. This study aimed to assess households' access to an improved latrine and its associated factors among sanitation marketing product users and non-users in Dessie Zuria District, Northeast Amhara, Ethiopia. A community-based comparative cross-sectional study was conducted among 640 households, in 2021. Multi-stage sampling techniques and a structured questionnaire were used. Data were checked, coded, and entered into Epi-info version 7 and exported to Statistical Package for Social Sciences version 23.0 for analysis. Binary logistic regression was employed to determine factors associated with improved latrine access. The study revealed that overall 59.8% of the households had access to improved latrines. Of this, 75.2% (95% Confidence Interval (CI): 70, 80) of households were Sanitation marketing products users; and 44.2% (95% CI: 39, 50) of households were from non-users of Sanitation marketing products. Being female household head, Adjusted Odds Ratio (AOR = 4.3, 95% CI: 1.69, 10.59); urban residence, AOR = 2.5, 95% CI: 1.23, 5.19; water access, AOR = 3.3, 95% CI: 1.63, 6.57 were significantly associated with access to the improved latrine in sanitation marketing products users households, while being a female household head, AOR = 7.3, 95% CI: 3.68, 14.39; urban residence, AOR = 2.8, 95% CI: 1.64, 4.77; water access, AOR = 2.4, 95% CI: 1.44, 4.10 were significantly associated with access to the improved latrine in non-user households of sanitation marketing products. Access to improved latrines is still a big problem in both households of sanitation marketing product users and sanitation marketing product non-users. Gender, residence, water access, supportive supervision, knowledge, and availability of sanitation hardware stores were found to be significant predictors of household access to an improved latrine. Hence, evaluating policies and strategies of sanitation marketing approach on improved sanitation facilities is recommended.


Effects of context and state of guilt on the detection of concealed crime information.
The effects of the state of guilt and the context in which critical information was received on the accuracy of the Concealed Information Test (CIT) were examined in a between-subjects mock crime experiment. 100 participants were randomly assigned to four experimental conditions and one control condition. The experimental conditions were created using a 2 x 2 factorial design (two conditions of the context in which the crime-related details were collected - crime context or neutral context, crossed with two guilt conditions - accomplices or innocents). Results indicated that accomplices were more effectively detected than innocent participants, although both were given the same critical information. Information gathered in the crime context yielded stronger orientation to the critical items than similar information gathered in a neutral context.


Prevalence of apical periodontitis and quality of root canal treatment in an adult Palestinian sub-population.
The aim of this study was to determine the prevalence of apical periodontitis and the technical quality of root canal fillings in a Palestinian sub-population. The panoramic radiographs of 258 patients (142 females, 116 males) attending dental clinics in 2010 were examined to identify the presence of apical lesions associated with any remaining teeth, excluding third molars. The technical quality of root canal fillings was also evaluated by assessing apical extension from the radiographic apex. The panoramic radiographs were taken by a well-trained radiology assistant and evaluated by a radiologist and an endodontist. Statistical analysis was performed with the chi-square test with a significant level set at P < 0.05%. Of 6482 teeth examined radiographically, 978 (15.1%) had radiographic signs of apical periodontitis (AP). The prevalence of AP was 8.3% in teeth without filled roots and 59.5% (509/855) in root canal-treated teeth. The prevalence of AP and endodontic treatment increased with age and differed significantly (p < 0.05) between males and females. The majority (74.5%) of root canal fillings was performed inadequately, and most (77.2%) inadequate fillings were >2 mm short of the radiographic apex. The presence of AP was correlated significantly with poorly executed root canal fillings (p < 0.05). The present study found a high prevalence and incidence of AP in association with root-filled teeth. The technical quality of many root canal treatments was unacceptable.


Depolymerization of holocellulose from Chinese herb residues by the mixture of lignin-derived deep eutectic solvent with water.
The depolymerization of biomass carbohydrate polymers usually happened in homogeneous medium, just a few in heterogeneous solution. Herein, holocellulose from two Chinese herb residues Cortex albiziae (HRCA) and Heteropogon contortus (HRHC) was prepared and characterized. Deep eutectic solvent (DES) of choline chloride/p-coumaric acid collaborating with water was employed for the dissociation of those two holocelluloses and selectively dissolved hemicellulose into xylose with maximal yields of 81.50 % and 72.47 %, respectively. Most cellulose remained as the polymer state with a maximum solubility of 9.38 %. The synergistic action of DES and water was investigated to unveil the depolymerization mechanism and the roles of each component in depolymerizing procedure. It was water that released hemicellulose polymers and dissolved polymers to soluble short oligosaccharides, and DES rapidly cleaved the latter to xylose. Contrarily, DES broke cellulose to only soluble cello-oligosaccharides, but water exhibited the ability to hydrolyze cellulose to glucose.


A novel patient-derived orthotopic xenograft (PDOX) mouse model of highly-aggressive liver metastasis for identification of candidate effective drug-combinations.
Liver metastasis is a recalcitrant disease that usually leads to death of the patient. The present study established a unique patient-derived orthotopic xenograft (PDOX) nude mouse model of a highly aggressive liver metastasis of colon cancer. The aim of the present study was to demonstrate proof-of-concept that candidate drug combinations could significantly inhibit growth and re-metastasis of this recalcitrant tumor. The patient's liver metastasis was initially established subcutaneously in nude mice and the subcutaneous tumor tissue was then orthotopically implanted in the liver of nude mice to establish a PDOX model. Two studies were performed to test different drugs or drug combination, indicating that 5-fluorouracil (5-FU) + irinotecan (IRI) + bevacizumab (BEV) and regorafenib (REG) + selumetinib (SEL) had significantly inhibited liver metastasis growth (p = 0.013 and p = 0.035, respectively), and prevented liver satellite metastasis. This study is proof of concept that a PDOX model of highly aggressive colon-cancer metastasis can identify effective drug combinations and that the model has future clinical potential.


Reduction of Waiting Times and Patients Leaving Without Being Seen in the Tertiary Pediatric Emergency Department: A Comparative Observational Study.
Analyze the effectiveness of an intervention to reduce waiting time and patients leaving without being seen in the pediatric emergency department. A comparative observational study was carried out from November 2018 to April 2019.Patients aged 3 months to 17 years were included. The new organizational model consisted of a dedicated outpatients' clinic for nonurgent codes and a fast track for traumatic and surgical emergency cases. The comparative group included 14,822, and the intervention group included 15,585 patients. The new organizational model significantly reduced the numbers of patients who left the ED without being seen from 12.9% to 5.9%. This new organizational model in the pediatric emergency department could be successfully used to reduce overcrowding, waiting time, and the numbers of patients leaving without being seen. However, more needs to be done by the pediatric services in the community to reduce nonurgent accesses to the emergency department.


'Okra' Hibiscus esculentus L.: A study of its hepatoprotective activity.
In the present study, an attempt has been made to validate the claimed uses of 'Okra' Hibiscus esculentus in liver diseases. The preventive action of ethanolic extract of okra (EEO) against liver injury was evaluated in rodents using carbon tetrachloride-induced hepatotoxicity model. EEO, at 250 and 500 mg/kg body weight, exerted significant dose-dependent hepatoprotection by decreasing the CCl4-induced elevation of serum SGOT, SGPT, ALP, GGT, cholesterol, triglycerides and malondialdehyde (MDA) non-protein sulfhydryls (NP-SH) and total protein (TP) levels in the liver tissue. A significant reduction was also observed in pentobarbital-induced sleeping time in mice. The hepatoprotective and antioxidant activities of the extract are being comparable to standard silymarin. These findings were supported by histological assessment of the liver biopsy. The ability of okra extract to protect chemically induced liver damage may be attributed to its potent antioxidant property.


Biologic agent use varies inversely with age at diagnosis in Crohn's disease.
For patients with Crohn's disease, age at onset is known to influence the clinical course of the illness. The aim of this study is to seek an association between age at onset of Crohn's disease and use of biologic agents for its treatment. We reviewed the medical records of 127 veteran patients with Crohn's disease treated at our hospital, and compared differences in age at disease onset between patients who had received biologics and those who had not. The mean age of our patients was 54.9 ± 15.4 years, and 34% were currently receiving or had previously received treatment with a biologic agent. For those with biologic use, average age at time of diagnosis of Crohn's disease was 32.3 ± 12.2 years, compared with 43.7 ± 16.3 years for those who had not received biologics (P = 0.005). This relationship remained significant even after controlling for disease severity. The frequency of use of biologic agents varied inversely with age at diagnosis. For patients diagnosed before age 21 years, 55.5% had used biologics, whereas no patient >70 years of age at time of diagnosis had used biologics. We found no significant correlation between biologic use and duration of disease, smoking or ethnicity. Perianal disease and concomitant arthritis were both significantly associated with use of biologics. In our veteran patients with Crohn's disease, frequency of treatment with a biologic agent varied inversely with age at disease onset.


The formation of cerebrospinal fluid in two amphibians, Rana catesbeiana and Rana pipiens.
The cerebrospinal fluid (CSF) system of two amphibians, Rana catesbeiana and Rana pipiens has been perfused from the lateral ventricle to a site in the subarachnoid space close to the roof of the fourth ventricle. The CSF production rate (Vf) was measured by the dilution method using a perfusion fluid containing [14C]dextran in artificial CSF. For Rana catesbeiana Vf was 1.43 microliter min-1 or 0.2 microliter min-1 mg choroid plexus-1 and for Rana pipiens Vf was 0.2 microliter min-1 or 0.1 microliter min-1 mg choroid plexus-1. These control values declined by 35% and 14% respectively in the second half of the experimental period. Ouabain (5 X 10(-5) M) in the perfusion fluid for the second half of the experiment resulted in a much greater reduction in Vf, viz. 65% for Rana catesbeiana and 71% for Rana pipiens. Acetazolamide (1 X 10(-4) M) in the perfusion fluid for the second half of the experiment gave no change in Vf values when compared with control 74.5 +/- 4.8 microliters.


Multifaceted mammalian transcriptome.
Despite surprisingly a small number of protein-coding gene in mammalian genomes, a large variety of different RNAs is being produced. These RNAs are amazingly different in their number, size, cell localization, and mechanism of actions. Although new classes of short RNAs (sRNAs) are being continuously discovered, it is not yet obvious how many of the sRNAs are originated. Altogether, the research in the recent few years has identified an unexpectedly rich variety of mechanisms by which noncoding RNAs act, suggesting that we have identified probably only few of the many potential functional mechanism and more investigation will be needed to comprehensively understand the complex nature and biology of mammalian RNAome. Here, we focus on various aspects of the diversity of the biological role of these nonprotein-coding RNAs (ncRNAs), with emphasis on functional mechanisms recently elucidated.


Intraoperative fluid and pharmacologic management and the anesthesiologist's supervisory role for nontraditional technologies during liver transplantation: a survey of US academic centers.
Volume resuscitation and use of vasoactive medications during liver transplantation has not been systematically assessed. Furthermore, the anesthesiologist's role for intraoperative oversight of technologies such as renal replacement therapy and procedures such as venovenous bypass is poorly defined, and it is unclear if the center's annual transplant frequency affects these practices. We conducted a database analysis of the Liver Transplant Anesthesia Consortium survey 202 that addresses these questions. Data from US academic liver transplant anesthesia programs meeting inclusion criteria were included. Results were categorized by their annual transplant volume. A representative sample of 66% of all eligible centers contributed to the results. Normal saline among crystalloids and albumin among colloids were the most frequently chosen maintenance and non-blood product volume expansion fluids, with little variation by center size. A large variety of vasoactive agents is routinely utilized across programs, with vasopressors as a cornerstone of hemodynamic support. Large programs seem to use less of these agents compared with lower volume centers. Anesthesiologists are increasingly involved in oversight and management of intraoperative renal replacement therapies, venovenous bypass and cell saver devices with rising transplant frequency. This new insight may be indicative of skill sets needed by members of liver transplantation anesthesia teams and should be considered in curriculum design for hepatobiliary transplant anesthesia fellowships.


Enzymological characteristics of a novel archaeal dye-linked D-lactate dehydrogenase showing loose binding of FAD.
A gene-encoding a dye-linked D-lactate dehydrogenase (Dye-DLDH) homolog was identified in the genome of the hyperthermophilic archaeon Thermoproteus tenax. The gene was expressed in Escherichia coli and the product was purified to homogeneity. The recombinant protein exhibited highly thermostable Dye-DLDH activity. To date, four types of Dye-DLDH have been identified in hyperthermophilic archaea (in Aeropyrum pernix, Sulfolobus tokodaii, Archaeoglobus fulgidus, and Candidatus Caldiarchaeum subterraneum). The amino acid sequence of T. tenax Dye-DLDH showed the highest similarity (45%) to A. pernix Dye-DLDH, but neither contained a known FAD-binding motif. Nonetheless, both homologs required FAD for enzymatic activity, suggesting that FAD binds loosely to the enzyme and is easily released unlike in other Dye-DLDHs. Our findings indicate that Dye-DLDHs from T. tenax and A. pernix are a novel type of Dye-DLDH characterized by loose binding of FAD.


U-500 insulin as a component of basal bolus insulin therapy in type 2 diabetes.
Changes in hemoglobin A1c (A1C), weight, and total daily insulin dose (TDD) were investigated following initiation of insulin U-500 (U500) alone or as part of a basal/bolus insulin (BBI) regimen. Records of patients with type 2 diabetes who were prescribed U500 were retrospectively reviewed. Logistic regression analysis was used to investigate relationships between changes in A1C and use of U500 alone or as BBI. Twelve patients were identified as using U500 alone (n=2) or in combination with long-acting (LAI) (n=7) or rapid-acting (RAI) (n=3) insulin. Reductions in A1C (9.5% at baseline vs. 7.7% at 6-9 months, P<0.0001) and increases in weight (128.8±32.7 vs. 131.5±31.3 kg, P<0.014) and TDD (260±111 to 333±106 units/day, P<0.0002) were observed. Concurrent use of LAI or RAI with U500 did not predict improvements in A1C. U500 resulted in improvements in A1C and weight gain and increased TDD when used alone or as part of combination insulin therapy. Further investigations to define the optimal use of U500 are recommended.


Electrophysiological localization of brain regions involved in perceptual memory.
Event-related potentials (ERP) were recorded during perceptual discrimination and short-term memory, varying the interstimulus interval (1-10 s) in delayed spatial frequency discrimination. Accuracy of discrimination remained unimpaired across this time interval, but choice reaction times increased. A brain source localization (BESA) model showed that the activity of the parietal and right temporal sources increased with long retention intervals in a sequential activation pattern where a long-latency component of the parietal source specific to the memory condition was observed, the latency of which matched a memory-related increase in choice reaction times in the cognitive task. It is suggested that the temporal sources are involved in encoding and storage of visual information, and the parietal source is involved in memory retrieval.


Tumours of the salivary glands: a histological and clinical review.
The aim of this paper is to try to identify points of correlation between the histological appearance and the clinical behaviour of minor salivary gland tumours. To this end 62 well-documented minor salivary gland tumours have been followed up for at least five years or until recurrence. The discussion is limited to the adenoidcystic carcinoma, the pleomorphic adenoma and the basal cell adenoma, since only these three tumours were represented in sufficient numbers to be analysed. For each tumour a number of histological pointers to prognosis are reviewed. In the case of the basal cell adenoma, a recently recognised tumour, the possibility of confusion with the adenoidcystic carcinoma is discussed.


Nutritional Assessment of Childhood Cancer Survivors (the Swiss Childhood Cancer Survivor Study-Nutrition): Protocol for a Multicenter Observational Study.
Childhood cancer survivors are at high risk of developing adverse late health effects. Poor nutritional intake may contribute to this risk, but information about dietary intake is limited. This study will assess childhood cancer survivors' dietary intake and compare two dietary assessment tools: a self-reported food frequency questionnaire, and dietary measurements from urine spot samples. In a substudy of the Swiss Childhood Cancer Survivor Study (SCCSS), SCCSS-Nutrition, we assessed childhood cancer survivors' dietary intake via a validated food frequency questionnaire. We sent a urine spot collection kit to a subset of 212 childhood cancer survivors from the French-speaking region of Switzerland to analyze urinary sodium, potassium, urea, urate, creatinine, and phosphate content. We will compare the food frequency questionnaire results with the urine spot analyses to quantify childhood cancer survivors' intake of various nutrients. We collected data between March 2016 and March 2018. We contacted 1599 childhood cancer survivors, of whom 919 (57.47%) returned a food frequency questionnaire. We excluded 11 childhood cancer survivors who were pregnant or were breastfeeding, 35 with missing dietary data, and 71 who had unreliable food frequency questionnaire data, resulting in 802 childhood cancer survivors available for food frequency questionnaire analyses. To a subset of 212 childhood cancer survivors in French-speaking Switzerland we sent a urine spot collection kit, and 111 (52.4%) returned a urine sample. We expect to have the results from analyses of these samples in mid-2019. The SCCSS-Nutrition study has collected in-depth dietary data that will allow us to assess dietary intake and quality and compare two dietary assessment tools. This study will contribute to the knowledge of nutrition among childhood cancer survivors and is a step toward surveillance guidelines and targeted nutritional recommendations for childhood cancer survivors in Switzerland. ClinicalTrials.gov NCT03297034; https://clinicaltrials.gov/ct2/show/NCT03297034. DERR1-10.2196/14427.


Swiss QUality of life and healthcare impact Assessment in a Real-world Erenumab treated migraine population (SQUARE study): interim results.
The fully human monoclonal antibody erenumab, which targets the calcitonin gene-related peptide (CGRP) receptor, was licensed in Switzerland in July 2018 for the prophylactic treatment of migraine. To complement findings from the pivotal program, this observational study was designed to collect and evaluate clinical data on the impact of erenumab on several endpoints, such as quality of life, migraine-related impairment and treatment satisfaction in a real-world setting. An interim analysis was conducted after all patients completed 6 months of erenumab treatment. Patients kept a headache diary and completed questionnaires at follow up visits. The overall study duration comprises 24 months. In total, 172 adults with chronic or episodic migraine from 19 different sites across Switzerland were enrolled to receive erenumab every 4 weeks. At baseline, patients had 16.6 ± 7.2 monthly migraine days (MMD) and 11.6 ± 7.0 acute migraine-specific medication days per month. After 6 months, erenumab treatment reduced Headache Impact Test (HIT-6™) scores by 7.7 ± 8.4 (p < 0.001), the modified Migraine Disability Assessment (mMIDAS) by 14.1 ± 17.8 (p < 0.001), MMD by 7.6 ± 7.0 (p < 0.001) and acute migraine-specific medication days per month by 6.6 ± 5.4 (p < 0.001). Erenumab also reduced the impact of migraine on social and family life, as evidenced by a reduction of Impact of Migraine on Partners and Adolescent Children (IMPAC) scores by 6.1 ± 6.7 (p < 0.001). Patients reported a mean effectiveness of 67.1, convenience of 82.4 and global satisfaction of 72.4 in the Treatment Satisfaction Questionnaire for Medication (TSQM-9). In total, 99 adverse events (AE) and 12 serious adverse events (SAE) were observed in 62 and 11 patients, respectively. All SAE were regarded as not related to the study medication. Overall quality of life improved and treatment satisfaction was rated high with erenumab treatment in real-world clinical practice. In addition, the reported impact of migraine on spouses and children of patients was reduced. BASEC ID 2018-02,375 in the Register of All Projects in Switzerland (RAPS).


1,5-Anhydro-d-glucitol derivative and galloylated flavonoids isolated from the leaves of Acer ginnala Maxim. as dual inhibitors of PTP1B and α-glucosidase enzymes: In vitro and in silico studies.
Four undescribed compounds (two 1,5-anhydro-d-glucitol derivatives and two galloyl derivatives) and fourteen known compounds were isolated and structurally identified from leaves of Acer ginnala Maxim. (Amur maple). Structures and absolute configurations of the four undescribed compounds were determined using extensive analysis of NMR spectroscopic, HRESI-MS, modified Mosher ester method, and comparison with spectroscopic data of known compounds. Bioactivity evaluation revealed that the isolated 1,5-anhydro-d-glucitol derivative, galloylated flavonol rhamnosides, and galloylated flavanols had inhibitory effects on both protein tyrosine phosphatase-1B (PTP1B, IC50 values ranging of 3.46-12.65 μM) and α-glucosidase (IC50 values ranging of 0.88-6.06 μM) in comparison with a positive control for PTP1B (ursolic acid, IC50 = 5.10 μM) or α-glucosidase (acarbose, IC50 = 141.62 μM). A combination of enzyme kinetic analysis and molecular docking provided additional evidence in favor of their inhibitory activities and mechanism. These data demonstrate that A. ginnala Maxim. together with its constituents are promising sources of potent candidates for developing novel anti-diabetic medications.


A cocaine-and-amphetamine-regulated-transcript peptide projection from the lateral hypothalamus to the ventral tegmental area.
Cocaine-and-amphetamine-regulated-transcript peptides play a role in the modulation of feeding and psychomotor stimulant-like behaviors. The ventral tegmental area and the lateral hypothalamus are likely structures where cocaine-and-amphetamine-regulated-transcript peptides mediate both of these functions. Although lateral hypothalamus inputs to the ventral tegmental area have long been known, the chemical nature of this pathway remains poorly understood. To address this issue, we tested the possibility that cocaine-and-amphetamine-regulated-transcript peptide-containing neurons in the lateral hypothalamus project to the ventral tegmental area using the retrograde transport of cholera toxin subunit B combined with cocaine-and-amphetamine-regulated-transcript peptide immunostaining. The largest density of retrogradely-labeled neurons in the hypothalamus after cholera toxin subunit B injection in the ventral tegmental area was found, ipsi- and contralaterally, in the lateral hypothalamus/perifornical area, although substantial numbers of retrogradely-labeled cells were also found in the medial preoptic area, lateral preoptic area, paraventricular nucleus, dorsomedial hypothalamus and ventromedial hypothalamus. More than 80% of the retrogradely-labeled cocaine-and-amphetamine-regulated-transcript peptide-immunoreactive neurons in the hypothalamus were found in the lateral hypothalamus/perifornical area both ipsilateral and contralateral to the injection sites. Although retrogradely-labeled neurons were seen in the amygdala, locus coeruleus, and raphe nucleus, none of them displayed cocaine-and-amphetamine-regulated-transcript peptide immunoreactivity. Therefore, the hypothalamic projection to the ventral tegmental area provides a substrate whereby cocaine-and-amphetamine-regulated-transcript peptides could mediate the rewarding aspects of feeding and psychomotor stimulant-like behaviors. These findings, combined with the fact that the lateral hypothalamus receives strong inputs from the shell of the nucleus accumbens and ventral pallidum, suggest that these structures are part of integrative functional loops that control reward and appetitive behaviors.


Efficacy and safety of bromfenac for the treatment of corneal ulcer pain.
To evaluate the efficacy and safety of bromfenac ophthalmic solution 0.09% (Xibrom™, ISTA Pharmaceuticals Inc., Irvine, CA, USA) for treating pain associated with corneal ulcers. Twenty-five eyes of 24 patients with corneal infiltrates (bacterial or fungal) were treated with appropriate anti-infective agents along with bromfenac twice daily for up to 102 days to treat the pain caused by the infection. Follow-up visits were frequent in the first 2 weeks upon initiation of treatment, then at least weekly until infections were resolved. The best corrected visual acuity, location, size, and density of corneal infiltrates, the size and presence of a corneal epithelial defect, subjective eye pain (scale of 0-4) and time to pain resolution, the ability to conduct daily activities, and adverse events were recorded at each follow-up visit. The results of these treated patients were compared with those of 10 control eyes with corneal infiltrates (bacterial or fungal) where appropriate anti-infectives were used without adjunct medications. Fifty-two percent of bromfenac-treated patients reported no pain by day 3, compared with 0% of untreated controls (P=0.023). Most of the treated patients' epithelium healed by day 20 (68%) compared with only 10% of controls (P=0.040). Most bromfenac-treated patients (71%) returned to normal activities within 2 days of starting treatment with bromfenac, compared with 0% of controls (P=0.018). No adverse events were recorded. Bromfenac was effective in treating pain associated with infectious keratitis and did not delay corneal epithelialization nor cause any corneal adverse events in this group of 25 eyes.


The spatial frequency sensitivity of bipolar cells.
Retinal bipolar cells constitute the output stage of the outer layer of the retina. There are several constraints on the ability of the bipolar cell array to respond to the different spatial frequency components of the visual image, including (i) electrical coupling in the dendritic tree receiving receptor input; (iii) the "lateral inhibition" mediated by horizontal cells. Using simple mathematical models, we derive analytical expressions for the spatial frequency response of the bipolar cell array for the case in which horizontal cells are presynaptic to bipolar cells (feedforward model) and also for the case in which horizontal cells are presynaptic to receptors (feedback model). The results illustrate the importance of the three factors mentioned in determining the bipolar cells' properties. The optimal spatial frequency for stimulating the bipolar cell array, and the range of spatial frequencies transmitted onward to the inner plexiform layer, are thus related to the anatomical and electrical properties of the cells in the outer plexiform layer.


Acute bilateral corneal hydrops caused by high temperature and high moisture in the Finnish sauna. A clinical and histological case report of a patient with keratoconus.
A 44-year-old healthy male with bilateral keratoconus developed acute hydrops of both his corneas with an interval of 3 years. On both occasions he had bathed in a hot, humid Finnish sauna the preceding evening. Penetrating keratoplasty had to be performed in the acute stage in both instances, as medical therapy brought no improvement. The contributory role of hot, moist air to the development of acute hydrops is discussed. Histopathological examination of the corneal buttons revealed clear-cut breaks in Descemet's membrane with marked posterior stromal oedema.


Studies of bystander effects in human fibroblasts using a charged particle microbeam.
To determine the role of cell-to-cell mediated effects in the response of cells to different radiations by using a charged particle microbeam capable of targeting individual cells with counted particles. Primary human fibroblasts were irradiated conventionally with X-rays or alpha-particles and scored for the induction of micronucleated or apoptotic cell formation at various times after irradiation. Cells were also individually irradiated with helium-3 particles from a microbeam and the distribution of damaged cells between hit and non-hit cells scored. Conventionally exposed fibroblasts showed a dose-dependent production of micronucleated and apoptotic cells 3 days after irradiation for both X-rays and alpha-particles, with a high RBE value for alpha-particles at low doses. Targeting individual alpha-particles, using a microbeam, to four cells within a population produced more micronucleated and apoptotic cells than expected on the basis of a direct effect only. This study provides direct evidence for the production of transmissible, cell-to-cell effects between hit and non-hit cells individually exposed to charged particles.


A phase II study of bendamustine in combination with rituximab as initial treatment for patients with indolent non-follicular non-Hodgkin lymphoma.
The purpose of this phase 2 study was to determine the activity and safety of six cycles of bendamustine and eight rituximab (RB) as first-line treatment of adult patients with advanced stage non-follicular indolent non-Hodgkin lymphomas (INFL). The primary end-point was the complete response rate (CRR) with expected CRR of 75%. Sixty-nine patients were enrolled; median age was 65 years (45-75), 65% were male, 93% of patients had stage IV disease. Complete and overall response rates were 48% (95% CI = 35.6-60.2) and 86% (CI = 75.0-92.8). The most common grade 3/4 adverse events were neutropenia (43%), thrombocytopenia (7%) and anemia (4%); whereas the rate of febrile neutropenia was very low (3%). At a median follow-up of 22 months (1-43 months), 2-year progression-free survival was 89% (CI = 79-95) and 2-year overall survival was 96% (CI = 87-99). RB combination is active and well tolerated in patients with advanced stage previously untreated INFL.


Low-molecular-weight methylcellulose-based thermo-reversible gel/pluronic micelle combination system for local and sustained docetaxel delivery.
To develop low-molecular-weight methylcellulose (LMw MC)-based gel/Pluronic F127 micelle combination system for local and sustained delivery of docetaxel (DTX). LMw MC and Pluronic F127 were used to formulate an injectable thermo-reversible gel/micelle combination system containing DTX. The DTX-loaded combination system was characterized and its therapeutic efficacy evaluated in a subcutaneous tumor model. Mixtures of LMw MC, AS, and Pluronic F127 formed gel at ~15-40°C depending on AS concentration. The combination system released DTX for >30 days with a biphasic and sustained release pattern, and DTX stability was maintained during release. The combination system significantly enhanced anti-cancer effects of DTX and prolonged survival of the model mouse in comparison with free DTX. The LMw MC gel/Pluronic F127 micelle combination system constitutes a promising tool for reducing tumor size and eradicating remaining tumor cells before and after surgery.


Medical and Surgical Management of Equine Recurrent Uveitis.
Equine recurrent uveitis (ERU) is characterized by recurrent bouts of inflammation interrupted by periods of quiescence that vary in duration. There is little consensus on the clinical manifestations, the underlying causes, or the management. The 3 commonly recognized syndromes of ERU (classic, insidious, and posterior) do not accurately separate the clinical manifestations of disease into distinct categories. An accurate diagnosis and early intervention are essential to minimizing the effects of disease and preserving vision. There are multiple medical and surgical options for controlling ERU as long as the disease is recognized early and targeted treatment is initiated immediately.


Long-term organic carbon preservation enhanced by iron and manganese.
The balance between degradation and preservation of sedimentary organic carbon (OC) is important for global carbon and oxygen cycles1. The relative importance of different mechanisms and environmental conditions contributing to marine sedimentary OC preservation, however, remains unclear2-8. Simple organic molecules can be geopolymerized into recalcitrant forms by means of the Maillard reaction5, although reaction kinetics at marine sedimentary temperatures are thought to be slow9,10. More recent work in terrestrial systems suggests that the reaction can be catalysed by manganese minerals11-13, but the potential for the promotion of geopolymerized OC formation at marine sedimentary temperatures is uncertain. Here we present incubation experiments and find that iron and manganese ions and minerals abiotically catalyse the Maillard reaction by up to two orders of magnitude at temperatures relevant to continental margins where most preservation occurs4. Furthermore, the chemical signature of the reaction products closely resembles dissolved and total OC found in continental margin sediments globally. With the aid of a pore-water model14, we estimate that iron- and manganese-catalysed transformation of simple organic molecules into complex macromolecules might generate on the order of approximately 4.1 Tg C yr-1 for preservation in marine sediments. In the context of perhaps only about 63 Tg C yr-1 variation in sedimentary organic preservation over the past 300 million years6, we propose that variable iron and manganese inputs to the ocean could exert a substantial but hitherto unexplored impact on global OC preservation over geological time.


The past, present, and future of chemotherapy with a focus on individualization of drug dosing.
While there have been rapid advances in developing new and more targeted drugs to treat cancer, much less progress has been made in individualizing dosing. Even though the introduction of immunotherapies such as CAR T-cells and checkpoint inhibitors, as well as personalized therapies that target specific mutations, have transformed clinical treatment of cancers, chemotherapy remains a mainstay in oncology. Chemotherapies are typically dosed on either a body surface area (BSA) or weight basis, which fails to account for pharmacokinetic differences between patients. Drug absorption, distribution, metabolism, and excretion rates can vary between patients, resulting in considerable differences in exposure to the active drugs. These differences result in suboptimal dosing, which can reduce efficacy and increase side-effects. Therapeutic drug monitoring (TDM), genotype guided dosing, and chronomodulation have been developed to address this challenge; however, despite improving clinical outcomes, they are rarely implemented in clinical practice for chemotherapies. Thus, there is a need to develop interventions that allow for individualized drug dosing of chemotherapies, which can help maximize the number of patients that reach the most efficacious level of drug in the blood while mitigating the risks of underdosing or overdosing. In this review, we discuss the history of the development of chemotherapies, their mechanisms of action and how they are dosed. We discuss substantial intraindividual and interindividual variability in chemotherapy pharmacokinetics. We then propose potential engineering solutions that could enable individualized dosing of chemotherapies, such as closed-loop drug delivery systems and bioresponsive biomaterials.


Centrally administered CYP2D inhibitors increase oral tramadol analgesia in rats.
Cytochrome P450 2D (CYP2D) mediates the activation and inactivation of several classes of psychoactive drugs, including opioids, which can alter drug response. Tramadol is a synthetic opioid with analgesic activity of its own as well as being metabolically activated by CYP2D to O-desmethyltramadol (ODMST) an opioid receptor agonist. We investigated the impact of brain CYP2D metabolism on central tramadol and ODSMT levels, and resulting analgesic response after oral tramadol administration in rats. CYP2D inhibitors propranolol and propafenone were administered intracerebroventricularly prior to oral tramadol administration and analgesia was measured by tail-flick latency. Drug levels of tramadol and its metabolites, ODSMT and N-desmethyltramadol, were assessed in plasma and in brain by microdialysis using LC-ESI-MS/MS. Inhibiting brain CYP2D with propafenone pretreatment increased analgesia after oral tramadol administration (ANOVA p = 0.02), resulting in a 1.5-fold increase in area under the analgesia-time curve (AUC0-60, p < 0.01). This effect was associated with changes in the brain levels of tramadol and its metabolites consistent with brain CYP2D inhibition. In conclusion, under oral tramadol dosing pretreatment with a central administration of the CYP2D inhibitor propafenone increased analgesia (without altering plasma drug or metabolite levels), indicating that tramadol itself (and activity of CYP2D within the brain) contributed to analgesia.


Comparing the impacts of hiking, skiing and horse riding on trail and vegetation in different types of forest.
Nature-based tourism in protected areas has increased and diversified dramatically during the last decades. Different recreational activities have a range of impacts on natural environments. This paper reports results from a comparison of the impacts of hiking, cross-country skiing and horse riding on trail characteristics and vegetation in northern Finland. Widths and depths of existing trails, and vegetation on trails and in the neighbouring forests were monitored in two research sites during 2001 and 2002. Trail characteristics and vegetation were clearly related to the recreational activity, research site and forest type. Horse trails were as deep as hiking trails, even though the annual number of users was 150-fold higher on the hiking trails. Simultaneously, cross-country skiing had the least effect on trails due to the protective snow cover during winter. Hiking trail plots had little or no vegetation cover, horse riding trail plots had lower vegetation cover than forest plots, while skiing had no impact on total vegetation cover. On the other hand, on horse riding trails there were more forbs and grasses, many of which did not grow naturally in the forest. These species that were limited to riding trails may change the structure of adjacent plant communities in the long run. Therefore, the type of activities undertaken and the sensitivity of habitats to these activities should be a major consideration in the planning and management of nature-based tourism. Establishment of artificial structures, such as stairs, duckboards and trail cover, or complete closure of the site, may be the only way to protect the most sensitive or deteriorated sites.


The Cambridge Neurological Inventory: a clinical instrument for assessment of soft neurological signs in psychiatric patients.
A schedule (the Cambridge Neurological Inventory) has been constructed for standardized neurological assessment of psychiatric patients. Normative data and data resulting from its application to a group of patients with schizophrenia are reported. The instrument is comprehensive, reliable, and easy to administer. In conjunction with other forms of clinical assessment, it may be useful for identifying soft neurological signs and other patterns of neurological impairment relevant to neurobiological localization and prognosis in schizophrenia and other psychiatric disorders.


Can social psychological models be used to promote bicycle helmet use among teenagers? A comparison of the Health Belief Model, Theory of Planned Behavior and the Locus of Control.
The bicycle helmet use rate is still low among teenagers despite the cumulating evidence that bicycle helmets can prevent cyclists from serious injuries and death. The objective of this study was to investigate the usefulness of the Health Belief Model (HBM; Health Education Monographs, 2 (1974) (1), Theory of Planned Behavior (TPB; Ajzen, I. (1988). Attitudes, personality and behavior. Open University Press, Milton Keynes) and Locus of Control model (LC; Psychological Monographs, (1966) (80) in understanding the intention to use bicycle helmet use among bicycle helmet owners. Data were collected at two schools in Helsinki, Finland. Students (N=965) completed a questionnaire including three social psychological models applied to helmet use. Models were compared by structural equation modeling techniques. Results showed that the TPB and LC model fitted the data well, whereas fit of the HBM model was lower than the fit of TPB and LC models. All components of TPB and external LC orientation were significantly related to the intention to use a helmet. TPB together with LC model provide a promising theoretical framework for helmet use promotion campaigns. Practical suggestions for future bicycle helmet campaigns were provided.


P53: A Key Target in the Development of Osteoarthritis.
Osteoarthritis (OA), a chronic degenerative disease characterized mainly by damage to the articular cartilage, is increasingly relevant to the pathological processes of senescence, apoptosis, autophagy, proliferation, and differentiation of chondrocytes. Clinical strategies for osteoarthritis can only improve symptoms and even along with side effects due to age, sex, disease, and other factors. Therefore, there is an urgent need to identify new ideas and targets for current clinical treatment. The tumor suppressor gene p53, which has been identified as a potential target for tumor therapeutic intervention, is responsible for the direct induction of the pathological processes involved in OA modulation. Consequently, deciphering the characteristics of p53 in chondrocytes is essential for investigating OA pathogenesis due to p53 regulation in an array of signaling pathways. This review highlights the effects of p53 on senescence, apoptosis, and autophagy of chondrocytes and its role in the development of OA. It also elucidates the underlying mechanism of p53 regulation in OA, which may help provide a novel strategies for the clinical treatment of OA.


Genetic variants in telomere-maintenance genes and bladder cancer risk.
Telomeres are critical in maintaining genomic stability. Genetic variants in telomere pathway genes may affect telomere and telomerase function, and subsequently cancer risk. We evaluated 126 SNPs from 10 genes related to telomere regulation in relation to bladder cancer risk. Five SNPs, 4 from TEP1 gene and 1 from PINX1 gene, were found to be highly significant (P<0.01). Out of these, the most significant association was found in rs2228041 of TEP1 (OR 1.66, 95% CI 1.19-2.31) while rs1469557 of PINX1 had a protective effect (OR 0.75, 95% CI 0.61-0.93). Haplotype analysis showed that a TEP1 haplotype consisting of the variant alleles of 7 SNPs exhibited a 2.28 fold increased risk (95% CI 1.13-4.60). We then performed cumulative analysis of multiple risk variants, as well as Classification and Regression Tree (CART) to look for gene-gene interactions. In cumulative effect analysis, the group with 4-5 risk variants had an OR of 2.57 (95% CI = 1.62-4.09) versus the reference group with 0 risk variants. The CART analysis categorized individuals into five subgroups with different bladder cancer risk profiles based on their distinct genotype background. To our knowledge, this is one of the largest, most comprehensive studies on bladder cancer risk concerning telomere-regulating pathway gene SNPs and our results support that genetic variations of telomere maintenance modulate bladder cancer risk individually and jointly.


Vascular endothelial growth factors C and D and lymphangiogenesis in gastrointestinal tract malignancy.
Vascular endothelial growth factor-C (VEGF-C) and VEGF-D are members of the VEGF family of cytokines and have angiogenic and lymphangiogenic actions. In gastric adenocarcinoma, VEGF-C mRNA and tissue protein expression correlate with lymphatic invasion, lymph node metastasis and in some reports, venous invasion and reduced 5-year survival. Patients with gastric adenocarcinomas containing high levels of VEGF-C expression have significantly reduced 5-year survival rates, and VEGF-C expression is an independent prognostic risk factor for death. The role of VEGF-C in oesophageal squamous and colorectal cancer and VEGF-D in colorectal cancer is not clear, with conflicting reports in the published literature. In order to exploit potential therapeutic applications, further research is necessary to define the precise roles of these cytokines in health and disease.


Dust fallout in Kuwait city: deposition and characterization.
Dust fallouts in Kuwait city was monitored on monthly basis during the period from March 2011 to February 2012 at 10 locations. The results of this study reveal that: (1) monthly dust deposition rates ranged from 0.002 to 0.32 kg/m(2) with average deposition rate of 0.053 kg/m(2) and annual average deposition rate of 0.59 kg/m(2), ranking the first out of 56 dust deposition rates observed throughout the world; (2) on average, about 55.9% of the settled dust have fine to very fine sand fraction sizes, while silt and clay comprise an average of 37.4 and 1.4% of the total sample, respectively; (3) the concentrations for Zn and Mo out of 15 other elements analyzed from the dust were up to 11 times higher than their soil background values in Kuwait, while Pb and Ni were about seven times higher; (4) Mo, Ni, Pb and Zn show maximum enrichment relative to the upper continental crustal component (Mn); (5) Sr, Zr and Zn show highest concretions among all collected samples; and (6) quartz and calcite were the dominant minerals in the dust samples. The distribution of the heavy metals in dust seems to be controlled mainly by the land uses and the volume of traffic emissions.


The risk of upper gastrointestinal cancer in familial adenomatous polyposis.
Adenomas with potential for malignancy occur frequently in the upper gastrointestinal tract of patients with familial adenomatous polyposis. However, an assessment of relative risk of upper gastrointestinal cancer in patients with adenomatous polyposis has never been performed. Therefore, the incidence rate of upper gastrointestinal cancer in patients with familial adenomatous polyposis in The Johns Hopkins Registry was compared with the rate of the general population through person-year analysis with adjustment for demographics. There was an increased relative risk of duodenal adenocarcinoma (relative risk, 330.82; 95% confidence limits, 132.66 and 681.49; P less than 0.001) and ampullary adenocarcinoma (relative risk, 123.72; 95% confidence limits, 33.65 and 316.72; P less than 0.001). No significant increased risk was found for gastric or nonduodenal small intestinal cancer. These results indicate that periodic surveillance of the upper gastrointestinal tract for duodenal and periampullary cancer is needed in patients with familial adenomatous polyposis. Prophylactic duodenectomy is a consideration when large adenoma(s) with high-grade dysplasia are identified but awaits risk benefit analysis.


Investigation of insect morphology by MRI: assessment of spatial and temporal resolution.
Classically, the investigation of the internal morphology of insects relies on histologic methods, e.g., the preparation of thin tissue sections. However, the preparation of serial sections is time consuming and means the irreversible loss of the animal. In the present investigation, we have analyzed the potential of NMR imaging as a tool for the morphologic classification of insects with sufficient spatial resolution. With a 512 matrix, 15 mm FOV, 200 microm slice thickness, images with an in-plane spatial resolution of 30 microm are obtained with a signal-to-noise ratio of 70. These conditions require only seven averages, resulting in an experimental time of only 50 min. Such image quality already permits the differentiation of fine structural and morphologic details such as e.g., intestinal tracts and copulation organ in a beetle. Also, wing controlling dorsal muscle groups as well as leg structures and joints are clearly distinguishable. We conclude that the spatial resolution and contrast condition of MR imaging are quite promising for the new approach of zoological insect classification using NMR imaging. Further principally available technical enhancement of sensitivity and spatial resolution will provide an attractive alternative to invasive techniques for the classification of, sometimes, rare and precious insect specimen.


Cloud Computing for Pharmacometrics: Using AWS, NONMEM, PsN, Grid Engine, and Sonic.
Cloud computing allows pharmacometricians to access advanced hardware, network, and security resources available to expedite analysis and reporting. Cloud-based computing environments are available at a fraction of the time and effort when compared to traditional local datacenter-based solutions. This tutorial explains how to get started with building your own personal cloud computer cluster using Amazon Web Services (AWS), NONMEM, PsN, Grid Engine, and Sonic.


Perinatal infection, inflammation, and retinopathy of prematurity.
The major known risk factors for retinopathy of prematurity (ROP) are extremely low gestational age, exposure to high levels of oxygen early after birth (phase I) and relatively lower oxygen levels later (phase II). In this review, we summarize recent data suggesting that exposure to perinatal infection/inflammation is associated with an increased risk for ROP. Part of this effect might be due to direct exposure of the developing retina to circulating products of infection and/or inflammation. Another potential mechanism that deserves exploration is that inflammation and/or oxidative stress can modify the known increased risk of oxygen-associated ROP. Taken together, accumulating evidence suggests that prenatal, perinatal, and postnatal systemic inflammation contribute to a 'pre-phase', sensitizing the pre-ROP retina for subsequent insults, setting the stage for what are now called phase I and phase II of ROP pathogenesis. Strategies targeting inflammatory responses might help reduce the risk for ROP in extremely low gestational age newborns.


Purpose in life, boredom, and volunteerism in a group of retirees.
In a pilot study of 40 retirees, those who volunteered more than 10 hours per week scored significantly higher on the Purpose In Life test than those who volunteered 10 or fewer hours per week. A significant negative correlation of -.75 was obtained between scores on purpose in life and boredom proneness.


Polyclonal B cell activation during the course of Angiostrongylus cantonensis infection.
The numbers of IgM antibody forming cells against various heterologous antigens: SRBC, HRBC, TNP and FITC, were found to be elevated in the spleens of rats after infection with Angiostrongylus cantonensis. In these rats, the number of splenic B cells and total IgG and IgM levels in serum also increased spontaneously about 2- to 3-fold of uninfected rats during the course of the infection. These results suggested that A. cantonensis infection may activate B cells polyclonally in the spleens of the infected rats. While, it was clearly observed that the antibody response to SRBC injection was significantly depressed in these rats, compared to those of uninfected rats. The relation between the polyclonal B cell activation and the immunodepression was discussed.


Risk factors associated with postoperative complications following free flap reconstruction of head and neck defects.
Free flap reconstruction of head and neck defects is routinely performed with a high success rate nowadays. However, postoperative complications are still commonly observed. The aim of this study is to investigate risk factors correlated with postoperative complications following free flap reconstruction of head and neck defects. A retrospective study of all patients undergoing free flap reconstruction of head and neck defects between January 2018 and January 2020 at Sun Yat-sen Memorial Hospita, Guangzhou, China was performed. Preoperative, intraoperative, and postoperative data were collected retrospectively. The primary outcome variables were postoperative complications, which were divided into medical and surgical complications. All patients were grouped by either complications or no complications. Univariate and multivariate logistic regression models were used to identify risk factors predicting complications. 850 patients underwent free flap reconstruction of head and neck defects during the study period (Male: 65.29%; Mean [SD] age: 54.90 [13.78] years). Postoperative complications developed in 125 (14.71%) patients, among which, 101 (11.88%) patients developed surgical complications, 29 (3.41%) patients developed medical complications and 5 (0.59%) patients developed both surgical and medical complications. Total flap necrosis was observed in 11 (1.29%) patients. After multivariate analysis, several risk factors incluing postoperative ICU admission, coronary heart disease, post radiotherapy surgery and flap types were identified correlated with postoperative complications. Our study identified related variables for a higher risk of postoperative complications development following free flap reconstruction of head and neck defects. Early detection of these risk factors will improve prognosis.


Double ligand ELISA technique for the estimation of antibodies to brain tissue antigens in patients with neurological disorders.
A double ligand enzyme-linked immunosorbent assay (ELISA) has been developed to detect antibodies against brain tissue antigens in the sera of patients with neurological diseases. The sera were tested on human white matter homogenate. The technique consists of successive incubations with the human serum to be tested, rabbit immunoglobulin G (IgG) to human immunoglobulins (Ig), alkaline phosphate-labeled protein A and alkaline phosphatase substrate. This procedure has the advantage of increased sensitivity compared to the classical ELISA. Application of this procedure to the sera of patients with neurological diseases showed that the unspecific binding is very low and the results are reliable. Moreover the test allows the detection of antibodies to chemically different antigenic structures that can occur in a variety of neurological diseases.


Oxidation and polymer degradation characteristics of high viscosity modified asphalts under various aging environments.
High viscosity modified asphalt (HVMA) was the core material to build ecological permeable pavement, while it was prone to aging, which limited its applications for urban sustainability. This study focused on the oxidation and polymer degradation characteristics of the high-content styrene-butadiene-styrene modified asphalt, high-viscosity composite particle modified asphalt and high-elastic modified asphalt under the simulated aging environments of thermal oxidation and weather. Gel permeation chromatography results showed that the increase percent of large molecular size percent and the decrease percent of polymer weight could characterize the oxidation degree and polymer degradation degree, respectively. The degrees of oxidation and polymer degradation in all HVMAs increased synchronously with aging, and reached the highest after the weather aging. The polymer molecular distribution of HVMA would become more uniform with aging from the proposed ratio of polymer weight to polymer content. Dynamic shear rheometer tests reflected that there existed the dual effects of coupling and parallelism during aging of HVMA, i.e. the oxidation-induced hardening effect and degradation-induced softening effect. Furthermore, the change percent of rheological indicators was proposed as the net aging degree. Considering the rheological properties of aged HVMA were the coupling results of dual effects, the net aging degree could represent the oxidation dominance degree or polymer degradation dominance degree of HVMA. Due to the differences of dual effects and polymer molecular distribution, various HVMAs showed the totally different net aging degree ranking, depending on the aging states and rheological indicators. Notably, the high-elastic modified asphalt showed the greatest aging resistance at all aging states as a result of its weak dual effects and most uniform polymer molecular distribution.


Oral dehydroepiandrosterone in physiologic doses modulates immune function in postmenopausal women.
This study tests the hypothesis that dehydroepiandrosterone or its metabolic products are immunomodulatory in postmenopausal women with relative adrenal androgen deficiency. A prospective, randomized, double-blind, crossover study of 11 subjects with 3-week treatment arms separated by a 2-week washout period was performed. Immunologic evaluation at the beginning and end of the treatment arms consisted of flow cytometry to delineate T-cell populations, in vitro T-cell mitogenic response and cytokine production, and natural killer cell cytotoxicity. Statistical analysis was based on a split-plot design with analysis of variance with repeated measures. Dehydroepiandrosterone supplementation decreased CD4+ (helper) T cells and increased CD8+/CD56+ (natural killer) cells. Although T-cell mitogenic and interleukin-6 responses were inhibited, natural killer cell cytotoxicity increased dramatically. These data provide the first in vivo evidence in human for an immunomodulatory effect of dehydroepiandrosterone. The salutary immune changes could account for clinical and experimental evidence of antioncogenic effects of this steroid. This study provides a strong rationale for further clinical studies on dehydroepiandrosterone supplementation in adrenal androgen-deficient states.


Study on the genus Morimospasma Ganglbauer, 1889 (Coleoptera, Cerambycidae, Lamiinae) from Hubei, China.
Totally nine species/subspecies of the genus Morimospasma Ganglbauer, 1889 are recorded from Hubei (China). Among of them, a new species, Morimospasma (Parvopama) shii sp. nov., from Shennongjia Forestry District, is described and illustrated and Morimospasma (Parvopama) tuberculatum Breuning, 1939 is newly recorded from Hubei.


Parallel intermediate conductance K+ and Cl- channel activity mediates electroneutral K+ exit across basolateral membranes in rat distal colon.
Transepithelial K+ absorption requires apical K+ uptake and basolateral K+ exit. In the colon, apical H+-K+-ATPase mediates cellular K+ uptake, and it has been suggested that electroneutral basolateral K+ exit reflects K+-Cl- cotransporter-1 (KCC1) operating in parallel with K+ and Cl- channels. The present study was designed to identify basolateral transporter(s) responsible for K+ exit in rat distal colon. Active K+ absorption was determined by measuring 86Rb+ (K+ surrogate) fluxes across colonic epithelia under voltage-clamp conditions. With zero Cl- in the mucosal solution, net K+ absorption was reduced by 38%, indicating that K+ absorption was partially Cl--dependent. Serosal addition of DIOA (KCC1 inhibitor) or Ba2+ (nonspecific K+ channel blocker) inhibited net K+ absorption by 21% or 61%, respectively, suggesting that both KCC1 and K+ channels contribute to basolateral K+ exit. Clotrimazole and TRAM34 (IK channel blockers) added serosally inhibited net K+ absorption, pointing to the involvement of IK channels in basolateral K+ exit. GaTx2 (CLC2 blocker) added serosally also inhibited net K+ absorption, suggesting that CLC2-mediated Cl- exit accompanies IK channel-mediated K+ exit across the basolateral membrane. Net K+ absorption was not inhibited by serosal addition of either IbTX (BK channel blocker), apamin (SK channel blocker), chromanol 293B (KV7 channel blocker), or CFTRinh172 (CFTR blocker). Immunofluorescence studies confirmed basolateral membrane colocalization of CLC2-like proteins and Na+-K+-ATPase α-subunits. We conclude that active K+ absorption in rat distal colon involves electroneutral basolateral K+ exit, which may reflect IK and CLC2 channels operating in parallel.NEW & NOTEWORTHY This study demonstrates that during active electroneutral K+ absorption in rat distal colon, K+ exit across the basolateral membrane mainly reflects intermediate conductance K+ channels operating in conjunction with chloride channel 2, with a smaller, but significant, contribution from K+-Cl- cotransporter-1 (KCC1) activity.


Divergent cardiac effects of the first and second generation hypoglycemic sulfonylurea compounds.
The effects of first and second generation hypoglycemic sulfonylureas on the incidence of ventricular ectopic beats and on the duration of transitional ventricular fibrillation in the ischemic rat heart were investigated. First generation sulfonylurea compounds (tolbutamide, carbutamide and gliclazide) in 105 preparations increased, while second generation sulfonylurea compounds (glibenclamide and glipizide) in 50 preparations decreased in a dose-dependent manner both the number of ventricular ectopic beats and the duration of transitional ventricular fibrillation during the first 30 min after ligation of the left anterior descending coronary artery. Therefore, second generation sulfonylureas should be preferred in the treatment of type 2 diabetics with ischemic heart diseases, if satisfactory metabolic control cannot be achieved by a treatment regimen and diet alone.


Pypreclin: An automatic pipeline for macaque functional MRI preprocessing.
Non-human primate functional MRI (fMRI) is a growing field in neuroscience. However, there is no standardized method for monkey fMRI data analysis, specifically for data preprocessing. The preprocessing of monkey fMRI data is challenged by several technical and experimental specificities of the monkey research such as artifacts related to body movements or to intracranial leads. Here we propose to address these challenges by developing a new versatile pipeline for macaque fMRI preprocessing. We developed a Python module, Pypreclin, to process raw images using state of the art algorithms embedded in a fully automatic pipeline. To evaluate its robustness, we applied Pypreclin to fMRI data acquired at 3T in both awake and anesthetized macaques, with or without iron oxide contrast agent, using single loop or multichannel phased-array coils, combined or not with intracranial implanted electrodes. We performed both resting-state and auditory evoked fMRI and compared the results of Pypreclin to a previously employed preprocessing pipeline. Pypreclin successfully achieved the registration of the fMRI data to the macaque brain template in all the experimental conditions. Moreover, Pypreclin enables more accurate locations of auditory evoked activations in relation to the gray matter at corrected level in the awake fMRI condition. Finally, using the Primate neuroimaging Data-Exchange open access platform, we could further validate Pypreclin for monkey fMRI images that were acquired at ultra-high fields, from other institutions and using different protocols. Pypreclin is a validated preprocessing tool that adapts to diverse experimental and technical situations of monkey fMRI. Pypreclin code is available on open source data sharing platform.


Effect of luminance on color perception of protanopes.
Small-field color-naming performance of two protanopes over a 4-log luminance range was impoverished in comparison with that of normal trichromats, and was more strongly affected by changes in luminance. At 200 cd/m2 responses to mid-spectral lights were dominated by 'yellow'; with lowering luminance, 'green' and 'red' were increasingly used. In the color spaces derived from these data the first two dimensions for trichromats are red-green and yellow-blue: those of the protanopes appear to be brightness and 'red-blue'. In the protanopes' color space the greater separation of stimuli at 0.2 cd/m2 suggests that with low luminance their color discrimination improves.


Nonuniform subduction of the Indian crust beneath the Himalayas.
Himalayan tectonic activity is triggered by downward penetration of the Indian plate beneath the Asian plate. The subsurface geometry of this interaction has not been fully investigated. This study presents novel constraints on this geometry provided by two newly obtained, deep seismic reflection profiles. The profiles cover 100- and 60-km transects across the Yarlung-Zangbo suture of the Himalaya-Tibet orogen at c. 88°E. Both profiles show a crustal-scale outline of the subducting Indian crust. This outline clearly shows Indian understhrusting southern Tibet, but only to a limited degree. When combined with a third seismic reflection profile of the western Himalayas, the new profiles reveal progressive, eastward steepening and shortening in the horizontal advance of the subducting Indian crust.


An obesogenic refined low-fat diet disrupts attentional and behavioral control processes in a vigilance task in rats.
Diets consisting of refined foods (REF) are associated with poor physical (e.g., obesity and diabetes) and mental (e.g., depression) health and impaired cognition. Few animal studies have explored the causal links between diet processing and health. Instead, most studies focus on the role of macronutrients, especially carbohydrate and fat concurrently with how processed are the ingredients. We previously showed that a REF low fat diet (LFD) caused greater adiposity and impaired motivation compared to an unrefined control (CON) diet consisting of similar macronutrient ratios (Blaisdell et al., 2014). Here we test the hypothesis that the same REF LFD adversely affects attentional processes and behavioral control relative to the CON diet. Rats with ad libitum access to the REF diet for two months gained greater adiposity than rats consuming the CON diet. Rats then completed training on a vigilance task involving pressing the correct lever signaled by a brief visual cue whose onset varied across trials. A REF diet reduced accuracy when there was a delay between the start of the trial and cue onset. Poorer accuracy was due to increased premature responses, reflecting impulsivity, and omissions, indicating an inability to sustain attention. These results corroborate the links between consumption of refined foods, obesity, and poor cognition in humans. We discuss the possible causal models that underlie this link.


In vivo and in vitro comparison of fire ant venom and fire ant whole body extract.
Thirty-four patients with a history of immediate hypersensitivity to the sting of the imported fire ant were evaluated in a study designed to compare the diagnostic usefulness of fire ant whole body extract (WBE) preparations with that of fire ant venom (IFAV). Ninety-one percent (31/34) of the hypersensitive patients skin tested with IFAV at a maximal concentration of 1:5 X 10(3), v/v, demonstrated a wheal equal to or greater than the histamine control. Fifty-three percent (18/34) of the group were skin test positive to a WBE preparation. When the criteria for a positive skin test were relaxed, 82% of the hypersensitive group could be identified with the IFAWBE. A comparison of skin test results in sensitive patients revealed variability in the sensitivity of the WBE preparations utilized in the study. Leukocyte histamine release demonstrated a dose-response release of histamine with both IFAV and SIWBEa preparations. Specific venom antisera produced in rabbits identified a precipitin line of common identity in a gel-diffusion system containing IFAWBE and IFAV. This finding was verified by the competitive inhibition of IFAWBE with IFAV in a solid-phase radioimmunoassay system. Fire ant WBEs contain venom constituents and are effective diagnostic agents in up to 82% of patients with hypersensitivity to the sting of the imported fire ant. Marked variability in the responsiveness of sensitive patients to different WBE preparations mandates standardization of these diagnostic preparations.


Assessment of pediatric patients by emergency medical technicians-basic.
To determine whether emergency medical technicians-basic can accurately assess children and whether this ability varies with the patient's age or diagnosis. This determination is important for educational program design for emergency medical technicians in pediatrics and for evaluation of the possibility of expanding their scope of practice. Retrospective chart review. Pediatric emergency department in a large, urban hospital. Patients (n = 2430) presenting to the pediatric emergency department via basic life support ambulance during a 12-month period. Data collected were name, age, field assessment (FA), and emergency department (ED) diagnosis. Patient's ages were organized into five groups: infant (0-1 y), toddler (1-3 y), preschool (3-6 y), school-aged (6-11 y), and adolescent (> 11 y), and the ED diagnoses were divided into seven categories. The accuracy of the FA was compared with the ED diagnosis. We then analyzed FA accuracy by patient's age and type of diagnosis. The chi(2) contingency table analysis was used for dichotomous variables (P < 0.05). In addition, logistic regression and stratified analysis were used. Both ambulance and hospital charts were available for 2064 patients. Age ranged from birth to 19 years with a bimodal distribution at the extremes of patient age and a mean age of 8.25 (SD, 5.64). The distribution was 11.7% (241) infants, 14.7% (303) toddlers, 14.9% (307) preschool, 21.2% (437) school-aged, and 37.6% (776) adolescents. Overall emergency medical technician-basic assessment was accurate 81.5% (1683) of the time. There was a statistically significant variation in accuracy with both age group (chi(2) = 40.07, P < 0.05) and diagnostic category (chi(2) = 185.7, P < 0.05). By age group, the accuracy of field assessment was 69.7% (168) infants, 75.9% (230) toddlers, 82.7% (254) preschool, 86.7% (379) school-aged, and 84.0% (652) adolescents. By category of diagnosis, the accuracy of the field assessment was 92.4% (292) major trauma, 91.4% (478) minor trauma, 88.9% (112) psychologic and social, 85.1% (229) major medical, 81.1% (180) wheezing-associated respiratory illness, 65.4% (350) minor medical, and 57.5% (42) non-wheezing-associated respiratory illness. Emergency medical technicians-basic were highly successful in assessing children with wheezing, serious illness, injuries, and psychologic and social conditions. Consideration should be given to expanding their scope of practice in these areas. They were less successful in assessing minor medical conditions and respiratory emergencies other than wheezing. They require additional training in these areas.


Receptor protein tyrosine phosphatase β/ζ regulates loss of neurogenesis in the mouse hippocampus following adolescent acute ethanol exposure.
Adolescence is a critical period for brain maturation in which this organ is more vulnerable to the damaging effects of ethanol. Administration of ethanol in mice induces a rapid cerebral upregulation of pleiotrophin (PTN), a cytokine that regulates the neuroinflammatory processes induced by different insults and the behavioral effects of ethanol. PTN binds Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ and inhibits its phosphatase activity, suggesting that RPTPβ/ζ may be involved in the regulation of ethanol effects. To test this hypothesis, we have treated adolescent mice with the RPTPβ/ζ inhibitor MY10 (60 mg/kg) before an acute ethanol (6 g/kg) administration. Treatment with MY10 completely prevented the ethanol-induced neurogenic loss in the hippocampus of both male and female mice. In flow cytometry studies, ethanol tended to increase the number of NeuN+/activated Caspase-3+ cells particularly in female mice, but no significant effects were found. Ethanol increased Iba1+ cell area and the total marked area in the hippocampus of female mice, suggesting sex differences in ethanol-induced microgliosis. In addition, ethanol reduced the circulating levels of IL-6 and IL-10 in both sexes, although this reduction was only found significant in males and not affected by MY10 treatment. Interestingly, MY10 alone increased the total marked area and the number of Iba1+ cells only in the female hippocampus, but tended to reduce the circulating levels of TNF-α only in male mice. In summary, the data identify a novel modulatory role of RPTPβ/ζ on ethanol-induced loss of hippocampal neurogenesis, which seems unrelated to glial and inflammatory responses. The data also suggest sex differences in RPTPβ/ζ function that may be relevant to immune responses and ethanol-induced microglial responses.


The use of SAMe in chemotherapy-induced liver injury.
Drug-induced liver injury (DILI) remains the most common cause of acute liver failure in the Western world. Chemotherapy is one of the major class of drugs most frequently associated with idiosyncratic DILI. For this reason, patients who receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs may not be appropriate and which drug doses should be modified. S-adenosylmethionine (SAMe) is an endogenous agent derived from methionine. Its supplementation is effective in the treatment of liver disease, in particular intrahepatic cholestasis (IHC). The target of this review is to analyze the mechanisms of hepatotoxicity of the principal anticancer agents and the role of SAMe in the prevention of this complication.


Cellular immune response to HTLV-1.
There is strong evidence at the individual level and the population level that an efficient cytotoxic T lymphocyte (CTL) response to HTLV-1 limits the proviral load and the risk of associated inflammatory diseases such as HAM/TSP. This evidence comes from host population genetics, viral genetics, DNA expression microarrays and assays of lymphocyte function. However, until now there has been no satisfactory and rigorous means to define or to measure the efficiency of an antiviral CTL response. Recently, methods have been developed to quantify lymphocyte turnover rates in vivo and the efficiency of anti-HTLV-1 CTLs ex vivo. Data from these new techniques appear to substantiate the conclusion that variation between individual hosts in the rate at which a single CTL kills HTLV-1-infected lymphocytes is an important determinant, perhaps the decisive determinant, of the proviral load and the risk of HAM/TSP. With these experimental data, it is becoming possible to refine, parameterize and test mathematical models of the immune control of HTLV-1, which are a necessary part of an understanding of this complex dynamic system.


[Effect of dibromothymoquinone on chlorophyll a fluorescence in Chlamydomonas reinhardtii cells incubated in complete or sulfur-depleted medium].
The influence of dibromothymoquinone on chlorophyll fluorescence was studied in Chlamydomonas reinhardtii cells using PAM and PEA fluorometers. The reagent affected differently control cells incubated in complete medium and S-starved cells. Thus, the fluorescence yield in the control essentially increased in the presence of dibromothymoquinone, which can be due to the inactivation of light-harvesting complex II protein kinase, followed by the suppression of membrane transition from high-fluorescence state 1 to low-fluorescence state 2. On the contrary, S-starved cells with membranes in state 2 showed a lower fluorescence yield in the presence of dibromothymoquinone than without it. The JIP test of OJIP fluorescence transients suggests that dibromothymoquinone inhibits both light-harvesting complex II kinase and photosynthetic electron transport when added to control, while in starved cells, it acts predominantly as an electron acceptor.


The application of potassium selective electrodes in the intensive care unit.
Recent advances in analytical electrochemistry have provided highly selective potassium ion exchangers and robust polymeric membranes that can be used to measure the potassium activity in plasma or whole blood. The relationship between the activity measurement and the more familiar concentration measurement is explored. The ion selective electrode (ISE) has certain practical advantages and these have been studied in relation to their use in an intensive care unit. The application of these membranes to the continuous measurement of potassium in the circulation is discussed.


Evaluating the transcriptional landscape and cell-cell communication networks in chronically irradiated parotid glands.
Understanding the transcriptional landscape that results in chronic salivary hypofunction after irradiation will help identify injury mechanisms and develop regenerative therapies. We present scRNA-seq analysis from control and irradiated murine parotid glands collected 10 months after irradiation. We identify a population of secretory cells defined by specific expression of Etv1, which may be an acinar cell precursor. Acinar and Etv1+ secretory express Ntrk2 and Erbb3, respectively while the ligands for these receptors are expressed in myoepithelial and stromal cells. Furthermore, our data suggests that secretory cells and CD4+CD8+T-cells are the most transcriptionally affected during chronic injury with radiation, suggesting active immune involvement. Lastly, evaluation of cell-cell communication networks predicts that neurotrophin, neuregulin, ECM, and immune signaling are dysregulated after irradiation, and thus may play a role in the lack of repair. This resource will be helpful to understand cell-specific pathways that may be targeted to repair chronic damage in irradiated glands.


A decrease in the permeability of aquaporin zero as a possible cause for presbyopia.
The crystalline lens appears to be a simple organ with the sole role of focusing light upon the retina. However, numerous studies have underscored its dynamic nature with a host of compartmentalized physiological processes. As the individual ages, the normal lens develops two inescapable processes, presbyopia and cataracts. Yet, to date, there is no uniform explanation for presbyopia and many factors have been proposed as contributors including continuous enlargement of the lens, loss of power of the ciliary muscle and hardening of the lens fibers. Proposed explanations are incomplete and need experimental confirmation. This paper analyzes the possible causes for presbyopia and proposes a new one for it: a decrease in the permeability of aquaporin zero (AQP-0) also known as major intrinsic protein (MIP). Based on original findings of our laboratory, this paper proposes that a fluid flow exists inside the avascular lens. This fluid enters and leaves the lens during the accommodation process. We believe that for this to occur the lens utilizes the permeability of aquaporin zero which is abundant in the membrane of the fiber cells. Volume change due to fluid traversing the surface of the lens occurs during accommodation. We present the hypothesis that increasing the permeability of AQP-0 would facilitate accommodation. Therefore, defects in AQP-0 permeability may be a cause for presbyopia. We would also like to propose that it is possible to visualize and measure the fluid volume lost during un-accommodation and determine if the fluid is lost across the anterior, posterior or both surfaces. An age-related loss in lens water permeability could reduce fluid fluxes during the shape changes of accommodation potentially contributing to presbyopia.


Ankle and foot fasciotomy: an adjunctive technique to optimize limb salvage after revascularization for acute ischemia.
Some patients with severely ischemic lower limbs continued to have severe ischemic changes in the foot after revascularization procedures and appropriate four leg compartment fasciotomies. Rather than abandon efforts at limb salvage, we performed adjunctive fasciotomies of the ankle and foot in 11 of these patients. These included five cases of acute traumatic superficial femoral or popliteal artery occlusions (three penetrating injuries; two blunt injuries) requiring primary repair or interposition vein graft; three cases of penetrating injury to all infrapopliteal arteries requiring tibiotibial vein bypasses; two cases of iatrogenic thrombosis of the common femoral artery requiring thrombectomy and patch angioplasty; and one case of a traumatically amputated leg requiring replantation. All bypasses remained patent after the distal fasciotomies. Limb salvage and good functional results were achieved in 10 of the 11 patients from 4 to 28 months postoperatively. One patient required a below-knee amputation because of bleeding from an infected graft. Thus fasciotomy of the ankle and foot should be considered during acute revascularizations when a distal bypass occludes without obvious reasons, or when the foot remains ischemic or shows signs of compartment syndrome unrelieved by standard leg fasciotomy.


Anti-HBs titers are not decreased after treatment with oral Cladribine in patients with Multiple Sclerosis vaccinated against Hepatitis B virus.
Oral cladribine is a novel treatment for Multiple Sclerosis (MS). It is a purine nucleoside antimetabolite analogue that is incorporated into the DNA, resulting in single-strand breaks in DNA and apoptosis of replicating lymphocytes. Specifically, Cladribine induces limited depletion of CD4 and CD8 T cell subsets and more marked depletion of memory B cell subsets. Therefore, natural and acquired humoral responses against pathogens may be potentially reduced. The aim of this study was to assess longitudinal variation of antiHBs titers in patients with MS treated with Cladribine. Patients with MS treated with 1 cycle of Cladribine (3,5 mg/kg) and previously vaccinated against Hepatitis B virus (HBV) were enrolled. Anti-HBs titers were compared before and after 12 months from Cladribine treatment. Total lymphocyte count was also analysed. Among the 13 RMS patients (10 F, 3 M, mean age 33,8, SD 5,9) enrolled, all had anti-HBs titers >10 mg/dl at baseline. Anti-HBs titer dropped below the reference value at 12 months after Cladribine only in 1 case. Pre-post Cladribine mean anti-HBs values were not significantly different considering the whole cohort (Wilcoxon-Mann-Whitney Test p = 0,762). Four patients had grade 1 and 1 patient grade 2 lymphocytopenia at 12 months. Cladribine does not seem to reduce humoral immune responses in subjects previously vaccinated against HBV, even in case of lymphocytopenia. These results, if confirmed in larger populations, appear reassuring also for other vaccinations (i.e. COVID19). The low impact of Cladribine on plasma cells may explain such findings.


Cellular immune response from Chagasic patients to CRA or FRA recombinant antigens of Trypanosoma cruzi.
We propose to analyze the relation between the cellular immune response of Chagas' disease patients after in vitro stimulation of peripheral blood mononuclear cells (PBMC) with recombinant antigens cytoplasmatic repetitive antigen (CRA) or flagellar repetitive antigen (FRA) of T. cruzi and the chronic clinical forms of disease. Cells were stimulated using phytohemagglutinin, CRA, FRA, or a soluble antigen of Epimastigota (Ag-Epi) for 24 hr, 72 hr, or 6 days. The proliferation of cells was evaluated after 6 days of culture by quantification of incorporated 3H-thymidine. Cytokines were measured in the supernatants obtained after 24 hr (tumor necrosis factor [TNF]-alpha and interleukin [IL]-4), 72 hr (IL-10), and 6 days (interferon [IFN]-gamma) using enzyme-linked immunosorbent assay (ELISA). Cells of the Chagas patients stimulated with the recombinant antigens exhibited higher proliferation responses compared with that of non-Chagas (NC) individuals. However, when proliferation was compared between patients with the cardiac form (CF) or indeterminate form (IF), it was not possible to establish a difference in the response. So far as the cytokines secreted in the culture supernatants after stimulation in vitro with T. cruzi antigens were concerned, the results showed that CRA, as well as Epi-Ag, were able to stimulate the production of TNF-alpha and IFN-gamma in Chagas patients as compared with NC individuals. However, the cytokine levels after stimulation with the T. cruzi antigens were not different between the patients with CF and IF. CRA was capable of inducing a T helper type 1 (Th1) immune response, with elevated production of TNF-alpha and IFN-gamma in Chagas patients that are carriers of CF and IF clinical forms.


Expression of ezrin, Bcl-2, and Ki-67 in chondrosarcomas.
The aim of the present study was to investigate whether the expression of ezrin, a membrane-cytoskeleton linker and regulator of cellular signaling, is associated with clinical features of chondrosarcoma. For this purpose, we studied the expression of ezrin in 54 chondrosarcomas by immunohistochemistry and correlated the expression with other tumor characteristics, markers of proliferation, apoptosis and with clinical parameters. The intensity of ezrin staining increased with the histologic grade, and a significant positive association existed between the tumor grade and ezrin expression (p = 0.0475). In addition, there was a positive correlation between the expression of ezrin and Bcl-2, an anti-apoptotic protein (r = 0.83, p < 0.0001), as well as between ezrin expression and increased proliferation as measured by Ki-67 index (r = 0.70, p < 0.0001). The positive correlation of ezrin expression with Bcl-2 and Ki-67 as well as with tumor grade suggests that an aggressive behavior of chondrosarcoma may be related to activation of ezrin and that ezrin inhibitors could provide a much needed adjuvant therapy in chondrosarcomas. In conclusion, our results indicate that high ezrin expression correlates with aggressive features of chondrosarcomas. Further analyses on the pathways downstream of ezrin are warranted.


Prevalence of Helicobacter pylori Positive Non-cardia Gastric Adenocarcinoma Is Low and Decreasing in a US Population.
Helicobacter pylori infection is an established causal factor for non-cardia gastric cancer. H. pylori negative gastric cancer prevalence among US patients is unclear. This retrospective cohort study examined H. pylori prevalence among consecutive patients with incident non-cardia gastric adenocarcinoma at the Houston VA Hospital (11/2007-10/2018). H. pylori positivity was defined by H. pylori on histopathology, positive antibody serology, stool antigen, or urea breath testing. We examined for trends in H. pylori negative gastric cancer based on year of diagnosis. Associations between histopathologic and cancer-related outcomes with H. pylori positivity were determined using regression models. Of 91 patients with gastric adenocarcinoma, most were men (N = 87, 95.6%), black (N = 47, 51.6%), with mean age at diagnosis of 68.0 years (SD 10.8). In addition to gastric cancer biopsy histopathology, 74 patients (81.3%) had ≥ 1 testing for H. pylori, including antibody serology (n = 34), non-cancer gastric biopsy histopathology (n = 63), or stool antigen (n = 1). The overall prevalence of H. pylori infection was 38.5% and 45.9% among patients with ≥ 2 H. pylori tests. The proportions of H. pylori positive gastric cancer decreased from 50.0% (2007-2010) to 43.4% (2011-2014) and 29.3% (2015-2018) (p = 0.096). Active/acute gastritis (adjOR 3.74), atrophic gastritis (adjOR 15.30), and gastric intestinal metaplasia (adjOR 3.65) were associated with H. pylori positive gastric cancer. The prevalence of H. pylori infection among patients with non-cardia gastric adenocarcinoma is relatively low (38.5-45.9%) and decreasing over time. This finding suggests there may be other important causal factors apart from H. pylori for gastric adenocarcinoma.


Efficient low-concentration phosphate removal from sub-healthy surface water by adsorbent prepared based on functional complementary strategy.
The remediation of low-concentration phosphorus polluted surface water (LP-SW) is one of most challenging environmental issues worldwide. Adsorption is more suitable for LP-SW remediation due to its low cost and operability. Based on the strategy of functional complementation among industrial solid wastes (ISWs), ISW-based phosphate absorbent material (PAM) was prepared from coal ash (CA, binder), rich‑calcium (Ca) carbide slag (CS, active component) and iron salt (functional reagent) by optimizing materials ratios and roasting conditions. PAM prepared under optimal conditions (Fe/CC-2opt) had good phosphate adsorption efficiency. Notably, Fe/CC-2opt not only ensured that the effluent met Environmental Quality Standards for Surface Water (pH = 6.0-9.0), but also facilitated the formation of brushite instead of hydroxyapatite due to FeSO4 addition. Compared with hydroxyapatite, brushite had greater potential application value as fertilizer due to its solubility and high P/Ca ratio. The possible mechanisms of phosphate adsorption by PAM included surface precipitation, surface complexation, electrostatic adsorption and release of Ca2+/OH-. Preparation cost of PAM was 80 US$/ton, and treatment cost was 0.07 US$/g P. Regeneration efficiency of PAM was still above 80 % after five cycles. The design idea and result of this study provide theoretical basis and technical support for the preparation of PAM with low cost, commercial production and great adsorption capacity.


Normative data of the Barratt Impulsiveness Scale 11 (BIS-11) for Brazilian adults.
The Barratt Impulsiveness Scale (BIS-11) is a valid and reliable instrument, and one of the most often used tools to assess impulsivity. This study assesses the performance of a large sample of adults by using a version of BIS-11 adapted to Brazilian Portuguese. We assessed 3,053 adults from eight Brazilian states. Internal consistencies and performance data were presented for two correction criteria of BIS-11: original and the two-factor score. The associations between age, sex, region, and education and the BIS-11 scores present very small effect sizes. Therefore, we provided a percentile rank parameter for the different BIS-11 subscores considering the whole sample. Given the internal consistency of the two correction systems, we found that only the two-factor system fulfills the psychometric criteria of Cronbach's alpha (cutoff value of at least 0.6). Our results support the use of the Brazilian adaptation of BIS-11 in different regions of the country as a measure of impulsivity. Since high impulsiveness is a characteristic of several dysfunctional behaviors, the establishment of normative parameters is of utmost relevance and should be extended to other age ranges and populations in future studies.


An extended echo state network using Volterra filtering and principal component analysis.
Echo state networks (ESNs) can be interpreted as promoting an encouraging compromise between two seemingly conflicting objectives: (i) simplicity of the resulting mathematical model and (ii) capability to express a wide range of nonlinear dynamics. By imposing fixed weights to the recurrent connections, the echo state approach avoids the well-known difficulties faced by recurrent neural network training strategies, but still preserves, to a certain extent, the potential of the underlying structure due to the existence of feedback loops within the dynamical reservoir. Moreover, the overall training process is relatively simple, as it amounts essentially to adapting the readout, which usually corresponds to a linear combiner. However, the linear nature of the output layer may limit the capability of exploring the available information, since higher-order statistics of the signals are not taken into account. In this work, we present a novel architecture for an ESN in which the linear combiner is replaced by a Volterra filter structure. Additionally, the principal component analysis technique is used to reduce the number of effective signals transmitted to the output layer. This idea not only improves the processing capability of the network, but also preserves the simplicity of the training process. The proposed architecture is then analyzed in the context of a set of representative information extraction problems, more specifically supervised and unsupervised channel equalization, and blind separation of convolutive mixtures. The obtained results, when compared to those produced by already proposed ESN versions, highlight the benefits brought by the novel network proposal and characterize it as a promising tool to deal with challenging signal processing tasks.


High pentraxin-3 plasma levels associate with thrombocytopenia in acute Puumala hantavirus-induced nephropathia epidemica.
Our aim was to investigate whether plasma levels of the long pentraxin-3 (PTX3) associate with the severity of Puumala hantavirus-induced nephropathia epidemica (NE). Sixty-one prospectively identified consecutively hospitalized NE patients were examined. Plasma PTX3, interleukin (IL)-6, terminal complement complex SC5b-9, complement component C3, C-reactive protein (CRP), creatinine, sodium, kynurenine, and tryptophan levels, as well as the blood cell count, were determined for up to five consecutive days after hospitalization. Receiver operating characteristic (ROC) analysis revealed that the maximum PTX3 level >101.6 ng/ml (high PTX3) showed a sensitivity of 71% and a specificity of 89% for detecting platelet level <50 × 10(9)/l, with an area under the curve (AUC) value of 0.78 (95% confidence interval [CI] 0.63-0.94). High PTX3 level was also associated with several other variables reflecting the severity of the disease: patients with high PTX3 level had higher maximum blood leukocyte (16.1 vs. 9.7 × 10(9)/l, p < 0.001), plasma IL-6 (16.9 vs. 9.0 pg/ml, p = 0.007), and creatinine (282 vs. 124 μmol/l, p = 0.007) levels than patients with low maximum PTX3 level. They also had longer hospital stays (8 vs. 5 days, p = 0.015) compared to patients with low PTX3 level. High plasma PTX3 levels are associated with thrombocytopenia and the overall severity of NE.


Methods for Evaluating Environmental Health Impacts at Different Stages of the Policy Process in Cities.
Evaluating the environmental health impacts of urban policies is critical for developing and implementing policies that lead to more healthy and equitable cities. This article aims to (1) identify research questions commonly used when evaluating the health impacts of urban policies at different stages of the policy process, (2) describe commonly used methods, and (3) discuss challenges, opportunities, and future directions. In the diagnosis and design stages of the policy process, research questions aim to characterize environmental problems affecting human health and to estimate the potential impacts of new policies. Simulation methods using existing exposure-response information to estimate health impacts predominate at these stages of the policy process. In subsequent stages, e.g., during implementation, research questions aim to understand the actual policy impacts. Simulation methods or observational methods, which rely on experimental data gathered in the study area to assess the effectiveness of the policy, can be applied at these stages. Increasingly, novel techniques fuse both simulation and observational methods to enhance the robustness of impact evaluations assessing implemented policies. The policy process consists of interdependent stages, from inception to end, but most reviewed studies focus on single stages, neglecting the continuity of the policy life cycle. Studies assessing the health impacts of policies using a multi-stage approach are lacking. Most studies investigate intended impacts of policies; focusing also on unintended impacts may provide a more comprehensive evaluation of policies.