Xenobiotic perturbation of ER stress and the unfolded protein response.
The proper folding, assembly, and maintenance of cellular proteins is a highly regulated process and is critical for cellular homeostasis. Multiple cellular compartments have adapted their own systems to ensure proper protein folding, and quality control mechanisms are in place to manage stress due to the accumulation of unfolded proteins. When the accumulation of unfolded proteins exceeds the capacity to restore homeostasis, these systems can result in a cell death response. Unfolded protein accumulation in the endoplasmic reticulum (ER) leads to ER stress with activation of the unfolded protein response (UPR) governed by the activating transcription factor 6 (ATF6), inositol requiring enzyme-1 (IRE1), and PKR-like endoplasmic reticulum kinase (PERK) signaling pathways. Many xenobiotics have been shown to influence ER stress and UPR signaling with either pro-survival or pro-death features. The ultimate outcome is dependent on many factors including the mechanism of action of the xenobiotic, concentration of xenobiotic, duration of exposure (acute vs. chronic), cell type affected, nutrient levels, oxidative stress, state of differentiation, and others. Assessing perturbations in activation or inhibition of ER stress and UPR signaling pathways are likely to be informative parameters to measure when analyzing mechanisms of action of xenobiotic-induced toxicity.


Phylogenetic analysis of symbiotic and free-living cyanobacterial cultures using DNA amplification fingerprinting.
DNA amplification fingerprinting (DAF) of 17 cyanobacterial isolates belonging to symbiotic and free-living forms of 6 different genera was done. The dendrogram analysis of 17 cyanobacterial cultures revealed three major clusters. All Westiellopsis cultures formed the first major cluster and their nucleotide relatedness ranged between 71-93%. In the second major cluster, the symbiotic cyanobacterium Anabaena sp dominated and all Anabaena cultures showed 60-75% similarity with each other. Nostoc muscorum is related to Anabaena variabilis by 85% and formed the third major cluster. The dendrogram analysis of cyanobacterial isolates clearly revealed that free-living cyanobacterial cultures were closely related with each other and were diverse from the symbiotic forms.


Current concepts in the management of acute pancreatitis.
Guidelines for the management of acute pancreatitis (AP) are based on the Western experience, which may be difficult to extrapolate in India due to socioeconomic constraints. Hence, modifications based on the available resources and referral patterns should be introduced so as to ensure appropriate care. We reviewed the current literature on the management of AP available in English on Medline and proposed guidelines locally applicable. Patients of AP presenting with systemic inflammatory response syndrome are at risk of moderate-severe pancreatitis and hence, should be referred to a tertiary center early. The vast majority of patients with AP have mild disease and can be managed at smaller centers. Early aggressive fluid resuscitation with controlled fluid expansion, early enteral nutrition, and culture-directed antibiotics improve outcomes in AP. Infected pancreatic necrosis should be managed in a tertiary care hospital within a multidisciplinary setup. The "step up" approach involving antibiotics, percutaneous drainage, and minimally invasive necrosectomy instituted sequentially based on clinical response has improved the outcomes in this subgroup of patients.


Expression of the water-channel protein aquaporin 4 in the H-Tx rat: possible compensatory role in spontaneously arrested hydrocephalus.
Aquaporin (AQP) water channels play an important role in water movement in the central nervous system. The authors used an animal model to examine the relationship between AQP4 expression and spontaneously arrested hydrocephalus. . Congenitally hydrocephalic H-Tx (hH-Tx) rats and nonhydrocephalic H-Tx (nH-Tx) rats were used in the study. Brain tissue sections were obtained from animals in both groups at 1 day, 1 week, 4 weeks, and 8 weeks of age. Sections were immunostained using AQP4 antibodies, and AQP4 expression was assessed. In the nH-Tx group, no AQP4 expression was seen in 1-day-old rats, and AQP4 expression was found in astrocytes around capillaries of the cerebral cortex and in ependymal cells lining the ventricles in 1-week-old rats. In the 4- and 8-week-old nH-Tx animals, AQP4 expression was seen in subpial zones of the cortex, on foot processes of pericapillary astrocytes, and in periventricular regions. A marked increase in cerebral cortical expression of AQP4 was observed at 8 weeks in the hH-Tx rats but not in the nH-Tx rats. The authors hypothesize that the differences in cerebral AQP4 expression in the 1-day-old and 1-week-old nH-Tx rats compared with the 4- and 8-week-old nH-Tx rats may be related to the fact that the cerebrospinal fluid (CSF) circulation of newborns and infants differs from that of adults. It is also possible that the increased expression of AQP4 seen in the 8-week-old hH-Tx animals was related to the development of alternative pathways of CSF circulation, which also may occur in instances of spontaneously arrested hydrocephalus.


Iridium(I) complexes with anionic N-heterocyclic carbene ligands as catalysts for the hydrogenation of alkenes in nonpolar media.
A series of lithium complexes of anionic N-heterocyclic carbenes that contain a weakly coordinating borate moiety (WCA-NHC) was prepared in one step from free N-heterocyclic carbenes by deprotonation with n-butyl lithium followed by borane addition. The reaction of the resulting lithium-carbene adducts with [M(COD)Cl]2 (M = Rh, Ir; COD = 1,5-cyclooctadiene) afforded zwitterionic rhodium(I) and iridium(I) complexes of the type [(WCA-NHC)M(COD)], in which the metal atoms exhibit an intramolecular interaction with the N-aryl groups of the carbene ligands. For M = Rh, the neutral complex [(WCA-NHC)Rh(CO)2] and the ate complex (NEt4)[(WCA-NHC)Rh(CO)2Cl] were prepared, with the latter allowing an assessment of the donor ability of the ligand by IR spectroscopy. The zwitterionic iridium-COD complexes were tested as catalysts for the homogeneous hydrogenation of alkenes, which can be performed in the presence of nonpolar solvents or in the neat alkene substrate. Thereby, the most active complex showed excellent stability and activity in hydrogenation of alkenes at low catalyst loadings (down to 10 ppm).


Malignant glomus tumor of trachea: a case report with literature review.
Glomus tumors of the trachea are extremely rare and generally benign, with very few cases of malignant transformation reported in literature. We present the case of a 74-year-old man explored for cough and dyspnea. Bronchoscopy showed a polypoid mass arising from the posterolateral tracheal wall. Computed tomography demonstrated a mid-tracheal tissular mass obliterating the tracheal lumen. Resection and anastomosis of the trachea were performed. The histological and immunohistochemical findings were consistent with malignant glomus tumor.


The ribosomal RNA gene region of Nosema apis (Microspora): DNA sequence for small and large subunit rRNA genes and evidence of a large tandem repeat unit size.
The ribosomal RNA (rRNA) gene region of the microsporidium, Nosema apis, has been examined. A new method for extracting microsporidian genomic DNA from infected host tissue is described. Complete DNA sequence data are presented for the small subunit gene (1242 bp), the internal transcribed space (33 bp), and the large subunit gene (2481 bp to a putative termination point). This is the first time that the complete large subunit rRNA gene has been published for any microsporidian species. DNA sequence is also presented for the regions flanking the 5' end of the small subunit gene and the 3' end of the large subunit gene. The intergenic spacer is shown to be heterogeneous, showing variation in sequence and restriction sites rather than length and containing sequence repeats, which are a characteristic feature of intergenic spacers. The rRNA gene region of N. apis is shown to occur in a head-to-tail, tandemly repeated manner, as in other eukaryotes. This repeat unit is shown to be approximately 18 kb in length. The nucleotide sequence presented has been submitted to the Genbank database under the accession number U97150.


Early childhood caries and infant oral health: Paediatricians' and family physicians' knowledge, practices and training.
To assess the knowledge of early childhood caries and to examine the current preventive oral health-related practices and training among Canadian paediatricians and family physicians who provide primary care to children younger than three years. A cross-sectional, self-administered survey was mailed to a random sample of 1928 paediatricians and family physicians. A total of 1044 physicians met the study eligibility criteria, and of those, 537 returned completed surveys, resulting in an overall response rate of 51.4% (237 paediatricians and 300 family physicians). Six questions assessed knowledge of early childhood caries; only 1.8% of paediatricians and 0.7% of family physicians answered all of these questions correctly. In total, 73.9% of paediatricians and 52.4% of family physicians reported visually inspecting children's teeth; 60.4% and 44.6%, respectively, reported counselling parents or caregivers regarding teething and dental care; 53.2% and 25.6%, respectively, reported assessing children's risk of developing tooth decay; and 17.9% and 22.3%, respectively, reported receiving no oral health training in medical school or residency. Respondents who felt confident and knowledgeable and who considered their role in promoting oral health as "very important" were significantly more likely to carry out oral health-related practices. Although the majority of paediatricians and family physicians reported including aspects of oral health in children's well visits, a reported lack of dental knowledge and training appeared to pose barriers, limiting these physicians from playing a more active role in promoting the oral health of children in their practices.


Development and long-term integration of MGE-lineage cortical interneurons in the heterochronic environment.
Interneuron precursors transplanted into visual cortex induce network plasticity during their heterochronic maturation. Such plasticity can have a significant impact on the function of the animal and is normally present only during a brief critical period in early postnatal development. Elucidating the synaptic and physiological properties of interneuron precursors as they mature is key to understanding how long-term circuit changes are induced by transplants. We studied the development of transplant-derived interneurons and compared it to endogenously developing interneurons (those that are born and develop in the same animal) at parallel developmental time points, using patch-clamp recordings in acute cortical slices. We found that transplant-derived interneurons develop into fast-spiking and non-fast-spiking neurons characteristic of the medial ganglionic eminence (MGE) lineage. Transplant-derived interneurons matured more rapidly than endogenously developing interneurons, as shown by more hyperpolarized membrane potentials, smaller input resistances, and narrower action potentials at a juvenile age. In addition, transplant-derived fast-spiking interneurons have more quickly saturating input-output relationships and lower maximal firing rates in adulthood, indicating a possible divergence in function. Transplant-derived interneurons both form inhibitory synapses onto host excitatory neurons and receive excitatory synapses from host pyramidal cells. Unitary connection properties are similar to those of host interneurons. These transplant-derived interneurons, however, were less densely functionally connected onto host pyramidal cells than were host interneurons and received fewer spontaneous excitatory inputs from host cells. These findings suggest that many physiological characteristics of interneurons are autonomously determined, while some factors impacting their circuit function may be influenced by the environment in which they develop.NEW & NOTEWORTHY Transplanting embryonic interneurons into older brains induces a period of plasticity in the recipient animal. We find that these interneurons develop typical fast-spiking and non-fast-spiking phenotypes by the end of adolescence. However, the input-output characteristics of transplant-derived neurons diverged from endogenously developing interneurons during adulthood, and they showed lower connection rates to local pyramidal cells at all time points. This suggests a unique and ongoing role of transplant-derived interneurons in host circuits, enabling interneuron transplant therapies.


Prediction of many-electron wavefunctions using atomic potentials.
For a given many-electron molecule, it is possible to define a corresponding one-electron Schrödinger equation, using potentials derived from simple atomic densities, whose solution predicts fairly accurate molecular orbitals for single- and multi-determinant wavefunctions for the molecule. The energy is not predicted and must be evaluated by calculating Coulomb and exchange interactions over the predicted orbitals. Potentials are found by minimizing the energy of predicted wavefunctions. There exist slightly less accurate average potentials for first-row atoms that can be used without modification in different molecules. For a test set of molecules representing different bonding environments, these average potentials give wavefunctions with energies that deviate from exact self-consistent field or configuration interaction energies by less than 0.08 eV and 0.03 eV per bond or valence electron pair, respectively.


[Sperm quality and features of the antioxidant defense system in men living in various regions of Siberia].
To investigate the quality of sperm, total antioxidant activity, concentrations of -tocopherol and lipid peroxidation in men of reproductive age living in Ulan-Ude, Irkutsk, and Novosibirsk. The analysis of sperm quality included measuring the volume and pH of the ejaculate, sperm cell count, the proportion of motile sperm cells of A and B categories. Healthy men living in Irkutsk were found to have 34.4 and 23.6% higher sperm count (millions per ml) compared to men living in the city of Novosibirsk and Ulan-Ude, respectively. They also had a 44 and 38% statistically significantly greater concentration of alpha-tocopherol than men living in Ulan-Ude and Novosibirsk, respectively. Men from Ulan-Ude had 16 and 11% greater counts of active spermatozoa than men from Novosibirsk, respectively, and 34 and 13% higher levels of total antioxidant activity of ejaculate, respectively. The findings on quality of the ejaculate and features of lipid peroxidation in men living in various Siberian cities show that the place of residence and ecological and geographical location affect functioning of the reproductive system and the heterogeneity of male infertility under anthropogenic pressure.


The use of statins and lung function in current and former smokers.
Smokers are affected by a variety of inflammatory diseases, including COPD. Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase inhibitors, are used for their lipid-lowering characteristics but also appear to have antiinflammatory and immunomodulatory activities. We assessed their ability to preserve lung function in current and former smokers. All smokers and ex-smokers seen at the Oklahoma City VA hospital in 2005 with abnormal baseline spirometry findings and two or more pulmonary function tests done 6 months apart were classified into obstructive and restrictive groups based on the initial PFT result. Statin use, annual decline in FEV(1) and FVC, and need for respiratory-related urgent care (emergency department or inpatient) were compared. Approximately one half, 215 of 418 patients, were receiving a statin. Compared to the control group, statin users had a lower decline in FEV(1) (- 0.005 +/- 0.20 L/yr vs 0.085 +/- 0.17 L/yr, p < 0.0001) and FVC (- 0.046 +/- 0.45 L/yr vs 0.135 +/- 0.32 L/yr, p < 0.0001) [mean +/- SD]. This difference remained significant irrespective of whether the patient had obstructive (n = 319), or restrictive (n = 99) disease, and regardless of whether the patient continued or stopped smoking. In patients with an obstructive spirometry finding, we found a lower incidence of respiratory-related urgent care in favor of the statin group (0.12 +/- 0.29 patient-years vs 0.19 +/- 0.32/patient-years; p = 0.02). In smokers and former smokers, statins are associated with a slower decline in pulmonary function, independent of the underlying lung disease. Prospective, randomized trials are needed to study the effect of statins on lung function.


Asymmetric Hydrogen Bonding Catalysis for the Synthesis of Dihydroquinazoline-Containing Antiviral, Letermovir.
A weak Brønsted acid-catalyzed asymmetric guanidine aza-conjugate addition reaction has been developed. C2-symmetric, dual hydrogen-bond donating bistriflamides are shown to be highly effective in activating α,β-unsaturated esters toward the intramolecular addition of a pendant guanidinyl nucleophile. Preliminary mechanistic investigation, including density functional theory calculations and kinetics studies, support a conjugate addition pathway as more favorable energetically than an alternative electrocyclization pathway. This methodology has been successfully applied to the synthesis of the 3,4-dihydroquinazoline-containing antiviral, Letermovir, and a series of analogues.


Chronic effects of atrazine on estrus and mammary tumor formation in female Sprague-Dawley and Fischer 344 rats.
The chronic effects of dietary administration of atrazine at levels as high as 400 ppm on selected endocrine and tumor profiles were evaluated in Fischer 344 and Sprague-Dawley female rats. The study showed that lifetime dietary administration of atrazine at a maximum tolerated dose (MTD) to Sprague-Dawley female rats caused (1) lengthening of the estrous cycle, (2) increased number of days in estrus or under the influence of exposure to estrogen, (3) earlier onset of galactocele formation, and (4) earlier onset of mammary and pituitary tumor formation but not an increased incidence of mammary and pituitary tumors when compared to concurrent control rats. Fischer 344 female rats fed atrazine at an MTD exhibited slightly lengthened estrous cycles, but no effects were observed on estradiol or progesterone levels, or on the onset or incidence of mammary tumors. These results support a hypothesis that high-dose atrazine administration in Sprague-Dawley females is related to an acceleration of age-related endocrine changes leading to an earlier onset and/or increased incidence of mammary tumors. This endocrine-mediated response, which appears to be unique to the Sprague-Dawley female rat, occurs only at or above a threshold dose (the MTD) that interferes with normal estrous cycling, promoting prolonged exposure to endogenous estrogen.


[Harmless acute pancreatitis score on admission can accurately predict mild acute pancreatitis].
To evaluate the efficacy of harmless acute pancreatitis score (HAPS) on admission for predicting mild acute pancreatitis (MAP). We prospectively collected the data from consecutive AP patients admitted to West China Hospital between January, 2016 and August, 2017, and HAPS scores were calculated on admission. The clinical outcomes of the patients with harmless AP (HAPS>2) and those with non-harmless AP (HAPS≤2) were compared. MAP was defined based on the severity classification of 2012 Revised Atlanta guidelines. The area under the curve (AUC) of the receiver- operator characteristic curve (ROC), specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of HAPS on admission for predicting MAP were analyzed. Of the 703 patients with AP analyzed, 182 were predicted to have harmless AP and 521 to have non- harmless AP, and the patients in the latter group had significantly worse clinical outcomes (P < 0.001). The total number of patients with MAP was 359 in the study. The specificity, the sensitivity, the PPV and NPV of HAPS on admission for predicting MAP was 97.7% (95% CI: 95.4-99.0), 48.2% (95% CI: 42.9-53.3), 95.6% (95% CI: 91.5- 98.1) and 64.1% (95% CI: 59.8- 68.2), respectively, and the AUC was 0.749 (95% CI: 0.72- 0.78). HAPS score on admission can accurately predict MAP.


CADM1 and MAL promoter methylation levels in hrHPV-positive cervical scrapes increase proportional to degree and duration of underlying cervical disease.
Combined detection of cell adhesion molecule 1 (CADM1) and T-lymphocyte maturation-associated protein (MAL) promoter methylation in cervical scrapes is a promising triage strategy for high-risk human papillomavirus (hrHPV)-positive women. Here, CADM1 and MAL DNA methylation levels were analysed in cervical scrapes of hrHPV-positive women with no underlying high-grade disease, high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. CADM1 and MAL methylation levels in scrapes were first related to CIN-grade of the corresponding biopsy and second to CIN-grade stratified by the presence of 'normal' or 'abnormal' cytology as present in the accompanying scrape preceding the cervical biopsy. The scrapes included 167 women with ≤ CIN1, 54 with CIN2/3 and 44 with carcinoma. In a separate series of hrHPV-positive scrapes of women with CIN2/3 (n = 48), methylation levels were related to duration of preceding hrHPV infection (PHI; <5 and ≥ 5 years). Methylation levels were determined by quantitative methylation-specific PCR and normal cytology scrapes of hrHPV-positive women with histologically ≤ CIN1 served as reference. CADM1 and MAL methylation levels increased proportional to severity of the underlying lesion, showing an increase of 5.3- and 6.2-fold in CIN2/3, respectively, and 143.5- and 454.9-fold in carcinomas, respectively, compared to the reference. Methylation levels were also elevated in CIN2/3 with a longer duration of PHI (i.e. 11.5- and 13.6-fold, respectively). Moreover, per histological category, methylation levels were higher in accompanying scrapes with abnormal cytology than in scrapes with normal cytology. Concluding, CADM1 and MAL promoter methylation levels in hrHPV-positive cervical scrapes are related to the degree and duration of underlying cervical disease and markedly increased in cervical cancer.


Short-term effects of workstation exercises on musculoskeletal discomfort and postural changes in seated video display unit workers.
In recent years, a number of exercise programs have been developed for computer operators in order to promote movement and to reduce musculoskeletal discomfort. Tests of the effectiveness of these exercise programs, especially in field trials, are rare. The authors tested the hypothesis that doing regular, short-term (<10 days) exercises while at a workstation would decrease musculoskeletal discomfort and increase in-chair movement (ICM). Eleven directory assistance operators (8 female, 3 male) with no recent history of musculoskeletal problems volunteered. In-chair movement was measured by tracking the center of pressure at the buttock-chair interface as subjects sat on a pressure-sensitive mat. Musculoskeletal discomfort was rated through the use of the Body Part Discomfort Scale (BPDS) and a body map. We used a revised Dataspan exercise program. Operators were tested for 2 hours, on 2 occasions: before and after doing exercises for 3- to 5-day shifts. During each test, ICM was measured during three 15-minute periods at the start of the test and at the end of hours 1 and 2. Subjects rated musculoskeletal discomfort per body part using the BPDS at 30, 60, and 120 minutes of each test. The effects of exercises on ICM and BPDS ratings were examined with a two-way repeated-measures analysis of variance with day (2) x time (3) designs. When subjects were doing their exercises, ICM was higher at the start and hour 1, and perceived discomfort was lower during each test period (start, hour 1, and hour 2). When not exercising, subjects' musculoskeletal discomfort increased over time and was higher during all test periods. Exercises done by video display unit operators while at a workstation resulted in short-term decreases in both musculoskeletal discomfort and postural immobility. These results suggest that workstation exercises may be beneficial.


Contamination susceptibility of three needleless and one standard needle injection systems.
To compare in vitro the contamination susceptibility of three needleless and one standard needle injection systems. The Baxter InterLink, St. Paul Medical Key-Lok, Braun SafSite, and Becton Dickinson heparin lock, were compared. Fifty of each were studied. Each system was connected to a culture bottle and injected 30 times over 72 hr. The manufacturers' directions were followed except for Braun's, which recommend that a new sterile cap be used after each injection. Instead, the same cap was used after each injection to reflect day-to-day clinical practice. Culture bottles were subsequently analyzed for bacterial growth. The contamination rates for the heparin lock, InterLink, Key-Lok, and SafSite were 3/50 (6%), 6/50 (12%), 4/50 (8%), and 36/50 (72%), respectively. All positive cultures grew coagulase-negative staphylococcus species. There was no difference in contamination rates between the InterLink, Key-Lok, and heparin lock designs. The contamination rate of the SafSite was higher (P < 0.001) than the other three systems. The InterLink and Key-Lok systems had a similarly low contamination susceptibility as a standard needle injection system. It was not clear if the high contamination rate found with the SafSite system was due to non-adherence to the manufacturer's directions for handling.


[Hernioplasty compared: Shouldice-Trabucco-Lichtenstein].
The authors report their experience with the mostly used technique of hernioplasty. They compare the Shouldice hernioplasty, development of the traditional Bassini, with the Trabucco and Lichtenstein techniques in which synthetic prosthesis are used. The two surgical departments participating to this study present 234 patients who underwent hernioplasty with the above mentioned techniques. The authors consider local and general complications during the postoperative time and after a 6-month follow-up. Results indicate that the surgical techniques used are efficient in terms of low complication rates and reduced hospitalization.


Libera me, Domine: Christian Roots of Palliative Care.
This article reviews key aspects of the history of the emergence of palliative care to point out that the language and expressions that are routinely used in communicating with palliative care patients are often infused with an unrecognized religious coloration.


Exploring Audiologists' Language and Hearing Aid Uptake in Initial Rehabilitation Appointments.
The study aimed (a) to profile audiologists' language during the diagnosis and management planning phase of hearing assessment appointments and (b) to explore associations between audiologists' language and patients' decisions to obtain hearing aids. Sixty-two audiologist-patient dyads participated. Patient participants were aged 55 years or older. Hearing assessment appointments were audiovisually recorded and transcribed for analysis. Audiologists' language was profiled using two measures: general language complexity and use of jargon. A binomial, multivariate logistic regression analysis was conducted to investigate the associations between these language measures and hearing aid uptake. The logistic regression model revealed that the Flesch-Kincaid reading grade level of audiologists' language was significantly associated with hearing aid uptake. Patients were less likely to obtain hearing aids when audiologists' language was at a higher reading grade level. No associations were found between audiologists' use of jargon and hearing aid uptake. Audiologists' use of complex language may present a barrier for patients to understand hearing rehabilitation recommendations. Reduced understanding may limit patient participation in the decision-making process and result in patients being less willing to trial hearing aids. Clear, concise language is recommended to facilitate shared decision making.


In vitro development of B lymphocytes from long-term cultured precursor cells.
An in vitro system for the study of B-lymphocyte differentiation from precursor elements has been established. Two separate sets of culture conditions are utilized to control B-lymphocyte precursor growth versus differentiation. The first, modeled after the bone marrow culture system of Dexter and colleagues [Dexter, T. M. & Testa, N. G. (1976) in Methods in Cell Biology, ed. Prescott, D. M. (Academic, New York), Vol. 14, pp. 387-395], allows precursor replication whereas the second set of culture conditions is permissive for differentiation to more mature members of the B-lymphocyte lineage. The shift from one set of conditions to the other allows us to follow the kinetics of this differentiation from precursor cells to pre-B and B lymphocytes over a 5-week period. The resulting population of B-lineage cells synthesizes heterogeneous immunoglobulin molecules as analyzed by two-dimensional gel electrophoresis and has a heterogeneous array of immunoglobulin gene rearrangements, suggesting an origin from very early uncommitted precursors. This in vitro system will allow the study of genes that regulate B-lymphocyte differentiation and will aid in the isolation of the cellular intermediates in the B-cell developmental pathway.


Chronic Imaging of Mouse Brain: From Optical Systems to Functional Ultrasound.
Utilization of functional ultrasound (fUS) in cerebral vascular imaging is gaining popularity among neuroscientists. In this article, we describe a chronic surgical preparation method that allows longitudinal studies and therefore is applicable to a wide range of studies, especially on aging, stroke, and neurodegenerative diseases. This method can also be used with awake mice; hence, the deleterious effects of anesthesia on neurovascular responses can be avoided. In addition to fUS imaging, this surgical preparation allows researchers to take advantage of common optical imaging methods to acquire complementary datasets to help increase the technical rigor of studies. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Surgical preparation of mouse chronic cranial windows using polymethylpentene Basic Protocol 2: Imaging of mice with chronic cranial windows.


Diagnostic policies of minor depressive illness by two differently trained groups of general practitioners.
Two homogeneous general practitioner groups were differently trained for approaching minor depressive illness. One group was presented the depression problem in a traditional manner while the other was led to particularly emphasize the importance of the doctor-patient relationship, according to Balint's suggestions. Both groups adopted the same case record form. The structural analysis of diagnostic judgement based on the logistic transformation of recorded data made it possible to evidence several qualitative differences between the groups, probably deriving from the different training.


Incidence of benign results after laparoscopic radical nephroureterectomy.
Studies of patients with benign pathologic lesions who underwent laparoscopic radical nephroureterectomy (RNU) with preoperative suspicion of upper urinary tract urothelial carcinoma are lacking. The aim of this retrospective cross-sectional study was to evaluate the incidence of benign pathologic lesions on laparoscopic RNU for upper urinary tract tumors that are presumed to be urothelial carcinoma. The clinicopathologic characteristics of these lesions were also determined. Between January 2004 and December 2010, 244 patients underwent laparoscopic RNU for possible upper urinary tract urothelial carcinoma at our institute. Seven (2.9%) had benign lesions at the final pathologic examination. The preoperative features of these patients were investigated, including imaging findings, urine cytologic results, and ureteroscopic findings. The 7 patients comprised 5 men and 2 women. The lesions were located in the ureter in 5 patients and in the renal pelvis in 2. All patients underwent preoperative voided urine cytology and cystoscopy. Two patients underwent preoperative ureteroscopy. In 1 patient, definite pathologic lesions were not identified in the surgical specimen. Urinary tract tuberculosis was diagnosed in 1 patient, inflammatory pseudotumor in 2, and fibroepithelial polyps in 1. In 2 patients, stones were detected (stone with atypical papillary urothelial hyperplasia and polypoid ureteritis with ureter stone, respectively) after laparoscopic RNU. Benign pathologic lesions were detected in 7 patients (2.9%) who had undergone laparoscopic RNU for upper urinary tract tumors that were presumed to be urothelial carcinoma. The description of these false-positive cases will help improve the preoperative counseling of these patients.


Identification and characterization of colorectal cancer using Raman spectroscopy and feature selection techniques.
This study aims to detect colorectal cancer with near-infrared Raman spectroscopy and feature selection techniques. A total of 306 Raman spectra of colorectal cancer tissues and normal tissues are acquired from 44 colorectal cancer patients. Five diagnostically important Raman bands in the regions of 815-830, 935-945, 1131-1141, 1447-1457 and 1665-1675 cm(-1) related to proteins, nucleic acids and lipids of tissues are identified with the ant colony optimization (ACO) and support vector machine (SVM). The diagnostic models built with the identified Raman bands provide a diagnostic accuracy of 93.2% for identifying colorectal cancer from normal Raman spectroscopy. The study demonstrates that the Raman spectroscopy associated with ACO-SVM diagnostic algorithms has great potential to characterize and diagnose colorectal cancer.


The receptor PTPRU is a redox sensitive pseudophosphatase.
The receptor-linked protein tyrosine phosphatases (RPTPs) are key regulators of cell-cell communication through the control of cellular phosphotyrosine levels. Most human RPTPs possess an extracellular receptor domain and tandem intracellular phosphatase domains: comprising an active membrane proximal (D1) domain and an inactive distal (D2) pseudophosphatase domain. Here we demonstrate that PTPRU is unique amongst the RPTPs in possessing two pseudophosphatase domains. The PTPRU-D1 displays no detectable catalytic activity against a range of phosphorylated substrates and we show that this is due to multiple structural rearrangements that destabilise the active site pocket and block the catalytic cysteine. Upon oxidation, this cysteine forms an intramolecular disulphide bond with a vicinal "backdoor" cysteine, a process thought to reversibly inactivate related phosphatases. Importantly, despite the absence of catalytic activity, PTPRU binds substrates of related phosphatases strongly suggesting that this pseudophosphatase functions in tyrosine phosphorylation by competing with active phosphatases for the binding of substrates.


High-grade serous ovarian cancer 3 years after bilateral salpingectomy: A case report.
Although epithelial ovarian cancer commonly originates from the ovarian surface epithelium and/or ovarian inclusion cysts, it was recently proposed that high-grade serous ovarian cancer (HGSC) develops from the Fallopian tubes. In our department, we encountered a case of HGSC that contradicts the hypothesis of a tubal origin for HGSC. A 51-year-old postmenopausal woman had undergone hysterectomy, left oophorectomy and bilateral salpingectomy for uterine myoma. Three years later, the patient was diagnosed with stage IV ovarian cancer and underwent primary debulking surgery. The pathological examination revealed HGSC, although there was no evidence of serous tubal intraepithelial carcinoma or any other type of cancer in the previously resected left ovary and bilateral Fallopian tubes. Moreover, p53 overexpression was not detected in the right ovarian cancer specimen, while paired box gene 8, a marker of Fallopian tube epithelium, was highly expressed. Therefore, HGSC may develop from an inclusion cyst with metaplasia of from the ovarian surface epithelium.


How does the media portray drinking water security in Indigenous communities in Canada? An analysis of Canadian newspaper coverage from 2000-2015.
Drinking water insecurity and related health outcomes often disproportionately impact Indigenous communities internationally. Understanding media coverage of these water-related issues can provide insight into the ways in which public perceptions are shaped, with potential implications for decision-making and action. This study aimed to examine the extent, range, and nature of newspaper coverage of drinking water security in Canadian Indigenous communities. Using ProQuest database, we systematically searched for and screened newspaper articles published from 2000 to 2015 from Canadian newspapers: Windspeaker, Toronto Star, The Globe and Mail, and National Post. We conducted descriptive quantitative analysis and thematic qualitative analysis on relevant articles to characterize framing and trends in coverage. A total of 1382 articles were returned in the search, of which 256 articles were identified as relevant. There was limited coverage of water challenges for Canadian Indigenous communities, especially for Métis (5%) and Inuit (3%) communities. Most stories focused on government responses to water-related issues, and less often covered preventative measures such as source water protection. Overall, Indigenous peoples were quoted the most often. Double-standards of water quality between Indigenous and non-Indigenous communities, along with conflict and cooperation efforts between stakeholders were emphasized in many articles. Limited media coverage could undermine public and stakeholder interest in addressing water-related issues faced by many Canadian Indigenous communities.


Social capital and psychological distress of elderly in Japanese rural communities.
The growing recognition of the social determinants of health has stimulated research on social capital and mental health. We explored new empirical evidence regarding whether social capital was a determinant of psychological distress. Baseline surveys examining psychological distress were conducted in two towns in 2006–2007 (participation rates for those aged 20 or over were 27.6 per cent, 6.1 per cent). We also conducted follow-up surveys in 2008 to capture the social capital measured by trust. By linking these data and excluding the missing data, 141 males and 234 females remained as the subjects of our study. Results showed that the odds ratios of psychological distress was higher in groups with low social capital measured by trust (odds ratio 2.17; 95 per cent CI, 1.40-3.36), than those in groups with high social capital. Further, we examined the interaction effect of social capital and social support. The odds ratios of psychological distress was higher in groups with some social support/lower trust (odds ratio 2.21; 95 per cent CI, 1.36-3.58) or no social support/lower trust (odds ratio 2.07; 95 per cent CI, 1.06–4.05), than those in groups with some social support/higher trust. These findings reinforce the hypothesized discussion regarding pathways from social capital to psychological distress via supportive relationships.


Early Cytomegalovirus Reactivation in Renal Recipients Is Associated with High Levels of B Cell Maturation Antigen Transcript Expression Prior to Transplantation.
Cytomegalovirus (CMV) infection is the most frequent infection episode in kidney transplant (KT) recipients. Reactivation usually occurs in the first three months after transplantation and is associated with higher cellular and/or antibody-mediated rejection rates and poorer graft performance. CMV induces the expression of BAFF (B-cell-activating factor, a cytokine involved in the homeostasis of B cells), which communicates signals for survival and growth to B cells and virus-specific plasma cells via the R-BAFF (BAFF receptor), TACI (the calcium modulator, the cyclophilin ligand interactor), and BCMA (B cell maturation antigen) receptors. These molecules of the BAFF system have also been suggested as biomarkers for the development of alloantibodies and graft dysfunction. This prospective study included 30 CMV-IgG seropositive KT recipients. The expression levels of the genes BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA) in peripheral blood leukocytes (PBL) pre-KT were determined using qPCR. qPCR was also used to monitor CMV reactivation in the first three months following KT. The remainder of the KT recipients were classified as CMV- reactivation, and those with more than 500 copies/mL in at least one sample were classified as CMV+ reactivation. There were no discernible variations in the BAFF-R and TACI transcript expression levels. In the CMV+ group, we examined the relationship between the transcript levels and peak viremia. Peak viremia levels and BCMA transcript levels showed a strong correlation. BAFF-R and TACI expressions showed no measurable differences. In patients with early CMV reactivation, high BCMA receptor expression was associated with increased plasmablast, lymphocyte B cell class-switched levels (LBCS), and viral load. Our findings demonstrate that pre-KT BCMA transcript levels increased in KT recipients with early CMV reactivation. These transcript levels positively correlate with peak viremia and weakly with plasmablast and LBCS levels in PBLs.


Psychological effects of the COVID-19 pandemic - what do we know about them?
The coronavirus disease 2019 (COVID-19) pandemic was a shock to the whole world. This pandemic caused not only many deaths of people of all ages and health effects that are still difficult to assess, but also economic, and psychological ones. Numerous studies have shown that chronic stress related to social isolation and fear of contagion increased the rates of development of anxiety, depression syndrome, emotional eating, and posttraumatic stress disorder (PTSD). The increased rate of substance use and antidepressant drugs has also been observed. Depression is included in the symptoms of long-COVID syndrome. The data on the deterioration of mental states of children and adolescents during the COVID-19 pandemic are particularly worrying. Some studies have shown increased suicide rates during and after the COVID-19 pandemic. The deterioration of mental health can also have long-term consequences in terms of physical health, for example, emotional eating (EE) associated with depressed mood and anxiety may increase the incidence of binge eating disorder (BED) and addictive eating. Consequently, the number of patients with overweight and obesity and its complications will increase. Problems related to the deterioration of the mental and physical health of the population will increase the burden on the healthcare system. Another important problem is psychological disturbances related to the COVID-19 pandemic developed in healthcare workers. It is necessary to take systemic actions aimed at improving mental health, although it will not be easy in the era of the general global economic crisis, which may deepen the psychological problems from the time of the pandemic. Therefore, the aim of our manuscript is to analyze the available data on the psychological effects of the COVID-19 pandemic on the general population and healthcare workers.


Can nurses rise to the public health challenge? How a novel solution in nurse education can address this contemporary question.
This paper raises the problem of how improvements in health outcomes, a key component in many governments' strategies, can be achieved. The work highlights a novel undergraduate educational approach which offers solutions to public health challenges within nursing. Against the backdrop of one UK university institution it discusses approaches that can guide nursing students towards a deeper understanding and engagement within the principles of public health. It then proposes how nurses can use their learning to become leaders of health improvement.


A Randomized Phase II Study of Maintenance Bevacizumab, Pemetrexed or Bevacizumab Plus Pemetrexed for Advanced Non-squamous Non-small Cell Lung Cancer.
Continuation maintenance therapy is standard for advanced nonsquamous non-small cell lung cancer; however, the optimal maintenance strategy has yet to be determined. Patients without disease progression after four cycles of carboplatin (CBDCA)+ pemetrexed (PEM)+ bevacizumab (BEV) were randomized to maintenance therapy with BEV, PEM, or BEV+PEM. The primary endpoint was 1-year progression-free survival (PFS) rate. Of the 90 patients enrolled, 64 were randomly assigned to maintenance therapy. The 1-year PFS rate was 9.1% in the BEV arm, 19.1% in the PEM arm, and 19.1% in the BEV+PEM arm. The median PFS and overall survival (OS) were 4.0 and 43.1 months in the BEV arm, 4.5 and 32.0 months in the PEM arm, and 6.4 and 41.8 months in the BEV+PEM arm. The median PFS was numerically better in the BEV+PEM arm, but the median OS was not significantly different among the three arms.


Identification of two novel regulated serines in the N terminus of beta-catenin.
Beta-catenin plays a key role in the Wnt signaling cascade. The levels of beta-catenin within a cell are regulated via phosphorylation of the N terminus of beta-catenin by GSK-3beta. The phosphorylation leads to ubiquitination and subsequent degradation of the protein. Thus far three serines (S33, 37, 45) and one threonine (T41) are considered to be the substrates for GSK-3beta phosphorylation. Indeed, these amino acids are regularly mutated in tumors, resulting in beta-catenin molecules with enhanced transcriptional activity. Aligning N-terminal sequences of beta-catenin homologues of different species revealed two other highly conserved serines (S23, 29), which have also been found mutated in tumors. We show that these serines are modified in the same fashion as that of the known regulatory residues. During embryogenesis, the phosphorylation status of S23 and S29 appears to be actively regulated. Nevertheless, constructs harboring the mutations found in tumors fail to show enhanced transcriptional activity or transforming properties.


Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide prevent inducible nitric oxide synthase transcription in macrophages by inhibiting NF-kappa B and IFN regulatory factor 1 activation.
High-output nitric oxide (NO) production from activated macrophages, resulting from the induction of inducible NO synthase (iNOS) expression, represents a major mechanism for macrophage cytotoxicity against pathogens. However, despite its beneficial role in host defense, sustained high-output NO production was also implicated in a variety of acute inflammatory diseases and autoimmune diseases. Therefore, the down-regulation of iNOS expression during an inflammatory process plays a significant physiological role. This study examines the role of two immunomodulatory neuropeptides, the vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptide (PACAP), on NO production by LPS-, IFN-gamma-, and LPS/IFN-gamma-stimulated peritoneal macrophages and the Raw 264.7 cell line. Both VIP and PACAP inhibit NO production in a dose- and time-dependent manner by reducing iNOS expression at protein and mRNA level. VPAC1, the type 1 VIP receptor, which is constitutively expressed in macrophages, and to a lesser degree VPAC2, the type 2 VIP receptor, which is induced upon macrophage activation, mediate the effect of VIP/PACAP. VIP/PACAP inhibit iNOS expression and activity both in vivo and in vitro. Two transduction pathways appear to be involved, a cAMP-dependent pathway that preferentially inhibits IFN regulatory factor-1 transactivation and a cAMP-independent pathway that blocks NF-kappa B binding to the iNOS promoter. The down-regulation of iNOS expression, together with previously reported inhibitory effects on the production of the proinflammatory cytokines IL-6, TNF-alpha, and IL-12, and the stimulation of the anti-inflammatory IL-10, define VIP and PACAP as "macrophage deactivating factors" with significant physiological relevance.


Value of EZSCAN parameters for diabetes screening in Chinese.
To study the parameters of EZSCAN as a screening tool for diabetes in Chinese. A total of 6,270 subjects participated in the study. All subjects underwent tests of EZSCAN, fasting plasma glucose (FPG), oral glucose tolerance test and HbA1c. 1. All subjects were divided into 4 groups: the normal group, sugar metabolic abnormalities as low-risk group, middle-risk group and high-risk group. The difference of diabetes incidence among the 4 groups was statistically significant. With the increase of EZSCAN score, the prevalence of diabetes increased significantly. But there is no statistically difference between the low-risk group and the middle-risk group. 2. After adjustment for other variables, there is significantly positive relationship among EZSCAN risk score and the risk of diabetes. Meanwhile there is no statistically difference between the low-risk group and the middle-risk group. 3. The cut-off point of EZSCAN for diabetes was 44.5% with the sensitivity was 73.2% which was higher than of FPG and HbA1c. As EZSCAN-diabetes risk score increases, the risk of diabetes increases. EZSCAN can be used as a tool for screening for diabetes. At the best screening diabetes cut-off point value 44.5%, the sensitivity is higher than traditional method of FPG and HbA1c.


Test-retest reliability in isokinetic muscle strength measurements of the shoulder.
Test-retest reliability is important for long-term follow-up; however, data on the reliability of isokinetic dynamometry of the shoulder are scarce. Twenty subjects (50% male) were measured; 10 with asymmetrical use of the arms (mean age 27 years) and 10 used their arms symmetrically (mean age 32 years). A Biodex dynamometer (Multi joint system 2) was used. Abduction/adduction and external/internal rotation were measured following a standardized protocol. Performed scheme: two sessions with a 2-week interval, all measurements were done with 60 degrees/second (5 repetitions) and respectively 120 degrees/second and 180 degrees/second (10 repetitions). Differences in the mean peak torques, split for muscle group and gender were significant. Intraclass correlation coefficients ranged from 0.69 to 0.92. This implies good to excellent reliability in research on groups. To determine test-retest reliability of two consecutive individual measurements smallest detectable differences (SDD) were computed and ranged from 21% to 43%. It is questionable whether the SDDs are small enough to detect real changes in muscle strength.


Placement predicament.
Regarding the fall in applications for nursing degree courses, the problem is that it is not possible for many people to attend placements as part of nurse training and hold a full-time job at the same time.


Evaluation of c-kit (CD 117) expression as a prognostic factor in testicular germ cell tumors: an Izmir Oncology Group (IZOG) study.
Despite the successful use of targeted and molecular therapies in other cancers, little progress has been made in the management of testicular germ cell tumors (TGCTs). c-kit (CD 117) is a good target for cancer treatment and possesses an impressive role in the current oncological practice. We aimed to evaluate c-kit expression in early stage TGCTs as a prognostic factor. Patients with TGCTs who were referred to the Medical Oncology Clinic and underwent curative surgical operation were included in our study before starting chemo- therapy. Immunohistochemistry was performed on formalin-fixed and paraffin-embedded three-micrometer thick sections with CD 117 Rabbit Anti c-kit in vitro gene kit. Biochemically, we utilized AFP and β-HCG Immunlite 2000 device with solid phase chemiluminescent immunometric method, and LDH Roche models with the DP-standardized UV method. AFP 0-15 ng/ml, β-HCG < 0.1 mlu/ml and LDH 240-480 mg/dl were considered as normal values. Sixty-five patients were included in our study. Forty-one (63%) patients had non-seminoma tumors (NSGCTs) and 24 (37%) had seminoma. Statistically significant c-kit expression was found in patients with seminoma (p<0.0001). There was no difference between negative or positive c-kit expression in terms of clinicopathological characteristics, including preoperative serum levels of AFP, β-HCG, LDH, lymph node involvement, distant metastasis, and IGCCCG risk classification. No correlation was found between these parameters and 5-year progression free survival (PFS) rate except for tumor stage, presence of lymph node metastasis and IGCCCG score (p=0.001, p=0.04, and p=0.0001, respectively). Five-year PFS rate of patients with positive CD 117 was 72.2% (95% CI, 54.6-89.8), and 56.6% (95% CI, 31.2-82.1) for those without CD 117 expression involvement (p=0.12). So far, there has been no significant breakthrough in the treatment of cisplatin-refractory TGCTs in the era of targeted therapies. No prognostic importance of c-kit expression has been found in our study. However, we believe that c-kit expression, in numerical terms, can be considered as a good prognostic factor for patients with TGCTs. The fact that all seminoma cases displayed positive c-kit expression is what we think has driven this result.


Muscarinic M2 receptor promotes vasopressin synthesis in mice supraoptic nuclei.
Muscarinic acetylcholine receptors have been suggested to be implicated in arginine-vasopressin secretion because intracerebroventricular muscarinic agonist administration induces arginine-vasopressin release into the circulation. Although which subtype is involved in the regulation of arginine-vasopressin secretion is unclear, M2 receptors have been reported to be highly expressed in the hypothalamus. In the present study, M2 receptor-knockout mice were used to elucidate whether M2 receptor regulates arginine-vasopressin synthesis in the paraventricular nuclei and supraoptic nuclei of the hypothalamus. The number of arginine-vasopressin-immunoreactive neurons in M2 receptor-knockout mice was significantly decreased in the supraoptic nuclei, but not in the paraventricular nuclei compared with wild-type mice. Plasma arginine-vasopressin level in M2 receptor-knockout mice was also significantly lower than in the wild-type mice. Urinary volume and frequency as well as water intake in M2 receptor-knockout mice were significantly higher than those in wild-type mice. The V2 vasopressin receptor expression in kidneys of M2 receptor-knockout mice was comparable with that of wild-type mice, and increased urination in M2 receptor-knockout mice was significantly decreased by administration of desmopressin, a specific V2 receptor agonist, suggesting that V2 receptors in the kidneys of M2 receptor-knockout mice are intact. These results suggest that M2 receptors promote arginine-vasopressin synthesis in the supraoptic nuclei and play a role in the regulation and maintenance of body fluid.


PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury.
Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI). Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C). The study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, -7.7 [6.1]; P < .001, 95 % CI: -8.4, -7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, -8.2 [-9.4, -7.0]) and numerically exceeds the improvement seen with placebo in that study (-5.7 [-6.8, -4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were "much" or "very much" improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related. DM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q. Clinicaltrials.gov, NCT01799941, registered on 25 February 2013.


Comparison of blue nucleic acid dyes for flow cytometric enumeration of bacteria in aquatic systems.
Seven blue nucleic acid dyes from Molecular Probes Inc. (SYTO-9, SYTO-11, SYTO-13, SYTO-16, SYTO-BC, SYBR-I and SYBR-II) were compared with the DAPI (4',6-diamidino-2-phenylindole) method for flow cytometric enumeration of live and fixed bacteria in aquatic systems. It was shown that SYBR-II and SYTO-9 are the most appropriate dyes for bacterial enumeration in nonsaline waters and can be applied to both live and dead bacteria. The fluorescence signal/noise ratio was improved when SYTO-9 was used to stain living bacteria in nonsaline waters. Inversely, SYBR-II is more appropriate than SYTO dyes for bacterial enumeration of unfixed and fixed seawater samples.


Considerations for curriculum design.
Educational values held by academic and clinical faculties subtly but strongly influence curriculum design in physical therapy education. Five major value orientations, Curriculum as the Development of Cognitive processes, Curriculum as Technology, Curriculum as Self-Actualization, Curriculum as Social Reconstruction-Relevance, and Curriculum as Academic Rationalism, are presented. The suggestion is made that these underlying value-orientations influence the choice of curriculum design more than do "available resources." A second component of curriculum design, i.e., evaluation of student performance, also influences and is influenced by the direction and development of physical therapy curricula. A plea is made for expressive objectives and outcome objectives to be considered along with instructional or behavioral objectives to yield more comprehensive and creative appraisals of student growth.


Present and future of anti-ageing epigenetic diets.
The rapid technological advancements achieved in the last years have boosted the progressive identification of age-associated epigenetic changes. These studies not only contribute to shed light on the molecular basis of ageing and age-related diseases but, given the plasticity of epigenetic modifications, also provide the basis for anti-ageing interventions to counteract the onset of age-related diseases. In this review we will discuss nutritional interventions as a promising approach that can positively counteract epigenetic changes associated with ageing and promote the health for the elderly. First, we will give an overview of age-associated epigenetic signatures, focusing on DNA methylation. Then, we will report recent evidences regarding the epigenetic changes induced by nutritional interventions in the adulthood (referred as "epigenetic diets"), such as (i) caloric/dietary restriction, (ii) diet supplementation with nutrients involved in one-carbon metabolism and (iii) diet supplementation with bioactive food components. Attention will be drawn on the limits of current studies and the need of proper human models, such as those provided by the ongoing European project NU-AGE. Finally, we will discuss the potential impact of epigenetic diets on inflammaging and age-related diseases, focusing on cardiovascular disease, highlighting the involvement of epigenetic modifications other than DNA methylation, such as microRNA.


Interactions between alcohol and gastric metabolizing enzymes: practical implications.
It has been demonstrated recently that some portion of ingested alcohol does not enter the systemic circulation and is not retained in the gastrointestinal tract; instead, gastric oxidation or first-pass metabolism of ethanol occurs in the stomach, catalyzed by gastric alcohol dehydrogenase. First-pass metabolism of ethanol is minimal in the fasting state; it is lower in women than in men, and in alcoholics than in nonalcoholics; and it is abolished in patients after subtotal gastrectomy. In addition, some drugs may affect first-pass ethanol metabolism. Studies of the effects of H2-receptor antagonists on blood ethanol levels are reviewed. It is concluded that some H2-receptor antagonists (cimetidine and nizatidine, in particular) can inhibit gastric ethanol oxidation and thus increase blood alcohol levels after drinking. The clinical and medicolegal implications of these findings are discussed.


Bulk Polymerization of Acrylic Acid Using Dielectric-Barrier Discharge Plasma in a Mesoporous Material.
This research investigated a non-thermal, dielectric-barrier discharge (DBD) plasma-based approach to prepare poly(acrylic acid) (PAA) from acrylic acid in its liquid state at atmospheric temperature and pressure. Neither additives nor solvents were needed, and the polymerization was accomplished both as a film and inside a sheet of mesoporous paper. All prepared samples were characterized and the DBD plasma-initiated kinetics were analyzed for the polymerization of acrylic acid. Using FTIR semi-quantitative analysis, the degree of polymerization was monitored, and the reaction followed an overall second-order kinetic model with respect to the DBD-initiated polymerization. Additionally, the application of a PAA-modified paper as a water retention cloth or 'wet wipe' was investigated. The results showed that the PAA-modified paper substrates using DBD plasma increased water retention as a function of plasma treatment time.


Photophysics of soret-excited tin(IV) porphyrins in solution.
The photophysics of low-chlorin tin(IV) tetraphenylporphyrin dihydroxide, a core building block for axially substituted supramolecular tin porphyrin constructs, has been studied in a variety of hydrogen-bonding, nonpolar, and aprotic polar solvents using steady-state, nanosecond, and femtosecond time-resolved emission, and femtosecond time-resolved absorption methods. In hydrogen-bonding solvents the metalloporphyrin exists as solvated monomers, and its Soret-excited S2 state in these solvents exhibits the expected linear energy gap law relationship with first-order population decay times in the 0.8 to 1.7 ps range. Evidence is presented that this metalloporphyrin aggregates in other solvents at the concentrations typically used for these ultrafast measurements and yields species-averaged time-resolved data. Cw laser excitation in the Q-band under deaerated conditions produces weak S2-S0 fluorescence (photon upconversion) as a result of triplet-triplet annihilation.


Prophylactic Therapy Response in Children with Abdominal Migraine: A Single Centre Experience in Oman.
Abdominal migraine (AM) is a very common functional gastrointestinal disorder in children. This study reports the clinical features and response of AM to prophylactic treatment in children. This retrospective study was conducted between January 2010 and December 2019 at the Royal Hospital in the Sultanate of Oman. This study included children aged ≤ 13 years with a diagnosis of AM based on the Rome IV criteria for functional diagnoses. Clinical, demographic, and treatment data were collected. Seventy-four children were identified, of which 43 were eligible for inclusion in this study. The median age at the onset of symptoms was 7 years (range, 2-12 years). The most frequent symptoms were headache (81.4%), nausea (79.1%), and vomiting (72.1%). Of the total cohort, 46.5%, 23.3%, and 6.9% received riboflavin, pizotifen, and propranolol monotherapy, respectively. Combination therapy was also used; 16.3% of children received pizotifen and propranolol, 4.7% received riboflavin and pizotifen, and 2.3% received riboflavin and propranolol. Patients treated with propranolol monotherapy showed 100% clinical improvement and those treated with riboflavin or pizotifen monotherapy showed 90% clinical improvement. Response to combination therapy with pizotifen and propranolol was 71.4%, and with riboflavin and pizotifen was 100%. In addition, treatment response was significantly associated with the presence of vomiting (p=0.039). We found a favorable response to various modalities and combination treatments with riboflavin, pizotifen, and propranolol in children with AM. In addition, the presence of vomiting may predict treatment response.


Short-segment and intrasphincteric gastroesophageal reflux.
The traditional gold standard for measuring gastroesophageal acid reflux has been by placing a pH sensor 5 cm proximal to the lower esophageal sphincter. It is known that damage induced by reflux is maximal near to the gastroesophageal junction and this has stimulated interest in determining acid reflux at that site. The extent of esophageal exposure from refluxing gastric acid is inversely related to the distance proximal to the gastroesophageal junction. In addition, the pH transition point from gastric to esophageal pH can be displaced proximally within the lower esophageal sphincter without complete loss of sphincter tone. This intrasphincteric reflux is associated with proximal extension of cardia mucosa because of columnar metaplasia of the most distal esophageal squamous mucosa. The most distal esophageal mucosa is exposed to substantially greater gastric acid refluxate than that recorded at the traditional site 5 cm proximal to the lower esophageal sphincter.


Mitochondrial Membrane Potential Independent Near-Infrared Mitochondrial Viscosity Probes for Real-Time Tracking Mitophagy.
Mitophagy is a vital cellular process playing vital roles in regulating cellular metabolism and mitochondrial quality control. Mitochondrial viscosity is a key microenvironmental index, closely associated with mitochondrial status. To monitor mitophagy and mitochondrial viscosity, three molecular rotors (Mito-1, Mito-2, and Mito-3) were developed. All probes contain a cationic quinolinium unit and a C12 chain so that they can tightly bind mitochondria and are not affected by the mitochondrial membrane potential. Optical studies showed that all probes are sensitive to viscosity changes with an off-on fluorescence response, and Mito-3 shows the best fluorescence enhancement. Bioimaging studies showed that all these probes can not only tightly locate and visualize mitochondria with near-infrared fluorescence but also effectively monitor the mitochondrial viscosity changes in cells. Moreover, Mito-3 was successfully applied to visualize the mitophagy process induced by starvation, and mitochondrial viscosity was found to show an increase during mitophagy. We expect Mito-3 to become a useful imaging tool for studying mitochondrial viscosity and mitophagy.


No wonder, it is a hybrid. Natural hybridization between Jacobaea vulgaris and J. erucifolia revealed by molecular marker systems and its potential ecological impact.
Progressive changes in the environment are related to modifications of the habitat. Introducing exotic species, and interbreeding between species can lead to processes that in the case of rare species or small populations threatens their integrity. Given the declining trends of many populations due to increased hybridization, early recognition of hybrids becomes important in conservation management. Natural hybridization is prevalent in Jacobaea. There are many naturally occurring interspecific hybrids in this genus, including those between Jacobaea vulgaris and its relatives. Although Jacobaea erucifolia and J. vulgaris often co-occur and are considered closely related, apart from the few reports of German botanists on the existence of such hybrids, there is no information on research confirming hybridization between them. Morphologically intermediate individuals, found in the sympatric distributions of J. vulgaris and J. erucifolia, were hypothesized to be their hybrids. Two molecular marker systems (nuclear and chloroplast DNA markers) were employed to test this hypothesis and characterize putative hybrids. Nuclear and chloroplast DNA sequencing results and taxon-specific amplified fragment length polymorphism (AFLP) fragment distribution analysis confirmed the hybrid nature of all 25 putative hybrids. The AFLP patterns of most hybrids demonstrated a closer relationship to J. erucifolia, suggesting frequent backcrossing. Moreover, they showed that several individuals previously described as pure were probably also of hybrid origin, backcrosses to J. erucifolia and J. vulgaris. This study provides the first molecular confirmation that natural hybrids between J. vulgaris and J. erucifolia occur in Poland. Hybridization appeared to be bidirectional but asymmetrical with J. vulgaris as the usual maternal parent.


Multi-exon Skipping Using Cocktail Antisense Oligonucleotides in the Canine X-linked Muscular Dystrophy.
Duchenne muscular dystrophy (DMD) is one of the most common lethal genetic diseases worldwide, caused by mutations in the dystrophin (DMD) gene. Exon skipping employs short DNA/RNA-like molecules called antisense oligonucleotides (AONs) that restore the reading frame and produce shorter but functional proteins. However, exon skipping therapy faces two major hurdles: limited applicability (up to only 13% of patients can be treated with a single AON drug), and uncertain function of truncated proteins. These issues were addressed with a cocktail AON approach. While approximately 70% of DMD patients can be treated by single exon skipping (all exons combined), one could potentially treat more than 90% of DMD patients if multiple exon skipping using cocktail antisense drugs can be realized. The canine X-linked muscular dystrophy (CXMD) dog model, whose phenotype is more similar to human DMD patients, was used to test the systemic efficacy and safety of multi-exon skipping of exons 6 and 8. The CXMD dog model harbors a splice site mutation in intron 6, leading to a lack of exon 7 in dystrophin mRNA. To restore the reading frame in CXMD requires multi-exon skipping of exons 6 and 8; therefore, CXMD is a good middle-sized animal model for testing the efficacy and safety of multi-exon skipping. In the current study, a cocktail of antisense morpholinos targeting exon 6 and exon 8 was designed and it restored dystrophin expression in body-wide skeletal muscles. Methods for transfection/injection of cocktail oligos and evaluation of the efficacy and safety of multi-exon skipping in the CXMD dog model are presented.


Anthropometric and performance variables discriminating elite American junior men weightlifters.
The purpose of this study is to identify physical and performance variables that discriminate elite American junior-aged men weightlifters from nonelite performers. Using a cross-sectional design, multiple discriminant analysis was used to determine field tests identifying elite male junior weightlifters. Young men who were participants (n = 115) at the Junior National and Junior Olympics Weightlifting Championships volunteered as subjects (mean +/- SD age = 14.8 +/- 2.3 years). Elite weightlifters (n = 20) were identified as the top 17.5% of national-level competitors when weightlifting performances were adjusted for body mass using the Sinclair equation. All other weightlifters were classified as nonelite (n = 95). Test batteries were performed immediately upon completion of a national-level weightlifting competition. Variables measured included easily-administered field tests of physical dimensions and body composition, muscular strength and power, flexibility, and gross motor control. The resulting regression equations correctly classified 84.35% of the weightlifters as elite or nonelite. Five variables significantly contributed to the discriminant analysis (Wilks Lambda = 0.6637392, chi(2) = 44.880, df = 5, p < 0.0001, adjusted R(2) = 0.67). Body mass index accounted for 23.13% of the total variance, followed by vertical jump (22.78%), relative fat (18.09%), grip strength (14.43%), and torso angle during an overhead squat (0.92%). The use of these 5 easily administered field tests is potentially useful as a screening tool for elite American junior men weightlifters.


Detection-theoretic analysis of same-different judgments for the amplitude discrimination of acoustic sinusoids.
Three methods were applied to determine which decision model best accounted for same-different judgments about the amplitude of acoustic sinusoids. The methods were (1) analysis of the shape of the receiver operating characteristic; (2) analysis of an observer's decision space; and (3) a correlation method based on the conditional-on-single-stimulus procedure. In one experiment, observers rated their confidence that a pair of 1-kHz sinusoids was drawn from the same or from different sets. The two sets had identical Gaussian distributions of decibel amplitudes, but their mean amplitudes differed by 3 dB. The differencing model, in which observers base their decision on the absolute difference between the two observations, accounted for the data better than the independent-observation model, in which observers compute independent likelihood ratios for each observation. A second experiment added to every trial an interval that contained a 1-kHz sinusoid whose amplitude equaled the grand mean of both stimulus sets. Despite this additional information, which is needed to adopt the independent-observation model, the differencing model again better accounted for the data.


Cross contamination of turkey carcasses by Salmonella species during defeathering.
Salmonella present on the feathers of live birds could be a source of contamination to carcass skin during defeathering. In this study, the possibility of transfer of Salmonella from the feathers of live turkeys to carcass tissue during the defeathering process at a commercial turkey processing plant was investigated. The contribution of scald water and the fingers of the picker machines to cross contamination were also examined. Over 4 visits, swab samples were collected from 174 randomly selected tagged birds before and after defeathering. Two swab samples from the fingers of the picker machines and a sample of scald water were also collected during each visit. Detection of Salmonella was carried out following standard cultural and identification methods. The DNA fingerprints obtained from pulsed field gel electrophoresis of Salmonella serotypes isolated before and after defeathering, from scald water, and from the fingers of the picker machines were compared to trace cross contamination routes. Salmonella prevalence was similar before and after defeathering during visits 2 and 3 and significantly increased after defeathering during visits 1 and 4. Over the 4 visits, all Salmonella subtypes obtained after defeathering were also isolated before defeathering. The results of this study suggest that Salmonella was transferred from the feathers to carcass skin during each visit. On each visit, the Salmonella subtypes isolated from the fingers of the picker machines were similar to subtypes isolated before and after defeathering, indicating that the fingers facilitate carcass cross contamination during defeathering. Salmonella isolated from scald water during visit 4 was related to isolates obtained before and after defeathering, suggesting that scald water is also a vehicle for cross contamination during defeathering. By using molecular subtyping, this study demonstrated the relationship between Salmonella present on the feathers of live turkeys and carcass skin after defeathering, suggesting that decontamination procedures applied to the external surfaces of live turkeys could reduce Salmonella cross contamination during defeathering.


Ionic currents in single smooth muscle cells of the human vas deferens.
Smooth muscle cells of the vas deferens have an important role in carrying sperms to the exterior but little is known of their electrophysiological properties. We characterized the voltage-gated ion channel currents in single smooth muscle cells of the human vas deferens (HVSMCs). We observed contractile responses of 8 circular smooth muscle strips of the human vas deferens to a high concentration (10 mM) of tetraethylammonium. HVSMCs were isolated using proteolytic enzymes (collagenase and papain), and were used for an electro-physiological study using whole cell and inside-out patch clamp configurations. The application of 10 mM tetraethylammonium induced rhythmic contractions of the strips. When HVSMCs were dialyzed with a KCl solution, step depolarizations of membrane potential evoked oscillatory outward K currents that were not inactivated. The large conductance Ca activated K (BKCa) and delayed rectifier components of the outward current were identified. The BKCa channel showed a large single channel conductance (162.7 +/- 13.2 pS with 5 mM K in the patch pipette). Two types of Ca currents were identified in the whole cell configuration. With a cell held at -50 mV an L-type Ca current was present during a depolarizing step pulse. From a holding potential of -90mV L-type and T-type Ca currents were elicited by depolarizing step pulses. HVSMCs have 2 (L and T) types of Ca channels and 2 types of K (BKCa and delayed rectifier) channels. Voltage dependent changes of these ion channels and their interactions may be important in regulating vas contractility.


Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL) amyloidosis.
Randomized studies have shown that bortezomib (BTZ) can be given weekly via intravenous (IV) route or twice weekly via subcutaneous (SC) route with lower neuropathy risk and no loss of anti-myeloma efficacy compared to original standard IV twice weekly schedule. Weekly SC should therefore yield the best therapeutic index and is widely used but has not been compared to established administration schedules in the context of a clinical trial. Comprehensive electronic medical record review was done for disease control and neuropathy symptoms of 344 consecutive patients who received their first BTZ-containing regimen for myeloma or AL amyloidosis before or after we changed to SC weekly in December 2010. Univariate and multivariable analyses were carried out that adjusted for age, underlying disease, concurrently used anticancer agents, underlying conditions predisposing to neuropathy, and number of prior regimens compared SC weekly to other schedules. Fifty-three patients received BTZ SC weekly, 17 SC twice weekly, 127 IV weekly and 147 IV twice weekly. Risk for neuropathy of any grade was higher with other schedules compared to SC weekly (44.3% vs. 26.9%, p = 0.001) while response rate was similar (72.1% vs. 76.6%, respectively, p = 0.15). Multivariable analyses upheld higher neuropathy risk (Odds ratio 2.45, 95% CI 1.26-4.76, p = 0.008) while the likelihood of not achieving a response (= partial response or better) was comparable (Odds ratio 1.25, 95% CI 0.58-2.71, p = 0.56) for other schedules compared to SC weekly, respectively. Lower neuropathy risk translated into longer treatment duration when BTZ was started SC weekly (p = 0.001). Weekly SC BTZ has activity comparable to other schedules and causes low rates of neuropathy.


FRET-based binding assay between a fluorescent cAMP analogue and a cyclic nucleotide-binding domain tagged with a CFP.
The cyclic nucleotide-binding domain (CNBD) functions as a regulatory domain of many proteins involved in cyclic nucleotide signalling. We developed a straightforward and reliable binding assay based on intermolecular fluorescence resonance energy transfer (FRET) between an adenosine-3', 5'-cyclic monophosphate analogue labelled with fluorescein and a recombinant CNBD of human EPAC1 tagged with a cyan fluorescence protein (CFP). The high FRET efficiency of this method (~ 80%) allowed us to perform several types of binding experiments with nanomolar range of sample using conventional equipment. In addition, the CFP tag on the CNBD enabled us to perform a specific binding experiment using an unpurified protein. Considering these advantages, this technique is useful to study poorly characterized CNBDs.


Distinct Roles of Brd2 and Brd4 in Potentiating the Transcriptional Program for Th17 Cell Differentiation.
The BET proteins are major transcriptional regulators and have emerged as new drug targets, but their functional distinction has remained elusive. In this study, we report that the BET family members Brd2 and Brd4 exert distinct genomic functions at genes whose transcription they co-regulate during mouse T helper 17 (Th17) cell differentiation. Brd2 is associated with the chromatin insulator CTCF and the cohesin complex to support cis-regulatory enhancer assembly for gene transcriptional activation. In this context, Brd2 binds the transcription factor Stat3 in an acetylation-sensitive manner and facilitates Stat3 recruitment to active enhancers occupied with transcription factors Irf4 and Batf. In parallel, Brd4 temporally controls RNA polymerase II (Pol II) processivity during transcription elongation through cyclin T1 and Cdk9 recruitment and Pol II Ser2 phosphorylation. Collectively, our study uncovers both separate and interdependent Brd2 and Brd4 functions in potentiating the genetic program required for Th17 cell development and adaptive immunity.


[Topics of cosmonauts' work and rest management on board the International Space Station].
Intensity of the rest and work cycle (WRC) of the ISS cosmonauts was examined in terms of overplanning, as well as frequency of sleep shifting and incidence of crew overstrain evidenced from the weekly reports of MCC-M medical operators. Level of WRC intensity in the recent ISS missions was compared with the WRC chronicles of early missions made by three crewmembers including one cosmonaut, and subsequent missions by six crewmembers including 2 or 3 cosmonauts. Though weak, a trend toward a WRC reduction in the period of 2010-2011 was achieved through a more realistic task planning for an average cosmonaut.


Induction of Ovulation with Clomiphene Citrate Versus Clomiphene with Bromocriptine in PCOS Patients with Normal Prolactin: A Comparative Study.
Polycystic ovarian syndrome (PCOS) is the main cause of anovulatory infertility. Various combination of drugs have been tried to induce ovulation in PCOS patients with varied result. So, this study was planned to compare the effect of bromocriptine combined with Clomiphene Citrate and Clomiphene Citrate alone, in patients of polycystic ovarian syndrome with normal prolactin level. On the basis of inclusion and exclusion criteria, seventy four PCOS patients with normal prolactin level (< 20 ng/ml) and BMI between 20-30 were randomly assigned into two groups. One group (n=38) received 50 mg clomiphene citrate (CC) from day3 to day7. The other group (CC+Bcrt) was given 50 mg of clomiphene citrate from day3 to day7 along with 0.8mg of bromocriptine daily for full cycle (n=36). Both the groups were treated for 3 cycles. The outcomes were measured by the hormonal status, follicular size, ovulation rate and pregnancy outcomes. The serum prolactin level was normal in both the groups before treatment. After 3 cycles the prolactin level decreased in (CC+Bcrt) group (p< 0.01). Follicular development (size >15mm) was observed in 30 patients (78.9%) in CC group and 28 patients (82.3%) in CC+Bcrt group. There was no significant change in hormonal status (LH, FSH and Estradiol) of both the groups. The rate of ovulation was 69.4% in CC group and 75.8% in CC+Bcrt group. During the treatment period, nine patients in CC group and seven patients in CC+Bcrt group became pregnant. There is no added benefit of bromocriptine with clomiphene citrate as compared to clomiphene alone in ovulation induction as well as pregnancy outcomes in PCOS patients with normal prolactin.


Chemical oceanography. Increasing anthropogenic nitrogen in the North Pacific Ocean.
The recent increase in anthropogenic emissions of reactive nitrogen from northeastern Asia and the subsequent enhanced deposition over the extensive regions of the North Pacific Ocean (NPO) have led to a detectable increase in the nitrate (N) concentration of the upper ocean. The rate of increase of excess N relative to phosphate (P) was found to be highest (~0.24 micromoles per kilogram per year) in the vicinity of the Asian source continent, with rates decreasing eastward across the NPO, consistent with the magnitude and distribution of atmospheric nitrogen deposition. This anthropogenically driven increase in the N content of the upper NPO may enhance primary production in this N-limited region, potentially leading to a long-term change of the NPO from being N-limited to P-limited.


Inhibition of proliferation and induction of apoptosis by the combination of β-carotene and 1,25-dihydroxyvitamin D3 in human esophageal cancer EC9706 cells.
Esophageal cancer is a common malignant tumor occurring in human esophageal epithelial tissue. The primary purpose of this paper was to define the effects of β-carotene and 1,25-dihydroxyvitamin D3, alone and in combination, on cell proliferation, cell cycle and apoptosis of human esophageal cancer EC9706 cells. Treatment with different concentrations of β-carotene and/or 1,25-dihydroxyvitamin D3. MTT assay showed that β-carotene and 1,25-dihydroxyvitamin D3 significantly inhibited proliferation of EC9706 cells in a dose- and time-dependent manner. Further studies also demonstrated that β-carotene alone or 1,25-dihydroxyvitamin D3 alone caused a marked increase on the induction of apoptosis in EC9706 cells. The percentage of G0/G1-phase cells significantly increased on addition of 1,25-dihydroxyvitamin D3 alone, but there were no significant changes with β-carotene alone. These two agents in combination synergistically inhibited cell growth and induced apoptosis. Therefore, our results indicate that β-carotene and 1,25-dihydroxyvitamin D3 in combination may provide a novel strategy for preventing and treating esophageal cancer.


Factors associated with emergency department avoidance during the COVID-19 pandemic and alternatives sought: a cross-sectional, telephone-based survey of frequent emergency department users in Beirut, Lebanon.
To explore avoidant behaviour of frequent emergency department (ED) users, reasons behind ED avoidance and healthcare-seeking behaviours in avoiders during the COVID-19 pandemic. Cross-sectional, telephone-based survey administered between March and August 2021 at a tertiary care centre in Beirut, Lebanon. Frequent ED users (defined as patients who visited the ED at least four times during the year prior to the first COVID-19 case in Lebanon). The primary outcome was ED avoidance among frequent ED users. Secondary outcomes included reasons behind ED avoidance and healthcare-seeking behaviours in avoiders. The study response rate was 62.6% and 286 adult patients were included in the final analysis. Within this sample, 45% (128/286) of the patients reported avoidant behaviour. Male patients were less likely to avoid ED visits than female patients (adjusted OR (aOR), 0.53; 95% CI 0.312 to 0.887). Other independent variables associated with ED avoidance included university education (aOR, 1.76; 95% CI 1.004 to 3.084), concern about contracting COVID-19 during an ED visit (aOR, 1.31; 95% CI 1.199 to 1.435) and underlying lung disease (aOR, 3.39; 95% CI 1.134 to 10.122). The majority of the patients who experienced acute complaints and avoided the ED completely (n=56) cited fear of contracting COVID-19 as the main reason (89.3% (50/56)). Most of the ED avoiders (83.9% (47/56)) adopted alternatives for seeking acute medical care, including messaging/calling a doctor (46.4% (26/56)), visiting a clinic (25.0% (14/56)), or arranging for a home visit (17.9% (10/56)). Of the avoiders, 64.3% (36/56) believed that the alternatives did not impact the quality of care, while 30.4% (17/56) reported worse quality of care. Among frequent ED users, ED avoidance during COVID-19 was common, especially among women, those with lung disease, those with university-level education and those who reported fear of contracting COVID-19 in the ED. While some patients resorted to alternative care routes, telemedicine was still underused in our setting. Developing strategies to reduce ED avoidance, especially in at-risk groups, may be warranted during pandemics.


Psychosocial complications of HIV/AIDS-metabolic disorder comorbidities among patients in a rural area of southeastern United States.
As people living with HIV experience longer life-expectancies resulting from antiretroviral therapy, comorbid conditions are increasing, particularly metabolic disorders. There is potential for psychosocial factors such as stigma experiences, depression, and alcohol use to complicate both HIV infection and metabolic disorders, including diabetes mellitus and hyperlipidemia. While the impact of these psychosocial factors on HIV infection alone are widely studied, their role in potentially complicating HIV co-morbid metabolic conditions has received little attention. This study examined the association between HIV-related stigma and depression, and the potential role of alcohol use as a mediating factor in a clinical sample of patients with comorbid HIV infection and metabolic conditions. Results demonstrated that HIV stigma is associated with depression and this relationship is in part accounted for by alcohol use. Our results indicate that interventions aiming to improve the health of people living with HIV and co-morbid metabolic disorders should prioritize addressing alcohol use as it is related to sources of stress, such as stigma, and depression.


Clinical pharmacology of topiramate in migraine prevention.
Migraine is a widespread disorder. Migraine patients experience worse health-related quality of life than the general population. The availability of effective and tolerable treatments for this disorder is an important medical need. This narrative review focuses on the clinical pharmacology of topiramate, an antiepileptic drug that was approved for the prophylaxis of migraine where it should act as a neuromodulator. A PubMed database search (from 2000 to 24 January 2011) and a review of the human studies published on topiramate and migraine was conducted. Topiramate is an important option for the prophylaxis of migraine and is of proven efficacy and tolerability. It has also been studied in chronic migraine with encouraging results, even in patients with medication overuse. However, in migraine prevention its efficacy is comparable to the other first-line drugs and there are no published trials with a superiority design which can establish topiramate's role in the available therapeutic armamentarium.


Calving system and weaning age effects on cow and preweaning calf performance in the Northern Great Plains.
A 3-yr study evaluated late winter (Feb), early spring (Apr), and late spring (Jun) calving systems in conjunction with varied weaning strategies on beef cow and calf performance from Northern Great Plains rangelands. Crossbred cows were randomly assigned to one of three calving systems (on average n= 168.calving system(-1).yr(-1)) and one of two weaning times (Wean 1, 2) within each calving system. The Feb and Apr calves were weaned at 190 and 240 d of age, whereas Jun calves were weaned at 140 and 190 d of age. Breeding by natural service occurred in a 32-d period that included estrous synchronization. Cows were managed throughout the year as appropriate for their calving season. Quantity and quality of hay and supplements were provided based on forage and weather conditions, physiological state of the cows, and available harvested feed resources within a year. After weaning, two-thirds of the early weaned steers were fed in confinement in Montana, and one-third were shipped to Oklahoma and were grazed or fed forage. One-half of the early weaned heifers grazed seeded pastures, and the other half was fed in confinement. Early weaned calves were weighed on approximately the same day as late-weaned calves. Birth weight and overall rate of gain from birth to weaning did not differ for calves from the three calving systems. Calf weaning weight differed by weaning age within calving system (P = 0.001), and calves from the Jun calving system that were weaned at 190 d of age tended (P = 0.06) to be lighter than calves of the same age from the Feb or Apr calving systems. Cow BW change and BCS dynamics were affected by calving system, but the proportion of cows pregnant in the fall was not. Cows suckled until later dates gained less or lost more BW during the 50 d between the first and second weaning than dry cows during this period. The previous year's weaning assignment did not affect production in the following year. Estimated harvested feed inputs were less for the Jun cows than for the Feb and Apr cows. We conclude that season of calving and weaning age affect outputs from rangeland-based beef cattle operations.


Assessing the Feasibility of Replacing Subjective Questionnaire-Based Sleep Measurement with an Objective Approach Using a Smartwatch.
In order to ensure sufficient recovery of the human body and brain, healthy sleep is indispensable. For this purpose, appropriate therapy should be initiated at an early stage in the case of sleep disorders. For some sleep disorders (e.g., insomnia), a sleep diary is essential for diagnosis and therapy monitoring. However, subjective measurement with a sleep diary has several disadvantages, requiring regular action from the user and leading to decreased comfort and potential data loss. To automate sleep monitoring and increase user comfort, one could consider replacing a sleep diary with an automatic measurement, such as a smartwatch, which would not disturb sleep. To obtain accurate results on the evaluation of the possibility of such a replacement, a field study was conducted with a total of 166 overnight recordings, followed by an analysis of the results. In this evaluation, objective sleep measurement with a Samsung Galaxy Watch 4 was compared to a subjective approach with a sleep diary, which is a standard method in sleep medicine. The focus was on comparing four relevant sleep characteristics: falling asleep time, waking up time, total sleep time (TST), and sleep efficiency (SE). After evaluating the results, it was concluded that a smartwatch could replace subjective measurement to determine falling asleep and waking up time, considering some level of inaccuracy. In the case of SE, substitution was also proved to be possible. However, some individual recordings showed a higher discrepancy in results between the two approaches. For its part, the evaluation of the TST measurement currently does not allow us to recommend substituting the measurement method for this sleep parameter. The appropriateness of replacing sleep diary measurement with a smartwatch depends on the acceptable levels of discrepancy. We propose four levels of similarity of results, defining ranges of absolute differences between objective and subjective measurements. By considering the values in the provided table and knowing the required accuracy, it is possible to determine the suitability of substitution in each individual case. The introduction of a "similarity level" parameter increases the adaptability and reusability of study findings in individual practical cases.


Provitamin A biofortification of crop plants: a gold rush with many miners.
Carotenoids are synthesized de novo by plants, where they play fundamental physiological roles as photosynthetic pigments and precursors for signaling molecules. They are also essential components of a healthy diet, as dietary antioxidants and vitamin A precursors. Vitamin A deficiency is a public health problem in developing countries, which has prompted a series of efforts toward the biofortification of plant-derived foods with provitamin A carotenoids (mainly β-carotene), giving rise to 'golden' crops. Since the 'golden rice' exploit, a number of biofortified crops have been generated, using transgenic approaches as well as conventional breeding. Bioavailability studies have demonstrated the efficacy of several 'golden' crops in maintaining vitamin A status. This review presents the state of the art and the areas that need further experimentation.