Pancreas preservation with TP-IV: a hyperosmolar colloid solution.
This study compares the efficacy of a new hyperosmolar colloid solution (TP-IV) with Euro-Collins solution for long-term (72 hr) hypothermic storage of canine pancreas autografts. Four experimental recipient groups and their survival (30-day study period) results were as follows: Gr. I (n = 6) pancreatectomized controls, without autotransplant (X +/- SD = 5.83 +/- 3.06 days); Gr. II (n = 6) fresh nonpreserved autografts (X +/- SD = 23.83 +/- 10.12 days, 5 of 6 greater than 30 days); and Gr. III (n = 7) and Gr. IV (n = 5) receiving pancreas autografts stored at 4 degrees C for 72 hr in either Euro-Collins or TP-IV, respectively (Gr. III, 13.85 +/- 9.04 days; Gr. IV, 21.2 +/- 12.37 days). The results appear to indicate that TP-IV is superior to Euro-Collins solution for 72-hr hypothermic storage of pancreas grafts. In fact, survival in the TP-IV-presented group was comparable to that of fresh, non-preserved autografts.


Converting Toxic Equivalents (TEQ) of dioxins and dioxin-like compounds in fish from one Toxic Equivalency Factor (TEF) scheme to another.
Toxic Equivalency Factors (TEFs) are an essential part of the Toxic Equivalent (TEQ) concept and have evolved for dioxins/dioxin-like compounds over the last two and half decades. Therefore, it is difficult to compare past and current TEQs that are reported using different TEFs without explicitly mentioning underlying congener concentrations. Using what likely is the largest known dioxin/furan (PCDD/F) and dioxin-like polychlorinated biphenyl (dl-PCB or DLP) fish database, here we present regression models that can facilitate conversion of a fish TEQ from an old to a newer TEF scheme. The results show that the mammalian PCDD/F-TEQ based on the latest TEF(WHO-05) is about 7.5% lower than that based on TEF(WHO-98). The mammalian DLP-TEQ(WHO-05) is on average 25-26% lower than almost identical DLP-TEQ(WHO-94) and DLP-TEQ(WHO-98). Total-TEQ(WHO-05) is on average 22% lower than Total-TEQ(WHO-98). According to the current toxicological standards for dioxins/furans, all previous major TEF schemes except TEF(Germany-85) and TEF(USEPA-87) were conservative (i.e., higher) in estimating TEQs. The major (> 75%) contribution to PCDD/F-TEQ(WHO-05) is from 2,3,7,8-TCDD (33%), 1,2,3,7,8-PCDD (26%), 2,3,7,8-TCDF (10%), and 2,3,4,7,8-PCDF (9%). The DLP-TEQ(WHO-05) is dominated by PCB-126 which on average contributes about 88%. The DLP-TEQ generally contribute > 70% of Total-TEQ. When reporting TEQs, we recommend that the underlying congener specific concentrations are presented, TEF scheme used is clearly stated, names of compounds included are explicitly expressed, and TEQs are identified accordingly (e.g., DLP-TEQ, PCDD/F-TEQ, Total-TEQ).


Na+ (Li+)-proline cotransport in Escherichia coli.
Na+ and Li+ were found to stimulate the transport of L-proline by cells of Escherichia coli induced for proline utilization. The gene product of the put P gene is involved in the expression of this transport activity since the put P+ strains CSH 4 and WG 148 show activity and the put P- strain RM 2 fails to show this cation coupled transport. The addition of proline was found to stimulate the uptake of Li+ and of Na+. Attempts to demonstrate proline stimulated H+ uptake were unsuccessful. It is concluded that the proline carrier (coded by the put P gene) is responsible for Na+ (or Li+)-proline cotransport.


Functional exercise capacity is associated with global functioning in patients with alcohol use disorder.
This study explored whether the Global Assessment of Functioning (GAF) score is associated with the functional exercise capacity among inpatients with alcohol use disorders (AUD). 45 (32 men) inpatients (41.1 ± 13.2 years, range = 18-70 years) performed a 6-minute walk test (6 MWT), a standing broad jump (muscle strength) and were assessed with several questionnaires. The GAF-score correlated significantly with the 6 MWT-score (Pearson's r = 0.47, p = 0.002). Variance in illness duration (11.1 ± 11.0 years) explained 27.9% of the GAF-score (50.8 ± 8.0) variance. Variance in GAF and muscle strength (148.3 ± 44.8 cm) explained 50.9% of the 6 MWT-score (638.2 ± 77.6 m) variance. Future research should explore whether improving the functional exercise capacity improves global functioning in this vulnerable population.


Model-based exploration of hypokalemia in dairy cows.
Hypokalemia in dairy cows, which is characterized by too low serum potassium levels, is a severe mineral disorder that can be life threatening. In this paper, we explore different originating conditions of hypokalemia-reduced potassium intake, increased excretion, acid-base disturbances, and increased insulin-by using a dynamic mathematical model for potassium balance in non-lactating and lactating cows. The simulations confirm observations described in literature. They illustrate, for example, that changes in dietary intake or excretion highly effect intracellular potassium levels, whereas extracellular levels vary only slightly. Simulations also show that the higher the potassium content in the diet, the more potassium is excreted with urine. Application of the mathematical model assists in experimental planning and therefore contributes to the 3R strategy: reduction, refinement and replacement of animal experiments.


The efficacy and safety of percutaneous nephrolithotomy under general versus regional anesthesia: a systematic review and meta-analysis.
This meta-analysis was performed to evaluate the efficacy and safety of percutaneous nephrolithotomy (PCNL) under regional anesthesia (RA) vs. general anesthesia (GA). A systematic literature search in the electronic databases (Cochrane CENTRAL, Medline and EMBASE) was performed up to April 2014. Twelve trials, including 1954 patients, met the inclusion criteria and were included in the final analysis. Our pooled analysis showed that PCNL under RA could reduce surgical duration (MD, -2.47; 95 % CI, -3.51 to -1.44), hospitalization period (MD, -0.48; 95 % CI -0.93 to -0.04), fluoroscopy time (MD, -0.48; 95 % CI, -0.83 to -0.14), blood transfusion (OR, 0.59; 95 % CI, 0.38-0.92), postoperative pain (MD, -1.99; 95 % CI, -2.2 to -1.78), and analgesic requirements (MD, -19.14; 95 % CI, -26.64 to -11.63). However, there was no difference between RA and GA groups with regard to stone-free rate (OR, 1.09; 95 % CI, 0.86-1.37) and postoperative complications associated with PCNL (OR, 0.95; 95 % CI 0.58-1.54). Our results show that PCNL under RA offers several potential advantages over GA in terms of surgical duration, hospitalization period, fluoroscopy time, blood transfusion, postoperative pain, and analgesic requirements, but both anesthetic techniques appear to be equivalent with regard to the stone-free rate and complication rate. Along with the suggested favorable hemodynamic profile and lower cost, RA may prove a better alternative than GA.


Continuous diffusion of oxygen improves diabetic foot ulcer healing when compared with a placebo control: a randomised, double-blind, multicentre study.
The aim of this study was to assess whether continuous diffusion of oxygen improves healing in people receiving treatment for diabetic foot ulcers (DFU). A double-blind, placebo control randomised study to receive either active continuous diffusion of oxygen (CDO) therapy using an active CDO device, or a fully operational placebo device without delivering oxygen. Patients were followed until closure or 12 weeks. Patients, caretakers, treating physicians and independent evaluators were blinded to the study arm. All patients received identical offloading, debridement, dressings and follow-up. We enrolled 146 people with DFUs (77% male, aged 56.3±12.4 years). A significantly higher proportion (195%) of DFUs healed in the CDO arm compared with placebo (32.4% versus 16.7%, p=0.033). The time to 50% DFU closure was significantly shorter in patients that received CDO therapy (mean 18.4 versus 28.9 days, p=0.001). There were no differences in overall adverse events (p=0.66) or ulcer-related adverse events (p=0.30) in the active and placebo treatment groups. The relative performance of active CDO over placebo became greater when used in larger wounds (273%), in more chronic wounds (334%) and in weight bearing wounds (465%). The results of this study demonstrate that CDO leads to higher proportion of healed DFUs (p=0.033) and a faster time to closure compared with placebo in people with DFUs (p=0.015). Relative performance did not vary significantly with wound size (p=0.80), but revealed better relative performance in more chronic wounds (p=0.008) and in weight-bearing wounds (p=0.003).


VIP like immunoreactive nerves in human respiratory tract. Light and electron microscopic study.
The present study provides light and electron microscopical evidence of Vasoactive Intestinal Peptide - (VIP) like immunoreactive nerves in human lower respiratory tract. Peroxidase antiperoxidase (PAP) technique was used to localize VIP-like immunoreactivity light microscopically and ultrastructurally. Under light microscopy, VIP-like immunoreactive nerves were observed in the smooth muscle layer of secondary bronchi to small bronchioli, and in bronchial glands. In addition, positive immunoreactive nervous network to VIP was found around nerve cell bodies in small microganglia. The bronchial epithelium of airway tract did not receive any VIP positive nerve fibers. Ultrastructurally VIP-like positive immunoreaction was localized in large granular vesicles ranging from 90 to 210 nm. Usually VIP-like positive immunoreactive nerve profiles contained several immunoreactive large vesicles (100-210). However, nerve profiles containing only a few positive large vesicles (80-150) were also observed. Under electron microscopy VIP-positive nerve profiles corresponded ultrastructurally to nerve profiles containing large granular vesicles observed in conventional electronmicroscopy. The present study provides new information about the innervation of human lower airway tract and widens the concept of their functional regulation on the anatomical basis reported here.


The MSH/ACTH analog ORG 2766 in anxiety disorders.
The anxiolytic effects of the MSH/ACTH analog ORG 2766 were assessed in three different groups of patients with an anxiety disorder: panic disorder, generalized anxiety and social phobia. Patients were treated with capsules containing 20 mg ORG 2766 or placebo and received 4 capsules daily for six weeks. A slight reduction on the Hamilton Anxiety Scale was found after ORG 2766 treatment in the panic disorder patients, while the peptide did not affect the number of panic attacks in these patients. In the other two patient groups no anxiolytic effect of ORG 2766 was observed.


Gender Equality and Gender Gaps in Mathematics Performance.
In a recent analysis of mathematics performance (Eriksson et al. 2020), national gender egalitarian values were positively associated with an increase in the average mathematics scores of high-school boys relative to girls. This study highlights that progressive gender egalitarian values at a national level might not translate into equality of opportunity at an individual level.


The dynamics of hypertension--an overview: present practices, new possibilities, and new approaches.
Contemporary clinical evaluation of hypertensive patients must include observations encompassing the impact of environment, behavior, and sociologic factors on metabolism and physiology. As evidenced by animal and human studies, catecholamines are an important mediator between psychologic factors and cardiovascular physiology, but direct measurement of catecholamine levels has not proved useful. Measurement of hemodynamic variables--blood pressure, heart rate, and stroke volume--during standardized psychophysiologic challenges is advocated. With low-challenge standardized stressors that include alpha- and beta-adrenergic stimuli, inappropriate reactors can be classified according to whether blood pressure is elevated primarily by cardiac output, total systemic resistance, or a combination of both. Hypertensive patients can be similarly distinguished, and medication can then be custom-tailored to the underlying physiology. Extensive laboratory and clinical evidence points to significant interrelationships between the central nervous system and the cardiovascular system. Furthermore, cardiovascular physiologic and metabolic perturbances are distinctly different under conditions of mental vs physical stress. Most clinical testing assesses physical performance whereas the real-life challenges of today are primarily mental.


Reliability and validity of the Dutch-language version of the Viking Speech Scale in children with cerebral palsy.
The Viking Speech Scale is used to classify speech performance in children with cerebral palsy (CP). A Dutch-language version (VSS-NL) has recently become available. This study aimed to determine the reliability and validity of the VSS-NL and the association with motor type of CP, Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS) and Communication Function Classification System (CFCS). A total of 90 children with CP, recruited throughout the Netherlands, took part in the study. VSS-NL classifications by speech and language therapists unfamiliar (SLT1) and familiar (SLT2) with the child, parents and physicians were compared. Convergent and discriminant validity were determined with the Intelligibility in Context Scale-Dutch (ICS-NL) and the Computer Based Instrument for Low Motor Language Testing (C-BiLLT). Inter- and intrarater reliability were determined by weighted Kappa (ƙw ). Validity and associations between VSS-NL and GMFCS, MACS and CFCS were determined with Spearman's coefficient. Association between VSS-NL and motor type of CP was determined with Fisher's exact test. Interrater reliability was excellent between SLT1-SLT2 (ƙw = 0.93, 95% confidence interval [CI] 0.87-0.99), good between SLT1-parent (ƙw = 0.71, 95% CI 0.60-0.83), SLT1-physician (ƙw = 0.70, 95% CI 0.58-0.81), SLT2-parent (ƙw = 0.71, 95% CI 0.57-0.84), SLT2-physician (ƙw = 0.73, 95% CI 0.62-0.85) and parent-physician (ƙ = 0.72, 95% CI 0.60-0.85). Intrarater reliability was excellent for SLTs familiar and unfamiliar to the child (ƙw = 1.00, 95% CI 1.00-1.00), and very good for physicians (ƙw = 0.89, 95% CI 0.75-1.00) and parents (ƙw = 0.72, 95% CI 0.62-1.00). Convergent validity was very strong (r = -0.81, p < 0.001) and discriminant validity moderate (r = -0.56, p < 0.001). Association with motor type of CP was significant (χ2 = 27.558, p < 0.001) and strong with GMFCS (r = 0.62, p < 0.001), MACS (r = 0.63, p < 0.01) and CFCS (r = 0.69, p < 0.001). The VSS-NL is a reliable and valid system to classify speech performance in children with cerebral palsy. Classifications can be performed by SLTs, parents and physicians.


A combination of immune cell types identified through ensemble machine learning strategy detects altered profile in recurrent pregnancy loss: a pilot study.
To compare the immunologic profiles of peripheral and menstrual blood (MB) of women who experience recurrent pregnancy loss and women without pregnancy complications. Explorative case-control study. Cross-sectional assessment of flow cytometry-derived immunologic profiles. Academic medical center. Women who experienced more than 2 consecutive miscarriages. None. Flow cytometry-based immune profiles of uterine and systemic immunity (recurrent pregnancy loss, n = 18; control, n = 14) assessed by machine learning classifiers in an ensemble strategy, followed by recursive feature selection. In peripheral blood, the combination of 4 cell types (nonswitched memory B cells, CD8+ T cells, CD56bright CD16- natural killer [NKbright] cells, and CD4+ effector T cells) classified samples correctly to their respective cohort. The identified classifying cell types in peripheral blood differed from the results observed in MB, where a combination of 6 cell types (Ki67+CD8+ T cells, (Human leukocyte antigen-DR+) regulatory T cells, CD27+ B cells, NKbright cells, regulatory T cells, and CD24HiCD38Hi B cells) plus age allowed for assigning samples correctly to their respective cohort. Based on the combination of these features, the average area under the curve of a receiver operating characteristic curve and the associated accuracy were >0.8 for both sample sources. A combination of immune subsets for cohort classification allows for robust identification of immune parameters with possible diagnostic value. The noninvasive source of MB holds several opportunities to assess and monitor reproductive health.


Pearsonema spp. (Family Capillariidae, Order Enoplida) Infection in Domestic Carnivores in Central-Northern Italy and in a Red Fox Population from Central Italy.
Pearsonema spp. nematodes infect the urinary bladder of domestic and wild carnivores. The red fox is considered a reservoir of Pearsonema plica, while the prevalence of Pearsonema spp. in domestic carnivores is still poorly known. This study aimed to assess the occurrence of Pearsonema spp. infection in privately owned cats (26) and dogs (83) from central and northern Italy alongside occurrence in red foxes (42) from central Italy. In positive dogs and cats, associated clinical signs were also evaluated. Urine samples were first examined under a stereomicroscope; then, they were centrifuged and microscopically examined after a flotation test. As for foxes, the urinary bladders were opened and urine was collected and processed as above, while collected nematodes were identified at the species level. Among examined animals, 2/26 cats (7.7%), 1/83 dogs (1.2%), and 38/42 foxes (90.5%) scored positive. Recurrent cystitis, pollakiuria, and hematuria were the main clinical signs in symptomatic dogs and cats. This is the first study on Pearsonema spp. infection in domestic carnivores examining a large number of privately owned pet animals. Obtained results confirm the role of the red fox as a reservoir for P. plica and suggest a possible high occurrence of Pearsonema spp. infection in domestic cats of central Italy.


Decompression for Bell's palsy: why I don't do it.
All decompression surgery is based on the lack of understanding that Bell's palsy is a viral demyelinating disease that is longitudinal--not perpendicular--to the facial canal and that surgery cannot possibly help a viral disease. These findings exclude the etiologic possibility of an "ischemic paralysis" and are in accord with our logically derived belief that treatment directed to relieve neural entrapment is a wasted effort.


Gross motor change after inpatient rehabilitation for children with acquired brain injury: A 10-year retrospective review.
To estimate gross motor change in inpatient school-aged children with subacute acquired brain injury (ABI), identify factors associated with gross motor change, and describe inpatient physiotherapy focus. This retrospective chart review involved inpatient children (5-18 years) with subacute ABI who had either two Gross Motor Function Measure (GMFM-88) assessments or one GMFM-88 with another pre/post gross motor outcome measure. Outcome change scores and Goal Attainment Scaling (GAS) T scores were calculated. Regression analyses examined factors predicting gross motor change. GAS goal areas were analysed to determine physiotherapy focus. Of the 546 charts screened, 266 (118 female) met study criteria. The GMFM-88 was generally administered first, followed by other measures. GMFM-88 (n = 202), Community Balance and Mobility Scale (n = 89), and Six-Minute Walk Test (6MWT) (n = 98) mean change scores were 18.03% (SD 19.34), 17.85% (SD 10.77), and 142.3 m (SD 101.8) respectively. The mean GAS T score was 55.06 (SD 11.50). Lower baseline scores and increased time between assessments were most predictive of greater GMFM-88 change (r ≥ 0.40). Twenty-five percent of GAS goals were ambulation-based. Appropriate outcome measure selection is integral to detecting gross motor change in pediatric inpatient ABI rehabilitation. Mean change score estimates can be used to compare standard inpatient rehabilitation with new treatment approaches.


An automated multi-order phase correction routine for processing ultra-wideline NMR spectra.
Efficient acquisition of wideline solid-state nuclear magnetic resonance (NMR) spectra with patterns affected by large inhomogeneous broadening is accomplished with the use of broadband pulse sequences. These specialized pulse sequences often use frequency-swept pulses, which feature time-dependent phase and amplitude modulations that in turn deliver broad and uniform excitation across large spectral bandwidths. However, the resulting NMR spectra are often affected by complex frequency-dependent phase dispersions, owing to the interplay between the frequency-swept excitations and anisotropic resonance frequencies. Such phase distortions necessitate the use of multi-order non-linear corrections in order to obtain absorptive, distortion-free patterns with uniform phasing. Performing such corrections is often challenging due to the complex interdependence of the linear and non-linear phase contributions, and how these may affect the NMR signal. Hence, processing of these data usually involves calculating the spectra in magnitude mode wherein the phase information is discarded. Herein, we present a fully automated phasing routine that is capable of processing and phase correcting such wideline NMR spectra. Its performance is corroborated via processing of NMR data acquired using both the WURST-CPMG (Wideband, Uniform-Rate, Smooth Truncation with Carr-Purcell Meiboom-Gill acquisition) and BRAIN-CP (BRoadband Adiabatic Inversion Cross Polarization) pulse sequences for a variety of nuclei (i.e., 119Sn, 195Pt, 35Cl, 87Rb, and 14N). Based on both simulated and experimental NMR datasets, it is demonstrated that automatic phase corrections up to and including second order can be readily achieved without a priori information regarding the nature of the phase-distorted NMR datasets, and independently of the exact manner in which time-domain NMR data are collected and subsequently processed. In addition, it is shown that NMR spectra acquired at both single and multiple transmitter frequencies that are processed with this automated phasing routine have improved signal-to-noise properties than those processed with conventional magnitude calculations, along with powder patterns that better match those of ideal NMR spectra, even for datasets possessing low signal-to-noise ratios and/or affected by spectral artifacts.


New environmentally friendly MSPD solid support based on golden mussel shell: characterization and application for extraction of organic contaminants from mussel tissue.
The use of golden mussel shells as a solid support in vortex-assisted matrix solid-phase dispersion (MSPD) was evaluated for the first time for extraction of residues of 11 pesticides and nine pharmaceutical and personal care products from mussel tissue samples. After they had been washed, dried, and milled, the mussel shells were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, infrared spectroscopy, and Brunauer-Emmett-Teller analysis. The MSPD procedure with analysis by liquid chromatography-tandem mass spectrometry allowed the determination of target analytes at trace concentrations (nanograms per gram), with mean recoveries ranging from 61 to 107 % and relative standard deviations lower than 18 %. The optimized method consisted of dispersion of 0.5 g of mussel tissue, 0.5 g of NaSO4, and 0.5 g of golden mussel shell for 5 min, and subsequent extraction with 5 mL of ethyl acetate. The matrix effect was evaluated, and a low effect was found for all compounds. The results showed that mussel shell is an effective material and a less expensive material than materials that have traditionally been used, i.e., it may be used in the MSPD dispersion step during the extraction of pesticides and pharmaceutical and personal care products from golden mussel tissues. Graphical Abstract Vortex-assited matrix solid-phase dispersion for extraction of 11 pesticides and 9 PPCPs care products from mussel tissue samples.


Fragmentation of wastewater sludge floc by planar ice front.
Floc size has substantial impact on sludge dewaterability, which might be increased or reduced after freezing and thawing. It is commonly assumed that floc size would be increased by low-speed freezing, with a planar ice front rejecting most flocs ahead of it to form large aggregates. We demonstrate in this work that an advancing planar ice front can not only engulf an activated sludge floc of size 3030 mum, but also fragment it. During floc freezing, when the ice engulfed a thin layer of floc, the latter would be pulled apart vertically by the action of the former. This particular portion of floc was then axially elongated and fixed in the frozen layer, with accumulated force pushing upward. In the present test the floc's vertical length was increased by over 92% and its width decreased by 37% over freezing. The force measurement and floc morphology tracking revealed that the force gradient that pulled apart the floc was 0.0027 N/m. The floc under investigation was fragmented at the point where the normal stress acting on the interior network exceeded 8 Pa.


Liver transplantation and inflammation: is lipopolysaccharide binding protein the link?
Lipopolysaccharide (LPS) binding protein (LBP) is an acute phase protein, which upregulated in response to surgical interventions. LBP plays an important role in modulating LPS-induced inflammatory response. We investigated the expression of LBP and the translocation of LPS in rat models of hepatic ischemia reperfusion injury and liver transplantation (LTx). We also elucidated the effect of LBP on the inflammatory response. In this study, cold ischemia (CI), warm ischemia/reperfusion (WI/R), and LTx models were used to model relevant physiologic situations during LTx. Serum and effluent protein levels as well as hepatic-mRNA and protein levels of LBP were examined. LBP released into the effluent during CI was used in a macrophage-LPS-stimulation assay to investigate the role of LBP in modulating the LPS-induced inflammatory response. Blocking experiments using an LBP-inhibitory peptide were performed to confirm the relevance of LPS/LBP for the induction of the inflammatory response. Impairment of the intestinal barrier and translocation of LPS into the liver was visualized by immunohistochemistry. Induction of tumor necrosis factor-alpha (TNF-α) mRNA expression in the liver was taken as indicator of the inflammatory response. Upregulation of LBP in serum and/or liver tissue was observed after WI/R, CI and LTx, respectively. The LBP released during CI enhanced the LPS induced inflammatory response in vitro as indicated by an induction of TNF-α. On the other hand, blocking LBP using LBP inhibitory peptide, suppressed the induction of TNF-α in vitro markedly. After LTx, elevated serum LBP levels were associated with post-operative LPS translocation and production of inflammatory cytokines. Our findings suggest that translocation of LPS occurs after LTx and that LBP is mediating the LPS-induced inflammatory response after LTx. Blocking LBP using LBP-inhibitory peptide might represent a novel strategy to reduce the I/R-induced inflammatory response.


Consensus-based recommendations on the diagnosis, referral and clinical management of patients with psoriatic arthritis.
Psoriatic arthritis (PsA) is a highly heterogeneous disease with complex manifestations. Limited understanding of the disease and non-availability of local guidelines pose challenges in the management of PsA in Saudi Arabia. Therefore, this expert consensus is aimed to provide recommendations on the management of patients with PsA, including referral pathway, definition of remission and treat-to-target (T2T) approach. A Delphi technique of consensus development was used involving an expert panel comprised of 10 rheumatologists, one dermatologist and one family physician. Based on the review of available published evidence and the opinions of clinical experts, key recommendations were developed. A consensus was achieved in defining the following: management guideline adaptable for Saudi Arabia, most useful screening tool, laboratory investigations, imaging tests and criteria for referring suspected PsA patients to a rheumatologist. In addition, an agreement was achieved in defining the T2T strategy and remission for the clinical management of PsA. Overall, these recommendations provide an evidence-based framework for the management of PsA patients in Saudi Arabia.


Tricuspid regurgitation after cardiac transplantation: an old problem revisited.
Tricuspid regurgitation (TR) is the most common valvular abnormality after orthotopic heart transplantation (OHT), with a reported incidence of up to 84%, depending on the definition of significant regurgitation and surgical methods of OHT employed. While multiple etiologies are implicated in the development of TR after OHT, endomyocardial biopsy (EMB), performed to detect allograft rejection, is the single most important contributor to significant TR by causing anatomic disruption of the tricuspid valvular structure. Although the clinical course of TR is heterogeneous, hemodynamically significant regurgitation generally leads to progressive right-heart dysfunction and symptoms. In cases refractory to diuretic-based medical therapy, surgical correction of TR has been shown to effectively alleviate the condition and provide symptomatic and organ function improvement. Tricuspid valve repair and replacement are viable surgical options, the application of which often depends on the institution's experience and underlying valve pathology. A non-invasive surveillance technique to detect allograft rejection is on the horizon, and may reduce the number of EMBs performed as well as the procedure-related tissue damage that leads to TR.


Perfusion of vasopressin within the ventral septum of the rabbit suppresses endotoxin fever.
The antipyretic action of arginine vasopressin (AVP), administered into a lateral cerebral ventricle or directly into the brain tissue via push-pull perfusion, was investigated in conscious New Zealand White rabbits. Administration of AVP into a lateral cerebral ventricle (ICV) was ineffective in reducing an endotoxin-induced fever and did not alter body temperature in the afebrile rabbit. Control push-pull perfusions with the carrier vehicle were without effect on endotoxin fevers or normal body temperature. Perfusion of the vehicle containing AVP provided significant antipyretic activity against both intravenous (IV) and ICV endotoxin without affecting normal body temperature. Both the maximum fever height and the fever index were significantly reduced during AVP perfusion. Tissue sites in which AVP was found to be antipyretic were located in the rostroventral parts of the septal region, at sites similar to those where perfusion of the peptide caused antipyresis in the sheep and rat. These results support the hypothesis that AVP, or a closely related molecule, may modulate fever within the central nervous system.


Risk Factors for Operation Complications of High Dose Rate 3-Dimensional Interstitial Brachytherapy for Lung Cancer.
The risk factors for operation complications of high-dose-rate dimensional (3D) interstitial brachytherapy for lung malignant tumors are still unclear. We aimed to provide a reliable reference for the preoperative safety assessment of interstitial brachytherapy. We analyzed the degree and incidence of operational complications in 120 eligible patients with lung carcinoma who underwent computed tomography (CT)-guided HDR interstitial brachytherapy. Univariate and multivariate analyses were used to study the relationships between patient-related factors, tumor-related factors, operation-related factors, and operational complications. The most frequent complications of CT-guided HDR interstitial brachytherapy were pneumothorax and hemorrhage. In univariate analysis, smoking, emphysema, distance of implanted needles through the normal lung tissue, number of implanted needle adjustments, and distance of the lesion from the pleura were the risk factors for pneumothorax; the tumor size, distance of the tumor from the pleura, number of implanted needle adjustments, and distance of the implanted needle through the normal lung tissue were risk factors for hemorrhage. In multivariate analysis, the depth of the implanted needle through the normal lung tissue and distance of the lesion from the pleura were independent risk factors for pneumothorax. Tumor size, number of implanted needle adjustments, and distance through normal lung tissue were independent risk factors for hemorrhage. This study provides a reference for the clinical treatment of lung cancer by analyzing the risk factors for complications of interstitial brachytherapy.


Decrease in emergency room or urgent care visits due to management of bronchial asthma inpatients and outpatients with pharmaceutical services.
To evaluate pharmaceutical care of bronchial asthma over a 1-year period and to investigate whether such care is effective. 79 male and 97 female asthma patients who were treated with theophylline and other drugs between June 1994 and September 1996 were studied. The 15 subjects received pharmaceutical care (group 1) and were all inpatient asthmatics who had been admitted to the hospital for treatment. The other patients acted as controls. In 1994, the average medication cost of asthma patients without pharmaceutical care was $199/month and $295/month when such care was provided in the outpatient clinic. The drug treatments which patients received generally included inhaled anti-inflammatory agents and theophylline, but the 161 non-pharmaceutical services patients (group 2) received fewer inhaled anti-inflammatory agents than group 1 patients. The number of visits to the emergency room and hospital admissions were significantly lower in patients after receiving pharmaceutical services than inpatients before receiving pharmaceutical services during our observation period. The serum theophylline concentrations of group 1 patients generally attained levels sufficient for favourable therapeutic effect after patients received pharmaceutical care. Pharmaceutical care offered at the hospital is effective in the management of asthma patients.


[Swallowing examination for ENT specialists].
Dysphagias, together with the diseases resulting therefrom, severely reduce patients' quality of life and substantially increase the costs of public health, making efficient therapy a prime concern. Among pathophysiologically oriented diagnostic procedures, the endoscopic examination of swallowing has emerged within the past 20 years as an indispensable standard examination with high sensitivity and specificity. Thus, every ears, nose, and throat (ENT) physician and phoniatric specialist should be familiar with this procedure, in order to ensure widest possible access to it, not only in hospitals but also in outpatient settings and in healthcare establishments. In this article, the preconditions, execution, and evaluation of the endoscopic examination are described and its relevance for immediate or long-term therapeutic treatment is discussed.


Pharmacogenetic testing in psychiatry: Perspective on clinical utility.
Pharmacogenetic studies the influence of inherited characteristics on medication. While different from pharmacogenomics, which is a study of the entire genome in relation to medication effect, their distinction remains inconsistent, and the two terms are used interchangeably. Although the potential of pharmacogenomics in psychiatry is apparent and its clinical utility is suboptimal, the uptake of recommendations and guidelines is minimal and research into PGx is not diverse. This article offers an overview of pharmacogenetics (PGx) in psychiatry, explores the difficulties, and provides recommendations on improving its applicability and clinical utility.


Effectiveness of social giving on the engagement of pharmacy professionals with a computer-based education platform: a pilot randomized controlled trial.
Computer-based education is gaining popularity in healthcare professional development education due to ease of distribution and flexibility. However, there are concerns regarding user engagement. This pilot study aims to: 1) assess the feasibility and acceptability of a social reward and the corresponding study design; and 2) to provide preliminary data on the impact of social reward on user engagement. A mixed method study combing a four-month pilot randomized controlled trial (RCT), surveys and interviews. The RCT was conducted using a computer-based education platform. Participants in the intervention group had access to a social reward feature, where they earned one meal for donation when completing a quiz with a passing score. Participants in the control group did not have access to this feature. Feasibility and acceptability of the social reward were assessed using surveys and telephone interviews. Feasibility of the RCT was assessed by participant recruitment and retention. User engagement was assessed by number of quizzes and modules completed. A total of 30 pharmacy professionals were recruited with 15 users in each arm. Participants reported high acceptability of the intervention. The total number of quizzes completed by the intervention group was significantly higher compared to the control group (n = 267 quizzes Vs. n = 97 quizzes; p-value 0.023). The study demonstrates the feasibility and acceptability of a web-based trial with pharmacy professionals and the social reward intervention. It also shows that the social reward can improve user engagement. A future definitive RCT will explore the sustainability of the intervention.


Responses of nursing home residents to intrainstitutional relocation.
Relocation effects may be positive when residents are prepared for the move. The degree to which they exercise control over their environment and participate in the decision-making process influences the outcome of relocation. Planned interventions may offset adverse effects of stress. Prerelocation involvement of the residents we observed in visiting the new facility, and in selecting their bedrooms and roommates, reduced their anxiety to an acceptable, even positive level. These choices had a direct impact on their quality of life. The greater the number of choices the residents had, the more predictable the new environment became. Any stress generated became a positive, rather than a negative, force.


Dihydrodibenzothiepine: Promising hydrophobic pharmacophore in the influenza cap-dependent endonuclease inhibitor.
This work describes a set of discovery research studies of an influenza cap-dependent endonuclease (CEN) inhibitor with a carbamoyl pyridone bicycle (CAB) scaffold. Using influenza CEN inhibitory activity, antiviral activity and pharmacokinetic (PK) parameters as indices, structure activity relationships (SAR) studies were performed at the N-1 and N-3 positions on the CAB scaffold, which is a unique template to bind two metals. The hydrophobic substituent at the N-1 position is extremely important for CEN inhibitory activity and antiviral activity, and dihydrodibenzothiepine is the most promising pharmacophore. The compound (S)-13i showed potent virus titer reduction over oseltamivir phosphate in an in vivo mouse model. The CAB compound described herein served as the lead compound of baloxavir marboxil with a tricyclic scaffold, which was approved in Japan and the USA in 2018.


Further observations of evoked potentials in obsessional patients.
This study was designed to replicate and extend earlier findings. Evoked potentials (EP) were recorded, using a task of varying complexity involving shape discrimination, with matched groups of obsessional and normal subjects. Results confirmed previous findings that obsessional patients are characterized by reduced amplitudes and decreased latencies of late EP components; divergences between the groups were more marked for tasks of increased complexity.


Additional N-glycosylation mutation in the major hydrophilic region of hepatitis B virus S gene is a risk indicator for hepatocellular carcinoma occurrence in patients with coexistence of HBsAg/anti-HBs.
The study aimed to determine the association of additional N-glycosylation mutations in the major hydrophilic region (MHR) of hepatitis B virus (HBV) S gene with hepatocellular carcinoma (HCC) occurrence in HBsAg/anti-HBs coexistent patients. A total of 288 HBsAg/anti-HBs coexistent patients and 490 single HBsAg-positive patients were enrolled, including 193 with HCC, 433 with chronic hepatitis B (CHB), and 152 with acute-on-chronic liver failure (ACLF). The HBV S genes were amplified from serum and sequenced. The frequency of additional N-glycosylation mutations was significantly higher in HCC patients (12.37%) than in CHB patients (4.39%) and ACLF patients (2.63%). The frequency escalated by an order of single HBsAg-positive non-HCC (1.61%), single HBsAg-positive HCC (5.98%), HBsAg/anti-HBs coexistent non-HCC (8.01%), and HBsAg/anti-HBs coexistent HCC (22.36%). Twelve kinds of mutations/mutation patterns were detected, five of which have not been reported. Multivariate analysis showed that age > 40 years [OR, 3.005; 95% CI, 1.177-7.674; P = 0.021], alpha-fetoprotein > 10 ng/mL [OR, 4.718; 95% CI, 2.406-9.251; P <0.001], cirrhosis [OR, 6.844; 95% CI, 2.773-16.891, P < 0.001], Hepatitis B e antigen negativity [OR, 2.218; 95% CI, 4.335, P = 0.020], and additional N-glycosylation mutation [OR, 2.831; 95% CI, 1.157-6.929; P = 0.023] were independent risk factors for HCC in HBsAg/anti-HBs coexistent patients. Dynamical analysis showed that the additional N-glycosylation mutations existed 1-4 years prior to HCC occurrence in eight of 18 patients observed. In conclusion, the dditional N-glycosylation mutations together with HBsAg/anti-HBs coexistence might serve as a predictive indicator for HCC occurrence in chronic HBV-infected patients.


Toxoplasmosis.
Recent research has shown that Toxoplasma gondii, the cause of human toxoplasmosis, is a protozoan close to the genus Isospora, whose life cycle involves cats as the definitive host, and other mammals, including man, and birds as intermediate hosts. Cats shed oocysts in their faeces; these are infective to the intermediate hosts when ingested. But the non-felid intermediate hosts can also become infected by eating other intermediate hosts. Probably most human infections occur in this manner and result from eating raw or insufficiently cooked meats. Most people become infected during their life time, but most infections are benign and unnoticed. Occasionally the disease picture may simulate infectious mononucleosis. However, in intrauterine or neonatal infections the disease may be most severe and chorioretinitis, encephalomyelitis, hydrocephalus or microcephaly may result. Diagnosis depends upon demonstrating the parasite in biopsy material or through changing titres in serological tests.


Effect of ozonolysis pretreatment on enzymatic digestibility of wheat and rye straw.
Wheat and rye straws were pretreated with ozone to increase the enzymatic hydrolysis extent of potentially fermentable sugars. Through a 2(5-1) factorial design, this work studies the influence of five operating parameters (moisture content, particle size, ozone concentration, type of biomass and air/ozone flow rate) on ozonization pretreatment of straw in a fixed bed reactor under room conditions. The acid insoluble lignin content of the biomass was reduced in all experiments involving hemicellulose degradation. Near negligible losses of cellulose were observed. Enzymatic hydrolysis yields of up to 88.6% and 57% were obtained compared to 29% and 16% in non-ozonated wheat and rye straw respectively. Moisture content and type of biomass showed the most significant effects on ozonolysis. Additionally, ozonolysis experiments in basic medium with sodium hydroxide evidenced a reduction in solubilization and/or degradation of lignin and reliable cellulose and hemicellulose degradation.


Comparison of absolute cerebral haemoglobin concentration in neonates measured directly and by the oxygen swing method both based on near infrared spectrophotometry.
The total cerebral haemoglobin concentration (tHb in mumol/l) as a major indicator of the oxygen transport capacity is investigated in neonates. Two methods to determine tHb by near infrared spectrophotometry (NIRS) have evolved so far: The first method requires a slow oxygenation change with reference to arterial oxygen saturation (tHbo-method). The second method is based on a geometrical principle and a two channel NIRS instrument (tHbg-method). The aim of this study was to compare both methods quantitatively. 15 clinically stable preterm infants needing supplemental oxygen were included in this study. For each method the measurements of three infants were excluded due to unsatisfactory measurement quality. The remaining 9 neonates had a mean gestational age of 29 (range 25.1 to 31.4) weeks, birthweight of 1272 (740 to 1690) g and a postnatal age of 2.6 (0.5 to 5) days. In each infant 6 tHbo measurements were carried out. During each tHbo measurement the mean of the continuously available tHbg (Cerebral Redox Monitor 2020, Johnson & Johnson Medical) was calculated. The mean of all successful tHbo and corresponding tHbg was determined for each infant. The mean tHbg was 151 mumol/l (range 62 to 223 mumol/l) and the mean tHbo was 59 mumol/l (27 to 113 mumol/l). The regression line between the two methods was tHbg = 1.34 x tHbo + 72 mumol/l. The r was 83.6%. The correlation suggests, that both methods can be applied to measure tHb. However, it has to be taken into account that the tHbg-method returns significantly higher values than the tHbo-method.


Quantitative trait loci-based genomics-assisted prediction for the degree of apple fruit cover color.
Apple fruit cover color is an important appearance trait determining fruit quality, high degree of fruit cover color or completely red fruit skin is also the ultimate breeding goal. MdMYB1 has repeatedly been reported as a major gene controlling apple fruit cover color. There are also multiple minor-effect genes affecting degree of fruit cover color (DFC). This study was to identify genome-wide quantitative trait loci (QTLs) and to develop genomics-assisted prediction for apple DFC. The DFC phenotype data of 9,422 hybrids from five full-sib families of Malus asiatica 'Zisai Pearl', M. domestica 'Red Fuji', 'Golden Delicious', and 'Jonathan' were collected in 2014-2017. The phenotype varied considerably among hybrids with the same MdMYB1 genotype. Ten QTLs for DFC were identified using MapQTL and bulked segregant analysis via sequencing. From these QTLs, ten candidate genes were predicted, including MdMYB1 from a year-stable QTL on chromosome 9 of 'Zisai Pearl' and 'Red Fuji'. Then, kompetitive allele-specific polymerase chain reaction (KASP) markers were designed on these candidate genes and 821 randomly selected hybrids were genotyped. The genotype effects of the markers were estimated. MdMYB1-1 (represented by marker H162) exhibited a partial dominant allelic effect on MdMYB1-2 and showed non-allelic epistasis on markers H1245 and G6. Finally, a non-additive QTL-based genomics assisted prediction model was established for DFC. The Pearson's correlation coefficient between the genomic predicted value and the observed phenotype value was 0.5690. These results can be beneficial for apple genomics-assisted breeding and may provide insights for understanding the mechanism of fruit coloration.


Editorial of Special Issue "Microalgal Molecules and Enzymes".
Microalgae are photosynthetic unicellular organisms that can be found in very different environments, both terrestrial and marine, including extreme environments such as cold, hot and high/low salinity [...].


Enhancing effects of cytosine arabinoside on ethyl methanesulfonate-induced 6-thioguanine resistance mutations in Chinese hamster V79 cells.
We studied the synergistic enhancement effects of two chemicals which are different in their mechanism of action on DNA in cells. The test chemicals used were ethyl methanesulfonate (EMS) as an alkylating agent and cytosine arabinoside (Ara-C) as an analogue of cytidine. For determination of mutagenesis we measured the induction of resistance to 6-thioguanine (6-TG) in Chinese hamster V79 cells. EMS had a strong mutagenic effect on V79 cells, but for Ara-C the results were less clear. In this study, Ara-C had no detectable effect in inducing mutation up to a concentration of 5 X 10(-4) M. The mutation frequency of combined treatment with EMS and Ara-C was significantly higher than that obtained with EMS alone. These results indicate that Ara-C had an enhancing effect on mutations induced by EMS.


Changes of activated partial thromboplastin time during constant intravenous and fixed intermittent subcutaneous administration of heparin.
Marked circadian variations in the activated partial thromboplastin time (APTt) during continuous heparin infusions for thromboembolic episodes have been reported in a French study. The aim of the present study was to test if these variations could be reproduced in a Swedish population. The frequency spectrum variations in APTt values were analysed with the Prony and the statistical Pearson product momentum correlation coefficient methods. In seven patients with pulmonary embolism, APTt was checked every fourth hour during 48 h of continuous, constant heparin treatment. In only one patient was a distinct circadian variation of APTt values seen. In six patients with venous leg thromboses, treated with s.c. heparin, marked variations in APTt were noticed over periods of 12 h. These variations paralleled the regular s.c. injections of heparin every twelfth hour. The results of the present study could not confirm the marked circadian variations in APTt reported in an earlier French study during continuous heparin infusions, except in one patient.


Ozanimod in the Treatment of Ulcerative Colitis: Initial Real-World Data From a Large Tertiary Center.
Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon and rectum. Long-term therapy is generally required to achieve and maintain disease control.1 In May 2021 the US Food and Drug Administration approved the use of ozanimod in patients with moderate to severe UC. We describe the first report of the use of ozanimod in real-world clinical practice.


Development of matrix patches for transdermal delivery of a highly lipophilic antiestrogen.
The aim of this study was to develop matrix-type transdermal systems (TDSs) containing the highly lipophilic (log P = 5.82) antiestrogen (AE) and the permeation enhancers propylene glycol and lauric acid. For that purpose, permeation of AE from various adhesive matrices through excised skin of hairless mice was evaluated. It was found that pretreatment of the skin with permeation enhancers raised the transdermal flux of subsequently applied antiestrogen. Highest steady-state transdermal fluxes (1.1 microg cm(-2) h(-1)) were obtained from Gelva, polyacrylate adhesive, followed by 0.55 microg cm(-2) h(-1) from Oppanol polyisobutylene, 0.31 microg cm(-2) h(-1) from BIO-PSA silicone, and 0.12 microg cm(-2) h(-1) from Sekisui polyacrylate matrices. In order to develop TDS with high content of fluid permeation enhancer propylene glycol, two different strategies were investigated. One strategy was the addition of hydroxypropyl cellulose (HPC) as thickening agent to Gelva matrices. This allowed for propylene glycol loading levels of up to 30%, resulting in transdermal AE fluxes of 0.09 microg cm(-2) h(-1). On the other hand, a fleece-laminated backing foil was loaded with the described permeation enhancer formulation and laminated with polyacrylate adhesive layer, resulting in transdermal AE fluxes of 0.06 microg cm(-2) h(-1). However, application of these TDSs on skin pretreated with permeation enhancers raised the fluxes to 2.6 microg cm(-2) h(-1) from Gelva/HPC and 0.46 microg cm(-2) h(-1) from fleece/Sekisui.


Default mode network connectivity: effects of age, sex, and analytic approach.
The 'default mode network' is a set of brain regions showing correlated, low-frequency activity during rest. It includes the posterior cingulate/precuneus, medial prefrontal cortex, and bilateral inferior parietal cortex. Earlier studies have characterized this network using either region of interest-based correlation analyses or data-driven techniques; however, there is some disagreement over which method is superior. We conducted both types of analysis on a large (N=40) data set and also investigated age and sex differences in the network. Both region of interest-based analyses and independent component analysis identified the default mode network. Age and sex differences were small and there was less agreement between analytic techniques regarding age and sex effects than regarding default mode network structure.


Studies on the in vivo synthesis of methotrexate polyglutamates and their efflux properties in normal, proliferative, and neoplastic mouse tissues.
Synthesis of poly-gamma-glutamyl metabolites of methotrexate was demonstrated in mouse small intestine, liver and bone marrow, and in L1210 leukemia, Sarcoma 180 and Ehrlich tumor cells after sc injections of [3H]methotrexate to tumor bearing mice. Ion exchange chromatography of tissue extracts resolved six peaks of radioactivity believed to represent methotrexate and metabolites with up to 4 additional glutamyl residues. Polyglutamate formation in L1210 cells and small intestine was shown to be independent of dose at least to 400 mg/kg as long as intracellular levels of drug in excess of the dihydrofolate reductase binding capacity (exchangeable) were maintained. Both the total amount of polyglutamates and the average length of the polyglutamyl chain increased with time as long as exchangeable level of drug were present intracellularily. The results also showed differences in the extent of metabolism of methotrexate polyglutamates among the tissues examined. Although, these differences were at times very large, there was no consistent correlation between these differences and other pharmacologic parameters or cytoxicity. Tumor cells appeared to synthesize more polyglutamates than the normal tissues examined. However, differences in total drug persistence and sensitivity to drug among tumor cells and among normal tissues did not reflect the relative extent of polyglutamate synthesis in each group. We observed no selective retention of polyglutamates as compared to methotrexate by L1210 cells in vitro as indicated by the extracellular accumulation during efflux of methotrexate and the polyglutamates. This could only be demonstrated by allowing efflux of intracellular drug in the presence of extracellular dihydrofolate reductase, which averted hydrolysis of the polyglutamates. It is concluded that the extent of polyglutamate synthesis per se may not be a determinant of drug sensitivity in murine tissues. However, the accumulation of these metabolites may contribute in some way to overall therapeutic response or relative cytotoxicity.


An improved double-tuned and isotope-filtered pulse scheme based on a pulsed field gradient and a wide-band inversion shaped pulse.
We have developed an improved isotope-filtered pulse scheme in combination with a double-tuned filter, a hyperbolic secant inversion pulse, and a z-filter with a pulsed field gradient. These filtering pulse schemes have been incorporated into several one-, two-, and three-dimensional experiments, which were applied to the (13)C/(15)N uniformly labeled N-terminal SH3 domain of Grb2 complexed with the unlabeled Sos-derived peptide. The proton resonances of the Sos-derived peptide were unambiguously assigned using isotope-filtered DQF-COSY, TOCSY and NOESY spectra. Furthermore, in the isotope-filtered, isotope-edited 3D NOESY spectrum, intermolecular NOEs between the labeled protein and the unlabeled peptide could be identified. Through these applications, we demonstrate the high filtering efficiency of the presented pulse scheme.


Distributions of total skin surface area to body weight ratios for use in dermal exposure assessments.
Surface area to body weight ratios were calculated for three age groups of the population using direct measurement data reported in the scientific literature. A strong negative correlation was observed between these ratios and age, and ratios did not differ as a function of sex. Distribution data for surface area to body weight ratios are presented for three age groups. Because of the strong correlation between these two factors, the use of these distributions in human exposure/risk assessments using point estimation techniques and/or Monte Carlo simulations may be more appropriate than treating surface area and body weight as independent variables.


Adriamycin stimulates canine kidney (MDCK) cells to deacylate cellular lipids and to produce prostaglandins.
Dog kidney (MDCK) cells treated with adriamycin (0.5 micrograms/ml) for 1 hr, produced from 2 to 7 times more prostaglandins E2 and F2alpha when measured in culture media 24, 48 and 72 hrs after the treatment. Indomethacin (ID50 less than 2 x 10(-8) M) and cycloheximide (0.5 micrograms/ml) inhibited this adriamycin-stimulated prostaglandin production. The aglycone of adriamycin (0.5 to 5.0 micrograms/ml) had little stimulating effect. Treatment of [3H]arachidonic acid-labeled MDCK cells with adriamycin (0.5 micrograms/ml) for 1 hr also stimulated deacylation of cellular lipids during subsequent incubation. Altered morphology of MDCK cells resulted from such treatment with adriamycin; indomethacin did not inhibit this change, but cycloheximide did.


Enhancement of host cell reactivation of ultraviolet-irradiated Herpes simplex virus by caffeine, hydroxyurea and 5-bromodeoxyuridine.
Enhancement of host cell reactivation (HCR) of ultraviolet (UV)-irradiated herpes simplex virus (HSV) was demonstrated in cell cultures pretreated with caffeine, hydroxyurea, or 5-bromodeoxyuridine (BrdUrd). The effect of caffeine on HCR was shown to depend on the time of drug treatment with respect to infection. In cultures treated with caffeine during the course of virus replication, the infectivity of irradiated HSV was reduced about nine-fold, while cultures pretreated with the drug before infection showed an increase in infectivity. The extent of HCR enhancement depended on the time interval between treatment with caffeine and infection, drug concentration, and the UV irradiation dose to which HSV was exposed. Magnitude of enhancement of HCR by caffeine differed in various cell species. The results suggest that enhanced HCR of UV-irradiated HSV by DNA antimetabolities is associated with DNA repair activated in consequence of cell DNA damage.


Cardiac rehabilitation in patients with severe ischemic left ventricular dysfunction.
Twenty patients who had had a myocardial infarction and who had a resting left ventricular ejection fraction of 25% or less participated in an 8-week outpatient supervised exercise and education program. No morbidity or mortality occurred during the program, and most patients achieved a substantial improvement in exercise capacity. During a follow-up interval of a mean of 29.7 +/- 13.0 months, four patients died, an annualized mortality of 8 +/- 4%. The outcome of cardiac rehabilitation was assessed 19.1 +/- 4.4 months after completion of the supervised program. Of the 16 survivors, all of whom had been fully employed before their most recent myocardial infarction, 9 (56%) had returned to full-time work, 6 (38%) were medically disabled, and 1 was retired (age 73 years) but fully active. Of the 16 survivors, 13 (81%) completed a questionnaire about their perceptions of their current quality of life. Of the 13 patients, 12 (92%) had continued to exercise regularly. Four patients (31%) reported the ability to perform all desired activities without symptoms, whereas nine patients (69%) noted some impairment in their functional capacity. Thus, in this group of patients with profound left ventricular dysfunction, the rehabilitation potential, as evidenced by return to productive employment and the ability to perform desired activities-including exercise training-was generally favorable.


Concentration of hydroxyl groups in dental apatites: a solid-state 1H MAS NMR study using inverse 31P -->1H cross-polarization.
The concentration of structural hydroxyl groups in the apatite mineral of enamel, dentin and cementum of healthy human teeth was estimated by reference to stoichiometric hydroxyapatite to be 73 +/- 3, 18 +/- 2 and 18 +/- 1%, respectively.


Correlations of oral tongue cancer invasion with matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) expression.
In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracellular matrix and neovascularization are related to tumor infiltration mechanism. By studying the tissues of early stage oral tongue cancer patients, we are intending to clarify the invasion-related factors. To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction-related molecules (MMP-2, MMP-9) and neovascularization-related molecule (VEGF) were observed by immunohistochemical study. Also, staining of CD31 was done for quantification of neovascularization. We analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates, and cervical lymph node metastasis rate. The expression rates of MMP-2, MMP-9, VEGF in 38 early oral cancer patients were 52.6%, 78.9%, and 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining (P < 0.001). VEGF expressions were significantly related with tumor invasion depth (P = 0.002). The tumor-free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors (P = 0.019). These results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer.


Isolation of the major herpes simplex virus type 1 (HSV-1)-specific glycoprotein by hydroxylapatite chromatography and its use in enzyme-linked immunosorbent assay for titration of human HSV-1-specific antibodies.
A 131,000 molecular weight herpes simplex virus type 1 (HSV-1) glycoprotein designated antigen number 6 (Ag-6) was previously shown to possess almost exclusively HSV-1-specific antigenic sites. Fused rocket and crossed immunoelectrophoresis of fractions obtained from hydroxylapatite chromatography of crude HSV-1 antigen (Triton X-100-solubilized, infected tissue culture cells) showed that a subfraction of Ag-6 could be separated from the other HSV antigens. Enzyme-linked immunosorbent assay with the isolated Ag-6 showed that sera from rabbits infected with HSV-1 and HSV-1 human antisera contained antibodies to Ag-6, whereas sera from HSV-2-infected rabbits and sera from patients with primary HSV-2 infections did not react with Ag-6. Enzyme-linked immunosorbent assay of 852 human sera for antibodies to HSV type-common glycoproteins, Ag-6, and HSV 2-specific antigens showed that 139 sera which reacted negatively with HSV type-common glycoproteins also did not react with Ag-6 with HSV-2 specific antigens. The 713 sera reacting positively to HSV type-common antigens either reacted with Ag-6 (328 sera) or with HSV-2-specific antigens (31 sera) or both (354 sera). This means that Ag-6 might be useful in large-scale human serology for the detection of past infection with HSV-1, irrespective of whether or not past infection with HSV-2 has occurred.


Role of estrogen and estrogen-related growth factor in the mechanism of hormone dependency of endometrial carcinoma cells.
The role of estrogen and estrogen-related growth factors in the mechanism of hormone dependency of endometrial adenocarcinoma cells was investigated. The proliferation of hormone-responsive human endometrial adenocarcinoma cells (Ishikawa cells), which possess both estrogen and progesterone receptors, was optimally stimulated by 10 nM estradiol. Both transforming growth factor (TGF)-alpha and epidermal growth factor (EGF), added to the culture media, stimulated the proliferation of Ishikawa cells in a dose-dependent manner. Anti-TGF-alpha antibody completely eliminated the stimulatory effects of TGF-alpha. Anti-EGF receptor antibody inhibited the proliferation of these cells. The production of TGF-alpha into culture media was 5-40 pg/10 cells/24 h in 9 human endometrial adenocarcinoma cells. Ten nanomoles of estradiol increased the TGF-alpha production of Ishikawa cells by approximately 2.5-fold of the control level. In contrast, the production of TGF-alpha in hormone-unresponsive HEC-50 cels was not influenced by estradiol. C-erbB-2 oncoprotein expression of human endometrial adenocarcinoma cells, detected by both immunocytochemical staining and Western blot analysis, was associated with the tumor grade of the original tumor tissues. Ten nanomoles of estradiol clearly increased the c-erbB-2 oncoprotein levels at an optimal incubation period of 72 h, whereas estradiol did not affect the expression in HEC-50 cells.


Primary sedimentation modelling with characterized setting velocity groups.
Within a plantwide water and resource recovery facility context, an important requirement for a primary sedimentation unit model is the correct fractionation of the settleable portion (primary sludge - PS) of the raw wastewater total suspended solids (TSS) according to the (i) unbiodegradable particulate organic (UPO), (ii) biodegradable particulate organic (BPO), and (iii) inorganic settleable solid (ISS) components. This paper focuses on improving a current TSS- based primary settling tank (PST) model to account for correct proportions of these three components, with characterized settling velocity groups. The steps taken towards development of the primary sedimentation unit model involved the development of a discrete particle settling model in Microsoft Excel and the utilisation of well characterised municipal wastewater data from previous studies in the discrete particle settling model, to reproduce PS and settled wastewater outputs in settling fractions of UPO, BPO and ISS, via steady state and dynamic calculations and under strict material mass balances. Finally, the insights obtained from discrete particle settling model calculations were implemented in the development of a dynamic University of Cape Town primary sedimentation unit (UCTPSU) model. This dynamic model was rigorously verified to be internally consistent with regards to material mass balances and utilised to simulate plantwide scenarios, under steady state conditions, whereby the impact of incorrect characterisation of TSS components (UPO, BPO and ISS) fractions was evaluated. From these evaluations, it was noted that the incorrect disaggregation of the TSS components of primary sludge can lead to incorrect predictions with regard to parameters such as the settled wastewater composition and the activated sludge system capacity. Thus, the investigation revealed the need to measure key wastewater parameters such as particle settling velocities and the UPO fraction, towards realistically modelling the primary sedimentation unit operations.


Glucose-induced inhibition of seed germination in Lotus japonicus is alleviated by nitric oxide and spermine.
Seed germination is sensitive to glucose (Glc), nitric oxide (NO) and polyamine (PA). To elucidate whether cross-talk among Glc, NO and PAs occurs in mediation of seed germination, effects of Glc, NO and spermine on seed germination of Lotus japonicus were studied. Glc retarded seed germination in a concentration-dependent manner. NO donor sodium nitroprusside (SNP) alleviated Glc-induced inhibition of seed germination, whereas the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO) diminished the SNP-dependent alleviation of seed germination. These observations indicate that Glc may inhibit seed germination by interacting with NO signaling pathways. Exogenous spermine enhanced and the inhibitor of the spermine synthase, methylglyoxal-bis-guanyl hydrazone (MGBG), inhibited seed germination, respectively. Like SNP, spermine alleviated the Glc-induced inhibition of seed germination, whereas MGBG exaggerated the Glc-induced inhibition of seed germination. These results suggest that Glc may inhibit the spermine synthesis, leading to reductions in seed germination. NO scavenger and spermine synthase inhibitor diminished the SNP-induced alleviation of Glc-induced inhibition of seed germination. These findings reveal that both NO and spermine participate in the Glc-induced inhibition of seed germination in L. japonicus.


Probing the self-diffusion process in Aluminium.
An in-depth understanding of the diffusion process in liquid metals is a key to design and engineering new high-performance materials. In this study, using molecular dynamics simulations supplemented with the embedded atom potential, we investigate/compare the self-diffusion process in liquid Aluminium. To understand the self-diffusion process, we analyse the radial distribution functions, velocity distributions, mean square displacements, and self-diffusion coefficients at various temperatures well above the melting temperature of Aluminium in the temperature range of 1000 K to 1800 K. As a key result, in both the [Formula: see text] and [Formula: see text] phases, the self-diffusion coefficients show a non-linear variation with rise in temperatures in the range of 1000 K to 1200 K. From 1300 K to 1800 K, the self-diffusion coefficients increase more or less monotonically with rise in temperature. We found that a higher temperature in the range of 1300 K to 1800 K leads to a greater self-diffusion coefficient, suggesting the more violent movement of the atoms around their equilibrium positions. The results presented in this work can help to understand the differences in the self-diffusion process in the technologically relevant Al phases.


Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis.
Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased for those undergoing anti-myeloma therapy. Current guidelines suggest low-dose direct oral anticoagulants (DOACs) as an alternative to aspirin for primary thromboprophylaxis in this population, but data comparing these two therapies are limited. We performed a systematic review and meta-analysis to compare DOACs with aspirin for primary thromboprophylaxis in individuals undergoing outpatient anti-myeloma therapy. Studies were selected when comparing DOACs versus aspirin for thrombotic and haemorrhagic outcomes. We included 10 randomised controlled trials and observational studies comprising 1026 patients with MM who received primary thromboprophylaxis with DOACs (n = 337) or aspirin (n = 689). DOAC thromboprophylaxis was associated with a significantly lower incidence of VTE compared with aspirin (OR 0.33; 95% CI 0.16-0.68; p < 0.001). Major, clinically relevant non-major and minor bleeding event rates did not differ significantly between groups. Overall, our meta-analysis suggests that DOACs may be a preferable option to aspirin for the prevention of MM-related thrombosis. However, these results should be interpreted in the context of heterogeneous baseline population characteristics and potential bias from including observational studies. Further research is needed to evaluate the optimal thromboprophylaxis strategy, particularly in high-risk individuals.


Surgical activity organization during COVID-19 outbreak: a teaching hospital experience.
In order to continue the oncological surgical activity and the surgical emergencies, we have elaborated a reorganization of the surgical department. In particular, differentiated pathways for COVID-19 and NON-COVID-19 patients were promptly planned. This arrangement has involved structural and organizational changes almost daily, with great efforts of the health personnel, but allowing our hospital to be the only one in the area still able to guarantee patients safe access to surgical treatment.


Voluntary relaxation of the external anal sphincter.
In this study five volunteers with special training in anal sphincter exercise (Scandinavian Yoga School) managed voluntarily to reduce anal pressure. The mean reduction of anal pressure was 20 mm Hg. In one of the subjects, this was shown by manometry during low spinal anesthesia and electromyography to be caused by relaxation of the external anal sphincter.


Sensing of micellar microenvironment with dual fluorescent probe, triazolylpyrene (TNDMBPy).
We report a dual fluorescent triazolylpyrene ((TNDMB) Py) as an efficient fluorescent light-up probe of various micellar microenvironments. The absorption spectra of (TNDMB) Py in an aqueous solution of varying surfactant concentration, CTAB, SDS and TX-100 showed that as the surfactant concentration was increased the absorbance increased with no shift in wavelength maxima. The increase of absorbance in each surfactant solution with increase in surfactant concentration was due to the enhanced solubilization of (TNDMB) Py in surfactant solutions. Our investigations based on steady state and time resolved fluorescence techniques showed that the probe reports the microenvironment of ionic surfactant solutions (CTAB and SDS) via dual emission (LE and ICT) at low surfactant concentration. The ICT band showed a blue shifting pattern with enhanced intensity that disappeared as the concentration of surfactant increases (> 1 mM for CTAB and > 3 mM for SDS). In non-ionic surfactant (Triton X-100) solution, the fluorophore showed dual emission with dominant ICT behaviour over LE emission at low concentration (up to 0.35 mM). In reverse micelle we observed a blue shifted ICT band with no LE band with increasing molar concentration of water. We found 100 nm blue shifting when we moved from R = 0 to R = 7, where R is the molar ratio of water to TX-100 (R = [H2O]/[TX-100]). The blue shifting of ICT band is because of the movement of the probe from hydrophilic core to hydrophobic core (surface) of the reverse micelle. Thus from the steady-state fluorescence study it was observed that the ICT band of the probe, (TNDMB) Py was more influenced by the micellar environment in comparison to the LE band. This difference in behaviour of the fluorophore is probably because of varying extent of hydrophobic/hydrogen bonding interactions experienced by the probe and its relative disposition inside the various micellar nanocores.


Effects of a diabetes mellitus-specific care intervention and home environment among older adults following hip fracture surgery.
To explore the impact of home environment on effects of a diabetes mellitus (DM)-specific care model among older adults following hip-fracture surgery. A secondary analysis using the Home Environmental Barriers Scale assessed home environment (intervention group=81, control group=79) at 1- and 3-months post-discharge. Outcomes of physical functioning were assessed at 1-, 3-, 6-, and 12-months post-discharge. The intervention group had better home environmental improvements compared with the control group. Participants were characterized as having good or poor environmental improvements. Those with good improvements and received the intervention had better activities of daily living compared with matched controls. Participants with poor improvements and received the intervention had better scores for hip range of motion and quadriceps muscle strength compared with matched controls. A DM-specific home rehabilitation for older adults following hip-fracture surgery that includes assessment of the home environment can facilitate complex postoperative functional recovery.


A comprehensive evaluation of microbial differential abundance analysis methods: current status and potential solutions.
Differential abundance analysis (DAA) is one central statistical task in microbiome data analysis. A robust and powerful DAA tool can help identify highly confident microbial candidates for further biological validation. Numerous DAA tools have been proposed in the past decade addressing the special characteristics of microbiome data such as zero inflation and compositional effects. Disturbingly, different DAA tools could sometimes produce quite discordant results, opening to the possibility of cherry-picking the tool in favor of one's own hypothesis. To recommend the best DAA tool or practice to the field, a comprehensive evaluation, which covers as many biologically relevant scenarios as possible, is critically needed. We performed by far the most comprehensive evaluation of existing DAA tools using real data-based simulations. We found that DAA methods explicitly addressing compositional effects such as ANCOM-BC, Aldex2, metagenomeSeq (fitFeatureModel), and DACOMP did have improved performance in false-positive control. But they are still not optimal: type 1 error inflation or low statistical power has been observed in many settings. The recent LDM method generally had the best power, but its false-positive control in the presence of strong compositional effects was not satisfactory. Overall, none of the evaluated methods is simultaneously robust, powerful, and flexible, which makes the selection of the best DAA tool difficult. To meet the analysis needs, we designed an optimized procedure, ZicoSeq, drawing on the strength of the existing DAA methods. We show that ZicoSeq generally controlled for false positives across settings, and the power was among the highest. Application of DAA methods to a large collection of real datasets revealed a similar pattern observed in simulation studies. Based on the benchmarking study, we conclude that none of the existing DAA methods evaluated can be applied blindly to any real microbiome dataset. The applicability of an existing DAA method depends on specific settings, which are usually unknown a priori. To circumvent the difficulty of selecting the best DAA tool in practice, we design ZicoSeq, which addresses the major challenges in DAA and remedies the drawbacks of existing DAA methods. ZicoSeq can be applied to microbiome datasets from diverse settings and is a useful DAA tool for robust microbiome biomarker discovery. Video Abstract.


Characterization of two paralysing protein toxins (A-MTX and B-MTX), isolated from a homogenate of the wasp Microbracon hebetor (Say).
Two paralysing toxins (A-MTX and B-MTX) from extracts of Microbracon hebetor (Say) wasps were isolated and purified by gel chromatography, ion exchange chromatography and gel electrophoresis. Both toxins are labile proteins with molecular weights of 43,700 and 56,700, respectively, as estimated by gel chromatography, and with isoelectric pH of 6.85 and 6.62, respectively. Both toxins are inactivated by proteolytic enzymes and by dithiothreitol, but A-MTX appears to be more resistant than B-MTX. The relative amino acid compositions of both toxins show great similarity. The biological effects of the two toxins were identical to those previously found for crude toxin preparations.


Studies of selenium in environmental samples and synthetic mixtures by spectrophotometry.
A rapid, highly sensitive and selective spectrophotometric method for the determination of traces of selenium(IV) is described. The method is based on oxidation of p-nitroaniline by selenium(IV) followed by coupling reaction with N-(1-naphthalene-1-yl)ethane-1,2-diamine dihydrochloride (NEDA) in neutral medium to give red colored derivative with lambda(max) 515 nm and is stable for more than 10 days at 35 degrees C. Beer's law is obeyed for selenium(IV) in the concentration range of 0.02-3.2 microg ml(-1) at the wavelength of maximum absorption. The optimum reaction conditions and other analytical parameters were investigated to enhance the sensitivity of the present method. The detailed study of various interferences made the method more selective. The proposed method was successfully applied to the analysis of selenium in polluted water, natural water samples, plant material, soil samples, and synthetic mixtures. The results obtained were agreed with the reported methods at the 95% confidence level. The performance of proposed method was evaluated in terms of Student's t-test and Variance ratio f-test which indicates the significance of proposed method over reported method.


Rare forms of genetic steroidogenic defects affecting the gonads and adrenals.
Pathogenic variants have been found in all genes involved in the classic pathways of human adrenal and gonadal steroidogenesis. Depending on their function and severity, they cause characteristic disorders of corticosteroid and/or sex hormone deficiency, may result in atypical sex development at birth and/or puberty, and mostly lead to sexual dysfunction and infertility. Genetic disorders of steroidogenesis are all inherited in an autosomal recessive fashion. Loss of function mutations lead to typical phenotypes, while variants with partial activity may manifest with milder, non-classic, late-onset disorders that share similar phenotypes. Thus, these disorders of steroidogenesis are diagnosed by comprehensive phenotyping, steroid profiling and genetic testing using next generation sequencing techniques. Treatment comprises of steroid replacement therapies, but these are insufficient in many aspects. Therefore, studies are currently ongoing towards newer approaches such as lentiviral transmitted enzyme replacement therapy and reprogrammed stem cell-based gene therapy.


A plastic composite of alginate with calcium phosphate granulate as implant material: an in vivo study.
A comparison of calcium phosphate granulate with a composite of alginate and calcium phosphate granulate, shows that the composite has less particle migration, less biodegradation and better handling properties. The tissue response to both materials is similar.


Meta-analysis of locking plate versus intramedullary nail for treatment of proximal humeral fractures.
This meta-analysis compared the clinical outcomes of locking plate with intramedullary nail in the treatment of displaced proximal humeral fractures. We searched PubMed, Embase, and the Cochrane databases for studies comparing locking plate and intramedullary nail treatment of displaced two-, three-, or four-part proximal humeral fractures. The quality of the studies was assessed, and meta-analysis was performed using the Cochrane Collaboration's REVMAN 5.1 software. A total of 615 patients from eight studies were included in this meta-analysis (348 fractures treated with locking plate and 267 with intramedullary nail). Similar Constant scores were observed between the locking plate and intramedullary nail both in randomized controlled trials (RCTs) (mean difference (MD) = 2.12, 95% confidence interval (CI), -2.54 to 6.79, P = 0.37) and observational studies (MD = -1.93, 95% CI, -4.95 to 1.09, P = 0.21). Only one RCT provided American Shoulder and Elbow Surgeons Standardized scores indicating that the locking plate was better than the intramedullary nail (MD = 7.20, 95% CI, 1.29-13.11, P = 0.02). The total complication rate did not specifically favor the locking plate or intramedullary nail both in the RCTs (risk ratio (RR), 2.44; 95% CI, 0.35-16.78; P = 0.37) and observational studies (RR, 1.01; 95% CI, 0.72-1.43; P = 0.94). In the existing literature, limited evidence suggests that the locking plate and intramedullary nail are both valuable options for the treatment of proximal humeral fractures. Because of the observed heterogeneity and variance between the subgroups, more RCT are needed to be able to definitively recommend a locking plate or intramedullary nail for specific fracture patterns.


Column study using modified banana pseudo stem as adsorbent for removal of Pb (II).
Eco-friendly adsorbents such as banana pseudo stem play a fundamental role in the removal of heavy metal elements from the wastewater. Key water resources and chemical industries have been encountering difficulties in removing heavy metal elements using existing conventional methods. The lead-removal process is currently a challenging task for environmental scientists and engineers in terms of cost, effluent disposal, and safety concerns. Hence, this work demonstrates the adsorption of Pb (II) onto modified banana pseudo stem (MBPS) powder as a potential adsorbent to treat different effluents. A characterization of modified banana pseudo-stem powder was performed using scanning electron microscopy (SEM) and Fourier-transform infrared (FTIR) spectroscopy which confirms the material. Experiments carried out using a column process for the removal of lead (II) from an aqueous solution at a fixed concentration of 50 ppm, pH 6 and contact time 120 min. The BET surface area of MBPS was found to be 7.27 m2/g. The results showed that the column studies explain better performance for the removal of Pb (II) and the maximum removal was found to be 49% at lower flow rate (5 mL/min) of fixed initial concentration of 50 ppm.


Culture as a mediator of gene-environment interaction: Cultural consonance, childhood adversity, a 2A serotonin receptor polymorphism, and depression in urban Brazil.
Research on gene-environment interaction was facilitated by breakthroughs in molecular biology in the late 20th century, especially in the study of mental health. There is a reliable interaction between candidate genes for depression and childhood adversity in relation to mental health outcomes. The aim of this paper is to explore the role of culture in this process in an urban community in Brazil. The specific cultural factor examined is cultural consonance, or the degree to which individuals are able to successfully incorporate salient cultural models into their own beliefs and behaviors. It was hypothesized that cultural consonance in family life would mediate the interaction of genotype and childhood adversity. In a study of 402 adult Brazilians from diverse socioeconomic backgrounds, conducted from 2011 to 2014, the interaction of reported childhood adversity and a polymorphism in the 2A serotonin receptor was associated with higher depressive symptoms. Further analysis showed that the gene-environment interaction was mediated by cultural consonance in family life, and that these effects were more pronounced in lower social class neighborhoods. The findings reinforce the role of the serotonergic system in the regulation of stress response and learning and memory, and how these processes in turn interact with environmental events and circumstances. Furthermore, these results suggest that gene-environment interaction models should incorporate a wider range of environmental experience and more complex pathways to better understand how genes and the environment combine to influence mental health outcomes.


A genome-wide association study of chronic otitis media with effusion and recurrent otitis media identifies a novel susceptibility locus on chromosome 2.
Chronic otitis media with effusion (COME) and recurrent otitis media (ROM) have been shown to be heritable, but candidate gene and linkage studies to date have been equivocal. Our aim was to identify genetic susceptibility factors using a genome-wide association study (GWAS). We genotyped 602 subjects from 143 families with 373 COME/ROM subjects using the Illumina Human CNV370-Duo DNA Bead Chip (324,748 SNPs). We carried out the GWAS scan and imputed SNPs at the regions with the most significant associations. Replication genotyping in an independent family-based sample was conducted for 53 SNPs: the 41 most significant SNPs with P < 10(-4) and 12 imputed SNPs with P < 10(-4) on chromosome 15 (near the strongest signal). We replicated the association of rs10497394 (GWAS discovery P = 1.30 × 10(-5)) on chromosome 2 in the independent otitis media population (P = 4.7 × 10(-5); meta-analysis P = 1.52 × 10(-8)). Three additional SNPs had replication P values < 0.10. Two were on chromosome 15q26.1 including rs1110060, the strongest association with COME/ROM in the primary GWAS (P = 3.4 ×10(-7)) in KIF7 intron 7 (P = 0.072), and rs10775247, a non-synonymous SNP in TICRR exon 2 (P = 0.075). The third SNP rs386057 was on chromosome 5 in TPPP intron 1 (P = 0.045). We have performed the first GWAS of COME/ROM and have identified a SNP rs10497394 on chromosome 2 is significantly associated with COME/ROM susceptibility. This SNP is within a 537 kb intergenic region, bordered by CDCA7 and SP3. The genomic and functional significance of this newly identified locus in COME/ROM pathogenesis requires additional investigation.


Cubic C₃N: A New Superhard Phase of Carbon-Rich Nitride.
Using the particle swarm optimization technique, we proposed a cubic superhard phase of C₃N (c-C₃N) with an estimated Vicker's hardness of 65 GPa, which is more energetically favorable than the recently proposed o-C₃N. The c-C₃N is the most stable phase in a pressure range of 6.5-15.4 GPa. Above 15.4 GPa, the most energetic favorable high pressure phase R3m-C₃N is uncovered. Phonon dispersion and elastic constant calculations confirm the dynamical and mechanical stability of c-C₃N and R3m-C₃N at ambient pressure. The electronic structure calculations indicate that both c-C₃N and R3m-C₃N are indirect semiconductor.


Cytomegalovirus Humoral Response Against Epithelial Cell Entry-Mediated Infection in the Primary Infection Setting After Hematopoietic Cell Transplantation.
The influence of humoral immunity on the prevention of primary cytomegalovirus (CMV) infection after hematopoietic cell transplantation (HCT) is poorly understood. To determine whether neutralizing antibodies (nAbs) against CMV pentameric complex (PC)-mediated epithelial cell entry decrease CMV infection after HCT, samples were analyzed from a randomized controlled trial of CMV intravenous immunoglobulin (IVIG) prophylaxis. Weekly serum from 61 CMV donor-positive/recipient-negative (D+/R-) HCT patients (33 control, 28 CMV IVIG) was tested using a PC-entry nAb assay and quantitative CMV polymerase chain reaction (PCR). There was a trend toward higher weekly PC-entry nAb titers (P = .07) and decreased CMV infection by PCR at viral load cutoffs of ≥1000 and ≥10 000 IU/mL in the CMV IVIG arm. High nAb titers were not significantly protective against CMV infection later after HCT in both study arms. Among CMV-infected patients, each log2 increase in nAb titer was associated with an average 0.2 log10 decrease in concurrent CMV viral load after infection (P = .001; adjusted for study arm). This study provides initial support that CMV IVIG prophylaxis moderately enhances PC-entry nAB activity in D+/R- HCT recipients.


Comparison between quantitative computed tomography, scintigraphy, and anatomical methods for prediction of postoperative FEV1 and DLCO: effects of chronic obstructive pulmonary disease status and resected lobes.
Postoperative assessment of pulmonary function is important for estimating the risk of thoracic surgery and long-term disability following pulmonary resection, including predicted postoperative (ppo) forced expiratory volume (FEV) in one second (ppoFEV1) and percent predicted lung diffusion capacity for carbon monoxide (ppo%DLCO) estimation. The ppo values were compared using four different estimation methods between chronic obstructive pulmonary disease (COPD) and non-COPD patients and according to the resected lobe. This prospective study included 59 eligible patients requiring single lobectomy and succeeded in performing pulmonary function tests at 3 and 12 months after lobectomy. The ppoFEV1 and ppo%DLCO were compared with poFEV1 and po%DLCO obtained at 3 and 12 months after lobectomy. The ppo values were estimated using the four usual methods: the 19-segment anatomical technique (S), perfusion scintigraphy (Q), quantitative CT (CT), and quantitative CT with low attenuation volume (CTLAV) subtraction. For non-COPD and COPD patients, the smallest mean difference between ppo and po values was observed by S for FEV1 and %DLCO. Based on the resected lobe, the smallest mean difference was observed by (I) Q for right upper lobectomy (RUL) excluding %DLCO at 12 months by S, (II) S for left upper lobectomy (LUL), (III) CT and CTLAV for right lower lobectomy (RLL), and (IV) CT and CTLAV for left lower lobectomy (LLL) at 12 months. The ppo values calculated by S for RUL (FEV1 at 3 and 12 months and %DLCO at 3 months) and by all four methods for LLL (FEV1 and %DLCO at 3 months) were smaller than the po values. The S method is adequate for calculating ppoFEV1 and ppo%DLCO when patients are classified as non-COPD and COPD. However, S sometimes overestimates the ppoFEV1 and ppo%DLCO when patients are classified according to the resected lobe. The CTLAV method may be the method of choice instead of S for calculating ppoFEV1 and ppo%DLCO in patients who undergo lung lobectomy despite the presence or absence of airflow limitation.


Expanding upon the relationship between gender-affirming hormone therapy, neural connectivity, mental health, and body image dissatisfaction.
Transgender/non-binary (TNB) youth are at increased risk for anxiety, depression, and suicidality compared to cisgender youth. Gender affirming hormone therapy (GAHT, i.e., testosterone or estrogen) is a standard of care option for TNB youth, and we have recently shown that GAHT (testosterone) in transgender youth assigned a female sex at birth is associated with reductions in internalizing symptomatology. The current analysis explores: 1) whether these benefits are observed in both TNB youth assigned female at birth (TNBAFAB) and TNB youth assigned male at birth (TNBAMAB) and 2) the extent to which body image dissatisfaction and alteration in neural circuitry relate to internalizing symptoms. The current study is an expansion of a previous publication from our lab that explored the association between gender-affirming testosterone and internalizing symptomatology. While participants in our previous study consisted of 42 TNBAFAB youth, participants in the current study included adolescent TNBAFAB receiving GAHT (n = 21; GAHT+) and not receiving GAHT (n = 29; GAHT-) as well as adolescent GAHT+ TNBAMAB (n = 15) and GAHT- TNBAMAB (n = 17). Participants reported symptoms of trait and social anxiety, depression, suicidality in the past year, and body image dissatisfaction. Brain activation was measured during a face processing task designed to elicit amygdala activation during functional MRI. GAHT+ TNBAFAB had significantly lower rates of social anxiety, depression, and suicidality compared to GAHT- TNBAFAB. While there were no significant relationships between estrogen and depression and anxiety symptoms, longer duration of estrogen was related to less suicidality. Both testosterone and estrogen administration were related to significantly lower rates of body image dissatisfaction compared to GAHT- youth. No significant differences emerged for BOLD response in the left or right amygdala during the face processing task, however, there was a significant main effect of GAHT on functional connectivity between the right amygdala and the ventromedial prefrontal cortex, such that GAHT+ youth had stronger co-activation between the two regions during the task. Body image dissatisfaction, greater functional connectivity, their interaction effect, and age predicted depression symptomatology and body image dissatisfaction additionally predicted suicidality in the past year. The current study suggests that GAHT is associated with fewer short-term internalizing symptoms in TNBAFAB than in TNBAMAB, although internalizing symptoms among TNBAMAB may diminish with longer durations of estrogen treatment. Controlling for age and sex assigned at birth, our findings indicate that less body image dissatisfaction and greater functional connectivity between the amygdala and ventromedial prefrontal cortex were both predictors of fewer levels of internalizing symptoms following GAHT.


Catecholamines in the carotid body are unaffected by hypercapnia.
In contrast to the increased content of dopamine and norepinephrine in rat carotid body during hypoxia (10% O2 in nitrogen) for 3 and 21 days, hypercapnia (8% CO2 in air) for 21 days failed to alter the catecholamine concentrations. DOPAC content was elevated in hypoxia whereas there were no significant changes in hypercapnia. This finding supports the view that the mechanisms of peripheral chemoreception differ, at least partly, in hypoxia and hypercapnia.