Quality of life and functional outcomes in tongue cancer patients: a long-term, prospective, comparative study.

BACKGROUND: The tongue has an indispensable role in communication, swallowing and breathing. Tongue cancer treatment involves direct resection of the tumor and surrounding tissue, which can limit many essential functions of the tongue. There are few patient-reported quality of life studies involving tongue cancer exclusively. There is also a lack of data on the outcomes of quality of life regarding different reconstructive methods, adjuvant non-surgical therapies and other predicting factors. Our objective is to assess the quality of life, functional status, and predicting factors in patients with tongue cancer up to one year after surgical resection. MATERIAL AND METHODS: Thirty-six patients with tongue cancer were prospectively identified between October of 2017 and January 2021. Patients were examined before and one, three, six and twelve months after surgical resection with the validated University of Washington Quality of Life questionnaire (UW-QOL). Data collection included patient age, sex, TNM staging, size of resection, neck dissection, tracheostomy, reconstructive method and adjuvant therapies. Outcome scores were compared using the Friedman test. Multiple linear regression analysis was used to identify the predictors of quality of life and functional status. RESULTS: The use of UWQOL scores as dependent variables revealed the following predicting factors: age, tobacco use, radiotherapy, chemotherapy, reconstruction method and neck dissection. CONCLUSIONS: The most relevant findings in our study are that flap reconstruction becomes increasingly necessary when a glossectomy resection is over 45 mm, in order to maintain tongue function. We established that the reconstructive flap type does not influence quality of life in the long term. Also, we have found that cervical sentinel node biopsy provides better quality of life over neck dissection in the first 3 months after surgery.

Disconnection in a left-hemispheric temporo-parietal network impairs multiplication fact retrieval.

Arithmetic fact retrieval has been suggested to recruit a left-lateralized network comprising perisylvian language areas, parietal areas such as the angular gyrus (AG), and non-neocortical structures such as the hippocampus. However, the underlying white matter connectivity of these areas has not been evaluated systematically so far. Using simple multiplication problems, we evaluated how disconnections in parietal brain areas affected arithmetic fact retrieval following stroke. We derived disconnectivity measures by jointly considering data from n = 73 patients with acute unilateral lesions in either hemisphere and a white-matter tractography atlas (HCP-842) using the Lesion Quantification Toolbox (LQT). Whole-brain voxel-based analysis indicated a left-hemispheric cluster of white matter fibers connecting the AG and superior temporal areas to be associated with a fact retrieval deficit. Subsequent analyses of direct gray-to-gray matter disconnections revealed that disconnections of additional left-hemispheric areas (e.g., between the superior temporal gyrus and parietal areas) were significantly associated with the observed fact retrieval deficit. Results imply that disconnections of parietal areas (i.e., the AG) with language-related areas (i.e., superior and middle temporal gyri) seem specifically detrimental to arithmetic fact retrieval. This suggests that arithmetic fact retrieval recruits a widespread left-hemispheric network and emphasizes the relevance of white matter connectivity for number processing.

The rocky road to freedom: number of countries transited during defection and risk of metabolic syndrome among North Korean Refugees in South Korea.

OBJECTIVES: North Korean Refugees (NKRs) undergo defection, and this has been shown to impact their current health status in South Korea. However, little is understood about how the defection process is related to metabolic syndrome (MetS). This study regarded the defection process to be a quasi-measurement of traumatic experience and investigated whether defection was a risk factor for MetS among NKRs living in South Korea. STUDY DESIGN: This cross-sectional study obtained data from the Korea University Anam Hospital in Seoul. NKRs (N = 847) voluntarily completed questionnaires and underwent at least one medical examination between October 2008 and July 2021. METHODS: Multivariable logistic regression models were used to evaluate whether the number of countries transited by NKRs was associated with MetS by controlling for covariates. RESULTS: The prevalence of MetS among male and female NKRs in South Korea was 12.3% and 13.3%, respectively. The highest prevalence of MetS (33.4%) was among NKRs who had transited two countries. The number of months in transit countries (mean: 49.9 ± 51.7) and period of residence in South Korea (mean: 40.9 ± 40.9 months) were also considered. NKRs who transited three countries had a higher probability of MetS (odds ratio [OR] 2.660, 95% confidence interval [CI] 1.161-6.097) than those who travelled directly to South Korea. NKRs who transited three countries and had only resided in South Korea for a short period had a higher probability of MetS (OR 3.424, 95% CI 1.149-10.208) than those who have lived in South Korea for a longer period. CONCLUSIONS: Considering the social vulnerability of NKRs and consequential health problems, there is an urgent need for appropriate support from the government and society.

Longitudinal Outcomes of COVID-19-Associated Collapsing Glomerulopathy and Other Podocytopathies.

BACKGROUND: The long-term outcome of COVID-19-associated collapsing glomerulopathy is unknown. METHODS: We retrospectively identified 76 native kidney biopsies from patients with history of COVID-19 between March 2020 and April 2021. Presenting and outcome data were obtained for all 23 patients with collapsing glomerulopathy and for seven patients with noncollapsing podocytopathies. We performed APOL1 genotyping by Sanger sequencing, immunostaining for spike and nucleocapsid proteins, and in situ hybridization for SARS-CoV-2. RESULTS: The 23 patients with COVID-19-associated collapsing glomerulopathy were median age 57 years (range, 35-72), included 16 men, and were predominantly (91%) Black. Severity of COVID-19 was mild or moderate in most (77%) patients. All but one patient presented with AKI, 17 had nephrotic-range proteinuria, and six had nephrotic syndrome. Fourteen (61%) patients required dialysis at presentation. Among 17 patients genotyped, 16 (94%) were high-risk APOL1. Among 22 (96%) patients with median follow-up at 155 days (range, 30-412), 11 (50%) received treatment for COVID-19, and eight (36%) received glucocorticoid therapy for podocytopathy. At follow-up, 19 (86%) patients were alive, and 15 (68%) were dialysis free, including seven of 14 who initially required dialysis. The dialysis-free patients included 64% (seven of 11) of those treated for COVID-19 and 75% (six of eight) of those treated with glucocorticoids for podocytopathy. Overall, 36% achieved partial remission of proteinuria, 32% had no remission, and 32% reached combined end points of ESKD or death. Viral infection of the kidney was not detected. CONCLUSIONS: Half of 14 patients with COVID-19-associated collapsing glomerulopathy requiring dialysis achieved dialysis independence, but the long-term prognosis of residual proteinuric CKD remains guarded, indicating a need for more effective therapy.

Integrase strand transfer inhibitor treatment does not increase the incidence of immune reconstitution inflammatory syndrome in HIV-infected Koreans.

OBJECTIVES: Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting antiretroviral therapy (ART) in patients with advanced HIV infection. The aim of this study was to determine the incidence and risk factors of IRIS in HIV-infected Koreans initiating ART, and whether integrase strand transfer inhibitor (INSTI) treatment increases the risk of IRIS. METHODS: This retrospective analysis included adults living with HIV, seen at four university-affiliated hospitals in South Korea, who were naïve to ART and had a CD4 T-cell count < 200 cells/µL between January 2004 and May 2019. IRIS was determined through a medical record review within 6 months of ART initiation. Propensity score-matched case-control study between the non-INSTI and INSTI groups was performed. RESULTS: The study included 501 patients; 192 were assigned to the INSTI group, who started ART based on INSTIs as the initial treatment. There were opportunistic infections (OIs) in 253 (50.5%) cases before ART initiation. The three most common OIs were Pneumocystis jirovecii pneumonia, candidiasis and tuberculosis (TB). We identified 47 cases of IRIS; TB-IRIS was the most common type. The incidence of IRIS within 6 months of ART initiation was 9.4%, and there were no significant differences in baseline characteristics and incidence of IRIS between the matched groups. The risk factors for IRIS were pre-ART CD4 T-cell count (< 30 cells/µL), higher pre-ART viral load (≥ 75 000 copies/mL), and TB-OI. CONCLUSIONS: The incidence of IRIS was 9.4% in Korean HIV patients. The INSTI regimen was not related to IRIS occurrence.

Effect of empagliflozin on ketone bodies in patients with stable chronic heart failure.

BACKGROUND: Recent studies indicated that sodium glucose cotransporter (SGLT)2 inhibition increases levels of ketone bodies in the blood in patients with type 1 and 2 diabetes. Other studies suggested that in patients with chronic heart failure (CHF), increased myocardial oxygen demand can be provided by ketone bodies as a fuel substrate. Experimental studies reported that ketone bodies, specifically beta-hydroxybutyrate (ß-OHB) may increase blood pressure (BP) by impairing endothelium-dependant relaxation, thereby leading to increased vascular stiffness. In our study we assessed whether the SGLT 2 inhibition with empagliflozin increases ketone bodies in patients with stable CHF and whether such an increase impairs BP and vascular function. METHODS: In a prospective, double blind, placebo controlled, parallel-group single centre study 75 patients with CHF (left ventricular ejection fraction 39.0 ± 8.2%) were randomised (2:1) to the SGLT-2 inhibitor empagliflozin 10 mg orally once daily or to placebo, 72 patients completed the study. After a run-in phase we evaluated at baseline BP by 24 h ambulatory blood pressure (ABP) monitoring, vascular stiffness parameters by the SphygmoCor system (AtCor Medical, Sydney, NSW, Australia) and fasting metabolic parameters, including ß-OHB by an enzymatic assay (Beckman Coulter DxC 700 AU). The same measurements were repeated 12 weeks after treatment. In 19 of the 72 patients serum levels of ß-OHB were beneath the lower border of our assay (< 0.05 mmol/l) therefore being excluded from the subsequent analysis. RESULTS: In patients with stable CHF, treatment with empagliflozin (n = 36) was followed by an increase of ß-OHB by 33.39% (p = 0.017), reduction in 24 h systolic (p = 0.038) and diastolic (p = 0.085) ABP, weight loss (p = 0.003) and decrease of central systolic BP (p = 0.008) and central pulse pressure (p = 0.008). The increase in ß-OHB was related to an attenuated decrease of empagliflozin-induced 24 h systolic (r = 0.321, p = 0.069) and diastolic (r = 0.516, p = 0.002) ABP and less reduction of central systolic BP (r = 0.470, p = 0.009) and central pulse pressure (r = 0.391, p = 0.033). No significant changes were seen in any of these parameters after 12 weeks of treatment in the placebo group (n = 17). CONCLUSION: In patients with stable CHF ketone bodies as assessed by ß-OHB increased after treatment with empagliflozin. This increase led to an attenuation of the beneficial effects of empagliflozin on BP and vascular parameters. Trial registration The study was registered at http://www.clinicaltrials.gov (NCT03128528).

Orbital Complexity in Intrinsic Magnetic Topological Insulators MnBi_{4}Te_{7} and MnBi_{6}Te_{10}.

Using angle-resolved photoelectron spectroscopy (ARPES), we investigate the surface electronic structure of the magnetic van der Waals compounds MnBi_{4}Te_{7} and MnBi_{6}Te_{10}, the n=1 and 2 members of a modular (Bi_{2}Te_{3})_{n}(MnBi_{2}Te_{4}) series, which have attracted recent interest as intrinsic magnetic topological insulators. Combining circular dichroic, spin-resolved and photon-energy-dependent ARPES measurements with calculations based on density functional theory, we unveil complex momentum-dependent orbital and spin textures in the surface electronic structure and disentangle topological from trivial surface bands. We find that the Dirac-cone dispersion of the topologial surface state is strongly perturbed by hybridization with valence-band states for Bi_{2}Te_{3}-terminated surfaces but remains preserved for MnBi_{2}Te_{4}-terminated surfaces. Our results firmly establish the topologically nontrivial nature of these magnetic van der Waals materials and indicate that the possibility of realizing a quantized anomalous Hall conductivity depends on surface termination.

Does serum vitamin D level affect the association between cardiovascular health and cognition? Results of the Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) study.

BACKGROUND AND PURPOSE: Few studies have assessed the role of vitamin D in the association between cardiovascular risk factors and cognitive function. Here, the aim was to investigate the association between cardiovascular health (CVH) and cognitive function according to vitamin D level in a middle-aged Korean population. METHODS: This cross-sectional study included 840 men and 1811 women (mean age 57.2 years) from the Cardiovascular and Metabolic Diseases Etiology Research Center study baseline enrolment (2013-2018). Life's Simple 7 tools from the American Heart Association were used to assess CVH. Cognitive function was evaluated using the Mini-Mental State Estimation for Dementia Screening (MMSE-DS), and the serum 25-hydroxyvitamin D level was measured. RESULTS: In the adjusted generalized linear regression models, no significant association between a high Life's Simple 7 score (4-7 metric at optimal level) and MMSE-DS score (ß = 0.01, P = 0.93) was found. Amongst men with a high vitamin D level, the high Life's Simple 7 score group showed a significantly higher MMSE-DS score (ß = 0.48, P = 0.03). However, amongst men in the low vitamin D group, the association was opposite with no statistical significance (ß = -0.23, P = 0.08). In women, the results were similar, but both strata according to vitamin D level showed no statistical significance. CONCLUSIONS: Our findings suggest that vitamin D is an effect modifier in the association between CVH and cognition, especially in men.

Bacteriocin production by Leuconostoc citreum ST110LD isolated from organic farm soil, a promising biopreservative.

AIMS: The objective of this study was to isolate a bacteriocin-producing strain and to characterize the expressed bacteriocin for the control of Listeria monocytogenes with aim of biopreservation application. METHODS AND RESULTS: Soil samples from a Korean organic farm were subjected to microbiological analysis for isolation of potential bacteriocinogenic LAB, based on a three-level approach, using L. monocytogenes ATCC 15313 as an indicator test micro-organism. From a total of 17 isolates with inhibitory potential, seven were confirmed to be bacteriocin producers. The selected isolates were differentiated based on their morphology, catalase reaction, sugar fermentation profile obtained by API50CHL and by RAPD-PCR generating two unique profiles. One of the isolates, ST110LD, a specific strong producer of anti-Listeria bacteriocins (12 800 AU ml-1 ) was identified as Leuconostoc citreum. The proteinaceous nature of the inhibitory compound produced by Leuc. citreum ST110LD was confirmed through treatment with pepsin and α-chymotrypsin. Bacteriocin activity was observed to be not affected by the presence of milk, NaCl, SDS, Tween 80 or glycerol. Bacteriocin ST110LD effectively inhibited the growth of exponentially growing L. monocytogenes ATCC 15313 during a 10-h incubation period in BHI at 37°C. In addition, this bacteriocin showed specific inhibition of only Listeria spp., but did not inhibit the growth of beneficial cultures included in the microbial test panel for assessment of the spectrum of activity. CONCLUSIONS: Leuconostoc citreum ST110LD was evaluated as safe bacterium strain, producing bacteriocin with high specificity against listerial and enterococcal species. Specificity of producer strain and expressed bacteriocin can be explored in biopreservation of different fermented food products or applied in biotherapy of antibiotic resistant listerial or enterococcal infections. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this is the first report of bacteriocin produced by Leuc. citreum strain with highly specific antimicrobial activity against Listeria sp. and Enterococcus sp.

Updating genome annotation for the microbial cell factory Aspergillus niger using gene co-expression networks.

A significant challenge in our understanding of biological systems is the high number of genes with unknown function in many genomes. The fungal genus Aspergillus contains important pathogens of humans, model organisms, and microbial cell factories. Aspergillus niger is used to produce organic acids, proteins, and is a promising source of new bioactive secondary metabolites. Out of the 14,165 open reading frames predicted in the A. niger genome only 2% have been experimentally verified and over 6,000 are hypothetical. Here, we show that gene co-expression network analysis can be used to overcome this limitation. A meta-analysis of 155 transcriptomics experiments generated co-expression networks for 9,579 genes (∼65%) of the A. niger genome. By populating this dataset with over 1,200 gene functional experiments from the genus Aspergillus and performing gene ontology enrichment, we could infer biological processes for 9,263 of A. niger genes, including 2,970 hypothetical genes. Experimental validation of selected co-expression sub-networks uncovered four transcription factors involved in secondary metabolite synthesis, which were used to activate production of multiple natural products. This study constitutes a significant step towards systems-level understanding of A. niger, and the datasets can be used to fuel discoveries of model systems, fungal pathogens, and biotechnology.

Lower Limb Takeoff Mechanics During a Leap in Dancers With and Without Flexor Hallucis Longus Tendinopathy.

OBJECTIVE: Altered ground reaction force (GRF) and joint torsional stiffness are associated with various lower extremity injuries, but these have yet to be examined in dancers with flexor hallucis longus (FHL) tendinopathy. Additionally, a simple, field-friendly kinematic correlate to ground contact kinetics would be useful for clinical application. The purpose of this study was to compare lower extremity biomechanics during takeoff of a dance leap (saut de chat) in dancers with and without FHL tendinopathy, and to examine lower limb posture at initial contact as a clinical correlate of injury-related kinetic factors. METHODS: Motion capture and inverse dynamics were used to analyze saut de chat takeoff performed by 11 uninjured dancers and 8 dancers with FHL tendinopathy. GRF parameters, joint torsional stiffness of the metatarsophalangeal, ankle, and knee joints, and lower extremity posture at initial contact were compared between groups using Welch's t-tests. RESULTS: Dancers with FHL tendinopathy maintained similar jump height as the uninjured dancers, but exhibited lower peak vertical GRF, longer time to peak force, and less joint torsional stiffness at the metatarsophalangeal, ankle, and knee joints during loading response of the takeoff step. Lower extremity contact angle was smaller and the horizontal distance between center-of-mass and center-of-pressure was greater in dancers with FHL tendinopathy. These two measures of lower limb posture at initial contact were significantly correlated with kinetic factors occurring later in ground contact (R2=0.29-0.51). CONCLUSION: Dancers with FHL tendinopathy demonstrated altered lower extremity kinetics during takeoff of a leap compared to uninjured dancers, which may contribute to, or be a compensation response to, injury.

Anchor, Spacer, and Ligand-Modified Engineered Exosomes for Trackable Targeted Therapy.

Exosomes have been widely demonstrated as an effective anticancer therapeutic moiety. However, their clinical translation has been limited by the requirement of prohibitively high therapeutic doses due to their lack of specificity in delivery and, consequently, short systemic half-life. To overcome these challenges, we engineered a platform for modifying exosomes with an active targeting modality composed of membrane Anchor (BODIPY)-Spacer (PEG)-targeting Ligands (cyclic RGD peptide) (ASL). Herein, we show that the intramembrane incorporation of a trackable, targeting system renders ASL exosomes (AExs) a modular platform. AExs significantly overcome challenges associated with exosome modification, including potential damage for functionalization, or destabilizing interactions between dyes and drugs. ASL-modification not only enhanced stability in imparting active targeting but also introduced a built-in bioimaging modality. Our studies show that AExs target B16F10 melanoma tumor sites by the specific interaction of cyclic RGD and integrin. Doxorubicin encapsulated AExs (dAExs) significantly inhibited the growth of melanoma in vitro and in vivo. Thus, we conclude that ASL-modification allows exosomes to be transformed into a novel therapeutic vehicle uniquely integrating in vivo tracking and robust targeting with drug delivery. We anticipate that the therapeutic, targeting, and diagnostic modularity provided by ASL will potentiate translational applications of exosome-based vehicles beyond anticancer therapy.

Possible Role of CRF-Hcrt Interaction in the Infralimbic Cortex in the Emergence and Maintenance of Compulsive Alcohol-Seeking Behavior.

Alcohol use disorder (AUD) is a chronic, relapsing disorder that is characterized by the compulsive use of alcohol despite numerous health, social, and economic consequences. Initially, the use of alcohol is driven by positive reinforcement. Over time, however, alcohol use can take on a compulsive quality that is driven by the desire to avoid the negative consequences of abstinence, including negative affect and heightened stress/anxiety. This transition from positive reinforcement- to negative reinforcement-driven consumption involves the corticotropin-releasing factor (CRF) system, although mounting evidence now suggests that the CRF system interacts with other neural systems to ultimately produce behaviors that are symptomatic of compulsive alcohol use, such as the hypocretin (Hcrt) system. Hypocretins are produced exclusively in the hypothalamus, but Hcrt neurons project widely throughout the brain and reach regions that perform regulatory functions for numerous behavioral and physiological responses-including the infralimbic cortex (IL) of the medial prefrontal cortex (mPFC). Although the entire mPFC undergoes neuroadaptive changes following prolonged alcohol exposure, the IL appears to undergo more robust changes compared with other mPFC substructures. Evidence to date suggests that the IL is likely involved in EtOH-seeking behavior, but ambiguities with respect to the specific role of the IL in this regard make it difficult to draw definitive conclusions. Furthermore, the manner in which CRF interacts with Hcrt in this region as it pertains to alcohol-seeking behavior is largely unknown, although immunohistochemical and electrophysiological experiments have shown that CRF and Hcrt directly interact in the mPFC, suggesting that the interaction between CRF and Hcrt in the IL may be critically important for the development and subsequent maintenance of compulsive alcohol seeking. This review aims to consolidate recent literature regarding the role of the IL in alcohol-seeking behavior and to discuss evidence that supports a functional interaction between Hcrt and CRF in the IL.

Early data on long-term efficacy and safety of inotersen in patients with hereditary transthyretin amyloidosis: a 2-year update from the open-label extension of the NEURO-TTR trial.

BACKGROUND AND PURPOSE: Hereditary transthyretin (hATTR) amyloidosis causes progressive polyneuropathy resulting from transthyretin (TTR) amyloid deposition throughout the body, including the peripheral nerves. The efficacy and safety of inotersen, an antisense oligonucleotide inhibitor of TTR protein production, were demonstrated in the pivotal NEURO-TTR study in patients with hATTR polyneuropathy. Here, the long-term efficacy and safety of inotersen are assessed in an ongoing open-label extension (OLE) study. METHODS: Patients who completed NEURO-TTR were eligible to enroll in the OLE (NCT02175004). Efficacy assessments included the modified Neuropathy Impairment Score plus seven neurophysiological tests composite score (mNIS + 7), the Norfolk Quality of Life - Diabetic Neuropathy (Norfolk QOL-DN) questionnaire total score and the Short-Form 36 Health Survey (SF-36) Physical Component Summary (PCS) score. Safety and tolerability were also assessed. RESULTS: Overall, 97% (135/139) of patients who completed NEURO-TTR enrolled in the OLE. Patients who received inotersen for 39 cumulative months in NEURO-TTR and the OLE continued to show benefit; patients who switched from placebo to inotersen in the OLE demonstrated improvement or stabilization of neurological disease progression by mNIS + 7, Norfolk QOL-DN and SF-36 PCS. No new safety concerns were identified. There was no evidence of increased risk for grade 4 thrombocytopenia or severe renal events with increased duration of inotersen exposure. CONCLUSION: Inotersen slowed disease progression and reduced deterioration of quality of life in patients with hATTR polyneuropathy. Early treatment with inotersen resulted in greater long-term disease stabilization than delayed initiation. Routine platelet and renal safety monitoring were effective; no new safety signals were observed.

Chicken PRDX3 is required for proliferation of chicken embryo fibroblast cells.

1. This experiment investigated the influence of chicken PRDX3 on cell proliferation in chick embryo fibroblast cells using PRDX3 knockdown technology.2. A methyl thiazolyl tetrazolium (MTT) assay was performed to assess the effect of chPRDX3 knockdown on fibroblast proliferation. The antioxidant effect was investigated to determine if it directly mediated fibroblast cell proliferation.3. To determine the role of chPRDX3 on cell proliferation, an siRNA mediated knockdown was performed in chick fibroblast cells using an in vitro assay. The proliferation of fibroblast cells transfected with siPRDX3 #3 and siPRDX3 Mix was significantly decreased after 48 h (P < 0.01). In addition, the knockdown of chicken PRDX3 suppressed cell proliferation through an increase in oxidative stress.4. The results demonstrated that chPRDX3 is required for cell proliferation in chicken fibroblast cells. Such findings have important implications for the maintenance of chicken fibroblast cells.

[Algorithm for flexible decision-making in the intra-hospital management of patients with the changing requirements of the SARS-CoV-2 pandemic]. / Flexibler Entscheidungsalgorithmus zum innerklinischen stationären Patient*innen-Management unter wechselnden Anforderungen der SARS-CoV-2-Pandemie.

After the initial fulminant outbreak, the SARS-CoV­2 pandemic has now taken a more protracted course which, nevertheless, challenges hospitals in returning to a "normal" mode and in preparing for a worst-case scenario of a second wave. Not only the organization of the first contact with the patient and the admission in the emergency department but also the admission as an in-patient and the subsequent management requires both flexibility and clear directions of action for the medical personnel involved. The aim of the algorithm was to develop a structured, easy to implement and easy to follow guideline while simultaneously preserving resources. The algorithm covers some key points of decision making such as clinical signs, first contact, admission for in-patient treatment, consequences of swab and computed tomography (CT) results, and allocation and isolation measures within the hospital. The algorithm is not intended to guide diagnostics, decisions and treatment in the narrower medical sense but to provide more general instructions for the management of in-patients considering specific aspects of SARS-CoV­2.

Linking Race, Cancer Outcomes, and Tissue Repair.

The burden of cancer in the United States is unevenly spread across its different populations, with stark differences in both disease prevalence and outcome on the basis of race and ethnicity. Although a large portion of these differences can be explained by a variety of sociobehavioral and socioeconomic factors, even after these exposures are taken into consideration, considerable disparities persist. In this review, we explore a conceptual framework of biological theories and unifying concepts, based on an evolutionary perspective, that may help better define common guiding principles for exploration of underlying causes of cancer health disparities. The ultimate goal of this conceptual perspective is to outline approaches that may aid in establishing integrated pathway and processes analyses to provide useful insights to guide the development of future interventions. These interventions will improve outcome, increase prevention, and ultimately eliminate all disparities.

Astrocytic water channel aquaporin-4 modulates brain plasticity in both mice and humans: a potential gliogenetic mechanism underlying language-associated learning.

The role of astrocytes in brain plasticity has not been extensively studied compared with that of neurons. Here we adopted integrative translational and reverse-translational approaches to explore the role of an astrocyte-specific major water channel in the brain, aquaporin-4 (AQP4), in brain plasticity and learning. We initially identified the most prevalent genetic variant of AQP4 (single nucleotide polymorphism of rs162008 with C or T variation, which has a minor allele frequency of 0.21) from a human database (n=60 706) and examined its functionality in modulating the expression level of AQP4 in an in vitro luciferase reporter assay. In the following experiments, AQP4 knock-down in mice not only impaired hippocampal volumetric plasticity after exposure to enriched environment but also caused loss of long-term potentiation after theta-burst stimulation. In humans, there was a cross-sectional association of rs162008 with gray matter (GM) volume variation in cortices, including the vicinity of the Perisylvian heteromodal language area (Sample 1, n=650). GM volume variation in these brain regions was positively associated with the semantic verbal fluency. In a prospective follow-up study (Sample 2, n=45), the effects of an intensive 5-week foreign language (English) learning experience on regional GM volume increase were modulated by this AQP4 variant, which was also associated with verbal learning capacity change. We then delineated in mice mechanisms that included AQP4-dependent transient astrocytic volume changes and astrocytic structural elaboration. We believe our study provides the first integrative evidence for a gliogenetic basis that involves AQP4, underlying language-associated brain plasticity.

Skin type differences in solar-simulated radiation-induced oxidative stress.

BACKGROUND: Human skin protects the body from external damage, pathogens and oxidative stress factors such as ultraviolet (UV) radiation. Excessive exposure to UV radiation can lead to increased production of free radicals and hence to skin damage such as inflammation, premature skin ageing and skin cancer. Besides UV, the visible and near infrared (NIR) regions are also a source of radical production. Half of all free radicals are induced by the visible + NIR region of the solar spectrum in people with skin types I-III, but data on the effects in people with skin types IV-VI are missing. OBJECTIVES: This in vivo pilot study addressed the distribution of radical production in skin types IV and V during irradiation in the UV, visible and NIR spectral regions, comparing the first results with those of skin type II. METHODS: The measurements were performed in vivo using L-band electron paramagnetic resonance spectroscopy and the spin probe PCA. RESULTS: In skin types IV-V most radicals were induced in the visible + NIR region, followed by the NIR and UV regions of the sun spectrum. Significantly (P ≤ 0·05) more radicals were induced in skin types IV-V than in type II during NIR irradiation, whereas skin types IV-V exhibited significantly less UV-induced radicals (P ≤ 0·01) than skin type II. CONCLUSIONS: All spectral regions (UV, visible and NIR) cause free radical formation in skin types II and IV-V. After 4 min of solar-simulated exposure (UV-NIR), the radical formation in skin types IV-V is 60% of that in skin type II. Therefore people with darker skin types also need solar protection.

Efficacy and safety of a non-mineral oil adjuvanted injectable vaccine for the protection of Atlantic salmon (Salmo salar L.) against Flavobacterium psychrophilum.

Flavobacterium psychrophilum is the causative agent of Rainbow Trout Fry Syndrome which has had a major impact on global salmonid aquaculture. Recent outbreaks in Atlantic salmon in Scotland and Chile have added to the need for a vaccine to protect both salmon and trout. At present no licensed vaccines are available in Europe, leaving antibiotics as the only course of action to contain disease outbreaks. Outbreaks generally occur in fry at temperatures between 10 and 15 °C. Recently outbreaks in larger fish have given added impetus to the development of a vaccine which can provide long term protection from this highly heterogeneous pathogen. Most fish injectable vaccines are formulated with oil emulsion adjuvants to induce strong and long lasting immunity, but which are known to cause side effects. Alternative adjuvants are currently sought to minimise these adverse effects. The current study was performed to assess the efficacy of a polyvalent, whole cell vaccine containing formalin-inactivated F. psychrophilum to induce protective immunity in Atlantic salmon. The vaccine was formulated with an adjuvant containing squalene and aluminium hydroxide, and was compared to a vaccine formulated with a traditional oil adjuvant, Montanide ISA 760VG, and a non-adjuvanted vaccine. Duplicate groups of salmon (23.5 ± 6.8 g) were vaccinated with each of the vaccine formulations or phosphate buffered saline by intraperitoneal injection. Fish were challenged by intramuscular injection with F. psychrophilum six weeks post-vaccination to test the efficacy of the vaccines. Cumulative mortality reached 70% in the control salmon, while the groups of salmon that received vaccine had significantly lower mortality than the controls (p = 0.0001), with no significant difference in survival between vaccinated groups. The squalene/alum adjuvant was safe, more readily metabolised by the fish and induced less histopathological changes than the traditional oil adjuvant.