Effect of Acute Ingestion of Green Tea Extract and Lemon Juice on Oxidative Stress and Lipid Profile in Pigs Fed a High-Fat Diet.

Green tea and its catechins have been shown to ameliorate high fat diet-induced oxidative stress and hyperlipidemia. However, low bioavailability of catechins limits their therapeutic potential. Lemon juice (LJ) has been suggested to enhance the bioavailability of catechins in vitro. This study investigated the antioxidative and hypolipidemic efficacy of a single dose of green tea extract (GTE) or GTE plus LJ (GTE + LJ) in high-fat diet fed pigs. Sixteen pigs ingested a single dose of GTE (190 mg/kg/day) or GTE + LJ (0.75 mL/kg/day) mixed with low-fat (LF; 5% fat) or high-fat (HF; 22% fat) diets and blood samples were collected for 24 h. Plasma catechin level peaked at two hours, and gradually returned to baseline after six hours following the intake. The addition of LJ significantly increased plasma catechin level. The diet containing GTE did not lower plasma cholesterol and triacylglycerol (TG) concentrations, superoxide dismutase (SOD) and catalase activity, or malondialdehyde concentration in 24 h in HF-fed pigs. Addition of a single dose of LJ, however, significantly decreased plasma TG level in LF groups but did not cause further changes on any other markers compared to the GTE alone. Our findings indicate limited effect of a single meal containing GTE on plasma antioxidant enzymes, lipid profile, and lipid peroxidation in pigs and no significant synergistic/additive action of adding LJ to GTE within 24 h in pigs. A study with a longer treatment period is warranted to further understand the potential role of GTE in reducing HF diet-induced oxidative stress and the possible synergistic role of LJ

Cross-sectional study of 24-hour urinary electrolyte excretion and associated health outcomes in a convenience sample of Australian primary schoolchildren: the salt and other nutrients in children (SONIC) study protocol

BACKGROUND: Dietary sodium and potassium are involved in the pathogenesis of cardiovascular disease. Data exploring the cardiovascular outcomes associated with these electrolytes within Australian children is sparse. Furthermore, an objective measure of sodium and potassium intake within this group is lacking. OBJECTIVE: The primary aim of the Salt and Other Nutrient Intakes in Children ("SONIC") study was to measure sodium and potassium intakes in a sample of primary schoolchildren located in Victoria, Australia, using 24-hour urine collections. Secondary aims were to identify the dietary sources of sodium and potassium, examine the association between these electrolytes and cardiovascular risk factors, and assess children\u27s taste preferences and saltiness perception of manufactured foods. METHODS: A cross-sectional study was conducted in a convenience sample of schoolchildren attending primary schools in Victoria, Australia. Participants completed one 24-hour urine collection, which was analyzed for sodium, potassium, and creatinine. Completeness of collections was assessed using collection time, total volume, and urinary creatinine. One 24-hour dietary recall was completed to assess dietary intake. Other data collected included blood pressure, body weight, height, waist and hip circumference. Children were also presented with high and low sodium variants of food products and asked to discriminate salt level and choose their preferred variant. Parents provided demographic information and information on use of discretionary salt. Descriptive statistics will be used to describe sodium and potassium intakes. Linear and logistic regression models with clustered robust standard errors will be used to assess the association between electrolyte intake and health outcomes (blood pressure and body mass index/BMI z-score and waist circumference) and to assess differences in taste preference and discrimination between high and low sodium foods, and correlations between preference, sodium intake, and covariates. RESULTS: A total of 780 children across 43 schools participated. The results from this study are expected at the end of 2015. CONCLUSIONS: This study will provide the first objective measure of sodium and potassium intake in Australian schoolchildren and improve our understanding of the relationship of these electrolytes to cardiovascular risk factors. Furthermore, this study will provide insight into child taste preferences and explore related factors. Given the cardiovascular implications of consuming too much sodium and too little potassium, monitoring of these nutrients during childhood is an important public health initiative

Perioperative characteristics, histologic diagnosis, complications, and outcomes of dogs undergoing percutaneous drainage, sclerotherapy or surgical management of intrarenal cystic lesions: 18 dogs (2004-2021)

BACKGROUND: Canine intrarenal cystic lesions (ICLs) are infrequently reported in the veterinary literature. Several treatment options have been described including cyst fenestration (partial nephrectomy/deroofing) +/- omentalization, sclerotherapy using alcohol as a sclerosing agent, percutaneous cyst drainage (PCD), and ureteronephrectomy. Information regarding presenting clinical signs, physical examination findings, histologic diagnosis and outcomes of dogs with ICLs treated by different methods is limited. Medical records of 11 institutions were retrospectively reviewed to identify dogs that underwent PCD, sclerotherapy, surgical deroofing +/- omentalization, or ureteronephrectomy for management of ICLs from 2004 to 2021. Six weeks postoperative/post-procedural follow-up was required. Cases suspected to represent malignancy on preoperative imaging were excluded. The study objective was to provide information regarding perioperative characteristics, complications, and outcomes of dogs undergoing treatment of ICLs. RESULTS: Eighteen dogs were included, with 24 ICLs treated. Ten had bilateral. There were 15 males and 3 females, with crossbreeds predominating. PCD, sclerotherapy, deroofing and ureteronephrectomy were performed in 5 (5 ICLs treated), 7 (11 ICLs), 6 (6), and 7 (7) dogs, respectively, with 5 dogs undergoing > 1 treatment. Seven dogs experienced 8 complications, with requirement for additional intervention commonest. PCD, sclerotherapy and deroofing resulted in ICL resolution in 0/5, 3/11 and 3/6 treated ICLs, respectively. Histopathology identified renal cysts (RCs) in 7/13 dogs with histopathology available and neoplasia in 6/13 (4 malignant, 2 benign). Of 5 dogs diagnosed histopathologically with neoplasia, cytology of cystic fluid failed to identify neoplastic cells. Among 7 dogs with histologically confirmed RCs, 4 had concurrent ICLs in ipsilateral/contralateral kidney, compared with 2/6 dogs with histologically confirmed neoplasia. CONCLUSIONS: Benign and neoplastic ICLs were approximately equally common and cystic fluid cytology failed to differentiate the 2. Among renal-sparing treatments, deroofing most commonly resulted in ICL resolution. Presence of concurrent ICLs in ipsilateral/contralateral kidney does not appear reliable in differentiating benign from malignant ICLs

Do people with risky behaviours participate in biomedical cohort studies?

BACKGROUND: Analysis was undertaken on data from randomly selected participants of a bio-medical cohort study to assess representativeness. The research hypotheses was that there was no difference in participation and non-participations in terms of health-related indicators (smoking, alcohol use, body mass index, physical activity, blood pressure and cholesterol readings and overall health status) and selected socio-demographics (age, sex, area of residence, education level, marital status and work status). METHODS: Randomly selected adults were recruited into a bio-medical representative cohort study based in the north western suburbs of the capital of South Australia – Adealide. Comparison data was obtained from cross-sectional surveys of randomly selected adults in the same age range and in the same region. The cohort participants were 4060 randomly selected adults (18+ years). RESULTS: There were no major differences between study participants and the comparison population in terms of current smoking status, body mass index, physical activity, overall health status and proportions with current high blood pressure and cholesterol readings. Significantly more people who reported a medium to very high alcohol risk participated in the study. There were some demographic differences with study participants more likely to be in the middle level of household income and education level. CONCLUSION: People with risky behaviours participated in this health study in the same proportions as people without these risk factors

A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less

Background: The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 (HIV-1) infection are not clear. We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine. Methods: A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count (50 or fewer vs. 51 to 200 cells per cubic millimeter) and randomly assigned to one of two daily regimens: 600 mg of zidovudine and 300 mg of lamivudine, or that regimen with 2400 mg of indinavir. Stavudine could be substituted for zidovudine. The primary end point was the time to the development of the acquired immunodeficiency syndrome (AIDS) or death. Results: The proportion of patients whose disease progressed to AIDS or death was lower with indinavir, zidovudine (or stavudine), and lamivudine (6 percent) than with zidovudine (or stavudine) and lamivudine alone (11 percent; estimated hazard ratio, 0.50; 95 percent confidence interval, 0.33 to 0.76; P�0.001). Mortality in the two groups was 1.4 percent and 3.1 percent, respectively (estimated hazard ratio, 0.43; 95 percent confidence interval, 0.19 to 0.99; P=0.04). The effects of treatment were similar in both CD4 cell strata. The responses of CD4 cells and plasma HIV-1 RNA paralleled the clinical results. Conclusions: Treatment with indinavir, zidovudine, and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine. (N Engl J Med 1997;337:725-33.

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

A prenylated dsRNA sensor protects against severe COVID-19

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response

Primary frontal sinus squamous cell carcinoma in a dog treated with surgical excision

An 8-year-old castrated male mixed breed dog was presented for a squamous cell carcinoma of the left frontal sinus. A partial craniectomy was performed and polytetrafluoroethylene mesh was placed over the craniectomy site. The dog recovered well with a good cosmetic outcome. Histopathology confirmed primary frontal sinus squamous cell carcinoma

Structural and functional analysis of the rat testis-specific histone H1t gene

A 6.86 kb rat genomic DNA fragment containing the testis-specific histone H1t gene and the histone H4t gene has been sequenced. S1-nuclease protection analyses of total cellular RNA from rat liver and testis showed that histone H1t mRNA was present only in testis. Examination of various highly enriched populations of rat testis cell types revealed that H1t mRNA was found exclusively in a fraction enriched in pachytene spermatocytes. When protein, DNA interactions within the proximal promoter region of the histone H1t gene were examined by electrophoretic mobility shift assays, only minor differences were found in mobility shift patterns of the H1t promoter in assays comparing binding of nuclear proteins from pachytene spermatocytes and early spermatids. However, major differences in binding were observed upon comparing nuclear proteins from rat pachytene spermatocytes to liver. Comparison of binding patterns of rat testis, rat hepatoma H4 cells, HeLa cells, and COS-1 cells also revealed dramatic differences. Transcriptional activity of the histone H1t promoter was examined by measuring H1t promoted chloramphenicol acetyltransferase (CAT) mRNA levels in transient expression assays in transfected rat hepatoma H4 cells, HeLa cells, and COS-1 cells. These assays revealed that the histone H1t promoted CAT gene functioned poorly in HeLa cells and COS-1 cells compared to expression with the parent SV40 promoted vector pSV2CAT. The H1t promoted CAT gene apparently did not work at all in transfected rat hepatoma H4 cells, which is consistent with testis germinal cell specific expression of the histone H1t gene

Comparison of the structural organization and expression of germinal and somatic rat histone H4 genes

A rat somatic histone H4 gene was isolated by screening a rat genomic library using a cloned cell-cycle-regulated human histone H4 gene as a probe. The somatic histone H4 gene was subcloned and the nucleotide sequence was determined. The structural organization and expression of the somatic histone H4 gene and the rat germinal histone H4t gene were compared. Although the predicted amino-acid sequences of the two histones were identical, 49 out of 102 codons differed. The leader sequence of the germinal histone H4t mRNA was 17 bases compared to 40 bases for the somatic histone H4 mRNA, and the 3\u27 terminal sequence of the germinal histone H4t mRNA was 52 bases compared to 75 bases for the somatic histone H4 mRNA. The germinal histone H4 gene also lacked a consensus purine-rich motif which was present in the 5\u27 noncoding region of the somatic histone H4 gene. Northern blot analyses and S1-nuclease protection analyses revealed that the germinal histone H4t and H1t genes were expressed during spermatogenesis in rat pachytene spermatocytes, and the somatic histone H4 gene was expressed only in nongerminal rat cells and tissues. The histone H4t gene was also expressed in some other rat cell types. The differences in expression of the histone H4t and H1t genes may reflect differences in transcription, differences in turnover rates of the mRNAs, or a combination of these factors