Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.

Subclinical paraganglioma of the retroperitoneum:A case report

BACKGROUND Paraganglioma(PGL)located in the retroperitoneum presents challenges in diagnosis and treatment due to its hidden location,lack of specific symptoms in the early stages,and absence of distinctive manifestations on imaging.CASE SUMMARY A 56-year-old woman presented with a left upper abdominal mass discovered 1 wk ago during a physical examination.She did not have a history of smoking,alcohol consumption,or other harmful habits,no surgical procedures or infectious diseases,and had a 4-year history of hypertension.Upon admission,she did not exhibit fever,vomiting,or abdominal distension.Physical examination indicated mild percussion pain in the left upper abdomen,with no palpable enlargement of the liver or spleen.Laboratory tests and tumor markers showed no significant abnormalities.Enhanced computed tomography and magnetic resonance imaging of the upper abdomen revealed a cystic solid mass in the left epigastrium measuring approximately 6.5 cm×4.5 cm,with inhomogeneous enhancement in the arterial phase,closely associated with the lesser curvature of the stomach and the pancreas.The patient underwent laparoscopic resection of the retroperitoneal mass,which was successfully removed without tumor rupture.A 12-month postoperative follow-up period showed good recovery.CONCLUSION This case report details the successful laparoscopic resection of a retroperitoneal subclinical PGL,resulting in a good recovery observed at the 12-month follow-up.Interestingly,the patient also experienced unexpected cure of hypertensive disease.

Subclinical hepatitis E virus genotype 1 infection:The concept of“dynamic human reservoir”

Hepatitis E virus(HEV)is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden.There are eight genotypes of HEV.Among them,the four common ones known to infect humans,genotypes 1 and 2 are prevalent in the developing world and genotypes 3 and 4 are causing challenge in the industrialized world.Asymptomatic HEV viremia in the general population,especially among blood donors,has been reported in the literature worldwide.The clinical implications related to this asymptomatic viremia are unclear and need further exploration.Detection of viremia due to HEV genotype 1 infection,apparently among healthy blood donors is also reported without much knowledge about its infection rate.Similarly,while HEV genotype 3 is known to be transmitted via blood transfusion in humans and has been subjected to screening in many European nations,instances of transmission have also been documented albeit without significant clinical consequences.Epidemiology of HEV genotype 1 in endemic areas often show waxing and waning pattern.Occasional sporadic occurrence of HEV infection interrupted by outbreaks have been frequently seen.In absence of known animal reservoir,where HEV exists in between outbreak is a mystery that needs further exploration.However,occurrence of asymptomatic HEV viremia due to HEV genotype 1 during epidemiologically quiescent period may explain that this phenomenon may act as a dynamic reservoir.Since HEV genotype 1 infection cannot cause chronicity,subclinical transient infection and transmission of virus might be the reason it sustains in interepidemic period.This might be the similar phenomenon with SARS COVID-19 corona virus infection which is circulating worldwide in distinct phases with peaks and plateaus despite vaccination against it.In view of existing evidence,we propose the concept of“Dynamic Human Reservoir.”Quiescent subclinical infection of HEV without any clinical consequences and subsequent transmission may contribute to the existence of the virus in a community.The potential for transmitting HEV infection by asymptomatic HEV infected individuals by fecal shedding of virus has not been reported in literature.This missing link may be a key to Pandora's box in understanding epidemiology of HEV infection in genotype 1 predominant region.

Methylome and transcriptome data integration reveals potential roles of DNA methylation and candidate biomarkers of cow Streptococcus uberis subclinical mastitis

Background:Mastitis caused by different pathogens including Streptococcus uberis(S.uberis)is responsible for huge economic losses to the dairy industry.In order to investigate the potential genetic and epigenetic regulatory mecha‑nisms of subclinical mastitis due to S.uberis,the DNA methylome(whole genome DNA methylation sequencing)and transcriptome(RNA sequencing)of milk somatic cells from cows with naturally occurring S.uberis subclinical mastitis and healthy control cows(n=3/group)were studied.Results:Globally,the DNA methylation levels of CpG sites were low in the promoters and first exons but high in inner exons and introns.The DNA methylation levels at the promoter,first exon and first intron regions were nega‑tively correlated with the expression level of genes at a whole‑genome‑wide scale.In general,DNA methylation level was lower in S.uberis‑positive group(SUG)than in the control group(CTG).A total of 174,342 differentially methylated cytosines(DMCs)(FDR<0.05)were identified between SUG and CTG,including 132,237,7412 and 34,693 DMCs in the context of CpG,CHG and CHH(H=A or T or C),respectively.Besides,101,612 methylation haplotype blocks(MHBs)were identified,including 451 MHBs that were significantly different(dMHB)between the two groups.A total of 2130 differentially expressed(DE)genes(1378 with up‑regulated and 752 with down‑regulated expression)were found in SUG.Integration of methylome and transcriptome data with MethGET program revealed 1623 genes with signifi‑cant changes in their methylation levels and/or gene expression changes(MetGDE genes,MethGET P‑value<0.001).Functional enrichment of genes harboring≥15 DMCs,DE genes and MetGDE genes suggest significant involvement of DNA methylation changes in the regulation of the host immune response to S.uberis infection,especially cytokine activities.Furthermore,discriminant correlation analysis with DIABLO method identified 26 candidate biomarkers,including 6 DE genes,15 CpG‑DMCs and 5 dMHBs that discriminated between SUG and CTG.Conclusion:The integration of methylome and transcriptome of milk somatic cells suggests the possible involve‑ment of DNA methylation changes in the regulation of the host immune response to subclinical mastitis due to S.uberis.The presented genetic and epigenetic biomarkers could contribute to the design of management strategies of subclinical mastitis and breeding for mastitis resistance.

Transcriptome‑wide mapping of milk somatic cells upon subclinical mastitis infection in dairy cattle

Background Subclinical intramammary infection(IMI)represents a significant problem in maintaining dairy cows’health.Disease severity and extent depend on the interaction between the causative agent,environment,and host.To investigate the molecular mechanisms behind the host immune response,we used RNA-Seq for the milk somatic cells(SC)transcriptome profiling in healthy cows(n=9),and cows naturally affected by subclinical IMI from Proto-theca spp.(n=11)and Streptococcus agalactiae(S.agalactiae;n=11).Data Integration Analysis for Biomarker discov-ery using Latent Components(DIABLO)was used to integrate transcriptomic data and host phenotypic traits related to milk composition,SC composition,and udder health to identify hub variables for subclinical IMI detection.Results A total of 1,682 and 2,427 differentially expressed genes(DEGs)were identified when comparing Prototheca spp.and S.agalactiae to healthy animals,respectively.Pathogen-specific pathway analyses evidenced that Proto-theca’s infection upregulated antigen processing and lymphocyte proliferation pathways while S.agalactiae induced a reduction of energy-related pathways like the tricarboxylic acid cycle,and carbohydrate and lipid metabolism.The integrative analysis of commonly shared DEGs between the two pathogens(n=681)referred to the core-mastitis response genes,and phenotypic data evidenced a strong covariation between those genes and the flow cytometry immune cells(r2=0.72),followed by the udder health(r2=0.64)and milk quality parameters(r2=0.64).Variables with r≥0.90 were used to build a network in which the top 20 hub variables were identified with the Cytoscape cyto-hubba plug-in.The genes in common between DIABLO and cytohubba(n=10)were submitted to a ROC analysis which showed they had excellent predictive performances in terms of discriminating healthy and mastitis-affected animals(sensitivity>0.89,specificity>0.81,accuracy>0.87,and precision>0.69).Among these genes,CIITA could play a key role in regulating the animals’response to subclinical IMI.Conclusions Despite some differences in the enriched pathways,the two mastitis-causing pathogens seemed to induce a shared host immune-transcriptomic response.The hub variables identified with the integrative approach might be included in screening and diagnostic tools for subclinical IMI detection.

Edible mushrooms as a potent therapeutics of subclinical thyroid dysfunction among adults,especially in obese individuals:a prospective cohort study

Background:Mushrooms are a good source of many nutrients which are potentially beneficial for chronic diseases.We speculated that due to its abundant nutrients edible mushrooms might have a beneficial effect on the prevention of subclinical thyroid dysfunction(SCTD).Therefore,we designed a large-scale cohort study to examine whether mushrooms consumption is a protective factor for SCTD in adults.Methods:This prospective cohort study investigated 6631 participants(mean age:(45.0±10.2)years;55.1%men).Edible mushrooms consumption was measured at baseline using a validated food frequency questionnaire.SCTD was defined as abnormal serum thyroid-stimulating hormone levels and normal free thyroxine.Cox proportional hazards regression models were used to examine the association of edible mushrooms consumption with incident SCTD.Results:During follow-up period,a total of 262 new cases of SCTD were identified,the incidence rate of subclinical hypothyroidism was 8.9/1000 person-years and subclinical hyperthyroidism was 7.2/1000 person-years.After adjusting potential confounding factors,the multivariable hazard ratios(95%confidence intervals)for subclinical hypothyroidism were 1.00(reference)for almost never,0.53(0.29,0.97)for 1-3 times/week and 0.30(0.10,0.87)for≥4 times/week(P for trend=0.02).It also showed edible mushrooms consumption was inversely associated with subclinical hypothyroidism in obese individuals but not non-obese individuals,the final hazard ratios(95%confidence intervals)were 0.14(0.03,0.73)(P for trend<0.01).Conclusions:This population-based prospective cohort study has firstly demonstrated that higher edible mushrooms consumption was significantly associated with lower incidence of subclinical hypothyroidism among general adult population,especially in obese individuals.

Effect of Danzhijiangtang capsule on monocyte chemoattractant protein-1 mRNA expression in newly diagnosed diabetes subclinical vascular lesions

AIM:To investigate the effect of Danzhijiangtang capsule(DJC) on monocyte chemoattractant protein-1(MCP-1) mRNA expression in newly diagnosed type 2 diabetes mellitus(T2DM) subclinical vascular lesions.METHODS:Sixty-two patients with newly diagnosed T2DM subclinical vascular lesions were randomly divided into a control group and treatment group of 31 cases each.Oral antidiabetic therapy with routine western medicine was conducted in both groups,and the treatment group was additionally treated with DJCs.The treatment course for both groups was 12 wk.Before and after treatment,the total efficiency and traditional Chinese medicine(TCM) syndrome score were calculated.The fasting plasma glucose(FPG),2-h plasma glucose(2hPG),fasting insulin(FINS),insulin resistance index(IRI),hemoglobin(Hb)A1c,blood lipids,and hemorheology indices were determined.In addition,the levels of vascular endothelial growth factors including thrombomodulin(TM),von Willebrand factor(vWF),P-selectin and MCP-1 mRNA were determined.RESULTS:After 12 wk of treatment,the TCM syndrome score was significantly decreased compared to before treatment in both groups.After treatment,FPG,2hPG,HbA1c,FINS,IRI,total cholesterol,triglycerides,low-density lipoprotein,high-density lipoprotein,whole blood low shear specific viscosity,plasma specific viscosity,TM,vWF,P-selectin and MCP-1 mRNA were significantly improved compared to before treatment in both groups.After treatment,the total efficiency and TCM syndrome score in the treatment group were better than in the control group.FINS,IRI,whole blood high shear specific viscosity,plasma specific viscosity,TM,vWF,P-selectin and MCP-1 mRNA level in the treatment group were significantly reduced after treatment compared with control group.CONCLUSION:DJCs are efficacious in supplementing qi,nourishing yin and invigorating blood circulation,and upregulate MCP-1 mRNA expression in patients with T2DM subclinical vascular lesions.

Factors Associated with Peripheral Neuropathy in Type 2 Diabetes： Subclinical versus Confirmed Neuropathy

This study determined the prevalence of diabetic peripheral neuropathy(DPN) and subclinical DPN(s DPN) in patients with type 2 diabetes mellitus(T2DM) using nerve conduction study(NCS) as a diagnostic tool. We also investigated the factors associated with the development of s DPN and compared factors between the sD PN and confirmed DPN(cDPN). This cross-sectional study involved 240 T2DM patients who were successively admitted to the endocrinology wards of Wuhan Union Hospital over the period of January to December 2014. Data on the medical history, physical and laboratory examinations were collected. DPN was diagnosed using NCS. One-way ANOVA with least significant difference(LSD) analysis or chi-square tests was used to compare parameters among DNP-free, s DPN and c DPN patients. Independent factors associated with s DPN were determined using logistic regression. The results showed that 50.8% of the participants had DPN, and among them, 17.1% had sDPN. sDPN showed significant independent associations with age, height, HbA1c, presence of atherosclerosis and diabetic retinopathy. Patients with DPN differed significantly from those without DPN with respect to age, duration of disease(DOD), HbA1c, presence of atherosclerosis, diabetic retinopathy, nephropathy and hypertension. Patients with cDPN, relative to those with sDPN, had significantly longer DOD and higher prevalence of peripheral artery disease(PAD) and coronary artery disease(CAD). Our study suggests that a significant number of T2DM patients are affected by s DPN, and the development of this condition is associated with advanced age, tall stature, poor glycaemic control, presence of diabetic retinopathy and atherosclerosis. On the other hand, patients with cDPN tend to have a longer DOD and are more likely to suffer from PAD and CAD.

Month-Wise Prevalence of Subclinical Mastitis in Dairy Cows in Guangdong Province,China

To evaluate the month-wise prevalence of subclinical mastitis （SM） and its relations with climatic temperature and humidity, and to provide references for control and prevention of mastitis in dairy cows in Guangdong, China, California mastitis test method was used to determine the monthly prevalence of SM （MPSM, %） of lactating Holstein cows from 11 dairy farms in Guangdong Province, China, including about 516 cows per monthly examination. The average MPSM on a cow and a quarter basis were 30 and 13% respectively, and there was a positive linear correlation between monthly mean air temperature （MT, °C） and MPSM on a cow basis （r=0.763, P=0.004） or a quarter basis （r=0.577, P=0.049）, but there were no correlations between MT and MPSM on a cow or a quarter basis （P〉0.05）. There was a shift in MPSM trend that the highest MPSM （38.4%） was not for the hottest July with MT at 30.8°C, but for the later September at 27.9°C. The farms need to develop new housing conditions to control cowshed temperatures in the hot season to reduce the mastitis prevalences in the post-hot months.

Dietary ellagic acid ameliorated Clostridium perfringens-induced subclinical necrotic enteritis in broilers via regulating inflammation and cecal microbiota

Background: Subclinical necrotic enteritis(SNE), a common intestinal disease of broiler caused by Clostridium perfringens, could reduce production performance of broilers by chronic intestinal damage and poor absorption of nutrients. Ellagic acid(EA) has been reported to present antioxidant and anti-inflammatory properties on human and animals in many aspects. This study was conducted to evaluate the effect and mechanism of EA in relieving SNE in broilers induced by C. perfringens.Results: C. perfringens challenge decreased body weight(BW), average daily gain(ADG), jejunal villi height/crypt depth(V/C) ratio, the activity of catalase(CAT) and the mRNA expression of zonula occludens 1(ZO-1) in jejunal mucosa of broilers. While feed conversion ratios(FCR), jejunal crypt depth(CD), the activities of myeloperoxidase(MPO) and diamine oxidase(DAO), as well as the concentrations of interleukin 6(IL-6), C-reactive protein(CRP) and procalcitonin(PCT) in serum, the activities of inducible nitric oxide synthase(iNOS) and lysozyme(LZM), the concentration of malondialdehyde(MDA), and the mRNA expressions of claudin-2, TNF-α, IL-1β, TLR-4, TLR-2, NF-κB,JAK3, STAT6 and iNOS in jejunal mucosa of broilers were increased by C. perfringens challenge. Dietary EA supplement relieved these adverse effects, and heightened jejunal villi height(VH), the concentration of D-xylose in plasma, activity of superoxide dismutase(SOD), and the mRNA expression of occludin in jejunal mucosa of broilers.The alpha diversity of cecal microbiota indicated that dietary EA supplement increased observed species and Shannon index. C. perfringens challenge increased the relative abundance of Firmicutes and decreased the relative abundance of Desulfobacterota in cecal microbiota. EA increased the relative abundance of Firmicutes in cecal microbiota. LEfSe analysis showed that C. perfringens challenge triggered the imbalance of cecal microbiota in broilers, dietary EA supplementation led to a small beneficial effect on microbiota, while the simultaneous effect of them seemed to stimulate the immune function of broilers by improving the microbiota balance.Conclusions: Dietary EA ameliorated C. perfringens-induced SNE in broilers via regulating jejunal inflammation signaling pathways TLR/NF-κB and JAK3/STAT6, relieving jejunal oxidative stress and balancing cecal microbiota to inhibit intestinal barrier damage, prevent systemic inflammatory response and improve nutrient absorption capacity,finally protect and enhance growth performance of broilers.

Subclinical Hypothyroidism and Isolated Hypothyroxinemia during Pregnancy and Their Association with Pregnancy Outcome: A 2-Year Study

INTRODUCTION: Overt hypothyroidism in pregnancy is associated with adverse outcomes, but the effects of subclinical hypothyroidism and isolated hypothyroxinemia on pregnancy outcomes are still controversial. Subclinical hypothyroidism might be associated with preterm delivery, low Apgar score, fetal death and miscarriages and isolated hypothyroxinemia with preterm labor, high birth weight and neurocognitive deficits in children. Other studies show no association with any complications at all. In the present study we tried to estimate whether maternal subclinical hypothyroidism and isolated hypothyroxinemia are associated with complications during pregnancy in our population which represents the pregnant population of Western Greece. METHODS: In a total of 469 pregnant women, third trimester serum was assayed for thyroid-stimulating hormone (TSH) and free thyroxine (free T4). Thyroid hypofunction was defined as 1) subclinical hypothyroidism with TSH levels above 3 mIU/L for the 3rd trimester and normal free T4 and 2) isolated hypothyroxinemia with TSH levels below 3 mIU/L for the 3rd trimester and free T4 below the 5th percentile. The results were associated with birth weight, week of labor, history of miscarriages and demographic characteristics. Patients with thyroid hypofunction were compared with euthyroid patients (TSH and free T4 between normal limits). The results were analyzed with one-way ANOVA and χ2 test. RESULTS: Subclinical hypothyroidism was documented in 10.9% and isolated hypothyroxinemia in 21.7% of pregnant women. Subclinical hypothyroidism was not associated with birth weight, week of labor, or history of miscarriages. On the contrary, hypothyroxinemia was associated with high birth weight (P < 0.05). CONCLUSION: In our study, we did not find a link between subclinical hypothyroidism and adverse pregnancy outcomes. Similarly, hypothyroxinemia was not associated with pregnancy complications. However, it was associated with higher birth weight. Our studies contribute to our understanding, whether or not subclinical hypothyroidism and isolated hypothyroxinemia are associated with pregnancy adverse outcomes and whether treatment and test for hypothyroidism should become routine during pregnancy.

Inverse relationship between bioavailable testosterone and subclinical coronary artery calcification in non-obese Korean men

Although low testosterone levels in men have been associated with high risk for cardiovascular disease, little is known about the association between male sex hormones and subclinical coronary disease in men with apparently low cardiometabolic risk. This study was performed to investigate the association between male sex hormones and subclinical coronary artery calcification measured as coronary calcium score in non-obese Korean men. We examined the relationship of total testosterone, sex hormone-binding globulin, bioavai lable testosterone and free testosterone with coronary calcium score in 291 non-obese Korean men （mean age： 52.8--- 9.3 years） not having a history of cardiovascular disease. Using multiple linear regression, we evaluated associations between log （sex hormone） levels and log （coronary calcium score） after adjusting for confounding variables in 105 men with some degree of coronary calcification defined as coronary calcium score ~〉 1. In multiple linear regression analysis, bioavailable testosterone was inversely associated with coronary calcium score （P=0.046） after adjusting for age, body mass index, smoking status, alcohol consumption, regular exercise, mean blood pressure, resting heart rate, C-reactive protein, fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein （HDL） cholesterol, hypertension medication and hyperlipidernia medication, whereas total testosterone, sex hormone-binding globulin and free testosterone were not （P=0.674, P=O. 121 and P=O. 102, respectively）. Our findings indicate that bioavailable testosterone is inversely associated with the degree of subclinical coronary artery calcification in non-obese men.

Ideal Cardiovascular Health is Inversely Associated with Subclinical Atherosclerosis: A Prospective Analysis

Objective Ideal cardiovascular health(CVH) could predict a lower risk of developing cardiovascular diseases. This study was conducted to investigate the association between ideal CVH and subclinical atherosclerosis in a population cohort of Chinese adults aged ≥ 40 years. Methods This study was designed as a cross-sectional analysis of 8,395 participants who had complete data at baseline and a prospective analysis of 4,879 participants who had complete data at 4.3 years of follow-up. Ideal CVH metrics were defined according to the American Heart Association. Subclinical atherosclerosis was evaluated by plaques in carotid arteries, carotid intima-media thickness(CIMT), brachial-ankle pulse wave velocity(baPWV), and urinary albumin-to-creatinine ratio(UACR). Results Both the prevalence and incidence of atherosclerosis measures were found to be decreased with increasing numbers of ideal CVH metrics at baseline(all P values for trend < 0.01). The levels of CIMT and UACR at follow-up showed an inverse and significant association with the numbers of ideal CVH metrics at baseline(both P values for trend < 0.05) but a borderline significant association with baPWV(P for trend = 0.0505). Taking participants with 0-1 ideal metric as reference, we found that participants with 5-6 ideal metrics had significantly lower risks of developing carotid plaques(odds ratio, OR = 0.46; 95% confidence interval, CI 0.27-0.79), increased CIMT(OR = 0.60; 95% CI 0.42-0.84), and increased baPWV(OR = 0.57; 95% CI 0.34-0.97) after full adjustments. A significant interactive effect of age and CVH was detected on CIMT and baPWV progression(both P values for interaction < 0.05). Conclusion The numbers of ideal CVH metrics showed a significant and inverse association with the risk of developing subclinical atherosclerosis in middle-aged and elderly Chinese adults, whereas its dose-response effect was attenuated in individuals aged ≥ 60 years and partially weakened in male participants.

Evaluation of corneal topographic,tomographic and biomechanical indices for detecting clinical and subclinical keratoconus:a comprehensive three-device study

AIM:To evaluate the diagnostic ability of topographic and tomographic indices with Pentacam and Sirius as well as biomechanical parameters with Corvis ST for the detection of clinical and subclinical forms of keratoconus(KCN).METHODS:In this prospective diagnostic test study,70 patients with clinical KCN,79 patients with abnormal findings in topography and tomography maps with no evidence on clinical examination(subclinical KCN),and 68 normal control subjects were enrolled.The accuracy of topographic,tomographic,and biomechanical parameters was evaluated using the area under the receiver operating characteristic curve(AUC)and cross-validation analysis.The Delong method was used for comparing AUCs.RESULTS:In distinguishing KCN from normal,all parameters showed statistically significant differences between the two groups(P<0.001).Indices with the perfect diagnostic ability(AUC≥0.999)were Sirius KCN vertex of back(KVb),Pentacam random forest index(PRFI),Pentacam index of height decentration(IHD),and Corvis integrated tomographic/biomechanical index(TBI).In distinguishing subclinical KCN from normal,Sirius symmetry index of back(SIb;AUC=0.908),Pentacam inferior-superior difference(IS)value(AUC=0.862),PRFI(AUC=0.847),and Corvis TBI(AUC=0.820)performed best.There were no significant differences between the highest AUCs within keratoconic groups(De Long,P>0.05).CONCLUSION:In clinical KCN,all topographic,tomographic,and biomechanical indices have acceptable outcomes in terms of sensitivity and specificity.However,in differentiating subclinical forms of KCN from normal corneas,curvature-based parameters(SIb and IS value)followed by integrated indices(PRFI and TBI)are the most powerful tools for early detection of KCN.

Changes of Cytokines in Serum and Whey of Dairy Cows with Subclinical Mastitis

In order to study the correlation of different degrees of subclinical mastitis and cytokines,the changes of interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-8(IL-8)and tumor necrosis factor-α(TNF-α)in blood and milk and whether the changes of these indexes were caused by mastitis were analyzed.The 40 Holstein cows in lactation period were tested and grouped by somatic cell count(SCC)method in milk:Group C(SCC<5×10~5 cells·mL^(-1)),Group I(5×10~5 cells·mL^(-1)5×10~6 cells·mL^(-1)).The contents of IL-1β,IL-6,IL-8 and TNF-αwere analyzed by radioimmunoassay.The results showed that the contents of IL-6,IL-8 and TNF-αin the blood and milk of different degrees of subclinical mastitis increased with the severity of mastitis,and were higher than those in normal group.The contents of IL-6,IL-8 and TNF-αin serum and whey of dairy cows affected by different degrees of subclinical mastitis were higher than those in normal group(Group C).The content of IL-1βincreased and decreased with the increase of inflammation,and it did not have the value of evaluating mastitis.In conclusion,the severities of cow subclinical mastitis and the contents of cytokines were positive correlations.These indexes could be used as the basis for judging mammary gland injury.

Primary aldosteronism due to bilateral micronodular hyperplasia and concomitant subclinical Cushing’s syndrome:A case report

BACKGROUND Adrenal incidentaloma(AI)has been frequently encountered in the clinical setting.It has been shown that primary aldosteronism(PA)or subclinical Cushing’s syndrome(SCS)are the representative causative diseases of AI.However,the coexistence of PA and SCS has been reportedly observed.Recently,we encountered a case of AI,in which PA and SCS coexisted,confirmed by histopathological examinations after a laparoscopic adrenalectomy.We believe that there were some clinical implications in the diagnosis of the present case.CASE SUMMARY A 58-year-old man presented with lower right abdominal pain with a blood pressure of 170/100 mmHg.A subsequent computed tomography scan revealed right ureterolithiasis,which was the cause of right abdominal pain,and right AI measuring 22 mm×25 mm.After the disappearance of right abdominal pain,subsequent endocrinological examinations were performed.Aldosterone-related evaluations,including adrenal venous sampling,revealed the presence of bilateral PA.In addition,several cortisol-related evaluations showed the presence of SCS on the right adrenal adenoma.A laparoscopic right adrenalectomy was then performed.The histopathological examination of the resected right adrenal revealed the presence of a cortisol-producing adenoma,while CYP11B2 immunoreactivity was absent in this adenoma.However,in the adjacent nonneoplastic adrenal,multiple CYP11B2-positive adrenocortical micronodules were detected,showing the presence of aldosterone-producing adrenocortical micronodules.CONCLUSION Careful clinical and pathological examination should be performed when a patient harboring AI presents with concomitant SCS and PA.

High Prevalence of Subclinical Mastitis and Multidrug Resistant <i>Staphylococcus aureus</i>Are a Threat to Dairy Cattle Production in Kiboga District (Uganda)

Subclinical mastitis (SCM) is one of the major factors affecting the productivity of dairy cattle all over the world. This study established the burden of SCM and determined the potent antibacterial formulation for control of Staphylococcus aureus (SA) related SCM in selected dairy cattle farms in Kiboga district. A total of 124 dairy cattle from 12 farms were screened for SCM using California Mastitis Test (CMT) from Kiboga Town-Council, Kapeke and Lwamata sub-counties. The offending bacteria were cultured and the antibiogram of SA was carried out using antibacterial susceptibility by the modified Kirby-Bauer disc diffusion method. Additional qualitative data on the factors that predispose cows to SCM was obtained through questionnaires and observation of milking Practice. The prevalence of SCM in the three sub-counties was 87.9%. Over 70% of the dairy cattle screened for SCM had more than 2 udder quarters affected. The majority (90%) of SCM was caused by mixed bacterial infections: Coagulase negative staphylococci (64.4%) and SA (16.6%) being the most prevalent. All the farmers (100%) lacked knowledge on SCM, udder towels, teat dipping and drug cow therapy. Overall, 71.4% of SA isolated was multi-drug resistant. There was a high level of resistance against penicillin (100%), neomycin (85.7%) and tetracycline (71.4%). In contrast, all the above isolates were susceptible to Trimethoprim-Sulphamethazole. In conclusion, the high burden of SCM and emergence of multidrug resistant SA are one of the constraints to dairy production in Kiboga district. Therefore, sensitization of dairy farmers in Kiboga district on proper hygienic, appropriate milking techniques and dry cow therapy using potentiated sulfonamide intra-mammary preparations are highly recommended in SA associated SCM.

Inhibited 131I Uptake but Normal Release of Thyroid Hormone by Thyroid Gland in Response to TSH Administration in Subclinical Hypothyroidism

Background: Subclinical hypothyroidism is characterized by normal circulating thyroid hormone levels with super-normal TSH concentrations in absence of clinical manifestations. In majority of subjects, an etiologic factor is often identified. Moreover, therapy with levothyroxine normalizes serum TSH concentration while maintaining normal thyroid hormone concentrations. However, the exact pathophysiology of these thyroid hormone alterations is not well defined. Objective: Major steps in synthesis i.e. iodine uptake and the release of thyroid hormones in response to SC TSH administration were assessed in subjects with subclinical hypothyroidism. Methods: 10 men and 5 women with subclinical hypothyroidism, ages 42 - 76 years and 10 euthyroid men (39 - 70 years) participated. 24 hr 131Iodine thyroid uptake and serum T3, T4 and TSH concentrations were determined prior to and after SC administration of recombinant human TSH, 0.9 mg for two consecutive days. Comparisons were conducted for 24 hour uptake values as well as serum T3, T4 and TSH levels obtained prior to and after TSH administration. Results: In subjects with subclinical hypothyroidism 24 hour 131I thyroidal uptakes were normal (10% - 30%). However, the mean value was significantly lower, (p 3 and T4 concentrations in subjects with subclinical hypothyroidism were not significantly different in comparison to normal subjects. Serum TSH concentrations were supernormal and therefore were significantly higher in subjects with subclinical hypothyroidism in comparison to normal subjects and rose markedly in both groups following TSH administration with no significant difference among groups. Serum T4 and T3 rose significantly from PreTSH levels in both groups (p 131I Thyroid uptake is inhibited prior to as well as following SC TSH administration in comparison to normal subjects with maintenance of normal hormone release.

SAT, a New Approach in Understanding and Treatment of Subclinical Endometritis in Dairy Cows

The aim of this work was to compare the use of local intrauterine moist heat infusion to intrauterine antibiotics infusion, for treatment of subclinical endometritis which affects reproduction and milk production. 42 repeat breeder cows were divided into 4 groups, group 1 was the untreated control (=10 cows). Group 2 (=10 cows) was treated by 50 ml of Oxytetracycline 5% intrauterine for three successive weeks. Group 3 (=10 cows) intrauterine infusion with 30 ml saline adding to them 10 ml Gentamycin 10% and 10 ml penicillin and streptomycin for three successive weeks. Group 4 (=12 cows) intrauterine infusion with 50 ml sterile boiling water (≈100°C) was applied directly to the uterus for only one time. Leukogram was done before and after treatment, it showed leukocytosis and neutrophilia in all the study groups. After treatment for 36 hours and one week, there were no significant changes in the leukogram results of groups 1, 2 and 3. While in Group 4 showed decreasing in numbers of leukocytes (11.92 ± 0.75) and neutrophils (0.87 ± 0.16) to its normal limits after 36 hours and one-week post-treatment. Our new method gave the highest cumulative pregnancy rate 83.3% while other groups using antibiotics or antibiotics with saline gave lower pregnancy rate 40% and 50% respectively (P > 0.001). We named this new treatment method “Samia-treat;SAT”. SAT is a whole new and effective treatment for cases of repeat breeder which are caused by SCE in dairy cows;it caused increase in reproductive performance and cumulative pregnancy rate without over use of antibiotics.

Cardiovascular Risk and Subclinical Atherosclerosis in Senegalese Patients with Rheumatoid Arthritis:A Cross-Sectional Study in a Single Centre

Introduction: Rheumatoid arthritis (RA) is associated with increasing of cardiovascular (CV) morbidity and mortality due to accelerated atherosclerosis. Several studies showed also the increasing of the prevalence of subclinical atherosclerosis, but there are little data from sub-Saharan Africa. The aim of our study was to assess the prevalence of cardiovascular risk factors, subclinical carotid atherosclerosis and the ability of the Systematic Coronary Risk Estimation (SCORE) modified by European League Against Rheumatism (EULAR) to predict the high CV risk in our patients. Patients and Method: We conducted a cross sectional study in Senegalese patients with RA. The RA was retained according to 2010 American College of Rheumatology (ACR)-European League Against Rheumatism (EULAR) criteria. Patients with RA were assessed in a clinical research consultation. Results: We included 50 RA patients. The mean age was 44 years (+/- 12.37) and the sex-ratiowas 0.06. The frequency distribution of traditional cardiovascular risk factors was: hypertension (HT) (30%), diabetes-mellitus (6%), smoking (2%), no-exercise (22%), obesity (16%), metabolic syndrome (8%). Fifty-eight percent of patients were classified at low cardiovascular risk according to mSCORE. 51.7% of patients classified as moderate-risk according to mSCORE, were reclassified as high cardiovascular risk according to carotid ultrasound evaluation (gold-standard). The sensitivity of the mSCORE in the prediction of high CV risk was low at 20%. In the present study, the prevalence of carotid subclinical atherosclerosis was 20%. Age (>45 years) and HT were correlated to subclinical atherosclerosis. Conclusion: In the present study, the prevalence of atherosclerosis in RA patients was higher than expected frequency in comparison with the prevalence in Senegalese general population. We showed that CV risk was underestimated by mSCORE which had a low sensitivity in the prediction of high risk. We showed also the importance of carotid ultrasound for an appropriate stratification of the risk.