CXC chemokine ligand 13 and galectin-9 plasma levels collaboratively provide prediction of disease activity and progression-free survival in chronic lymphocytic leukemia.

The clinical outcome of lymphocytic leukemia (CLL) is quite heterogeneous. The purpose of this observational study was to investigate the clinical merit of measuring plasma galectin-9 and CXCL-13 concentrations as predictors of CLL activity, prognosis, and early indicators of therapeutic response. These biomarkers were compared with other prognostic indicators, progression-free survival (PFS), time to first treatment (TTT), and overall survival (OS) over a follow-up period (4 years). First, plasma galectin-9 and CXCL-13 concentrations were analyzed in CLL patients at the time of diagnosis as well as healthy controls. Compared to controls, CLL patients had significantly higher serum levels of CXCL-13 and galectin-9. Second, we observed that CLL patients with high soluble CXCL-13 and galectin-9 levels had advanced clinical stages, poor prognosis, 17p del, short PFS, short TTT, and therapy resistance. The levels of CXCL-13, ß2-microglobulin, LDH, CD38%, and high grade of Rai-stage were all strongly correlated with the galectin-9 levels. Soluble CXCL-13 and galectin-9 had very good specificity and sensitivity in detecting CLL disease progression and high-risk patients with the superiority of galectin-9 over CXCL-13. Although the two biomarkers were equal in prediction of TTT and treatment response, the soluble CXCL13 was superior in prediction of OS. High CXCL-13 and galectin-9 plasma levels upon CLL diagnosis are associated with disease activity, progression, advanced clinical stages, short periods of PFS, short TTT, and unfavorable treatment response.

Extended-spectrum ß-lactamase-producing E. coli from retail meat and workers: genetic diversity, virulotyping, pathotyping and the antimicrobial effect of silver nanoparticles.

BACKGROUND: The spread of extended-spectrum ß-lactamases (ESBL) producing E. coli from food animals and the environment to humans has become a significant public health concern. The objectives of this study were to determine the occurrence, pathotypes, virulotypes, genotypes, and antimicrobial resistance patterns of ESBL-producing E. coli in retail meat samples and workers in retail meat shops in Egypt and to evaluate the bactericidal efficacy of silver nanoparticles (AgNPs-H2O2) against multidrug resistant (MDR) ESBL-producing E. coli. RESULTS: A total of 250 retail meat samples and 100 human worker samples (hand swabs and stool) were examined for the presence of ESBL- producing E. coli. Duck meat and workers' hand swabs were the highest proportion of ESBL- producing E. coli isolates (81.1%), followed by camel meat (61.5%). Pathotyping revealed that the isolates belonged to groups A and B1. Virulotyping showed that the most prevalent virulence gene was Shiga toxin 2 (stx2) associated gene (36.9%), while none of the isolates harbored stx1 gene. Genotyping of the identified isolates from human and meat sources by REP-PCR showed 100% similarity within the same cluster between human and meat isolates. All isolates were classified as MDR with an average multiple antibiotic resistance (MAR) index of 0.7. AgNPs-H2O2 at concentrations of 0.625, 1.25, 2.5 and 5 µg/mL showed complete bacterial growth inhibition. CONCLUSIONS: Virulent MDR ESBL-producing E. coli were identified in retail meat products in Egypt, posing significant public health threats. Regular monitoring of ESBL-producing E. coli frequency and antimicrobial resistance profile in retail meat products is crucial to enhance their safety. AgNPs-H2O2 is a promising alternative for treating MDR ESBL-producing E. coli infections and reducing antimicrobial resistance risks.

Frequency of toll-like receptor 4 variants and association with treatment response in children with primary immune thrombocytopenia.

OBJECTIVES: To investigate the frequency of toll-like receptor 4 (TLR4) variants c.896A>G (p.Asp299Gly) and c.1196C>T (p.Thr399Ile) among Egyptian children with primary immune thrombocytopenia (pITP), and their association with disease course and response to treatment. METHODS: A case-control study that included 80 children with pITP and 50 age- and sex-matched healthy controls. TLR4 c.896A>G and c.1196C>T variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Patients were classified according to their response to treatment after 3 months as responders and nonresponders. RESULTS: Compared with controls, children with pITP had significantly higher minor allele frequencies of TLR4 p.Asp299Gly (16.25% vs. 6%, odds ratio [OR] 3.04, 95% confidence interval [CI]: 1.16-9.36, p = .014) and p.Thr399Ile (20% vs. 4%, OR 6, 95% CI: 2.02-24.01, p < .001). The presence of p.Asp299Gly variant was significantly associated with chronic ITP (OR 7.78, 95% CI: 2.04-35.69, p < .001) and non-response to therapy with steroid (OR 11.67, 95% CI: 1.32-104.08, p = .012), but not thrombopoietin-receptor agonist (OR 1.67, 95% CI: 0.35-8.19, p = .464). Likewise, having p.Thr399Ile variant was significantly associated with chronic ITP (OR 5.14, 95% CI: 1.6-17.4, p = .002) and non-response to therapy with steroid (OR 6.1, 95% CI: 1.01-49.06, p = .046) but not thrombopoietin-receptor agonist (OR 1.57, 95% CI: 0.33-7.58, p = .515). CONCLUSION: The presence of TLR4 p.Asp299Gly or p.Thr399Ile variant may be associated with ITP predisposition, chronicity, and non-response to upfront steroid therapy. These findings enhance our understanding of the complex pathophysiology of pITP with potentially important clinical implications.

Peripheral Mononuclear Cells Surface Markers Evaluation in Different Stages of Hepatocellular Carcinoma; in a Trial for Early and Accurate Diagnosis in Patients with Post-Hepatitis Liver Cirrhosis and Unremarkable Raised AFP.

Introduction: HCC is frequently diagnosed late, when only palliative treatment is available. So, we try to use different immunological markers to identify early HCC in patients with unremarkable raised AFP. Methods: This study was conducted on 112 participants divided into two equal groups: Group I, 56 patients with liver cirrhosis and different stages of HCC; Group II, 56 patients with liver cirrhosis. The diagnosis of HCC was based on AASLD guidelines. TNM and BCLC classification systems are used for staging of HCC. Results: A significant reduction in the median percentage of lymphocyte subset (CD3+, CD4+, CD8+, CD19+) and NK cell percentage (CD56+) has been detected in HCC patients (all P < 0.001). In the HCC group the median monocyte subpopulations CD14+ CD16- Classical, CD14++ CD16+ Intermediate, and CD14-+ CD16++ Non-Classical were 11.7, 4.0, and 3.5, respectively, with marked reduction compared with liver cirrhosis group (all P < 0.001). Patients with advanced stages (BCLC C and D) were more likely to have significantly higher median CD33+ than patients with early stages (BCLC A and B) (P = 0.05); also, the median levels of HLA DR+ lymphocytes % in the HCC case group were 21.8 in patients with advanced disease (BCLC C and D) and 13.1 in patients with early stages of the disease (P = 0.04). Patients with late stage (TNM III) were more likely to have significantly higher median CD14+ CD16- Classical monocyte subset, CD36+ HLA DR+, and CD36+ CD16- than patients with early stages (TNM I and II). Conclusion: Patients with HCC with unremarkable raised AFP showed marked reduction in lymphocytes, natural killer cells, and all monocyte subpopulations. In addition, patients with advanced HCC showed increased CD33+ and HLA DR+ lymphocytes %, CD14+ CD16- Classical monocyte subset, CD36+ HLA DR+, and CD36+ CD16- compared with patients with early stages of HCC.

Bayesian Evaluation of Three Serological Tests for Diagnosis of Brucella infections in Dromedary Camels Using Latent Class Models.

Brucellosis is a zoonotic disease with significant economic and public health impacts. The disease has been found in ruminants, including camels, but clinical diagnosis of camel brucellosis is difficult due to the lack of clinical signs. Thus, this study aimed to estimate the sensitivity (Se) and specificity (Sp) of the Buffered Plate Antigen Test (BPAT), Rose Bengal Test (RBT), and indirect ELISA (i-ELISA) for the diagnosis of Brucella infection in dromedary camels imported from Sudan to Egypt. The secondary objective of the study was to calculate the animal-level true prevalence of Brucella infection in imported camels. A cross-sectional study was carried out on 921 apparently healthy camels randomly selected from those imported from Sudan and kept in the quarantine stations in the Shalateen area of the Red Sea Governorate, Egypt, between June 2018 and January 2019. Serum samples were collected and analyzed using BPAT, RBT, and i-ELISA. The posterior estimates [medians and 95% Bayesian probability intervals (95% BPI)] for Se and Sp of the three serological tests were obtained using Bayesian latent class models (BLCMs). The BLCM was fitted with the assumption that the BPAT and RBT tests were conditionally dependent on the true brucellosis status of camels. All tests had comparable and high Se (>86%) and Sp (>98%). The animal-level true prevalence of Brucella infection in imported camels was 8.6% (95% BPI: 6.8 - 10.7). Based on these findings, the three assays could be used for the initial screening of Brucella infection in camels. However, the BPAT and RBT are more suitable for use in camel brucellosis control and eradication program in Egypt because of their low unit cost and fast turnaround time compared to the i-ELISA. In addition, BPAT and RBT could be performed in the field where in-vivo tests are rarely used due to logistic and management constraints.

Coagulation parameters abnormalities and their relation to clinical outcomes in hospitalized and severe COVID-19 patients: prospective study.

There has been growing attention toward the predictive value of the coagulation parameters abnormalities in COVID-19. The aim of the study was to investigate the role of coagulation parameters namely Prothrombin concentration (PC), activated Partial thromboplastin Time (aPTT), D-Dimer (DD), Anti Thrombin III (ATIII) and fibrinogen (Fg) together with hematological, and biochemical parameters in predicting the severity of COVID-19 patients and estimating their relation to clinical outcomes in hospitalized and severe COVID-19 Patients. In a prospective study, a total of 267 newly diagnosed COVID-19 patients were enrolled. They were divided into two groups; hospitalized group which included 144 patients and non-hospitalized group that included 123 patients. According to severity, the patients were divided into severe group which included 71 patients and non-severe group that included 196 patients who were admitted to ward or not hospitalized. Clinical evaluation, measurement of coagulation parameters, biochemical indices, outcome and survival data were recorded. Hospitalized and severe patients were older and commonly presented with dyspnea (P ≤ 0.001). Differences in coagulation parameters were highly significant in hospitalized and severe groups in almost all parameters, same for inflammatory markers. D-dimer, AT-III and LDH showed excellent independently prediction of severity risk. With a cut-off of > 2.0 ng/L, the sensitivity and specificity of D dimer in predicting severity were 76% and 93%, respectively. Patients with coagulation abnormalities showed worse survival than those without (p = 0.002). Early assessment and dynamic monitoring of coagulation parameters may be a benchmark in the prediction of COVID-19 severity and death.

Candesartan Effectively Preserves Cognition in Senescence Accelerated Mouse Prone 8 (SAMP8) mice.

Background: Alzheimer's disease (AD) has become a worldwide crisis with no effective therapeutic options. The medications currently available for AD are only palliative; their effect is temporary, and they are associated with unfavorable side effects. Even the newest medication aducanumab, granted accelerated FDA approval in 2021, failed to show cognitive benefits in clinical trials and continued approval requires verification in subsequent clinical trials. There is an urgent need for safe and effective therapies to preserve cognition and effectively manage AD. Generally, a new drug product takes several years for FDA approval and exceeds 2.5 billion dollars in research and development, with most new drug products never even reaching the market. This has led to a recent shift for repurposing/repositioning existing FDA-approved medications, to new therapeutic indications. Objective: To investigate the effects of long-term treatment with candesartan, an FDA-approved angiotensin-II type-1 receptor blocker (ARB), on the development of cognitive impairment associated with premature aging. Methods: Candesartan was given at a dose of 1 mg/kg/d in an AD model of senescence-accelerated mouse prone-8 (SAMP8) and senescence-accelerated mouse resistant (SAMR1) mice. Oral treatment with candesartan or vehicle was started, in 2-month-old mice and administered continuously for 4-months. Results: Low-dose candesartan prevented the development of cognitive impairment, otherwise associated with accelerated aging, in SAMP8 mice, by reducing inflammation and nitro-oxidative stress. Candesartan did not affect the cognitive function of control SAMR1 mice. Conclusion: Early ARB treatment might be beneficial in preventing age-related cognitive deficits in AD-prone individuals.

Hematological, Biochemical Properties, and Clinical Correlates of Hemoglobin S Variant Disorder: A New Insight Into Sickle Cell Trait.

Background: The sickle cell trait (SCT) disorder possesses a clinical heterogeneity ranging from a symptomless condition to sudden death. This study aimed to develop a diagnostic approach that helps the characterization and identification of SCT from normal subjects and sickle cell disease (SCD) patients, and to assess its severity. Methods: Sixty controls, 24 SCD patients and 31 SCT subjects were assessed clinically, radiologically and by laboratory investigations. Results: Of the SCT subjects, 12.8% were symptomatic (3.2% anemic, 6.4% hemolytic crisis, and 3.2% painful crises). Anemia was normocytic in 66.6%, and normochromic and polychromatic in 33.4%. Significantly lower red blood cells (RBCs), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), hematocrit (Hct), Shine and Lal index (SL), and hemoglobin A (Hb A), and higher mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), Ricerca index (RI), and Huber-Herklotz index (HH) were found in SCT subjects compared with the controls. Hb A and hemoglobin S (Hb S) were excellent in discriminating SCT from SCD (cut-off for SCT > 50% and < 40%) followed by Hct, MCHC, Hb, Green and King index (GK), and England and Fraser index (EF) (cut-off for SCT > 33%, > 32, > 11, < 71, and < 10, respectively). Radiologically normal findings were detected in 87% of SCT subjects; they had nearly normal liver and renal function tests (except one case each). A schematic diagnostic paradigm for SCT was proposed. Conclusion: This study allowed understanding of SCT in various aspects, i.e., clinical, hematological, biochemical and radiological. Thus, it could help prevention of the Hb S variant disorder and proper management of carriers. This might be applied in pre-marital screening, particularly in those with family history of Hb S disorder.

Contralesional angiotensin type 2 receptor activation contributes to recovery in experimental stroke.

We and others have previously shown that angiotensin II receptor type 2 receptor (AT2R) is upregulated in the contralesional hemisphere after stroke in normoglycemic Wistar rats. In this study, we examined the expression of AT2R in type 2 diabetic Goto-Kakizaki (GK) rats and control Wistars after stroke. We also tested the contribution of the contralesional AT2R in recovery after stroke through a specific knockdown of the AT2R in this hemisphere only. Two experiments were conducted. In the first experiment, GK rats were subjected to middle cerebral artery occlusion (MCAO) and treated with the angiotensin II receptor type 1 receptor (AT1R) blocker candesartan or saline at reperfusion. Stroke outcomes, as well as AT2R expression, were examined and compared to control Wistars at 24 h. In the second experiment, localized AT2R knockdown was achieved through intrastriatal injection of short hairpin RNA (shRNA) lentiviral particles or non-targeting control into the left-brain hemisphere of Wistar rats. After 14 days, rats were subjected to right MCAO and treated with the AT2R agonist, Compound 21 (C21), or saline for 7 days. Behavioral outcomes were assessed for up to 10 days. In the first experiment, stroke reduced the expression of AT2R in GK rats. Candesartan treatment failed to improve the neurobehavioral outcomes, preserve vascular integrity or reduce oxidative/nitrative stress or apoptotic markers at 24 h post stroke in these animals. In the second experiment, contralesional AT2R knockdown reduced the C21-mediated functional recovery after stroke. In conclusion, contralesional AT2R upregulation after stroke is blunted in diabetic rats which show reduced sensitivity to post-stroke candesartan treatment. Contralesional AT2R could be involved in C21-mediated functional recovery after stroke.

Biotyping, virulotyping and biofilm formation ability of ESBL-Klebsiella pneumoniae isolates from nosocomial infections.

The aim of this study was to investigate the frequency, molecular characterization, virulence genes, resistance genes and antimicrobial profile of nosocomial extended spectrum beta lactamase producing Klebsiella species. A total of 22 (12.2%) K. pneumoniae strains were isolated from 180 clinical samples collected from hospitalized patients in Egypt. K. pneumoniae biotypes were B1 (72.8%), B3 (13.6%) and B4 (13.6%). The isolates were classified for the capsular serotypes, 86.4% (20/22) were of K1 serotype, while only two isolates (13.64%) were of K2 serotype. Hypermucoviscous K. pneumoniae isolates accounted for 68.2%. Biofilm formation ability of K. pneumoniae was determined by microtitre plate method. The majority of the isolates (40.9%) were moderate biofilm producers, while 27.3% were strong biofilm producers. All K. pneumoniae strains were positive for fimH and traT genes, while magA was identified in only 63.6% of the isolates. The antibiotic susceptibility profile of the isolates (n = 22) was determined by the disc diffusion technique using 23 different antibiotics. Streptomycin and imipenem are the most effective antibiotics against 22 tested K. pneumoniae isolates with sensitivity rates of 63.64% and 54.54% respectively. All tested K. pneumoniae isolates showed high resistance to amoxicillin∕clavulanate (100%), cefuroxime (100%) and ceftazidime (95.45%). Extended spectrum beta lactamases (ESBL) production and the presence of ESBL-related genes were tested in the isolates. All the isolates tested positive for blaVIM, NDM1 and blaTEM, while only 81.8 %tested positive for the blaSHV gene. Increasing antimicrobial resistance in K. pneumoniae causing nosocomial infections limits the use of antimicrobial agents for treatment. Furthermore, the spread of biofilm, multiple drug resistant and ESBL-producing K. pneumoniae isolates is a public threat for hospitalized patients.

Spastic Paraplegia 20 and Serine/Threonine Protein Kinase 31 Expression for the Detection of Colorectal Cancer.

BACKGROUND/AIMS: Genetic alterations, including changes in the expression of spastic paraplegia 20 (SPG20) and serine/threonine protein kinase 31 (STK31), may play an important role in the carcinogenesis of colorectal cancer (CRC). Identification of such changes is suitable for the recognition of tumors at an early stage, which would significantly improve patient survival. While recent studies have identified that SPG20 and STK31 expression levels increase in CRC tissues, their use as a biomarker is yet to be investigated. Our aim was to determine whether circulating SPG20 and STK31 mRNAlevels could help distinguish between patients with CRC and healthy individuals. Additionally, we aimed to analyze the correlation between SPG20 and STK31 expression patterns and the tumor stage in patients with CRC. METHODS: Venous blood samples from 50 patients with CRC and 50 healthy controls were used. RNA extraction was performed, and the mRNA expression of SPG20 and STK31 was determined using RT-qPCR. RESULTS: STK31 and SPG20 mRNA levels were significantly upregulated in patients compared to those in controls. There was a strong positive correlation between the expression of the two potential tumor biomarkers, STK31 and SPG20 (R=0.636, p=0.000). However, there was no significant relationship between the expression of STK31 or SPG20 and patient data, including demographic, clinical, pathological, and laboratory data. Additionally, there was a significant correlation between the expression level of STK31, but not SPG20, and patient disease-free survival (DFS) and overall survival (OS). CONCLUSION: Circulating mRNA levels of SPG20 and STK31 could be used as ideal noninvasive biomarkers for early diagnosis of CRC. They could assist the oncologist in recommending appropriate management strategies for individual patients.

Direct AT2R Stimulation Slows Post-stroke Cognitive Decline in the 5XFAD Alzheimer's Disease Mice.

Alzheimer's disease (AD), currently the single leading cause of death still on the rise, almost always coexists alongside vascular cognitive impairment (VCI). In fact, the ischemic disease affects up to 90% of AD patients, with strokes and major infarctions representing over a third of vascular lesions. Studies also confirmed that amyloid plaques, typical of AD, are much more likely to cause dementia if strokes or cerebrovascular damage also exist, leading to the term "mixed pathology" cognitive impairment. Although its incidence is expected to grow, there are no satisfactory treatments. There is hence an urgent need for safe and effective therapies that preserve cognition, maintain function, and prevent the clinical deterioration that results from the progression of this irreversible, neurodegenerative disease. To our knowledge, this is the first study to investigate the effects of long-term treatment with C21, a novel angiotensin II type 2 receptor (AT2R) agonist, on the development of "mixed pathology" cognitive impairment. This was accomplished using a unique model that employs the fundamental elements of both AD and VCI. Treatment with C21/vehicle was started 1 h post-stroke and continued for 5 weeks in mice with concurrent AD pathology. Efficacy was established through a series of functional tests assessing various aspects of cognition, including spatial learning, short-term/working memory, long-term/reference memory, and cognitive flexibility, in addition to the molecular markers characteristic of AD. Our findings demonstrate that C21 treatment preserves cognitive function, maintains cerebral blood flow, and reduces Aß accumulation and toxic tau phosphorylation in AD animals post-stroke.

Genetic Relatedness, Antibiotic Resistance, and Effect of Silver Nanoparticle on Biofilm Formation by Clostridium perfringens Isolated from Chickens, Pigeons, Camels, and Human Consumers.

In this study, we determined the prevalence and toxin types of antibiotic-resistant Clostridium perfringens in chicken, pigeons, camels, and humans. We investigated the inhibitory effects of AgNPs on biofilm formation ability of the isolates and the genetic relatedness of the isolates from various sources determined using RAPD-PCR. Fifty isolates were identified using PCR, and all the isolates were of type A. The cpe and cpb2 genes were detected in 12% and 56% of the isolates, respectively. The effect of AgNPs on biofilm production of six representative isolates indicated that at the highest concentration of AgNPs (100 µg/mL), the inhibition percentages were 80.8-82.8%. The RAPD-PCR patterns of the 50 C. perfringens isolates from various sources revealed 33 profiles and four clusters, and the discriminatory power of RAPD-PCR was high. Multidrug-resistant C. perfringens isolates are predominant in the study area. The inhibition of biofilm formation by C. perfringens isolates was dose-dependent, and RAPD-PCR is a promising method for studying the genetic relatedness between the isolates from various sources. This is the first report of AgNPs' anti-biofilm activity against C. perfringens from chickens, pigeons, camels, and humans, to the best of our knowledge.

Acute Hyperglycemia Exacerbates Hemorrhagic Transformation after Embolic Stroke and Reperfusion with tPA: A Possible Role of TXNIP-NLRP3 Inflammasome.

OBJECTIVES: Acute hyperglycemia (HG) exacerbates reperfusion injury after stroke. Our recent studies showed that acute HG upregulates thioredoxin-interacting protein (TXNIP) expression, which in turn induces inflammation and neurovascular damage in a suture model of ischemic stroke. The aim of the present study was to investigate the effect of acute HG on TXNIP-associated neurovascular damage, in a more clinically relevant murine model of embolic stroke and intravenous tissue plasminogen activator (IV-tPA) reperfusion. MATERIALS AND METHODS: HG was induced in adult male mice, by intraperitoneal injection of 20% glucose. This was followed by embolic middle cerebral artery occlusion (eMCAO), with or without IV-tPA (10 mg/kg) given 3 h post embolization. Brain infarction, edema, hemoglobin content, expression of matrix metalloproteinase (MMP-9), vascular endothelial growth factor A (VEGFA), tight junction proteins (claudin-5, occluding, and zonula occludens-1), TXNIP, and NOD-like receptor protein3 (NLRP3)-inflammasome activation were evaluated at 24 h after eMCAO. RESULTS: HG alone significantly increased TXNIP in the brain after eMCAO, and this was associated with exacerbated hemorrhagic transformation (HT; as measured by hemoglobin content). IV-tPA in HG conditions showed a trend to decrease infarct volume, but worsened HT after eMCAO, suggesting that HG reduces the therapeutic efficacy of IV-tPA. Further, HG and tPA-reperfusion did not show significant differences in expression of MMP-9, VEGFA, junction proteins, and NLRP3 inflammasome activation between the groups. CONCLUSION: The current findings suggest a potential role for TXNIP in the occurrence of HT in hyperglycemic conditions following eMCAO. Further studies are needed to understand the precise role of vascular TXNIP on HG/tPA-induced neurovascular damage after stroke.

Phenotypic and genetic parameters of productive traits in Rahmani and Romanov sheep and crossbreds.

Data of 651 lambs (68 Romanov, 49 Rahmani, 151 [♀1/2 Rahmani X ♂1/2 Romanov) and 383 (♀3/4 Rahmani and 1/4♂ Romanov]) were collected from Mehalet Mousa Farm, belonging to Animal Production Research Institute from the period of 2009 to 2016 to estimate phenotypic and genetic parameters. The traits studied were birth weight (BW), body weight at four week (BW4), body weight at eight weeks (BW8) and body weight at twelve weeks (BW12) or weaning weight. Least squares analysis of variance shows significance of the effects of breed groups, gender of lambs, birth type; month of birth and year of birth on all traits studied. Rahmani lambs had heavier BW, BW4, BW8 and BW12 while Romanov lambs had the lowest ones. The first generation (♀1/2 Rhamani X ♂1/2 Romanov) had heavier body weights than Romanov and the second generation (♀3/4 Rahmani X ♂1/4 Roamnov). Gender of lambs had highly significant effect on body weights. Males were significantly (p < 0.01) heavier than females for all traits studied. Least square means of BW, BW4, BW8 and BW12 for single lambs were 2.69, 10.43, 13.53 and 16.10 kg, respectively. Least square means of BW, BW4, BW8 and BW12 for twin lambs were 2.50, 9.37, 12.5 and 15.16 kg, respectively, while least square means of BW, BW4, BW8 and BW12 for triple lambs were 2.09, 7.86, 10.83 and 13.67 kg, respectively. Estimates of direct heritability measured by single trait animal model were 0.14, 0.23, 0.25 and 0.26 for BW, BW4, BW8 and BW12, respectively, and the corresponding measured by multi trait animal model were 0.17, 0.24, 0.32 and 0.36 for the same traits, respectively. All genetic and phenotypic correlations among different traits studied are positive and significant.

Bayesian Estimation of Diagnostic Accuracy of Three Diagnostic Tests for Bovine Tuberculosis in Egyptian Dairy Cattle Using Latent Class Models.

The aim of the present study was to calculate the sensitivity (Se) and specificity (Sp) of the single cervical tuberculin test (SCT), rapid lateral flow test (RLFT), and real-time polymerase chain reaction (RT-PCR) for the diagnosis of Mycobacterium bovis (M. bovis) infection in Egyptian dairy cattle herds within a Bayesian framework. The true M. bovis infection within-herd prevalence was assessed as a secondary objective. Data on the test results of SCT, RLFT, and RT-PCR for the detection of M. bovis were available from 245 cows in eleven herds in six major governorates in Egypt. A Bayesian latent class model was built for the estimation of the characteristics of the three tests. Our findings showed that Se of SCT (0.93 (95% Posterior credible interval (PCI): 0.89-0.93)) was higher than that of RT-PCR (0.83 (95% PCI: 0.28-0.93)) but was similar to the Se of RLFT (0.93 (95% PCI: 0.31-0.99)). On the contrary, SCT showed the lowest Sp estimate (0.60 (95% PCI: 0.59-0.65)), whereas Sp estimates of RT-PCR (0.99 (95% PCI: 0.95-1.00)) and RLFT (0.99 (95% PCI: 0.95-1.00)) were comparable. The true prevalence of M. bovis ranged between 0.07 and 0.71. In conclusion, overall, RT-PCR and RLFT registered superior performance to SCT, making them good candidates for routine use in the Egyptian bovine tuberculosis control program.

Renin-Angiotensin System Alterations in the Human Alzheimer's Disease Brain.

BACKGROUND: Understanding Alzheimer's disease (AD) in terms of its various pathophysiological pathways is essential to unravel the complex nature of the disease process and identify potential therapeutic targets. The renin-angiotensin system (RAS) has been implicated in several brain diseases, including traumatic brain injury, ischemic stroke, and AD. OBJECTIVE: This study was designed to evaluate the protein expression levels of RAS components in postmortem cortical and hippocampal brain samples obtained from AD versus non-AD individuals. METHODS: We analyzed RAS components in the cortex and hippocampus of postmortem human brain samples by western blotting and immunohistochemical techniques in comparison with age-matched non-demented controls. RESULTS: The expression of AT1R increased in the hippocampus, whereas AT2R expression remained almost unchanged in the cortical and hippocampal regions of AD compared to non-AD brains. The Mas receptor was downregulated in the hippocampus. We also detected slight reductions in ACE-1 protein levels in both the cortex and hippocampus of AD brains, with minor elevations in ACE-2 in the cortex. We did not find remarkable differences in the protein levels of angiotensinogen and Ang II in either the cortex or hippocampus of AD brains, whereas we observed a considerable increase in the expression of brain-derived neurotrophic factor in the hippocampus. CONCLUSION: The current findings support the significant contribution of RAS components in AD pathogenesis, further suggesting that strategies focusing on the AT1R and AT2R pathways may lead to novel therapies for the management of AD.

Endothelial Thioredoxin-Interacting Protein Depletion Reduces Hemorrhagic Transformation in Hyperglycemic Mice after Embolic Stroke and Thrombolytic Therapy.

We hypothesize that endothelial-specific thioredoxin-interacting protein knock-out (EC-TXNIP KO) mice will be more resistant to the neurovascular damage (hemorrhagic-transformation-HT) associated with hyperglycemia (HG) in embolic stroke. Adult-male EC-TXNIP KO and wild-type (WT) littermate mice were injected with-streptozotocin (40 mg/kg, i.p.) for five consecutive days to induce diabetes. Four-weeks after confirming HG, mice were subjected to embolic middle cerebral artery occlusion (eMCAO) followed by tissue plasminogen activator (tPA)-reperfusion (10 mg/kg at 3 h post-eMCAO). After the neurological assessment, animals were sacrificed at 24 h for neurovascular stroke outcomes. There were no differences in cerebrovascular anatomy between the strains. Infarct size, edema, and HT as indicated by hemoglobin (Hb)-the content was significantly higher in HG-WT mice, with or without tPA-reperfusion, compared to normoglycemic WT mice. Hyperglycemic EC-TXNIP KO mice treated with tPA tended to show lower Hb-content, edema, infarct area, and less hemorrhagic score compared to WT hyperglycemic mice. EC-TXNIP KO mice showed decreased expression of inflammatory mediators, apoptosis-associated proteins, and nitrotyrosine levels. Further, vascular endothelial growth factor-A and matrix-metalloproteinases (MMP-9/MMP-3), which degrade junction proteins and increase blood-brain-barrier permeability, were decreased in EC-TXNIP KO mice. Together, these findings suggest that vascular-TXNIP could be a novel therapeutic target for neurovascular damage after stroke.

Stimulation of angiotensin II receptor 2 preserves cognitive function and is associated with an enhanced cerebral vascular density after stroke.

Angiotensin signaling is known to be sexually dimorphic. Although it is a well-studied target for intervention in stroke and cognitive impairment, female studies are rare. With females suffering a disproportionately greater negative impact of stroke and dementia vs. males, effective interventions are of utmost urgency. The aim of the current study was to determine the impact of activation of the angiotensin II type 2 receptor (AT2R) with the agonist compound 21 (C21) on the development of post-stroke cognitive impairment, after experimental ischemic stroke. Ovariectomized (OVX) spontaneously hypertensive rats (SHRs) were subjected to 1 h of middle cerebral artery occlusion (MCAO). At 24 h, rats with a significant neurologic deficit were randomized to receive either saline or C21 (0.03 mg/kg/day) intraperitoneally (IP) for 5 days, then orally (0.12 mg/kg/day) for a total of 6 weeks. Cognitive function, brain structure by MRI and vascular architecture by microCT angiography were measured. C21 preserved cognitive function, specifically spatial memory, and improved vascular density in the ischemic hemisphere at 6 weeks, reflecting both arteriogenesis and angiogenesis. In conclusion, C21 prevented cognitive impairment after stroke, likely through a mechanism involving vascular protection and restoration.