T cell activation markers “CD45RO and CD45RA”; neutrophil CD11b expression and soluble tumor necrosis factor receptor (p55) in early diagnosis of neonatal sepsis

Background: Neonatal sepsis is a common and life threatening disorder whose outcome and prognosis depend on early and efficient therapy. A sensitive and specific indicator at an early stage of the disease would certainly aid the early diagnosis of neonatal sepsis. Objective: We sought to investigate the diagnostic value of measuring the up-regulation of T-lymphocyte activation markers CD45RA/CD45RO, CD45RO, neutrophil CD11b expression, and soluble tumor necrosis factor receptor (P55) as tests for early detection of neonatal sepsis; as well as comparing them with the conventional methods of diagnosis. Methods: The subjects of this study comprised 39 neonates: 25 males (64%) and 14 females (36%). In addition to the clinical assessment, different laboratory investigations for the diagnosis of sepsis were done. These included a complete blood picture, quantitative measurement of C-reactive protein and blood and or CSF culture and sensitivity. Assays for T cell activation markers CD45RA/CD45RO and neutrophil CD11b by flow cytometry and soluble tumor necrosis factor receptor sTNFR1 by ELISA were carried out as well as chest plain x-raying. Results: The up-regulation of CD45RA/ CD45RO dual expression and CD45RO expression on T-lymphocytes was observed in the septic group. The percent expression of CD45RA/CD45RO and CD45RO was significantly elevated in the high-risk group when compared to the control group. However, CD45RA/CD45RO and CD45RO showed no significant difference in percent expression between the septic group and the high-risk group. CD11b expression was also significantly higher in the septic (72.8± 17.8) than the control group (17.2 ±9.9%, p < 0.05) and also in the high- risk group (42.2 ± 25.9%, p < 0.05) as compared to the control group. sTNFR55 was significantly high in septic group (18.14 ± 9.38 ng/ml) as well as in the high risk group (26.90 ± 16.89 ng/ml) when compared to the control group (6.44 ± 1.49 ng/ml, p < 0.05) with no significant difference between the former two groups (p > 0.05). In addition and according to the follow up sample taken after one week, a significant increase in the expression of CD45RO was realized in the septic group. Conclusion: The surface activation markers of T-lymphocytes (CD45RA/ CD45RO, CD45RO), neutrophil activation marker (CD11b) and soluble TNF receptor 1 are useful early indicators of neonatal sepsis, and are superior to the hematological scoring system and CRP in the early detection of the disease.Keywords: neonatal sepsis, surface activation markers, neutrophil activation marker, CD45RA/CD45RO, CD45RO, CD11b, soluble TNF receptor 1Egypt J Pediatr Allergy Immunol 2003; 1(2): 110-

Fertility restoration of racing mare with persistent corpus luteum

Background and aim: Persistent corpus luteum (PCL) causes anestrus in mares. This study aimed to determine the effect of intrauterine prostaglandin F2α (PGF2α) treatment on PCL of racing mares to restore fertility. Materials and methods: Twelve racing mares suspected with PCL were diagnosed using transrectal palpation and confirmed by serum progesterone (P4) concentration measurement. PGF2α was infused intrauterine, followed by serum collection at 24, 48, and 72 h after. Estrous symptoms were monitored, and mating was conducted on day 3 of estrus with an earlier injection of 8.4 μg gonadotropin-releasing hormone twice a day. Transrectal palpation was performed on days 21-30 to observe the corpus luteum. Pregnancy diagnosis was performed rectally on 40-45 days post-mating and confirmed using Doppler ultrasound scanning. Results: Eleven of the 12 mares had PCL. There was a dramatic reduction in the P4 concentration following PGF2α treatment of mares with PCL. All mares exhibited estrus 2.6±0.55 days post-treatment with a P4 concentration of 0.12±0.12 ng/mL. Rectal palpation and P4 concentration on 21-30 days after estrous onset showed that all mares were ovulating. The evaluation of P4 concentration on days 40-45 post-mating showed that all mares were still in the luteal phase. However, the pregnancy rate was only 54.5% based on rectal palpation and Doppler ultrasound scanning. Conclusion: Treatment of PCL in racing mares with an intrauterine infusion of PGF2α restored the estrous cycle and induced ovulation and pregnancy. Keywords: estrus; fertility; good health and well-being; ovulation; progesterone; racing mar

Patients' values and preferences of the expected efficacy of hip arthroscopy for osteoarthritis : a protocol for a multinational structured interview-based study combined with a randomised survey on the optimal amount of information to elicit preferences

Peer reviewe

Long‐term care facilities' response to the COVID ‐19 pandemic: An international, cross‐sectional survey

Aims To (i) assess the adherence of long‐term care (LTC) facilities to the COVID‐19 prevention and control recommendations, (ii) identify predictors of this adherence and (iii) examine the association between the adherence level and the impact of the pandemic on selected unfavourable conditions. Design Cross‐sectional survey. Methods Managers (n = 212) and staff (n = 2143) of LTC facilities (n = 223) in 13 countries/regions (Brazil, Egypt, England, Hong Kong, Indonesia, Japan, Norway, Portugal, Saudi Arabia, South Korea, Spain, Thailand and Turkey) evaluated the adherence of LTC facilities to COVID‐19 prevention and control recommendations and the impact of the pandemic on unfavourable conditions related to staff, residents and residents' families. The characteristics of participants and LTC facilities were also gathered. Data were collected from April to October 2021. The study was reported following the STROBE guidelines. Results The adherence was significantly higher among facilities with more pre‐pandemic in‐service education on infection control and easier access to information early in the pandemic. Residents' feelings of loneliness and feeling down were the most affected conditions by the pandemic. More psychological support to residents was associated with fewer residents' aggressive behaviours, and more psychological support to staff was associated with less work–life imbalance. Conclusions Pre‐pandemic preparedness significantly shaped LTC facilities' response to the pandemic. Adequate psychological support to residents and staff might help mitigate the negative impacts of infection outbreaks. Impact This is the first study to comprehensively examine the adherence of LTC facilities to COVID‐19 prevention and control recommendations. The results demonstrated that the adherence level was significantly related to pre‐pandemic preparedness and that adequate psychological support to staff and residents was significantly associated with less negative impacts of the pandemic on LTC facilities' staff and residents. The results would help LTC facilities prepare for and respond to future infection outbreaks. Patient or public contribution No Patient or Public Contribution

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

PENGARUH MOTIVASI DAN PELATIHAN TERHADAP KINERJA KARYAWAN PT. MONOKEM SURYA

This research was conducted at PT. Monokem Surya, located in the district. Rengasdengklok Kab. Karawang. Where the researcher wants to know whether there is an influence between reward on employee performance, the influence of motivation on employee performance and the effect of training on employee performance. The dependent variable is employee performance and the independent variables are reward, motivation and training. This research method uses quantitative methods, the data used are premier and secondary data. Primary data obtained by the questionnaire method (questionnaire). The population in this study were employees of PT. Monokem Surya as many as 70 people. The sampling technique used in this research is the total sample is saturated. The data analysis technique used in this research is validity test, reliability test, classical assumption test, normality test, multicollinearity test, heteroscedasticity test, t test, determination test using spss software. The results showed that all independent variables had a significant effect on the performance of the employees of PT. Monokem SuryaThis research was conducted at PT. Monokem Surya, located in the district. Rengasdengklok Kab. Karawang. Where the researcher wants to know whether there is an influence between reward on employee performance, the influence of motivation on employee performance and the effect of training on employee performance. The dependent variable is employee performance and the independent variables are reward, motivation and training. This research method uses quantitative methods, the data used are premier and secondary data. Primary data obtained by the questionnaire method (questionnaire). The population in this study were employees of PT. Monokem Surya as many as 70 people. The sampling technique used in this research is the total sample is saturated. The data analysis technique used in this research is validity test, reliability test, classical assumption test, normality test, multicollinearity test, heteroscedasticity test, t test, determination test using spss software. The results showed that all independent variables had a significant effect on the performance of the employees of PT. Monokem Sury

Evaluation of the immune response in patients with chronic HCV infection

No Abstract. The Egyptian Journal of Biochemistry and Molecular Biology Vol. 22(2) 2004: 41-5

Matrix Metalloproteinase-2, Squamous Cell Carcinoma Antigen, and Tissue Polypeptide-Specific Antigen Expression in Egyptian Patients with Cervical Carcinoma: Relationship with Prognosis

Matrix metalloproteinases (MMPs), a family of proteolytic enzymes produced by both stromal and tumor cells, appear to have a key role in the events leading to local invasion and metastasis by malignant neoplasms. In the present study, we evaluated the role of MMP-2, squamous cell carcinoma antigen (SCCA), and tissue polypeptide – specific antigen (TPS) in cervical neoplasia. Using Western blotting and enzyme immunoassay (EIA), we analyzed 50 patients with cervical carcinoma (CC) and 25 normal controls for expression of MMP-2 in tissue cell lysates. We also quantified SCCA and TPS with microparticle immunoassay and EIA, respectively. The results were correlated with human papilloma virus (HPV) infection, clinicopathological findings, and disease outcome. The cutoff point for each marker was estimated from receiver operating characteristic curves. Logistic regression analysis was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for each marker. MMP-2, SCCA, and TPS protein expression were significantly higher in patients with CC than in normal controls. While TPS was the best marker for discriminating between patients and controls, MMP-2 was associated with an advanced tumor stage (OR, 13.9 [95% CI, 1.4-133.9]) and poor histological grade (OR, 10.2 [95% CI, 1.7-60.5]). Moreover, independent of the effect of an advanced CC stage and grade, the patients' age, and the presence of HPV infection, MMP-2 was considered a strong predictor for CC recurrence (OR, 8.1 [95% CI, 1.3- 49.1]). Tissue markers may be used to select high-risk patients for early detection of and adjuvant therapy for recurrence. Our MMP-2 findings are particularly relevant to the development of protease inhibitors as a new cancer therapy approach

CRISPR/Cas9 mediated knock-out of VPREB1 gene induces a cytotoxic effect in myeloma cells.

BackgroundMultiple Myeloma (MM) is a heterogeneous, hematological neoplasm that accounts 2% of all cancers. Although, autologous stem cell transplantation and chemotherapy are currently the most effective therapy, it carries a notable hazards, in addition for being non curative. Recently, the Clustered Regular Interspaced Short Palindromic Repeats (CRISPR-cas9) has been successfully tried at the experimental level, for the treatment of several hematological malignancies.ObjectivesWe aimed to investigate the in-vitro effect of CRISPR-cas9-mediated knock-out of V-set pre B-cell surrogate light chain 1"VPREB1" gene on the malignant proliferation of primary cultured myeloma cells.MethodsBioinformatics' analysis was performed to explore the gene expression profile of MM, and the VPREB1 gene was selected as a target gene for this study. We knocked-out the VPREB1 gene in primary cultured myeloma cells using CRISPR-cas9, the VPREB1 gene editing efficacy was verified by determining VPREB1 gene expression at both the mRNA and protein levels by qPCR and immunofluorescence, respectively. Furthermore, the cytotoxic effect on primary myeloma cells proliferation was evaluated using cytotoxicity assay.ResultsThere was a statistically significant reduction of both VPREB1 mRNA and protein expression levels (pConclusionCRISPR-cas9-mediated knock-out of VPREB1 gene is effective for inhibiting the proliferation of primary myeloma cells. This would provide a basis for a promising therapeutic strategy for patients with multiple myeloma