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Viruses May 2024Duck Tembusu Virus (DTMUV) is a pathogen of the Flaviviridae family that causes infections in poultry, leading to significant economic losses in the duck farming... (Review)
Review
Duck Tembusu Virus (DTMUV) is a pathogen of the Flaviviridae family that causes infections in poultry, leading to significant economic losses in the duck farming industry in recent years. Ducks infected with this virus exhibit clinical symptoms such as decreased egg production and neurological disorders, along with serious consequences such as ovarian hemorrhage, organ enlargement, and necrosis. Variations in morbidity and mortality rates exist across different age groups of ducks. It is worth noting that DTMUV is not limited to ducks alone; it can also spread to other poultry such as chickens and geese, and antibodies related to DTMUV have even been found in duck farm workers, suggesting a potential risk of zoonotic transmission. This article provides a detailed overview of DTMUV research, delving into its genomic characteristics, vaccines, and the interplay with host immune responses. These in-depth research findings contribute to a more comprehensive understanding of the virus's transmission mechanism and pathogenic process, offering crucial scientific support for epidemic prevention and control.
Topics: Animals; Ducks; Flavivirus; Flavivirus Infections; Genome, Viral; Poultry Diseases; Viral Vaccines; Farmers; Antibodies, Viral; Humans
PubMed: 38793692
DOI: 10.3390/v16050811 -
Antioxidants (Basel, Switzerland) May 2024Ascorbate (vitamin C) is an essential vitamin for the human body and participates in various physiological processes as an important coenzyme and antioxidant.... (Review)
Review
Ascorbate (vitamin C) is an essential vitamin for the human body and participates in various physiological processes as an important coenzyme and antioxidant. Furthermore, the role of ascorbate in the prevention and treatment of cancer including gynecological cancer has gained much more interest recently. The bioavailability and certain biological functions of ascorbate are distinct in males versus females due to differences in lean body mass, sex hormones, and lifestyle factors. Despite epidemiological evidence that ascorbate-rich foods and ascorbate plasma concentrations are inversely related to cancer risk, ascorbate has not demonstrated a significant protective effect in patients with gynecological cancers. Adequate ascorbate intake may have the potential to reduce the risk of human papillomavirus (HPV) infection and high-risk HPV persistence status. High-dose ascorbate exerts antitumor activity and synergizes with chemotherapeutic agents in preclinical cancer models of gynecological cancer. In this review, we provide evidence for the biological activity of ascorbate in females and discuss the potential role of ascorbate in the prevention and treatment of ovarian, endometrial, and cervical cancers.
PubMed: 38790722
DOI: 10.3390/antiox13050617 -
Genes Apr 2024P53 overexpression plays a critical role in cancer pathogenesis by disrupting the intricate regulation of cellular proliferation. Despite its firmly established function...
P53 overexpression plays a critical role in cancer pathogenesis by disrupting the intricate regulation of cellular proliferation. Despite its firmly established function as a tumor suppressor, elevated p53 levels can paradoxically contribute to tumorigenesis, influenced by factors such as exposure to carcinogens, genetic mutations, and viral infections. This phenomenon is observed across a spectrum of cancer types, including bladder (BLCA), ovarian (OV), cervical (CESC), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), diffuse large B-cell lymphoma (DLBC), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). This broad spectrum of cancers is often associated with increased aggressiveness and recurrence risk. Effective therapeutic strategies targeting tumors with p53 overexpression require a comprehensive approach, integrating targeted interventions aimed at the p53 gene with conventional modalities such as chemotherapy, radiation therapy, and targeted drugs. In this extensive study, we present a detailed analysis shedding light on the multifaceted role of TP53 across various cancers, with a specific emphasis on its impact on disease-free survival (DFS). Leveraging data from the TCGA database and the GTEx dataset, along with GEPIA, UALCAN, and STRING, we identify TP53 overexpression as a significant prognostic indicator, notably pronounced in prostate adenocarcinoma (PRAD). Supported by compelling statistical significance ( < 0.05), our analysis reveals the distinct influence of TP53 overexpression on DFS outcomes in PRAD. Additionally, graphical representations of overall survival (OS) underscore the notable disparity in OS duration between tumors exhibiting elevated TP53 expression (depicted by the red line) and those with lower TP53 levels (indicated by the blue line). The hazard ratio (HR) further emphasizes the profound impact of TP53 on overall survival. Moreover, our investigation delves into the intricate TP53 protein network, unveiling genes exhibiting robust positive correlations with TP53 expression across 13 out of 27 cancers. Remarkably, negative correlations emerge with pivotal tumor suppressor genes. This network analysis elucidates critical proteins, including SIRT1, CBP, p300, ATM, DAXX, HSP 90-alpha, Mdm2, RPA70, 14-3-3 protein sigma, p53, and ASPP2, pivotal in regulating cell cycle dynamics, DNA damage response, and transcriptional regulation. Our study underscores the paramount importance of deciphering TP53 dynamics in cancer, providing invaluable insights into tumor behavior, disease-free survival, and potential therapeutic avenues.
Topics: Humans; Tumor Suppressor Protein p53; Neoplasms; Computational Biology; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor
PubMed: 38790205
DOI: 10.3390/genes15050577 -
Genes Apr 2024germline monoallelic variants have been detected in a number of patients affected by breast/ovarian cancer or endometrial cancer, suggesting a potential susceptibility...
BACKGROUND
germline monoallelic variants have been detected in a number of patients affected by breast/ovarian cancer or endometrial cancer, suggesting a potential susceptibility role, though their significance remains elusive since the disease mechanism is normally recessive. Hence, the aim of this research was to explore the hypothesis that a second hit could have arisen in the other allele in the tumor tissue.
METHODS
we used Sanger sequencing and immunohistochemistry to search for a second variant in the tumoral DNA and to assess protein expression, respectively.
RESULTS
we detected one variant of unknown significance, one variant with conflicting interpretation of pathogenicity and three benign/likely benign variants; the protein was not detected in the tumor tissue of half of the patients, and in others, its expression was reduced.
CONCLUSIONS
our results fail to demonstrate that germinal monoallelic variants increase cancer risk through a LOH (loss of heterozygosity) mechanism in the somatic tissue; however, the absence or partial loss of the protein in many tumors suggests its dysregulation regardless of genetic status.
Topics: Humans; DNA Glycosylases; Female; Endometrial Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Middle Aged; Loss of Heterozygosity; Genetic Predisposition to Disease; Aged; Adult
PubMed: 38790183
DOI: 10.3390/genes15050554 -
Journal of Dairy Science May 2024An economic simulation was carried out over 183 milk-producing countries to estimate the global economic impacts of 12 dairy cattle diseases and health conditions:...
An economic simulation was carried out over 183 milk-producing countries to estimate the global economic impacts of 12 dairy cattle diseases and health conditions: mastitis (subclinical and clinical), lameness, paratuberculosis (Johne's disease), displaced abomasum, dystocia, metritis, milk fever, ovarian cysts, retained placenta, and ketosis (subclinical and clinical). Estimates of disease impacts on milk yield, fertility, and culling were collected from the literature, standardized, meta-analyzed using a variety of methods ranging from simple averaging to random-effects models, and adjusted for comorbidities to prevent overestimation. These comorbidity-adjusted disease impacts were then combined with a set of country-level lactational incidence and/or prevalence estimates, herd characteristics, and price estimates within a series of Monte Carlo simulations that estimated and valued the economic losses due to these diseases. It was estimated that total annual global losses are USD 65 billion (B). Subclinical ketosis, clinical mastitis, and subclinical mastitis were the costliest diseases modeled, resulting in mean annual global losses of approximately USD 18B, USD 13B, and USD 9B, respectively. Estimated global annual losses due to clinical ketosis, displaced abomasum, dystocia, lameness, metritis, milk fever, ovarian cysts, paratuberculosis, and retained placenta were estimated to be USD 0.2B, 0.6B, 0.6B, 6B, 5B, 0.6B, 4B, 4B, and 3B, respectively. Without adjustment for comorbidities, when statistical associations between diseases were disregarded, mean aggregate global losses would have been overestimated by 45%. Although annual losses were greatest in India (USD 12B), the USA (USD 8B), and China (USD 5B), depending on the measure of losses used (losses as a percent of GDP, losses per capita, losses as a percent of gross milk revenue), the relative economic burden of these dairy cattle diseases across countries varied markedly.
PubMed: 38788837
DOI: 10.3168/jds.2023-24626 -
Toxins Apr 2024Recent discoveries establish DNA and RNA as bona fide substrates for ADP-ribosylation. NADAR ("NAD- and ADP-ribose"-associated) enzymes reverse guanine ADP-ribosylation...
Recent discoveries establish DNA and RNA as bona fide substrates for ADP-ribosylation. NADAR ("NAD- and ADP-ribose"-associated) enzymes reverse guanine ADP-ribosylation and serve as antitoxins in the DarT-NADAR operon. Although NADARs are widespread across prokaryotes, eukaryotes, and viruses, their specificity and broader physiological roles remain poorly understood. Using phylogenetic and biochemical analyses, we further explore de-ADP-ribosylation activity and antitoxin functions of NADAR domains. We demonstrate that different subfamilies of NADAR proteins from representative strains and an -infecting phage retain biochemical activity while displaying specificity in providing protection from toxic guanine ADP-ribosylation in cells. Furthermore, we identify a myxobacterial enzyme within the YbiA subfamily that functions as an antitoxin for its associated DarT-unrelated ART toxin, which we termed YarT, thus presenting a hitherto uncharacterised ART-YbiA toxin-antitoxin pair. Our studies contribute to the burgeoning field of DNA ADP-ribosylation, supporting its physiological relevance within and beyond bacterial toxin-antitoxin systems. Notably, the specificity and confinement of NADARs to non-mammals infer their potential as highly specific targets for antimicrobial drugs with minimal off-target effects.
Topics: ADP-Ribosylation; Escherichia coli; Escherichia coli Proteins; Bacterial Toxins; Adenosine Diphosphate Ribose; Phylogeny; Toxin-Antitoxin Systems; DNA, Bacterial; DNA
PubMed: 38787060
DOI: 10.3390/toxins16050208 -
The Libyan Journal of Medicine Dec 2024Breast cancer (BC) is a leading cause of cancer deaths in Libyan women. variants differ globally due to the diversity of genetic makeup and populations history. Their...
Breast cancer (BC) is a leading cause of cancer deaths in Libyan women. variants differ globally due to the diversity of genetic makeup and populations history. Their distribution, prevalence, and significance in Libyans remain largely unexplored. This study investigated the characteristics and distribution of variants in exons 5, 11, and 20 in Libyan families with BC. Thirty-six BC patients at ≤ 45 years, between 46-50 years and with a family history of breast, ovarian, pancreatic or prostate cancer in close relatives, or with triple-negative BC, were selected from 33 unrelated families during 2018-2020 at the National Cancer Institute, Sabratha, Libya. From these 33 families, 20 women (18 BC patients and two unaffected) were screened for exons 5, 11 and 20 using Sanger sequencing. All families completed an epidemiology and family history questionnaire. Twenty-seven variants (26 in exon 11 and 1 in exon 20, minor allele frequency of < 0.01) were detected in 10 of 18 unrelated families (55.6%.) Among the 27 variants, 26 (96%) were heterozygous. A frameshift pathogenic variant, c.2643del, and one novel variant c.1366A>G were identified. Furthermore, seven variants with unknown clinical significance were detected: c.1158T>A, c.1346C>G, c.1174C>G, c.3630 G>T, c.3599A>T, and c.3400 G>C in exon 11, and c.5244T>A in exon 20. Six variants with conflicting pathogenicity interpretations, c. 3460T>A, c. 3572 G>A, c. 3700 G>C, c. 1246C>G, c. 1344C>G, and c. 1054 G>A, were also identified. Twelve benign/likely benign variants were identified. Rare variants that have not been reported in North Africa were found in Libyan patients. These findings provide preliminary insights into the variants that could contribute to hereditary BC risk in Libyans. Further functional, computational, and population analyses are essential to determine their significance and potential impact on BC risk, which could ultimately lead to more personalized management strategies.
Topics: Humans; Libya; Female; Middle Aged; Breast Neoplasms; Germ-Line Mutation; BRCA1 Protein; Exons; Adult; Genetic Predisposition to Disease; Gene Frequency
PubMed: 38785139
DOI: 10.1080/19932820.2024.2356906 -
Ethiopian Journal of Health Sciences Sep 2023In the female population, pelvic organ prolapse is a common problem that lowers people's quality of life in terms of their health. Depending on the severity of the...
BACKGROUND
In the female population, pelvic organ prolapse is a common problem that lowers people's quality of life in terms of their health. Depending on the severity of the prolapse and the symptoms, there are many treatment options. Simple observation, vaginal pessaries, or surgical management are all possible treatments. Reconstructive pelvic surgery with or without mesh augmentation and obliterative surgery are two surgical treatments that are available. Due to the contentious concerns surrounding the use of mesh and the rising demand for uterine preservation, surgical practices are currently shifting.
METHODS
Just two cases are included in this study due to the rarity of this condition. In this study, I introduce a new technique to the literature (Mostafa Maged sling technique) which will be challenging. This technique depends on round ligaments and ovarian ligament to hitch up the whole uterus.
RESULTS
There were no difficulties following the procedure. None of the patients required blood transfusions, and there were no signs of dehiscence or incision infection. Non-steroidal antiinflammatory medications were administered to both patients as analgesia. On the first postoperative day, the foley catheters were removed from both patients.
CONCLUSION
A simple and new manueuver is applied in the literature to treat the uterine prolapse. It is easy to learn and easy to perform. We need further studies to compare different techniques including Mostafa Maged sling operation to manage uterine prolapse.
Topics: Humans; Female; Uterine Prolapse; Middle Aged; Suburethral Slings; Uterus; Gynecologic Surgical Procedures; Pelvic Organ Prolapse; Surgical Mesh
PubMed: 38784517
DOI: 10.4314/ejhs.v33i5.22 -
JAMA Network Open May 2024
Topics: Humans; COVID-19; Neoplasms; Male; Female; Middle Aged; SARS-CoV-2; Aged; Adult; Antineoplastic Agents; Withholding Treatment
PubMed: 38780944
DOI: 10.1001/jamanetworkopen.2024.11859 -
JAMA Network Open May 2024Racially and ethnically minoritized US adults were disproportionately impacted by the COVID-19 pandemic and experience poorer cancer outcomes, including inequities in...
IMPORTANCE
Racially and ethnically minoritized US adults were disproportionately impacted by the COVID-19 pandemic and experience poorer cancer outcomes, including inequities in cancer treatment delivery.
OBJECTIVE
To evaluate racial and ethnic disparities in cancer treatment delays and discontinuations (TDDs) among patients with cancer and SARS-CoV-2 during different waves of the COVID-19 pandemic in the United States.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used data from the American Society of Clinical Oncology Survey on COVID-19 in Oncology Registry (data collected from April 2020 to September 2022), including patients with cancer also diagnosed with SARS-CoV-2 during their care at 69 US practices. Racial and ethnic differences were examined during 5 different waves of the COVID-19 pandemic in the United States based on case surge (before July 2020, July to November 2020, December 2020 to March 2021, April 2021 to February 2022, and March to September 2022).
EXPOSURES
Race and ethnicity.
MAIN OUTCOMES AND MEASURES
TDD was defined as any cancer treatment postponed more than 2 weeks or cancelled with no plans to reschedule. To evaluate TDD associations with race and ethnicity, adjusted prevalence ratios (aPRs) were estimated using multivariable Poisson regression, accounting for nonindependence of patients within clinics, adjusting for age, sex, body mass index, comorbidities, cancer type, cancer extent, and SARS-CoV-2 severity (severe defined as death, hospitalization, intensive care unit admission, or mechanical ventilation).
RESULTS
A total of 4054 patients with cancer and SARS-CoV-2 were included (143 [3.5%] American Indian or Alaska Native, 176 [4.3%] Asian, 517 [12.8%] Black or African American, 469 [11.6%] Hispanic or Latinx, and 2747 [67.8%] White; 2403 [59.3%] female; 1419 [35.1%] aged 50-64 years; 1928 [47.7%] aged ≥65 years). The analysis focused on patients scheduled (at SARS-CoV-2 diagnosis) to receive drug-based therapy (3682 [90.8%]), radiation therapy (382 [9.4%]), surgery (218 [5.4%]), or transplant (30 [0.7%]), of whom 1853 (45.7%) experienced TDD. Throughout the pandemic, differences in racial and ethnic inequities based on case surge with overall TDD decreased over time. In multivariable analyses, non-Hispanic Black (third wave: aPR, 1.56; 95% CI, 1.31-1.85) and Hispanic or Latinx (third wave: aPR, 1.35; 95% CI, 1.13-1.62) patients with cancer were more likely to experience TDD compared with non-Hispanic White patients during the first year of the pandemic. By 2022, non-Hispanic Asian patients (aPR, 1.51; 95% CI, 1.08-2.12) were more likely to experience TDD compared with non-Hispanic White patients, and non-Hispanic American Indian or Alaska Native patients were less likely (aPR, 0.37; 95% CI, 0.16-0.89).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of patients with cancer and SARS-CoV-2, racial and ethnic inequities existed in TDD throughout the pandemic; however, the disproportionate burden among racially and ethnically minoritized patients with cancer varied across SARS-CoV-2 waves. These inequities may lead to downstream adverse impacts on cancer mortality among minoritized adults in the United States.
Topics: Humans; COVID-19; Male; Female; Neoplasms; Cross-Sectional Studies; United States; Middle Aged; Healthcare Disparities; SARS-CoV-2; Aged; Continuity of Patient Care; Adult; Pandemics; Ethnicity; Ethnic and Racial Minorities; Hispanic or Latino
PubMed: 38767916
DOI: 10.1001/jamanetworkopen.2024.12050