Prevention Options Research Articles

Awareness and Candidacy for Endocrine Prevention and Risk Reducing Mastectomy in Unaffected High-Risk Women Referred for Breast Cancer Risk Assessment.

Primary prevention of breast cancer in women at elevated risk includes several strategies such as endocrine prevention and risk-reducing mastectomy (RRM). The objective of this study was to evaluate awareness of different preventive strategies across high-risk subgroups. Women referred for high risk evaluation between 2020 and 2023 completed an initial risk-assessment questionnaire that included questions around perceived lifetime risk and consideration of preventive strategies. One-way analysis of variance (ANOVA) and chi-squared tests were used to compare differences across different high-risk subgroups. 482 women with a median age of 43 years (20-79 years) met inclusion criteria; 183 (38.0%) germline pathogenic variant carriers (GPV), 90 (18.7%) with high-risk lesions (HRL) on breast biopsy, and 209 (43.4%) with strong family history (FH) without a known genetic predisposition. Most high-risk women reported that they had considered increased screening and surveillance (83.7%) and lifestyle strategies (80.6%), while fewer patients had considered RRM (39.8%) and endocrine prevention (27.0%). Prior to initial consultation, RRM was more commonly considered in GPV carriers (59.4%) relative to those with HRL (33.3%) or strong FH (26.3%, p < 0.001). Based on current guidelines, 206 (43%) patients were deemed eligible for endocrine prevention, including 80.5% with HRL and 39.0% with strong FH. Prior consideration of endocrine prevention was highest in patients with HRL and significantly lower in those with strong FH (47.2% HRL versus 31.1% GPV versus 18.7% FH, p = 0.001). Endocrine prevention is the least considered preventive option for high-risk women, despite eligibility in a significant proportion of those presenting with HRL or strong FH.

ZNF643/ZFP69B Exerts Oncogenic Properties and Associates with Cell Adhesion and Immune Processes.

The global cancer burden remains high; thus, a better understanding of the molecular mechanisms driving carcinogenesis is needed to improve current prevention and treatment options. We previously detected the ZNF643/ZFP69B gene upregulated in multiple tumors, and we speculated it may play a role in tumor biology. To test this hypothesis, we employed TCGA-centered databases to correlate ZNF643 status with various clinicopathological parameters. We also performed RNA-seq analysis and in vitro studies assessing cancer cell phenotypes, and we searched for ZNF643-bound genomic loci. Our data indicated higher levels of ZNF643 in most analyzed tumors compared to normal samples, possibly due to copy number variations. ZNF643 mRNA correlated with diverse molecular and immune subtypes and clinicopathological features (tumor stage, grade, patient survival). RNA-seq analysis revealed that ZNF643 silencing triggers the deregulation of the genes implicated in various cancer-related processes, such as growth, adhesion, and immune system. Moreover, we observed that ZNF643 positively influences cell cycle, migration, and invasion. Finally, our ChIP-seq analysis indicated that the genes associated with ZNF643 binding are linked to adhesion and immune signaling. In conclusion, our data confirm the oncogenic properties of ZNF643 and pinpoint its impact on cell adhesion and immune processes.

Efficient regulatory approval of two novel HIV prevention interventions in a resource-limited setting: experiences from Zimbabwe.

The global burden of HIV remains unacceptably high despite significant progress made in HIV treatment and prevention. There is an urgent need to scale up the comprehensive HIV prevention strategies that include pre-exposure prophylaxis (PrEP). Oral PrEP is highly effective in preventing HIV acquisition when taken regularly, but this remains a challenge for some at-risk individuals. Therefore, there is a need for other HIV prevention options. The dapivirine vaginal ring (DVR) and long-acting injectable cabotegravir (CAB-LA) are novel biomedical interventions that are safe and efficacious for HIV pre-exposure prophylaxis, as demonstrated in recently completed clinical trials. Timely roll-out and scalability of efficacious interventions depend on the registration process with the national medicine regulatory authorities (NMRAs). The Medicines Control Authority of Zimbabwe (MCAZ) was the first NMRA globally to approve the DVR in July 2021 and the first in Africa to approve CAB-LA for HIV prevention in July 2022. The regulatory review process for DVR and CAB-LA by MCAZ took 4.5 and 5.5 months, respectively. This efficient review process of the two interventions by MCAZ, a regulatory body in a resource-limited setting, provides important lessons to shorten timelines between the completion of the clinical development process and the registration of essential medicines.

Family influences on oral PrEP use among adolescent girls and young women in Kenya and South Africa.

Effective use of oral HIV pre-exposure prophylaxis (PrEP) has been lower among African adolescent girls and young women (AGYW) than among older women, young men who have sex with men, and serodiscordant heterosexual couples in the region. Efforts to build PrEP support have centered around peers and male partners, but the family may also play an important role. This qualitative study aimed to describe family influence on PrEP use among AGYW in in three African cities. POWER (Prevention Options for Women Evaluation Research) was a PrEP demonstration project among 2550 AGYW (16-25 years old) in Johannesburg and Cape Town, South Africa and Kisumu, Kenya conducted from 2017 to 2020. In-depth interviews and focus group discussions were conducted with 136 AGYW participants to explore their PrEP views and experiences, including awareness and interest in PrEP; barriers and facilitators to uptake and use; the influence of family, peers, intimate partners, and community; and the key types of support for their PrEP use. Transcripts were coded and analysed thematically. The decision to initiate PrEP was associated with fear and anxiety linked to anticipated stigma from family members, and with family's lived HIV experience. Family disclosure, especially to mothers, was important to participants, as most lived with their families and considered it essential for them to obtain their mother's approval to use PrEP. Most family members, particularly mothers, provided instrumental, emotional, informational and appraisal support to participants using PrEP, including reminders, encouragement, and problem-solving. Participants reported that family members with insufficient information about PrEP safety and efficacy and who voiced concerns were a substantial barrier to their use. However, they often became supportive after receiving more PrEP information. Families, particularly mothers, can play an important role in supporting PrEP use. PrEP programmes should leverage family support to help with PrEP persistence by providing basic information to families about PrEP safety and efficacy. AGYW using PrEP should be encouraged to selectively disclose PrEP use to build support and counseled on how to disclose and address family concerns.

Young People Need More HIV Prevention Options, Delivered in an Acceptable Way

Young People Need More HIV Prevention Options, Delivered in an Acceptable Way

Sin Nombre Virus and the Emergence of Other Hantaviruses: A Review of the Biology, Ecology, and Disease of a Zoonotic Pathogen.

Sin Nombre virus (SNV) is an emerging virus that was first discovered in the Four Corners region of the United States in 1993. The virus causes a disease known as Hantavirus Pulmonary Syndrome (HPS), sometimes called Hantavirus Cardiopulmonary Syndrome (HCPS), a life-threatening illness named for the predominance of infection of pulmonary endothelial cells. SNV is one of several rodent-borne hantaviruses found in the western hemisphere with the capability of causing this disease. The primary reservoir of SNV is the deer mouse (Peromyscus maniculatus), and the virus is transmitted primarily through aerosolized rodent excreta and secreta. Here, we review the history of SNV emergence and its virus biology and relationship to other New World hantaviruses, disease, treatment, and prevention options.

Cassandra speaks: a case series of unanticipated subcutaneous ICD premature battery depletion in a single-centre experience

Abstract Background Subcutaneous ICDs (S-ICD) are a valuable option in sudden cardiac death prevention. The main advantage over conventional transvenous ICDs is the absence of intravascular hardware for patients without the need for cardiac stimulation, resynchronization therapy or anti-tachycardia pacing. The claim of reduced lead-related complications has on the contrary been challenged by recent warnings of unexpected lead fracture. Moreover, concerns related to premature battery depletion (PBD) leading to unanticipated device replacement are increasing. Purpose To evaluate retrospectively the incidence of unanticipated S-ICD premature battery depletion in a single-centre experience. Method 168 consecutive patients implanted with S-ICD from February 2015 to November 2022 in our tertiary cardiology centre were included in this study. 4 patients moved to other sites and were thus lost to follow-up, leaving a total of 164 patients. PBD was defined as the occurrence of battery depletion requiring generator replacement earlier than 60 months post-implantation in the absence of therapy being delivered, or as a result of manufacturer recommendations. Results Most patients were implanted for primary prevention (101 patients, 60%). The main aetiology was hypertrophic cardiomyopathy (47 patients, 28%), followed by arrhythmogenic (35, 21%) and dilated idiopathic cardiomyopathy (24, 14%). Mean age and left ventricular ejection fraction at baseline were 46±18yrs and 51±16%, respectively. Over a total follow up period of 44±25 months, at 58±17 months following implantation 19 (11,6%) patients needed early replacement due to PBD, while 2 (1.2%) patients had lead fracture after respectively 41 and 26 months, for a total of 12,8% of patients with system-related complications. In addition to those patients requiring early replacement due to PBD or lead fracture, two underwent S-ICD extraction due to infection. Analysis of freedom from unanticipated PBD per year of implantation showed higher rates in years 2016 and 2017, with 67% and 27% of all implanted patients, respectively (Figure 1). Conclusions In this study, the incidence of PBDs appear to be higher than reported in literature though confined to a limited device series. However, if on the contrary the trend should remain remarkably high, that would not only endanger patients health due to repeated replacements, but also pose a huge economic burden to health systems.

Unveiling the inhibition mechanism of Clostridioides difficile by Bifidobacterium longum via multiomics approach.

Antibiotic-induced gut microbiota disruption constitutes a major risk factor for Clostridioides difficile infection (CDI). Further, antibiotic therapy, which is the standard treatment option for CDI, exacerbates gut microbiota imbalance, thereby causing high recurrent CDI incidence. Consequently, probiotic-based CDI treatment has emerged as a long-term management and preventive option. However, the mechanisms underlying the therapeutic effects of probiotics for CDI remain uninvestigated, thereby creating a knowledge gap that needs to be addressed. To fill this gap, we used a multiomics approach to holistically investigate the mechanisms underlying the therapeutic effects of probiotics for CDI at a molecular level. We first screened Bifidobacterium longum owing to its inhibitory effect on C. difficile growth, then observed the physiological changes associated with the inhibition of C. difficile growth and toxin production via a multiomics approach. Regarding the mechanism underlying C. difficile growth inhibition, we detected a decrease in intracellular adenosine triphosphate (ATP) synthesis due to B. longum-produced lactate and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. Via the differential regulation of proteins involved in translation and protein quality control, we identified B. longum-induced proteinaceous stress. Finally, we found that B. longum suppressed the toxin production of C. difficile by replenishing proline consumed by it. Overall, the findings of the present study expand our understanding of the mechanisms by which probiotics inhibit C. difficile growth and contribute to the development of live biotherapeutic products based on molecular mechanisms for treating CDI.

Challenging the Safety Profile of Bipolar TURP Regarding Dilutional Hyponatremia

Objective: To measure the extent of Dilutional Hyponatremia after Transurethral resection of prostate using Bipolar Resection Technique. Material and Methods: The study was conducted at Social Security Teaching Hospital Lahore. The study was carried out between 1st June 2022 to 30th November 2022. All patients who were candidates of surgical option and were planned TURP were included. They had pre-operative sodium levels done and this was compared to post operative levels on first post operative day. All patients included in the study had moderate prostate size and had resection time less than one hour. Results: Total 45 patients having undergone bipolar TURP were included in the study. Among these 45 patients, 19 patients had a decrease in sodium levels postoperatively ,further in these 19 patients, 14 patients had a decrease of less than 5 mEq/L .In 2 out of total 45 patients the sodium levels remained same post operatively. In 24 patients out of total 45 there was an increase in sodium levels, further in these 24 patients ,19 patients had an increase of less than 5mEq/L . In all 45 patients no clinical symptoms of dilutional hyponatremia were observed. Conclusion: There was no significant dilutional hyponatremia seen after bipolar TURP and wherever observed did not caused any clinical impact , proclaiming Bipolar TURP as a safe option for prevention of dilutional Hyponatremia during surgery for Benign prostate enlargement (BPE).

Abstract 16269: Heart Failure With Preserved Ejection Fraction and Sudden Cardiac Death in the General Population

Background: Published data indicate that 50% of individuals with heart failure and reduced ejection fraction (HFrEF) suffer sudden cardiac death (SCD), however the burden of SCD in heart failure with preserved ejection fraction (HFpEF) remains inconclusive. Aim: Determine the prevalence of HFpEF in a community-based cohort of SCD. Methods: We prospectively identified cases with out-of-hospital SCD in a large metro area of the US Northwest (Pop. 1 million, 2002-2017) and determined HF status prior to SCD based on review of clinical records. Heart failure was subdivided into HFpEF (EF≥50%), HFmrEF (EF 40%-50%), and HFrEF (EF≤40%). In addition, since HFpEF is often underdiagnosed, we evaluated a modified H2FPEF algorithm for the identification of HFpEF among our SCD cohort with unknown HF subtypes. The score was comprised of clinical variables including age, BMI, atrial fibrillation, hypertension, and myocardial infarction. Score accuracy was assessed using receiver operating characteristic (ROC) analysis comparing known HFpEF from clinical records and echocardiography versus non-HF subjects. Next, the score was used to identify missing HFpEF cases within the HF and SCD population. Results: Among 4,683 total SCD cases, 1,013 (22%) had a clinical history of HF. Prevalence of HF sub-types was 42% for HFpEF, 19% for HFmEF and 39% for HFrEF cases. An algorithm score of 5 or greater differentiated HFpEF subjects from non-HF subjects with an AUC of 0.68 (p &lt; 0.01). The algorithm was then deployed on cases with an unknown heart failure subtype and an additional 117 HFpEF subjects were identified. The adjusted total prevalence of HFpEF was 542 subjects (53%) in the SCD the cohort with HF. Conclusion: At least 40% of the SCD cases with HF carry a diagnosis of HFpEF, and our estimates suggest the prevalence may be as high as 53%. Ultimately, these findings highlight the need to develop effective options for primary prevention of SCD in HFpEF patients.

Sea buckthorn, its bioactive constituents, and mechanism of action: potential application in female reproduction.

Sea buckthorn (Hippophae rhamnoides L.) is a flowering shrub, and its berries have been utilized for decades as a raw ingredient in cuisines and herbal remedies. This evidence-based study focuses on its key bioactive constituents, and mechanism of protective effects with a focus on female reproductive processes. Parts of the plant contain phenols, carotenoids (lycopene, carotene, lutein, and zeaxanthin), flavonoids (isorhamnetin, quercetin, glycosides, and kaempferol), tocopherols, sterols, polyunsaturated fatty acids, minerals, vitamins, omega 3, 6, 9 and rare omega 7 fatty acids etc. Key polyphenolic flavonoids such as isorhamnetin and quercetin are believed to be mainly responsible behind its health benefits (against cardiovascular diseases, metabolic syndrome, obesity etc.) through properties including anti-cancer, antioxidant, and anti-inflammatory activities. These sea buckthorn constituents appear to mediate healthy ovarian cell proliferation, death, and hormone release, as well as decrease ovarian cancer possibly through apoptosis, and hormonal (estrogen) release. Thus, sea buckthorn and its bioactive ingredients may have potential in the management of gynecological problems such as uterine inflammation, endometriosis, and easing symptoms of vulvovaginal atrophy in postmenopausal women (by targeting inflammatory cytokines and vascular endothelial growth factor - VEGF). Apigenin, myricetin, and luteolin have also been recommended as prospective ovarian cancer preventative and adjuvant therapy options as they can inhibit ovarian cancerogenesis by triggering apoptosis and halting the cell cycle in ovarian tumors. Furthermore, its oil (containing carotenoid, sterol, and hypericin) has been speculated as an alternative to estrogen replacement therapy for postmenopausal women particularly to improve vaginal epithelial integrity. However, it is uncertain whether steroid hormone receptors, reactive oxygen species (ROS), and inflammatory regulators are actually behind sea buckhorn's actions. Sea buckthorn, and its compounds' health promoting potential warrants further validation not just in vitro and in animal research, but also in clinical trials to identify and/or standardize optimal methods of delivery of biologically active molecules.

Abstract 13229: Coiled-Coil Domain-Containing Protein 80 Protects Against Aortic Dissection by Maintaining the Contractile Smooth Muscle Cell Phenotype

Background: Aortic dissection (AD) is a life-threatening medical emergency characterized by adverse vascular remodeling. Effective prevention and treatment options are lacking for AD. Coiled-coil domain-containing protein 80 (CCDC80) plays an essential role in regulating vascular remodeling. In the present study, we aimed to define the role of CCDC80 in the formation and development of AD. Methods: The expression and subcellular localization of CCDC80 were determined in human and mouse AD. CCDC80 knockout mice (CCDC80 –/– ) and vascular smooth muscle cell (VSMC)-specific CCDC80 knockout mice (CCDC80 fl/fl SM22α Cre + ) were treated with angiotensin II (Ang II) or Ang II combined with β-aminopropionitrile monofumarate (BAPN) to induce AD models. RNA-Seq analysis combined with immunoprecipitation and blockage of the JAK2/STAT3 signaling pathway in CCDC80 –/– mice were used to evaluate the effect of CCDC80 deficiency on this pathway. Results: CCDC80 was downregulated in VSMCs in human and mouse AD. CCDC80 – / – mice challenged with Ang II and BAPN developed AD with higher frequency and severity compared with their littermate controls (66.7% vs. 100%, p &lt; 0.05). Remarkably, compared with littermate controls treated with Ang II, CCDC80 –/– mice (8.3% vs. 87.5%, p &lt; 0.05) and CCDC80 fl/fl SM22α Cre + mice (12.5% vs. 80%, p &lt; 0.05) frequently developed AD with severe elastin fragmentation and collagen deposition. CCDC80 interacted with JAK2; CCDC80 deficiency could promote VSMC phenotype switching, proliferation, and migration as well as matrix metalloproteinase production by activating the JAK2/STAT3 signaling pathway. The JAK2/STAT3 pathway-specific inhibitor ameliorated adverse vascular remodeling and reduced AD formation (90% vs. 55%, p &lt; 0.05) in CCDC80 knockout mice. Conclusion: CCDC80 deficiency exacerbates the progression of AD by activating the JAK2/STAT3 pathway involved in regulating the phenotype switching and function of VSMCs. Our findings suggest that CCDC80 is a potential target for the prevention and treatment of AD.

Tick-Borne Encephalitis Virus Vaccination among Tourists in a High-Prevalence Area (Italy, 2023): A Cross-Sectional Study.

Tick-borne encephalitis (TBE) represents a potential health threat for tourists in high-risk areas, including the Dolomite Mountains in northeastern Italy. The present questionnaire-based survey was, therefore, designed in order to assess knowledge, attitudes, and preventive practices (KAP) in a convenience sample of Italian tourists visiting the Dolomite Mountains, who were recruited through online discussion groups. A total of 942 participants (39.2% males, with 60.2% aged under 50) filled in the anonymous survey from 28 March 2023 to 20 June 2023. Overall, 24.1% of participants were vaccinated against TBE; 13.8% claimed to have previously had tick bites, but no cases of TBE were reported. The general understanding of TBE was relatively low; while 79.9% of participants acknowledged TBE as a potentially severe disease, its occurrence was acknowledged as high/rather high or very high in the Dolomites area by only 51.6% of respondents. Factors associated with the TBE vaccine were assessed by the calculation of adjusted odds ratios (aOR) and 95% confidence intervals through a logistic regression analysis model. Living in areas considered at high risk for TBE (aOR 3.010, 95%CI 2.062-4.394), better knowledge on tick-borne disorders (aOR 1.515, 95%CI 1.071-2.142), high risk perception regarding tick-borne infections (aOR 2.566, 95%CI 1.806-3.646), a favorable attitude toward vaccinations (aOR 3.824, 95%CI 1.774-8.224), and a tick bite(s) in a previous season (aOR 5.479, 95%CI 3.582-8.382) were characterized as being positively associated with TBE vaccination uptake. Conversely, being <50 years old (aOR 0.646, 95%CI, 0.458-0.913) and with a higher risk perception regarding the TBE vaccine (aOR 0.541, 95%CI 0.379-0.772) were identified as the main barriers to vaccination. In summary, tourists to the high-risk area of the Dolomites largely underestimate the potential occurrence of TBE. Even though the uptake of the TBE vaccine in this research was in line with European data, public health communication on TBE is required in order to improve acceptance of this effective preventive option.

Inhibition of influenza a virus infection by natural stilbene piceatannol targeting virus hemagglutinin.

Given the magnitude of influenza pandemics as a threat to the global population, it is crucial to have as many prevention and treatment options as possible. Piceatannol (PIC) is a tetrahydroxylated stilbenoid (trans-3,4,3',5'-tetrahydroxystilbene), also known as 3'- hydroxy resveratrol, which has demonstrated many different biological activities such as anti-inflammatory and antiviral activities. In this study, the anti-influenza A virus (IAV) activities and mechanisms of PIC in vitro and in vivo were investigated in order to provide reference for the development of novel plant-derived anti-IAV drugs. The viral plaque assay, RT-PCR and western blot assay were used to evaluate the anti-IAV effects of PIC in vitro. The anti-IAV mechanism of PIC was determined by HA syncytium assay, DARTS assay and Surface Plasmon Resonance assay. The mouse pneumonia model combined with HE staining were used to study the anti-IAV effects of PIC in vivo. PIC shows inhibition on the multiplication of both H1N1 and H3N2 viruses, and blocks the infection of H5N1 pseudovirus with low toxicity. PIC may directly act on the envelope of IAV to induce the rupture and inactivation of IAV particles. PIC can also block membrane fusion via binding to HA2 rather than HA1 and cleavage site of HA0. PIC may interact with the two residues (HA2-T68 and HA2-I75) of HA2 to block the conformational change of HA so as to inhibit membrane fusion. Importantly, oral therapy of PIC also markedly improved survival and reduced viral titers in IAV-infected mice. PIC possesses significant anti-IAV effects both in vitro and in vivo and may block IAV infection mainly through interaction with HA to block membrane fusion. Thus, PIC has the potential to be developed into a new broad-spectrum anti-influenza drug for the prevention and treatment of influenza.

Sacral agenesis without maternal diabetes: a case report.

Sacral agenesis is a rare congenital condition that is characterized by sacrococcygeal bone agenesis. It is associated with spinal cord anomalies as well as problems with the genitourinary system, large bowel, and lower extremities. Fetal ultrasound allows for diagnosis even before birth. The authors present the case of a 1-year-old girl with sacral agenesis type III and bilateral congenital talipes equinovarus with spina bifida who was born to a nondiabetic mother and had a normal anomaly scan. People with less severe forms of sacral agenesis can live a normal life, and it is not connected with cognitive impairment; however, concomitant bladder, colon, and lower limb disorders cause considerable morbidity. The majority of treatment is supportive, frequently requiring orthopedic, urological, gastroenterological, pediatric, and physiotherapy support. Genetic and prepregnancy counseling, as well as early screening of high-risk mothers, remain the only options for prevention of the disease since treatment is mostly supportive.

Younger dogs of specific breeds are more likely to experience a rare adverse event after administration of extended-release injectable moxidectin heartworm preventive.

To estimate the incidence of and identify patient risk factors for an acute adverse event in dogs after administration of a sustained-release injectable heartworm preventive product. Canine patients that received the injectable heartworm preventive product during routine preventive care visits. Retrospective analysis of electronic medical records of canine visits within a large network of primary care veterinary clinics in which the product was administered from January 1, 2016, through December 31, 2020. Visits during which vaccination(s) were also administered were excluded from analysis. Identification of acute adverse events was based on diagnostic entries and other clinical presentations suggestive of an adverse event within 3 days of product administration. Data were analyzed using mixed-effects logistic regression. In the 5-year study period, 1,399,289 visits with 694,030 dogs led to an incidence estimate of approximately 14.3 events/10,000 doses. Regression analysis found younger dogs and 7 breeds (relative to mixed-breed dogs) to have statistically significant greater odds of an event. Understanding of incidence and patient risk factors provides veterinary professionals and dog owners more information when deciding on heartworm preventive options for their dog when considering risk for adverse event in dogs of certain ages or breeds.

Prognostic and therapeutic potential of senescent stromal fibroblasts in prostate cancer.

The stromal component of the tumour microenvironment in primary and metastatic prostate cancer can influence and promote disease progression. Within the prostatic stroma, fibroblasts are one of the most prevalent cell types associated with precancerous and cancerous lesions; they have a vital role in the structural composition, organization and integrity of the extracellular matrix. Fibroblasts within the tumour microenvironment can undergo cellular senescence, which is a stable arrest of cell growth and a phenomenon that is emerging as a recognized hallmark of cancer. Supporting the idea that cellular senescence has a pro-tumorigenic role, a subset of senescent cells exhibits a senescence-associated secretory phenotype (SASP), which, along with increased inflammation, can promote prostate cancer cell growth and survival. These cellular characteristics make targeting senescent cells and/or modulating SASP attractive as a potential preventive or therapeutic option for prostate cancer.

Drug-induced hearing loss: Listening to the latest advances

Sensorineural hearing loss (SNHL) is the most common type of hearing loss. Causes include degenerative changes in the sensory hair cells, their synapses and/or the cochlear nerve. As human inner ear hair cells have no capacity for regeneration, their destruction is irreversible and leads to permanent hearing loss. SNHL can be genetically inherited or acquired through ageing, exposure to noise or ototoxic drugs. Ototoxicity generally refers to damage to the structures and functions of the inner ear following exposure to specific drugs. Ototoxicity can be multifactorial, causing damage to cochlear hair cells or cells with homeostatic functions that modulate cochlear hair cell function. Clinical strategies to limit ototoxicity include identifying patients at risk, monitoring drug concentrations, performing serial hearing assessments and switching to less ototoxic therapy. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the PubMed® database. The search terms "ototoxicity", "hearing loss" and "drugs" were combined. We included studies published between September 2013 and June 2023, and focused on medicines and drugs used in hospitals. The review highlighted a number of articles reporting the main drug classes potentially involved: namely, immunosuppressants, antimalarials, vaccines, antibiotics, antineoplastic agents, diuretics, nonsteroidal anti-inflammatory drugs and analgesics. The presumed ototoxic mechanisms were described, together with the therapeutic and preventive options developed over the last ten years.

Role of neutrophil / lymphocyte ratio, uric acid / albumin ratio and uric acid / creatinine ratio as predictors to severity of preeclampsia

BackgroundPre-eclampsia (PE) is an intractable obstetric disorder with high mortality and morbidity, affecting 6–8% of pregnancies worldwide. As its etiology and pathogenesis remain unclear, there are no specific prevention or treatment options. This study aimed to determine the association between neutrophil to lymphocyte ratio (NLR), uric acid to albumin ratio (UAR) and uric acid to creatinine ratio (UA/Cr) and severity of pre-eclampsia.MethodsA cross-sectional hospital-based study was conducted among pre-eclamptic women in Kosti Maternity Hospital from September to December 2022. Forty-five pre-eclamptic women were enrolled in this study and were classified according to the WHO classification of PE into mild PE (23 PE patients) and severe PE (22 PE patients). Data were collected using a semi-structured questionnaire covering medical history and clinical assessment. A blood sample was taken from each participant for measurements of the complete blood count (CBC), liver functions test (LFT) with enzymes, renal functions test (RFT) with electrolytes, and uric acid by standard techniques.ResultsNLR was found to be statistically significantly higher in mothers with severe PE (6.3–9.9) than in those with mild PE (2.2–1.5) (p-value 0.048). Alanine aminotransferase (ALT) was significantly higher in women with severe PE than in those with mild PE (p-value = 0.02). The total means of platelet-lymphocyte ratio (PLR), UA/Cr, and UAR were insignificantly higher in women with severe PE compared with those with mild PE (p-values 0.666, 0.427, and 0.525, respectively). The means of uric acid and serum creatinine showed insignificant statistical elevation in women with severe PE compared with mild PE (p-values of 0.27 and 0.44, respectively). Serum albumin was found to be insignificantly lower in mothers with severe PE (3.3 ± 0.6 g/dl) than in those with mild PE (3.6 ± 0.6 g/dl); p-value = 0.21.ConclusionsPE showed a significant statistical increase in WBC, neutrophils, alanine transaminase (ALT), and NLR in severe PE compared to mild PE and a significant statistical decrease in lymphocyte count in severe PE compared to mild PE. The measurement of NLR may be a useful laboratory marker for predicting the severity of PE.

The bidirectional associations between self-esteem and problematic eating behaviors in adolescents.

Theories propose that low self-esteem and problematic eating behaviors (PEBs) negatively impact each other. While previous studies suggested bidirectional associations between self-esteem and PEBs, they did not separate within-person from between-person associations. Therefore, this prospective study investigated the within-person bidirectional associations between self-esteem and four PEBs in adolescence, while accounting for between-person differences. We used two independent longitudinal samples of Dutch adolescents, each including three annually collected waves of data. Sample 1 consisted of 1856 adolescents (Baseline: 50.4% males; Mage = 13.79 years, SDage = 0.72), with measures of self-esteem, emotional eating, restrained eating, and loss of control (LOC) while overeating. Sample 2 consisted of 555 adolescents (Baseline: 49.7% males; Mage = 13.13 years, SDage = 0.68), with measures of self-esteem and LOC eating. The data were analyzed using random intercept cross-lagged panel models (CLPMs). Within persons, lower self-esteem was associated with higher emotional and restrained eating (both Sample 1) one year later, and vice versa. Self-esteem did not predict, nor was predicted by, LOC while overeating (Sample 1) or LOC eating (Sample 2). Between persons, self-esteem was negatively correlated with all PEBs (Samples 1 and 2). We found within-person bidirectional associations between low self-esteem and emotional and restrained eating (but not LOC while overeating/LOC eating), and between-person correlations between low self-esteem and all PEBs. These results have theoretical and practical implications. Within-person processes clarify underlying mechanisms that explain the occurrence of PEBs; between-person associations are important to identify adolescents at risk of PEBs. While theories indicate that low self-esteem and PEBs are inversely associated within individuals, empirical studies have not disentangled within-person processes from between-person differences. This study addressed this disparity, finding that lower self-esteem was bidirectionally associated with higher emotional and restrained eating (but not LOC eating) within persons. These findings suggest that enhancing self-esteem is a viable option for prevention and intervention.