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Effects of orally administered clioquinol on the fecal microbiome of horses

J Vet Intern Med. 2025 Jan-Feb;39(1):e17276. doi: 10.1111/jvim.17276.

ABSTRACT

BACKGROUND: Whereas restoration of fecal consistency after treatment with clioquinol for chronic diarrhea and free fecal water syndrome has been attributed to its antiprotozoal properties, actions of clioquinol on the colonic bacterial microbiota have not been investigated.

OBJECTIVES: Characterize the dynamics of fecal microbial diversity before, during, and after PO administration of clioquinol to healthy horses.

STUDY DESIGN: Experimental prospective cohort study using a single horse group.

METHODS: Eight healthy adult horses received PO clioquinol (10 g, daily) for 7 days. Feces were obtained daily for 7 days before, during, and after conclusion of treatment, and again 3 months later. Libraries of 16S rRNA V4 region amplicons generated from fecal DNA were sequenced using the Illumina sequencing platform. Bioinformatic analysis was undertaken with QIIME2 and statistical analyses included analysis of variance (ANOVA) and permutational multivariate ANOVA (PERMANOVA).

RESULTS: The richness and composition of the fecal microbiome was altered after administration of clioquinol, reaching a maximum effect by the fifth day of administration. Changes included a 90% decrease in richness, and compensatory expansion of facultative anaerobes including Streptococcaceae, Enterococcaceae, and Enterobacteriaceae. Multiple horses had Salmonella cultured from feces.

MAIN LIMITATIONS: Limitations including lack of control group and modest sample size are obviated by robust longitudinal study design and strong effect size associated with drug exposure.

CONCLUSIONS: Clioquinol has broad-spectrum antibacterial effects on the fecal microbiome of horses, but spares certain bacterial families including several pathogens and pathobionts. Clioquinol should be used with caution in horses, in an environment free of contamination with fecal pathogens.

PMID:39709594 | DOI:10.1111/jvim.17276

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Relationships between blood cadmium concentration and risk of nine cancers: evidence from the NHANES 1999-2018 and Mendelian randomization analyses

Discov Oncol. 2024 Dec 22;15(1):823. doi: 10.1007/s12672-024-01692-9.

ABSTRACT

BACKGROUND: Previous observational studies examining the relationship between cadmium exposure and various cancers have yielded conflicting results. This study aims to comprehensively clarify the relationship between blood cadmium concentration (BCC) and nine specific cancers.

METHODS: A retrospective analysis of National Health and Nutrition Examination Survey (NHANES) 1999-2018 identified 36,991 participants. Multivariable logistic regression was used to assess the association between BCC and the risk of nine specific cancers. Additionally, Mendelian randomization (MR) analyses were conducted to investigate potential causal relationships.

RESULTS: Multivariable logistic regression analysis of the NHANES data indicated a positive association between BCC and the risk of bladder and lung cancers (P < 0.05) and a negative association with the risk of kidney and prostate cancers (P < 0.05). The MR analyses demonstrated a causal relationship between BCC and kidney cancer (P < 0.05). Additionally, it uncovered causal associations with breast, cervical, and colon cancers (P < 0.05).

CONCLUSION: Elevated BCC was associated with an increased risk of bladder and lung cancers while demonstrating an inverse relationship with kidney and prostate cancers. MR analysis revealed that cadmium exposure may act as a protective factor against breast, cervical, colon, and kidney cancers, that must be confirmed with new studies.

PMID:39709583 | DOI:10.1007/s12672-024-01692-9

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Prognostic value of HER2 2 + expression in patients with TNBC receiving adjuvant capecitabine

Clin Transl Oncol. 2024 Dec 22. doi: 10.1007/s12094-024-03812-x. Online ahead of print.

ABSTRACT

BACKGROUND: In triple-negative breast cancer (TNBC) patients receiving adjuvant capecitabine, the impact of HER2 expression on survival outcomes is unclear.

METHODS: Between June 2017 and December 2023, 112 patients with TNBC who received adjuvant capecitabine due to residual masses after neoadjuvant chemotherapy (NACT) in three hospitals were identified. HER2 is analyzed through immunohistochemistry (IHC) and/or in situ hybridization in the core biopsy and/or post-surgical histopathologies. Relapse-free survival (RFS) and overall survival (OS), according to HER2 expression (0, 1 + , 2 +) status, were calculated (Kaplan-Meier method).

RESULTS: Seventy-eight (69.6%) patients had HER2 zero, 20 (17.9%) patients had HER2 + 1, and 14 (12.5%) patients had HER2 + 2/ISH- BC. The 5-year OS was 62.6%, and the 5-year RFS was 55.8%. HER2 2 + expression was associated with worse OS (27.5 vs. 84.5 months; HR 4.82, 95% CI 2.15-10.80, p < 0.001) and worse RFS (11.90 months vs. not reached; HR 4.30, 95% CI 2.06-8.99, p < 0.001) compared with HER2 0/1 + expression. The 5-year OS rates were 32.7% and 72.1%, and the 5-year RFS rates were 30.6% and 64.7% in the HER2 2 + and HER2 0/1 + groups, respectively. No statistically significant differences were detected in clinicopathologic features or pathologic responses to NACT according to the HER2 expression level.

CONCLUSIONS: Despite the use of the adjuvant capecitabine in HER2 2 + TNBC patients, these poor results will pave the way for further investigations of anti-HER2 therapeutic agents in adjuvant treatment.

PMID:39709575 | DOI:10.1007/s12094-024-03812-x

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Detection of Phage’s Lytic Activity Against Carbapenemase-Producing Klebsiella pneumoniae Isolates Using a High-Throughput Microbroth Growth Inhibition Assay

Infect Dis Ther. 2024 Dec 22. doi: 10.1007/s40121-024-01092-0. Online ahead of print.

ABSTRACT

INTRODUCTION: The host range of phages is usually assessed with the agar overlay method. However, this method is both cumbersome and subjective. Therefore, a microbroth assay was developed to assess host range and lytic activity patterns of phages in the agar overlay method against a collection of carbapenemase-producing Klebsiella pneumoniae (CRKP) isolates.

METHODS: The host range of 11 K. pneumoniae-specific phages against 8 non-repetitive well-characterized CRKP isolates was assessed with the agar overlay method and a microbroth assay by monitoring optical density (OD) at 630 nm for 24 h at different phage concentrations (5 × 109-5 × 103 PFU/ml) and two bacterial inocula (5 × 106 and 5 × 108 CFU/ml). The lytic activity of phage-bacteria pairs with transparent/semi-transparent (N = 7), turbid (N = 6), and no (N = 6) lysis in overlay agar method was compared statistically with the growth inhibition at 6 and 24 h in the microbroth assay with analysis of variance (ANOVA), receiver operating characteristic curves (ROC) curves and Fisher’s exact test. Optimal cutoffs were determined, and sensitivity and specificity were calculated.

RESULTS: Statistically significant differences of growth inhibition at 6 and 24 h for phage concentrations ≥ 5 × 108 PFU/ml for both inocula were found between phages with transparent/semi-transparent, turbid, and no lysis. ROC curve analysis indicated an optimal growth inhibition cutoff of ≥ 31% at high phage and bacteria concentrations for detecting phages with lysis and ≥ 61% at high-phage and low-bacteria concentrations for detecting phages with transparent/semi-transparent lysis with sensitivity/specificity 100%/100% and 100%/86%, respectively.

CONCLUSIONS: The microbroth growth inhibition assay provided fast, reliable, and objective results for K. pneumoniae phage host-range lytic activity differentiating different patterns of lysis in a high-throughput format.

PMID:39709574 | DOI:10.1007/s40121-024-01092-0

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Lost working time due to ill health in Hungary in 2021

Orv Hetil. 2024 Dec 22;165(51):2026-2032. doi: 10.1556/650.2024.33205. Print 2024 Dec 22.

ABSTRACT

Bevezetés: A munkavállalók egészségének megromlása a munkáltatók számára csökkent teljesítményt, a munkavállalóknak alacsonyabb jövedelmet jelent, az országnak növekvő egészségügyi kiadásokat okoz. Célkitűzés: Az egészség megromlása miatt fellépő 2021. évi munkaidő-veszteség, annak nemi különbségeinek, illetve 2019-hez viszonyított változásának, továbbá a magyar értékek más országokéitól való eltérésének vizsgálata. Módszer: A 30–64 éves korosztályban a munkaidő-veszteség a korlátozottság és az „idő előtti” halálozás miatt 2021-ben elveszett munkanapok számával, illetve az elhunytaknak a nyugdíjkorhatárig elveszett évei számával került elemzésre. A korlátozottsági és a halálozási adatok a Global Burden of Disease Study adatbázisából származnak; felhasználásra kerültek még a Központi Statisztikai Hivatal és az Eurostat népességi, illetve halálozási adatai. A magyar adatokat a visegrádi országok és Ausztria megfelelő értékeivel vetette össze a tanulmány. Eredmények: 2021-ben a 30–64 évesek minden 7. munkanapja kiesett, azaz 37 munkanapon egyáltalán nem tudtak dolgozni. Emellett a nyugdíjig ledolgozható, több mint 117 ezer év is elveszett. Nőknél a korlátozottság, férfiaknál inkább a halálozás okozta a munkaidő-veszteséget. 2019-hez képest az egy főre számított kiesett munkanapok 7%-kal, a halálozás jövőbeli veszteségei 40%-kal növekedtek. Magyarország a korlátozottság miatt elveszett napok számában a többi országhoz hasonló értéket mutatott, de a halálozások száma a többiekhez képest jóval nagyobb volt. Megbeszélés: A korlátozottság női többlete és a halálozás férfitúlsúlya mögött a betegségekhez való eltérő viszonyulás feltételezhető: a férfiak jobbnak tartják egészségüket, emiatt ritkábban vesznek igénybe egészségügyi ellátást. A más országokhoz képest kiemelkedő magyar halálozás a megelőzés és az orvosi ellátás gyengébb voltára utal. A megelőzhető és az orvosi beavatkozással elkerülhető halálozás nagy aránya jórészt az egészségügyi rendszer működésének hiányosságaira, és nem az orvoshoz fordulási kisebb hajlandóságra vezethető vissza. Következtetés: Az eredmények rámutatnak, hogy a munkaidő-veszteségek csökkentése nemenként eltérő megközelítést igényel. A veszteségek enyhítéséhez a népegészségügyi és az orvosi ellátás javulása szükséges. Az ország versenyképességének növeléséhez továbbá elengedhetetlenek az egészséges életmód előmozdítását és az azt támogató környezet kialakítását célzó intézkedések is. Orv Hetil. 2024; 165(51): 2026–2032.

PMID:39709572 | DOI:10.1556/650.2024.33205

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PI-RADS in Predicting csPCa: A Comparison Between Academic and Nonacademic Centers

Prostate. 2024 Dec 22. doi: 10.1002/pros.24832. Online ahead of print.

ABSTRACT

INTRODUCTION: The introduction of multiparametric prostate magnetic resonance imaging (mpMRI) has revolutionized prostate cancer (PCa) diagnosis, enhancing the localization of clinically significant prostate cancer (csPCa) and guiding targeted biopsies. However, significant disparities in the execution, interpretation, and reporting of prostate MRI examinations across centers necessitate greater standardization and accuracy. This study compares the diagnostic efficacy of mpMRI from academic and nonacademic centers in detecting csPCa and identifies factors associated with csPCa detection.

MATERIALS AND METHODS: Between July 2018 and October 2023, we prospectively followed 810 men at SS. Annunziata Hospital of Chieti who underwent MRI/US fusion biopsies due to elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE). Patients with mpMRI-documented suspicious lesions classified as PI-RADS ≥ 3 were included. Patients were divided into two groups based on the source of their mpMRI (academic or nonacademic centers). All biopsies were conducted using the MRI/US fusion technique. Clinical, mpMRI, and pathological data were collected and analyzed. Statistical analyses were performed using R software.

RESULTS: The cohort included 354 patients from academic centers and 456 from nonacademic centers. There were no significant differences in patient demographics, such as age and PSA levels, between the groups. Patients at academic centers were more likely to receive a higher number of elevated PI-RADS scores compared to those at nonacademic centers (PI-RADS > 3: 72.6% vs. 62.3%, p = 0.003). Histopathological analysis revealed no significant differences in the ISUP grade distribution between groups. Increased age, PSA levels, and positive DRE were significantly associated with higher odds of detecting csPCa. Median PSA density was significantly higher in patients with csPCa compared to those without csPCa (0.14 vs. 0.11 ng/mL/cm³, p < 0.001). Academic centers exhibited a higher odds ratio for csPCa detection in patients with PI-RADS scores > 3 compared to nonacademic centers.

CONCLUSION: Our study highlights significant variability in PI-RADS score assignments between academic and nonacademic centers, affecting csPCa detection rates. This variability underscores the need for greater standardization in PI-RADS scoring to reduce disparities and improve diagnostic uniformity across centers.

PMID:39709541 | DOI:10.1002/pros.24832

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Radiological Sublingual Space Invasion in Tongue Squamous Cell Carcinoma: Clinicopathological Associations and Impact on Survival

Otolaryngol Head Neck Surg. 2024 Dec 22. doi: 10.1002/ohn.1097. Online ahead of print.

ABSTRACT

OBJECTIVES: We investigate if sublingual space invasion (SLI) determined on magnetic resonance imaging confers differences in clinicopathological manifestations and treatment outcomes of oral tongue squamous cell carcinoma (OTSCC).

STUDY DESIGN: Retrospective cohort study.

SETTING: Tertiary Academic Medical Center.

METHODS: 221 OTSCC patients were included. Cox regression models and Kaplan-Meier methods were used, and nomogram construction was performed, incorporating SLI with other adverse factors, to predict the prognosis.

RESULTS: On multivariable analysis, the following were associated with cervical nodal metastasis: (1) greater MRI T classification of T3/T4 versus T1/T2: adjusted odds ratio (aOR) 2.784, 95% CI = 1.459 to 5.313, P = .001; (2) gender (female vs male): aOR 4.117, 95% CI = 1.602 to 10.576, P = .003; (3) presence of MRI-determined SLI: aOR 2.588, 95% CI = 1.393 to 4.808, P = .002. For survival outcomes, extranodal extension (adjusted hazard ratio [aHR]: 3.380, 95% CI = 2.024-5.644, P < .001), poorly-differentiated type (aHR: 1.720, 95% CI = 1.006-2.943, P = .047), lymphovascular invasion (aHR: 2.100, 95% CI = 1.220-3.614, P = .007), and SLI (aHR: 1.700, 95% CI = 1.086-2.661, P = .020) were statistically significant prognosticators of disease-free survival. In overall survival, when controlled for age, gender, overall TNM stage, Charlson morbidity index, surgical margins, depth of invasion and adjuvant therapy, SLI was a statistically significant prognosticator (aHR: 1.622, 95% CI = 1.012-2.602, P = .044). A proposed novel nomogram for overall survival combining SLI and other risk factors showed a higher concordance index compared to a nomogram with TNM staging alone (0.783 vs 0.629, P < .001).

CONCLUSION: SLI is an independent prognostic factor for treatment outcomes in OTSCC. Incorporating SLI into a novel nomogram demonstrated improved predictive accuracy for post-treatment outcomes.

PMID:39709539 | DOI:10.1002/ohn.1097

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Assessing attitudes toward seeking psychological professional help among adolescents: the roles of demographics and self-esteem

BMC Psychol. 2024 Dec 21;12(1):772. doi: 10.1186/s40359-024-02294-4.

ABSTRACT

BACKGROUND: Various factors associated with attitudes toward the utilization of professional psychological help among the school-going population have been explored, but studies from Arabian Gulf countries are lacking. This study aimed to assess attitudes toward seeking professional psychological help, examine how demographic factors and self-esteem are associated with seeking psychological help, and understand the interaction between these variables.

METHODS: A cross-sectional correlational design was used. A random sample of Omani secondary school students (n = 2165) aged 15-18 years completed the demographics sheet, the Scale of Attitudes Toward Seeking Professional Psychological Help (SATSPH), and the Rosenberg self-esteem scale. Hierarchical regression analysis with interaction was performed to test the moderating role of self-esteem in the relationship between selected demographics and attitudes toward seeking professional psychological help (ATSPH).

RESULTS: Most of the adolescents exhibited poor attitudes toward ATSPH. The findings demonstrated a significant moderating effect of self-esteem on the relationship between demographics (sex and age) and ATSPH (ΔR 2 = 0.002, F (7, 2156) = 4.839, p < 0.001). In terms of sex, women may have more positive attitudes toward seeking help than men. However, when self-esteem is considered, the positive effect of being female can reverse at higher levels of self-esteem, suggesting that men with higher self-esteem may have more positive attitudes toward seeking help than women with higher self-esteem. Furthermore, initially, age was not significant. However, when self-esteem was introduced as a moderator, age was a significant predictor. These findings indicate that the effect of age on seeking professional psychological help is influenced by self-esteem.

CONCLUSIONS: This study highlights that attitudes toward seeking professional psychological help among Omani adolescents are generally poor and are influenced by both demographic factors and self-esteem. Although women tend to have more positive attitudes than men do, this can change with varying levels of self-esteem. Similarly, the effect of age on these attitudes is dependent on self-esteem levels. This underscores the complex interplay between demographic factors and self-esteem in shaping attitudes toward psychological help-seeking behaviors. Therefore, more studies of this nature are warranted.

PMID:39709498 | DOI:10.1186/s40359-024-02294-4

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Impact on fluid balance of an optimized restrictive strategy targeting non-resuscitative fluids in intensive care patients with septic shock: a single-blind, multicenter, randomized, controlled, pilot study

Crit Care. 2024 Dec 21;28(1):429. doi: 10.1186/s13054-024-05155-z.

ABSTRACT

BACKGROUND: In septic shock, the classic fluid resuscitation strategy can lead to a potentially harmful positive fluid balance. This multicenter, randomized, single-blind, parallel, controlled pilot study assessed the effectiveness of a restrictive fluid strategy aiming to limit daily volume.

METHODS: Patients 18-85 years’ old admitted to the ICU department of three French hospitals were eligible for inclusion if they had septic shock and were in the first 24 h of vasopressor infusion. Exclusion criteria were acute kidney injury requiring renal replacement therapy, end stage chronic kidney disease, and severe malnutrition. Patients were electronically randomized 1:1 to either an optimized fluid restriction (reducing fluid intake as much as possible in terms of maintenance fluids and fluids for drug dilution during the first 7 days) or standard fluid strategy. The primary outcome was cumulative fluid balance (ml/kg) in the first 5 days. Patients and statisticians were blinded to group arm, but not clinicians.

RESULTS: Between September 2021 and February 2023, 1201 patients were screened and 50 included, with two in the control group withdrawing, thus 48 patients were analyzed (24 in each group). In the first 5 days, the optimized restrictive strategy and control groups received 89.7 (IQR 35; 128.9) and 114.3 (IQR 78.8; 168.5) ml/kg of fluid, respectively (mean difference: 35.9 ml/kg [0.0; 71.8], p = 0.0506). After 5 days, the median cumulative fluid balance was 6.9 (IQR – 13.7; 52.1) and 35.0 (IQR – 7.9; 40.2) ml/kg in the optimized restrictive strategy and control groups, respectively (absolute difference 13.2 [95%CI – 15.2; 41.6], p = 0.42). After 28 days, mortality and the numbers of days alive without life support were similar between groups. The main adverse events were severe hypernatremia in 1 and 2 patients in the fluid restriction strategy and control groups, respectively, and acute kidney injury KDIGO 3 in 4 and 7 patients in the fluid restriction strategy and control groups, respectively.

CONCLUSIONS: In ICU patients with septic shock, an optimized restrictive fluid strategy targeting hidden fluid intakes did not reduce the overall fluid balance at day 5. Trial registration ClinicalTrials.gov identifier NCT04947904, registered on 1 July 2021.

PMID:39709493 | DOI:10.1186/s13054-024-05155-z

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Factor structure of the HIV-SM LMIC self-management questionnaire for people living with HIV in low- and middle-income countries

AIDS Res Ther. 2024 Dec 21;21(1):97. doi: 10.1186/s12981-024-00676-7.

ABSTRACT

INTRODUCTION: Despite the need for reliable questionnaires to monitor self-management in chronic disease patients, such tools are lacking in developing countries. This study aims to pilot and assess the construct validity of the HIV-SM LMIC questionnaire.

METHOD: The validation of the HIV-SM LMIC questionnaire involved two cross-sectional studies in Ethiopia. The first round, for exploratory factor analysis (EFA), included 261 patients, while the second round, for confirmatory factor analysis (CFA), included 300 patients. Data was collected using the Kobo Collect electronic data entry template.

RESULT: The sample adequacy test showed a good value of 0.82. In the first round, 6 of the 32 items were not loaded, forming three factors in the EFA. Four of these items were dropped, but two (PSMB2 and PSMB12) were retained for their content. In the second round, CFA on the remaining 28 items led to dropping 8 more items due to conceptual overlap, resulting in a 20-item questionnaire. The final items were structured into three dimensions: awareness and well-being (4 items), self-regulation (6 items), and self-management practices (10 items).

CONCLUSION: The study refined the original 32-item HIV-SM LMIC questionnaire to a validated 20-item, three-dimensional tool with an acceptable goodness of fit. The authors recommend further cross-cultural and predictive validation and adaptation for newly diagnosed HIV patients, those with poor treatment outcomes.

PMID:39709486 | DOI:10.1186/s12981-024-00676-7