Category: Nevin Manimala

Psychol Med. 2024 Oct 31:1-10. doi: 10.1017/S0033291724002526. Online ahead of print.

ABSTRACT

BACKGROUND: There is a compelling need for innovative intervention strategies for patients with affective disorders, given their increasing global prevalence and significant associated disability and impaired functioning. This study aimed to investigate whether a comprehensive multimodule individualized intervention (AWARE), targeting known mediators of functioning, improves functioning in affective disorders.

METHODS: AWARE was a randomized, controlled, rater-blind clinical trial conducted at two centers in the Capital Region of Denmark (Clinicaltrials.gov, NCT04701827). Participants were adults with bipolar disorder or major depressive disorder and impaired functioning. Participants were randomized to the six-month AWARE intervention or treatment as usual (TAU). The AWARE intervention is based on the International Classification of Functioning, Disability and Health (ICF) Brief Core Set for Bipolar and Unipolar Disorder.The primary outcome was observation-based functioning using the Assessment of Motor and Process Skills (AMPS). Secondary outcomes were functioning, QoL, stress, and cognition.

RESULTS: Between February 2021 and January 2023, 103 patients were enrolled; 50 allocated to AWARE treatment and 53 to TAU (96 included in the full analysis set). There was no statistically significant differential change over time between groups in the primary outcome (AMPS), however, both groups showed a statistically significant improvement at endpoint. The AWARE intervention had a statistically significant effect compared with TAU on secondary outcomes of patient-reported functioning, stress and cognition.

CONCLUSION: Compared with TAU, the AWARE intervention was ineffective at improving overall functioning on the primary outcome, presumably due to the short duration of the intervention. Further development of effective treatments targeting functioning is needed.

PMID:39479758 | DOI:10.1017/S0033291724002526

Curr Med Res Opin. 2024 Oct 31:1-13. doi: 10.1080/03007995.2024.2423736. Online ahead of print.

ABSTRACT

OBJECTIVES: Polyethylene glycol recombinant human granulocyte colony-stimulating factors (PEG-rhG-CSFs) are used to prevent or treat chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). This study aimed to compare the efficacy and safety of same-day versus next-day PEG-rhG-CSF administration following chemotherapy and the effects of 3 mg versus 6 mg dosages.

METHODS: We retrospectively analyzed cohort data of patients with breast cancer who underwent chemotherapy and received PEG-rhG-CSF either within 24 h (same-day group) or 24 h (next-day group) after chemotherapy. The incidences of CIN and FN were assessed in each chemotherapy cycle between the two groups. The primary endpoint was the incidence of FN in the first cycle and throughout all cycles. The secondary endpoints included the incidences of various grades of CIN (CIN1-CIN4), antibiotic use, chemotherapy regimen modifications, and overall safety.

RESULTS: Among the 2385 chemotherapy cycles with prophylactic PEG-rhG-CSF in 620 patients, 798 and 1587 cycleswere in the same-day and next-day group, respectively. No statistically significant differences were observed in the incidence of FN in the first cycle or across all cycles, CIN1-4, or adverse reactions between the two groups. However, the same-day group exhibited significantly higher rates of antibiotic use (2.88% vs. 0.42%, P = 0.03) and chemotherapy regimen modification (4.68% vs. 1.45%, P < 0.001). Subgroup analysis indicated no differences in outcomes for the 6 mg dosage, but a significantly lower incidence of CIN was observed in the same-day group receiving 3 mg (P = 0.025).

CONCLUSIONS: These findings suggest that same-day administration of PEG-rhG-CSF is as effective and safe as next-day administration in preventing FN and CIN during chemotherapy.

PMID:39479731 | DOI:10.1080/03007995.2024.2423736

Food Sci Nutr. 2024 Aug 13;12(10):7842-7853. doi: 10.1002/fsn3.4296. eCollection 2024 Oct.

ABSTRACT

Isothiocyanates (ITCs), prevalent in cruciferous vegetables, are known for their anticarcinogenic properties. Prior research has indicated that heparin can stimulate the growth of colon cancer cells. However, the implications of ITCs in the diet of cancer patients receiving heparin-based therapies have yet to be fully understood. This exploratory in vitro study examines the proliferative effects of low-molecular-weight heparin (LMWH) on human colon cancer cells and assesses the antiproliferative potential of four ITC compounds, exploring possible epidermal growth factor family of receptor tyrosine kinases (Erb-B) related mechanisms. We evaluated cell viability in HCT-116 and HT-29 cell lines following treatment with ITCs alone or combined with LMWH (20 μg/mL) at various concentrations (1-100 μM). Clonogenic and wound-healing assays were performed after 24 h of treatment with 5 μM ITCs. Additionally, messenger RNA (mRNA) and protein expression of Erb-B family genes was measured using quantitative polymerase chain reaction (qPCR) and Western blotting. Statistical analysis was conducted using analysis of variance (ANOVA) with Dunnett’s post hoc test. Results indicated that the half-maximal inhibitory concentration (IC₅₀) values for Phenylethyl isothiocyanate (PEITC), Benzyl isothiocyanate (BITC), and Sulforaphane (SFN) were lower than those of Allyl isothiocyanate (AITC) in LMWH-stimulated HCT-116 (20.77, 19.10, and 44.05 μM, respectively) and HT-29 (74.94, 26.77, and 43.49 μM, respectively). PEITC and SFN significantly reduced ErbB1 (epidermal growth factor receptor (EGFR)) and ErbB4 (receptor tyrosine-protein kinase erbB-4) expression, while BITC decreased ErbB2 (receptor tyrosine-protein kinase erbB-2) and transforming growth factor beta (TGF-β) expression in HCT-116 cells (all, p < .05). PEITC, BITC, and SFN also increased proapoptotic Bax expression and decreased the antiapoptotic B-cell lymphoma 2 (Bcl-2) expression (all, p < .05). These findings suggest that specific ITCs may mitigate cancer cell proliferation induced by LMWH in cancer therapies, highlighting their potential therapeutic efficacy.

PMID:39479720 | PMC:PMC11521738 | DOI:10.1002/fsn3.4296

Food Sci Nutr. 2024 Jul 17;12(10):7273-7286. doi: 10.1002/fsn3.4348. eCollection 2024 Oct.

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is a growing public health concern characterized by fat accumulation and severe disorders like nonalcoholic steatohepatitis (NASH), which are influenced by obesity, inflammatory processes, and metabolic pathways. This research investigates the potential of silymarin-supplemented cookies in managing NAFLD by evaluating their impact on liver enzyme activity, inflammatory markers, and lipid profiles. A clinical trial in Lahore, Pakistan, involved 64 NAFLD patients. Participants were divided into placebo and three treatment groups, with the latter receiving silymarin-supplemented cookies for 3 months. The study assessed liver enzyme levels and inflammatory markers, at baseline and after the intervention, utilizing statistical analyses to evaluate differences. The lipid profile and renal function test (RFT) were also measured at baseline and after 3 months in each group for safety assessment. After 3 months, the treatment groups indicated more significant decreases in liver enzymes compared to the placebo group (p ≤ .05). Treatment 3 showed significant reductions in alanine aminotransferase (ALT) (64.39-49.38 U/L) and aspartate aminotransferase (AST) (61.53-45.38 U/L). Treatment 3 also showed improvements in alkaline phosphatase (ALP) levels and the AST/ALT ratio. Additionally, the treatment group demonstrated a significant reduction in inflammatory markers. Treatment 3 showed a significant decrease in C-reactive protein (CRP) (6.32-3.39 mg/L) and erythrocyte sedimentation rate (ESR) (38.72-23.86 mm/h), indicating that individuals with NAFLD may benefit from the intervention’s potential benefits in lowering inflammation. The study revealed that an intervention significantly improved the inflammatory markers, liver enzymes, and lipid profiles of NAFLD participants, suggesting potential benefits for liver health.

PMID:39479680 | PMC:PMC11521666 | DOI:10.1002/fsn3.4348

Food Sci Nutr. 2024 Aug 19;12(10):7977-7988. doi: 10.1002/fsn3.4365. eCollection 2024 Oct.

ABSTRACT

Varicocele (VC) is widely recognized as a prevalent etiological factor contributing to male infertility. It has been established that the generation of reactive oxygen species (ROS) plays a significant role in the progression and development of VC. Antioxidants may regulate ROS levels in these patients. Astaxanthin (ASX) is a carotenoid compound with notable antioxidant and anti-inflammatory characteristics. The current study postulated that the administration of ASX following varicocelectomy (VCT) could potentially enhance antioxidant status and semen quality in these patients. A total of 40 infertile males with clinical VC and abnormal semen analyses were randomly assigned to take part in the current trial. For 3 months following surgery, the intervention group took ASX (6 mg/day) while the control group received a placebo. After intervention, semen parameters, _antioxidant status, _and pro-inflammatory cytokines were compared between the two groups. Regarding semen parameters, antioxidant treatment led to a significant improvement in total and progressive motility in the treatment group (p < 0.05). Additionally, ASX led to a considerable increase in the expression levels of NRF2, Keap1, SOD2, SOD3, and BCL2, though the enhancement in the expression level of SOD3 was not statistically significant (p > .05). However, ASX significantly decreased the BAX expression level (p < .05). Even though the level of total antioxidant capacity (TAC) of seminal fluid (SF) increased significantly in the treatment group (p < .05), the level of total oxidative stress (TOS) in SF did not differ substantially between treatment and control groups (p > .05). Based on inflammatory factors in SF, ASX led to a considerable reduction in levels of TNF-α, IL-1β, and IL-6 (p < .05). Our findings demonstrated that ASX treatment provides an important contribution to VCT outcomes by modulating antioxidant status and pro-inflammatory cytokines. Our results indicated that ASX may be beneficial as an adjuvant therapy for infertile men following VCT.

PMID:39479675 | PMC:PMC11521721 | DOI:10.1002/fsn3.4365

J Appl Toxicol. 2024 Oct 30. doi: 10.1002/jat.4712. Online ahead of print.

ABSTRACT

Most predictive models that use alternatives to animal experiments divide judgements into two classes with a cutoff value for each model. However, if the results of alternative methods are close to the cutoff values, the true result may be ambiguous because of variability in the data. Therefore, the OECD GL497 uses a judgement method that establishes a borderline range (BR) around a cutoff value using a statistical method. However, because there is no detailed description of how the BR is calculated, we clarified two specific points. The scale-constant correction method was used to calculate the median absolute deviation (MAD) around the median. In addition, the bottom-raised transformation method was used when the data were “0” because calculation of the BR requires that all data are logarithmic. Indeed, the BRs for the amino acid derivative reactivity assay (ADRA), interleukin-8 reporter gene assay (IL-8 Luc), and epidermal sensitization assay (EpiSensA) were calculated using data from each validation study. The results showed that the BR for ADRA and IL-8 Luc ranged from 4.1 to 5.9 and 1.25 to 1.57, respectively. Furthermore, the BRs of four genes (ATF3, GCLM, DNAJB4, and IL-8) evaluated using EpiSensA ranged from 10.71 to 21.02, 1.64 to 2.45, 1.61 to 2.52, and 3.11 to 5.16, respectively. The difference (deviation) between the lower and upper BR limits and cutoff value for each alternative method were comparable to those of the alternative methods listed in the guidelines (DPRA, KerarinoSens, and h-CLAT) and thus were considered as adequate.

PMID:39477804 | DOI:10.1002/jat.4712

Anal Chem. 2024 Oct 30. doi: 10.1021/acs.analchem.4c04691. Online ahead of print.

ABSTRACT

Dark-field microscopy (DFM) imaging based on plasmonic metal nanoparticles has garnered significant attention. Here, we exploit the susceptibility of MnO₂ to reduction to modulate the local dielectric environment of an Au nanoparticle core through the etching/antietching effects of specific targets on the encapsulated MnO₂ shell. The presence of d-penicillamine promotes MnO₂ etching, while the chelation of d-penicillamine with Cu²⁺ effectively inhibits this etching. By recording the Cu²⁺-induced color shift of scattered light from orange to bright green at the single-particle level and performing the statistical analysis of the green-to-red (G/R) values in DFM images, we achieved quantitative determination of Cu²⁺ with a wide linear range (0.1-10 μM) and a low limit of detection (4.55 nM). With the facile and reliable Cu²⁺ assay in real-world samples exemplifying the practicality of the single-particle nanoplasmonic imaging method, this work may inspire future DFM-based investigations of nanoshell etching inhibition processes.

PMID:39477797 | DOI:10.1021/acs.analchem.4c04691

Sci Bull (Beijing). 2024 Oct 21:S2095-9273(24)00765-5. doi: 10.1016/j.scib.2024.10.022. Online ahead of print.

ABSTRACT

Metal halide perovskite light-emitting diodes (PeLEDs) and large-area perovskite color conversion layers for liquid crystal display exhibit great potential in the field of illumination and display. Blade-coating method stands out as a highly suitable technique for fabricating large-scale films, albeit with challenges such as uneven nucleation coverage and non-uniformity crystallization process. In this work, we developed an in-situ characterization measurement system to monitor the perovskite nucleation, and crystallization process. By incorporating formamidine acetate (FAAc) into perovskite precursor solutions, the nucleation rate and nuclei density of perovskite were increased, leading to more uniform nucleation. In addition, we inserted a layer of [2-(9H-carbazol-9-yl)ethyl] phosphonic acid above the poly(9-vinylcarbazole) hole transport layer. This layer acts as an anchor for the perovskite nano-crystal nuclei formed in the precursor, enhancing the steric hindrance of the solute and subsequently slowing down the crystal growth rate, thereby improving crystal quality. Based on these improvements, large-area perovskite nano-polycrystalline films with significantly improved uniformity and enhanced photoluminescence quantum yield were obtained. A small-area PeLED (2 mm × 2 mm) with a maximum external quantum efficiency of 25.91% was realized, marking the highest record of PeLED prepared by blade-coating method to date. An ultra-large-area PeLED (5 cm × 7 cm) was also prepared, which is the largest PeLED prepared by the solution method reported so far.

PMID:39477787 | DOI:10.1016/j.scib.2024.10.022

Pathology. 2024 Sep 30:S0031-3025(24)00240-X. doi: 10.1016/j.pathol.2024.07.008. Online ahead of print.

ABSTRACT

The aim of this study was to determine whether the presence and extent of lymphovascular invasion (LVI) is prognostic in surgical stage I cervical squamous cell carcinoma (SCC). All available tumour slides and/or paraffin blocks from 426 patients with stage I cervical SCC treated surgically with curative intent were collected from 18 institutions and retrospectively analysed. Presence and extent of LVI (focal <5 spaces, extensive ≥5 spaces) were assessed on scanning magnification in large haematoxylin and eosin slide sets in 366 cases. Progression-free survival (PFS) was calculated as the time from surgery to first progression or death or last follow-up, whichever occurred first. Overall survival (OS) was defined as the time from surgery to death or last follow-up. Clinicopathological and statistical analyses were performed on 97 patients with the International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IA and 329 patients with stage IB SCC of the cervix. LVI, both focal and extensive, was more frequent in stage IB than in stage IA (p<0.001). Patients with stage IB carcinomas with extensive LVI had worse PFS [hazard ratio (HR) 2.86; 95% confidence interval (CI) 1.49, 5.49; p=0.005] and OS (HR 2.88; 95% CI 1.38, 6.02; p=0.012) than those with focal or no LVI. In stage IA, in contrast, the presence and extent of LVI did not associate with PFS (p=0.926) or OS. Extensive LVI was not statistically correlated with PFS and OS in substages IA1, IA2 or IB2. PFS (HR 3.7; 95% CI 1.61, 8.46; p<0.001) and OS (HR 4.18; 95% CI 1.58, 11.04; p=0.002) in stage IB1, and PFS (HR 7.78; 95% CI 0.87, 69.82; p=0.039) in stage IB3 were diminished in the presence of extensive LVI. In conclusion, in patients with FIGO stage I cervical SCC, the presence and extent of LVI has prognostic significance in stage IB carcinoma, and quantifying LVI is recommended.

PMID:39477763 | DOI:10.1016/j.pathol.2024.07.008

Pediatr Neonatol. 2024 Oct 19:S1875-9572(24)00186-4. doi: 10.1016/j.pedneo.2024.05.005. Online ahead of print.

ABSTRACT

BACKGROUND: Babies born in winter have greater incidence of developmental dysplasia of the hip (DDH) and related surgeries. How weather conditions impact hip development and how screening program reacts weather issue remain unknown. This study tests a hypothesis that winter born babies have more newborn acetabular dysplasia and laxity that is responsible of later DDH.

METHODS: Retrospective data from newborns who had hip ultrasonography in the first 3 days of life were analyzed. The Graf type IIc, III, IV (shallow acetabulum) and type D (laxity) were classified as abnormal. The association and risks of an abnormal hip were analyzed with gender, gestational age, fetal presentation, parity and external temperature of birth month and the last 3 months before birth using the Pearson chi-square test and logistic regression.

RESULTS: A total of 10962 newborns participated in hip ultrasound exams voluntarily in nurseries from 2016 to 2022. Distribution of babies with Graf type I, IIa, IIc, D, III/IV hips were 88.8%, 10%, 0.5%, 0.6%, and 0.1%, respectively. Female was the most significant factor for congenital shallow acetabulum (3.8x) and hip laxity (4x) compared to male (p < 0.001). Preterm babies had a borderline lower risk of abnormal hips (0.4x, p = 0.05). Winter season is not associated with newborn abnormal hips (p = 0.36, statistical power = 80%), but a positive correlation was noted between external temperature and incidence of abnormal hips (r = 0.62, p = 0.03). Cold weather does not have a direct internal effect in acetabular dysplasia or hip laxity at birth.

CONCLUSIONS: Babies who were born in winter were not associated with acetabular dysplasia and hip laxity at birth but had greater risks of late-diagnosed DDH and surgeries. The postnatal effects from weather should be addressed by a public awareness campaign, and hip screening may not be limited on the neonatal stage.

LEVEL OF EVIDENCE: level III, diagnostic.

PMID:39477761 | DOI:10.1016/j.pedneo.2024.05.005