Detection of SARS-CoV-2 variants in hospital wastewater in Peru, 2022. / Detección de variantes del SARS-CoV-2 en aguas residuales de hospitales en Perú, 2022.

OBJECTIVE.: To identify the presence of the SARS-CoV-2 virus in wastewater from hospitals in Peru. MATERIALS AND METHODS.: Water samples were collected from the effluents of nine hospitals in Peru during March and September 2022. SARS-CoV-2 was identified by using Illumina sequencing. Variant, lineage and clade assignments were carried out using the Illumina and Nextclado tools. We verified whether the SARS-CoV-2 variants obtained from wastewater were similar to those reported by the National Institute of Health of Peru from patients during the same period and region. RESULTS.: Eighteen of the 20 hospital wastewater samples (90%) provided sequences of sufficient quality to be classified as the Omicron variant according to the WHO classification. Among them, six (30%) were assigned by Nextclade to clades 21K lineage BA.1.1 (n=1), 21L lineage BA.2 (n=2), and 22B lineages BA.5.1 (n=2) and BA .5.5 (n=1). CONCLUSIONS.: SARS-CoV-2 variants were found in hospital wastewater samples and were similar to those reported by the surveillance system in patients during the same weeks and geographic areas. Wastewater monitoring could provide information on the environmental and temporal variation of viruses such as SARS-CoV-2.Motivation for the study. To contribute to the surveillance of environmental samples from hospital effluents in order to achieve early warning of possible infectious disease outbreaks. Main findings. The Omicron variant of the COVID-19 virus was detected in wastewater from hospitals in Puno, Cuzco and Cajamarca; these results are similar to the reports by the Peruvian National Institute of Health based on nasopharyngeal swab samples. Implications. The presence of the Omicron variant in hospital wastewater during the third wave of the pandemic should raise awareness of the treatment system before wastewater is discharged into the public sewer system.

Antidepressant class and concurrent rTMS outcomes in major depressive disorder: a systematic review and meta-analysis.

Background: Repetitive transcranial magnetic stimulation (rTMS) is frequently used as an adjunctive treatment with antidepressants for depression. We aimed to evaluate the clinical efficacy and safety of antidepressant classes when administered concurrently with rTMS for the management of major depressive disorder (MDD). Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from inception to April 12th 2024 for terms relating to medication, depression, and rTMS and appraised by 2 independent screeners. All randomized clinical trials that prospectively evaluated a specific antidepressant adjunctively with sham rTMS as a control in MDD were included. The study was registered with PROSPERO (CRD42023418435). The primary outcome measure assessed symptomatic improvement measured by formal depression scales. We used a random-effects model with pooled Standardized Mean Differences (SMDs) and log odds ratios (OR). All studies were assessed for their methodological quality and bias using the Cochrane Collaboration Risk of Bias tool version 2 (RoB2). Findings: 14 articles from 5376 identified studies were included in the systematic review and meta-analysis. There was only sufficient trial data to evaluate the effects of rTMS and combination therapy with selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs). Across studies, 848 participants (mean [SD] age:41.1 [18.7] years for SSRIs, 51.8 [3.8] years for SNRIs) prospectively examined the efficacy of antidepressant medication with rTMS. Combining rTMS with SSRIs led to significantly lower depression scores, (SMD [CI] of -0.65 [-0.98, -0.31], p = 0.0002, I2 = 66.1%), higher response (OR = 0.97 [0.50, 1.44], p < 0.0001, I2 = 25.33%) and remission rates (OR = 1.04 [0.55, 1.52], p < 0.0001, I2 = 0.00%) than medication with sham rTMS. No additive benefit was found for SNRIs with rTMS (SMD of 0.10 [-0.14, 0.34], p = 0.42, I2 = 0.00%; OR = 0.12 [-0.39, 0.62], p = 0.64, I2 = 0.00%; OR = -0.31 [-0.90, 0.28], p = 0.86, I2 = 39.9%). The overall risk of bias for the included studies ranged from low to high, with 1 study having a high risk of bias. Interpretation: The combination of rTMS with SSRIs, but not SNRIs, significantly reduced depression severity, increasing response and remission rates. Some analyses demonstrated high heterogeneity, which was influenced by an SSRI trial with a high effect size. Overall, these results suggest that not all antidepressant combination therapies are alike, and SSRIs should be considered when initiating rTMS. Funding: Donald T. Stuss Young Investigator Research Innovation Award from the Sandra Black Centre for Brain Resilience & Recovery and the Harquail Centre for Neuromodulation through the Sunnybrook Foundation.

The anti-inflammatory properties of green tea extract protect against gentamicin-induced kidney injury.

We assessed in vivo the protective effects and underlying antioxidant and anti-inflammatory properties of dry green tee extract (GTE) on glomerular and tubular kidney function and structure in an experimental model of gentamicin (GEN)-induced nephrotoxicity. Wistar rats were divided into four groups and treated daily for 10 days. The control group received distilled water; the GTE group received 20 µg/g body weight (BW) GTE by gavage; the GEN group received 100 mg/g BW GEN intraperitoneally; and the GEN+GTE group received GTE and GEN simultaneously, as described above. At the beginning and end of treatment, the serum creatinine, fractional excretion of sodium and potassium, and plasma heme oxygenase (HO)-1 levels and oxidative stress (OS) were assessed. At the end of the experiment, kidney fragments were collected for histological evaluation and immunohistochemical studies of cyclooxygenase (COX)-2 and nuclear factor (NF)kB. The levels of interleukin (IL)-1b, IL-4, IL-6, IL-10 and monocyte chemotactic protein (MCP)-1 were measured in kidney tissue. The results showed that GTE attenuated significantly kidney structural injury and prevented GEN-induced kidney functional injury (glomerular and tubular function). GTE significantly attenuated the kidney tissue increase of the proinflammatory mediators NF-kB, COX2, IL-1b and MCP-1 and significantly increased the kidney expression of the anti-inflammatory cytokines IL-6 and IL-10. However, GTE did not prevent OS increase in GEN-treated animals. In conclusion, GTE protected against GEN nephrotoxicity, likely due to direct blockade of the inflammatory cascade, which might had occurred independently of its antioxidant effect.

Anemia and intestinal parasites in Mbya Guarani children, Misiones, Argentina.

This study aimed to assess the prevalence of anemia in children of two Guarani communities in Misiones, Argentina, and to analyze its association with socioenvironmental and parasitic factors. This cross-sectional study took place in two villages, Koen Ju and Kaa Poty, and included Mbya Guarani children aged 6 months to 14 years. A multivariable analysis was performed to evaluate the association of anemia with the presence of intestinal parasites. Altogether, 162 children were included in the study: 53.1% were boys, 32.7% had low weight-for-age, and 22.2% low height-for-age. Nearly half (46.9%, n=76) had anemia, which was mainly mild (92.1%), with a few moderate cases (7.9%). Of the 109 children who underwent testing for intestinal parasites, 89 (81.7%) had at least one, and 53 (59.5%) had more than one. The main parasite was Blastocystis hominis (49.5%), followed by Entamoeba coli (47.7%), hookworms (36.7%), and Ascaris lumbricoides (31.5%). In the multivariable analysis, anemia was associated with intestinal parasitosis (adjusted odds ratio [OR] 4.24, 95% confidence interval [CI] 1.08-16.5; p=0.038) and male sex (adjusted OR 2.66; 95% CI 1.08-6.47; p= 0.01). Overall, we found that both anemia and intestinal parasites are common in the pediatric population of the Guarani ethnic group. Intestinal parasites and male sex were associated with the presence of anemia.

Bridging the Gap in Genomic Implementation: Identifying User Needs for Precision Nephrology.

Introduction: Genomic medicine holds transformative potential for personalized nephrology care; however, its clinical integration poses challenges. Automated clinical decision support (CDS) systems in the electronic health record (EHR) offer a promising solution but have shown limited impact. This study aims to glean practical insights into nephrologists' challenges using genomic resources, informing precision nephrology decision support tools. Methods: We conducted an anonymous electronic survey among US nephrologists from January 19, 2021 to May 19, 2021, guided by the Consolidated Framework for Implementation Research. It assessed practice characteristics, genomic resource utilization, attitudes, perceived knowledge, self-efficacy, and factors influencing genetic testing decisions. Survey links were primarily shared with National Kidney Foundation members. Results: We analyzed 319 surveys, with most respondents specializing in adult nephrology. Although respondents generally acknowledged the clinical use of genomic resources, varying levels of perceived knowledge and self-efficacy were evident regarding precision nephrology workflows. Barriers to genetic testing included cost/insurance coverage and limited genomics experience. Conclusion: The study illuminates specific hurdles nephrologists face using genomic resources. The findings are a valuable contribution to genomic implementation research, highlighting the significance of developing tailored interventions to support clinicians in using genomic resources effectively. These findings can guide the future development of CDS systems in the EHR. Addressing unmet informational and workflow support needs can enhance the integration of genomics into clinical practice, advancing personalized nephrology care and improving kidney disease outcomes. Further research should focus on interventions promoting seamless precision nephrology care integration.

The DNA methyltransferase DMAP1 is required for tissue maintenance and planarian regeneration.

The precise regulation of transcription is required for embryonic development, adult tissue turnover, and regeneration. Epigenetic modifications play a crucial role in orchestrating and regulating the transcription of genes. These modifications are important in the transition of pluripotent stem cells and their progeny. Methylation, a key epigenetic modification, influences gene expression through changes in DNA methylation. Work in different organisms has shown that the DNA methyltransferase-1-associated protein (DMAP1) may associate with other molecules to repress transcription through DNA methylation. Thus, DMAP1 is a versatile protein implicated in a myriad of events, including pluripotency maintenance, DNA damage repair, and tumor suppression. While DMAP1 has been extensively studied in vitro, its complex regulation in the context of the adult organism remains unclear. To gain insights into the possible roles of DMAP1 at the organismal level, we used planarian flatworms that possess remarkable regenerative capabilities driven by pluripotent stem cells called neoblast. Our findings demonstrate the evolutionary conservation of DMAP1 in the planarian Schmidtea mediterranea. Functional disruption of DMAP1 through RNA interference revealed its critical role in tissue maintenance, neoblast differentiation, and regeneration in S. mediterranea. Moreover, our analysis unveiled a novel function for DMAP1 in regulating cell death in response to DNA damage and influencing the expression of axial polarity markers. Our findings provide a simplified paradigm for studying DMAP1's function in adult tissues.

Identification and expression analysis of Phosphate Transporter 1 (PHT1) genes in the highly phosphorus-use-efficient Hakea prostrata (Proteaceae).

Heavy and costly use of phosphorus (P) fertiliser is often needed to achieve high crop yields, but only a small amount of applied P fertiliser is available to most crop plants. Hakea prostrata (Proteaceae) is endemic to the P-impoverished landscape of southwest Australia and has several P-saving traits. We identified 16 members of the Phosphate Transporter 1 (PHT1) gene family (HpPHT1;1-HpPHT1;12d) in a long-read genome assembly of H. prostrata. Based on phylogenetics, sequence structure and expression patterns, we classified HpPHT1;1 as potentially involved in Pi uptake from soil and HpPHT1;8 and HpPHT1;9 as potentially involved in Pi uptake and root-to-shoot translocation. Three genes, HpPHT1;4, HpPHT1;6 and HpPHT1;8, lacked regulatory PHR1-binding sites (P1BS) in the promoter regions. Available expression data for HpPHT1;6 and HpPHT1;8 indicated they are not responsive to changes in P supply, potentially contributing to the high P sensitivity of H. prostrata. We also discovered a Proteaceae-specific clade of closely-spaced PHT1 genes that lacked conserved genetic architecture among genera, indicating an evolutionary hot spot within the genome. Overall, the genome assembly of H. prostrata provides a much-needed foundation for understanding the genetic mechanisms of novel adaptations to low P soils in southwest Australian plants.

Breaking the mold: Insights into the clinical management and outcomes of rhinocerebral mucormycosis in adults.

Background: Rhinocerebral mucormycosis is a rare, life-threatening fungal infection that affects the sinuses, nasal passages, and brain. Its management remains challenging owing to high mortality rates. Combination antifungal therapy is an area of ongoing research aimed at improving outcomes. We aimed to describe the clinical management and outcomes of patients with rhinocerebral mucormycosis who were treated with antifungal combination therapy. Methods: This retrospective case series included 10 patients diagnosed with rhinocerebral mucormycosis at two academic medical centers between January 2008 and July 2023 who received initial antifungal therapy with liposomal amphotericin B (L-AmB), alone or in combination, within 24 h of diagnosis. Clinical data were extracted from the medical records. Results: Most patients were males (70 %) with uncontrolled diabetes (71.4 %). L-AmB was used as the initial therapy in all patients, either as monotherapy (n = 4) or combination therapy (n = 6), followed by posaconazole maintenance. The combinations included L-AmB with posaconazole (n = 4), L-AmB with micafungin (n = 3), or both (n = 3). The overall mortality rate was 50 %. Survivors had high morbidity, with median 31-day hospitalizations and 50 % readmission rate. Conclusions: Despite aggressive management, rhinocerebral mucormycosis has high mortality and morbidity rates. While combination antifungal therapy aims to improve cure rates, our case series showed higher mortality rates than monotherapy. Additional research is warranted to optimize management approaches for this devastating infection.

LIVER RESPONSE TO THE CONSUMPTION OF FRIED SUNFLOWER OIL.

Sunflower oil is one of the most commonly used fat sources in Argentina, and deep-fat frying is the popular food preparation process. The liver response of feeding a diet containing fried sunflower oil (SFOx) on growing rats was studied. Thirty-nine male weanling Wistar rats were randomly assigned to one of three diets for 8 wks: control (C), a sunflower oil (SFO) and a diet containing SFOx, both of the sunflower diets were mixed with a commercial rat chow at weight ratio of 13% (w/w). Body weight and food consumption were recorded weekly. At t=8 wk, lipid profile and glycemia were measured. Visceral adiposity was registered. Liver was weighed and preserved for histological analysis, relative fatty acid profile, fibrosis markers and oxidative status. The three diets did not alter body weights; however, the SFOx fed rats showed increased energy intake and visceral fat; therefore, in liver saturated fat content, trans fatty acids, plus other unidentified minor components, such as hydroperoxides, hydroxides, epidioxides, hydroperoxy epidioxides, hydroxylepidioxides, and epoxides, were detected. The hepatosomatic index of SFOx rats was altered and showed hepatic steatosis. SFOx rats exhibited increased liver dichlorodihydrofluorescein-diacetate and thiobarbituric acid substance levels and oxidized-proteins content. Their livers had lower relative levels of monounsaturated, polyunsaturated fatty acids and catalase activity, but matrix metalloproteinase-9 activity was unchanged. Consumption of a diet rich in fried oil during growth could induce liver damage due to steatosis, excessive lipid toxicity and the accumulation of reactive oxygen species. Further progression could lead to hepatic fibrosis.

AnNoBrainer, An Automated Annotation of Mouse Brain Images using Deep Learning.

Annotation of multiple regions of interest across the whole mouse brain is an indispensable process for quantitative evaluation of a multitude of study endpoints in neuroscience digital pathology. Prior experience and domain expert knowledge are the key aspects for image annotation quality and consistency. At present, image annotation is often achieved manually by certified pathologists or trained technicians, limiting the total throughput of studies performed at neuroscience digital pathology labs. It may also mean that simpler and quicker methods of examining tissue samples are used by non-pathologists, especially in the early stages of research and preclinical studies. To address these limitations and to meet the growing demand for image analysis in a pharmaceutical setting, we developed AnNoBrainer, an open-source software tool that leverages deep learning, image registration, and standard cortical brain templates to automatically annotate individual brain regions on 2D pathology slides. Application of AnNoBrainer to a published set of pathology slides from transgenic mice models of synucleinopathy revealed comparable accuracy, increased reproducibility, and a significant reduction (~ 50%) in time spent on brain annotation, quality control and labelling compared to trained scientists in pathology. Taken together, AnNoBrainer offers a rapid, accurate, and reproducible automated annotation of mouse brain images that largely meets the experts' histopathological assessment standards (> 85% of cases) and enables high-throughput image analysis workflows in digital pathology labs.

Malaria burden and residual transmission: two thirds of mosquito bites may not be preventable with current vector control tools on Bioko Island, Equatorial Guinea.

OBJECTIVES: This study assesses exposure to malaria vector mosquitos that is non-preventable through use of nets, the contribution of outdoor and indoor biting towards residual vector exposure, and the risk factors for being bitten and for being infected with malaria parasites on Bioko Island, Equatorial Guinea. METHODS: Human behaviour and malaria infection data were collected from 13,735 randomly selected residents during cross-sectional surveys, concomitantly with entomological human landing catches, indoors and outdoors, in 20 locations on the Island. Self-reported time of going indoors, going to bed and whether using a net were analysed to impute for each respondent the number of bites received outdoors and indoors during the night before the survey. RESULTS: On average, each person received 2.7 (95% CI 2.6 to 2.8) bites per night outdoors, 8.5 (8.3 to 8.7) bites indoors if not using a net, and 4.7 (4.5 to 4.8) bites indoors if using a net. Malaria infection was associated with more bites, regardless of whether received indoors or outdoors. Older age, male gender, not using a net, rural location and going indoors later increased the risk of being bitten. The proportion of bites not averted by using a net was estimated as 66% (61 to 71). CONCLUSIONS: A large proportion of biting, mostly indoors, may not be preventable by LLINs. Tools targeting indoor biting should be prioritised in Bioko. Novel vector control tools are urgently needed to reduce overall exposure to mosquito bites.

Identifying digital biomarkers of illness activity and treatment response in bipolar disorder with a novel wearable device (TIMEBASE): protocol for a pragmatic observational clinical study.

BACKGROUND: Bipolar disorder is highly prevalent and consists of biphasic recurrent mood episodes of mania and depression, which translate into altered mood, sleep and activity alongside their physiological expressions. AIMS: The IdenTifying dIgital bioMarkers of illnEss activity and treatment response in BipolAr diSordEr with a novel wearable device (TIMEBASE) project aims to identify digital biomarkers of illness activity and treatment response in bipolar disorder. METHOD: We designed a longitudinal observational study including 84 individuals. Group A comprises people with acute episode of mania (n = 12), depression (n = 12 with bipolar disorder and n = 12 with major depressive disorder (MDD)) and bipolar disorder with mixed features (n = 12). Physiological data will be recorded during 48 h with a research-grade wearable (Empatica E4) across four consecutive time points (acute, response, remission and episode recovery). Group B comprises 12 people with euthymic bipolar disorder and 12 with MDD, and group C comprises 12 healthy controls who will be recorded cross-sectionally. Psychopathological symptoms, disease severity, functioning and physical activity will be assessed with standardised psychometric scales. Physiological data will include acceleration, temperature, blood volume pulse, heart rate and electrodermal activity. Machine learning models will be developed to link physiological data to illness activity and treatment response. Generalisation performance will be tested in data from unseen patients. RESULTS: Recruitment is ongoing. CONCLUSIONS: This project should contribute to understanding the pathophysiology of affective disorders. The potential digital biomarkers of illness activity and treatment response in bipolar disorder could be implemented in a real-world clinical setting for clinical monitoring and identification of prodromal symptoms. This would allow early intervention and prevention of affective relapses, as well as personalisation of treatment.

Nomenclature in Palliative and Kidney Supportive Care: Not Just at the End-of-Life.

The multidimensional view of disease is fundamental in the care of complex diseases such as chronic kidney disease (CKD). It is appropriate to define and unify concepts that allow the different professionals involved in care to provide a multidisciplinary approach tailored to the needs of each individual. Given the increasing incidence of CKD worldwide and the fact that the disease may progress at different rates, there is a need to establish personalized, comprehensive approaches for each patient and their families at an earlier stage. This approach goes beyond the simple control of uremic symptoms or congestion and consists of addressing not only symptomatic but also functional, social and coping problems at an early stage, facilitating decision making both in the CKD and in acute situations, potentially irreversible or interventions that do not improve life expectancy. To ensure excellence in care, it is important to assess indicators of palliative care and kidney support, such as the presence of advance and shared care planning, the inclusion of psychosocial, ethical, spiritual and bereavement care. This enables the provision of comprehensive, humanized, and high-quality care for patients and their families. Palliative and kidney care is not just about patients in the last days of life. Defining, unifying, and evaluating the concepts will allow them to be applied in a timely manner at each specific moment of the CKD trajectory.

Sublobar resection for lung adenocarcinoma less than 2 cm containing solid or micropapillary components radiologically presented as consolidation-to-tumor ratio (CTR) ≤0.25 [ground-glass opacity (GGO)].

Background: The suitability of sublobar resection as a surgical approach for early-stage non-small cell lung cancer (NSCLC) remains unclear. This study investigated the feasibility of sublobar resection in patients with pathological-stage IA adenocarcinoma less than 2 cm characterized by a high-risk pathological subtype but exhibiting radiologically noninvasive features. Methods: We conducted a retrospective review of patients diagnosed with pathological stage IA lung adenocarcinoma who underwent surgical intervention between 2013 and 2017. The inclusion criteria included a maximum tumor diameter of 2.0 cm or less, a consolidation-to-tumor ratio (CTR) of 0.25 or less, and a histopathological confirmation of a solid or micropapillary component. Patients were categorized into sublobar resection and lobectomy groups, and propensity score matching was employed to mitigate potential confounders. The primary endpoints were lung cancer-specific survival (LCSS) and overall survival (OS). Results: The study comprised 149 patients, with 84 in the lobectomy group and 65 in the limited resection group. In the overall cohort, the 5-year LCSS was 100% for both groups, while the 5-year OS was 97.6% (95% CI: 94.41-100.00%) in the lobectomy group and 100% in the sublobar resection group (P=0.21). After propensity score matching, the LCSS remained at 100% for both groups, and the 5-year OS was 97.14% in the lobectomy group and 100% in the sublobar resection group (P=0.32). Conclusions: Based on our experience, for lung adenocarcinoma containing solid/micropapillary subtype, a size less than 2 cm, and a CTR ≤0.25, the oncological outcomes appeared to be comparable between sublobar resection and lobectomy, suggesting that sublobar resection might serve as an equivalent alternative to lobectomy for such lesions.

Lesion characteristics using high-frequency low-tidal volume ventilation versus standard ventilation during ablation of paroxysmal atrial fibrillation.

INTRODUCTION: High-frequency low-tidal-volume (HFLTV) ventilation during radiofrequency catheter ablation (RFCA) for paroxysmal atrial fibrillation (PAF) has been shown to be superior to standard ventilation (SV) in terms of procedural efficiency, acute and long-term clinical outcomes. Our study aimed to compare ablation lesions characteristics utilizing HFLTV ventilation versus SV during RFCA of PAF. METHODS: A retrospective analysis was conducted on patients who underwent pulmonary vein isolation (PVI) for PAF between August 2022 and March 2023, using high-power short-duration ablation. Thirty-five patients underwent RFCA with HFLTV ventilation and were matched with another cohort of 35 patients who underwent RFCA with SV. Parameters including ablation duration, contact force (CF), impedance drop, and ablation index were extracted from the CARTONET database for each ablation lesion. RESULTS: A total of 70 patients were included (HFLTV = 35/2484 lesions, SV = 35/2830 lesions) in the analysis. There were no differences in baseline characteristics between the groups. While targeting the same ablation index, the HFLTV ventilation group demonstrated shorter average ablation duration per lesion (12.3 ± 5.0 vs. 15.4 ± 8.4 s, p < .001), higher average CF (17.0 ± 8.5 vs. 10.5 ± 4.6 g, p < .001), and greater impedance reduction (9.5 ± 4.6 vs. 7.7 ± 4.1 ohms, p < .001). HFLTV ventilation group also demonstrated shorter total procedural time (61.3 ± 25.5 vs. 90.8 ± 22.8 min, p < .001), ablation time (40.5 ± 18.6 vs. 65.8 ± 22.5 min, p < .001), and RF time (15.3 ± 4.8 vs. 22.9 ± 9.7 min, p < .001). CONCLUSION: HFLTV ventilation during PVI for PAF was associated with improved ablation lesion parameters and procedural efficiency compared to SV.

Encoding of female mating dynamics by a hypothalamic line attractor.

Females exhibit complex, dynamic behaviors during mating with variable sexual receptivity depending on hormonal status1-4. However, how their brains encode the dynamics of mating and receptivity remains largely unknown. The ventromedial hypothalamus, ventro-lateral subdivision contains estrogen receptor type 1-positive neurons that control mating receptivity in female mice5,6. Unsupervised dynamical systems analysis of calcium imaging data from these neurons during mating uncovered a dimension with slow ramping activity, generating a line attractor in neural state space. Neural perturbations in behaving females demonstrated relaxation of population activity back into the attractor. During mating population activity integrated male cues to ramp up along this attractor, peaking just before ejaculation. Activity in the attractor dimension was positively correlated with the degree of receptivity. Longitudinal imaging revealed that attractor dynamics appear and disappear across the estrus cycle and are hormone-dependent. These observations suggest that a hypothalamic line attractor encodes a persistent, escalating state of female sexual arousal or drive during mating. They also demonstrate that attractors can be reversibly modulated by hormonal status, on a timescale of days.

Association of information technology ability, workplace social engagement, and successful ageing: validation of a short measure with three African samples.

This study examined the association of workplace social engagement (WSE) and information technology ability (ITA) with successful ageing and validated a brief scale measuring WSE. The interaction of WSE and ITA on successful ageing was also assessed. A cross-sectional design was adopted, and the participants were 1186 older adults living in Kenya (n = 350), Nigeria (n = 260), and Ghana (n = 576). Pearson's correlation and factor analyses of two datasets (i.e., waves 1 and 2) from the sample were utilised to validate the WSE scale. Hierarchical linear regression analysis with relevant sensitivity analyses were utilised to assess the associations with wave 2 data. The WSE scale produced satisfactory psychometric properties (i.e., reliability and validity) as a unidimensional measure. WSE and ITA were positively associated with successful ageing in Kenya and Ghana and in the consolidated data. The interaction between WSE and ITA was positively associated with successful ageing and its domains (i.e., illness avoidance, functioning, and engagement with life) in Kenya, Ghana, and consolidated data. At higher ITA or the use of information technologies, WSE is less strongly associated with successful ageing. WSE is more strongly associated with successful ageing only at moderate ITA.

Impact of radiological follow-up frequency on resected lung cancer: a propensity score matching analysis.

Background: Despite advances in lung cancer treatment and the subsequent improvement in oncological outcomes, the optimal frequency of radiological follow-up remains unclear. Current recommendations lack consensus and do not consider individual patient characteristics and tumor factors. This study aimed to examine the impact of radiological follow-up frequency on oncological outcomes following lung cancer resection. Methods: A prospective multicenter study, involving patients who underwent anatomical lung resection in the GEVATS database between December 2016 and March 2018. The relationship between surveillance frequency and oncological outcomes was evaluated. Two groups were established based on follow-up frequency: low frequency (LF) and high frequency (HF). Subgroup analyses were performed based on tumor stage, histology, lymphadenectomy, and adjuvant therapy. Propensity score matching (PSM) was applied to balance the groups. Results: A total of 1,916 patients were included in the study, LF 444 (23.17%), HF 1,472 (76.83%). Factors associated with HF surveillance included higher stage, adjuvant chemotherapy and adjuvant radiotherapy. Subanalyses were performed after PSM for various factors, revealing significant differences between LF and HF groups in cancer-specific survival among who received adjuvant therapy {LF 53.021 months [95% confidence interval (CI): 48.622-57.421] vs. HF 58.836 months (95% CI: 55.343-62.330); HR 0.453, 95% CI: 0.242-0.849; P=0.013}, as well as overall survival for patients with squamous cell carcinoma [LF 54.394 months (95% CI: 51.424-57.364) vs. HF 61.578 months (95% CI: 59.091-64.065); HR 0.491, 95% CI: 0.299-0.806; P=0.005] and those who received adjuvant therapy LF 50.176 months [95% CI: 45.609-54.742) vs. HF 57.189 months (95% CI: 53.599-60.778); HR 0.503, 95% CI: 0.293-0.865; P=0.013]. Conclusions: Findings suggest that high-frequency surveillance only improves survival outcomes in lung cancer patients who received adjuvant treatment or had squamous cell carcinoma. Therefore, future guidelines for lung cancer follow-up should consider individualizing the frequency of radiological surveillance based on patients' risk profiles.

Copper Overload Increased Rat Striatal Levels of Both Dopamine and Its Main Metabolite Homovanillic Acid in Extracellular Fluid.

Copper is a trace element whose electronic configuration provides it with essential structural and catalytic functions. However, in excess, both its high protein affinity and redox-catalyzing properties can lead to hazardous consequences. In addition to promoting oxidative stress, copper is gaining interest for its effects on neurotransmission through modulation of GABAergic and glutamatergic receptors and interaction with the dopamine reuptake transporter. The aim of the present study was to investigate the effects of copper overexposure on the levels of dopamine, noradrenaline, and serotonin, or their main metabolites in rat's striatum extracellular fluid. Copper was injected intraperitoneally using our previously developed model, which ensured striatal overconcentration (2 mg CuCl2/kg for 30 days). Subsequently, extracellular fluid was collected by microdialysis on days 0, 15, and 30. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and noradrenaline (NA) levels were then determined by HPLC coupled with electrochemical detection. We observed a significant increase in the basal levels of DA and HVA after 15 days of treatment (310% and 351%), which was maintained after 30 days (358% and 402%), with no significant changes in the concentrations of 5-HIAA, DOPAC, and NA. Copper overload led to a marked increase in synaptic DA concentration, which could contribute to the psychoneurological alterations and the increased oxidative toxicity observed in Wilson's disease and other copper dysregulation states.