Cationic Liposomes Carrying HPV16 E6-siRNA Inhibit the Proliferation, Migration, and Invasion of Cervical Cancer Cells.

The E6 and E7 oncoproteins of high-risk types of human papillomavirus (HR-HPV) are crucial for the development of cervical cancer (CC). Small interfering RNAs (siRNAs) are explored as novel therapies that silence these oncogenes, but their clinical use is hampered by inefficient delivery systems. Modification (pegylation) with polyethylene glycol (PEG) of liposomal siRNA complexes (siRNA lipoplexes) may improve systemic stability. We studied the effect of siRNA targeting HPV16 E6, delivered via cationic liposomes (lipoplexes), on cellular processes in a cervical carcinoma cell line (CaSki) and its potential therapeutic use. Lipoplexes-PEG-HPV16 E6, composed of DOTAP, Chol, DOPE, and DSPE-PEG2000 were prepared. The results showed that pegylation (5% DSPE-PEG2000) provided stable siRNA protection, with a particle size of 86.42 ± 3.19 nm and a complexation efficiency of over 80%; the siRNA remained stable for 30 days. These lipoplexes significantly reduced HPV16 E6 protein levels and restored p53 protein expression, inhibiting carcinogenic processes such as proliferation by 25.74%, migration (95.7%), and cell invasion (97.8%) at concentrations of 20 nM, 200 nM, and 80 nM, respectively. In conclusion, cationic lipoplexes-PEG-HPV16 E6 show promise as siRNA carriers for silencing HPV16 E6 in CC.

Complications and adverse events in lymphadenectomy of the inguinal area: worldwide expert consensus.

BACKGROUND: Inguinal lymph node dissection plays an important role in the management of melanoma, penile and vulval cancer. Inguinal lymph node dissection is associated with various intraoperative and postoperative complications with significant heterogeneity in classification and reporting. This lack of standardization challenges efforts to study and report inguinal lymph node dissection outcomes. The aim of this study was to devise a system to standardize the classification and reporting of inguinal lymph node dissection perioperative complications by creating a worldwide collaborative, the complications and adverse events in lymphadenectomy of the inguinal area (CALI) group. METHODS: A modified 3-round Delphi consensus approach surveyed a worldwide group of experts in inguinal lymph node dissection for melanoma, penile and vulval cancer. The group of experts included general surgeons, urologists and oncologists (gynaecological and surgical). The survey assessed expert agreement on inguinal lymph node dissection perioperative complications. Panel interrater agreement and consistency were assessed as the overall percentage agreement and Cronbach's α. RESULTS: Forty-seven experienced consultants were enrolled: 26 (55.3%) urologists, 11 (23.4%) surgical oncologists, 6 (12.8%) general surgeons and 4 (8.5%) gynaecology oncologists. Based on their expertise, 31 (66%), 10 (21.3%) and 22 (46.8%) of the participants treat penile cancer, vulval cancer and melanoma using inguinal lymph node dissection respectively; 89.4% (42 of 47) agreed with the definitions and inclusion as part of the inguinal lymph node dissection intraoperative complication group, while 93.6% (44 of 47) agreed that postoperative complications should be subclassified into five macrocategories. Unanimous agreement (100%, 37 of 37) was achieved with the final standardized classification system for reporting inguinal lymph node dissection complications in melanoma, vulval cancer and penile cancer. CONCLUSION: The complications and adverse events in lymphadenectomy of the inguinal area classification system has been developed as a tool to standardize the assessment and reporting of complications during inguinal lymph node dissection for the treatment of melanoma, vulval and penile cancer.

Measures of performance validity for Hispanic/Latin American adults: A PRISMA systematic review.

Objective: Use of performance validity tests (PVTs) to assess suboptimal performance has become a recommended feature in neuropsychological evaluations. However, most of the literature has examined the utility of PVTs in primarily non-Hispanic White, monolingual English-speaking samples. Given the continual growth of culturally and linguistically diverse (CALD) populations, especially Hispanic/Latin Americans (H/Ls), it is necessary to provide an updated review on the available literature involving the use of PVTs in H/L adults. Methods: We conducted a systematic review that examined the available literature surrounding use of performance validity measures in H/L adults. This review identified evidence for the utility of PVTs in assessing invalid performance in H/Ls and compiled psychometric properties related to these measures, specifically rates of specificity and sensitivity when available. Results: We identified six standalone and four embedded performance validity measures that have been examined in H/Ls. The Test of Memory Malingering (TOMM) was identified as the PVT most studied in various H/L heritage groups. Across the studies reviewed, adjustments to cutoff scores are generally recommended for the majority of PVTs discussed. Within H/Ls, specificity rates tend to be bolstered when sociocultural factors, like education, are considered. Conclusions: Recommended cutoff scores across the different PVTs reviewed are not typically suitable for use in heritage groups of H/L adults, especially in groups that include adults with lower levels of education and literacy. Therefore, education may need to be considered when applying cutoffs to these populations.

Optimal outbreeding is shaped during larval life-history in the splash pool copepod Tigriopus californicus.

Inbreeding and outbreeding depression are dynamic forms of selection critical to mating system evolution and the efficacy of conservation biology. Most evidence on how the relative severity and timing of these forces are shaped is confined to self-fertilization, distant outcrossing, and intermediate 'optimal outcrossing' in hermaphrodites. We tested the notion that closed population demographics may reduce and delay the costs of inbreeding relative to distant outbreeding in an intertidal copepod with separate sexes and a biphasic larval / post-metamorphic life-history (Tigriopus californicus). At three lifecycle stages (fecundity, metamorphosis, and post-metamorphosis), we quantified the effects of inbreeding and outbreeding in crosses with varying degrees of recent common ancestry. Although inbreeding and outbreeding depression have distinct genetic mechanisms, both manifested the same stage-specific consequences for fitness. Inbreeding and outbreeding depression were not apparent for fecundity, post-metamorphic survival, sex ratio, or the ability to acquire mates, but inbreeding between full siblings and outbreeding between interpopulation hybrids reduced the fraction of offspring that completed metamorphosis by 32% and 47%, respectively. On average, the effects of inbreeding on metamorphic rate were weaker and nearly twice as variable among families than those of outbreeding, suggesting genetic load was less pervasive than the incompatibilities accrued between divergent populations. Overall, our results indicate the transition from larval to juvenile life stages is markedly susceptible to both inbreeding and outbreeding depression in T. californicus. We suggest stage-specific selection acting concurrently with the timing of metamorphosis may be an instrumental factor shaping reproductive optima in species with complex life-histories.

LPS-induced whole-blood cytokine production and depressive symptoms in dementia spousal caregivers: The moderating effect of childhood trauma.

Dementia spousal caregivers are at risk for adverse mental and physical health outcomes. Caregiver burden, anticipatory grief, and proinflammatory cytokine production may contribute to depressive symptoms among caregivers. People who report childhood trauma are more likely to have exaggerated stress responses that may also contribute to depressive symptoms in adulthood. This study aimed to test whether the relationship between whole-blood cytokine production and depressive symptoms is strongest in caregivers who report high levels of childhood trauma. METHODS: A sample of 103 dementia spousal caregivers provided self-report data on demographics, health information, caregiver burden, anticipatory grief, and depressive symptoms. We also determined lipopolysaccharide-induced whole-blood cytokine production as the primary measure of immune cell reactivity. We measured interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) and converted z-scores of each cytokine into a composite panel. We regressed depressive symptoms on proinflammatory cytokine production, caregiver burden, and anticipatory grief, adjusting for demographic and health-related covariates. RESULTS: Whole-blood cytokine production and childhood trauma were associated with depressive symptoms. Childhood trauma moderated the relationship between whole-blood cytokine production and depressive symptoms. Whole-blood cytokine production was only associated with depressive symptoms at mean and high levels of childhood trauma, but not at low levels of childhood trauma. The main effects of burden and anticipatory grief on depressive symptoms were strongest for caregivers reporting high levels of childhood trauma. DISCUSSION: Childhood trauma has lasting impacts on psychosocial experiences later in life and has effects that may confer susceptibility to inflammation-related depression. Our findings contribute to ongoing efforts to identify risk factors for adverse mental health in dementia spousal caregivers.

Development of the Telephone-based Daily Instrumental Activities of Living (T-DIAL) to assess financial management remotely in older adults.

The current study evaluated the reliability and validity of a novel, performance-based banking task in 60 younger (18-34 years) and 60 older (50-85 years) adults. All participants completed the Telephone-based Daily Instrumental Activities of Living (T-DIAL) using interactive voice response technology to complete a series of mock actions with a financial institution via telephone. The T-DIAL showed strong inter-rater reliability and internal consistency. T-DIAL accuracy was significantly and independently related to better self-reported instrumental activities of daily living and executive functions at a large effect size. Findings from this study provided preliminary supportive evidence for the reliability and validity of the T-DIAL, which had robust associations with manifest everyday functioning and higher-order cognitive ability. Future work is needed on the psychometrics (e.g. test-retest reliability, normative standards), and construct validity (e.g. diagnostic accuracy) of the T-DIAL in neurocognitive disorders and under-served communities for whom remote evaluations might be particularly relevant.

HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study.

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.

Liquid biopsy for gastric cancer: Techniques, applications, and future directions.

After the study of circulating tumor cells in blood through liquid biopsy (LB), this technique has evolved to encompass the analysis of multiple materials originating from the tumor, such as nucleic acids, extracellular vesicles, tumor-educated platelets, and other metabolites. Additionally, research has extended to include the examination of samples other than blood or plasma, such as saliva, gastric juice, urine, or stool. LB techniques are diverse, intricate, and variable. They must be highly sensitive, and pre-analytical, patient, and tumor-related factors significantly influence the detection threshold, diagnostic method selection, and potential results. Consequently, the implementation of LB in clinical practice still faces several challenges. The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases, monitoring treatment response, early identification of relapses, or assessing patient risk. On the other hand, gastric cancer (GC) is a disease often diagnosed at advanced stages. Despite recent advances in molecular understanding, the currently available treatment options have not substantially improved the prognosis for many of these patients. The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients. In this comprehensive review, from a pathologist's perspective, we provide an overview of the main options available in LB, delve into the fundamental principles of the most studied techniques, explore the potential utility of LB application in the context of GC, and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.

Mitochondrial Health, Physical Functioning, and Daily Affect: Bioenergetic Mechanisms of Dementia Caregiver Well-Being.

OBJECTIVE: Chronic stress adversely affects mental and physical well-being. However, health outcomes vary among people experiencing the same stressor. Individual differences in physical and emotional well-being may depend on mitochondrial biology, as energy production is crucial for stress regulation. This study investigated whether mitochondrial respiratory capacity corresponds to individual differences in dementia spousal caregivers' mental and physical health. METHODS: Spousal caregivers of individuals with Alzheimer's disease and related dementias ( N = 102, mean age = 71, 78% female, 83% White) provided peripheral blood samples and completed self-report questionnaires on quality of life, caregiver burden, and a 7-day affect scale. Multiple and mixed linear regressions were used to test the relationship between mitochondrial biology and well-being. RESULTS: Spare respiratory capacity ( b = 12.76, confidence interval [CI] = 5.23-20.28, p = .001), maximum respiratory capacity ( b = 8.45, CI = 4.54-12.35, p < .0001), and ATP-linked respiration ( b = 10.11, CI = 5.05-15.18, p = .0001) were positively associated with physical functioning. At average ( b = -2.23, CI = -3.64 to -0.82, p = .002) and below average ( b = -4.96, CI = -7.22 to 2.70, p < .0001) levels of spare respiratory capacity, caregiver burden was negatively associated with daily positive affect. At above average levels of spare respiratory capacity, caregiver burden was not associated with positive affect ( p = .65). CONCLUSIONS: Findings suggest that higher mitochondrial respiratory capacity is associated with better psychological and physical health-a pattern consistent with related research. These findings provide some of the earliest evidence that cellular bioenergetics are related to well-being.

Tratamiento endovascular exitoso de aneurisma del arco aórtico en un paciente pediátrico / Successful endovascular treatment of aortic arch aneurysm in a pediatric patient

Resumen Antecedentes: Los aneurismas de la aorta ascendente son patologías poco frecuentes en la infancia, sobre todo en ausencia de enfermedades previas como el síndrome de Marfan. Objetivo: Dar a conocer la posibilidad del manejo endovascular exitoso de los aneurismas de grandes vasos, usando stent y micro catéter con embolización del saco aneurismático. Método: Presentamos el caso de una paciente de 10 años y 2 meses, previamente sana, en quien se documentó un pseudoaneurisma entre el origen de la arteria carótida común izquierda y la arteria subclavia izquierda, que logró manejarse de forma endovascular, inicialmente con un stent cubriendo el cuello del aneurisma con el fin de remodelarlo y posteriormente por medio de microcatéter se realizó embolización del saco del aneurisma con coils, con resultado exitoso. Resultados: Los aneurismas de los grandes vasos, como la arteria carótida común y la arteria subclavia, tienen riesgo de ruptura con complicaciones devastadoras; el manejo endovascular se plantea como una opción poco invasiva de manejo, con resultados favorables. Conclusión: El manejo de aneurismas de grandes vasos, por vía endovascular usando stent y microcatéter con embolización del saco aneurismático, es una opción novedosa de manejo que logra resultados exitosos.

Abstract Background: Ascending aortic aneurysms are rare pathologies in childhood, especially in the absence of previous diseases such as Marfan syndrome. Objective: Present the possibility of successful endovascular management of large vessel aneurysms, using stents and microcatheters with embolization of the aneurysm sac. Method: We present the case of a previously healthy ten-year-old patient, in whom a pseudoaneurysm was documented between the origin of the left common carotid artery and left subclavian artery, successfully managed endovascularly, initially with a stent covering the neck of the aneurysm to remodel it and later with embolization of the aneurysm sac using a microcatheter. Results: Aneurysms of large vessels, such common carotid artery and subclavian artery, are at risk of rupture with devastating complications; endovascular management is considered a minimally invasive management option, with favorable results. Conclusion: The endovascular management of large vessel aneurysms using stents and microcatheters with embolization of the aneurysmal sac is a novel management option that achieves successful results.

Molecular Classifications in Gastric Cancer: A Call for Interdisciplinary Collaboration.

Gastric cancer (GC) is a heterogeneous disease, often diagnosed at advanced stages, with a 5-year survival rate of approximately 20%. Despite notable technological advancements in cancer research over the past decades, their impact on GC management and outcomes has been limited. Numerous molecular alterations have been identified in GC, leading to various molecular classifications, such as those developed by The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG). Other authors have proposed alternative perspectives, including immune, proteomic, or epigenetic-based classifications. However, molecular stratification has not yet transitioned into clinical practice for GC, and little attention has been paid to alternative molecular classifications. In this review, we explore diverse molecular classifications in GC from a practical point of view, emphasizing their relationships with clinicopathological factors, prognosis, and therapeutic approaches. We have focused on classifications beyond those of TCGA and the ACRG, which have been less extensively reviewed previously. Additionally, we discuss the challenges that must be overcome to ensure their impact on patient treatment and prognosis. This review aims to serve as a practical framework to understand the molecular landscape of GC, facilitate the development of consensus molecular categories, and guide the design of innovative molecular studies in the field.

L-2 hydroxyglutaric aciduria: report of a Mexican-Mayan patient with the mutation c.569C>T and response to vitamin supplements and levocarnitine.

Background: L-2-hydroxyglutaric aciduria (L2HGA) is a rare inherited autosomal recessive neurometabolic disorder caused by pathogenic variants in the L2HGDH gene which encodes mitochondrial 2-hydroxyglutarate dehydrogenase. Here, we report a case of L2HGA in a Mexican-Mayan patient with a homozygous mutation at L2HGDH gene and clinical response to vitamin supplements and levocarnitine. Case report: A 17-year-old, right-handed female patient with long-term history of seizures, developmental delay and ataxia was referred to a movement disorders specialist for the evaluation of tremor. Her brain MRI showed typical findings of L2HGA. The diagnosis was corroborated with elevated levels of 2-hydroxyglutaric acid in urine and genetic test which revealed a homozygous genetic known variant c.569C>T in exon 5 of L2HGDH gene. She was treated with levocarnitine and vitamin supplements, showing improvement in tremor and gait. Discussion: To our knowledge this is the first report of a Mexican patient with L2HGA. This case adds information about a rare condition in a different ethnic group and supports the findings of other authors which encountered symptomatic improvement with the use of flavin adenine dinucleotide (and its precursor riboflavin), and levocarnitine. Highlights: We report the first case of Mexican-Mayan patient with L2HGA showing a missense homozygous mutation in L2HGDH gene, and improvement of symptoms with vitamin supplements and levocarnitine.

Successful endovascular treatment of aortic arch aneurysm in a pediatric patient.

BACKGROUND: Ascending aortic aneurysms are rare pathologies in childhood, especially in the absence of previous diseases such as Marfan syndrome. OBJECTIVE: Present the possibility of successful endovascular management of large vessel aneurysms, using stents and microcatheters with embolization of the aneurysm sac. METHOD: We present the case of a previously healthy ten-year-old patient, in whom a pseudoaneurysm was documented between the origin of the left common carotid artery and left subclavian artery, successfully managed endovascularly, initially with a stent covering the neck of the aneurysm to remodel it and later with embolization of the aneurysm sac using a microcatheter. RESULTS: Aneurysms of large vessels, such common carotid artery and subclavian artery, are at risk of rupture with devastating complications; endovascular management is considered a minimally invasive management option, with favorable results. CONCLUSION: The endovascular management of large vessel aneurysms using stents and microcatheters with embolization of the aneurysmal sac is a novel management option that achieves successful results.

ANTECEDENTES: Los aneurismas de la aorta ascendente son patologías poco frecuentes en la infancia, sobre todo en ausencia de enfermedades previas como el síndrome de Marfan. OBJETIVO: Dar a conocer la posibilidad del manejo endovascular exitoso de los aneurismas de grandes vasos, usando stent y micro catéter con embolización del saco aneurismático. MÉTODO: Presentamos el caso de una paciente de 10 años y 2 meses, previamente sana, en quien se documentó un pseudoaneurisma entre el origen de la arteria carótida común izquierda y la arteria subclavia izquierda, que logró manejarse de forma endovascular, inicialmente con un stent cubriendo el cuello del aneurisma con el fin de remodelarlo y posteriormente por medio de microcatéter se realizó embolización del saco del aneurisma con coils, con resultado exitoso. RESULTADOS: Los aneurismas de los grandes vasos, como la arteria carótida común y la arteria subclavia, tienen riesgo de ruptura con complicaciones devastadoras; el manejo endovascular se plantea como una opción poco invasiva de manejo, con resultados favorables. CONCLUSIÓN: El manejo de aneurismas de grandes vasos, por vía endovascular usando stent y microcatéter con embolización del saco aneurismático, es una opción novedosa de manejo que logra resultados exitosos.

Molecular Study of Pneumocystis jirovecii in Respiratory Samples of HIV Patients in Chile.

Pneumocystis is an opportunistic fungus that causes potentially fatal pneumonia (PCP) in immunocompromised patients. The objective of this study was to determine the prevalence of P. jirovecii in HIV patients through phenotypic and molecular study, to investigate the genetic polymorphisms of P. jirovecii at the mitochondrial gene mtLSU and at the nuclear dihydropteroate synthase gene (DHPS), and by analysis of molecular docking to study the effect of DHPS mutations on the enzymatic affinity for sulfamethoxazole. A PCP prevalence of 28.3% was detected, with mtLSU rRNA genotypes 3 (33.3%) and 2 (26.6%) being the most common. A prevalence of 6.7% (1/15) mutations in the DHPS gene was detected, specifically at codon 55 of the amino acid sequence of dihydropteroate synthase. Molecular docking analysis showed that the combination of mutations at 55 and 98 codons is required to significantly reduce the affinity of the enzyme for sulfamethoxazole. We observed a low rate of mutations in the DHPS gene, and molecular docking analysis showed that at least two mutations in the DHPS gene are required to significantly reduce the affinity of dihydropteroate synthase for sulfamethoxazole.

[Tratamiento endovascular exitoso de aneurisma del ventrículo izquierdo en un paciente pediátrico].

BACKGROUND: Aneurysms and diverticula of the left ventricle are rare entities in childhood, with a prevalence of less than 0.1%. Described since 1886, as a severe and potentially fatal disease if not corrected, mainly due to the presence of associated anomalies and the risk of rupture. OBJETIVE: Present other management options for ventricular diverticula, different from surgical options, using alternative materials that are not used very often in daily practice. METHOD: A detailed description of a case successfully managed with these new treatment modalities. RESULTS: Endovascular management of the left ventricular diverticulum, diagnosed prenatally in the patient presented, was successful after initial failure with surgical management. CONCLUSIONS: Endovascular management of ventricular diverticula, using alternative materials to those commonly used, is an attractive option with satisfactory results in these patients.

Health literacy mediates the association between cognition and healthcare provider interactions among gay and bisexual men with HIV disease.

Introduction: Gay and bisexual men (GBM) account for the highest rates of incident infection with HIV in the U.S., and experience social, systemic barriers to accessing and engaging in healthcare services. Interacting with healthcare providers can be a complex process for some GBM with HIV disease. The current study examined the contributions of cognition and health literacy to perceived interactions with healthcare providers among GBM with HIV disease. Methods: The sample included 100 adults with HIV disease (ages 24-75) who identified as GBM. All participants completed the Dealing with Health Professionals subscale of the Beliefs Related to Medication Adherence survey, as well as the Cogstate neuropsychological battery, self-report measures of cognitive symptoms, and well-validated measures of health literacy. Results: Worse performance-based cognition and subjective cognitive symptoms were both associated with perceived difficulties dealing with healthcare providers, but these associations were fully mediated by lower health literacy. Conclusion: Health literacy may play a role in the association between poorer cognitive functioning and difficulties navigating healthcare interactions among GBM with HIV disease. Further studies are needed to determine whether cognitive approaches to enhancing the access, understanding, and use of health information in GBM with HIV disease improves healthcare interactions and outcomes.

Apathy in persons living with HIV disease: A systematic narrative review.

BACKGROUND: Apathy was identified as a feature of HIV early in the epidemic; however, there are no systematic reviews of the diverse literature on the sociodemographic and clinical correlates of apathy in HIV disease. METHODS: The current study adopted a hybrid systematic-narrative review methodology in which we used PRISMA guidelines to identify, summarize, and critique peer-reviewed, empirical studies of apathy in HIV disease in the era of combination antiretroviral therapy. RESULTS: A total of 34 studies of apathy in persons living with HIV (PLWH) were identified. Findings across these studies showed that apathy was reliably related to the structure of grey and white matter pathways commonly implicated in apathy, poorer everyday functioning, education, and other neuropsychiatric symptoms (e.g., depression). Apathy was not reliably associated with age, sex, race/ethnicity, cognition, and clinical markers of HIV disease. LIMITATIONS: The current review does not provide rigorous quantitative estimates of clinical correlates of apathy, and the exclusion criteria of non-English and non-peer reviewed publications introduces risk of bias and Type I error. CONCLUSIONS: Apathy occurs at higher rates in PLWH and is linked to neuroanatomical differences, as well as negative outcomes for everyday functions, aspects of neurocognition, and neuropsychiatric symptoms. As such, apathy is an important component to consider in the clinical assessment, diagnosis, and management of neurocognitive disorders in PLWH. Future work is needed to replicate existing findings with larger sample sizes and longitudinal designs, examine apathy as a multi-dimensional construct, and develop evidence-based treatments for apathy in PLWH.

Correlation between Peptacetobacter hiranonis, the baiCD Gene, and Secondary Bile Acids in Dogs.

Bile acid metabolism is a key pathway modulated by intestinal microbiota. Peptacetobacter (Clostridium) hiranonis has been described as the main species responsible for the conversion of primary into secondary fecal unconjugated bile acids (fUBA) in dogs. This multi-step biochemical pathway is encoded by the bile acid-inducible (bai) operon. We aimed to assess the correlation between P. hiranonis abundance, the abundance of one specific gene of the bai operon (baiCD), and secondary fUBA concentrations. In this retrospective study, 133 fecal samples were analyzed from 24 dogs. The abundances of P. hiranonis and baiCD were determined using qPCR. The concentration of fUBA was measured by gas chromatography-mass spectrometry. The baiCD abundance exhibited a strong positive correlation with secondary fUBA (ρ = 0.7377, 95% CI (0.6461, 0.8084), p < 0.0001). Similarly, there was a strong correlation between P. hiranonis and secondary fUBA (ρ = 0.6658, 95% CI (0.5555, 0.7532), p < 0.0001). Animals displaying conversion of fUBA and lacking P. hiranonis were not observed. These results suggest P. hiranonis is the main converter of primary to secondary bile acids in dogs.

Prognostic role of the log odds of positive lymph nodes in Western patients with resected gastric cancer: A comparison with the 8th edition of the TNM staging system.

OBJECTIVES: Several alternative lymph node staging systems have recently been described for gastric cancer. The log odds of positive lymph nodes (LODDS) system may be superior to the pN stage (American Joint Committee on Cancer) and lymph node ratio systems in predicting outcomes for patients with gastric cancers, as indicated by some researchers. Most studies, however, have been conducted in Asian countries, and conflicting results have been reported by other investigators. METHODS: We conducted a retrospective study of all 377 cases of gastric cancer resected at a tertiary hospital in Spain between 2000 and 2019. Clinicopathologic features were collected, LODDS were calculated and categorized into 5 groups (S1-S5), and statistical analysis was performed. RESULTS: The cases included (n = 315) were classified as S1 (25.6%), S2 (18.4%), S3 (21.3%), S4 (20.3%), and S5 (14.4%). The LODDS classification was significantly associated with tumor size, Laurén subtype, presence of signet ring cells, tumor grade, perineural infiltration, lymphovascular invasion, growth pattern, pT, tumor recurrence, and death. Kaplan-Meier analysis based on the LODDS classification demonstrated improved patient stratification compared with the pN stage for both overall survival (OS) and disease-free survival (DFS). Area under the curve values for recurrence and death were superior for the LODDS classification, and this classification was independently related to OS and DFS. In addition, the LODDS classification successfully divided patients without lymph node metastases (pN0) into subgroups with distinct prognoses. CONCLUSIONS: For our cohort, the LODDS system showed better prognostic performance than pN stage; it was an independent predictor of OS and DFS, and it provided valuable prognostic information in cases without lymph node metastases. Its prognostic accuracy, however, decreased in cases with fewer than 16 lymph nodes resected.

The Relationship Between Apathy and Cognitive Impairment Among Hispanic/Latin Americans: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses Systematic Review.

OBJECTIVES: The primary aim was to evaluate apathy assessment measures in relation to cognitive impairment among Hispanic/Latin Americans. METHODS: A systematic review on the relationship between apathy and cognitive impairment among Hispanic/Latin Americans across normal aging and neurocognitive disorders was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and using APA PsycInfo, Embase, and PubMed databases. Inclusion criteria required (1) a sample of English or Spanish-speaking adults ages 18 years and older, (2) with measures of apathy, (3) assessment of cognitive functioning or diagnosis of neurocognitive disorder, (4) with at least 18.5% Hispanic/Latin American represented in the sample. RESULTS: Only 14 papers met criteria to be included in this review. Of the 12 cross-sectional studies, 9 demonstrated significant associations between increased apathy and cognitive impairment, 1 demonstrated a descriptive difference between apathy and cognitive status (ie, no hypothesis test conducted), while 2 demonstrated null effects. These cross-sectional studies consisted of community and clinic samples of participants across North and South America. Two longitudinal studies conducted in North America demonstrated non-significant associations of apathy with cognitive status. CONCLUSIONS: The Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) apathy subscales were the most used measures for apathy in this review (85.7% of included studies). However, validity evidence from a review of apathy measures has warranted caution against the use of the NPI outside the context of screening for apathy. This potential measurement bias with Hispanic/Latin Americans apathy research limits conclusions drawn from the present review.