Cognitive effects of piracetam in adults with memory impairment: A systematic review and meta-analysis.

INTRODUCTION: Piracetam, a widely recognized nootropic drug, is hypothesized to enhance memory function through its influence on synaptic plasticity and neurotransmitter levels. However, despite its popularity, there remains a lack of conclusive evidence regarding its impact on memory. Therefore, the present study aims to explore the effects of piracetam on memory in individuals with impaired cognitive function, comparing it to a placebo control group. OBJECTIVES: This study will evaluate how piracetam affects memory function, compared to placebo in adults with impairment in this area. METHODS: We carried out bibliographical research and meta-analysis of scientific clinical trials comparing memory function in people taking piracetam with those in the placebo group. The PubMed, Dimensions, Embase, and Cochrane Library databases were used. Statistical analysis was performed in R Studio version 4.3.1. RESULTS: In our analysis, 199 articles were identified, of which we included eighteen studies, comprising a total of 886 patients, of which Piracetam was the treatment option in 442 (49.88 %) patients. Memory enhancement (SMD 0.75; 95 % CI [-0.19; 1.69]; p=0.12; I²=96 %) had no clinical difference between the intervention and the control group. CONCLUSION: Upon the conclusion of this study, it is apparent that we cannot definitively ascertain the impact of piracetam on memory function. Further research is warranted to provide a clearer understanding of the cognitive effects of piracetam in individuals with memory impairment. This investigation serves as a significant contribution to the ongoing quest to elucidate the potential benefits of piracetam in the field of cognitive neuroscience.

Comparison between high-flow nasal oxygen (HFNO) alternated with non-invasive ventilation (NIV) and HFNO and NIV alone in patients with COVID-19: a retrospective cohort study.

BACKGROUND: Non-invasive respiratory support (conventional oxygen therapy [COT], non-invasive ventilation [NIV], high-flow nasal oxygen [HFNO], and NIV alternated with HFNO [NIV + HFNO] may reduce the need for invasive mechanical ventilation (IMV) in patients with COVID-19. The outcome of patients treated non-invasively depends on clinical severity at admission. We assessed the need for IMV according to NIV, HFNO, and NIV + HFNO in patients with COVID-19 according to disease severity and evaluated in-hospital survival rates and hospital and intensive care unit (ICU) lengths of stay. METHODS: This cohort study was conducted using data collected between March 2020 and July 2021. Patients ≥ 18 years admitted to the ICU with a diagnosis of COVID-19 were included. Patients hospitalized for < 3 days, receiving therapy (COT, NIV, HFNO, or NIV + HFNO) for < 48 h, pregnant, and with no primary outcome data were excluded. The COT group was used as reference for multivariate Cox regression model adjustment. RESULTS: Of 1371 patients screened, 958 were eligible: 692 (72.2%) on COT, 92 (9.6%) on NIV, 31 (3.2%) on HFNO, and 143 (14.9%) on NIV + HFNO. The results for the patients in each group were as follows: median age (interquartile range): NIV (64 [49-79] years), HFNO (62 [55-70] years), NIV + HFNO (62 [48-72] years) (p = 0.615); heart failure: NIV (54.5%), HFNO (36.3%), NIV + HFNO (9%) (p = 0.003); diabetes mellitus: HFNO (17.6%), NIV + HFNO (44.7%) (p = 0.048). > 50% lung damage on chest computed tomography (CT): NIV (13.3%), HFNO (15%), NIV + HFNO (71.6%) (p = 0.038); SpO2/FiO2: NIV (271 [118-365] mmHg), HFNO (317 [254-420] mmHg), NIV + HFNO (229 [102-317] mmHg) (p = 0.001); rate of IMV: NIV (26.1%, p = 0.002), HFNO (22.6%, p = 0.023), NIV + HFNO (46.8%); survival rate: HFNO (83.9%), NIV + HFNO (63.6%) (p = 0.027); ICU length of stay: NIV (8.5 [5-14] days), NIV + HFNO (15 [10-25] days (p < 0.001); hospital length of stay: NIV (13 [10-21] days), NIV + HFNO (20 [15-30] days) (p < 0.001). After adjusting for comorbidities, chest CT score and SpO2/FiO2, the risk of IMV in patients on NIV + HFNO remained high (hazard ratio, 1.88; 95% confidence interval, 1.17-3.04). CONCLUSIONS: In patients with COVID-19, NIV alternating with HFNO was associated with a higher rate of IMV independent of the presence of comorbidities, chest CT score and SpO2/FiO2. Trial registration ClinicalTrials.gov identifier: NCT05579080.

The impact of arthritogenic viruses in oral tissues.

Arthritis and periodontitis are inflammatory diseases that share several immunopathogenic features. The expansion in the study of virus-induced arthritis has shed light on how this condition could impact other parts of the human body, including the mouth. Viral arthritis is an inflammatory joint disease caused by several viruses, most notably the alphaviruses Chikungunya virus (CHIKV), Sindbis virus (SINV), Ross River virus (RRV), Mayaro virus (MAYV), and O'nyong'nyong virus (ONNV). These viruses can induce an upsurge of matrix metalloproteinases and immune-inflammatory mediators such as Interleukin-6 (IL6), IL-1ß, tumor necrosis factor, chemokine ligand 2, and receptor activator of nuclear factor kappa-B ligand in the joint and serum of infected individuals. This can lead to the influx of inflammatory cells to the joints and associated muscles as well as osteoclast activation and differentiation, culminating in clinical signs of swelling, pain, and bone resorption. Moreover, several data indicate that these viral infections can affect other sites of the body, including the mouth. The human oral cavity is a rich and diverse microbial ecosystem, and viral infection can disrupt the balance of microbial species, causing local dysbiosis. Such events can result in oral mucosal damage and gingival bleeding, which are indicative of periodontitis. Additionally, infection by RRV, CHIKV, SINV, MAYV, or ONNV can trigger the formation of osteoclasts and upregulate pro-osteoclastogenic inflammatory mediators, interfering with osteoclast activation. As a result, these viruses may be linked to systemic conditions, including oral manifestations. Therefore, this review focuses on the involvement of alphavirus infections in joint and oral health, acting as potential agents associated with oral mucosal inflammation and alveolar bone loss. The findings of this review demonstrate how alphavirus infections could be linked to the comorbidity between arthritis and periodontitis and may provide a better understanding of potential therapeutic management for both conditions.

Molecular mechanism of cellulose depolymerization by the two-domain BlCel9A enzyme from the glycoside hydrolase family 9.

Carbohydrate-active enzymes from the glycoside hydrolase family 9 (GH9) play a key role in processing lignocellulosic biomass. Although the structural features of some GH9 enzymes are known, the molecular mechanisms that drive their interactions with cellulosic substrates remain unclear. To investigate the molecular mechanisms that the two-domain Bacillus licheniformis BlCel9A enzyme utilizes to depolymerize cellulosic substrates, we used a combination of biochemical assays, X-ray crystallography, small-angle X-ray scattering, and molecular dynamics simulations. The results reveal that BlCel9A breaks down cellulosic substrates, releasing cellobiose and glucose as the major products, but is highly inefficient in cleaving oligosaccharides shorter than cellotetraose. In addition, fungal lytic polysaccharide oxygenase (LPMO) TtLPMO9H enhances depolymerization of crystalline cellulose by BlCel9A, while exhibiting minimal impact on amorphous cellulose. The crystal structures of BlCel9A in both apo form and bound to cellotriose and cellohexaose were elucidated, unveiling the interactions of BlCel9A with the ligands and their contribution to substrate binding and products release. MD simulation analysis reveals that BlCel9A exhibits higher interdomain flexibility under acidic conditions, and SAXS experiments indicate that the enzyme flexibility is induced by pH and/or temperature. Our findings provide new insights into BlCel9A substrate specificity and binding, and synergy with the LPMOs.

Examining feasibility, acceptability, and participant experiences of an anti-racist parenting intervention for White U.S. parents.

Many White parents engage in minimal discussion of race and racism with their children, instead engaging in color-evasive practices that communicate that race is unimportant and that White people are racially neutral. Even White parents who express a commitment to anti-racist parenting frequently struggle to act on this commitment and feel underprepared to do so. The current mixed methods pilot study focused on the feasibility, acceptability, and participant experiences of an intervention ("CounterACT") that aimed to address this gap in White U.S.-based parents' skills and knowledge. Participants in the study were 27 White U.S.-based parents of 4- to 6-year-old White children who completed pre- and postintervention surveys as well as postintervention interviews. Findings suggest that the CounterACT model was feasible and acceptable. Parent self-report further suggests that CounterACT had beneficial effects on parenting, parents' beliefs regarding White privilege, and children's critical reflection. Parents reported positive experiences of CounterACT, particularly group components of the intervention. Key elements of participants' experience included learning to understand their own and their children's experience of Whiteness; learning to better tolerate and regulate emotional discomfort; connecting with others for motivation, accountability, and learning; and approaching racial socialization with greater intentionality. However, parents also experienced limits in their progress toward anti-racist parenting. Many indicated a desire for more concrete guidance and greater support enacting what they were learning in their own parenting. A particular concern was how to discuss White racial identities effectively. Our discussion highlights the implications of these findings for future work in this area. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Hysterectomy and Oophorectomy for Transgender Patients: Preoperative and Intraoperative Considerations.

OBJECTIVE: To review the preoperative and intraoperative considerations for gynecologic surgeons when performing hysterectomy with or without oophorectomy for transgender patients. DESIGN: Stepwise demonstration of techniques with narrated video footage. SETTING: Approximately 0.3% of hysterectomies performed annually in the United States are for transgender men. While some transgender men choose hysterectomy for the same indications as cisgender women, the most prevalent diagnosis for the performed surgeries is gender dysphoria [1]. Hysterectomy with or without oophorectomy can be offered to patients who meet the World Professional Association for Transgender Health criteria [2]. INTERVENTIONS: Important perioperative counseling points for transgender patients include establishing the terminology for the relevant anatomy as well as the patient's name and pronouns; if applicable, discussing options for fertility preservation if the patient desires biological children [3,4] and discussing the use of hormone therapy post oophorectomy to reduce the loss of bone density [5,6]; and reviewing intraoperative and postoperative expectations. When performing an oophorectomy on a transgender patient for gender affirmation, it is especially important to minimize the risk of ovarian remnant syndrome and the need for additional surgery, as, for example, caused by persistent menstruation. A 2-layer vaginal cuff closure should be considered to reduce the risk of vaginal cuff complications and is preferable for patients whose pelvic organs cause gender dysphoria [7,8]. CONCLUSION: Special considerations outlined in this video and the World Professional Association for Transgender Health guidelines should be reviewed by gynecologic surgeons to minimize the transgender patient's experiences of gender dysphoria before, during, and after surgery.

Mismatch repair deficiency is not sufficient to elicit tumor immunogenicity.

DNA mismatch repair deficiency (MMRd) is associated with a high tumor mutational burden (TMB) and sensitivity to immune checkpoint blockade (ICB) therapy. Nevertheless, most MMRd tumors do not durably respond to ICB and critical questions remain about immunosurveillance and TMB in these tumors. In the present study, we developed autochthonous mouse models of MMRd lung and colon cancer. Surprisingly, these models did not display increased T cell infiltration or ICB response, which we showed to be the result of substantial intratumor heterogeneity of mutations. Furthermore, we found that immunosurveillance shapes the clonal architecture but not the overall burden of neoantigens, and T cell responses against subclonal neoantigens are blunted. Finally, we showed that clonal, but not subclonal, neoantigen burden predicts ICB response in clinical trials of MMRd gastric and colorectal cancer. These results provide important context for understanding immune evasion in cancers with a high TMB and have major implications for therapies aimed at increasing TMB.

COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.

Fourth ventricular subarachnoid stent for Chiari malformation type I-associated persistent syringomyelia.

OBJECTIVE: Syringomyelia (syrinx) associated with Chiari malformation type I (CM-I) is commonly managed with posterior fossa decompression, which can lead to resolution in most cases. A persistent syrinx postdecompression is therefore uncommon and challenging to address. In the setting of radiographically adequate decompression with persistent syrinx, the authors prefer placing fourth ventricular subarachnoid stents that span the craniocervical junction particularly when intraoperative observation reveals arachnoid plane scarring. The objective of this study was to evaluate the safety and efficacy of a fourth ventricle stent for CM-I-associated persistent syringomyelia, assess dynamic changes in syrinx dimensions, and report stent-reduction durability, clinical outcomes, and procedure-associated complications. METHODS: The authors performed a single-institution, retrospective review of patients who underwent fourth ventricular subarachnoid stent placement for persistent CM-I-associated syringomyelia following a prior posterior fossa decompression. The authors' institutional Chiari database contains 600 cases with 149 decompressions for CM-I-associated syringomyelia, of which 13 met criteria for inclusion. Data on patient demographics, clinical presentation and outcomes, and MRI findings were collected. The maximal syrinx diameter was estimated by calculating the area of an elliptical cross-section in the largest axial plane from preoperative, immediately postoperative, and late postoperative T2-weighted MR images. RESULTS: All 13 patients experienced a significant decrease in mean syrinx area from the preoperative to the late postoperative MRI (mean syrinx diameter 114.1 ± 81.8 mm2 vs 24.5 ± 23.8 mm2, p < 0.001). The mean time until late postoperative MRI was 19.7 months (range 2.0-70.7 months). The syrinx area reduced on average by 75.0% ± 23.9% at the time of the last postoperative scan. Syrinx resolution was variable, with 4 patients (30.8%) achieving near-complete resolution (> 90%, grade III reduction), 7 patients (50%) having 50%-90% reduction (grade II), and 2 patients (14.3%) having < 50% decrease (grade I). One patient experienced catheter migration into the left brachium pontis with an associated cyst at the tip of the catheter that decreased in size on follow-up imaging. CONCLUSIONS: Placement of fourth ventricular subarachnoid stents spanning the craniocervical junction in patients with persistent CM-I-associated syringomyelia after posterior fossa decompression is a safe therapeutic option and significantly reduced the mean syrinx area, with a greater reductive effect seen over longer follow-up periods.

Intraoperative occipital to C2 angle and external acoustic meatus-to-axis angular measurements for optimizing alignment during posterior fossa decompression and occipitocervical fusion for complex Chiari malformation.

Background: Excess flexion or extension during occipitocervical fusion (OCF) can lead to postoperative complications, such as dysphagia, respiratory problems, line of sight issues, and neck pain, but posterior fossa decompression (PFD) and OCF require different positions that require intraoperative manipulation. Objective: The objective of this study was to describe quantitative fluoroscopic morphometrics in Chiari malformation (CM) patients with symptoms of craniocervical instability (CCI) and demonstrate the intraoperative application of these measurements to achieve neutral craniocervical alignment while leveraging a single axis of motion with the Mayfield head clamp locking mechanism. Methods: A retrospective cohort study of patients with CM 1 and 1.5 and features of CCI who underwent PFD and OCF at a single-center institution from March 2015 to October 2020 was performed. Patient demographics, preoperative presentation, radiographic morphometrics, operative details, complications, and clinical outcomes were analyzed. Results: A total of 39 patients met the inclusion criteria, of which 37 patients (94.9%) did not require additional revision surgery after PFD and OCF. In this nonrevision cohort, preoperative to postoperative occipital to C2 angle (O-C2a) (13.5° ± 10.4° vs. 17.5° ± 10.1°, P = 0.047) and narrowest oropharyngeal airway space (nPAS) (10.9 ± 3.4 mm vs. 13.1 ± 4.8 mm, P = 0.007) increased significantly. These measurements were decreased in the two patients who required revision surgery due to postoperative dysphagia (mean difference - 16.6°° in O C2a and 12.8°° in occipital and external acoustic meatus to axis angle). Based on these results, these fluoroscopic morphometrics are intraoperatively assessed, utilizing a locking Mayfield head clamp repositioning maneuver to optimize craniocervical alignment prior to rod placement from the occipital plate to cervical screws. Conclusion: Establishing a preoperative baseline of reliable fluoroscopic morphometrics can guide surgeons intraoperatively in appropriate patient realignment during combined PFD and OCF, and may prevent postoperative complications.

Differential Engagement by Race/Ethnicity in Experimental Trials of Mental Health Treatment Interventions: A Systematic Review.

Objective: Research on mental health interventions, largely from observational studies, suggests that individuals who are Black, Indigenous, and People of Color (BIPOC) have lower treatment engagement than non-Latino Whites. This systematic review focuses on prospective, experimental treatment trials, which reduce variability in patient and intervention characteristics and some access barriers (eg, cost), to examine the association of race/ethnicity and engagement.Data Sources: A systematic search of PubMed and PsycINFO through May 2020 using terms covering mental health treatment, engagement, and race/ethnicity.Study Selection: US-based, English-language, prospective experimental (including quasi-experimental) trials of adults treated for DSM-defined mental disorders were included. Studies had to compare engagement (treatment initiation and retention, medication adherence) across 2 or more ethnoracial groups. Fifty-five of 2,520 articles met inclusion criteria.Data Extraction: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Collaboration bias-risk assessment tool were used to report study findings.Results: Twenty-nine articles (53%) reported significant ethnoracial engagement differences, of which 93% found lower engagement among BIPOC groups compared largely to non-Latino Whites. The proportion of significant findings was consistent across quality of studies, covariate adjustments, ethnoracial groups, disorders, treatments, and 4 engagement definitions. Reporting limitations were found in covariate analyses and disaggregation of results across specific ethnoracial groups.Conclusions: Prospective experimental treatment trials reveal consistently lower BIPOC engagement, suggesting persisting disparities despite standardized study designs. Future research should improve inclusion of understudied groups, examine covariates systematically, and follow uniform reporting and analytic practices to elucidate reasons for these disparities.

Financial Hardship, Hope, and Life Satisfaction Among Un/Underemployed Individuals With Psychiatric Diagnoses: A Mediation Analysis.

Background: Individuals with psychiatric diagnoses who are unemployed or underemployed are likely to disproportionately experience financial hardship and, in turn, lower life satisfaction (LS). Understanding the mechanisms though which financial hardship affects LS is essential to inform effective economic empowerment interventions for this population. Aim: To examine if subjective financial hardship (SFH) mediates the relationship between objective financial hardship (OFH) and LS, and whether hope, and its agency and pathways components, further mediate the effect of SFH on LS among individuals with psychiatric diagnoses seeking employment. Methods: We conducted structured interviews with participants (N = 215) of two peer-run employment programs using indicators of OFH and SFH and standardized scales for hope (overall hope, hope agency, and hope pathways) and LS. Three structural equation models were employed to test measurement models for OFH and SFH, and mediational relationships. Covariates included gender, age, psychiatric diagnosis, race/ethnicity, education, income, employment status, SSI/SSDI receipt, and site. Results: Confirmatory factor analysis (CFA) for items measuring OFH and SFH supported two separate hypothesized factors. OFH had a strong and significant total effect on SFH [standardized beta (B) = 0.68] and LS (B = 0.49), and a weak-to-moderate effect on hope (B = -0.31). SFH alone mediated up to 94% of the effect of OFH on LS (indirect effect B = -0.46, p < 0.01). The effect of SFH on LS through hope was small (indirect effect B = -0.09, p < 0.05), primarily through hope agency (indirect effect B = -0.13, p < 0.01) and not hope pathways. Black and Hispanic ethno-racial identification seemed to buffer the effect of financial hardship on hope and LS. Individuals identifying as Black reported significantly higher overall hope (B = 0.41-0.47) and higher LS (B = 0.29-0.46), net of the effect of OFH and SFH. Conclusion: SFH is a strong mediator of the relationship between OFH and LS in our study of unemployed and underemployed individuals with psychiatric diagnoses. Hope, and particularly its agency component, further mediate a modest but significant proportion of the association between SFH and LS. Economic empowerment interventions for this population should address objective and subjective financial stressors, foster a sense of agency, and consider the diverse effects of financial hardship across ethno-racial groups.

Pancreaticopleural Fistula: A Rare Presentation of Bilateral Pleural Effusions and Trapped Lung.

A pancreaticopleural fistula (PPF) is a rare complication of chronic pancreatitis secondary to a pancreatic pseudocyst or any disruption of the main pancreatic duct. It commonly presents as a recurrent left-sided pleural effusion after multiple thoracentesis. We present a rare case of a 41-year-old woman with numerous flares of chronic pancreatitis presenting with large bilateral serosanguinous pleural effusions and trapped lung secondary to a PPF. To our knowledge, this is the first documented case of a PPF leading to bilateral pleural effusions resulting in a trapped lung.

Propagation of yellow passion fruit seedlings by cutting, grafting and seeds under salt stress

Salinity is one of the most limiting abiotic stresses in the global agricultural sector. The objective of this study was to evaluate the effect of irrigation water salinity on the initial development of P. edulis Sims. seedlings propagated by seeds, grafting and cuttings. Treatments were distributed in a completely randomized design, in a 5 x 3 factorial arrangement, corresponding to 5 levels of irrigation water electrical conductivity (0.3 - control, 1.8, 3.3, 4.8, and 6.3 dS m-1) and 3 propagation methods (seeds, cuttings and grafting), with four replicates and one plant per plot. Fifty days after the imposition of treatments with saline water, plant height, number of leaves, stem diameter, total chlorophyll, stomatal conductance, relative leaf water content, total water consumption, dry matter of root, shoot and total, root length and root volume were evaluated. The increase in water salinity affected with greater intensity the growth and development variables (height, total dry matter and root volume of the plant) and the physiological characteristics (stomatal conductance) of the species Passiflora edulis, regardless of the method of propagation. Seedlings propagated by grafting showed better development compared to the other propagation methods (seeds and cuttings). The interaction between the propagation methods and water salinity affected seedlings propagated by seeds and cuttings with greater intensity.

Adaptation and validation of a method for evaluating the bactericidal activity of ethyl alcohol in gel format 70% (w/w).

Ethyl alcohol 70% (w/w) is a broad-spectrum bactericidal agent that is mandatorily marketed as a gel in Brazil since 2002. However, there is no method described for the microbiological quality control of surface disinfectants in the form of gel, which makes it impossible to monitor the effectiveness of these products by the Health Surveillance. Thus, the present study aimed to adapt an analytical method and validate it so that it is possible to evaluate the bactericidal activity of ethyl alcohol-based disinfectants at 70% (w/w) in gel form. The proposed analytical method is an adaptation of a method developed by the Association of Official Analytical Chemists (AOAC), which is currently used to evaluate the bacterial activity of disinfectants in the form of spray and aerosol. The method consisted of challenging the disinfectant by putting it in contact with 60 carriers - previously contaminated with the test microorganism - during the contact time established by the manufacturer. The bacteria used in this work were Staphylococcus aureus CBRVS 00039 ATCC 6538, Salmonella enterica CBRVS 00028 ATCC 10708, and Pseudomonas aeruginosa CBRVS 00025 ATCC 15442. The parameters chosen for the validation of the method were: matrix effect, robustness, and repeatability. The experiments performed with a disinfectant matrix showed that there is no interference of the gel on the effectiveness of alcohol. Satisfactory results regarding the evaluation of bactericidal activity were obtained for the three microorganisms tested when the volume of 100 µL of disinfectant was applied. The method also showed good repeatability, as it proved to be robust with modification of incubation times, equipment and analysts. The development and validation of this method were extremely important for the quality monitoring of these products, besides being the first method described for the evaluation of gel disinfectants.

Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors.

CD8 T cell responses against different tumor neoantigens occur simultaneously, yet little is known about the interplay between responses and its impact on T cell function and tumor control. In mouse lung adenocarcinoma, we found that immunodominance is established in tumors, wherein CD8 T cell expansion is predominantly driven by the antigen that most stably binds MHC. T cells responding to subdominant antigens were enriched for a TCF1+ progenitor phenotype correlated with response to immune checkpoint blockade (ICB) therapy. However, the subdominant T cell response did not preferentially benefit from ICB due to a dysfunctional subset of TCF1+ cells marked by CCR6 and Tc17 differentiation. Analysis of human samples and sequencing datasets revealed that CCR6+ TCF1+ cells exist across human cancers and are not correlated with ICB response. Vaccination eliminated CCR6+ TCF1+ cells and dramatically improved the subdominant response, highlighting a strategy to optimally engage concurrent neoantigen responses against tumors.

Ventral Tonsillar Herniation Predicts Headaches in Adults With Chiari Malformation.

BACKGROUND: Radiographic characterization of Chiari malformation (CM) has historically focused on caudal tonsillar herniation (CH) below the foramen magnum. Previously, we published evidence linking ventral tonsillar herniation (VH) and medullary symptoms in very young children. We sought to extend that investigation by studying the radiographic and clinical significance of VH in adults diagnosed with CM. METHODS: We retrospectively reviewed adults with cerebellar ectopia who underwent posterior fossa decompression with or without duraplasty (PFD/D) at our institution. VH was defined as tonsils crossing a line bisecting the caudal medulla at the level of the foramen magnum on axial MRI. Degree of VH was measured as distance between this bisecting line and the ventral tip of the herniated tonsil. Dorsal brainstem compression was qualitatively determined by assessing for obliteration of CSF space between the dorsal brainstem and the tonsils. RESULTS: Out of 89 cases reviewed, 54 had some degree of VH. Compared with those without VH, the VH group was significantly older in age and more likely to also present with dorsal brainstem compression and headaches. No correlation was observed between degrees of CH and VH in the VH group. The degree of VH significantly decreased 3 months after PFD/D. CONCLUSIONS: VH is relatively common in CM patients and might be an important independent radiographic metric to evaluate and consider as part of the decision-making process, especially in those presenting with Chiari-like symptomatology referable to the medulla but who do not meet the traditional criteria of cerebellar ectopia greater than 5 mm.

Impactos da pandemia da COVID-19 na percepção de estresse e estressores em diferentes estágios do ciclo de vida / Impacts of the COVID-19 pandemic on the perception of stress and stressors at different stages of the life cycle

A pandemia da COVID-19 tem causado impactos psicológicos na população mundial, e seu consequente estresse pode levar a problemas de longo prazo. Este trabalho objetivou analisar o impacto da pandemia da COVID-19 na percepção de estresse e estressores na população do Estado de São Paulo ­ Brasil, quando comparada a um período anterior à pandemia, nas diferentes fases do ciclo vital. Realizou-se um estudo exploratório, com amostra não probabilística, por acessibilidade, dividida em período Antes da Pandemia (AP) e Pandemia (P). Foi aplicado o IPEEB ­ Inventário de Percepção de Estresse e Estressores e um questionário demográfico em duas etapas: AP e P. Participaram 1181 adultos (N = 854 AP e N = 327 P). A análise foi feita em grupos divididos por fases do ciclo vital. Os resultados se mostraram consistentes (alfa de Cronbach 0,93), e a percepção de estresse e estressores foi maior no período P em relação ao período AP, com diferenças significativas nos grupos divididos por fases do ciclo vital. Os dados sugerem que pessoas em diferentes estágios da vida reagem de maneiras distintas aos estressores durante a pandemia, exigindo diferentes ações de apoio psicossocial atual e futuro dependendo da faixa etária.

The pandemic of COVID-19 has caused psychological impacts on the world population, and its consequent stress can cause long-term problems. The aim of this work was to analyze the impact of COVID-19 pandemic on the perception of stress and stressors among the population of State of São Paulo - Brazil, when compared to a period before the pandemic, in the different phases of the life cycle stages. An exploratory study was carried out, with a non-probabilistic sample, by accessibility divided in period Before Pandemic (BP) and Pandemic (P). The IPEEB - Inventory of Perceived Stress and Stressors and a demographic questionnaire were applied in two steps: BP and P. 1181 adults participated (N=854 BP and N=327 P). The analysis was done in groups divided by life cycle stage, which are ending of the youth, early adulthood, middle age and senior age. The results presented to be consistent (Cronbach's alfa .93), And the perception of stress and stressors was higher in the P period compared to the BP period, with significant differences in the groups divided by vital cycle stages. The results suggest that people at different life stages react in different ways to the stressors during pandemic, requiring different current and future psychosocial support actions depending on the age group.

Predicting clinical outcomes using morphometric changes in adults with complex Chiari malformation undergoing occipitocervical fusion with or without ventral decompression: patient series.

BACKGROUND: The authors assessed the connection between clinical outcomes and morphometrics in patients with complex Chiari malformation (CM) who have undergone posterior fossa decompression (PFD) and subsequent occipitocervical fusion (OCF) with or without ventral decompression (VD). OBSERVATIONS: The authors retrospectively reviewed 33 patients with CM aged over 21 years who underwent PFD and OCF with or without endoscopic endonasal odontoidectomy at the authors' institution (21 OCF only and 12 OCF + VD). Clivoaxial angle (CXA), pB-C2 (perpendicular line to the line between the basion and C2), atlantodental interval (ADI), basion-dens interval (BDI), basion-axial interval (BAI), and C1 canal diameter were measured on preoperative and approximately 3-month postoperative computed tomography or magnetic resonance imaging scans. Common symptoms included headache, paresthesia, and bulbar symptoms. Clinical improvement after surgery was observed in 78.8% of patients. CXA, ADI, and BDI all significantly increased after surgery, whereas pB-C2 and BAI significantly decreased. OCF + VD had a significantly more acute CXA and longer pB-C2 preoperatively than OCF only. Patients who clinically improved postoperatively showed the same significant morphometric changes, but those who did not improve showed no significant morphometric changes. LESSONS: Patients showing improvement had greater corrections in skull base morphometrics than those who did not. Although there are various mutually nonexclusive reasons why certain patients do not improve after surgery, smaller degrees of morphometric correction could play a role.

Increase in clivo-axial angle is associated with clinical improvement in children undergoing occipitocervical fusion for complex Chiari malformation: patient series.

BACKGROUND: The authors analyzed the pre- and postoperative morphometric properties of pediatric patients with complex Chiari malformation undergoing occipitocervical fusion (OCF) to assess clinical outcomes and morphometric properties that might influence postoperative outcomes. OBSERVATIONS: The authors retrospectively reviewed 35 patients younger than 22 years with Chiari malformation who underwent posterior fossa decompression and OCF with or without endoscopic endonasal odontoidectomy at their institution (13 with and 22 without odontoidectomy). Clivo-axial angle (CXA), pB-C2, atlantodental interval, basion-dens interval, basion-axial interval, and canal diameter at the level of C1 were measured on preoperative and approximately 3-month postoperative computed tomography or magnetic resonance imaging. The authors further stratified the patient cohort into three age groups and compared the three cohorts. The most common presenting symptoms were headache, neck/shoulder pain, and dysphagia; 80% of the cohort had improved clinical outcomes. CXA increased significantly after surgery. When stratified into those who showed postoperative improvement and those who did not, only the former showed a significant increase in CXA. After age stratification, the significant changes in CXA were observed in the 7- to 13-year-old and 14- to 21-year-old cohorts. LESSONS: CXA may be the most important morphometric predictor of clinical outcomes after OCF in pediatric patients with complex Chiari malformation.