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Currently, immunotherapy based on PD-1/PD-L1 pathway blockade has improved survival of non-small cell lung cancer (NSCLC) patients. However, differential responses have been observed by sex, where men appear to respond better than women. Additionally, adverse effects of immunotherapy are mainly observed in women. Studies in some types of hormone-dependent cancer have revealed a role of sex hormones in anti-tumor response, tumor microenvironment and immune evasion. Estrogens mainly promote immune tolerance regulating T-cell function and modifying tumor microenvironment, while androgens attenuate anti-tumor immune responses. The precise mechanism by which sex and sex hormones may modulate immune response to tumor, modify PD-L1 expression in cancer cells and promote immune escape in NSCLC is still unclear, but current data show how sexual differences affect immune therapy response and prognosis. This review provides update information regarding anti-PD-1/PD-L immunotherapeutic efficacy in NSCLC by sex, analyzing potential roles for sex hormones on PD-L1 expression, and discussing a plausible of sex and sex hormones as predictive response factors to immunotherapy.

BackgroundTransition in health care is a process wherein adolescents gradually prepare for and shift towards care in the adult system. An initial assessment of the readiness of these adolescents is fundamental in providing appropriate health services for them. This paper aims to determine the readiness of adolescent patients towards transitioning to adult care.MethodsThis is a prospective cross-sectional study utilizing an interviewer-guided modified Transition Readiness Assessment Questionnaire (TRAQ). Sixty-three adolescents ages 15 to 18 years seen in the Pediatric Outpatient Department (OPD) of a tertiary hospital in Baguio City from July 1 to October 31, 2020 were enrolled. Frequency and percentages were used to describe the demographic data; while mean score and standard deviation determined readiness based on a Likert scale. One-way ANOVA was utilized to determine association between factors and readiness to transition.ResultsFor all domains of TRAQ, the mean score was 3.64, implying that they are not yet ready to transition. 49.2% belong to General Pediatrics. 44.4% belong to the Igorot ethnic groups. Most are still in High school, and majority of their parents finished High School level. Furthermore, the P-values were more than 0.05 for all variables suggesting no association between readiness to transition and the identified factors in this study.DiscussionThis study showed that adolescents who had both acute and chronic illnesses, were not yet ready to transition. Provision of a platform for assisting the adolescents in their assumption of bigger roles/responsibilities for their own health care is necessary to ensure proper transitioning to adult health care.

La tuberculosis (tb) es una enfermedad infecto-contagiosa causada por el complejo Mycobacterium tuberculosis. La Organización Mundial de la Salud (OMS) la considera como una epidemia y un problema para la salud global dada su incidencia, mortalidad y secuelas para los pacientes. (1) Dentro de los factores de riesgo de relevancia clínica para adquirir tb se encuentra la Diabetes Mellitus (DM), que es considerada también como una epidemia mundial. Lo que afecta el deterioro del sistema inmunológico del paciente y que además puede repercutir de forma negativa en el éxito terapéutico y sobrevida del paciente. (2) La diabetes como la tuberculosis son enfermedades crónicas e importantes problemas de salud pública mundial. Resultado de un análisis preliminar realizado por la Organización Panamericana de la Salud (OPS) indica que más de 30,000 casos de tuberculosis se relacionan con la diabetes mellitus en las Américas cada año, con los números más altos correspondientes en Brasil y México con más de 9,000 y 3.000 casos por año respectivamente. (3,4) A su vez en México, la comorbilidad que se presentó con más frecuencia en los nuevos casos de tuberculosis fue la DM en un 30%. (5) Se ha observado que el abandono del tratamiento antituberculoso y falta de adherencia al tratamiento antidiabético trae connotaciones graves, entre ellos el deterioro físico del paciente y la posibilidad de estimular los mecanismos de resistencia bacteriana, identificados de la propagación de la infección y perpetuando la existencia de esta enfermedad (6) Según el informe mundial de tuberculosis 2022 se estimó el gasto global anual en servicios esenciales de TB de 5,4 millones US$ (7) A su vez, Rodríguez Bolaños y cols., en su artículo Costos directos de atención médica en pacientes con diabetes mellitus tipo 2 en México: análisis de microcosteo indicaron que el costo promedio anual por paciente con DM2 fue de 3,193.8 US$, correspondiendo 2,740.34 US $ para los pacientes sin complicaciones y 3.550,17 US$ para quienes sí las aparecieron. (8) Según el Centro de Investigación Sobre Enfermedades Infecciosas (CISEI) del Instituto Nacional de Salud Pública y Antonio Arques y cols., han establecido ciertas recomendaciones: (9,10) Garantizar la continuidad de los servicios de tamizaje, prevención, diagnóstico y tratamiento en ambas enfermedades Garantizar los insumos que extiendan la detección de la infección y la enfermedad activa, asimismo ampliar la cobertura de las pruebas para identificar la farmacorresistencia entre los casos confirmados bacteriológicamente. En los pacientes con TB conviene llevar a cabo un control estricto de la glicemia, aprovechando los controles analíticos (en el momento del diagnóstico y en los meses 1, 2, 4 y 6 de tratamiento en los pacientes con pauta de tratamiento de seis meses. Mejorar la calidad de atención centrada en el paciente con TB y con otras comorbilidades colaborando con programas tales como los de control y prevención de diabetes.

Perivascular spaces (PVS) visible on brain MRI signal cerebral small vessel disease (CSVD). The coexistence of PVS with other CSVD manifestations likely increases the risk of adverse neurological outcomes. We related PVS to other CSVD manifestations and brain volumes that are markers of vascular brain injury and neurodegeneration. Framingham Heart Study (FHS) participants with CSVD ratings on brain MRI were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) into grades I–IV and a category reflecting high burden in single or mixed CSO-BG regions. We related PVS to covert brain infarcts (CBI), white matter hyperintensities (WMH), cerebral microbleeds (CMB), total brain, hippocampal, and cortical gray matter volumes using adjusted multivariable regression analyses. In 2454 participants (mean age 54 ± 12 years), we observed that higher PVS burden in both BG and CSO was related to CMB in lobar and deep brain regions and increased WMH. Greater CSO PVS burden was associated with decreased total cortical gray volumes. PVS are associated with ischemic markers of CSVD and neurodegeneration markers. Further studies should elucidate the causality between PVS and other CSVD manifestations.

The representation of Spanish-speaking students in STEM identity literature, particularly in physics identity, is conspicuously minimal. This study addresses this gap with a two-pronged approach. First, a physics identity instrument was adapted for Spanish-speaking STEM students to promote inclusivity in educational research. Data from 334 Mexican STEM students was collected and analysed for validation through factor analyses and Cronbach's alpha, confirming the structural integrity and reliability of the adapted instrument. Second, the instrument was employed to examine the correlation between physics identity and academic performance in a separate dataset from 200 engineering students, using multivariate linear and logistic regressions. The findings underscore gender's impact on physics course grades. Notably, variations in physics identity among engineering students indicated a potential link with their chosen field. Despite the importance of physics in engineering, physics identity was lower than expected, and performance in physics courses did not consistently correlate with a strong physics identity. However, the 'interest in physics topics' subconstruct did correlate with physics course grades. This research fills a critical void by providing an adapted instrument for assessing physics identity in Spanish-speaking students and underscores the need for pedagogical shifts to enhance physics identity and STEM outcomes for Latino students. [ABSTRACT FROM AUTHOR]

Introduction: A striking pattern in young children after severe TBI is when the entire cortical ribbon displays tissue damage: hemispheric hypodensity (HH). HH is often a result of abusive head trauma (AHT). We previously reported a model of HH in a gyrencephalic species where a combination of injuries consisting of (1) cortical impact, (2) midline shift, (3) subdural hematoma/subarachnoid hemorrhage, (4) traumatic seizures, and (5) brief apnea and hypoventilation resulted in extensive, hypoxic-ischemic-type injury. Importantly, this mechanism closely resembles that seen in children, with relative sparing of the contralateral cortex, thus ruling out a pure asphyxia mechanism. In this model, piglets of similar developmental stage to human toddlers (postnatal day 30, PND30) have extensive hypoxic-ischemic damage to the cortical ribbon with sparing of the contralateral hemisphere and deep gray matter areas. However, piglets of similar developmental stage to human infants (postnatal day 7, PND7) have less hypoxic-ischemic damage that is notably bilateral and patchy. We therefore sought to discover whether the extensive tissue damage observed in PND30 was due to a greater upregulation of matrix metalloproteinases (MMPs). Materials and Methods: In PND7 or PND30 piglets receiving AHT injuries (cortical impact, midline shift, subdural hematoma/subarachnoid hemorrhage, traumatic seizures, and brief apnea and hypoventilation) or a sham injury, the pattern of albumin extravasation and MMP-9 upregulation throughout the brain was determined via immunohistochemistry, brain tissue adjacent to the cortical impact where the tissue damage spreads was collected for Western blots, and the gelatinase activity was determined over time in peripheral plasma. EEG was recorded, and piglets survived up to 24 h after injury administration. Results: The pattern of albumin extravasation, indicating vasogenic edema, as well as increase in MMP-9, were both present at the same areas of hypoxic-ischemic tissue damage. Evidence from immunohistochemistry, Western blot, and zymogens demonstrate that MMP-2, -3, or -9 are constitutively expressed during immaturity and are not different between developmental stages; however, active forms are upregulated in PND30 but not PND7 after in response to AHT model injuries. Furthermore, peripheral active MMP-9 was downregulated after model injuries in PND7. Conclusions: This differential response to AHT model injuries might confer protection to the PND7 brain. Additionally, we find that immature gyrencephalic species have a greater baseline and array of MMPs than previously demonstrated in rodent species. Treatment with an oral or intravenous broad-spectrum matrix metalloproteinase inhibitor might reduce the extensive spread of injury in PND30, but the exposure to metalloproteinase inhibitors must be acute as to not interfere with the homeostatic role of matrix metalloproteinases in normal postnatal brain development and plasticity as well as post-injury synaptogenesis and tissue repair. [ABSTRACT FROM AUTHOR]

Urban barriers are often a consequence of the unplanned expansion of transport infrastructures, housing growth nearby existing transport infrastructures, and the vehicular traffic itself. This process, also known as “community severance”, is a problem that affects the travel patterns of the population and causes negative impacts to adjacent communities, but it is not easy to assess. As an alternative to the costly technologies and restricted-access data sometimes used to analyze urban barriers, we propose an analytical approach that assesses community severance levels by classifying the quality of Pedestrian Crossings on Urban Streets (the PeCUS index). Additionally, the approach is used to identify possible inequities nearby the different classification groups regarding demographic data. We used the chi-square (χ2) test of independence and the standardized Pearson residuals to indicate deficits and excesses of residents regarding the demographic characteristics studied surrounding the urban streets. We found the following evidences of associations: residents with low-income or those aged up to 19 tend to live close to the worst crossings, whereas residents with permanent mobility constraints or the elderly tend to live near the crossings with the best classifications. Therefore, the study shows that the assessment of community severance by the analysis of the PeCUS index is feasible. Moreover, it reveals that the distribution of residents surrounding the distinct classes of quality of crossings is equitable for vulnerable social groups, except for low-income or young residents.

This study investigated whether expert acrobatic gymnasts respond differentially than their non-trained counterparts during a single-legged stance task performed before and after a protocol designed to induce fatigue in the ankle plantarflexor muscles in terms of (a) postural steadiness and (b) electromyography (EMG) activation. We hypothesized that neuromuscular adaptation due to training would lead to different behavior of center of pressure (COP) and EMG quantifiers after fatigue. Twenty eight female volunteers (aged 11 to 24 years) formed two groups: expert acrobatic gymnastics athletes (GYN, n = 14) and age-matched non-gymnasts [control (CTRL), n = 14]. Fatigue of the ankle plantarflexors (dominant leg) was induced by a sustained posture (standing on the toes) until exhaustion. Traditional COP parameters (area, RMS, mean velocity, and power spectrum at low and high frequency ranges) were obtained with a force plate, and time and frequency-domain EMG parameters were obtained by surface electrodes positioned on the tibialis anterior, soleus, lateral gastrocnemius, medial gastrocnemius, vastus lateralis, biceps femoris, spinal erector and rectus abdominis muscles. The main results showed that fatigue induced a significant increase in postural oscillations in the ML axis (including RMS, velocity and frequency components of the power spectrum), with no significant effects in the AP axis. In terms of postural sway parameters (i.e., COP quantifiers), no superior balance stability was found for the GYN group as compared to CTRL, irrespective of the fatigue condition. On the other hand, the modulation of EMG parameters (in both time and frequency domains) indicated that expert acrobatic gymnastics athletes (as compared to healthy untrained matched controls) used different neuromuscular control strategies to keep their postures on single-legged quiet standing after the fatiguing protocol. The present results improve our knowledge of the mechanisms behind the interplay between fatigue and postural performance associated with the neuromuscular adaptations induced by sport practice. The design of gymnastics training might consider strategies aimed at improving the performance of specific muscles (i.e., tibialis anterior, soleus, biceps femoris, spinal erector) for which particular activation patterns were used by the acrobatic gymnastics to control single-legged quiet standing.

Objective: Seizures can be difficult to control in infants and toddlers. Seizures with periods of apnea and hypoventilation are common following severe traumatic brain injury (TBI). We previously observed that brief apnea with hypoventilation (A&H) in our severe TBI model acutely interrupted seizures. The current study is designed to determine the effect of A&H on subsequent seizures and whether A&H has potential therapeutic implications. Methods: Piglets (1 week or 1 month old) received multifactorial injuries: cortical impact, mass effect, subdural hematoma, subarachnoid hemorrhage, and seizures induced with kainic acid. A&H (1 min apnea, 10 min hypoventilation) was induced either before or after seizure induction, or control piglets received subdural/subarachnoid hematoma and seizure without A&H. In an intensive care unit, piglets were sedated, intubated, and mechanically ventilated, and epidural electroencephalogram was recorded for an average of 18 h after seizure induction. Results: In our severe TBI model, A&H after seizure reduced ipsilateral seizure burden by 80% compared to the same injuries without A&H. In the A&H before seizure induction group, more piglets had exclusively contralateral seizures, although most piglets in all groups had seizures that shifted location throughout the several hours of seizure. After 8–10 h, seizures transitioned to interictal epileptiform discharges regardless of A&H or timing of A&H. Significance: Even brief A&H may alter traumatic seizures. In our preclinical model, we will address the possibility of hypercapnia with normoxia, with controlled intracranial pressure, as a therapeutic option for children with status epilepticus after hemorrhagic TBI. [ABSTRACT FROM AUTHOR]

Objective: Tongue-tie, which is also known as ankyloglossia, is a common condition where the lingual frenulum is unusually tight or short. While most literature investigates the impact of tongue-tie on breastfeeding, recent articles have examined its role in speech production in children. However, these have not previously been reviewed systematically. This study aims to determine the impact of tongue-tie on speech outcomes and assess whether frenectomy can improve speech function. Methods: In this systematic review, we conducted a comprehensive search of PubMed/MEDLINE, Cochrane Library, Embase, and speechBITE to analyze primary studies investigating the impact of frenectomy for tongue-tie on speech outcomes. We extracted data regarding patient age, male to female ratio, procedure type, follow-up time, and speech outcomes and ran statistical analyses to determine if frenectomy for tongue-tie leads to improvement in speech issues in pediatric patients. Speech outcomes extracted were subjectively measured based on the interpretation of a speech and language pathologist or parent. Results: Our analysis included 10 studies with an average patient age of 4.10 years, and average cohort size of 22.17 patients. Overall, frenectomy for tongue-tie was associated with an improvement in speech articulation (0.78; 95% CI: 0.64-0.87; P <.01). Increasing patient age was found to be negatively correlated with post-frenectomy speech outcomes (P =.01). However, this relationship disappeared in the adjusted model. Conclusion: Overall, we conclude that frenectomy is a suitable treatment to correct speech issues in select patients with tongue-tie if caught early in childhood. Despite the limited investigations around speech outcomes post-frenectomy, these results are informative to providers treating tongue-tie. [ABSTRACT FROM AUTHOR]

Lung cancer incidence and mortality have significantly increased in women worldwide. Lung adenocarcinoma is the most common form of lung cancer globally. This type of lung cancer shows differences by sex, including the mutational burden, behavior, clinical characteristics, and response to treatment. The effect of sex on lung cancer patients' survival is still controversial; however, lung adenocarcinoma is considered a different disease in women and men. Moreover, lung adenocarcinoma is strongly influenced by estrogen and is also different depending on the hormonal status of the patient. Young pre-menopausal women have been explored as an independent group. They presented in more advanced stages at diagnosis, exhibited more aggressive tumors, and showed poor survival compared to men and post-menopausal women, supporting the role of sex hormones in this pathology. Several reports indicate the estrogen's role in lung carcinogenesis and tumor progression. Thus, there are currently some clinical trials testing the efficacy of antihormonal therapy in lung cancer treatment. This mini review shows the updated data about lung cancer in women, its characteristics, the etiological factors that influence carcinogenesis, and the critical role of estrogen in lung cancer and treatment.

Introduction: The Hypoglossal Nerve Stimulator (HNS) is a novel therapy that has been extensively studied in adults and more recently, it has been incorporated in children with Down Syndrome (DS) with persistent obstructive sleep apnea after adenotonsillectomy and trial of continuous positive airway pressure treatment. This systematic review article aims to examine the existing literature on HNS use in children to explore the benefits, efficacy, and parental experiences. Methods: MEDLINE, Web of Science and EMBASE were searched to include all studies published up to March 2nd, 2023, on the topic of HNS use in pediatric population under 21 years old. Results: A total of 179 studies were initially identified from which 10 articles were consistent with the inclusion criteria. Nine articles addressed outcomes after implantation of the HNS device in children with DS and 1 article explored the parental experiences. Findings were similar across studies where after implantation of HNS, there was marked improvement in polysomnographic outcomes and quality of life scores with high level of compliance. Conclusions: HNS holds promise as an effective treatment option for pediatric patients with DS and persistent OSA after AT and CPAP trials. It significantly improves sleep-disordered breathing, quality of life, and neurocognitive measures, leading to substantial and sustained benefits for these children. While the findings are encouraging, further research is needed to explore the potential of HNS in other pediatric populations without DS and to raise awareness among healthcare providers about this treatment option. Overall, HNS may offer significant long-term benefits for the overall well-being and health of pediatric patients with DS and persistent OSA. [ABSTRACT FROM AUTHOR]

Currently, immunotherapy based on PD-1/PD-L1 pathway blockade has improved survival of non-small cell lung cancer (NSCLC) patients. However, differential responses have been observed by sex, where men appear to respond better than women. Additionally, adverse effects of immunotherapy are mainly observed in women. Studies in some types of hormone-dependent cancer have revealed a role of sex hormones in anti-tumor response, tumor microenvironment and immune evasion. Estrogens mainly promote immune tolerance regulating T-cell function and modifying tumor microenvironment, while androgens attenuate anti-tumor immune responses. The precise mechanism by which sex and sex hormones may modulate immune response to tumor, modify PD-L1 expression in cancer cells and promote immune escape in NSCLC is still unclear, but current data show how sexual differences affect immune therapy response and prognosis. This review provides update information regarding anti-PD-1/PD-L immunotherapeutic efficacy in NSCLC by sex, analyzing potential roles for sex hormones on PD-L1 expression, and discussing a plausible of sex and sex hormones as predictive response factors to immunotherapy. [ABSTRACT FROM AUTHOR]

We report experimental evidence on second-movers' behavior in the investment game (also known as the trust game) when there exists endowment heterogeneity. Using a within-subject analysis, we investigate whether or not second-movers exhibit some taste for inequality aversion by returning a larger (smaller) share of the available funds to first-movers who are initially endowed with a lesser (larger) endowment, respectively. Our data suggest that second-movers do not take into consideration the level of endowments when making their decisions as their behavior is consistent across distribution of endowments; i.e., they return the same proportion of the available funds regardless of the endowments. We indeed find that some second-movers have a tendency to return what they have received from first-movers. In our data, there is also a substantial proportion of second-movers who are selfish and return nothing. (JEL Codes: C72, C91, D3, D63).

Currently, immunotherapy based on PD-1/PD-L1 pathway blockade has improved survival of non-small cell lung cancer (NSCLC) patients. However, differential responses have been observed by sex, where men appear to respond better than women. Additionally, adverse effects of immunotherapy are mainly observed in women. Studies in some types of hormone-dependent cancer have revealed a role of sex hormones in anti-tumor response, tumor microenvironment and immune evasion. Estrogens mainly promote immune tolerance regulating T-cell function and modifying tumor microenvironment, while androgens attenuate anti-tumor immune responses. The precise mechanism by which sex and sex hormones may modulate immune response to tumor, modify PD-L1 expression in cancer cells and promote immune escape in NSCLC is still unclear, but current data show how sexual differences affect immune therapy response and prognosis. This review provides update information regarding anti-PD-1/PD-L immunotherapeutic efficacy in NSCLC by sex, analyzing potential roles for sex hormones on PD-L1 expression, and discussing a plausible of sex and sex hormones as predictive response factors to immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) visible perivascular spaces (PVS) are associated with the risk of incident dementia but their association with the early stages of cognitive impairment remains equivocal. Objective: We examined the association between MRI visible PVS and the risk of incident mild cognitive impairment (MCI) in the community-based Framingham Heart Study (FHS). Methods: FHS participants aged at least 50 years free of stroke, cognitive impairment, and dementia at the time of MRI were included. PVS were rated according to severity in the basal ganglia and centrum semiovale (CSO) using established criteria. Cox regression analyses were used to relate PVS to incident MCI adjusted for demographic and cardiovascular variables. Results: The mean age of the sample (1,314 participants) at MRI was 68 years (SD, 9; 54% women). There were 263 cases of incident MCI over a median 7.4 years follow-up (max, 19.8 years). MCI risk increased with higher PVS severity in the CSO. Relative to persons with the lowest severity rating, persons with the highest severity rating in the CSO had a higher risk of incident MCI (hazard ratio [HR] = 2.55; 95% confidence interval [CI], 1.48–4.37; p = 0.0007). In secondary analysis, this association seemed stronger in women. Risk of incident MCI was nominally higher for participants with the highest severity grade of PVS in the basal ganglia, though not statistically significant relative to the lowest grade (HR = 2.19; 95% CI, 0.78–6.14; p = 0.14). Conclusions: PVS burden in the CSO may be a risk marker for early cognitive impairment. [ABSTRACT FROM AUTHOR]

Perivascular spaces (PVS) visible on brain MRI signal cerebral small vessel disease (CSVD). The coexistence of PVS with other CSVD manifestations likely increases the risk of adverse neurological outcomes. We related PVS to other CSVD manifestations and brain volumes that are markers of vascular brain injury and neurodegeneration. Framingham Heart Study (FHS) participants with CSVD ratings on brain MRI were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) into grades I–IV and a category reflecting high burden in single or mixed CSO-BG regions. We related PVS to covert brain infarcts (CBI), white matter hyperintensities (WMH), cerebral microbleeds (CMB), total brain, hippocampal, and cortical gray matter volumes using adjusted multivariable regression analyses. In 2454 participants (mean age 54 ± 12 years), we observed that higher PVS burden in both BG and CSO was related to CMB in lobar and deep brain regions and increased WMH. Greater CSO PVS burden was associated with decreased total cortical gray volumes. PVS are associated with ischemic markers of CSVD and neurodegeneration markers. Further studies should elucidate the causality between PVS and other CSVD manifestations. [ABSTRACT FROM AUTHOR]