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BACKGROUND In May 2022 the Food and Drug Administration approved fam-trastuzumab deruxtecan-nxki (FAM-TRAS) for adult patients with unresectable or metastatic Her-2 positive breast cancer who have received prior Her-2-based regimen and developed recurrence withing 6 months of completing therapy. Efficacy of the drug was established in the DESTINY-BreastO3 study. It has been suggested that fam-trastuzumab deruxtecan crosses blood-brain barrier, similarly to trastuzumab and another drug conjugate trastuzumab-DM1. CNS responses in patients with Her2 positive metastatic breast cancer have been reported. ERBB2 is a receptor tyrosine kinase from the family of EGFR/ERBB/HER family of kinases and its alterations can serve as a biomarker and actionable target in solid tumors. Here we present a case of CNS metastases from ERBB2 positive lung adenocarcinoma treated successfully with FAM-TRAS alone. METHODS Case report. RESULTS 50 y old man presented with a persistent cough. CT chest showed RUL nodule and peribronchial lymphadenopathy. Biopsy was positive for adenocarcinoma. Molecular testing has shown ERBB2 exon20 insertion, TP53 pathogenic variant, PDL1 positive (1%), and BRACA1 mutation. The patient had a solitary brain metastasis at the time of the initial diagnosis. He was started on FAM-TRAS and CNS response was seen while lung disease progressed. He was switched to immunotherapy but developed pneumonitis and therapy was stopped. He subsequently developed innumerable brain metastases and was restarted on FAM-TRAS. After 2 doses, dramatic response in CNS was seen with lung disease was stable. CONCLUSIONS This case demonstrates the critical importance of molecular testing in neuro-oncology in the era of novel systemic therapies, many with good blood-brain barrier penetration. Systemic therapies for brain metastases can be successfully implemented in the right clinical setting and they can allow for the deferral of radiotherapy. ERBB2 mutations can guide clinicians when choosing therapy for many solid tumors, including those with brain metastases.

Cardiovascular health declines with age, increasing the risk of hypertension and elevated heart rate in middle and old age. Here, we used multivariate techniques to investigate the associations between cardiovascular health (diastolic blood pressure, systolic blood pressure, and heart rate) and white matter macrostructure (lesion volume and number) and microstructure (as measured by diffusion-weighted imaging) in the cross-sectional, population-based Cam-CAN cohort (N = 667, aged 18–88). We found that cardiovascular health and age made approximately similar contributions to white matter health and explained up to 56% of variance therein. Lower diastolic blood pressure, higher systolic blood pressure, and higher heart rate were each strongly, and independently, associated with white matter abnormalities on all indices. Body mass and exercise were associated with white matter health, both directly and indirectly via cardiovascular health. These results highlight the importance of cardiovascular risk factors for white matter health across the adult lifespan and suggest that systolic blood pressure, diastolic blood pressure, and heart rate affect white matter health via separate mechanisms., Highlights • Cardiovascular health is related to white matter lesion burden and diffusivity. • Low diastolic pressure, high systolic pressure, and higher heart rate contribute independently. • Cardiovascular health and age explain up to 56% of variance in white matter health. • The uncinate fasciculus, inferior fronto-occipital fasciculus, and forceps minor show most sensitivity. • Lower BMI and more exercise may have protective effects.

The adaption of movement to changes in the environment varies across life span. Recent evidence has linked motor adaptation and its reduction with age to differences in “explicit” learning processes. We examine differences in brain structure and cognition underlying motor adaptation in a population-based cohort (n = 322, aged 18–89 years) using a visuomotor learning task and structural magnetic resonance imaging. Reduced motor adaptation with age was associated with reduced volume in striatum, prefrontal, and sensorimotor cortical regions, but not cerebellum. Medial temporal lobe volume, including the hippocampus, became a stronger determinant of motor adaptation with age. Consistent with the role of the medial temporal lobes, declarative long-term memory showed a similar interaction, whereby memory was more positively correlated with motor adaptation with increasing age. By contrast, visual short-term memory was related to motor adaptation, independently of age. These results support the hypothesis that cerebellar learning is largely unaffected in old age, and the reduction in motor adaptation with age is driven by a decline in explicit memory systems., Highlights • Reduced motor adaptation with age relates to less graey matter in motor regions. • These regions are striatum, premotor and prefrontal cortex, but not the cerebellum. • With age, motor adaptation is more positively related to medial temporal lobe areas. • Motor adaptation relates to short-term memory measures regardless of age. • With age, motor adaptation is more positively related to long-term memory scores.

Population-level study of pregnancy and infancy, including the monitoring of its several key mortality rates (maternal, infant, perinatal) is an important contributor to the ongoing success of perinatal medical care. Sharp declines in US infant mortality began in the 1960's and persisted into the 1990's, with a slower rate of decline since then. While mortality has declined, there has been little improvement in the key drivers of infant mortality over this period – preterm birth and congenital malformations – attesting to the impact of newborn intensive care in reducing mortality in high risk newborns. A high prevalence of disability is found in survivors of newborn intensive care, although recently developed interventions in labor and the newborn period may ameliorate this risk in some situations. Two notable preventive interventions developed in recent decades have been the encouragement of back and side sleeping to reduce the risk of sudden infant death syndrome, and periconceptional folate supplementation to reduce the risk of neural tube defects.

Teaching poetry and chemistry together reveals how the humanities and sciences require similar analytical and problem-solving skills. While students typically see poetry as more “subjective” and chemistry as more “objective,” close interdisciplinary reading can help them understand that all forms of inquiry include affective and interpretive, as well as evidence-based, elements.

Slowing is a common feature of ageing, yet a direct relationship between neural slowing and brain atrophy is yet to be established in healthy humans. We combine magnetoencephalographic (MEG) measures of neural processing speed with magnetic resonance imaging (MRI) measures of white and grey matter in a large population-derived cohort to investigate the relationship between age-related structural differences and visual evoked field (VEF) and auditory evoked field (AEF) delay across two different tasks. Here we use a novel technique to show that VEFs exhibit a constant delay, whereas AEFs exhibit delay that accumulates over time. White-matter (WM) microstructure in the optic radiation partially mediates visual delay, suggesting increased transmission time, whereas grey matter (GM) in auditory cortex partially mediates auditory delay, suggesting less efficient local processing. Our results demonstrate that age has dissociable effects on neural processing speed, and that these effects relate to different types of brain atrophy., Neural processing speed slows with age, but the relationship between this slowing and brain atrophy is unknown. Here, authors show that age-related functional brain differences in auditory and visual processing are partly due to structural differences in the distinct brain regions underlying these processes.

Objective: The 22q11.2 deletion syndrome is the most common known genetic risk factor for the development of schizophrenia. The authors conducted a longitudinal evaluation of adolescents with 22q11.2 deletion syndrome to identify early risk factors for the development of psychotic disorders. Method: Sixty children, 31 with 22q11.2 deletion syndrome and 29 comparison subjects with idiopathic developmental disability matched for age and IQ, underwent a baseline evaluation between 1998 and 2000; of these, 51 children (28 and 23 in the two groups, respectively) underwent follow-up evaluation between 2003 and 2005. A standardized comprehensive psychiatric, psychological, and adaptive functioning evaluation was conducted in both waves. Participants with 22q11.2 deletion syndrome were also genotyped for the catechol O -methyltransferase (COMT) Met/Val polymorphism and underwent magnetic resonance imaging scans. Results: The two groups had similar baseline neuropsychiatric profiles. At follow-up, 32.1% of subject...

Project FIT was a two-year multi-component nutrition and physical activity intervention delivered in ethnically-diverse low-income elementary schools in Grand Rapids, MI. This paper reports effects on children's nutrition outcomes and process evaluation of the school component. A quasi-experimental design was utilized. 3rd, 4th and 5th-grade students (Yr 1 baseline: N = 410; Yr 2 baseline: N = 405; age range: 7.5-12.6 years) were measured in the fall and spring over the two-year intervention. Ordinal logistic, mixed effect models and generalized estimating equations were fitted, and the robust standard errors were utilized. Primary outcomes favoring the intervention students were found regarding consumption of fruits, vegetables and whole grain bread during year 2. Process evaluation revealed that implementation of most intervention components increased during year 2. Project FIT resulted in small but beneficial effects on consumption of fruits, vegetables, and whole grain bread in ethnically diverse low-income elementary school children.

This study evaluated a community-based and social marketing healthy corner store program (FIT store) to improve the affordability and availability of healthy foods in low-income, urban, and ethnically diverse neighborhoods in Michigan. The Nutrition Environment Measures Survey in Stores data were analyzed for the FIT (N = 4) stores. Two cross-sectional surveys were conducted among the FIT store customers before (N = 401) and after (N = 318) the intervention. Three FIT stores improved their total Nutrition Environment Measures Survey in Stores availability score from before to after the intervention. A significantly higher level of FIT awareness and monthly bean and nut consumption was reported in the postintervention.

Background This paper describes Project FIT, a collaboration between the public school system, local health systems, physicians, neighborhood associations, businesses, faith-based leaders, community agencies and university researchers to develop a multi-faceted approach to promote physical activity and healthy eating toward the general goal of preventing and reducing childhood obesity among children in Grand Rapids, MI, USA. Methods/design There are four overall components to Project FIT: school, community, social marketing, and school staff wellness - all that focus on: 1) increasing access to safe and affordable physical activity and nutrition education opportunities in the schools and surrounding neighborhoods; 2) improving the affordability and availability of nutritious food in the neighborhoods surrounding the schools; 3) improving the knowledge, self-efficacy, attitudes and behaviors regarding nutrition and physical activity among school staff, parents and students; 4) impacting the 'culture' of the schools and neighborhoods to incorporate healthful values; and 5) encouraging dialogue among all community partners to leverage existing programs and introduce new ones. Discussion At baseline, there was generally low physical activity (70% do not meet recommendation of 60 minutes per day), excessive screen time (75% do not meet recommendation of < 2 hours per day), and low intake of vegetables and whole grains and high intake of sugar-sweetened beverages, French fries and chips and desserts as well as a high prevalence of overweight and obesity (48.5% including 6% with severe obesity) among low income, primarily Hispanic and African American 3rd-5th grade children (n = 403). Trial registration ClinicalTrials.gov NCT01385046

The Reserve Components of the Army have traditionally been a strategic force. Large scale mobilizations were likely only in times of national crises, such as Operations Desert Storm or Iraqi Freedom. Strategic leaders have ordered a formal conversion of the Army's Reserve Components into an operational force, capable of deploying one year out of every five or six under the Army Force Generation Model. This is a dramatic departure. It leads to an unknown the U.S. has not faced since changing to an all-volunteer army. Who will man this force? This challenge must be viewed from two key perspectives: First, civilian employers will confront an entirely new set of costs when faced with hiring a reserve service member. Second, the soldiers and potential soldiers will view an operational reserve through the new prism of guaranteed and repeated mobilization. How will their influencers parents, teachers, coaches and clergy- affect their decisions? How will spouses and significant others view service in an operational reserve? Finally, service members must consider their children in any decision to enlist or reenlist. This paper explores some of these issues and offers some suggested approaches to mitigate the impact of the conversion to an operational reserve.