Immunotherapy for leptomeningeal disease from solid tumors: current clinical outcomes and future opportunities.

Leptomeningeal disease is a debilitating, late-stage form of metastatic cancer disseminated within the cerebrospinal fluid, subarachnoid space, and leptomeninges, leading to significant neurological morbidity and mortality. As systemic cancer treatments improve, rates of leptomeningeal disease have increased, yet prognosis remains exceedingly poor. A wide range of treatment modalities have been trialed; however, no standard of care has been established.

Fractionated Radiotherapy With Stereotactic Radiosurgery Boost Controls Gross Disease in Grade 2 Meningioma.

Objective: Opportunity exists for improved local control rates of grade 2 meningiomas that recur despite maximal surgical resection and adjuvant fractionated radiotherapy (RT). We describe a dose escalation strategy of increasing the total tumor radiation dose by adding a stereotactic radiosurgery (SRS) boost targeting gross disease to fractionated RT.

Methods: A single-institution retrospective cohort of patients from 2009-2023 with grade 2 meningioma treated with surgical resection, fractionated RT, and SRS boost were evaluated for baseline characteristics, local disease control, and adverse events (AE).

Can we improve the management of inoperable malignant bowel obstruction? Results of a feasibility study of elemental diet as an alternative to parenteral nutrition in patients with advanced gynaecological cancer.

Purpose: Nutrition support in inoperable bowel obstruction (IBO) remains challenging. Parenteral nutrition (PN) is recommended if the prognosis is > 2 months. An elemental diet (ED) is licensed for strictures in Crohn's disease but has not been used in malignant bowel obstruction.

Tumor-intrinsic CDC42BPB confers resistance to anti-PD-1 immune checkpoint blockade in breast cancer.

Immune checkpoint blockade has been used to treat breast cancer, but the clinical responses remain relatively poor. We have used the CRISPR-Cas9 kinome knockout library consisting of 763 kinase genes to identify tumor-intrinsic kinases conferring resistance to anti-PD-1 immune checkpoint blockade. We have identified the CDC42BPB kinase as a potential target to overcome the resistance to anti-PD-1 immune checkpoint blockade immunotherapy.

Fueling the future of neurosurgery: increasing trends in female enrollment expanding the neurosurgical workforce from 2010 to 2019.

Objective: Regular reporting on recruitment of women into neurosurgery is a mechanism to track the progress of minority inclusion and diversity. For more than 20 years, half of US medical students have been women, yet a disproportionate minority pursue a career in neurosurgery. The authors previously published data tracking women in neurosurgery for the prior decade from 2000 to 2009, which showed an increasing match rate of women over time, from 18 women matched at the beginning of the decade to 36 matched at the end.

The inhibitory effect of a recent distractor: singleton vs. multiple distractors.

In the complex interplay between sensory and cognitive processes, the brain must sift through a flood of sensory data to pinpoint relevant signals. This selective mechanism is crucial for the effective control of behaviour, by allowing organisms to focus on important tasks and blocking out distractions. The Inhibition of a Recent Distractor (IRD) Task examines this selection process by exploring how inhibiting distractors influences subsequent eye movements towards an object in the visual environment.

Diagnosis and treatment of dehydration after stroke: A synthesis of existing evidence.

Dehydration after stroke is associated with poor health outcomes, increased mortality, and poses a significant economic burden to health services. Yet research suggests that monitoring and assessment of hydration status is not routinely undertaken. In this commentary, we critically appraise a systematic review which aimed to synthesise the existing evidence regarding diagnosis and treatment of dehydration after stroke.

Analysis of intestinal epithelial cell responses to Cryptosporidium highlights the temporal effects of IFN-γ on parasite restriction.

The production of IFN-γ is crucial for control of multiple enteric infections, but its impact on intestinal epithelial cells (IEC) is not well understood. Cryptosporidium parasites exclusively infect epithelial cells and the ability of interferons to activate the transcription factor STAT1 in IEC is required for parasite clearance. Here, the use of single cell RNA sequencing to profile IEC during infection revealed an increased proportion of mid-villus enterocytes during infection and induction of IFN-γ-dependent gene signatures that was comparable between uninfected and infected cells.

Family Accommodation in Children and Adolescents With Misophonia.

Family accommodation (e.g., reassurance, modifying routines, assisting avoidance) has not been explored among youth with misophonia but may have important clinical and intervention implications.

Assessing clinicians' and trainees' knowledge and practice of the IDSA guidelines for asymptomatic bacteriuria in older adults.

A survey of advanced practice clinicians (APCs), physicians, residents, and medical students at an academic medical center and community practices in southeastern Texas revealed a gap in knowledge and practice related to testing and treatment for asymptomatic bacteriuria (ASB) in older adults.

A meta-analysis of cognitive flexibility in autism spectrum disorder.

Cognitive flexibility is a fundamental process that underlies adaptive behaviour in response to environmental change. Studies examining the profile of cognitive flexibility in autism spectrum disorder (ASD) have reported inconsistent findings. To address whether difficulties with cognitive flexibility are characteristic of autism, we conducted a random-effects meta-analysis and employed subgroup analyses and meta-regression to assess the impact of relevant moderator variables such as task, outcomes, and age.

Alterations in attentional processing in youth with misophonia: A phenotypical cross-comparison with anxiety patients.

Background: Misophonia is a complex condition characterized by extreme emotional distress in response to specific sounds or specific visual stimuli. Despite a growing body of clinical and neuroscientific literature, the etiology of this condition remains unclear. Hyperarousal, that is, a state of heightened alertness and disinhibition, as a core feature of misophonia is supported by behavioral and neuroimaging literature and might represent a viable clinical target for the development of both behavioral and pharmacological interventions.

Analysis of intestinal epithelial cell responses to highlights the temporal effects of IFN-γ on parasite restriction.

The production of IFN-γ is crucial for control of multiple enteric infections, but its impact on intestinal epithelial cells (IEC) is not well understood. parasites exclusively infect epithelial cells and the ability of interferons to activate the transcription factor STAT1 in IEC is required for parasite clearance. The use of single cell RNA sequencing to profile IEC during infection revealed induction of IFN-γ-dependent gene signatures that was comparable between uninfected and infected cells, and IEC expression of the IFN-γ receptor was required for parasite control.

Staff resilience and innovation essential to New York City diabetes prevention programs going virtual during COVID-19 pandemic lockdowns.

Background: COVID-19 lockdowns in March 2020 forced National Diabetes Prevention Programs (DPPs) to pause, cancel or reformulate. This qualitative study sought to (a) document if/how New York City(NYC) DPPs adapted and served participants during lockdowns, and (b) identify successes and challenges to operating programs during the lockdowns and restrictions on social gathering.

Methods: Researchers contacted 47 CDC-registered DPPs in NYC.

Validation of an open source, remote web-based eye-tracking method (WebGazer) for research in early childhood.

Measuring eye movements remotely via the participant's webcam promises to be an attractive methodological addition to in-person eye-tracking in the lab. However, there is a lack of systematic research comparing remote web-based eye-tracking with in-lab eye-tracking in young children. We report a multi-lab study that compared these two measures in an anticipatory looking task with toddlers using WebGazer.

Dendritic cell-mediated responses to secreted effectors are required for parasite-specific CD8 T cell responses.

causes debilitating diarrheal disease in patients with primary and acquired defects in T cell function. However, it has been a challenge to understand how this infection generates T cell responses and how they mediate parasite control. Here, was engineered to express a parasite effector protein (MEDLE-2) that contains the MHC-I restricted SIINFEKL epitope which is recognized by TCR transgenic OT-I CD8 T cells.

Monitoring ADO dependent proteolysis in cells using fluorescent reporter proteins.

2-Aminoethanethiol dioxygenase (ADO) is the mammalian orthologue of the plant cysteine oxidases and together these enzymes are responsible for catalysing dioxygenation of N-terminal cysteine residues of certain proteins. This modification creates an N-degron motif that permits arginylation and subsequent proteasomal degradation of such proteins via the Arg-branch of the N-degron pathway. In humans 4 proteins have been identified as substrates of ADO; regulators of G-protein signalling (RGS) 4, 5 and 16, and interleukin-32 (IL-32).

Measuring misophonia in youth: A psychometric evaluation of child and parent measures.

Background: Misophonia is characterized by intense emotional reactions to specific sounds or visual stimuli and typically onsets during childhood. An obstacle for research and clinical practice is that no comprehensively evaluated measures for pediatric misophonia exist.

Methods: In a sample of 102 youth meeting the proposed diagnostic criteria of misophonia, we evaluated the child and parent-proxy versions of the self-reported Misophonia Assessment Questionnaire (MAQ; assessing broad aspects of misophonia) and the child version of the Amsterdam Misophonia Scale (A-MISO-S; assessing misophonia severity).

Access to Medications Is a Health Care Right: Filling Prescriptions Should Not Be a Luxury.

In the summer of 2022, my daughter came down with an ear infection after suffering from several different upper respiratory infections that followed an initial infection of COVID-19. Her cough had been ongoing for about six to eight weeks after her COVID-19 infection had resolved. At this juncture, her primary care physician prescribed an inhaler.

Clinical characteristics, impairment, and psychiatric morbidity in 102 youth with misophonia.

Background: There is little information on the clinical presentation, functional impact, and psychiatric characteristics of misophonia in youth, an increasingly recognized syndrome characterized by high emotional reactivity to certain sounds and associated visual stimuli.

Method: One-hundred-two youth (8-17 years-old) with misophonia and their parents were recruited and compared with 94 youth with anxiety disorders. Participants completed validated assessments of misophonia severity, quality of life, as well as psychiatric symptoms and diagnoses.