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We developed a pandemic telephone outreach protocol to identify risk for social isolation, health destabilization, medication issues, inadequate services and supports, and caregiver stress among older adults at high risk of destabilization. Screening, conducted between April 1, 2020, and May 8, 2020, was targeted to those who had previously been screened as frail or who were identified as vulnerable by their family physician. This study describes the implementation and results of this risk screening protocol and describes patient, caregiver, and health professional perceptions of this outreach initiative. Mixed methods included satisfaction surveys and interviews completed by patients/caregivers (N = 300 and N = 26, respectively) and health professionals (N = 18 and N = 9, respectively). A medical record audit collected information on patient characteristics and screening outcomes. A total of 335 patients were screened in the early weeks of the pandemic, of whom 23% were identified with at least one risk factor, most commonly related to the potential for health destabilization and medication risk. Follow-up referrals were made most frequently to physicians, a pharmacist, and a social worker. The outreach calls were very well received by patients and caregivers who described feeling cared for and valued at a time when they were socially isolated and lonely. The outreach calls provided access to trusted COVID-19 information and reassurance that health care was still available. The majority of health professionals (>86%) were “very” or “extremely” satisfied with the ease of completing the screening via telephone and value for time spent; for 79% the protocol was “very” or “extremely” feasible to implement. Health professional interviews revealed that patients were unaware they could access care during the pandemic lockdown but were reassured that care was available, potential crises were averted, and they supported future implementation. Risk screening provides a significant opportunity to provide information, support, and mitigate potential risks and is an important and feasible component of pandemic planning in primary care.

Tadlac Lake, Los Baños, Laguna has been visited a lot of visitors recently. With the increase of number of visitors, environmental issues confront the integrity of Tadlac Lake Ecotourism Project (TLEP). The study was conducted to address these issues using proper communication strategy since the masterplan lacks communication component by identifying the key elements and their communication need and resources. A descriptive method using case study was used to answer the research problem and objectives. Focus Group Discussions and Key Informant Interview were used for gathering data wherein representatives of different stakeholders were categorized into three namely: government agencies, civil society groups, and private business served as the respondents of the study. Based on the findings, environmental issues in TLEP affect the land, water, waste, biodiversity and environmental pollution. Further, stakeholders indicated that they want to know about ecotourism; benefits and drawbacks and the projects of the government related to it. The information source preferred by the stakeholders are barangay consultations, brochures, flyers, and leaflets while the most accessible way for information sharing is face-to-face interaction. A communication strategy with key elements was also proposed based on all the results of this study.

Neoadjuvant chemotherapy (NAC) is an established treatment option for patients with human epidermal growth factor receptor 2-positive (Her2+) or triple-negative breast cancer (TNBC). However, the toxicities associated with NAC may lead to reduced tolerance in geriatric patients due to medical comorbidities. Our objective is to evaluate the tolerance and outcomes of NAC in geriatric patients with TNBC and Her2+ breast cancer.An institutional review board approved, retrospective study of 43 geriatric (≥70 y) and 103 non-geriatric (70 y) patients with TNBC and Her2+ breast cancer was conducted. Demographic, comorbidity, treatment, and toxicity variables were collected. Log-rank tests and Cox regression visualized survival outcomes evaluated associations with clinical and demographic variables. Descriptive statistics were performed.Following NAC, 30% geriatric patients had a pathologic complete response in the primary tumor, 54% had a partial response, and 16% had no response. Of the non-geriatric patients, 24% had a pathologic complete response, 64% had a partial response, and 12% showed no response. NAC-associated toxicities occurred in 81% of geriatric patients and 73% non-geriatric patients, with neutropenia occurring most frequently in both groups. Dose reduction and early discontinuation of NAC each occurred more frequently in the geriatric group (14%; 23%) than the non-geriatric group (7%; 6%). Higher post-treatment Eastern Cooperative Oncology Group scores were associated with worse overall survival and worse recurrence-free survival in both groups.NAC was associated with reduced tumor and nodal stage in most geriatric patients; however, NAC-associated toxicities were common and led some patients to reduce or stop their NAC regimen prematurely.

The risk of adverse events from ascending thoracic aorta aneurysm (TAA) is poorly understood but drives clinical decision-making.To evaluate the association of TAA size with outcomes in nonsyndromic patients in a large non-referral-based health care delivery system.The Kaiser Permanente Thoracic Aortic Aneurysm (KP-TAA) cohort study was a retrospective cohort study at Kaiser Permanente Northern California, a fully integrated health care delivery system insuring and providing care for more than 4.5 million persons. Nonsyndromic patients from a regional TAA safety net tracking system were included. Imaging data including maximum TAA size were merged with electronic health record (EHR) and comprehensive death data to obtain demographic characteristics, comorbidities, medications, laboratory values, vital signs, and subsequent outcomes. Unadjusted rates were calculated and the association of TAA size with outcomes was evaluated in multivariable competing risk models that categorized TAA size as a baseline and time-updated variable and accounted for potential confounders. Data were analyzed from January 2018 to August 2021.TAA size.Aortic dissection (AD), all-cause death, and elective aortic surgery.Of 6372 patients with TAA identified between 2000 and 2016 (mean [SD] age, 68.6 [13.0] years; 2050 female individuals [32.2%] and 4322 male individuals [67.8%]), mean (SD) initial TAA size was 4.4 (0.5) cm (828 individuals [13.0% of cohort] had initial TAA size 5.0 cm or larger and 280 [4.4%] 5.5 cm or larger). Rates of AD were low across a mean (SD) 3.7 (2.5) years of follow-up (44 individuals [0.7% of cohort]; incidence 0.22 events per 100 person-years). Larger initial aortic size was associated with higher risk of AD and all-cause death in multivariable models, with an inflection point in risk at 6.0 cm. Estimated adjusted risks of AD within 5 years were 0.3% (95% CI, 0.3-0.7), 0.6% (95% CI, 0.4-1.3), 1.5% (95% CI, 1.2-3.9), 3.6% (95% CI, 1.8-12.8), and 10.5% (95% CI, 2.7-44.3) in patients with TAA size of 4.0 to 4.4 cm, 4.5 to 4.9 cm, 5.0 to 5.4 cm, 5.5 to 5.9 cm, and 6.0 cm or larger, respectively, in time-updated models. Rates of the composite outcome of AD and all-cause death were higher than for AD alone, but a similar inflection point for increased risk was observed at 6.0 cm.In a large sociodemographically diverse cohort of patients with TAA, absolute risk of aortic dissection was low but increased with larger aortic sizes after adjustment for potential confounders and competing risks. Our data support current consensus guidelines recommending prophylactic surgery in nonsyndromic individuals with TAA at a 5.5-cm threshold.

Axillary lymph node metastases are a key prognostic factor in breast cancer treatment. Our aim was to evaluate how tumor size, tumor location, and imaging results correlate to axillary lymph node diseases for patients with stage I-III HER2/neu+ breast cancer. This is a single-institution retrospective chart review of female breast cancer patients diagnosed with primary invasive Her2/neu+ breast cancer who were treated with upfront surgical resection from 2000–2021. Of 75 cases, 44/75 (58.7%) had nodal metastasis, and there was a significant association of larger tumor size to nodal metastases (p ≤ 0.001). Patients with negative nodes had a smaller mean tumor size (n = 30; 15.10 mm) than patients with positive nodes (n = 45; 23.9 mm) (p = 0.002). Preoperative imaging detected suspicious nodes in 36 patients, and ultrasound detected the most positive nodes (14/18; p = 0.027). Our data confirms that tumor size at diagnosis is correlated with a higher likelihood of axillary involvement in patients with Her2/neu+ breast cancer; notably, a large proportion of Her2/neu+ breast cancers have metastatic involvement of axillary lymph nodes even with small primary lesions.

Neoadjuvant systemic therapy (NAST) can be an effective treatment option for patients with HER2 + or triple negative breast cancer (TNBC). However, its use in geriatric patients is largely understudied. Our aim is to investigate the effect of NAST in both septuagenarians and octogenarians with HER2 + or TNBC to better understand its role in the geriatric patient population.We utilized the National Cancer Database (NCDB) to analyze female patients with HER2 + or TNBC between 70 and 89 years. We compared the baseline demographic and clinical characteristics of septuagenarians and octogenarians using mixed-effect modeling for continuous variables and conditional logistic regressions for categorical variables. Overall survival (OS) between several subgroups was compared based on a propensity score model. Kaplan-Meier method was used to calculate OS between the subgroups, and log-rank test was used to compare OS results.A total of 16,443 patients met inclusion/exclusion criteria, of which 92.9% had infiltrative ductal carcinoma and 73.5% were TNBC. Most patients received NAST as a first course of therapy (58.8%). Septuagenarians were more likely to receive NAST (65.9%), whereas octogenarians were more likely to receive upfront surgical resection (67.7%). Our analysis demonstrated OS benefit with NAST among patients who received surgical resection. However, in patients who received NAST, decline during therapy was associated with a significantly poorer OS outcomes in general.When combined with surgical resection, NAST is an effective treatment option in both septuagenarians and octogenarians. Nonetheless, careful selection of NAST recipients in this population remains critical to optimize patient outcome.

This article explores the issue of workplace visibility and signs and symbols of LGBTQ + identity in a UK university. A poststructuralist Butlerian theoretical framework underpins this article. Sexual and gender identities are understood as multiple and fragmented, and constructed in relation to others and within the systems of power and knowledge that exist in universities and society more widely. An anonymous survey and focus group discussions were conducted with LGBTQ + staff in a higher education institution in England awarded university status in 1992. Results showed that staff felt relatively comfortable coming out to their peer-groups in the workplace but were less confident in coming out to students. Signs and symbols of LGBTQ + identities were fundamentally important to LGBTQ + staff members in helping them feel safe in the workplace and indicating to LGBTQ + students that they were potentially a source of support. The visibility of LGBTQ + senior leaders was important in empowering staff to believe that they too might progress within the university.

Background Little is known about the prevalence of undiagnosed cognitive impairment and its impact on instrumental activities of daily living (IADL) among people with HIV (PWH) in primary care Setting U.S. integrated healthcare system Methods PWH were recruited from an integrated healthcare setting. PWH were eligible for recruitment if they were ≥50 years old, taking antiretroviral therapy (i.e., ≥1 ART prescription fill in the past year), and had no clinical diagnosis of dementia. Participants completed a cognitive screen (St. Louis University Mental Status exam) and a questionnaire on IADL (modified Lawton-Brody). Results Study participants (N=47) were mostly male (85.1%), 51.1% White, 25.5% Black, 17.0% Hispanic, and the average age was 59.7 years (standard deviation, SD=7.0 years). Overall, 27 (57.5%) participants were categorized as cognitively normal, 17 (36.2%) as having mild cognitive impairment, and 3 (6.4%) as having possible dementia. Of the 20 participants with mild cognitive impairment or possible dementia, 85.0% were men, the average age was 60.4 years (SD=7.1 years); 45.0% were White, 40.0% were Black, 10.0% were Hispanic, and 30.0% reported difficulty with at least one IADL. Most (66.7%) attributed difficulty with IADL primarily (33.3%) or in part (33.3%) to cognitive problems. Conclusion Undiagnosed cognitive impairment is frequent among ART-treated PWH, with possible elevated risk among Black PWH, and may be accompanied by difficulty with IADL. Efforts are needed to optimize identification of factors contributing to cognitive and IADL difficulties among ART-treated PWH in primary care.

KRAS is one of the most commonly mutated oncogenes in lung, colorectal, and pancreatic cancers. Recent clinical trials directly targeting KRAS G12C presented encouraging results for a large population of non-small cell lung cancer (NSCLC), but resistance to treatment is a concern. Continued exploration of new inhibitors and preclinical models is needed to address resistance mechanisms and improve duration of patient responses. To further enable the development of KRAS G12C inhibitors, we present a preclinical framework involving translational, non-invasive imaging modalities (CT and PET) and histopathology in a conventional xenograft model and a novel KRAS G12C knock-in mouse model of NSCLC. We utilized an in-house developed KRAS G12C inhibitor (Compound A) as a tool to demonstrate the value of this framework in studying in vivo pharmacokinetic/pharmacodynamic (PK/PD) relationship and anti-tumor efficacy. We characterized the Kras G12C-driven genetically engineered mouse model (GEMM) and identify tumor growth and signaling differences compared to its Kras G12D-driven counterpart. We also find that Compound A has comparable efficacy to sotorasib in the Kras G12C-driven lung tumors arising in the GEMM, but like observations in the clinic, some tumors inevitably progress on treatment. These findings establish a foundation for evaluating future KRAS G12C inhibitors that is not limited to xenograft studies and can be applied in a translationally relevant mouse model that mirrors human disease progression and resistance.

Medulloblastoma and central nervous system primitive neuroectodermal tumors (CNS-PNET) are aggressive, poorly differentiated brain tumors with limited effective therapies. Using Sleeping Beauty (SB) transposon mutagenesis, we identified novel genetic drivers of medulloblastoma and CNS-PNET. Cross-species gene expression analyses classified SB-driven tumors into distinct medulloblastoma and CNS-PNET subgroups, indicating they resemble human Sonic hedgehog and group 3 and 4 medulloblastoma and CNS neuroblastoma with FOXR2 activation. This represents the first genetically induced mouse model of CNS-PNET and a rare model of group 3 and 4 medulloblastoma. We identified several putative proto-oncogenes including Arhgap36, Megf10, and Foxr2. Genetic manipulation of these genes demonstrated a robust impact on tumorigenesis in vitro and in vivo. We also determined that FOXR2 interacts with N-MYC, increases C-MYC protein stability, and activates FAK/SRC signaling. Altogether, our study identified several promising therapeutic targets in medulloblastoma and CNS-PNET.Significance:A transposon-induced mouse model identifies several novel genetic drivers and potential therapeutic targets in medulloblastoma and CNS-PNET.

Figure S4. Shows ARHGAP36 expression in mouse and human neural tissue. Figure S5. Shows characterization of ARHGAP36 and Megf10 in C17.2 cells Figures S6-S7 show mechanistic analysis of FOXR2 in C17.2 and HSC1L cells

Characterization of SB-induced medulloblastomas and CNS-PNETs.

This study evaluated the role of the Pediatric Sleep Questionnaire (PSQ) and associated subscales in predicting the severity of obstructive sleep apnea (OSA) in children referred for attended polysomnography (PSG).This is a retrospective study of children (0-18 years) who completed PSQs the night of their initial diagnostic PSG (2019-2020). We excluded children with previous PSG, positive airway pressure titrations, or underlying genetic or craniofacial syndromes. Area under the receiver operating characteristic curve (AUC [95%CIs]) were estimated for prediction of varying severities of obstructive apnea-hypopnea index (oAHI 2, 5, 10, and 25/h) by the PSQ's sleep-related breathing disorders (SRBD) scale and subscales.Of 477 children, median (IQR) age at PSG was 5.7 (4.3); 60% of children were male, 21% were obese, and 4% had oAHI 25/h. SRBD score did not improve discrimination of OSA cases at any oAHI threshold, with AUC CI that crossed 50% at all severities. Snoring subscale scores were predictive at oAHI 2/h (AUC = 64.5% [59.5-69.5%]), oAHI 5/h (AUC = 64.3% [59.6-69.0%]), and oAHI 10 (AUC = 67.2% [62.0-72.4%]) thresholds, but were not predictive at oAHI 25/h. The addition of demographic data (age and gender) improved the classification of the SRBD scale.When utilized in children referred for attended PSG due to concerns for an underlying sleep disorder, the PSQ snoring subscale was more predictive of OSA at varying thresholds than the SRBD scale. While the original intent of the PSQ was not for the purpose of predicting severity in children referred for PSG, future directions include augmenting the questionnaire with additional clinical variables.