Menstruating while homeless: navigating access to products, spaces, and services.

BACKGROUND: People experiencing homelessness (PEH) in the United States face substantial challenges related to menstruation, exacerbated by the COVID-19 pandemic. Limited access to period products, heightened stigma, and gynecological challenges contribute to increased hardships for PEH, highlighting the need for improved services and policies to address period equity and overall well-being for this vulnerable population. METHODS: We conducted semi-structured qualitative interviews with PEH (n = 12) and community healthcare and social service providers (e.g., case managers, shelter directors, community health workers, and nurses, n = 12) in Lafayette, Indiana, a city located between Indianapolis and Chicago in the United States. We used thematic analysis techniques for data analysis. RESULTS: PEH's limited access to products, services, and safe spaces hindered effective menstruation management within restrictive community contexts. Although community healthcare and service providers offered some support, complex interactions with the healthcare system, stigma, and limited access to spaces exacerbated barriers. The COVID-19 pandemic further intensified these difficulties by closing public spaces, worsening economic conditions, and straining service provider resources. CONCLUSIONS: Results highlight critical organizational and policy gaps in the United States for menstruation management resources and services, emphasizing the need for better integration into health and well-being programs for PEH. These insights will advance reproductive and public health research, shedding light on the disparities faced by PEH in managing menstruation in Indiana and contributing to the national discourse on addressing these barriers. Amid the complex landscape of public health, particularly during and after the pandemic, prioritizing menstrual health remains essential for all individuals' overall well-being, including those experiencing homelessness.

Germicidal efficacy of continuous and pulsed ultraviolet-C radiation on pathogen models and SARS-CoV-2.

Ultraviolet radiation's germicidal efficacy depends on several parameters, including wavelength, radiant exposure, microbial physiology, biological matrices, and surfaces. In this work, several ultraviolet radiation sources (a low-pressure mercury lamp, a KrCl excimer, and four UV LEDs) emitting continuous or pulsed irradiation were compared. The greatest log reductions in E. coli cells and B. subtilis endospores were 4.1 ± 0.2 (18 mJ cm-2) and 4.5 ± 0.1 (42 mJ cm-2) with continuous 222 nm, respectively. The highest MS2 log reduction observed was 2.7 ± 0.1 (277 nm at 3809 mJ cm-2). Log reductions of SARS-CoV-2 with continuous 222 nm and 277 nm were ≥ 3.4 ± 0.7, with 13.3 mJ cm-2 and 60 mJ cm-2, respectively. There was no statistical difference between continuous and pulsed irradiation (0.83-16.7% [222 nm and 277 nm] or 0.83-20% [280 nm] duty rates) on E. coli inactivation. Pulsed 260 nm radiation (0.5% duty rate) at 260 nm yielded significantly greater log reduction for both bacteria than continuous 260 nm radiation. There was no statistical difference in SARS-CoV-2 inactivation between continuous and pulsed 222 nm UV-C radiation and pulsed 277 nm radiation demonstrated greater germicidal efficacy than continuous 277 nm radiation. Greater radiant exposure for all radiation sources was required to inactivate MS2 bacteriophage. Findings demonstrate that pulsed irradiation could be more useful than continuous UV radiation in human-occupied spaces, but threshold limit values should be respected. Pathogen-specific sensitivities, experimental setup, and quantification methods for determining germicidal efficacy remain important factors when optimizing ultraviolet radiation for surface decontamination or other applications.

Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans.

BACKGROUND: Humans routinely shift their sleepiness and wakefulness levels in response to emotional factors. The diversity of emotional factors that modulates sleep-wake levels suggests that the ascending arousal network may be intimately linked with networks that mediate mood. Indeed, while animal studies have identified select limbic structures that play a role in sleep-wake regulation, the breadth of corticolimbic structures that directly modulates arousal in humans remains unknown. OBJECTIVE: We investigated whether select regional activation of the corticolimbic network through direct electrical stimulation can modulate sleep-wake levels in humans, as measured by subjective experience and behavior. METHODS: We performed intensive inpatient stimulation mapping in two human participants with treatment resistant depression, who underwent intracranial implantation with multi-site, bilateral depth electrodes. Stimulation responses of sleep-wake levels were measured by subjective surveys (i.e. Stanford Sleepiness Scale and visual-analog scale of energy) and a behavioral arousal score. Biomarker analyses of sleep-wake levels were performed by assessing spectral power features of resting-state electrophysiology. RESULTS: Our findings demonstrated three regions whereby direct stimulation modulated arousal, including the orbitofrontal cortex (OFC), subgenual cingulate (SGC), and, most robustly, ventral capsule (VC). Modulation of sleep-wake levels was frequency-specific: 100Hz OFC, SGC, and VC stimulation promoted wakefulness, whereas 1Hz OFC stimulation increased sleepiness. Sleep-wake levels were correlated with gamma activity across broad brain regions. CONCLUSIONS: Our findings provide evidence for the overlapping circuitry between arousal and mood regulation in humans. Furthermore, our findings open the door to new treatment targets and the consideration of therapeutic neurostimulation for sleep-wake disorders.

Overview of the Medical Management of the Critically Ill Patient.

The medical management of the critically ill patient focuses predominantly on treatment of the underlying condition (e g, sepsis or respiratory failure). However, in the past decade, the importance of initiating early prophylactic treatment for complications arising from care in the intensive care unit setting has become increasingly apparent. As survival from critical illness has improved, there is an increased prevalence of postintensive care syndrome-defined as a decline in physical, cognitive, or psychologic function among survivors of critical illness. The Intensive Care Unit Liberation Bundle, a major initiative of the Society of Critical Care Medicine, is centered on facilitating the return to normal function as early as possible, with the intent of minimizing iatrogenic harm during necessary critical care. These concepts are universally applicable to patients seen by nephrologists in the intensive care unit and may have particular relevance for patients with kidney failure either on dialysis or after kidney transplant. In this article, we will briefly summarize some known organ-based consequences associated with critical illness, review the components of the ABCDEF bundle (the conceptual framework for Intensive Care Unit Liberation), highlight the role nephrologists can play in implementing and complying with the ABCDEF bundle, and briefly discuss areas for additional research.

Primary care management of Long-Term opioid therapy.

The United States underwent massive expansion in opioid prescribing from 1990-2010, followed by opioid stewardship initiatives and reduced prescribing. Opioids are no longer considered first-line therapy for most chronic pain conditions and clinicians should first seek alternatives in most circumstances. Patients who have been treated with opioids long-term should be managed differently, sometimes even continued on opioids due to physiologic changes wrought by long-term opioid therapy and documented risks of discontinuation. When providing long-term opioid therapy, clinicians should document opioid stewardship measures, including assessments, consents, medication reconciliation, and offering naloxone, along with the rationale to continue opioid therapy. Clinicians should screen regularly for opioid use disorder and arrange for or directly provide treatment. In particular, buprenorphine can be highly useful for co-morbid pain and opioid use disorder. Addressing other substance use disorders, as well as preventive health related to substance use, should be a priority in patients with opioid use disorder. Patient-centered practices, such as shared decision-making and attending to related facets of a patient's life that influence health outcomes, should be implemented at all points of care.Key messagesAlthough opioids are no longer considered first-line therapy for most chronic pain, management of patients already taking long-term opioid therapy must be individualised.Documentation of opioid stewardship measures can help to organise opioid prescribing and protect clinicians from regulatory scrutiny.Management of resultant opioid use disorder should include provision of medications, most often buprenorphine, and several additional screening and preventive measures.

"COVID knocked me straight into the dirt": perspectives from people experiencing homelessness on the impacts of the COVID-19 pandemic.

BACKGROUND: People experiencing homelessness are uniquely susceptible and disproportionately affected by the impacts of the COVID-19 pandemic. Understanding context-specific challenges, responses, and perspectives of people experiencing homelessness is essential to improving pandemic response and mitigating the long-term consequences of the pandemic on this vulnerable population. METHODS: As part of an ongoing community-based participatory research study in partnership with a homeless service organization in Indiana, semi-structured interviews were conducted with a total of 34 individuals experiencing homelessness between January and July 2021. Guided by the NIMHD Health Disparities Research Framework, which builds on the socio-ecological model, data was thematically coded using Nvivo12 qualitative coding software and themes were organized by levels of influence (individual, interpersonal, community, societal) and domains of influence (biological, behavioral, physical/built environment, sociocultural environment, health care system). RESULTS: Narratives revealed numerous and compounding factors affecting COVID-19 risks and health outcomes among people experiencing homelessness across all levels and domains of influence. At the individual level, people experiencing homelessness face unique challenges that heightened their susceptibility to COVID-19, including pre-existing physical and mental health conditions, substance use and behavioral health risks, socioeconomic precarity, and low health literacy and COVID-related knowledge. At the interpersonal level, poor communication between people experiencing homelessness and service providers led to limited understanding of and poor compliance with COVID safety measures. At the community level, closures and service disruptions restricted access to usual spaces and resources to meet basic needs. At a policy level, people experiencing homelessness were disregarded in ways that made pandemic relief resources largely inaccessible to them. CONCLUSIONS: Our findings reveal important and mitigable issues with ongoing pandemic response efforts in homeless populations through direct, first-hand accounts of their experiences during COVID-19. These insights offer opportunities for multilevel interventions to improve outreach, communication, and impact mitigation strategies for people experiencing homelessness. This study highlights the importance of centering the voices of vulnerable communities to inform future pandemic response for homeless and other underserved and marginalized populations.

Refractory Short-Lasting Unilateral Neuralgiform Headache Attacks With Conjunctival Injection and Tearing (SUNCT) Responding to Erenumab Adjuvant Therapy: A Case Report.

Many patients with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) fail to respond to the first-line treatment of lamotrigine. Additionally, data for other treatments are limited in this rare headache disorder. SUNCT involves activation of the trigeminal nerve which uses the neuropeptide calcitonin gene-related peptide (CGRP); thus CGRP-targeted treatments may be beneficial in this disorder. We present a patient with SUNCT who failed to respond optimally to 10 medications and four surgical treatments. However, she had minimal attacks after erenumab 140 mg was added to carbamazepine 200 mg three times daily and pregabalin 75 mg twice daily. Decreasing any of these three medications worsened her attacks. Our case represents the second case report of a SUNCT patient responding to a CGRP monoclonal antibody, suggesting this treatment may be a consideration in refractory SUNCT.

Activation of Drp1 promotes fatty acids-induced metabolic reprograming to potentiate Wnt signaling in colon cancer.

Cancer cells are known for their ability to adapt variable metabolic programs depending on the availability of specific nutrients. Our previous studies have shown that uptake of fatty acids alters cellular metabolic pathways in colon cancer cells to favor fatty acid oxidation. Here, we show that fatty acids activate Drp1 to promote metabolic plasticity in cancer cells. Uptake of fatty acids (FAs) induces mitochondrial fragmentation by promoting ERK-dependent phosphorylation of Drp1 at the S616 site. This increased phosphorylation of Drp1 enhances its dimerization and interaction with Mitochondrial Fission Factor (MFF) at the mitochondria. Consequently, knockdown of Drp1 or MFF attenuates fatty acid-induced mitochondrial fission. In addition, uptake of fatty acids triggers mitophagy via a Drp1- and p62-dependent mechanism to protect mitochondrial integrity. Moreover, results from metabolic profiling analysis reveal that silencing Drp1 disrupts cellular metabolism and blocks fatty acid-induced metabolic reprograming by inhibiting fatty acid utilization. Functionally, knockdown of Drp1 decreases Wnt/ß-catenin signaling by preventing fatty acid oxidation-dependent acetylation of ß-catenin. As a result, Drp1 depletion inhibits the formation of tumor organoids in vitro and xenograft tumor growth in vivo. Taken together, our study identifies Drp1 as a key mediator that connects mitochondrial dynamics with fatty acid metabolism and cancer cell signaling.

Downregulation of PHLPP induced by endoplasmic reticulum stress promotes eIF2α phosphorylation and chemoresistance in colon cancer.

Aberrant activation of endoplasmic reticulum (ER) stress by extrinsic and intrinsic factors contributes to tumorigenesis and resistance to chemotherapies in various cancer types. Our previous studies have shown that the downregulation of PHLPP, a novel family of Ser/Thr protein phosphatases, promotes tumor initiation, and progression. Here we investigated the functional interaction between the ER stress and PHLPP expression in colon cancer. We found that induction of ER stress significantly decreased the expression of PHLPP proteins through a proteasome-dependent mechanism. Knockdown of PHLPP increased the phosphorylation of eIF2α as well as the expression of autophagy-associated genes downstream of the eIF2α/ATF4 signaling pathway. In addition, results from immunoprecipitation experiments showed that PHLPP interacted with eIF2α and this interaction was enhanced by ER stress. Functionally, knockdown of PHLPP improved cell survival under ER stress conditions, whereas overexpression of a degradation-resistant mutant PHLPP1 had the opposite effect. Taken together, our studies identified ER stress as a novel mechanism that triggers PHLPP downregulation; and PHLPP-loss promotes chemoresistance by upregulating the eIF2α/ATF4 signaling axis in colon cancer cells.

Homelessness during COVID-19: challenges, responses, and lessons learned from homeless service providers in Tippecanoe County, Indiana.

BACKGROUND: The COVID-19 pandemic laid bare some of the United States' most devastating health and social inequities faced by people experiencing homelessness. Homeless populations experience disproportionate rates of underlying health conditions, stigma and marginalization that often disenfranchise them from health and social services, and living conditions that potentiate the risk of COVID-19 transmission and adverse outcomes. METHODS: Guided by the socio-ecological model, this community-based participatory research study examined the impacts of the COVID-19 public health crisis on people experiencing homelessness in Tippecanoe County, Indiana, and the ways in which homeless service providers prepared for, experienced, and responded to the pandemic. Eighteen (18) semi-structured interviews were conducted with representatives of 15 community-based organizations, including shelters and other homeless service providers. RESULTS: Qualitative content analysis revealed myriad challenges at the individual and interpersonal levels faced by people experiencing homelessness as a result of the pandemic, and multilevel responses for COVID-19 impact mitigation in this community. Many of the emergency measures put in place by homeless service providers in Tippecanoe County, Indiana created opportunities for innovative solutions to longstanding challenges faced by homeless populations that are informing better service delivery moving forward, even beyond the COVID-19 pandemic. CONCLUSIONS: Community-based organizations, including homeless shelters, are uniquely qualified to inform pandemic response and disaster risk mitigation in order to respond appropriately to the specific needs of people experiencing homelessness. The lessons learned and shared by homeless service providers on the frontline during the COVID-19 pandemic have important implications to improve future disaster response for homeless and other vulnerable populations.

A brief diagnostic screen for cluster headache: Creation and initial validation of the Erwin Test for Cluster Headache.

OBJECTIVE: To use 1) newly generated data, 2) existing evidence, and 3) expert opinion to create and validate a new cluster headache screening tool. METHODS: In phase 1 of the study, we performed a prospective study of an English translation of an Italian screen on 95 participants (45 with cluster headache, 17 with other trigeminal autonomic cephalalgias, 30 with migraine, and 3 with trigeminal neuralgia). In phase 2, we performed a systematic review in PubMed of all studies until September 2019 with diagnostic screening tools for cluster headache. In phase 3, a 6-person panel of cluster headache patients, research coordinators, and headache specialists analyzed the data from the first two phases to generate a new diagnostic screening tool. Finally, in phase 4 this new screen was validated on participants at a single headache center (all diagnoses) and through research recruitment (trigeminal autonomic cephalalgias only, as recruitment was essential but was otherwise low). RESULTS: In total, this study included 319 unique participants including 109 cluster headache participants (95 total participants/45 cluster headache participants in phase 1, and 224 total participants/64 cluster headache participants in phase 4). It also found 123 articles on potential screening tools in our systematic review. In phase 1, analysis of the English translation of an Italian screen generated 7 questions with high sensitivity and specificity against migraine, trigeminal neuralgia, and other trigeminal autonomic cephalalgias, but had grammatical and other limitations as a general screening tool. In phase 2, the systematic review revealed nine studies that met inclusion criteria as diagnostic screening tools for cluster headache, including four where sensitivity and specificity were available for individual questions or small groups of questions. In phase 3, this data was reviewed by the expert panel to generate a brief (6-item), binary (yes/no), written screening test. In phase 4, a total of 224 participants completed the new 6-item screening test (81 migraine, 64 cluster headache, 21 other trigeminal autonomic cephalalgias, 35 secondary headaches, 7 neuralgias, 5 probable migraine, and 11 other headache disorders). Answers to the 6 items were combined in a decision tree algorithm and three items had a sensitivity of 84% (confidence interval or 95% confidence interval 73-92%), specificity of 89% (95% confidence interval 84-94%), positive predictive value of 76% (95% confidence interval 64-85%), and negative predictive value of 93% (95% confidence interval 88-97%) for the diagnosis of cluster headache. These three items focused on headache intensity, duration, and autonomic features. CONCLUSION: The 3-item Erwin Test for Cluster Headache is a promising diagnostic screening tool for cluster headache.

Germline and somatic mutations in the pathology of pineal cyst: A whole-exome sequencing study of 93 individuals.

BACKGROUND: Pineal cyst is a benign lesion commonly occurring in people of any age. Until now, the underlying molecular alterations have not been explored. METHODS: We performed whole exome sequencing of 93 germline samples and 21 pineal cyst tissue samples to illustrate its genetic architecture and somatic mutations. The dominant and recessive inheritance modes were considered, and a probability was calculated to evaluate the significance of variant overrepresentation. RESULTS: By analyzing pineal cyst as a Mendelian disease with a dominant inheritance pattern, we identified 42,325 rare germline variants, and NM_001004711.1:c.476A>G was highly enriched (FDR<0.2). By analyzing it as a recessive disorder, we identified 753 homozygous rare variants detected in at least one pineal cyst sample each. One STIM2 rare variant, NM_001169117.1:c.1652C>T, was overrepresented (FDR<0.05). Analyzing at a gene-based level, we identified a list of the most commonlymutated germline genes, including POP4, GNGT2 and TMEM254. A somatic mutation analysis of 21 samples identified 16 variants in 15 genes, which mainly participated in the biological processes of gene expression and epigenetic regulation, immune response modulation, and transferase activity. CONCLUSION: These molecular profiles are novel for this condition and provide data for investigators interested in pineal cysts.

Challenges in the management of pain in hospital patients with opioid use disorder.

This article explores the challenges and barriers to the effective nursing management of pain in patients with a history of opioid use disorder. It also identifies recommendations for improving patient care and possible areas for further research. The author examined the relevant literature, which revealed that patients with opioid use disorder may experience stigmatisation by nurses; such negative attitudes are often in conflict with nurses' professional and ethical duties. This issue is compounded by a lack of knowledge and understanding of dependence, addiction and withdrawal. It was also identified that patients often recognise the effects of stigma and this can cause resentment, frustration and anxiety, in some cases leading to aggressive or disruptive behaviours that reinforce negative stereotypes of people who use opioids. A breakdown in the nurse-patient relationship can result in suboptimal pain management in this often-marginalised patient group. Therefore, effective pain management relies on a nurse-patient relationship that minimises anxiety, as well as multidisciplinary team collaboration.

What obstetricians should know about obstetric anesthesia during the COVID-19 pandemic.

The COVID-19 pandemic has prompted obstetric anesthesiologists to reconsider the ways in which basic anesthesia care is provided on the Labor and Delivery Unit. Suggested modifications include an added emphasis on avoiding general anesthesia, a strong encouragement to infected individuals to opt for early neuraxial analgesia, and the prevention of emergent cesarean delivery, whenever possible. Through team efforts, adopting these measures can have real effects on reducing the transmission of the viral illness and maintaining patient and caregiver safety in the labor room.

Building an obstetric intensive care unit during the COVID-19 pandemic at a tertiary hospital and selected maternal-fetal and delivery considerations.

During the novel Coronavirus Disease 2019 pandemic, New York City became an international epicenter for this highly infectious respiratory virus. In anticipation of the unfortunate reality of community spread and high disease burden, the Anesthesia and Obstetrics and Gynecology departments at NewYork-Presbyterian / Columbia University Irving Medical Center, an academic hospital system in Manhattan, created an Obstetric Intensive Care Unit on Labor and Delivery to defray volume from the hospital's preexisting intensive care units. Its purpose was threefold: (1) to accommodate the anticipated influx of critically ill pregnant and postpartum patients due to novel coronavirus, (2) to care for critically ill obstetric patients who would previously have been transferred to a non-obstetric intensive care unit, and (3) to continue caring for our usual census of pregnant and postpartum patients, who are novel Coronavirus negative and require a higher level of care. In this chapter, we share key operational details for the conversion of a non-intensive care space into an obstetric intensive care unit, with an emphasis on the infrastructure, personnel and workflow, as well as the goals for maternal and fetal monitoring.

Interplay between persistent activity and activity-silent dynamics in the prefrontal cortex underlies serial biases in working memory.

Persistent neuronal spiking has long been considered the mechanism underlying working memory, but recent proposals argue for alternative 'activity-silent' substrates. Using monkey and human electrophysiology data, we show here that attractor dynamics that control neural spiking during mnemonic periods interact with activity-silent mechanisms in the prefrontal cortex (PFC). This interaction allows memory reactivations, which enhance serial biases in spatial working memory. Stimulus information was not decodable between trials, but remained present in activity-silent traces inferred from spiking synchrony in the PFC. Just before the new stimulus, this latent trace was reignited into activity that recapitulated the previous stimulus representation. Importantly, the reactivation strength correlated with the strength of serial biases in both monkeys and humans, as predicted by a computational model that integrates activity-based and activity-silent mechanisms. Finally, single-pulse transcranial magnetic stimulation applied to the human PFC between successive trials enhanced serial biases, thus demonstrating the causal role of prefrontal reactivations in determining working-memory behavior.

Coronavirus disease 2019 infection among asymptomatic and symptomatic pregnant women: two weeks of confirmed presentations to an affiliated pair of New York City hospitals.

Novel coronavirus disease 2019 is rapidly spreading throughout the New York metropolitan area since its first reported case on March 1, 2020. The state is now the epicenter of coronavirus disease 2019 outbreak in the United States, with 84,735 cases reported as of April 2, 2020. We previously presented an early case series with 7 coronavirus disease 2019-positive pregnant patients, 2 of whom were diagnosed with coronavirus disease 2019 after an initial asymptomatic presentation. We now describe a series of 43 test-positive cases of coronavirus disease 2019 presenting to an affiliated pair of New York City hospitals for more than 2 weeks, from March 13, 2020, to March 27, 2020. A total of 14 patients (32.6%) presented without any coronavirus disease 2019-associated viral symptoms and were identified after they developed symptoms during admission or after the implementation of universal testing for all obstetric admissions on March 22. Among them, 10 patients (71.4%) developed symptoms of coronavirus disease 2019 over the course of their delivery admission or early after postpartum discharge. Of the other 29 patients (67.4%) who presented with symptomatic coronavirus disease 2019, 3 women ultimately required antenatal admission for viral symptoms, and another patient re-presented with worsening respiratory status requiring oxygen supplementation 6 days postpartum after a successful labor induction. There were no confirmed cases of coronavirus disease 2019 detected in neonates upon initial testing on the first day of life. Based on coronavirus disease 2019 disease severity characteristics by Wu and McGoogan, 37 women (86%) exhibited mild disease, 4 (9.3%) severe disease, and 2 (4.7%) critical disease; these percentages are similar to those described in nonpregnant adults with coronavirus disease 2019 (about 80% mild, 15% severe, and 5% critical disease).

Mogadishu calling: mental health awareness in Somalia via an innovative, live video-based mental health teaching programme established between Liverpool and Mogadishu.

In 2013 the Federal Government of Somalia contacted the Mersey Care National Health Service Foundation Trust (MCFT), asking whether they could formulate a teaching programme tailored towards improving mental health provision in Somalia, and the E-learning Mental Health Training Programme (SOM-Health) was eventually conceived. The fundamental aim was to provide mental health awareness to practitioners and trainees in Somalia so that they could deliver mental healthcare services confidently and effectively.