Helpful and Harmful Approaches to Integrating Religion and Spirituality into Mental Health Care: A National Survey of Current Clients' Experiences in the United States.

This article describes a national sample of 989 current mental health clients' views regarding whether and how their mental health care providers integrated the client's religion/spirituality (RS) into treatment. Within the online Qualtrics survey, two open-ended items asked respondents what (if anything) the client perceived their therapist having done regarding the client's RS that was (1) helpful/supportive or (2) hurtful/harmful. Participants also reported various ways therapists included the topic of RS in practice, if any. Nearly half freely described helpful ways their providers integrated the client's RS, and half indicated it was not discussed or applicable. Although 9.6% described hurtful experiences, most indicated their provider had not done anything harmful related to integrating RS. Implications for practice and training across mental health disciplines are discussed.

Detailed phenotype and long-term follow-up of RAB28-associated cone-rod dystrophy.

PURPOSE: To gain an insight into the pathophysiology of RAB28-associated inherited retinal degeneration through detailed phenotyping and long-term longitudinal follow-up. METHODS: The patient underwent complete ophthalmic examinations. Visual function was assessed with microperimetry, full-field electroretinography (ffERG), imaging with optical coherence tomography (OCT), short-wave (SW), and near-infrared (NIR) fundus autofluorescence (FAF). RESULTS: A healthy Haitian woman with homozygous pathogenic variants (c.68C > T; p.Ser23Phe) in RAB28 presented at 16 years of age with a four-year history of blurred vision. Visual acuities were 20/125 in each eye, which remained relatively stable since. At age 27, cone ffERGs were non-detectable and borderline for rod-mediated responses. Kinetic fields were full to a V-4e target, undetectable to a small I-4e stimulus. Microperimetry showed an absolute central scotoma surrounded by a pericentral relative scotoma. SD-OCT showed an undetectable or barely detectable foveal and parafoveal photoreceptor outer nuclear layer (ONL), photoreceptor outer segment (POS), and retinal pigment epithelium (RPE) signals and loss of the SW- and NIR-FAF signals. This atrophic region was separated from a normally laminated retina by a narrow transition zone (TZ) of hyper SW- and NIR-FAF that co-localized with preserved ONL but abnormally thinned POS and RPE. There was minimal centrifugal (<100 µm) expansion over a six-year period. CONCLUSION: The cone-rod dystrophy phenotype documented herein supports a critical role of RAB28 for cone function and POS maintenance. Severe central photoreceptor and RPE loss with a predilection for POS loss in TZs suggests possible disruptions of complex mechanisms that maintain central cone photoreceptor and RPE homeostasis.

Adverse childhood experiences (ACEs), resilience, and outcomes in older adulthood: A scoping review.

BACKGROUND: Previous research has demonstrated a dose-response relationship between exposure to adverse childhood experiences (ACEs) and adverse outcomes in adulthood. Despite widely known associations, previous reviews have primarily focused on outcomes in younger and middle-aged adults exposed to ACEs to the exclusion of older adults and do not consider the potential role of resilience for understanding outcomes in older adulthood. OBJECTIVE: The present scoping review aimed to examine the extent and nature of existing literature on the influence of ACEs and resilience on the cognitive, physical, mental, and social health outcomes among older adults. METHODS: We conducted a search of five electronic databases (CINAHL, MEDLINE, PsycINFO, AgeLine, Scopus) using the following keywords: adversity, resilience, aging, and older adults. We limited our inclusion criteria to works published in English or French after 1998 as Felitti et al. published the first study describing ACEs in this year. RESULTS: Of the 4926 studies screened, 27 studies met the inclusion criteria. Overall, results from the included studies indicated that exposure to adversity during childhood was associated with worse outcomes in older adulthood. Additionally, we found that resilience and resiliency-related factors (e.g., problem-focused coping strategies) mitigated or reduced harms associated with ACEs to improve outcomes in older adulthood. CONCLUSIONS: Exposure to ACEs is associated with reduced functioning in later adulthood. Findings from this review indicate a need for further exploration into the role of ACEs, and the potential effects of resilience, on health outcomes in older adults to develop better individual- and population-level interventions for this group.

Renal function in PUSH-AHF: a summary of newly released data from the 2024 Annual Congress of the Heart Failure Association of the ESC.

The Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure (PUSH-AHF) study, published in August of 2023, was the first randomized clinical trial to compare natriuresis-guided decongestion (based on spot urinary sodium measurement) to standard of care in patients with acute heart failure with congestion receiving loop diuretic therapy. Based on results from their trial, the authors concluded that natriuresis-guided loop diuretic treatment was safe and improved natriuresis and diuresis without impacting long-term clinical outcomes. The original PUSH-AHF trial included limited information about renal outcomes and left clinicians with important questions about how natriuresis-guided decongestion might affect their patients' renal function. On May 12, 2024, however, at the 2024 Annual Congress of the HFA-ESC, Dr. Kevin Damman provided an in-depth exploration of renal outcomes from the trial when he presented a pre-specified, secondary analysis, renal function in the PUSH-AHF trial. This review puts the sub-study findings into context by considering the history of the original trial from which they came from and explaining the need for a close study of its renal outcomes particularly. It highlights the potential impact of renal function in PUSH-AHF on clinical practice and future directions that should be considered by the cardiology research community.

Seizure-Related Falls and Near Falls in LGI1-IgG Autoimmune Encephalitis.

Objectives: To study the frequency, causes, and consequences of seizure-related falls and near falls in LGI1-IgG autoimmune encephalitis. Methods: We retrospectively reviewed 136 patients seen at Mayo Clinic with (1) LGI1-IgG seropositivity, (2) clinical phenotypes compatible with LGI1-IgG autoimmune encephalitis, and (3) falls or near falls related to seizures. The clinical documentation, MRI, and EEG data were collected and reviewed. Results: In this cohort of 136 patients, 27% (n = 36) had falls or near falls related to seizures. The median age was 67 years (range 49-86 years) and 23/36 (64%) were male. Facio-brachio-crural dystonic seizures (21/36, 58%) and drop attacks (9/36, 25%) were the most common causes. Seizure-related falls resulted in injuries in 18/30 (60%), ranging from skin lacerations, joint dislocations, bone fractures to life-threatening intracranial hemorrhage. The injuries occurred most with drop attacks 8/9 (89%). Seizure-related falls or near falls resolved with immunotherapy in 24/32 (75%) whereas the responsiveness to anti-seizure medication alone was poor (4/32, 13%). Discussion: Our study demonstrates that seizure-related falls and near falls are common in LGI1-IgG autoimmune encephalitis. Early diagnosis, prompt immunotherapy initiation, and proper counseling are key to improving functional outcomes and preventing secondary injuries.

Stem Cells and Acellular Preparations in Bone Regeneration/Fracture Healing: Current Therapies and Future Directions.

Bone/fracture healing is a complex process with different steps and four basic tissue layers being affected: cortical bone, periosteum, fascial tissue surrounding the fracture, and bone marrow. Stem cells and their derivatives, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells, skeletal stem cells, and multipotent stem cells, can function to artificially introduce highly regenerative cells into decrepit biological tissues and augment the healing process at the tissue level. Stem cells are molecularly and functionally indistinguishable from standard human tissues. The widespread appeal of stem cell therapy lies in its potential benefits as a therapeutic technology that, if harnessed, can be applied in clinical settings. This review aims to establish the molecular pathophysiology of bone healing and the current stem cell interventions that disrupt or augment the bone healing process and, finally, considers the future direction/therapeutic options related to stem cells and bone healing.

Adherence to Mediterranean, Dietary Approaches to Stop Hypertension and Healthy Eating Indices are Associated with Lower Risk of Disability among Puerto Rican Adults from the Longitudinal Boston Puerto Rican Health Study.

BACKGROUND: Emerging evidence suggests that poor dietary quality is an important risk factor for disability. However, few studies have compared adherence to dietary patterns and disability, and none among Puerto Rican adults. OBJECTIVE: This study was designed to examine relationships between three dietary patterns, including DASH, Mediterranean (MeDS), and Healthy Eating Index (HEI-2010), and ∼6-y incidence of activities of daily living (ADL) and instrumental ADL (IADL) disability, and to assess potential mediation by handgrip strength. METHODS: Data are from the Boston Puerto Rican Health Study (BPRHS), a longitudinal cohort of Puerto Rican adults aged 45-75 y (n=1502). Adherence to dietary pattern variables were derived from food frequency questionnaire (FFQ) data averaged at baseline and ∼2-y. Handgrip strength was assessed at baseline. Cox proportional hazards models were used to assess longitudinal associations between DASH, MeDS, HEI-2010, and incident ∼6-y ADL (and subscales) and IADL disability. Mediation by handgrip strength was also tested. RESULTS: Participants with higher adherence DASH had lower risk of ADL, ADL mobility, and ADL manual dexterity disabilities (HR = 0.96, 95%CI: 0.91, 0.98; HR = 0.96, 95%CI: 0.92, 0.99; HR = 0.95, 95%CI: 0.92, 0.98, respectively).Higher adherence to MeDS was associated with lower risk of ADL and ADL mobility disabilities (HR = 0.89, 95%CI: 0.81, 0.98; HR = 0.90, 95%CI: 0.82, 1.00), and higher adherence to HEI with lower risk of ADL manual dexterity (HR = 0.98, 95%CI: 0.97, 0.99) in fully adjusted models. Only DASH tended to be associated with IADL (HR = 0.97, 95%CI: 0.94, 1.00). Baseline handgrip strength was a mediator between HEI and ADL manual dexterity (23.7% of the indirect effect was explained through handgrip strength). CONCLUSIONS: Higher adherence to a healthy diet pattern may decrease risk of disability and may be an important prevention strategy for ADL and IADL disability associated with aging.

AI Efficacy as a Function of Trainee Interpreter Proficiency: Lessons from a Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Recently, AI tools have been deployed with increasing speed in educational and clinical settings. However, the use of AI by trainees across different levels of experience has not been well studied. This study investigates the impact of AI assistance on diagnostic accuracy for intracranial hemorrhage (ICH) and large vessel occlusion (LVO) by medical students (MS) and resident trainees (RT). MATERIALS AND METHODS: This prospective study was conducted between March 2023 and October 2023. MS and RT were asked to identify ICH and LVO in 100 non-contrast head CTs and 100 head CTAs, respectively. One group received diagnostic aid simulating AI for ICH only (n = 26), the other for LVO only (n = 28). Primary outcomes included accuracy, sensitivity, and specificity for ICH / LVO detection without and with aid. Study interpretation time was a secondary outcome. Individual responses were pooled and analyzed with chi-square; differences in continuous variables were assessed with ANOVA. RESULTS: 48 participants completed the study, generating 10,779 ICH or LVO interpretations. With diagnostic aid, MS accuracy improved 11.0 points (P < .001) and RT accuracy showed no significant change. ICH interpretation time increased with diagnostic aid for both groups (P < .001) while LVO interpretation time decreased for MS (P < .001). Despite worse performance in detection of the smallest vs. the largest hemorrhages at baseline, MS were not more likely to accept a true positive AI result for these more difficult tasks. Both groups were considerably less accurate when disagreeing with the AI or when supplied with an incorrect AI result. CONCLUSIONS: This study demonstrated greater improvement in diagnostic accuracy with AI for MS compared to RT. However, MS were less likely than RT to overrule incorrect AI interpretations and were less accurate, even with diagnostic aid, than the AI was by itself. ABBREVIATIONS: ICH = intracranial hemorrhage; LVO = large vessel occlusion; MS = medical students; RT = resident trainees.

Collaboration between IL-7 and IL-15 enables adaptation of tissue-resident and circulating memory CD8+ T cells.

Interleukin-7 (IL-7) is considered a critical regulator of memory CD8+ T cell homeostasis, but this is primarily based on analysis of circulating and not tissue-resident memory (TRM) subsets. Furthermore, the cell-intrinsic requirement for IL-7 signaling during memory homeostasis has not been directly tested. Using inducible deletion, we found that Il7ra loss had only a modest effect on persistence of circulating memory and TRM subsets and that IL-7Rα was primarily required for normal basal proliferation. Loss of IL-15 signaling imposed heightened IL-7Rα dependence on memory CD8+ T cells, including TRM populations previously described as IL-15-independent. In the absence of IL-15 signaling, IL-7Rα was upregulated, and loss of IL-7Rα signaling reduced proliferation in response to IL-15, suggesting cross-regulation in memory CD8+ T cells. Thus, across subsets and tissues, IL-7 and IL-15 act in concert to support memory CD8+ T cells, conferring resilience to altered availability of either cytokine.

Unpredictable Mixed-Valence Outcomes Induce a Chronic and Reversible Generalized Anxiety-like Phenotype in Male Mice.

Background: Clinical anxiety is a generalized state characterized by feelings of apprehensive expectation and is distinct from momentary responses such as fear or stress. In contrast, most laboratory tests of anxiety focus on acute responses to momentary stressors. Methods: Apprehensive expectation was induced by subjecting mice (for 18 days) to manipulations in which a running response (experiment 1) or a conditioned stimulus (experiment 2) were unpredictably paired with reward (food) or punishment (footshock). Before this treatment, the mice were tested in an open field and light/dark box to assess momentary responses that are asserted to reflect state anxiety. After treatment, the mice were assessed for state anxiety in an elevated plus maze, social interaction test, startle response test, intrusive object burying test, and stress-induced corticosterone elevations. In experiment 3, we treated mice similarly to experiment 1, but after mixed-valence training, some mice received either no additional training, additional mixed-valence training, or were shifted to consistent (predictable) reinforcement with food. Results: We consistently observed an increase in anxiety-like behaviors after the experience with mixed-valence unpredictable reinforcement. This generalized anxiety persisted for at least 4 weeks after the mixed-valence training and could be reversed if the mixed-valence training was followed by predictable reinforcement with food. Conclusions: Results indicate that experience with unpredictable reward/punishment can induce a chronic state analogous to generalized anxiety that can be mitigated by exposure to stable, predictable conditions. This learned apprehension protocol provides a conceptually valid model for the study of the etiology and treatment of anxiety in laboratory animals.

Anxiety disorders have a complex etiology that is difficult to study in laboratory animals because most laboratory manipulations do not induce a chronic, generalized condition analogous to the clinical disorder. Here, laboratory mice developed approach-avoidance conflicts when a response was unpredictably rewarded or punished. These conditions (but not predictable outcomes) promoted a long-lasting general increase in a range of behaviors and stress hormones that reflect underlying anxiety, and remedial exposure to predictable conditions of reward and punishment ameliorated the generalized state. These results represent the development of a conceptually valid animal model for the study of anxiety and suggest conditions that can contribute to the etiology and treatment of anxiety.

Educating Nursing and Health Care Professionals to Create Sustainable Change Through Innovation Education.

BACKGROUND: Health care needs new solutions to address enduring challenges faced by our nurses, health care professionals, patients, and populations. This paper describes the need for preparing nurses and health care professionals with health care innovation education. METHOD: One School of Nursing formalized innovation education through a new health care innovation online graduate certificate program. The Health Care Innovation certificate program is a 12 credit, four course online program open to nurses and health care professionals aiming to create positive change in the health care industry. RESULTS: Graduates of the Health Care Innovation Certificate program reflected on 1) their motivations to pursue the program; 2) how the program helped inform their innovation knowledge to develop their innovations; and 3) how the program supported their life transformative education. CONCLUSION: There is great potential to drive positive change for our health care industry through the availability of formalized innovation education for nurses and health care professionals in the United States. [J Nurs Educ. 2024;63(X):XXX-XXX.].

Risk of Seizure Recurrence Due to Autoimmune Encephalitis With NMDAR, LGI1, CASPR2, and GABABR Antibodies: Implications for Return to Driving.

BACKGROUND AND OBJECTIVES: Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABABR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months. This would render them eligible for noncommercial driving according to driving regulations in several countries. METHODS: This retrospective multicenter cohort study analyzed follow-up data from patients aged 15 years or older with seizures resulting from NMDAR-, LGI1-, CASPR2-, or GABABR-AIE, who had been seizure-free for ≥3 months. We used Kaplan-Meier (KM) estimates for the seizure recurrence risk at 12 months for each antibody group and tested for the effects of potential covariates with regression models. RESULTS: We included 383 patients with NMDAR-, 440 with LGI1-, 114 with CASPR2-, and 44 with GABABR-AIE from 14 international centers. After being seizure-free for 3 months after an initial seizure period, we calculated the probability of remaining seizure-free for another 12 months (KM estimate) as 0.89 (95% confidence interval [CI] 0.85-0.92) for NMDAR, 0.84 (CI 0.80-0.88) for LGI1, 0.82 (CI 0.75-0.90) for CASPR2, and 0.76 (CI 0.62-0.93) for GABABR. DISCUSSION: Taking a <20% recurrence risk within 12 months as sufficient, patients with NMDAR-AIE and LGI1-AIE could be considered eligible for noncommercial driving after having been seizure-free for 3 months.

Enhancing client engagement and alleviating period product insecurity: A cross-sectional study of community-based period supply banks' distribution of free period products through intermediary partner agencies in the United States.

BACKGROUND: Period products like pads, tampons, and a variety of disposable and reusable hygiene supplies constitute just one facet essential for effectively managing menstruation in a way that allows an individual to feel comfortable carrying out their daily routine. Given the absence of comprehensive public policies ensuring access to period products for economically disadvantaged menstruating individuals, community-based basic needs banks, particularly period supply banks, were established to alleviate the challenges faced by those experiencing period product insecurity. These initiatives specifically aim to furnish essential menstrual products to individuals in need. OBJECTIVES: This study aimed to assess any organizational benefits experienced by community-based organizations distributing period products on behalf of period supply banks. DESIGN: This cross-sectional study is a formative evaluation of the distribution of free period products by period supply banks, which provide access to essential menstrual hygiene products for individuals in need through partnership with community-based partner agencies. METHODS: Staff members at agencies distributing period products were invited to complete an anonymous web-based survey at two different time points about their agency's experiences distributing free period products. All participants provided informed consent via the web-based survey. RESULTS: Agency staff reported that since they started providing period products, clients were more likely to: start a conversation about other needs (66.7%), extend the length of their relationship with the agency (60.0%), keep scheduled appointments (62.1%), ask for assistance with another need (75.0%), communicate between visits (42.4%), participate in other agency programming (55.9%), and seek other agency services (73.5%). Due to a shortage of period products, 41% of agencies have had to turn away clients needing period supplies. CONCLUSION: Period supply banks, in collaboration with community-based partner agencies, enhance access to both menstrual products and the associated support, fostering engagement with diverse resources and opportunities among recipients. However, addressing unmet needs necessitates policies and additional funding to ensure universal access to essential hygiene supplies for everyone to thrive and actively participate in society.

Positive benefits for agencies giving away free period products from a period supply bank in the United StatesWhy we did this study: In the United States, many people with periods cannot afford to buy period supplies when needed. When people do not have enough period products, they may have to stay home from places they want to go, like work, school, or community spaces. Period supply banks want to help ensure everyone has period supplies, so that, they take in donations and buy more supplies. Then, period supply banks partner with other agencies that give period supplies for free to individuals experiencing need.What we wanted to learn: We wanted to know if the agencies that give away free period products through partnerships with period supply banks have any benefits from doing so.What we did: We asked people who work at an agency that gives away free period products received through a partnership with a period supply bank to take an online survey at two different times, when the agency began the collaboration with the period supply bank and after distributing period supplies for several months. Only people who wanted to be in the study did the survey.What we learned: Agencies who give away free period products benefit because clients are more likely to talk to them about other needs they have, enroll in a program or receive another resource from the agency, miss fewer appointments, and stay in an agency program longer. Sometimes, agencies do not have enough products for everyone who needs period supplies. More funding and policies are needed to help period supply banks buy enough period products for everyone who needs them.

Dendritic spine head diameter is reduced in the prefrontal cortex of progranulin haploinsufficient mice.

Loss-of-function mutations in the progranulin (GRN) gene are an autosomal dominant cause of Frontotemporal Dementia (FTD). These mutations typically result in haploinsufficiency of the progranulin protein. Grn+/- mice provide a model for progranulin haploinsufficiency and develop FTD-like behavioral abnormalities by 9-10 months of age. In previous work, we demonstrated that Grn+/- mice develop a low dominance phenotype in the tube test that is associated with reduced dendritic arborization of layer II/III pyramidal neurons in the prelimbic region of the medial prefrontal cortex (mPFC), a region key for social dominance behavior in the tube test assay. In this study, we investigated whether progranulin haploinsufficiency induced changes in dendritic spine density and morphology. Individual layer II/III pyramidal neurons in the prelimbic mPFC of 9-10 month old wild-type or Grn+/- mice were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and 3D reconstruction for morphometry analysis. Dendritic spine density in Grn+/- mice was comparable to wild-type littermates, but the apical dendrites in Grn+/- mice had a shift in the proportion of spine types, with fewer stubby spines and more thin spines. Additionally, apical dendrites of Grn+/- mice had longer spines and smaller thin spine head diameter in comparison to wild-type littermates. These changes in spine morphology may contribute to altered circuit-level activity and social dominance deficits in Grn+/- mice.

Pay-for-Performance Incentives for Home Dialysis Use and Kidney Transplant.

Importance: The Centers for Medicare & Medicaid Services' mandatory End-Stage Renal Disease Treatment Choices (ETC) model, launched on January 1, 2021, randomly assigned approximately 30% of US dialysis facilities and managing clinicians to financial incentives to increase the use of home dialysis and kidney transplant. Objective: To assess the ETC's association with use of home dialysis and kidney transplant during the model's first 2 years and examine changes in these outcomes by race, ethnicity, and socioeconomic status. Design, Setting, and Participants: This retrospective cross-sectional study used claims and enrollment data for traditional Medicare beneficiaries with kidney failure from 2017 to 2022 linked to same-period transplant data from the United Network for Organ Sharing. The study data span 4 years (2017-2020) before the implementation of the ETC model on January 1, 2021, and 2 years (2021-2022) following the model's implementation. Exposure: Receiving dialysis treatment in a region randomly assigned to the ETC model. Main Outcomes and Measures: Primary outcomes were use of home dialysis and kidney transplant. A difference-in-differences (DiD) approach was used to estimate changes in outcomes among patients treated in regions randomly selected for ETC participation compared with concurrent changes among patients treated in control regions. Results: The study population included 724 406 persons with kidney failure (mean [IQR] age, 62.2 [53-72] years; 42.5% female). The proportion of patients receiving home dialysis increased from 12.1% to 14.3% in ETC regions and from 12.9% to 15.1% in control regions, yielding an adjusted DiD estimate of -0.2 percentage points (pp; 95% CI, -0.7 to 0.3 pp). Similar analysis for transplant yielded an adjusted DiD estimate of 0.02 pp (95% CI, -0.01 to 0.04 pp). When further stratified by sociodemographic measures, including age, sex, race and ethnicity, dual Medicare and Medicaid enrollment, and poverty quartile, there was not a statistically significant difference in home dialysis use across joint strata of characteristics and ETC participation. Conclusions and Relevance: In this cross-sectional study, the first 2 years of the ETC model were not associated with increased use of home dialysis or kidney transplant, nor changes in racial, ethnic, and socioeconomic disparities in these outcomes.

Inflammatory myofibroblastic tumor in a patient with X-Linked hypophosphatemia: A case of Occam's razor or Hickam's dictum?

We present the case of a patient with X-Linked Hypophosphatemia (XLH) and an inflammatory myofibroblastic tumor (IMT) of the bladder which prompted further investigation into the possible relationship between XLH and IMT i.e. a case of Occam's Razor or Hickam's Dictum?

The Mosquito Fauna of Arizona: Species Composition and Public Health Implications.

Arizona is home to many mosquito species, some of which are known vectors of infectious diseases that harm both humans and animals. Here, we provide an overview of the 56 mosquito species that have been identified in the State to date, but also discuss their known feeding preference and the diseases they can (potentially) transmit to humans and animals. This list is unlikely to be complete for several reasons: (i) Arizona's mosquitoes are not systematically surveyed in many areas, (ii) surveillance efforts often target specific species of interest, and (iii) doubts have been raised by one or more scientists about the accuracy of some collection records, which has been noted in this article. There needs to be an integrated and multifaceted surveillance approach that involves entomologists and epidemiologists, but also social scientists, wildlife ecologists, ornithologists, representatives from the agricultural department, and irrigation and drainage districts. This will allow public health officials to (i) monitor changes in current mosquito species diversity and abundance, (ii) monitor the introduction of new or invasive species, (iii) identify locations or specific populations that are more at risk for mosquito-borne diseases, and (iv) effectively guide vector control.

Analysis of unknown (unlabeled/mislabeled) drug products for active pharmaceutical ingredients and related substances by an international mail facility satellite laboratory equipped with rapid screening devices.

Two chemists employed a three-device rapid screening "toolkit" consisting of a handheld Raman spectrometer, transportable mass spectrometer, and portable Fourier transform infrared (FT-IR) spectrometer at an international mail facility (IMF) satellite laboratory to examine unknown (unlabeled/mislabeled) products for the presence of active pharmaceutical ingredients (APIs). Phase I of this project previously demonstrated that this toolkit was the most effective collection of instruments for identifying APIs in product types collected at IMFs during a nationwide mail blitz and Phase II of this project previously demonstrated that results generated using the toolkit during a satellite laboratory pilot program were as reliable as those generated by a full-service library when two or more of these instruments identify an API. This study (Phase III) described the results of the satellite laboratory toolkit during production mode and encompassed the period ranging from June 2021 through December 2022. During this study, a total of 858 products were examined on-site at the IMF. The satellite laboratory yielded conclusive results for 726 (84.6%) products, which were used to support regulatory action, and identified 132 (15.4%) products that required additional full-service laboratory analyses due to inconclusive results. The satellite and full-service laboratory verified/confirmed at least one API/related substance in 617 (71.9%) products. A total of 709 APIs/related substances were found in the 617 products, and 202 of these 709 compounds were unique/different. Overall, during Phases I through III of this program, 350 different substances have been identified in products collected at IMFs.

Short- and long-range roles of UNC-6/Netrin in dorsal-ventral axon guidance in vivo in Caenorhabditis elegans.

Recent studies in vertebrates and Caenorhabditis elegans have reshaped models of how the axon guidance cue UNC-6/Netrin functions in dorsal-ventral axon guidance, which was traditionally thought to form a ventral-to-dorsal concentration gradient that was actively sensed by growing axons. In the vertebrate spinal cord, floorplate Netrin1 was shown to be largely dispensable for ventral commissural growth. Rather, short range interactions with Netrin1 on the ventricular zone radial glial stem cells was shown to guide ventral commissural axon growth. In C. elegans, analysis of dorsally-migrating growth cones during outgrowth has shown that growth cone polarity of filopodial extension is separable from the extent of growth cone protrusion. Growth cones are first polarized by UNC-6/Netrin, and subsequent regulation of protrusion by UNC-6/Netrin is based on this earlier-established polarity (the Polarity/Protrusion model). In both cases, short-range or even haptotactic mechanisms are invoked: in vertebrate spinal cord, interactions of growth cones with radial glia expressing Netrin-1; and in C. elegans, a potential close-range interaction that polarizes the growth cone. To explore potential short-range and long-range functions of UNC-6/Netrin, a potentially membrane-anchored transmembrane UNC-6 (UNC-6(TM)) was generated by genome editing. Unc-6(tm) was hypomorphic for dorsal VD/DD axon pathfinding, indicating that it retained some unc-6 function. Polarity of VD growth cone filopodial protrusion was initially established in unc-6(tm), but was lost as the growth cones migrated away from the unc-6(tm) source in the ventral nerve cord. In contrast, ventral guidance of the AVM and PVM axons was equally severe in unc-6(tm) and unc-6(null). Together, these results suggest that unc-6(tm) retains short-range functions but lacks long-range functions. Finally, ectopic unc-6(+) expression from non-ventral sources could rescue dorsal and ventral guidance defects in unc-6(tm) and unc-6(null). Thus, a ventral directional source of UNC-6 was not required for dorsal-ventral axon guidance, and UNC-6 can act as a permissive, not instructive, cue for dorsal-ventral axon guidance. Possibly, UNC-6 is a permissive signal that activates cell-intrinsic polarity; or UNC-6 acts with another signal that is required in a directional manner. In either case, the role of UNC-6 is to polarize the pro-protrusive activity of UNC-40/DCC in the direction of outgrowth.