Epidemiologic Characteristics of Mpox among People Experiencing Homelessness, Los Angeles County, California, USA, 2022.

In Los Angeles County, California, USA, public health surveillance identified 118 mpox cases among persons experiencing homelessness (PEH) during July-September 2022. Age and sex were similar for mpox case-patients among PEH and in the general population. Seventy-one (60%) PEH mpox case-patients were living with HIV, 35 (49%) of them virally suppressed. Hospitalization was required for 21% of case-patients because of severe disease. Sexual contact was likely the primary mode of transmission; 84% of patients reported sexual contact <3 weeks before symptom onset. PEH case-patients lived in shelters, encampments, cars, or on the street, or stayed briefly with friends or family (couch surfed). Some case-patients stayed at multiple locations during the 3-week incubation period. Public health follow-up and contact tracing detected no secondary mpox cases among PEH in congregate shelters or encampments. Equitable efforts should continue to identify, treat, and prevent mpox among PEH, who often experience severe disease.

Evaluation of the Homeless Management Information System for COVID-19 Surveillance Among People Experiencing Homelessness.

BACKGROUND: Variable and incomplete reporting of housing status creates challenges in the surveillance of coronavirus disease 2019 (COVID-19) among the homeless population in Los Angeles County (LA County) and nationwide. METHODS: We developed standard investigation procedures to assess the housing status of LA County COVID-19 patients. Using data sharing procedures, we matched COVID-19 patients to Homeless Management Information System (HMIS) client profiles and supplemented with additional data sources for contributory data points and to further housing status ascertainment. RESULTS: We identified 10 586 COVID-19 patients among people experiencing homelessness (PEH) between 30 March 2020 and 30 December 2021; 2801 (26.5%) patients were first identified from HMIS profile matches, 1877 (17.7%) from quarantine/isolation housing intake rosters, 573 (5.4%) from hospital records, 749 (7.1%) from case and contact interviews, 3659 (34.6%) directly from PEH medical and service providers, and 927 (8.8%) had unknown sources. Among COVID-19 patients matched to HMIS profiles, 5351 (42.5%) were confirmed to be PEH at the time of COVID-19 diagnosis. CONCLUSIONS: Interoperability between public health data, HMIS, and external partners have been critical components in evaluating the impact of COVID-19 among the LA County homeless population. No one data source was complete for COVID-19 surveillance in this population.

Device use errors with soft mist inhalers: A global systematic literature review and meta-analysis.

Inhaled bronchodilators are the cornerstone of treatment for chronic obstructive pulmonary disease (COPD). Soft mist inhalers (SMIs) are devices that deliver bronchodilators. Although correct device use is paramount to successful medication delivery, patient errors are common. This global systematic literature review and meta-analysis examined device use errors with SMIs among patients with obstructive lung diseases. PubMed, EMBASE, PsycINFO, Cochrane, and Google Scholar were searched to identify studies published between 2010 and 2019 that met the following inclusion criteria: (a) English language; (b) a diagnosis of COPD, bronchitis, or emphysema; and (c) reported device use errors among adults receiving long-acting bronchodilator treatment with Respimat® SMI (i.e. Spiriva®, Stiolto®, Spiolto®, and Striverdi®). Descriptive statistics examined sociodemographics, clinical characteristics, and device use errors. Meta-analysis techniques were employed with random-effects models to generate pooled mean effect sizes and 95% confidence intervals (CIs) for overall and step-by-step errors. The I2 statistic measured heterogeneity. Twelve studies (n = 1288 patients) were included in this meta-analysis. Eighty-eight percent of patients had COPD, and most had moderate/very severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease spirometric stages II to IV). Aggregate results revealed that 58.9% (95% CI: 42.4-75.5; I2 = 92.8%) of patients made ≥1 device use errors. Among 11 studies with step-by-step data, the most common errors were failure to (1) exhale completely and away from the device (47.8% (95% CI: 33.6-62.0)); (2) hold breath for up to 10 seconds (30.6% (95% CI: 17.5-43.7)); (3) take a slow, deep breath while pressing the dose release button (27.9% (95% CI: 14.5-41.2)); (4) hold the inhaler upright (22.6% (95% CI: 6.2-39.0)); and (5) turn the base toward the arrows until it clicked (17.6% (95% CI: 3.0-32.2)). Device use errors occurred in about 6 of 10 patients who used SMIs. An individualized approach to inhalation device selection and ongoing training and monitoring of device use are important in optimizing bronchodilator treatment.

RSK1 activation promotes invasion in nodular melanoma.

The two major melanoma histologic subtypes, superficial spreading and nodular melanomas, differ in their speed of dermal invasion but converge biologically once they invade and metastasize. Herein, we tested the hypothesis that distinct molecular alterations arising in primary melanoma cells might persist as these tumors progress to invasion and metastasis. Ribosomal protein S6 kinase, 90 kDa, polypeptide 1 (RSK1; official name RPS6KA1) was significantly hyperactivated in human melanoma lines and metastatic tissues derived from nodular compared with superficial spreading melanoma. RSK1 was constitutively phosphorylated at Ser-380 in nodular but not superficial spreading melanoma and did not directly correlate with BRAF or MEK activation. Nodular melanoma cells were more sensitive to RSK1 inhibition using siRNA and the pharmacological inhibitor BI-D1870 compared with superficial spreading cells. Gene expression microarray analyses revealed that RSK1 orchestrated a program of gene expression that promoted cell motility and invasion. Differential overexpression of the prometastatic matrix metalloproteinase 8 and tissue inhibitor of metalloproteinases 1 in metastatic nodular compared with metastatic superficial spreading melanoma was observed. Finally, using an in vivo zebrafish model, constitutive RSK1 activation increased melanoma invasion. Together, these data reveal a novel role for activated RSK1 in the progression of nodular melanoma and suggest that melanoma originating from different histologic subtypes may be biologically distinct and that these differences are maintained as the tumors invade and metastasize.

The risk of childhood brain tumors associated with delivery interventions: A Danish matched case-control study.

BACKGROUND: Head trauma has been associated with increased brain tumor risk in adults. Instrument assisted delivery can be a cause of head trauma in newborns. The goal of this study was to determine if instrument-assisted deliveries influenced the odds of childhood brain tumors in Denmark. METHODS: We conducted a matched case-control study of childhood (<20 years) brain tumors in Denmark born between 1978 and 2013 and diagnosed 1978-2016. A total of 1678 brain tumor cases were identified and 25 controls were matched to each case based on the child's sex and birth date (N = 40,934). Conditional logistic regression was used to estimate effects (odds ratios (OR) and 95% confidence intervals (95%CI)) for variables of interest. RESULTS: Compared to children birthed by spontaneous vaginal delivery, children who later developed ependymomas (N = 118) had a greater likelihood of having experienced vacuum assisted deliveries (OR=1.74, 95% CI 1.02-2.96). Forceps use was low, and declined across the study period. We did not observe an overall increase in all CNS tumors (combined) with either vacuum delivery (OR=0.99, 95% CI 0.84-1.18) or forceps delivery (OR=1.26, 95% CI 0.78-2.03). CONCLUSION: Our findings suggest an association between vacuum assisted deliveries and ependymomas.

Impact of obesity on the severity and therapeutic responsiveness of acute episodes of asthma.

BACKGROUND: It has been suggested that obesity adversely influences both the severity and the therapeutic responsiveness of chronic asthma. However, it is unclear if it also impacts acute situations. METHODS: To determine whether adiposity worsens the clinical and physiological manifestations of acute asthma and limits therapeutic effectiveness of standard treatment, we contrasted signs, symptoms, medication use, arterial oxygen saturation, peak expiratory flow rate, and the bronchodilator response to standard doses of albuterol in 90 non-obese and 90 obese asthmatics as they presented for urgent care. Treatment and clinical decisions were systematized using published care paths and the peak flow was measured with standard techniques. Body mass index (BMI) was calculated according to consensus criteria. RESULTS: Other than BMI (p < .001), there were no between-group differences in age, gender, race, signs, symptoms, pulse oximetry, or pre-presentation medication use. The pretreatment peak flow in the obese population was 22.4% higher on average (p = .007), but there were no differences in the distribution of severity (p = .38), the response to albuterol (p = .61), or admission-discharge ratios (p = .62). CONCLUSIONS: Obesity does not adversely influence the severity or the resolution of acute episodes of asthma.

Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes fails to predict breast cancer recurrence: a final analysis of a prospective multi-institutional cohort study.

BACKGROUND: To address the clinical relevance of molecular detection of occult breast cancer in sentinel lymph nodes and nonsentinel axillary lymph nodes (ALN), we initiated the Minimally Invasive Molecular Staging of Breast Cancer (MIMS) trial, a multi-institutional prospective cohort study. This trial represents the first prospective cohort study in which a multimarker, real-time reverse transcription polymerase chain reaction (RT-PCR) analysis was applied to the detection of breast cancer micrometastases in ALN. MATERIALS AND METHODS: Sentinel and/or nonsentinel ALN from 501 breast cancer subjects with T1-T3 primary tumors were analyzed by standard histopathology and multimarker, real-time RT-PCR analysis. Seven breast cancer-associated genes (mam, mamB, PIP, CK19, muc1, PSE, and CEA) known to be overexpressed in metastatic breast cancer compared with control lymph nodes were used. Follow-up data were collected for 5 years. RESULTS: Of the 501 breast cancer subjects enrolled, 348 were node negative and completed the 5-year follow-up. Of these patients (n = 94), 27% demonstrated evidence of molecular overexpression. The 5-year relapse-free survival rate was 95.4% (95% confidence interval [95% CI], 92.4-97.2%). No single gene or combination of study genes was predictive of recurrence. CONCLUSIONS: The genes in this study panel failed to be predictive of clinical relapse. This may be a function of several factors: the low event rate at 5 years, the particular gene set, the methodology used for detection/analysis or that our original hypothesis was wrong and that the presence of positive marker signal by real-time RT-PCR is not associated with a worsened clinical outcome.

Inhaler device feature preferences among patients with obstructive lung diseases: A systematic review and meta-analysis.

BACKGROUND: Bronchodilators administered through inhalation devices are the mainstay treatment for patients with obstructive lung diseases. Patients do not view devices as interchangeable. This systematic review and meta-analysis examined device feature preferences among patients with obstructive lung diseases treated with handheld inhalers. STUDY APPRAISAL AND SYNTHESIS METHODS: PubMed, EMBASE, PsycINFO, Cochrane, and Google Scholar were searched to identify publications between 2010 and 2019 that met the following criteria:A manual search extended the study period from 2001 to 2019. Random-effects models were used to generate pooled mean effect sizes and 95% confidence intervals (CIs) for preferred device features. Heterogeneity was measured by the I statistic. RESULTS: Nineteen studies (n = 11,256) were included in this meta-analysis. Average age ranged from 50.4 to 74.3 years. The majority of patients were male (57%) and had chronic obstructive pulmonary disease (92%).Patients preferred the following device features: CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS:: Adults with obstructive lung diseases preferred small inhaler devices that were portable, durable, perceived as easy to use, and fast in medication administration. Healthcare providers should give due consideration to the patient's device feature preferences when developing a treatment plan that prescribes an inhalation device.

Inhalation Technique Errors with Metered-Dose Inhalers Among Patients with Obstructive Lung Diseases: A Systematic Review and Meta-Analysis of U.S. Studies.

BACKGROUND: Metered dose inhalers (MDIs) are commonly prescribed for inhalation therapy, but correct use is critical to promoting effective medication delivery. This systematic literature review and meta-analysis evaluates the overall and step-by-step prevalence of errors among adults with obstructive lung diseases in the United States who used MDIs. METHODS: Electronic and manual searches conducted between 1979-2018 using PubMed, EMBASE, PsycINFO, Cochrane, and Google identified 10 articles that met the following inclusion criteria: (a) English language, (b) U.S. adults diagnosed with chronic obstructive pulmonary disease, and (c) MDI use error rates. Meta-analytic techniques using random-effects models were applied to calculate effect sizes, weighted proportions, and 95% confidence intervals (CIs). Heterogeneity was assessed by the I2 statistic. RESULTS: Aggregate findings revealed that 86.7% of patients (n=390, 95% CI 77.5-96.0) made at least 1 inhalation technique error, and 76.9% (n=885, 95% CI 65.8-87.9) incorrectly performed ≥ 20% of device use steps. The most prevalent step-by-step errors across the studies (n=1105) were failure to: (a) exhale fully and away from the inhaler before inhalation (65.5% [95% CI 52.0, 78.9]); (b) hold breath for 5-10 seconds (41.9% [95% CI 29.8, 53.9]); (c) inhale slowly and deeply (39.4% [95% CI 26.2, 52.5]); (d) exhale after inhalation (35.9% [95% CI 17.0, 54.8]); and (e) shake the inhaler before use (34.2% [95% CI 30.6, 37.7]). CONCLUSIONS: Across the studies used in this meta-analysis more than three-fourths of U.S. adults with obstructive lung diseases used MDIs incorrectly. Our findings suggest the need for ongoing patient education and consideration of alternative devices to mitigate errors.

Defining hepatic dysfunction parameters in two models of fatty liver disease in zebrafish larvae.

Fatty liver disease in humans can progress from steatosis to hepatocellular injury, fibrosis, cirrhosis, and liver failure. We developed a series of straightforward assays to determine whether zebrafish larvae with either tunicamycin- or ethanol-induced steatosis develop hepatic dysfunction. We found altered expression of genes involved in acute phase response and hepatic function, and impaired hepatocyte secretion and disruption of canaliculi in both models, but glycogen deficiency in hepatocytes and dilation of hepatic vasculature occurred only in ethanol-treated larvae. Hepatic stellate cells (HSCs) become activated during liver injury and HSC numbers increased in both models. Whether the excess lipids in hepatocytes are a direct cause of hepatocyte dysfunction in fatty liver disease has not been defined. We prevented ethanol-induced steatosis by blocking activation of the sterol response element binding proteins (Srebps) using gonzo(mbtps1) mutants and scap morphants and found that hepatocyte dysfunction persisted even in the absence of lipid accumulation. This suggests that lipotoxicity is not the primary cause of hepatic injury in these models of fatty liver disease. This study provides a panel of parameters to assess liver disease that can be easily applied to zebrafish mutants, transgenics, and for drug screening in which liver function is an important consideration.

Acute manipulation of diacylglycerol reveals roles in nuclear envelope assembly & endoplasmic reticulum morphology.

The functions and morphology of cellular membranes are intimately related and depend not only on their protein content but also on the repertoire of lipids that comprise them. In the absence of in vivo data on lipid asymmetry in endomembranes, it has been argued that motors, scaffolding proteins or integral membrane proteins rather than non-lamellar bilayer lipids such as diacylglycerol (DAG), are responsible for shaping of organelles, local membrane curvature and fusion. The effects of direct alteration of levels of such lipids remain predominantly uninvestigated. Diacylglycerol (DAG) is a well documented second messenger. Here we demonstrate two additional conserved functions of DAG: a structural role in organelle morphology, and a role in localised extreme membrane curvature required for fusion for which proteins alone are insufficient. Acute and inducible DAG depletion results in failure of the nuclear envelope (NE) to reform at mitosis and reorganisation of the ER into multi-lamellar sheets as revealed by correlative light and electron microscopy and 3D reconstructions. Remarkably, depleted cells divide without a complete NE, and unless rescued by 1,2 or 1,3 DAG soon die. Attenuation of DAG levels by enzyme microinjection into echinoderm eggs and embryos also results in alterations of ER morphology and nuclear membrane fusion. Our findings demonstrate that DAG is an in vivo modulator of organelle morphology in mammalian and echinoderm cells, indicating a fundamental role conserved across the deuterostome superphylum.

beta-Catenin has sequential roles in the survival and specification of ventral dermis.

The dermis promotes the development and maintains the functional components of skin, such as hair follicles, sweat glands, nerves and blood vessels. The dermis is also crucial for wound healing and homeostasis of the skin. The dermis originates from the somites, the lateral plate mesoderm and the cranial neural crest. Despite the importance of the dermis in the structural and functional integrity of the skin, genetic analysis of dermal development in different parts of the embryo is incomplete. The signaling requirements for ventral dermal cell development have not been established in either the chick or the mammalian embryo. We have shown previously that Wnt signaling specifies the dorsal dermis from the somites. In this study, we demonstrate that Wnt/beta-catenin signaling is necessary for the survival of early ventral dermal progenitors. In addition, we show that, at later stages, Wnt/beta-catenin signaling is sufficient for ventral dermal cell specification. Consistent with the different origins of dorsal and ventral dermal cells, our results demonstrate both conserved and divergent roles of beta-catenin/Wnt signaling in dermal development.

Continuous abdominal fascial closure: a randomized controlled trial of poly(L-lactide/glycolide).

OBJECTIVE: The objective was to compare the handling characteristics and

Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes correlates with traditional predictors of prognosis: an interim analysis of a prospective multi-institutional cohort study.

OBJECTIVE: We sought to establish the clinical relevance of micrometastatic disease detected by reverse transcription polymerase chain reaction (RT-PCR) in axillary lymph nodes (ALN) of breast cancer patients. BACKGROUND: The presence of ALN metastases remains one of the most valuable prognostic indicators in women with breast cancer. However, the clinical relevance of molecular detection of micrometastatic breast cancer in sentinel lymph nodes (SLN) and nonsentinel ALN has not been established. METHODS: Four hundred eighty-nine patients with T1-T3 primary breast cancers were analyzed in a prospective, multi-institutional cohort study. ALN were analyzed by standard histopathology (H&E staining) and by multimarker, real-time RT-PCR analysis (mam, mamB, muc1, CEA, PSE, CK19, and PIP) designed to detect breast cancer micrometastases. RESULTS: A positive marker signal was observed in 126 (87%) of 145 subjects with pathology-positive ALN, and in 112 (33%) of 344 subjects with pathology-negative ALN. In subjects with pathology-negative ALN, a positive marker signal was significantly associated with traditional indicators of prognosis, such as histologic grade (P = 0.0255) and St. Gallen risk category (P = 0.022). Mammaglobin was the most informative marker in the panel. CONCLUSION: This is the first report to show that overexpression of breast cancer-associated genes in breast cancer subjects with pathology-negative ALN correlates with traditional indicators of disease prognosis. These interim results provide strong evidence that molecular markers could serve as valid surrogates for the detection of occult micrometastases in ALN. Correlation of real-time RT-PCR analyses with disease-free survival in this patient cohort will help to define the clinical relevance of micrometastatic disease in this patient population.