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Objective: We sought to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on perinatal outcomes while accounting for maternal depression or perceived stress and to describe COVID-specific stressors, including changes in prenatal care, across specific time periods of the pandemic., Study Design: Data of dyads from 41 cohorts from the National Institutes of Health Environmental influences on Child Health Outcomes Program ( N  = 2,983) were used to compare birth outcomes before and during the pandemic ( n  = 2,355), and a partially overlapping sample ( n  = 1,490) responded to a COVID-19 questionnaire. Psychosocial stress was defined using prenatal screening for depression and perceived stress. Propensity-score matching and general estimating equations with robust variance estimation were used to estimate the pandemic's effect on birth outcomes., Results: Symptoms of depression and perceived stress during pregnancy were similar prior to and during the pandemic, with nearly 40% of participants reporting mild to severe stress, and 24% reporting mild depression to severe depression. Gestations were shorter during the pandemic ( B  =  - 0.33 weeks, p  = 0.025), and depression was significantly associated with shortened gestation ( B  =  - 0.02 weeks, p  = 0.015) after adjustment. Birth weights were similar ( B  =  - 28.14 g, p  = 0.568), but infants born during the pandemic had slightly larger birth weights for gestational age at delivery than those born before the pandemic ( B  = 0.15 z-score units, p  = 0.041). More women who gave birth early in the pandemic reported being moderately or extremely distressed about changes to their prenatal care and delivery (45%) compared with those who delivered later in the pandemic. A majority (72%) reported somewhat to extremely negative views of the impact of COVID-19 on their life., Conclusion: In this national cohort, we detected no effect of COVID-19 on prenatal depression or perceived stress. However, experiencing the COVID-19 pandemic in pregnancy was associated with decreases in gestational age at birth, as well as distress about changes in prenatal care early in the pandemic., Key Points: · COVID-19 was associated with shortened gestations.. · Depression was associated with shortened gestations.. · However, stress during the pandemic remained unchanged.. · Most women reported negative impacts of the pandemic.., Competing Interests: C.M. served as Chair of the Data Safety Monitoring Board (DSMB) for an Aerogen-supported trial: A Partially-Blind, Randomized, Controlled, Parallel-Group Dose Ranging Study to Determine the Efficacy, Safety and Tolerability of AeroFactTM (SF-RI 1 surfactant for inhalation combined with a dedicated drug delivery system) in Preterm Infants at Risk for Worsening Respiratory Distress Syndrome; Chair of the DSMB for the NIH RCT evaluating Sildenafil in Preterm Infants with Pulmonary Hypertension. J.N. served on the Advisory Board for the Twin Life Study (Germany); received royalties or licenses from Macmillan and consulting fees from the University of Southern California. J.H. served on the New York State Drinking Water Quality Council. The other authors have no conflicts of interest to disclose., (Thieme. All rights reserved.)

Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance and increasing paracellular flux, partially by NET-induced airway cell apoptosis. NETs selectively impact the expression of tight junction genes claudins 4, 8 and 11. Bronchial epithelia exposed to NETs demonstrate visible gaps in E-cadherin staining, a decrease in full-length E-cadherin protein and the appearance of cleaved E-cadherin peptides. Pretreatment of NETs with alpha-1 antitrypsin (A1AT) inhibits NET serine protease activity, limits E-cadherin cleavage, decreases bronchial cell apoptosis and preserves epithelial integrity. In conclusion, NETs disrupt human airway epithelial barrier function through bronchial cell death and degradation of E-cadherin, which are limited by exogenous A1AT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hudock, Collins, Imbrogno, Kramer, Brewington, Ziady, Zhang, Snowball, Xu, Carey, Horio, O’Grady, Kopras, Meeker, Morgan, Ostmann, Skala, Siefert, Na, Davidson, Gollomp, Mangalmurti, Trapnell and Clancy.)

Background: Despite over 150000 amputations of lower limbs annually, there remains a wide variation in tourniquet practice patterns and no consensus on their necessity, especially among orthopedic patient populations. The purpose of this study was to determine whether tourniquet use in orthopedic patients undergoing below knee amputation (BKA) was associated with a difference in calculated blood loss relative to no tourniquet use., Aim: To determine if tourniquet use in orthopedic patients undergoing BKA was associated with a difference in calculated blood loss relative to no tourniquet use., Methods: We performed a retrospective review of consecutive patients undergoing BKA by orthopedic surgeons at a tertiary care hospital from 2008 through 2018. Blood loss was calculated using a combination of the Nadler equation for preoperative blood volume and a novel formula utilizing preoperative and postoperative hemoglobin levels and transfusions. Univariate and forwards step-wise multivariate linear regressions were performed to determine the association between tourniquet use and blood loss. A Wilcoxon was used to determine the univariate relationship between tourniquet use and blood loss for in the restricted subgroups of patients who underwent BKA for trauma, tumor, and infection., Results: Of 97 eligible patients identified, 67 underwent surgery with a tourniquet and 30 did not. In multivariate regression, tourniquet use was associated with a 488 mL decrease in calculated blood loss (CI 119-857, P = 0.01). In subgroup analysis, no individual group showed a statistically significant decrease in blood loss with tourniquet use. There was no significant association between tourniquet use and either postoperative transfusions or reoperation at one year., Conclusion: We found that tourniquet use during BKA is associated with decreased calculated intraoperative blood loss. We recommend that surgeons performing this procedure use a tourniquet to minimize blood loss., Competing Interests: Conflict-of-interest statement: Each author certifies that he or she has no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/Licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

To increase the effectiveness of social assistance on child nutrition, programmes are increasingly combined with behaviour change communication for improved infant and young child feeding (BCC for IYCF). Unfortunately, there is limited knowledge about which BCC strategies are most effective when combined with social assistance. A systematic scoping review and an expert consultation was conducted to (1) describe the landscape of BCC for IYCF strategies used in social assistance within low- and middle-income countries and (2) to examine the effects of these BCC strategies on IYCF practices and child nutrition. Ten quantitative, three qualitative and four mixed methods studies were reviewed and complemented by 12 expert consultations carried out between August and October 2020. In most of the studies attendance in BCC for IYCF was conditional for receiving social assistance, although experts agreed that this conditionality may be counterproductive. A variety of BCC strategies were used with two being most common-group sessions with pre-determined topics and individual counselling. Context-specific adaptation, interactive delivery and building on existing IYCF knowledge emerged as crucial but was perceived as economically infeasible in social assistance programmes. Given the variety of BCC strategies and inconsistency in outcomes, it is impossible to draw conclusions regarding effectiveness. Nevertheless, tentative evidence suggests that the promotion of existing nutrition services, educational group sessions and individual counselling may be effective in improving IYCF. BCC for IYCF can make social assistance more beneficial, but may increase costs, demands on beneficiaries, and deviate from the original focus of the programmes., (© 2022 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Environmental disasters are anthropogenic catastrophic events that affect health. Famous disasters include the Seveso disaster and the Fukushima-Daiichi nuclear meltdown, which had disastrous health consequences. Traditional methods for studying environmental disasters are costly and time-intensive. We propose the use of electronic health records (EHR) and informatics methods to study the health effects of emergent environmental disasters in a cost-effective manner. An emergent environmental disaster is exposure to perfluoroalkyl substances (PFAS) in the Philadelphia area. Penn Medicine (PennMed) comprises multiple hospitals and facilities within the Philadelphia Metropolitan area, including over three thousand PFAS-exposed women living in one of the highest PFAS exposure areas nationwide. We developed a high-throughput method that utilizes only EHR data to evaluate the disease risk in this heavily exposed population. We replicated all five disease/conditions implicated by PFAS exposure, including hypercholesterolemia, thyroid disease, proteinuria, kidney disease and colitis, either directly or via closely related diagnoses. Using EHRs coupled with informatics enables the health impacts of environmental disasters to be more easily studied in large cohorts versus traditional methods that rely on interviews and expensive serum-based testing. By reducing cost and increasing the diversity of individuals included in studies, we can overcome many of the hurdles faced by previous studies, including a lack of racial and ethnic diversity. This proof-of-concept study confirms that EHRs can be used to study human health and disease impacts of environmental disasters and produces equivalent disease-exposure knowledge to prospective epidemiology studies while remaining cost-effective., (© 2021. The Author(s).)

As of August 2020, there were ~6 million COVID-19 cases in the United States of America, resulting in ~200,000 deaths. Informatics approaches are needed to better understand the role of individual and community risk factors for COVID-19. We developed an informatics method to integrate SARS-CoV-2 data with multiple neighborhood-level factors from the American Community Survey and opendataphilly.org. We assessed the spatial association between neighborhood-level factors and the frequency of SARS-CoV-2 positivity, separately across all patients and across asymptomatic patients. We found that neighborhoods with higher proportions of individuals with a high-school degree and/or who were identified as Hispanic/Latinx were more likely to have higher SARS-CoV-2 positivity rates, after adjusting for other neighborhood covariates. Patients from neighborhoods with higher proportions of individuals receiving public assistance and/or identified as White were less likely to test positive for SARS-CoV-2. Our approach and its findings could inform future public health efforts., (©2021 AMIA - All rights reserved.)

Cases: Intraosseous (IO) access is an effective surrogate for intravascular access in critically ill patients. We present 2 cases of IO complications. The first patient is a 44-year-old man with deep peroneal nerve sensorimotor dysfunction due to possible missed acute compartment syndrome from improper placement of a tibial IO needle. The second patient is an immunosuppressed 69-year-old man with idiopathic factor VIII deficiency who required amputation 7 months after right tibia IO access., Conclusion: These adverse events of IO access are limited in the literature. We make recommendations to reduce these outcomes., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B322)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Schantz pin placement in the calcaneal tuberosity is a common procedure known to be complicated by pin site infections and nerve injuries. Fractures through Schantz pin sites has been reported mostly in diaphyseal bone. This case series highlights three patients with type 2 diabetes mellitus and diabetic neuropathy who were fixed in an external fixator frame with a pin through the calcaneal tuberosity. At an average of 13 weeks, the patients presented with fracture through the pin site at the calcaneal tuberosity. One patient was treated with open reduction and internal fixation of the calcaneus and two patients were treated nonoperatively. These cases suggest that placement of calcaneal pins in patients with diabetic neuropathy harbors risk of iatrogenic fracture, a complication that has not been reported in the literature., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cold panniculitis and perniosis are the most common cold-induced dermatologic disorders and are clinically characterized by indurated and erythematous nodules and plaques that develop at sites exposed to excessive cold and wet conditions. Cold panniculitis is most commonly seen in infants, but adult cases involving the thighs of equestrians are well known and have come to be known as equestrian cold panniculitis or equestrian perniosis. Recently, similar cases have been described in nonequestrian settings with the prolonged use of ice-packs or other cold-therapy devices. We describe the case of 51-year-old female patient who underwent recent arthroscopic shoulder surgery for repair of a rotator cuff tear and presented to the dermatology clinic for painful and erythematous nodules on her arm. A punch biopsy demonstrated a superficial and deep perivascular and periappendageal lymphocytic infiltrate with some spillover into the superficial subcutaneous adipose tissue. Focal vacuolar changes along the basal layer of the epidermis with a few dyskeratotic keratinocytes were present. A mild increase in interstitial mucin was seen, but no significant papillary dermal edema. On clinical questioning she admitted to sustained use of icepacks on the injured shoulder postoperatively for up to 18 hours a day. Based on clinical and histopathologic features the diagnosis of ice-pack dermatosis was made. A review of cold-induced dermatoses is considered with a focus on the main histologic differential diagnoses.

This study examined the relationship of surgical management of humerus shaft fractures (HSFs) with race, gender, insurance status, and presence of lower extremity fracture in 19,818 patients from the National Trauma Data Bank years 2007-2012. Using a multivariate logistic regression model, black males (OR 0.73, 95% CI 0.66-0.81, p < 0.001) and white females (OR 0.85, 95% CI 0.80-0.91, p < 0.001) had reduced odds of surgery compared to white males. Insurance status was not significant. These disparities may reflect bias within the surgical treatment team.

Background: Although patients prefer that physicians initiate advance care planning (ACP) conversations, few physicians regularly do so. Physicians may be reluctant to initiate ACP conversations because they lack self-efficacy in their skills. Yet, no validated scale on self-efficacy for ACP exists. Our objective was to develop a scale that measures physicians' ACP self-efficacy (ACP-SE) and to investigate the validity of the tool., Methods: Electronic questionnaires were administered to a random sample of family medicine physicians (n = 188). Exploratory factor analysis was performed to determine whether the scale was multidimensional. An initial assessment of the scale's validity was also conducted., Results: The exploratory factor analysis indicated that a single factor was appropriate using all 17 items. A single, unidimensional scale was created by averaging the 17 items, yielding good internal consistency (Cronbach α = 0.95). The average scale score was 3.94 (standard deviation = 0.71) on a scale from 1 to 5. The scale was moderately correlated with a global single-item measure of self-efficacy for ACP ( r = .79, P < .001), and the scale differentiated between physician groups based on how much ACP they were doing, how recently they had an ACP conversation, formal training on ACP, and knowledge of ACP. In a multivariate analysis, the ACP-SE scale was a strong predictor of the percentage of patients with chronic life-limiting diseases with whom the physician discussed ACP., Conclusion: The final ACP-SE scale included 17 items and demonstrated high internal consistency.

Background: Twin-to-twin transfusion syndrome (TTTS) affects 10-20 % of monochorionic diamniotic (MCDA) births and accounts for 50 % of fetal loss in MCDA pregnancies. This exploratory qualitative study identified shared experiences, including potential emotional and psychosocial impacts, of this serious disease., Methods: Forty-five publicly accessible, online stories posted by families who experienced TTTS were analyzed using grounded theory., Results: Shared TTTS experiences included a common trajectory: early pregnancy experiences, diagnostic experiences, making decisions, interventions and variable outcomes. Families vacillated between emotional highs such as joy, excitement and relief, and lows including depression, anxiety, anger and grief., Conclusions: TTTS disease experience can be considered an "emotional roller coaster" exacerbated by TTTS's unpredictable and quickly changing nature with the potential for emotional and psychosocial effects. Increased TTTS awareness and research about its corresponding impacts can ensure appropriate patient and family support at all phases of the TTTS experience.

Background: Pesticides are associated with poorer neurodevelopmental outcomes, but little is known about the effects on sensory functioning., Methods: Auditory brainstem response (ABR) and pesticide data were available for 27 healthy, full-term 9-month-old infants participating in a larger study of early iron deficiency and neurodevelopment. Cord blood was analyzed by gas chromatography-mass spectrometry for levels of 20 common pesticides. The ABR forward-masking condition consisted of a click stimulus (masker) delivered via ear canal transducers followed by an identical stimulus delayed by 8, 16, or 64 milliseconds (ms). ABR peak latencies were evaluated as a function of masker-stimulus time interval. Shorter wave latencies reflect faster neural conduction, more mature auditory pathways, and greater degree of myelination. Linear regression models were used to evaluate associations between total number of pesticides detected and ABR outcomes. We considered an additive or synergistic effect of poor iron status by stratifying our analysis by newborn ferritin (based on median split)., Results: Infants in the sample were highly exposed to pesticides; a mean of 4.1 pesticides were detected (range 0-9). ABR Wave V latency and central conduction time (CCT) were associated with the number of pesticides detected in cord blood for the 64ms and non-masker conditions. A similar pattern seen for CCT from the 8ms and 16ms conditions, although statistical significance was not reached. Increased pesticide exposure was associated with longer latency. The relation between number of pesticides detected in cord blood and CCT depended on the infant's cord blood ferritin level. Specifically, the relation was present in the lower cord blood ferritin group but not the higher cord blood ferritin group., Conclusions: ABR processing was slower in infants with greater prenatal pesticide exposure, indicating impaired neuromaturation. Infants with lower cord blood ferritin appeared to be more sensitive to the effects of prenatal pesticide exposure on ABR latency delay, suggesting an additive or multiplicative effect., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Problems paying medical bills have been reported to be associated with increased stress, bankruptcy, and forgone medical care. Using the Behavioral Model for Vulnerable Populations developed by Gelberg et al as a framework, as well as data from the 2010 Ohio Family Health Survey, this study examined the relationships between difficulty paying medical bills and forgone medical and prescription drug care. Logistic regression was used to examine associations between difficulty paying medical bills and predisposing, enabling, need (health status), and health behaviors (forgoing medical care). Difficulty paying medical bills increased the effect of lack of health insurance in predicting forgone medical care and had a conditional effect on the association between education and forgone prescription drug care. Those who had less than a bachelor's degree were more likely to forgo prescription drug care than those with a bachelor's degree, but only if they had difficulty paying medical bills. Difficulty paying medical bills also accounted for the relationships between several population characteristics (eg, age, income, home ownership, health status) in predicting forgone medical and prescription drug care. Policies to cap out-of-pocket medical expenses may mitigate health disparities by addressing the impact of difficulty paying medical bills on forgone care.

Background: Chiari malformation (CM) is characterized by herniation of the cerebellar tonsils into the cervical spine. While ample literature on CM exists for clinical and procedural aspects of the disease, few studies have measured the impact CM has on daily activities., Objective: The objective of this study was to measure the impact that CM has on daily living activities., Methods: Data was analyzed from 798 CM patients gathered by the national Conquer Chiari Patient Registry database., Results: Results indicate CM is associated with negative impact on daily living and physical activities for patients, even those exhibiting mild symptoms. Participants with severe symptoms experience the greatest deficit with regards to daily living such as difficulty walking, driving, housecleaning and food preparation., Conclusions: As 96.1% of CM patients report impact in one or more areas of daily living, CM is classified as a disability according to 42 U.S. CODE § 12101 (Americans with Disabilities Act). The degree of self-reported CM symptom severity is strongly related to the frequency and extent of limitations in both physical and daily activities., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: The purpose of this study was to conduct an exploratory examination of the current state of non-malignant acute and chronic back and neck pain assessment and management among primary care providers in a multi-site, practice-based research network., Background: Acute and chronic pain are distinct conditions that often require different assessment and management approaches, however, little research has examined assessment and management of acute and chronic pain as separate conditions. The large majority of patients with acute and chronic back and neck pain are managed in primary care settings. Given the differences between acute and chronic pain, it is necessary to identify differences in patient characteristics, practitioner evaluation, treatment and management in primary care settings., Methods: Over a two-week period, 24 practitioners in a multi-site practice-based research network completed 196 data cards about 39 patients experiencing acute back and neck pain and 157 patients suffering from chronic back and neck pain. Findings There were significant differences between the patients experiencing acute and chronic pain in regards to practitioner evaluation, current medication management and current treatment for depression. In addition, diagnostics differed between patients experiencing acute versus chronic back and neck pain. Further, primary care providers' review of online drug monitoring program reports during the current visit was associated with current medication management using short term opioids, long-term opioids or tramadol. Most research examining acute and chronic pain focuses on the low back. Additional research needs to be conducted to explore and compare acute and chronic pain across the whole spine.

Chiari malformation (CM) is a condition in which cerebellar tonsillar ectopia may manifest with various clinical presentations. This study reports from the only national, online patient registry available, the symptoms, comorbid neurocognitive and psychological conditions, and diagnostic experiences of patients living with CM type I (CM I). The current research is one component of a large investigation designed to collect information from individuals with CM through the online Conquer Chiari Patient Registry questionnaire. Analyses included descriptive statistics to study body system impact and patient diagnostic experiences. Participants were 768 individuals with CM I and were predominantly female (86.8 %) and Caucasian (93.8 %) with an average age of 35 years. Pain was the most frequently reported symptom (76.69 %) experienced prior to diagnosis with headaches implicated most often (73.44 %). Neurocognitive comorbidities included memory difficulties (43.88 %) and aphasia (43.75 %) and psychological disorders such as depression (31.77 %) and anxiety disorders (19.92 %) were reported. Average time to diagnosis from first physician visit to diagnosis was 3.43 years, and only 8.46 % of patients had previous awareness of CM. CM I diagnosis was found incidentally for 24.87 % of participants. Common misdiagnoses were classified as psychological (19.26 %) and neurological (19.26 %). Fear was the most frequent emotion elicited at the time of correct diagnosis (42.19 %). CM I can be a challenging condition for patients and physicians, during both the search for diagnosis and management of symptoms. Patient and physician education about CM I may permit early intervention and the prevention of further deterioration and patient suffering.

Polychlorinated dibenzo-p-dioxins (PCDDs) occur naturally in ball clay at elevated concentrations. Thus, persons who habitually work with clay may be at risk for exposure to PCDDs. An earlier case report provided some evidence of elevated PCDD levels in serum for long-term hobby ceramicists; however, no previous study has measured serum dioxin concentrations among ceramicists. This study measured PCDD serum levels for 27 individuals involved in ceramics making. The average residual, defined as the average of the [log measured serum lipid concentration – log background serum lipid concentration], was calculated and then tested to determine whether it was significantly different from zero. The p-values for the average residuals indicated that the serum lipid concentrations for several PCDD congeners were elevated relative to background. The number of significant residuals increased dramatically if the background concentrations were adjusted to account for the fact that they were not contemporaneous with the measurements for the ceramicists. The ratio of the 1,2,3,6,7,8-HxCDD concentration to the 1,2,3,7,8,9-HxCDD concentration was greater than 1.0, unlike in ball clay, suggesting that although long-term working with ball clay elevates the PCDD levels in serum somewhat, it is not the predominant source of the PCDD body burden for ceramicists.

Objective: There is a recognised need to strengthen capacity in the nutrition in emergencies sector and for greater clarity on the role of emergency nutritionists and the skills they require. Competency frameworks are an important tool for human resource development and have been developed for several other humanitarian sectors. We therefore developed a technical competency framework for practitioners in nutrition in emergencies., Design: Existing competency frameworks were reviewed and interviews conducted to explore methods used in developing competency frameworks for other sectors. Competencies were identified through interviews with field experts, feedback from course trainees, academic course content and job specifications. Competencies were then categorised and behavioural indicators developed for each. The draft framework was then reviewed by members of the Global Nutrition Cluster and modified in an iterative process., Setting: Global., Subjects: Not applicable., Results: A wide range of competencies were identified as essential for nutritionists working in emergencies, covering technical skills and general core competencies. The proposed framework contains twenty competency areas with 161 behavioural indicators categorised into three levels, corresponding to the requirements of progressively more senior roles. Many of the competencies are common across development and emergency nutrition., Conclusions: The proposed technical competency framework should prove to be a valuable tool in creating standards within the sector and promoting effective capacity strengthening and professionalisation. Continued research is needed to validate the framework, optimise methods for assessment, develop approaches to integrate it within the sector and measure its impact on performance.

This study used event-related potentials (ERPs) to assess effects of low-level prenatal lead exposure on auditory recognition memory in 2-month-old infants. Infants were divided into four groups according to cord-blood lead concentration: (1) <2.00 μ g/dL, (2) 2.00-2.99 μ g/dL, (3) 3.0-3.7 μ g/dL, and (4) ≥3.7 μ g/dL. The first group showed the normally expected differences in P2, P750, and late slow wave (LSW) amplitudes elicited by mothers' and strangers' voices. These differences were not observed for one or more ERP components in the other groups. Thus, there was electrophysiological evidence of poorer auditory recognition memory at 2 months with cord-blood lead ≥2.00 μ g/dL.

The woodwasp Sirex noctilio F. (Hymenoptera: Siricidae) has become established in North America. A primary tactic for the management of S. noctilio in the southern hemisphere has been the development of a biological control agent, Deladenus siricidicola Bedding. This nematode has a bicyclic life cycle including a mycetophagous free-living and parasitic cycle. During oviposition, female Sirex woodwasps inject a symbiotic fungus. Because D. siricidicola only develops well on Amylostereum areolatum (Chaillet ex Fries) Boidin (Russulales: Amylostereaceae) and North American woodwasps were thought to all have Amylostereum chailletii (Persoon) Boidin as their fungal symbiont, the risk of unintended impacts from D. siricidicola in North America was considered low. Specific polymerase chain reaction primers were designed to amplify the intergenic spacer region of Amylostereum symbionts in a population of the native woodwasp Sirex nigricornis F. located in central Louisiana (i.e., well outside the known distribution of S. noctilio); identity of the symbiont was confirmed by phylogenetic analyses. Overall, 95 out of 100 fungal isolates obtained from the mycangia of S. nigricornis were identified as Amylostereum species. Contrary to expectations, 60% were identified as A. chailletii (N = 60), while 35% were identified as A. areolatum (N = 35). The remaining 5% of these isolates (N = 5) were identified as Bipolaris papendorfii (Aa) Alcorn, Alternaria alternata (Fr.) Keissl, Penicillium marneffei Segretain, Scytalidium cuboideum (Sacc. & Ellis) Sigler & Kang, and Hyphopichia heimii (Pignal) Kurtzman based on sequencing of the internal transcribed spacer (ITS) region. The five non-Amylostereum isolates were likely contaminants during mycangia-spore extraction process. This study confirms the presence of A. areolatum in a population of the native woodwasp S. nigricornis well outside the known distribution of S. noctilio.

Objectives: We investigated the role of negative pressure therapy (NPT) in postoperative primary wound treatment and closure. To date, extensive evidence exists demonstrating the benefit of negative pressure dressings in the treatment of open wounds; our experiment tested the hypothesis that negative pressure dressings improve healing of closed (sutured) wounds., Methods: A porcine model was used to collect data on the characteristics of closed wounds after 3 days of treatment with NPTs as compared with control dressings., Results: In six pigs with a total of 56 wounds, load to failure (N/mm) in controls was 0.348 (standard deviation [SD] 0.109) versus NPT at 0.470 (SD, 0.194) with a P value of 0.001; energy to failure (mJ/mm) in controls was 0.85 (SD, 0.378) versus NPT at 1.128 (SD, 0.638) with a P value of 0.035. Blinded grading of clinical wound appearance and cross-sectional hematoma size were also improved at 72 hours., Conclusions: NPT dressings applied to surgically closed wounds enhance the healing characteristics of porcine wounds at 3 days., Clinical Relevance: We have observed that primarily closed surgical wounds may benefit from treatment with NPT. The benefit of using NPTs may be most pronounced in situations in which wounds are closed under tension, involve considerable soft tissue trauma, or may be at risk of subdermal hematoma formation.

The mechanisms that regulate the differentiation program of multipotential stem cells remain poorly understood. In order to define the cues that delineate endothelial commitment from precursors, we screened for candidate regulatory genes in differentiating mouse embryoid bodies. We found that the PR/SET domain protein, PRDM6, is enriched in flk1(+) hematovascular precursor cells using a microarray-based approach. As determined by 5' RACE, full-length PRDM6 protein contains a PR domain and four Krüppel-like zinc fingers. In situ hybridization in mouse embryos demonstrates staining of the primitive streak, allantois, heart, outflow tract, paraaortic splanchnopleura (P-Sp)/aorto-gonadal-mesonephric (AGM) region and yolk sac, all sites known to be enriched in vascular precursor cells. PRDM6 is also detected in embryonic and adult-derived endothelial cell lines. PRDM6 is co-localized with histone H4 and methylates H4-K20 (but not H3) in vitro and in vivo, which is consistent with the known participation of PR domains in histone methyltransferase activity. Overexpression of PRDM6 in mouse embryonic endothelial cells induces apoptosis by activating caspase-3 and inducing G1 arrest. PRDM6 inhibits cell proliferation as determined by BrdU incorporation in endothelial cells, but not in rat aortic smooth muscle cells. Overexpression of PRDM6 also results in reduced tube formation in cultured endothelial cells grown in Matrigel. Taken together, our data indicate that PRDM6 is expressed by vascular precursors, has differential effects in endothelial cells and smooth muscle cells, and may play a role in vascular precursor differentiation and survival by modulating local chromatin-remodeling activity within hematovascular subpopulations during development.

Background and Objective: Metformin is an effective treatment for type 2 diabetes mellitus. The pharmacokinetic characteristics of the conventional immediate-release (IR) formulation of metformin (Glucophage), however, necessitate two- or three-times-daily dosing. Development of a novel extended-release (XR) formulation of metformin (Glucophage XR) using GelShield Diffusion System technology provides a once-daily dosing option. The objective of this study was to assess the steady-state pharmacokinetics of metformin XR tablets., Study Design: This was an open-label, multiple-dose, five-regimen, two-sequence clinical study lasting 5 weeks., Methods: Subjects were 16 healthy volunteers aged 18-40 years. Three 1-week regimens of metformin XR (500, 1000 and 1500 mg once daily) were administered sequentially. Subjects were alternately given either metformin XR 2000 mg once daily or metformin IR 1000 mg twice daily during weeks 4 and 5. The pharmacokinetic properties of metformin XR were assessed on two separate days at steady state and compared with those of metformin IR., Results: Absorption of metformin XR was slower than that of metformin IR (time to maximum plasma concentration = 7 versus 3 hours). Maximum plasma concentrations (Cmax) following the administration of metformin XR 2000 mg once daily was 36% higher than that following the evening dose of metformin IR 1000 mg twice daily. The extent of absorption, determined by area under the plasma concentration-time curve (AUC), was equivalent for both formulations. The mean accumulation ratio of metformin XR was 1.0, indicating no accumulation with multiple-dose administration. Intrasubject variabilities in Cmax and AUC of metformin were comparable between metformin XR and metformin IR. This novel formulation of metformin XR was well tolerated at single doses up to 2000 mg once daily for 7 days, and adverse events were similar to those reported with metformin IR., Conclusion: The pharmacokinetic parameters of metformin XR tablet using GelShield Diffusion System technology were similar to those of metformin IR. Metformin XR was well tolerated at single doses up to 2000 mg once daily.

An ordnance-disposal expert was killed while disposing of a cache of explosives. The likely position of the body was reconstructed by modeling the explosion as an omnidirectional emission of particles from a model of the explosion site and noting the distribution of particles on a model of a human. The applications and limitations of this method in reconstructing the events and correlation with the injuries noted at autopsy are discussed.

Rationale: Tobacco use during initial experimentation often involves modest nicotine exposure, escalating to larger doses and more frequent exposure with the onset of tobacco dependence. Threshold doses for nicotine discrimination therefore may differ between naive and experienced tobacco users., Objectives: We determined the lowest (threshold) dose of nasal spray nicotine that smokers and non-smokers could reliably discriminate from placebo spray., Methods: Male and female smokers (n=18) and non-smokers (n=17) were initially trained to discriminate 20 microg/kg from placebo before proceeding to threshold determination sessions, which involved discrimination of progressively lower doses below 20 microg/kg ("descending order" subgroup) or higher doses above 1 microg/kg ("ascending order" subgroup). Threshold was determined by the lowest dose reliably discriminated from placebo (correct on > or =80% of testing trials) and by failure to discriminate the next lowest dose., Results: Threshold doses for nicotine discrimination were low and not different between smokers and non-smokers (median thresholds of 3 versus 2 microg/kg and approximate blood levels of 2.6 versus 1.6 ng/ml, respectively). Thresholds were similar between descending and ascending order subgroups. Several subjective responses differentiated threshold dose from the dose just below threshold, particularly in non-smokers., Conclusions: Threshold doses for nasal spray nicotine discrimination in humans are low, well below the typical nicotine delivery of most cigarette brands, and may not change after long-term smoking exposure.

Although nicotine intake clearly reinforces cigarette smoking behavior, non-nicotine smoke stimuli may become conditioned reinforcers of smoking. In Study 1, we compared the acute subjective and reinforcing effects of cigarette smoking in men and women under two conditions: blockade of visual and olfactory/taste smoke stimuli vs. no blockade. Subjective hedonic ratings of 'like puffs' and 'satisfying', but not 'strength', 'high in nicotine', or CO boost, were significantly reduced under the blockade vs. no blockade conditions. During subsequent ad lib puffing, significantly fewer puffs were self-administered under the blockade condition, particularly among women. In Study 2, we examined the influences of these stimuli separately and found that olfactory/taste stimuli, but not visual stimuli, reduced hedonic ratings and puff self-administration in women but not in men. In Study 3, procedures similar to those in Study 1 were used to examine whether this sex difference in responses to conditioned stimuli generalizes to a non-drug consummatory behavior, eating (pizza). However, hedonic ratings and ad lib consumption of pizza were substantially reduced in both men and women following blockade of visual and olfactory/taste food stimuli. These results indicate that the presumably conditioned stimuli of olfactory/taste from cigarette smoke may influence subjective hedonic ratings and reinforcement from smoking more in women than in men. However, this sex difference may not generalize beyond smoking or other drug reinforcement.

Smokers often report that the first cigarette of the day is the most rewarding, and subsequent smoking is less rewarding. Reduction in smoking enjoyment later in the day may be related to acute tolerance to the discriminative stimulus effects of nicotine. We examined changes in nicotine discrimination behaviour in humans as a function of acute nicotine pretreatment. Male and female dependent smokers (n = 15) were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo (0 microg/kg) without nicotine pretreatment. They then were tested on generalization of discrimination across a range of spray doses from 0-20 microg/kg following pretreatment with placebo, moderate dose (14-21 mg) or high dose (28-42 mg) transdermal nicotine. Generalization testing involved both two- and three-response ('novel' option) quantitative procedures. Subjects also engaged in a self-administration phase at the end of each session, involving choices between nicotine (20 microg/kg) and placebo spray. Nicotine pretreatment significantly attenuated nicotine-appropriate responding at higher nicotine spray doses, suggesting acute tolerance, but only in women. Similar results were seen for subjective 'head rush', suggesting this effect may be related to discrimination behaviour in women. However, nicotine pretreatment also increased novel-appropriate responding, especially in men, following intermediate generalization doses, suggesting qualitatively different stimulus effects. Although differences were not significant, nicotine self-administration tended to be inversely associated with nicotine pretreatment dose in men but not in women. These results only modestly support the notion of acute tolerance to the discriminative stimulus effects of nicotine, and even then only in women and not in men.

Two randomized crossover studies were conducted to evaluate the pharmacokinetics (including food effect) of fixed-combination metformin/glyburide tablets. Pharmacokinetics and bioavailability of two strengths (500 mg/2.5 mg and 500 mg/5 mg) of metformin/glyburide tablets were assessed relative to coadministered metformin and glyburide tablets in study 1. The effect of a high-fat meal on the bioavailability of a metformin/glyburide (500 mg/5 mg) tablet was assessed relative to the fasted condition in study 2. The fixed combination metformin/glyburide tablets showed bioequivalence for the metformin component with the reference metformin tablet and comparable bioavailability for the glyburide component with the reference glyburide tablet. Food does not appear to affect the bioavailability of either component to an appreciable extent.

Regulatory guidelines for aseptic manufacture of pharmaceuticals recommend validation of sterilizing filters by bacterial challenge under "worst case" conditions. The microbial retention characteristics of a sterilizing grade, 0.2-microns-rated Nylon 66 membrane filter were evaluated for filtration of high viscosity fluids. Glycerol (80%) was used as the carrier fluid and Pseudomonas diminuta ATCC 19146 as the challenge organism. Testing was carried out at a constant differential pressure of 60 psig over a six-hour test period. Test runs were undertaken at three different temperature conditions (25 +/- 5 degrees C, 42 +/- 1 degree C, and 50 +/- 1 degree C). Under the test conditions, the Nylon 66 membranes provided total retention of P. diminuta. The results demonstrated that a high pressure differential challenge using a high viscosity fluid over a six-hour test period at ambient and elevated temperatures did not alter the retention characteristics of the membrane filter.

Possible arrhythmogenic side-effects of the positive inotropic agent prenalterol were studied in conscious dogs, three to four days after coronary artery ligation. Prenalterol showed a propensity to cause arrhythmias in one out of eight dogs, thereby confirming published data from clinical studies.