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This study aimed to describe community-acquired bacterial coinfection (CAI) and antimicrobial use among COVID-19 patients.Electronic records were retrospectively reviewed, and clinical data, laboratory data, antibiotic use, and outcomes of patients with and without CAI were compared.Of 1116 patients, 55.1% received antibiotics within 48 hours, but only 66 (5.9%) had documented CAI, mainly respiratory (40/66, 60.6%). Patients with CAI were more likely to present with myalgia (Overall CAI rate was low (5.9%) and antimicrobial use disproportionately high (55.0%), varying little over time. The mortality rate of coinfected patients was high. Certain parameters can be used to better identify those with CAI and those who need blood cultures.

The aim of this study was to determine the predictors of mortality and describe laboratory trends among adults with confirmed COVID-19.The medical records of adult patients admitted to a referral hospital with COVID-19 were retrospectively reviewed. Demographic and clinical characteristics, and laboratory parameters, were compared between survivors and non-survivors. Predictors of mortality were determined by multivariate analysis. Mean laboratory values were plotted across illness duration.Of 1215 patients, 203 (16.7%) had mild, 488 (40.2%) moderate, 183 (15.1%) severe, and 341 (28.1%) critical COVID-19 on admission. In-hospital mortality was 18.2% (0% mild, 6.1% moderate, 15.8% severe, 47.5% critical). Predictors of mortality were age ≥ 60 years, COPD, qSOFA score ≥ 2, WBC10 × 10The overall mortality rate was high. Predictors of mortality were similar to those of other reports globally. Marked inflammation and worsening pulmonary and renal function were evident among non-survivors by the 2nd-3rd week of illness.

BackgroundIntersectoral collaboration in the context of the prevention and control of vector-borne diseases has been broadly described in both the literature and the current global strategy by the World Health Organization. Our aim was to develop a framework that will distill the currently known multiple models of collaboration.MethodsQualitative content analysis and logic modeling of data abstracted from 69 studies included in a scoping review done by the authors were used to develop 9 recommendation statements that summarized the composition and attributes of multisectoral approaches, which were then subjected to a modified Delphi process with 6 experts in the fields of health policy and infectious diseases.ResultsConsensus for all statements was achieved during the first round. The recommendation statements were on (1–3) sectoral engagement to supplement government efforts and augment public financing; (4) development of interventions for most systems levels; (5–6) investment in human resource, including training; (7–8) intersectoral action to implement strategies and ensure sustainability of initiatives; and (9) research to support prevention and control efforts.ConclusionsThe core of intersectoral action to prevent vector-borne diseases is collaboration among multiple stakeholders to develop, implement, and evaluate initiatives at multiple levels of intervention.

Background. Tuberculous arthritis is a rare extra-pulmonary manifestation of tuberculosis (TB) that can lead to significant disability when left untreated. This study described the clinical profile of patients with TB arthritis admitted in a tertiary hospital in the Philippines. Methods. We reviewed medical records of 65 patients with TB arthritis admitted in the Philippine General Hospital from 2006 to 2019. Results. Majority of patients were male (41, 63.0%) and the mean age upon diagnosis was 46.7 ± 1.7 years (20– 85). Majority (33, 50.8%) had underlying co-morbidities including hypertension (16, 24.6%), type 2 diabetes mellitus (10, 15.4%), and chronic kidney disease (8, 12.3%). A history of previous TB treatment (10, 15.4%), intake of immunosuppressive drugs (7, 10.8%), and trauma on affected joints (13, 20.0%) were also reported. Majority presented with chronic mono-arthritis (50, 76.9%) involving the knees (27, 41.5%) and hips (21, 32.3%) with a mean duration of symptoms of 20.9 ± 3.9 months. The most frequent initial diagnosis upon admission was septic arthritis (21, 32.3%). Confirmed septic arthritis (10, 15.6%), pulmonary TB (9, 14.3%), and disseminated TB (4, 6.3%) were also observed. Majority were diagnosed based on positive acid-fast bacilli (AFB) smear, polymerase chain reaction (PCR) for Mycobacterium tuberculosis, or synovium biopsy (34, 54.0%). Anemia (43, 68.3%) and elevated inflammatory biomarkers (erythrocyte sedimentation rate, ESR [36, 97.3%] and C-reactive protein, CRP [40, 87%]) were also seen in majority of patients. The most common radiographic findings on x-ray were joint space narrowing (42, 84.0%), soft tissue swelling (22, 44.0%), and erosions (21, 42.0%). The mean length of hospital stay was 23.8 ± 2.8 days (2–113). Majority underwent surgical interventions (35, 55.6%) including debridement (28, 80.0%) and arthrotomy (25, 71.4%). All received anti-tuberculosis treatment upon diagnosis. Conclusion. Majority of patients with TB arthritis in this study were male, with mean age in the 5th decade of life, presenting with mono-arthritis, anemia, elevated inflammatory markers, and radiologic findings of joint narrowing. All patients received medical treatment while more than half underwent surgery. There should be a high index of suspicion for TB arthritis in a patient from an endemic country presenting with chronic mono arthritis in weight-bearing joints to prevent delay in diagnosis and significant joint destruction and disability

To describe the clinical profile and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) across the spectrum of disease severity.This retrospective study included adult patients with confirmed COVID-19 infection admitted to a referral hospital. Descriptive statistics, tests for trend, Kaplan-Meier curve and log-rank test were used to compare characteristics and outcomes across disease severity categories.Of 1500 patients with COVID-19, 14.8% were asymptomatic, 13.5% had mild disease, 36.6% had moderate disease, 12.3% had severe disease and 22.7% had critical disease. Asymptomatic patients were admitted for a concurrent condition or for isolation. Patients aged60 years, male gender and with co-morbidities had more severe disease. Fever, cough, shortness of breath, malaise, gastrointestinal symptoms and decreased sensorium were more common in patients with severe disease. Bilateral pulmonary infiltrates were common (51.1%), with sicker patients having more abnormal findings. The overall mortality rate was 15.1%. Adopting a symptom-based strategy reduced the length of hospitalization from a median of 13 [interquartile range (IQR) 7-21] days to 9 (IQR 5-14) days.The clinical profile and outcomes for this cohort of patients with COVID-19 was consistent with published reports. Asymptomatic infection was common, and universal testing may be a valuable strategy in the correct context, given the implications for infection control. A symptom-based strategy was found to reduce the length of hospitalization considerably.

BACKGROUND: Interventions targeting weight-related experiential avoidance (EA) and disinhibited eating (DE) may also improve diet quality. Participants with overweight/obesity and DE who recently completed a behavioral weight-loss program were randomized to receive Acceptance and Commitment Therapy or continued behavioral weight-loss treatment. In this secondary analysis we explored (1) change in diet quality from baseline to 6-month follow-up (FU), and (2) whether weight-related EA at baseline and (3) change in weight-related EA during treatment were related to change in diet quality from baseline to FU. METHOD: Veterans (N=68) completed food frequency questionnaires at baseline and FU, which were used to generate diet quality scores on the healthy eating index-15 (HEI-15). Weight-related EA was assessed using the Acceptance and Action Questionnaire for Weight-Related Difficulties-Revised (AAQW-R) at baseline, post-treatment, and FU. Aims were examined with mixed ANOVA analyses. RESULTS: Across both treatment groups, HEI-15 scores declined from baseline to FU. Women’s HEI-15 decreased by about 5 times that of men. Baseline AAWQ-R was negatively associated with change in HEI-15. Neither AAWQ-R at post-treatment nor change in AAQW-R from baseline to post-treatment were significantly associated with change in HEI-15 at FU. CONCLUSIONS: Greater weight-related EA at baseline was associated with lower diet quality at FU, but change in weight-related EA during treatment did not predict change in diet quality at FU. Interventions targeting DE and weight-loss may require specific components to improve and sustain healthy dietary intake in Veterans with obesity and DE.

Setting The 3rd national tuberculosis (TB) survey in the Philippines in 2007 reported a significant decline in the prevalence of TB. Since then, more significant investments for TB control have been made, yet TB burden estimates from routine surveillance data remain relatively stable. Objective To estimate the prevalence of bacteriologically confirmed pulmonary TB in the Philippines amongst individuals aged ≥15 years in 2016. Design In March–December 2016, we conducted a population-based survey with stratified, multi-stage cluster sampling of residents in 106 clusters aged ≥15 years. Survey participants were screened for TB by symptom-based interview and digital chest X-ray. Those with cough ≥2 weeks and/or haemoptysis and/or chest X-ray suggestive of TB were requested to submit 2 sputum specimens for Xpert MTB/RIF, direct sputum smear microscopy using LED fluorescent microscopy, and mycobacterial solid culture (Ogawa method). Bacteriologically confirmed pulmonary TB was defined as MTB culture positive and/or Xpert positive. Results There were 46,689 individuals interviewed, and 41,444 (88.8%) consented to a chest X-ray. There were 18,597 (39.8%) eligible for sputum examination and 16,242 (87.3%) submitted at least one specimen. Out of 16,058 sputum-eligible participants, 183 (1.1%) were smear-positive. There were 466 bacteriologically confirmed TB cases: 238 (51.1%) Xpert positive, 69 (14.8%) culture positive, and 159 (34.1%) positive by both Xpert and culture. The estimated TB prevalence per 100,000 population aged ≥15 years was 434 (95% CI: 350−518) for smear-positive TB, and 1,159 (95% CI: 1,016−1,301) for bacteriologically confirmed TB. Conclusion This nationally representative survey found that the TB burden in the Philippines in 2016 was higher than estimated from routine TB surveillance data. There was no evidence of a decline in smear and culture positive TB from the 2007 survey despite significant investments in TB control. New strategies for case-finding and patient-centered care must be intensified and expanded.

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100 000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100 000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit. © 2020 John Wiley & Sons Ltd

Hypervirulent strains of Klebsiella pneumoniae are known to cause liver abscesses and other metastatic infections. Being Asian and having diabetes are known host risk factors. Here we present an unusual case of a Filipino ballet dancer–choreographer with diabetes presenting with bilateral leg pains initially thought to be cellulitis, but was eventually diagnosed as bilateral subcutaneous leg abscesses. He also had a liver abscess, thankfully asymptomatic, which was only discovered on imaging. The occurrence of three distant abscesses in one patient, hence ‘3-in-1,’ makes this case worth reporting. Bilateral subcutaneous leg abscesses as the presenting manifestation of this infection have not been reported yet. We hypothesise that his occupation which makes use of frequent contractions of leg muscles led to increased blood flow and preferentially directed blood-borne bacteria to localise in both legs. We have also characterised the pathogen with regards to its hypermucoviscous phenotype, capsular type, virulence genes and phylogeny.

Disseminated histoplasmosis, with the adrenal glands as being the only site of demonstrable disease in an immunocompetent adult, is a rare infection leading to adrenal insufficiency. This disease carries high mortality when unrecognised. We describe the first reported case of adrenal histoplasmosis in the Philippines in a 72-year-old immunocompetent, Filipino man who presented with a 3-month history of intermittent flank pain, weight loss and generalised weakness. His imaging demonstrated bilateral adrenal masses on ultrasonography and contrast-enhanced CT scan. The initial impression was adrenal cancer, however, fine-needle aspiration cytology revealed the presence of yeast cells and blood culture grew Histoplasma capsulatum. The diagnosis of the case represents a diagnostic challenge in immunocompetent individuals because they manifest with non-specific symptoms. A heightened suspicion is therefore needed to prevent significant morbidity and mortality.

Author(s): Afari, N; Herbert, MS; Godfrey, KM; Cuneo, JG; Salamat, JS; Mostoufi, S; Gasperi, M; Ober, K; Backhaus, A; Rutledge, T; Wetherell, JL | Abstract: ObjectiveThe current study tested the efficacy of an acceptance and commitment therapy (ACT) group intervention for disinhibited eating behaviour as an adjunct to the Veterans Affairs MOVE!© weight management programme.MethodsVeterans (N = 88) with overweight or obesity who completed the MOVE! weight management programme and self-identified as having problems with 'stress-related eating' were randomized to four 2-h weekly ACT sessions or a continued behavioural weight-loss (BWL) intervention. Assessments were completed at baseline, post-treatment and 3- and 6-month follow-up on outcomes of interest including measures of disinhibited eating patterns, obesity-related quality of life, weight-related experiential avoidance and weight.ResultsThe BWL group exhibited significantly greater reductions in binge eating behaviour at post-treatment compared with the ACT group. Significant improvements in other outcomes were found with minimal differences between groups. In both groups, decreases in weight-related experiential avoidance were related to improvements in binge eating behaviour.ConclusionsTaken together, the continued BWL intervention resulted in larger improvements in binge eating behaviour than the ACT intervention. The two groups showed similar improvements in other disinhibited eating outcomes. Future studies are encouraged to determine if more integrated or longer duration of ACT treatment may maximize eating outcomes in MOVE.Trial Registration Number: This trial was registered with ClinicalTrials.gov database (NCT01757847).

Objectives. This scoping review aimed to support a landscape analysis to identify lessons learned about intersectoral collaborations (ISCs) by describing their existing models in the context of dengue, malaria and yellow fever. Methods. A scoping review following the methodology of Joanna Briggs Institute was performed using the following inclusion criteria: studies involving humans; studies discussing intersectoral collaborations, malaria/dengue/yellow fever, and prevention or control at any level; and studies in countries endemic for the aforementioned diseases. Studies were screened using Covidence, while data were extracted using NVivo. Results. Of the 7,535 records retrieved, 69 were included in the qualitative analysis. Most ISCs were initiated by multilateral organizations and ministries of health, and none by communities. Strategies included advocacy, health education, research, public health measures, resource mobilization, service delivery and training; mostly employed on a community level. Monitoring and evaluation were mostly formative, ongoing, and participatory. Gaps included administrative and policy barriers, resource shortages, and inadequate research and training. Conclusions. Multiple models of ISC exist in the literature. There is a need to develop a comprehensive framework for an effective and sustainable multisectoral approach for the prevention and control of VBDs ensuring adequate resources, active stakeholders, and strategies that span the entire socio-ecological spectrum.

Schistosoma japonicum infection is believed to be endemic in 28 of the 80 provinces of The Philippines and the most recent data on schistosomiasis prevalence have shown considerable variability between provinces. In order to increase the efficient allocation of parasitic disease control resources in the country, we aimed to describe the small-scale spatial variation in S. japonicum prevalence across The Philippines, quantify the role of the physical environment in driving the spatial variation of S. japonicum, and develop a predictive risk map of S. japonicum infection. Data on S. japonicum infection from 35,754 individuals across the country were geolocated at the barangay level and included in the analysis. The analysis was then stratified geographically for the regions of Luzon, the Visayas and Mindanao. Zero-inflated binomial Bayesian geostatistical models of S. japonicum prevalence were developed and diagnostic uncertainty was incorporated. Results of the analysis show that in the three regions, males and individuals aged ≥ 20 years had significantly higher prevalence of S. japonicum compared with females and children < 5 years. The role of the environmental variables differed between regions of The Philippines. Schistosoma japonicum infection was widespread in the Visayas whereas it was much more focal in Luzon and Mindanao. This analysis revealed significant spatial variation in the prevalence of S. japonicum infection in The Philippines. This suggests that a spatially targeted approach to schistosomiasis interventions, including mass drug administration, is warranted. When financially possible, additional schistosomiasis surveys should be prioritized for areas identified to be at high risk but which were under-represented in our dataset.

Background Polyradiculopathy (PRP) and encephalitis are neurologic syndromes associated with 1% of cytomegalovirus (CMV) disease among patients with advanced HIV infection. Untreated patients die within 8 weeks. This case series and literature review highlights the clinical and laboratory features integral to the prompt diagnosis and treatment of these rare but serious manifestations of CMV disease among AIDS patients. Methods We document CMV PRP and encephalitis in two HIV-seropositive men seen in a tertiary hospital in the Philippines. Both patients presented with bilateral leg weakness, paresthesias, hyporeflexia, and urinary retention associated with confusion and memory lapses. In the two cases described, diagnosis of CMV disease was delayed because it was not immediately entertained. Tuberculosis involving the nervous system was first ruled out. Results The first case was a 31-year-old male with a baseline CD4 count of 9 cells/mm3 who presented with signs and symptoms of bilateral leg weakness and paresthesias 3 weeks after initiation of antiretrovirals (ART). CMV viremia was detected by PCR. Ganciclovir was initiated late, and he subsequently died of multiorgan failure. The second case is a 29-year-old male with a baseline CD4 count of 2 cells/mm3. CMV DNA PCR was detected in the CSF. He died prior to initiation of anti-CMV therapy. Conclusion CMV-related neurologic complications are uncommon, but often fatal when appropriate anti-CMV therapy is not initiated promptly. The diagnosis of CMV PRP should be considered in patients with advanced immunosuppression presenting with ascending paraplegia, areflexia, and urinary retention with typical CSF abnormalities (polymorphonuclear pleocytosis, elevated protein concentration, and hypoglycorrhachia). Table 1. Summary of Presenting Signs and Symptoms of the Two Cases in Comparison to the 103 Patients with CMV PRP in Anders and Goebel’s Review Sign or Symptom Anders and Goebel [2] Case 1 Case 2 Lower limb weakness 100% Present Present Lower limb areflexia 100% Present Present Urinary retention 94% Present Present Paresthesia 79% Present Present Sensory loss (legs) 72% Present Present Fecal incontinence 67% Absent Absent Lumbar pain 36% Absent Absent Babinski sign 16% Absent Absent Disclosures All authors: No reported disclosures.

Viruses are appreciated as etiological agents of certain human tumors, but the number of different cancer types induced or exacerbated by viral infections is unknown. Glioblastoma multiforme (GBM)/astrocytoma grade IV is a malignant and lethal brain cancer of unknown origin. Over the past decade, several studies have searched for the presence of a prominent herpesvirus, human cytomegalovirus (HCMV), in GBM samples. While some have detected HCMV DNA, RNA, and proteins in GBM tissues, others have not. Therefore, any purported association of HCMV with GBM remains controversial. In most of the previous studies, only one or a select few viral targets were analyzed. Thus, it remains unclear the extent to which the entire viral genome was present when detected. Here we report the results of a survey of GBM specimens for as many as 20 different regions of the HCMV genome. Our findings indicate that multiple HCMV loci are statistically more likely to be found in GBM samples than in other brain tumors or epileptic brain specimens and that the viral genome was more often detected in frozen samples than in paraffin-embedded archival tissue samples. Finally, our experimental results indicate that cellular genomes substantially outnumber viral genomes in HCMV-positive GBM specimens, likely indicating that only a minority of the cells found in such samples harbor viral DNA. These data argue for the association of HCMV with GBM, defining the virus as oncoaccessory. Furthermore, they imply that, were HCMV to enhance the growth or survival of a tumor (i.e., if it is oncomodulatory), it would likely do so through mechanisms distinct from classic tumor viruses that express transforming viral oncoproteins in the overwhelming majority of tumor cells.

Summary Numerous cases of primary hypophysitis have been described over the past 25 years with, however, little insight into the cause(s) of this disease. In order to guide treatment, a better understanding of the pathogenesis is needed. We studied the pathogenesis of primary hypophysitis by analysing systematically the immune response at the pituitary tissue level of consecutive cases of ‘lymphocytic’ hypophysitis who underwent pituitary biopsy. In order to investigate further the pathogenesis of their diseases we characterized two cases at clinical, cellular and molecular levels. We show here, for the first time, that lymphocytic hypophysitis probably encompasses at least two separate entities. One entity, in agreement with the classical description of lymphocytic hypophysitis, demonstrates an autoimmune process with T helper 17 cell dominance and lack of T regulatory cells. The other entity represents a process in which T regulatory cells seem to control the immune response, which may not be self- but foreign-targeted. Our data suggest that it may be necessary to biopsy suspected primary hypophysitis and to analyse pituitary tissue with immune markers to guide treatment. Based on our results, hypophysitis driven by an immune homeostatic process should not be treated with immunosuppression, while autoimmune-defined hypophysitis may benefit from it. We show here for the first time two different pathogenic processes classified under one disease type and how to distinguish them. Because of our findings, changes in current diagnostic and therapeutic approaches may need to be considered.

Many ultrasonic parameters, primarily related to attenuation and scatterer size, have been used to characterize the composition of atherosclerotic plaque tissue. In this study, we combine elastographic (axial strain ratio) and ultrasonic tissue characterization parameters, namely the attenuation coefficient and a scattering parameter associated with an "equivalent" scatterer size to delineate between fibrous, calcified, and lipidic plaque tissue. We present results obtained from 44 ex vivo atherosclerotic plaque specimens obtained after carotid endarterectomy on human patients. Our results in the frequency range 2.57.5 MHz indicate that softer plaques (with higher values of the strain ratio) are usually associated with larger equivalent scatterer size estimates (200 500 m) and lower values of the attenuation coefficient slope (

The current investigation examined changes in working memory (WM) component processes following total sleep deprivation (TSD) in a sample of healthy young persons. Forty subjects were administered a verbal form of a continuous recognition test (CRT) before and after 42 hr of TSD. Parameters of a computational model of the CRT reflecting attention, WM span, and rate of episodic memory encoding were estimated for each individual. Subjects made more errors on the test following sleep deprivation. Analysis of model parameters revealed statistically independent declines in both the attention and WM span parameters, with a larger effect observed for the decline in WM span. Examination of individual profiles suggested that the effects of TSD on verbal WM component processes vary from person to person. Declines in global verbal WM functioning appear to be primarily driven by reduced WM span and attention; however, these effects may be individual-specific. Further applications of the computational model for examining WM component processes with sleep deprivation and other clinical populations are discussed.

A 3- to 4-month-old female Golden Retriever dog presented with right hind limb enlargement. Physical examination of the limb and radiographic findings initially included soft tissue swelling with elongation, bowing, and cortical irregularity of the femur and tibia. During a period of approximately 7 months, pathology in the limb progressed to include tarsal laxity, muscle atrophy, avulsion of the gastrocnemius muscle, and luxation of the patella. During surgical intervention to shorten the limb and repair the patellar luxation, a large soft tissue cyst was identified along the caudal aspect of the femur and stifle. The limb was later amputated, and a final diagnosis of malignant peripheral nerve sheath (PNS) tumor of the sciatic nerve and surrounding soft tissues was made. The unilateral limb enlargement in this dog appears to have been because of the development and progression of a malignant PNS tumor. The presentation and associated pathologic changes in the limb are unusual for canine PNS tumor but have similarities with neurofibromatosis in the limbs of humans.

Ultrasonic aspirators are commonly used to resect brain tumours because they allow safe, rapid and accurate removal of diseased tissue. Since ultrasonic aspirators generate a spray of aerosolized irrigating fluid around the instrument tip, we questioned whether this spray might contain viable tumours cells that could contribute to intraoperative spread of tumour fragments. To test this hypothesis, we collected the spray produced during the resection of nine brain tumours with an ultrasonic aspirator and semi-quantitatively analysed it for tumour presence. The aerosolized irrigation fluid was found to contain intact tumour cells or clumps of tumour cells in all nine instances, and there was a trend of increasing tumour cell dispersion with increasing ultrasonic aspiration times. Further examination is required to determine if this intraoperative dispersion of apparently viable tumour fragments contributes to local neoplasm recurrence.

Disrupted sleep is more common in older adults (OLD) than younger adults (YOUNG), often co-morbid with other conditions. How these sleep disturbances affect cognitive performance is an area of active study. We examined whether brain activation during verbal encoding correlates with sleep quantity and quality the night before testing in a group of healthy OLD and YOUNG. Twenty-seven OLD (ages 59–82) and 27 YOUNG (ages 19–36) underwent one night of standard polysomnography. Twelve hours post-awakening, subjects performed a verbal encoding task while undergoing functional magnetic resonance imaging. Analyses examined the group (OLD vs. YOUNG) by prior sleep quantity (total sleep time, TST) or quality (sleep efficiency, SE) interaction on cerebral activation, controlling for performance. Longer TST promoted higher levels of activation in the bilateral anterior parahippocampal in OLD and lower activation levels in the left anterior parahippocampus in YOUNG. Greater SE promoted higher activation levels in the left posterior parahippocampus and right inferior frontal gyrus in YOUNG, but not in OLD. The roles of these brain regions in verbal encoding suggest, in OLD, longer sleep duration may be linked to the ability to engage in functional compensation during cognitive challenges. By contrast, in YOUNG, shorter sleep duration may necessitate functional compensation to maintain cognitive performance, similar to what is seen following acute sleep deprivation. Additionally, in YOUNG, better sleep quality may improve semantic retrieval processes, thereby aiding encoding.

Background The European Respiratory Society guidance on bronchoalveolar lavage (BAL) in children was published in 2000. It recommended taking one BAL specimen from the most affected lobe or from the right middle lobe in diffuse disease. In 2007, the European Respiratory Society modified the recommendations for children with cystic fibrosis (CF), suggesting two BAL specimens (right middle lobe and the lingula or the most affected lobe). Objective To determine if BAL samples from one or two lobes give the full picture of lower airway infection in children with CF. Design, setting and patients A retrospective review of all paediatric patients with CF who underwent flexible bronchoscopy between May 2007 and May 2009 was undertaken. Main outcome measures As BAL specimens from all six lobes were collected, the BAL results were reviewed to identify if positive cultures would have been missed if only one lobe (right middle or most affected) or two lobes (right middle plus the lingula or most affected) had been sampled. Results The results of 39 bronchoscopic procedures in 31 children were reviewed. The BAL samples were taken from 6 lobes in all 39 procedures. Had only one lobe been used, 26 positive cultures (14 organisms) would have been missed in 11 patients. Had two lobes been used, 12 positive cultures (8 organisms) would have been missed in 7 patients. Conclusion A single-lobe BAL is insufficient in assessing patients with CF for lower airway infection. Even when BAL specimens are taken from two lobes, a number of infections may be missed.

Background In order to increase the efficient allocation of soil-transmitted helminth (STH) disease control resources in the Philippines, we aimed to describe for the first time the spatial variation in the prevalence of A. lumbricoides, T. trichiura and hookworm across the country, quantify the association between the physical environment and spatial variation of STH infection and develop predictive risk maps for each infection. Methodology/Principal Findings Data on STH infection from 35,573 individuals across the country were geolocated at the barangay level and included in the analysis. The analysis was stratified geographically in two major regions: 1) Luzon and the Visayas and 2) Mindanao. Bayesian geostatistical models of STH prevalence were developed, including age and sex of individuals and environmental variables (rainfall, land surface temperature and distance to inland water bodies) as predictors, and diagnostic uncertainty was incorporated. The role of environmental variables was different between regions of the Philippines. This analysis revealed that while A. lumbricoides and T. trichiura infections were widespread and highly endemic, hookworm infections were more circumscribed to smaller foci in the Visayas and Mindanao. Conclusions/Significance This analysis revealed significant spatial variation in STH infection prevalence within provinces of the Philippines. This suggests that a spatially targeted approach to STH interventions, including mass drug administration, is warranted. When financially possible, additional STH surveys should be prioritized to high-risk areas identified by our study in Luzon., Author Summary Soil-transmitted helminth (STH) infections with A. lumbricoides, T. trichiura and hookworms are endemic in all 80 provinces of the Philippines, but the spatial variation in the prevalence of these infections has not been previously described. This analysis revealed that while A. lumbricoides and T. trichiura infections were widespread and highly endemic, hookworm infections were more circumscribed to smaller foci in the Visayas and Mindanao. The results also suggest that it may be necessary to place greater emphasis on improving the provision of water, sanitation and the promotion of behavioral change for improved hygiene for the control and prevention of STH infections, particularly for hookworm.

To test the role of task difficulty in the cerebral compensatory response after total sleep deprivation (TSD).Subjects performed a modified version of Baddeley's logical reasoning task while undergoing functional magnetic resonance imaging twice: once after normal sleep and once following 35 hours of TSD. The task was modified to parametrically manipulate task difficulty.Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center.16 young adults (7 women; mean age, 27.6 +/- 6.1 years; education, 15.4 +/- 1.8 years) were included in the final analyses.None.Behaviorally, subjects performed the same after TSD as while well rested. Neuroimaging data revealed a linear increase in cerebral response with a linear increase in task demands in several brain regions after normal sleep. Even stronger linear responses were found after TSD in several brain regions, including bilateral inferior parietal lobes, bilateral temporal cortex, and left inferior and dorsolateral prefrontal cortex.Task difficulty facilitates the cerebral compensatory response observed following TSD. Compensation manifests as both new regions that did not show significant responses to task demands in the well-rested condition, as well as stronger responses within regions typically underlying task performance. The possible significance of these 2 types of responses should be explored further, as should the importance of the parietal lobes for cognitive performance after TSD.

Study Objectives: To test the role of task difficulty in the cerebral compensatory response after total sleep deprivation (TSD). Design: Subjects performed a modified version of Baddeley's logical reasoning task while undergoing functional magnetic resonance imaging twice: once after normal sleep and once following 35 hours of TSD. The task was modified to parametrically manipulate task difficulty. Setting: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. Patients or Participants: 16 young adults (7 women; mean age, 27.6 ± 6.1 years; education, 15.4 ± 1.8 years) were included in the final analyses. Interventions: None Measurements and Results: Behaviorally, subjects performed the same after TSD as while well rested. Neuroimaging data revealed a linear increase in cerebral response with a linear increase in task demands in several brain regions after normal sleep. Even stronger linear responses were found after TSD in several brain regions, including bilateral inferior parietal lobes, bilateral temporal cortex, and left inferior and dorsolateral prefrontal cortex. Conclusions: Task difficulty facilitates the cerebral compensatory response observed following TSD. Compensation manifests as both new regions that did not show significant responses to task demands in the well-rested condition, as well as stronger responses within regions typically underlying task performance. The possible significance of these 2 types of responses should be explored further, as should the importance of the parietal lobes for cognitive performance after TSD. Citation: Drummond SPA; Brown GG; Salamat JS; Gillin JC. Increasing task difficulty facilitates the cerebral compensatory response to total sleep deprivation.

Grammatical transformation is a verbal reasoning task requiring judging the veracity of statements describing the spatial order of letter sets. We studied 18 adults with FMRI while they performed grammatical transformations of varying complexity levels (2-letter, 3-letter, and 4-letter sentences). Brain regions activated by 2-letter sentences included the visuospatial processing regions of the bilateral parietal lobes and the frontal operculum. A linear increase in sentence complexity engaged dorsolateral and ventrolateral prefrontal cortex as well as significantly increased activation within 2LTR areas. These data provide evidence that grammatical transformation reasoning relies primarily on the posterior visuospatial working memory system and need not necessarily engage the prefrontal cortex. Increasing the complexity of grammatical transformation, though, activates prefrontal cortex.

We report a case of fibrosarcoma arising in the pineal of a 36-year-old female patient. She died at the age 43 following biopsy, radiation therapy, tumor resection, chemotherapy, and stereotactic radiosurgery. Light microscopic study of all tissues obtained, including immunohistochemistry and electron microscopy of surgically resected tumor and autopsied tissue revealed a slowly progressing primary fibrosarcoma.

Interleukin-2 (IL-2) and granulocyte-macrophage-colony stimulating factor (GM-CSF) are cytokines with nonoverlapping pleiotropic effects. In a prior Phase Ib study, this combination of agents exhibited antitumor effects in the lungs of four of eight patients with renal cell carcinoma and pulmonary metastases. We conducted this Phase Ib/II trial to determine the response rate of renal cell carcinoma patients with pulmonary metastases treated with continuous infusion IL-2 plus GM-CSF.Patients with renal cell carcinoma and pulmonary metastases were treated with 1.5, 2.25, or 4.5 x 10(6) IU/m(2)/day 96-hour continuous infusion IL-2 on Days 1-4, 8-11, and 15-18, and 1.25, 2.25, or 2.5 microg/kg/day GM-CSF on Days 8-19.Sixteen patients were treated per protocol, 14 of whom could be evaluated for disease progression. None of these 14 patients had50% shrinkage of either total tumor burden or pulmonary metastasis. One patient developed Grade 5 neurotoxicity. Autopsy revealed acute multifocal cerebral venous thrombosis as well as acute subdural and subarachnoid hemorrhage.The combination of IL-2 and GM-CSF may be associated with marked morbidity and, as in one case in this study, mortality. No significant antitumor activity was appreciated. Thus, the combination of IL-2 and GM-CSF, when administered at this dose and according to this schedule, does not appear to be active in renal cell carcinoma and is associated with significant toxicities. Further studies using this combination of agents should only be undertaken with extreme caution and particular attention to neurotoxicity.

Ultrasonic aspirators are commonly used to resect brain tumours because they allow safe, rapid and accurate removal of diseased tissue. Since ultrasonic aspirators generate a spray of aerosolized irrigating fluid around the instrument tip, we questioned whether this spray might contain viable tumours cells that could contribute to intraoperative spread of tumour fragments. To test this hypothesis, we collected the spray produced during the resection of nine brain tumours with an ultrasonic aspirator and semi-quantitatively analysed it for tumour presence. The aerosolized irrigation fluid was found to contain intact tumour cells or clumps of tumour cells in all nine instances, and there was a trend of increasing tumour cell dispersion with increasing ultrasonic aspiration times. Further examination is required to determine if this intraoperative dispersion of apparently viable tumour fragments contributes to local neoplasm recurrence.

PURPOSE: To evaluate the in vivo and in vitro properties of collagen-coated acrylic microspheres and to compare them with polyvinyl alcohol (PVA) particles. METHODS: Samples of 100- to 300-microns, 300- to 500-microns, 500- to 700-microns, and 700- to 900-microns collagen-coated acrylic microspheres and 200- to 300-microns PVA particles were suspended in solutions of 50% saline and 50% contrast material. The samples were evaluated for quantitative and qualitative microscopic characteristics (shape, size, deformability); injectability via standardized microcatheters; degree of particulate penetration in the pig rete mirabile; and reaction of tissue to the particles in 48-hour- and 4-week-old specimens. RESULTS: The acrylic microspheres were spherical and deformable. The sample of 100- to 300-microns microspheres (n = 202) had a mean diameter of 210 microns (standard deviation, 43 microns). Hub accumulation, particle aggregation, and catheter occlusion were not observed with the microspheres (all sizes) but were noted with the PVA particles. The 200- to 300-microns PVA particles formed aggregates in the proximal rete. The 100- to 300-microns microspheres were found throughout the rete and beyond. Chronic transmural and perivascular inflammation was observed with the microspheres and the PVA particles. CONCLUSIONS: Particle aggregation and catheter occlusion do not complicate the transcatheter delivery of collagen-coated acrylic microspheres as they do with PVA particles. For a given particle and vessel size, acrylic microspheres penetrate to a much greater extent than the PVA particles. Tissue reaction to acrylic microspheres and PVA particles is similar.

To identify the sonographic appearance of normal fetal midface anatomy of in vitro fetal specimens and to correlate the appearance with that of in utero fetuses to determine which aspects of this anatomy can be evaluated clinically.The midface structures of 12 normal fetal specimens were examined in the axial, sagittal, and coronal planes with ultrasound. The results were correlated with those of other modalities. One hundred consecutive, normal in utero fetuses were scanned in the same planes in an attempt to identify the same anatomic landmarks identified in the fetal specimens.In the fetal specimens, the upper lip (coronal plane), alveolar ridge, tooth sockets, point of fusion of primary and secondary palates (axial plane), and fusion line of the secondary palate (sagittal plane) were consistently observed. In the 100 in utero fetuses, the same anatomy was visualized in the coronal plane in 95 (95%), in the axial plane in 97 (97%), and in the sagittal plane in 26 (26%). The mean scanning time was 2.8 minutes.Important aspects of fetal midface anatomy that relate to facial clefts can be observed in utero at prenatal sonography in the coronal and axial planes.

PURPOSE: To trace the development of the normal fetal temporal bone by means of plain radiography, MR, and CT. METHODS: Eighteen formalin-fixed fetal specimens, 13.5 to 24.4 weeks' gestational age, were examined with a mammographic plain film technique, CT, and MR imaging at 1.5 T. Temporal bone development and ossification were assessed. RESULTS: The membranous labyrinth grows with amazing rapidity and attains adult size by the middle of the gestation period. The cochlea, vestibule, and semicircular canals are very prominent and easily recognized on MR images. The otic capsule develops from a cartilage model. Ossification of the otic capsule proceeds rapidly between 18 and 24 weeks from multiple ossification centers that replace the cartilaginous framework. The mastoid, internal auditory canal, vestibular aqueduct, and external auditory canal continue to grow after birth. CONCLUSION: The study of fetal developmental anatomy may lead to a better understanding of congenital disorders of the ear. Faster MR scanning techniques may provide a method for in utero evaluation of the fetal temporal bone.