Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions: A Randomized Clinical Trial.

Importance: Malignant pleural effusion (MPE) is challenging to manage. Talc pleurodesis is a common and effective treatment. There are no reliable data, however, regarding the optimal method for talc delivery, leading to differences in practice and recommendations. Objective: To test the hypothesis that administration of talc poudrage during thoracoscopy with local anesthesia is more effective than talc slurry delivered via chest tube in successfully inducing pleurodesis. Design, Setting, and Participants: Open-label, randomized clinical trial conducted at 17 UK hospitals. A total of 330 participants were enrolled from August 2012 to April 2018 and followed up until October 2018. Patients were eligible if they were older than 18 years, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were excluded if they required a thoracoscopy for diagnostic purposes or had evidence of nonexpandable lung. Interventions: Patients randomized to the talc poudrage group (n = 166) received 4 g of talc poudrage during thoracoscopy while under moderate sedation, while patients randomized to the control group (n = 164) underwent bedside chest tube insertion with local anesthesia followed by administration of 4 g of sterile talc slurry. Main Outcomes and Measures: The primary outcome was pleurodesis failure up to 90 days after randomization. Secondary outcomes included pleurodesis failure at 30 and 180 days; time to pleurodesis failure; number of nights spent in the hospital over 90 days; patient-reported thoracic pain and dyspnea at 7, 30, 90, and 180 days; health-related quality of life at 30, 90, and 180 days; all-cause mortality; and percentage of opacification on chest radiograph at drain removal and at 30, 90, and 180 days. Results: Among 330 patients who were randomized (mean age, 68 years; 181 [55%] women), 320 (97%) were included in the primary outcome analysis. At 90 days, the pleurodesis failure rate was 36 of 161 patients (22%) in the talc poudrage group and 38 of 159 (24%) in the talc slurry group (adjusted odds ratio, 0.91 [95% CI, 0.54-1.55]; P = .74; difference, -1.8% [95% CI, -10.7% to 7.2%]). No statistically significant differences were noted in any of the 24 prespecified secondary outcomes. Conclusions and Relevance: Among patients with malignant pleural effusion, thoracoscopic talc poudrage, compared with talc slurry delivered via chest tube, resulted in no significant difference in the rate of pleurodesis failure at 90 days. However, the study may have been underpowered to detect small but potentially important differences. Trial Registration: ISRCTN Identifier: ISRCTN47845793.

Population pharmacokinetic and pharmacodynamic properties of artesunate in patients with artemisinin sensitive and resistant infections in Southern Myanmar.

BACKGROUND: Artemisinins are the most effective anti-malarial drugs for uncomplicated and severe Plasmodium falciparum malaria. However, widespread artemisinin resistance in the Greater Mekong Region of Southeast Asia is threatening the possibility to control and eliminate malaria. This work aimed to evaluate the pharmacokinetic and pharmacodynamic properties of artesunate and its active metabolite, dihydroartemisinin, in patients with sensitive and resistant falciparum infections in Southern Myanmar. In addition, a simple nomogram previously developed to identify artemisinin resistant malaria infections was evaluated. METHODS: Fifty-three (n = 53) patients were recruited and received daily oral artesunate monotherapy (4 mg/kg) for 7 days. Frequent artesunate and dihydroartemisinin plasma concentration measurements and parasite microscopy counts were obtained and evaluated using nonlinear mixed-effects modelling. RESULTS: The absorption of artesunate was best characterized by a transit-compartment (n = 3) model, followed by one-compartment disposition models for artesunate and dihydroartemisinin. The drug-dependent parasite killing effect of dihydroartemisinin was described using an Emax function, with a mixture model discriminating between artemisinin sensitive and resistant parasites. Overall, 56% of the studied population was predicted to have resistant malaria infections. Application of the proposed nomogram to identify artemisinin-resistant malaria infections demonstrated an overall sensitivity of 90% compared to 55% with the traditional day-3 positivity test. CONCLUSION: The pharmacokinetic-pharmacodynamic properties of artesunate and dihydroartemisinin were well-characterized with a mixture model to differentiate between drug sensitive and resistant infections in these patients. More than half of all patients recruited in this study had artemisinin-resistant infections. The relatively high sensitivity of the proposed nomogram highlights its potential clinical usefulness.

A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy.

BACKGROUND: This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. PATIENTS AND METHODS: Patients were randomly assigned (1 : 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. RESULTS: A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P = 0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). CONCLUSIONS: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%. CLINICALTRIALS: gov identifier NCT01732549.

Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways.

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.

A decision impact, decision conflict and economic assessment of routine Oncotype DX testing of 146 women with node-negative or pNImi, ER-positive breast cancer in the U.K.

BACKGROUND: Tumour gene expression analysis is useful in predicting adjuvant chemotherapy benefit in early breast cancer patients. This study aims to examine the implications of routine Oncotype DX testing in the U.K. METHODS: Women with oestrogen receptor positive (ER+), pNO or pN1mi breast cancer were assessed for adjuvant chemotherapy and subsequently offered Oncotype DX testing, with changes in chemotherapy decisions recorded. A subset of patients completed questionnaires about their uncertainties regarding chemotherapy decisions pre- and post-testing. All patients were asked to complete a diary of medical interactions over the next 6 months, from which economic data were extracted to model the cost-effectiveness of testing. RESULTS: Oncotype DX testing resulted in changes in chemotherapy decisions in 38 of 142 (26.8%) women, with 26 of 57 (45.6%) spared chemotherapy and 12 of 85 (14.1%) requiring chemotherapy when not initially recommended (9.9% reduction overall). Decision conflict analysis showed that Oncotype DX testing increased patients' confidence in treatment decision making. Economic analysis showed that routine Oncotype DX testing costs £6232 per quality-adjusted life year gained. CONCLUSION: Oncotype DX decreased chemotherapy use and increased confidence in treatment decision making in patients with ER+ early-stage breast cancer. Based on these findings, Oncotype DX is cost-effective in the UK setting.

Infrared thermography as a possible technique for the estimation of parturition onset in sows.

BACKGROUND: This study explores the possibility of using infrared thermography to estimate the onset of parturition in sows. Infrared camera (IRC) and infrared laser thermometer (IRT) were used to obtain the auricular skin temperature of sows along with rectal temperatures, from approximately one week before the anticipated farrowing until 24 h post-partum. Three commercial piglet producing farms were included in the study. RESULTS: There were large variations in observed auricular skin temperature, both by IRC and IRT per time point. Graphical exploration of the observed auricular skin temperature measured by the two methods showed the same parallel patterns, although temperatures measured by IRC were higher at any time point compared to IRT. Auricular skin thermography revealed a clear increase in temperatures before farrowing. Statistical analyses, adjusting for differences between farms, sow activity and respiration rate, confirmed this increase. When controlling for these variables, and comparing the baseline temperatures to temperatures at farrowing, the difference was 3.9 and 4.1 °C measured with IRT and IRC, respectively. The greatest increase, of more than 2 °C, was found between 16 and 8 h and 8 to 4 h before farrowing. Rectal temperature increased by 0.5 °C in the same time interval and reached a temperature peak after farrowing. CONCLUSION: Sows showed a more than 2 °C increase in auricular skin temperature, measured by either IRC or IRT, 8 to16 hours before the first piglet was born. Hence, monitoring auricular skin temperatures of sows using infrared thermography one week before expected farrowing may provide a baseline temperature for each sow from which a sudden rise is indicative of parturition in the following 8 to 16 h. This may lead to more efficient allocation of human assistance during farrowing time and thereby improve farrowing management and the welfare of sows and their offspring.

A Thyrotoxicosis Surprise: Jod-Basedow Phenomenon Following IV Contrast Administration.

Jod-Basedow phenomenon (JBP) is a rare thyrotoxic condition due to increased exogenous iodine exposure, also known as iodine-induced hyperthyroidism (IIH). Historically JBP was typically seen in iodine-deficient patients when exposed to increased amounts of iodine. However, in today's era, the most common cause of JBP is exposure to iodinated contrast media commonly used in various radiological examinations and interventional procedures, resulting in massive iodine exposure. Patients with normal thyroid function usually experience no ill effects. There has been increasing use of iodinated contrast in imaging and procedures over recent decades. Deposition of iodine in the thyroid in a person with normal functioning thyroid glands would usually be autoregulated and inhibited by the Wolff Chaikoff effect. However, a small albeit a significant portion of patients, particularly those with pre-existing thyroid conditions, can escape this auto-regulatory effect and be subject to life-threatening conditions, such as arrhythmias, heart failure, pulmonary arterial hypertension, cerebrovascular and pulmonary embolism, and cardiomyopathy. We present a case of a 59-year-old female with pre-existing goiter who presented with altered mentation and seizures, requiring endotracheal intubation for airway protection. She underwent a CT angiogram of the head and neck for a suspected stroke, receiving iodinated IV contrast in the process. Thyroid function tests on admission showed a thyroid-stimulating hormone (TSH) of 0.974 mIU/L (reference range 0.465-4.650 mIU/L) and free T4 of 0.46 ng/dL (reference range 0.75-2.19 ng/dL). The ensuing ICU course was complicated by thyrotoxicosis eight days after contrast administration with a surge of free T4 from 0.46 ng/dL on admission to 4.07 ng/dL and a TSH suppression to <0.015 mIU/L. She subsequently required three sessions of emergent plasmapheresis to remove excess free T4 before undergoing partial thyroidectomy and cardiac catheterization. Iodine-induced hyperthyroidism solidifies the need for awareness of a potential JBP following contrast administration, especially in an aging population and undiagnosed thyroid conditions, and timely diagnosis and intervention can greatly influence outcomes.

Root Canal Configuration of Burmese (Myanmar) Maxillary First Molar: A Micro-Computed Tomography Study.

AIM: To investigate the root canal anatomy of Burmese (Myanmar) permanent maxillary first molar (BMFM) with micro-computed tomography. Methodology. One hundred and one extracted BMFMs were scanned by a SkyScan 1272 scanner (Bruker microCT, Belgium) and reconstructed with NRecon software (Bruker microCT). CTAn software (Bruker microCT) was used to create 3D models of root and internal canal anatomy, while CTVol software (Bruker microCT) was used to visualize 3D models. In each root, Vertucci's canal types, incidence and location of the lateral canal, incidence, location, and type of isthmus, and number and position of foramina were examined. RESULTS: In 101 specimens, 83 (82.18%) mesiobuccal roots had multiple canals. The most common canal type is type IV (45.5%), followed by type II (17.8%) and I (17.8%) canals. Type III, V, VI, VII, and VIII canals are less than 10% in total. Seven additional canal types were seen for 10% in total. Fourteen (13.86%) distobuccal roots had multiple canals, and the predominant canal type is type I (86.1%), followed by type II (5.9%) and V (4%) canals. Three additional canal types were observed for 4% in total. All palatal roots possessed the simplest type I canal. Apical ramification occurred in 69 mesiobuccal roots (68.3%), 36 distobuccal roots (35.6%), and 37 palatal roots (36.6%). A total of 240 lateral canals were observed in 101 specimens. Each specimen had 2.38 ± 2.22 lateral canals on average. The highest incidence, 136 (56.67%) lateral canals, occurred in the mesiobuccal root, followed by 57 (23.75%) and 47 (19.58%) lateral canals from the distobuccal root and the palatal root, respectively. Each specimen had 6.17 ± 2.42 foramina. Mesiobuccal root had the highest incidence of apical foramina compared to other roots. Seventy-two mesiobuccal roots (71.29%) had isthmus, while only 7 distobuccal roots (6.93%) had isthmus somewhere along the root. CONCLUSIONS: The root canal anatomy of BMFM was quite complex, especially in the mesiobuccal root. The predominant canal type was Vertucci type IV in the mesiobuccal root and type I in the distobuccal and palatal roots. In addition, this micro-computed tomography study disclosed complemented canal types and a higher prevalence of lateral canal than the previous studies.

Sevoflurane and propofol depolarize mitochondria in rat and human cerebrocortical synaptosomes by different mechanisms.

BACKGROUND AND OBJECTIVES: The mitochondrial membrane potential drives the main functions of the mitochondria. Sevoflurane depolarizes neural mitochondria. There is still, however, limited information concerning the effect of anaesthetics on neural mitochondria in humans. The effect of sevoflurane and propofol on the intracellular Ca(2+) concentration [Ca(2+)](i) and the mitochondrial membrane potential (DeltaPsi(m)) was therefore compared in rat and human synaptosomes, and the changes were related to interventions in the electron transport chain. METHODS: Synaptosomes from rat and human cerebral cortex were loaded with the fluorescent probes fura-2 ([Ca(2+)](i)) and JC-1 (DeltaPsi(m)) before exposure to sevoflurane 1 and 2 minimum alveolar concentration (MAC), and propofol 30 and 100 microM. The effect on the electron transport chain was investigated by blocking complex V. RESULTS: Sevoflurane and propofol decreased DeltaPsi(m) in rat synaptosomes in a dose-dependent manner, and to the same extent by equipotent doses. Inhibition of complex V enhanced the depolarizing effect of sevoflurane 2 MAC, but not of propofol 100 microM. Neither sevoflurane nor propofol affected [Ca(2+)](i) significantly. Sevoflurane and propofol decreased DeltaPsi(m) in human synaptosomes to the same extent as in the rat experiments. CONCLUSIONS: Sevoflurane and propofol at equipotent doses depolarize the mitochondria in rat and human nerve terminals to the same extent. The depolarizing effect of propofol on Psi(m) was more rapid in onset than that of sevoflurane. Whereas sevoflurane inhibits the respiratory chain sufficiently to cause ATP synthase reversal, the depolarizing effect of propofol seems to be related to inhibition of the respiratory chain from complex I to V.

Isoflurane-induced depolarization of neural mitochondria increases with age.

BACKGROUND AND OBJECTIVES: The mitochondrial membrane potential (DeltaPsi(m)) drives the three fundamental functions of mitochondria, namely adenosine triphosphate (ATP) generation, Ca(2+) uptake/storage, and generation/detoxification of ROS. Isoflurane depolarizes neural mitochondria. The sensitivity for general anesthetics increases with age, but the mechanism for this age-related sensitivity is still unknown. We compared the effect of isoflurane on [Ca(2+)](i) and DeltaPsi(m) in isolated pre-synaptic terminals (synaptosomes) from neonatal, adolescent, and adult rats and the influence of interventions in the respiratory chain was assessed. METHODS: Synaptosomes were loaded with the fluorescent probes fura-2 ([Ca(2+)](i)) and JC-1 (DeltaPsi(m)) and exposed to isoflurane 1 and 2 minimum alveolar concentration (MAC). The effect on the electron transport chain was investigated by blocking complexes I and V. RESULTS: In neonatal rats isoflurane had no significant effect on DeltaPsi(m). In adolescent and adult synaptosomes, however, isoflurane 1 and 2 MAC decreased DeltaPsi(m). Isoflurane 2 MAC increased [Ca(2+)](i) in neonatal and adolescent rats, but not in adult synaptosomes. In Ca(2+)-depleted medium, isoflurane still decreased DeltaPsi(m), while [Ca(2+)](i) remained unaltered. By blocking complex V of the respiratory chain, the isoflurane-induced mitochondrial depolarization was enhanced in all age groups. Blocking complex I depolarized the mitochondria to the same extent as isoflurane 2 MAC, but without any additive effect. CONCLUSIONS: The depolarizing effect of isoflurane on neural mitochondria is more pronounced in the adolescent and adult than in neonatal synaptosomes. The increased mitochondrial sensitivity with age seems to be related to the reversed function of the ATP synthase of the electron transport chain.

Microbiological contamination during transgastric and transvaginal endoscopic techniques.

Natural orifice transluminal endoscopic surgery (NOTES) has gained widespread interest as a potentially alternative to laparoscopic surgery, but concerns over peritoneal contaminations are unsolved. The aim of our study was to assess the safety of transluminal surgery by investigating the intraperitoneal bacterial load and contamination during transgastric and transvaginal surgeries. Twelve female pigs underwent transgastric (n = 7; tubal ligation and oophorectomy) and transvaginal procedures (n = 5; cholecystectomy). All animals were sacrificed after 2 weeks. The procedures were performed by using a double-channel endoscope (GIF-2T160; Olympus, Tokyo, Japan) under general anesthesia. Peritoneal fluid sampling was taken immediately after entry into the abdomen, at the end of the surgical procedure and during the autopsy, and sent for microbiologic assessment. In the transgastric group, 6 animals completed the surgical procedures and survived. Three pigs experienced signs of postoperative peritonitis with abscesses and adhesions visible and Escherichia Coli isolated at autopsy. In the transvaginal group, a cholecystectomy was performed without technical problems in all animals. No signs of postoperative sepsis nor growth in the microbiologic samples were recorded. In conclusion, the transvaginal approach seemed to be safer and produced less intra-abdominal contamination and sepsis, compared to the transgastric approach. Although both transgastric tubal ligation and oophorectomy and transvaginal cholecystectomy were feasible using equipment and accessories currently available for conventional endoscopy, new procedure-specific instruments and equipment should be developed to allow the operator safer access into the peritoneum.

Stridor: an unexpected complication from chemoradiotherapy for anal cancer.

The treatment of choice for anal cancer is chemoradiotherapy. Skin reaction and bowel symptoms such as tenesmus, diarrhoea and bleeding are common side effects. We report a patient who developed stridor as a result of chemoradiotherapy for anal cancer and discuss the pathogenesis and potential consequences.

Porcine circovirus type 2 associated reproductive failure in a specific pathogen free (SPF) piglet producing herd in Norway: a case report.

BACKGROUND: Since 1999, scientists have published evidence of transplacental infection by porcine circovirus type 2 (PCV2) and reproductive failure in pigs. Affected herds have frequently been start-up herds, either naïve or with a high proportion of PCV2 susceptible gilts. Here, delayed farrowing in non-vaccinated gilts was observed in a commercial specific pathogen free (SPF) herd. Mummified fetuses and stillborn piglets recovered from these gilts were PCV2 positive. CASE PRESENTATION: The case herd was a self-recruiting, piglet producing unit of 240 sows. After detecting livestock associated methicillin resistant Staphylococcus aureus (LA-MRSA, CC398), stamping out was imposed by the authorities. An SPF herd was re-established and all dams were vaccinated against PCV2 until the farmer decided to exclude this vaccine. The first non-vaccinated batch consisted of 76% gilts. Here, one gilt showed signs of impending farrowing. This gilt was slaughtered three to four weeks after the expected farrowing date without having expelled any uterine contents. In the subsequent batch consisting of 79% gilts, three gilts showed similar clinical signs. Delayed farrowing was observed in two of these gilts and the uterine contents from the third gilt were recovered at the abattoir. Mummified fetuses and stillborn piglets were recovered from all three gilts. High levels of PCV2 DNA (>107 viral genomic copies/ 500 ng tissue) were found in myocardial samples by real-time PCR analysis. One myocardial sample submitted for immunohistochemical (IHC) analysis showed moderate amounts of PCV2 antigen. In the subsequent batch consisting of 77% gilts, several weak-born piglets were seen across different litters. CONCLUSIONS: This case report describes an apparent link between in utero PCV2 infection, pre partum nest-building behaviour, mammary development and delayed farrowing. To date, no reports have described imminent signs of farrowing and delayed farrowing as clinical signs in conjunction with transplacental PCV2 infection in Norway. Reinitiation of PCV2 vaccination was strongly advised in this herd due to recent depopulation and repopulation and the high proportion of gilts. Vaccination was effective because no further cases have occurred since.

Zinc oxide enriched peat influence Escherichia coli infection related diarrhea, growth rates, serum and tissue zinc levels in Norwegian piglets around weaning: five case herd trials.

BACKGROUND: Zinc oxide (ZnO), commonly used to control post-weaning diarrhea in piglets, has been highlighted as of potential concern from an environmental perspective. The aim of this field trial was to examine effects of different sources and levels of ZnO added to peat on average daily weight gain (ADG), fecal score in pens and serum and tissue zinc (Zn) levels around time of weaning in order to reduce the environmental impact without loss of the beneficial effect of ZnO on intestinal health and growth. Five case herds with enterotoxic colibacillosis challenges were included. The piglets entered the study aged three or five weeks. All piglets received a commercial diet containing <150 mg Zn/ per kg of complete feed. Four treatment groups received commercial peat added A: uncoated ZnO, B: lipid microencapsulated ZnO, C: solely commercial peat or D: no peat (Farms 2 and 3). RESULTS: At Farms 1, 2 and 3, a significant effect of treatment was identified for fecal score (P < 0.05). Treatment A led to lower fecal scores compared to treatments C (P < 0.05) and D (P < 0.01). At Farms 2 and 3, there was a significant difference in individual average daily weight gain (iADG) between treatment A and D (P < 0.05). The iADG of piglets receiving treatment B did not differ significantly from treatment A. CONCLUSIONS: In 2016, The European Medicines Agency's Committee on Veterinary Medicinal Products concluded that the benefits of ZnO for the prevention of diarrhea in pigs do not outweigh the risks to the environment. Effective alternative measures to reduce the accumulation of Zn in the environment have not been identified. Our results imply that peat added low concentration of both coated and uncoated ZnO influences the gut health of weaned piglets reflected by enhanced weight gain and reduced occurrence of diarrhea. This preventive approach certainly represents a favourable alternative in the "One Health" perspective. It will also contribute to reduced antibiotic use in pig farming while diminishing the environmental consequences caused by ZnO.

Comparison of total energy expenditure between school and summer months.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Childhood obesity has increased 3 to 4 fold. Some children gain excess weight in summer. WHAT THIS STUDY ADDS: Total energy expenditure increases almost linearly with fat-free mass. A lower total energy expenditure was not detected in summer. OBJECTIVE: Recent data report that the youth experience greater weight gain during summer than during school months. We tested the hypothesis that a difference in total energy expenditure (TEE) between school and summer months exists and may contribute to summer weight gain. SUBJECTS AND METHODS: A secondary analysis was performed on cross-sectional TEE data from school-age, sedentary African-American and Caucasian youth based in or near the District of Columbia who were at-risk for adult obesity because they had body mass index (BMI) ≥ 85th percentile or had overweight parents. TEE was estimated from 18-O and deuterium measurements during 1-week intervals using urine samples collected after ingestion of doubly labelled water. Differences in summer- and school-time TEE were assessed using analysis of covariance. The data were adjusted for fat-free mass (FFM) as determined by deuterium dilution to adjust for the effect of body size on TEE. RESULTS: Data were collected from 162 youth (average age 10 ± 2 years, BMI 28 ± 8 kg m(-2) and BMI z-score 1.96 + 0.96). Of these, 96 youth had TEE measured during the school year (September-June); 66 different youths had TEE measured during summer months (June-August). After adjustment for FFM, average summertime TEE was 2450 ± 270 kcal d(-1) and average school-time TEE was 2510 ± 350 kcal d(-1) (P = 0.26). CONCLUSION: No difference in TEE was detected between the school year and the summer months. These data suggest that seasonal differences in youth weight gain are not necessarily due to differences in energy expenditures.

Reduced susceptibility of Plasmodium falciparum to artesunate in southern Myanmar.

BACKGROUND: Plasmodium falciparum resistance to artemisinins, the first line treatment for malaria worldwide, has been reported in western Cambodia. Resistance is characterized by significantly delayed clearance of parasites following artemisinin treatment. Artemisinin resistance has not previously been reported in Myanmar, which has the highest falciparum malaria burden among Southeast Asian countries. METHODS: A non-randomized, single-arm, open-label clinical trial of artesunate monotherapy (4 mg/kg daily for seven days) was conducted in adults with acute blood-smear positive P. falciparum malaria in Kawthaung, southern Myanmar. Parasite density was measured every 12 hours until two consecutive negative smears were obtained. Participants were followed weekly at the study clinic for three additional weeks. Co-primary endpoints included parasite clearance time (the time required for complete clearance of initial parasitemia), parasite clearance half-life (the time required for parasitemia to decrease by 50% based on the linear portion of the parasite clearance slope), and detectable parasitemia 72 hours after commencement of artesunate treatment. Drug pharmacokinetics were measured to rule out delayed clearance due to suboptimal drug levels. RESULTS: The median (range) parasite clearance half-life and time were 4.8 (2.1-9.7) and 60 (24-96) hours, respectively. The frequency distributions of parasite clearance half-life and time were bimodal, with very slow parasite clearance characteristic of the slowest-clearing Cambodian parasites (half-life longer than 6.2 hours) in approximately 1/3 of infections. Fourteen of 52 participants (26.9%) had a measurable parasitemia 72 hours after initiating artesunate treatment. Parasite clearance was not associated with drug pharmacokinetics. CONCLUSIONS: A subset of P. falciparum infections in southern Myanmar displayed markedly delayed clearance following artemisinin treatment, suggesting either emergence of artemisinin resistance in southern Myanmar or spread to this location from its site of origin in western Cambodia. Resistance containment efforts are underway in Myanmar. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000896077.

Total transvaginal endoscopic abdominal wall hernia repair: a NOTES survival study.

HYPOTHESIS: Natural orifice transluminal endoscopic surgery (NOTES) has gained widespread interest as a potentially less invasive alternative to laparoscopic surgery or, else, an evolution as the next-generation surgery. The main objective of this study was to assess the safety of transluminal abdominal wall hernia repair for potential human application by specifically investigating the feasibility and challenges of using a transvaginal approach. DESIGN: NOTES ventral hernia repair via a transvaginal approach. SETTING: University Hospital (National University Health System, Singapore). PARTICIPANTS: The study utilized five female pigs (30-40 kg) between 5 and 7 months of age, which underwent abdominal wall hernia repair using a transvaginal approach. INTERVENTION: The procedures were performed using a double-channel endoscope under general endotracheal anesthesia. A mesh was placed and fixed to the abdominal wall using standard laparoscopic and endoscopic equipment. The animals survived for 2 weeks and were then euthanized and a necropsy performed. MAIN OUTCOME MEASURES: To assess the safety and feasibility of NOTES ventral hernia repair in a survival experimental model. RESULTS: All of the procedures could be safely performed using the standard equipment. At the necropsy, all meshes were well in place and mild adhesions were recorded in one animal with a small abscess in the subcutaneous area. CONCLUSION: This novel approach seems technically challenging but feasible using equipment and accessories currently available for conventional laparoscopic and interventional endoscopy with low intra-abdominal contamination and sepsis. New procedure-specific instruments and equipment need to be developed to allow the surgeon safer access and more degrees of instrument freedom.

Expression of 3beta-hydroxysteroid dehydrogenase, cytochrome P450-c17, and sulfotransferase 2B1 proteins in liver and testis of pigs of two breeds: relationship with adipose tissue androstenone concentration.

An excessive accumulation of androstenone in pig adipose tissue is a major contributor to the phenomenon of boar taint. Androstenone deposition is dependent on the rate of androstenone biosynthesis in testis and androstenone degradation in liver. The aim of the current study was to examine the possibility of the existence of breed-specific mechanisms controlling androstenone accumulation in pig adipose tissue. The specific objective was to investigate the expression of some of the key enzymes involved in testicular and hepatic androstenone metabolism in pigs of 2 breeds by using animals with high and low androstenone concentrations within each breed. The study was conducted with Norwegian Landrace (N. Landrace) and Duroc boars. The mean androstenone values for the low- and high-androstenone groups were 0.1 +/- 0.01 microg/g and 7.58 +/- 0.68 microg/g for N. Landrace boars, and 0.22 +/- 0.04 microg/g and 13.55 +/- 1.14 microg/g for Duroc boars. The enzymes investigated were 3beta-hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450-c17, and sulfotransferase 2B1 (SULT2B1). Expression of cytochrome P450-c17 in liver and testis did not differ between animals with high and low androstenone concentrations in either the N. Landrace or Duroc breed. Expression of hepatic 3beta-HSD, which catalyzes the first stage of androstenone degradation, was decreased in high-androstenone N. Landrace boars (P < 0.01), but not in high-androstenone Duroc boars. In contrast, the expression of hepatic SULT2B1, which catalyzes the second stage of steroid catabolism, was decreased in high-androstenone Duroc animals (P < 0.05), but not in high-androstenone N. Landrace animals. Sulfotransferase 2B1 was also inhibited in testis of high-androstenone pigs of both breeds compared with low-androstenone animals. We report breed differences in expression of the androstenone-metabolizing enzymes 3beta-HSD and SULT2B1 in the liver of high- and low-androstenone pigs. It is suggested that accumulation of androstenone in adipose tissue of N. Landrace boars might be related to a low rate of hepatic androstenone degradation in metabolic stage I, whereas the high androstenone concentration in Duroc boars might be related to a low rate of androstenone metabolism in metabolic stage II.