Sustained positive impact on tuberculosis treatment outcomes of TB-HIV integrated care in Uganda.

To examine tuberculosis (TB) treatment outcomes from a long-term TB-HIV (human immunodeficiency virus) integrated model of care at the Infectious Diseases Institute Clinic, Kampala, Uganda. We included HIV-positive adults who were new TB cases initiated on anti-tuberculosis treatment between 2009 and 2015 during TB-HIV integration. Trends in TB treatment outcomes and TB-associated deaths were analyzed using respectively the χ² trend test and Kaplan-Meier methods. The analysis involved 1318 cases: most patients were female (>50%); the median age ranged from 34 to 36 years, and >60% were late presenters (CD4 count <200 cells/µl), with a median CD4 cell count of 100-146 cells/µl at TB diagnosis. TB treatment success (cured or treatment completed) was 67-76%. Loss to follow-up (LTFU) declined systematically from 7% in 2010 to 3.4% in 2015 (P < 0.01). Antiretroviral therapy (ART) initiation during the intensive phase improved from 47% in 2009 to 97% in 2015 (P < 0.01). The mortality rate was >15% over time, and the probability of death at month 2 of anti-tuberculosis treatment was 52% higher among late presenters than in early presenters (13% vs. 6%, P < 0.01). Significant LTFU improvement and prompt ART initiation could be due to well-implemented TB-HIV integration care; however, static TB-associated deaths may be due to late presentation. .

Development of swimming in the medicinal leech, the gradual acquisition of a behavior.

Observing the development of behavior provides an assay for the developmental state of an embryo's nervous system. We have previously described the development of behaviors that were largely confined to one or a few segments. We now extend the work to a kinematic analysis of the development of swimming, a behavior that requires coordination of the entire body. When leech embryos first begin to swim they make little forward progress, but within several days they swim as effectively as adults. This increase in efficacy depends on changes in body shape and on improved intersegmental coordination of the swim central pattern generator. These kinematic details suggest how the swim central pattern generating circuit is assembled during embryogenesis.

Chick development in free-living great tits Parus major in relation to calcium availability and egg composition.

Evidence from a number of avian studies suggests that limitation of exogenous calcium (Ca) may reduce egg quality and retard nestling growth. However, it is poorly understood whether reduction in chick growth in Ca-poor areas is due to insufficient intake of dietary Ca or caused by maternal Ca limitation mediated through subtle changes in composition of eggs. In this study, we provide new evidence that Ca availability during egg formation may indeed affect egg composition and influence chick development of the great tit Parus major at early developmental stages. Ca-supplemented birds breeding in base-poor pine forests produced eggs with elevated yolk Ca concentration compared with controls, while no such effect of supplementation was detected in case of eggshell thickness. Nestling tarsus length in the first half of the nestling period was positively influenced by both yolk dry mass and yolk Ca concentration. The effect of supplementary Ca did not persist throughout the nestling period; initial effects of egg components disappeared as nestlings aged. We conclude that apparently normal eggs may harbor poor nutrient and mineral conditions for chick growth. Such subtle changes in composition of eggs can depress chick growth, especially in harsh years.

Food supplementation and possible mechanisms underlying early breeding in the Florida Scrub-Jay (Aphelocoma coerulescens).

Food supplementation studies demonstrate the importance of resources in the timing of reproduction. Studies of Florida Scrub-Jays (Aphelocoma coerulescens) found that supplemented jays bred earlier than unsupplemented jays and that protein may play a critical role. In this study, free-living scrub-jays were provided with supplemental diets high in fat and protein (HFHP) or high in fat and low in protein (HFLP). Jays in both treatments bred earlier than unsupplemented controls (CNT), but HFHP-supplemented jays bred earlier than HFLP jays. To assess possible mechanisms, we measured testosterone (T) in males, estradiol (E2) in females, and corticosterone (CORT) in both. HFHP males had higher T than HFLP and CNT males, but treatment did not affect E2 levels of females. Pilot studies of scrub-jays in suburban environments suggest that the spatial and temporal predictability of food may influence corticosterone (CORT) levels. Suburban jays have year-round access to human-provided foods and breed earlier than wildland jays; thus, we compared CORT in all treatments in the natural site (wildlands) with those of suburban jays. CORT levels of suburban jays were lower than HFLP, HFHP, and CNT jays. HFHP-supplemented jays had lower CORT levels than those of HFLP and CNT jays. The observed differences in the timing of breeding, both between suburban and wildland populations and between experimental groups in the wildlands, may result from differences in the spatial and temporal predictability of food, and the nutritional differences in diets. Because CORT can negatively affect the reproductive axis, we postulate that nutrient availability, the predictability of food, CORT levels, and initiation of reproduction are inextricably linked.

Dying to be thin: a dinitrophenol related fatality.

2, 4-dinitrophenol (DNP) was originally used as an explosive and later introduced in the 1930's to stimulate metabolism and promote weight loss. It's also a component of pesticides still available globally. Concerns about hyperpyrexia lead to DNP being banned as a dietary aid in 1938. A 22-y-old male presented to the Emergency Department (ED) with a change in mental status 16 h after his last dose of DNP. On admission he was diaphoretic and febrile with an oral temperature of 102 F, but lucid and cooperative. He became agitated and delirious. Intravenous midazolam was initiated with mechanical cooling. Pancuronium was administered later and the patient was intubated. Over the next hour the patient became bradycardic, then asystolic, and despite resuscitative efforts, died. Advertisements claim DNP safe at the dose our patient ingested. It is widely available and with the potential to cause severe toxicity is an understudied public health concern.

Vegetable oil sprinkling as a dust reduction method in swine confinement.

The aim of this project was evaluate the effectiveness of an oil sprinkling system as a dust-reduction method for swine production facilities. This article presents the results of the second-year experiment of a multi-year study. The first-year experiment demonstrated that a 5% oil-water emulsion automatically applied at the rate of 3 and 5 g/pig/day achieved a 23% to 34% reduction in total dust. The modifications for the second year experiment included: (1) increasing oil application rate to 7 and 8 g/pig/day, (2) replacing sprinkler heads to achieve a smaller droplet size and a more direct spray pattern on pen-floor surfaces, and (3) more closely matching the treatment and control rooms by stage in the pig production cycle. Four swine finishing rooms were used for this study; two were treatment rooms (soybean oil at 7 g/pig/day, and canola oil 8 g/pig/day) and two were control rooms. The treatment rooms had a low-pressure oil-sprinkling system, which sprinkled 5% oil-to-water mixture 12 times per day, 12 s each time. Concentrations of several environmental contaminants were measured. The average total dust concentration in the control rooms was 1.39 mg/m3. The average total dust concentration in the treatment rooms was 0.65 mg/m3. The treatment reduced dust by an average of 52%, (p = 0.0001). There was no difference in the degree of dust control between soybean oil and canola oil. The respirable dust concentrations were very low in all rooms, and there were no significant differences between rooms in ammonia, carbon dioxide, temperature, or humidity.

Nutritional quality of prebreeding diet influences breeding performance of the Florida scrub-jay.

Food supplementation studies of breeding birds have traditionally concentrated on energetic constraints on breeding performance. It is only recently that the nutritional quality of the prebreeding diet has also been considered influential. We examined the importance of specific nutrients in the prebreeding diet of the Florida scrub-jay ( Aphelocoma coerulescens). Birds were provided with one of two supplements (rich in protein and fat or rich in fat only) prior to breeding in 2000 and 2001 and their breeding performance, in relation to unsupplemented (control) birds, was examined. Birds receiving both supplements significantly advanced laying in both years, and increased clutch size in 2000 but not in 2001. Laying date explained variation in clutch size in birds on dietary supplements. Egg mass and volume declined with laying order, irrespective of dietary treatment, but birds on the high fat, high protein diet laid heavier third eggs than controls and this was independent of laying date. Laboratory analysis of 14 abandoned and unhatched eggs revealed that as egg mass increased so did the absolute amount of protein and water while fat content remained relatively fixed. Using these relationships between the masses of egg components and fresh egg mass, we calculated that heavier third eggs laid by birds on high fat and high protein, compared with those laid by controls, contained more water that may be fundamental to chick growth and survival. This is the first demonstration for an avian species that nutritional quality of prebreeding diet can simultaneously influence laying date, clutch size, and egg size and composition.

Staging of middle and late embryonic development in the medicinal leech, Hirudo medicinalis.

We present a description of the last half of embryonic development in the European medicinal leech, Hirudo medicinalis, based entirely on externally visible morphological features, and establish reliably observable stages during that development. Embryogenesis, from the time fertilized eggs are deposited in an eggcase (called a cocoon) to the emergence of juveniles from the cocoon, takes approximately 4 weeks at room temperature. The stages described in this paper extend from the completion of segmentation to the appearance of the final bands of pigmentation. Developmental stages are expressed as percentages of total embryonic developmental time. This staging table was constructed for embryos kept at 20 degrees C. In addition, the development of animals kept at 17 degrees C or at 24 degrees C was compared with those held at 20 degrees C. Development proceeds more quickly at higher temperatures. Because development in embryos held at higher or lower temperatures was linearly related to the stages determined for embryos held at 20 degrees C, the rate of development at any intermediate temperature can be predicted from the staging table at 20 degrees C by simple multiplication.

Development of spontaneous and evoked behaviors in the medicinal leech.

ABSTRACT The ontogeny of behavior in an organism must reflect developmental events in the nervous system, and it thus provides a noninvasive measure of neuronal development. This approach may be particularly fruitful in the medicinal leech because the neuronal basis of several behaviors has been characterized in adult leeches, providing a rich background against which behavioral development can be interpreted. We have investigated the order in which behaviors arise during the period of embryonic development and have determined the time at which each behavior is first expressed. Some behaviors, such as lateral ridge formation, germinal plate bending, spiral twisting, and sidewinding, were produced spontaneously by embryos. Others, such as shortening, circumferential indentation, local bending, and elongation, occurred only when they were elicited by weak mechanical stimulation. Such stimulation rarely evoked a behavioral response in young embryos (at 45% of the time required for complete embryonic development, 45% ED), but by 80% ED embryos responded to nearly 100% of the stimuli presented. In embryos older than 50% ED, the behavior most frequently evoked by stimulation of the anterior end, the posterior end, or the rear sucker was shortening. Stimulation of the midbody usually evoked behavior other than shortening, illustrating that the body was behaviorally compartmentalized, at least in part. Some behaviors observed during embryogenesis are never seen in adult leeches. For example, in response to stimulation of the midbody, young embryos produced a behavior that we have called "circumferential indentation," whereas older embryos produced local bending, a response previously described for adults. The switch from circumferential indentation to local bending may signal the formation of new synaptic connections.

The carry-through of residues of maleic hydrazide from treated potatoes, following manufacture into potato crisps and 'jacket' potato crisps.

Potatoes, which had been treated 'in the field' with a commercial formulation of maleic hydrazide, were processed into potato crisps and jacket potato crisps on a factory production line using standard manufacturing conditions. Samples were taken at strategic points throughout the process and analysed to determine the degree of carry-through of residues. Results demonstrated that ca 56% of the maleic hydrazide residue in a potato could be carried through into the potato crisps, irrespective of which type of crisp was being manufactured. Results from a similarly constructed study investigating the fate of pesticides applied post-harvest showed that carry-through was less than 10%. This difference is explained in terms of the different modes of action of the two classes of pesticides being investigated. It is known that, as maleic hydrazide is a systemic pesticide, it will be located within the flesh of the potato tuber and is therefore likely to be protected from the various stages of the crisping process. However, the post-harvest non-systemic pesticides are applied to the exterior surface of the tuber and are therefore not likely to be protected in the same way. The results also showed that, due to the concentration effect caused by the loss of moisture during crisp manufacture, the levels of maleic hydrazide residues in crisps (on a mg/kg product basis) were approximately twice those measured in the original potatoes.

Extraction of maleic hydrazide residues from potato crisps and their determination using high-performance liquid chromatography with UV and atmospheric pressure chemical ionisation mass spectrometric detection.

A method was required for the determination of maleic hydrazide residues in potato crisps. A published method for the extraction of the analyte from onions and potatoes was evaluated and found to be inappropriate due to the inability of the extracting solvent to penetrate the oily matrix. A method was developed to overcome this problem; the resulting recovery data (mean = 92.9%, R.S.D. = 8.3%, n = 16) confirmed its efficiency, and was used to analyse 48 retail potato crisp samples. To confirm possible residues identified by screening with HPLC-UV, an HPLC-atmospheric pressure chemical ionization MS method was developed. There was good agreement between the data obtained from the two detection techniques (R2 = 0.978, slope = 1.11).

Identification and characterization of a unique chondrocyte gene involved in transition to hypertrophy.

The character of differentiating chondrocytes in growing long bones has been defined by altered expression of a limited number of genes. To expand this set we have applied differential display to identify genes expressed in either mineralizing or nonmineralizing chondrocytes. One such gene, Band 17, has the following characteristics: (1) Band 17 expression is predominantly found in cartilage destined for mineralization. Band 17 mRNA is undetectable in articular cartilage and undetectable or weak in all other tissues tested. (2) Band 17 expression is spatially restricted to the lower proliferative/upper hypertrophic zone of chondrocytes in the growth plate of long bones and embryonic vertebrae. (3) Induction of a hypertrophic phenotype in progenitor sternal chondrocytes by treatment with ascorbate increases expression of Band 17. (4) Induction of hypertrophy in growth plate chondrocytes in short-term monolayer cultures correlates with a rapid but transient rise in Band 17 message. Our interpretation of these findings is that Band 17 expression is associated with the transition to hypertrophy, not maintenance of the hypertrophic phenotype. Molecular analysis of the 3' end of Band 17 cDNAs and genomic structure has shown that Band 17 is a single copy gene transcribed into four messages. Alternative splicing of these messages is predicted to result in two proteins that differ at the C-terminal by 131 amino acids. The longer protein contains a C-terminal consensus sequence that potentially targets this protein to the lumen of the endoplasmic reticulum. There is a Band 17 homologue in humans, suggesting conservation of Band 17 function in mammals. In summary, the pattern of expression and the predicted primary structure identify Band 17 as unique among all previously known chondrocyte genes.

The carry-through of residues of thiabendazole, tecnazene and chlorpropham from potatoes following manufacture into potato crisps and jacket potato crisps.

Potatoes, commercially treated with thiabendazole, tecnazene and chlorpropham, were processed into potato crisps and jacket potato crisps at a crisp factory using standard manufacturing conditions. A multi-residue method based on gas chromatography with mass spectrometric detection was developed and used to determine pesticide residue levels in the potatoes and potato crisps. Results showed that the residues of all three pesticides were significantly reduced to less than 2% and less than 10% of the maximum theoretical residue carry-through level for potato crisps and jacket potato crisps respectively.

Plasma beta-endorphin levels and childhood intussusception.

To determine whether childhood intestinal intussusception is associated with elevated plasma beta-endorphin levels, a series of patients was studied prospectively. Fourteen patients (age range between 3 months and 7 years) presented to two university pediatric emergency departments in Chicago with clinical symptoms and signs of intussusception. Venous blood (2cc) was withdrawn for plasma beta-endorphin determination, followed by barium enema. Plasma beta-endorphin levels were measured by radioimmunoassay. The mean beta-endorphin level of the 8 patients with barium enema proven intussusception was 14.1 +/- 12.0 pg/ml. Two of these patients presented with marked lethargy and had beta-endorphin levels of 7.5 and 21.2 pg/ml. The mean plasma beta-endorphin level of the 5 patients with negative barium enema studies was 18.1 +/- 10.0 pg/ml (P = 0.56). A sixth control patient had a plasma beta-endorphin level of 1569 pg/ml. In conclusion, childhood intestinal intussusception is not associated with elevated plasma beta-endorphin levels.

Testosterone levels during systemic and inhaled corticosteroid therapy.

Testosterone has importance both as a sex hormone and as an anabolic steroid promoting bone formation. Osteoporosis is associated with both hypogonadism and corticosteroid therapy. Testosterone levels are reduced by long term prednisolone treatment. Although high dose inhaled corticosteroid therapy may cause a variety of systemic effects including adrenal suppression, dermal thinning and a reduction in total bone calcium, its effect on testosterone levels is not known. Testosterone, luteinizing hormone, follicle stimulating hormone and sex hormone binding globulin were therefore measured in 35 male patients with respiratory disease attending an outpatient clinic (median age 58, range 21-75 years). They were grouped according to steroid therapy and compared with 19 age matched controls. Mean (SD) testosterone levels were 33% lower in 12 men on long term oral prednisolone [14.5 (6.0) nmol 1-1] than in controls [21.7 (6.3) nmol 1-1], but were not significantly reduced in 10 patients on low dose inhaled beclomethasone [200-800 micrograms day-1: 19.7 (3.7)] nor in 13 men taking high dose inhaled beclomethasone [1500-2,250 micrograms day-1: 17.9 (5.6)]. Levels of luteinizing hormone, follicle stimulating hormone and sex hormone binding globulin were similar in all four groups. These cross sectional data confirm that long term systemic corticosteroid therapy reduces testosterone levels. However, testosterone was reduced by only 18% (NS) by long term inhaled corticosteroids. Other mechanisms to explain the disordered bone metabolism should now be explored.

Age differences and changes in reaction time: the Baltimore Longitudinal Study of Aging.

This study analyzed auditory reaction time (RT) data from 1,265 community-dwelling volunteers (833 males and 432 females) who ranged in age from 17 to 96. Cross-sectional analyses revealed slowing of simple (SRT) and relatively greater slowing of disjunctive (DRT; aka "go-no-go") reaction time across decades for both males and females. Repeated testing within participants (longitudinal analyses) over eight years showed consistent slowing and increased variability with age. Males were faster than females cross age groups, RT tasks, and visits. Beginning at about age 20, RTs increased at a rate of approximately 0.5 msec/yr for SRT and 1.6 msec/yr for DRT. Errors also increased, making unlikely a tradeoff of accuracy for faster responses. The findings are consistent with the hypotheses that slowing of behavior is: (a) a continuous process over the adult life span; (b) characterized by age-associated increases in within-participant variability; (c) a direct function of task complexity and, presumably, the degree of mediation by higher regions in the central nervous system; and (d) greater in women than men.

Characterization of the principal colouring components of annatto using high performance liquid chromatography with photodiode-array detection.

The principal colouring components of the natural food colouring material annatto, the 9'-cis- and all-trans- isomers of bixin and norbixin, have been prepared in pure form. A reverse-phase HPLC method utilizing photodiode-array detection has been developed to enable their chromatographic and spectroscopic characterization. One minor component, a di-cis-isomer of norbixin has also been identified and characterized.

Survey of animal livers for vitamin A content.

Retail samples of livers from calf (23), ox (18), lamb (17), pig (15), chicken (16) and turkey (1) were analysed to determine levels of vitamin A (all trans-retinol) and to aid assessment of the effects of using vitamin supplemented compound feedingstuffs for livestock. For comparison, 22 liver samples from lambs reared on diets not containing vitamin-supplemented compound feedingstuffs and four samples of liver from ox which had received supplemented feed but not during the last four months prior to slaughter were also analysed. The chosen method of analysis utilized saponification, solvent extraction and normal-phase high performance liquid chromatography with fluorescence detection. For all species analysed, the levels of vitamin A ranged from 10 to 1100 mg/kg, with all but seven at or below 400 mg/kg. For lamb and ox livers, the mean levels were 310 mg/kg and 200 mg/kg respectively for retail samples. The mean levels were 220 mg/kg (lamb) and 120 mg/kg (ox) in liver samples from animals fed controlled diets. The results are of the same order as those reported over recent years.

The effects of microwave-baking and oven-baking on thiabendazole residues in potatoes.

The effect of microwave- and oven-baking on residues of the postharvest fungicide thiabendazole (E 233) in potatoes was investigated by comparing amounts present in raw, microwave- and oven-baked tubers. The levels of residues in the whole potato tubers were based on the determination of thiabendazole in peelings and flesh of potato tubers by reversed-phase HPLC analysis with fluorescence and UV detection after extraction with dichloromethane in the presence of anhydrous sodium sulphate. Amounts of thiabendazole determined after microwave- and oven-baking showed that thiabendazole was predominantly retained in the peelings (96.3-98.8%) and not lost during the two types of processing treatments at ca. 100 degrees C. Thus residues did not migrate into the flesh of the tubers.

Intravenous beta agonist in severe acute asthma.

STUDY OBJECTIVE: To determine whether salbutamol is more effective in treating severe asthma when given intravenously or by inhalation. DESIGN: Randomised trial of short term response to intravenous versus nebulised salbutamol in acute severe asthma. SETTING: District general hospital (secondary care centre). PARTICIPANTS: 76 patients aged 16-70 admitted to hospital with acute severe asthma (peak expiratory flow rate less than 50% of predicted) during study period. Five withdrawn because of adverse effects of treatment or non-response. Of remaining 71, 34 allocated to nebuliser group and 37 to intravenous treatment group. Patients with history of cardiovascular disease or recent corticosteroid or intravenous bronchodilator treatment excluded. Admission characteristics similar in the two groups. INTERVENTIONS: All patients given 5 mg nebulised salbutamol on admission before randomisation plus 200 mg hydrocortisone bolus intravenously and 35% inspired oxygen throughout. Nebuliser group received two more 5 mg doses of nebuliser salbutamol at 30 minutes and 2 hours; intravenous group received 4 hours' continuous salbutamol infusion (12 micrograms/min) starting at 30 minutes plus supplementary intravenous potassium chloride. No other bronchodilators used. ENDPOINT: Change in peak expiratory flow rate over 4 hours. MEASUREMENTS AND MAIN RESULTS: Peak expiratory flow rate improved more in intravenous group (25.2%) than in nebuliser group (14.3%) (p less than 0.01, 95% confidence interval 2.4 to 19.1%). Tachycardia caused two withdrawals from intravenous group; non-response caused three withdrawals from nebuliser group. CONCLUSIONS: Intravenous salbutamol is more effective than nebulised salbutamol in acute severe asthma but may have unacceptable cardiovascular effects.