Understanding patient-level costs of weekly isoniazid-rifapentine (3HP) among people living with HIV in Uganda.

BACKGROUND: Twelve weeks of weekly isoniazid and rifapentine (3HP) prevents TB disease among people with HIV (PWH), but the costs to people of taking TB preventive treatment is not well described.METHODS: We surveyed PWH who initiated 3HP at a large urban HIV/AIDS clinic in Kampala, Uganda, as part of a larger trial. We estimated the cost of one 3HP visit from the patient perspective, including both out-of-pocket costs and estimated lost wages. Costs were reported in 2021 Ugandan shillings (UGX) and US dollars (USD; USD1 = UGX3,587)RESULTS: The survey included 1,655 PWH. The median participant cost of one clinic visit was UGX19,200 (USD5.36), or 38.5% of the median weekly income. Per visit, the cost of transportation was the largest component (median: UGX10,000/USD2.79), followed by lost income (median: UGX4,200/USD1.16) and food (median: UGX2,000/USD0.56). Men reported greater income loss than women (median: UGX6,400/USD1.79 vs. UGX3,300/USD0.93), and participants who lived further than a 30-minute drive to the clinic had higher transportation costs than others (median: UGX14,000/USD3.90 vs. UGX8,000/USD2.23).CONCLUSION: Patient-level costs to receive 3HP accounted for over one-third of weekly income. Patient-centered approaches to averting or defraying these costs are needed.

Cost to perform door-to-door universal sputum screening for TB in a high-burden community.

BACKGROUND: Population-based active case-finding (ACF) identifies people with TB in communities but can be costly. METHODS: We conducted an empiric costing study within a door-to-door household ACF campaign in an urban community in Uganda, where all adults, regardless of symptoms, were screened by sputum Xpert Ultra testing. We used a combination of direct observation and self-reported logs to estimate staffing requirements. Study budgets were reviewed to collect costs of overheads, equipment, and consumables. Our primary outcome was the cost per person diagnosed with TB. RESULTS: Over a 28-week period, three teams of two people collected sputum from 11,341 adults, of whom 48 (0.4%) tested positive for TB. Screening 1,000 adults required 258 person-hours of effort at a cost of US$35,000, 70% of which was for GeneXpert cartridges. The estimated cost per person screened was $36 (95% uncertainty range [95% UR] 34­38), and the cost per person diagnosed with Xpert-positive TB was $8,400 (95% UR 8,000­8,900). The prevalence of TB in the underlying community was the primary modifiable determinant of the cost per person diagnosed. CONCLUSION: Door-to-door screening can be feasibly performed at scale, but will require effective triage and identification of high-prevalence populations to be affordable and cost-effective.

A purse-string suture at the level of internal inguinal ring, taking only the peritoneum leaving the distal sac: is it enough for inguinal hernia in pediatric patients?

PURPOSE: Although laparoscopic surgery in children has expanded in recent years. Laparoscopic hernia repair in children is still debatable. We aimed to summarize and describe our results of laparoscopic inguinal hernia repair and techniques among children. METHODS: Between March 2011 and April 2013, 98 children (67 male, 31 female) underwent laparoscopic inguinal hernia repair at the department of surgery. The clinical outcomes were collected retrospectively. RESULTS: The mean follow-up period was 22.6 months. Twelve patients were ex-premature infants and a contralateral patent processus vaginalis (PPV) was present in 37 of the 91 unilateral inguinal hernia patients. There were two postoperative complications (transient hydrocele, umbilical port site infection). The mean operative time was 46 min. Recurrence, metachronous hernia and testicular atrophy were not observed during the follow-up period. CONCLUSIONS: Our preliminary experiences suggest that the laparoscopic purse-string suture of internal inguinal opening of hernia sac could be a safe, effective, and reliable alternative for management of pediatric inguinal hernia.

Effect of precursor ratio on the structural properties of ZnO thin films deposited by low pressure MOCVD.

The effect of precursor ratio (H2O/DEZ) on the texture orientation, surface morphology, optical transparency and electrical resistivity of ZnO thin films deposited by MOCVD was investigated. Deposition temperature and pressure were fixed at 120 degrees C and 0.67 torr, respectively. The precursor ratio was varied between 0.1 and 4. It was found that the texture orientation changed from (0002) to (1120) with increase of the precursor ratio. (1120) textured film shows well facetted tetrapod like rough surface morphology, which scatters the incident light very effectively. The electrical resistivity was in the range of about 0.1 omega cm in the undoped state, which was found to decrease with increase of the film thickness and decrease of the precursor ratio.

Lactic acid fermentation of food waste for swine feed.

This study was conducted to determine the effects of lactic acid bacteria (LAB, Lactobacillus salivarius) inoculation on the microbial, physical and chemical properties of food waste mixture (FWM) stored at ambient temperature (25 degrees C) for 10 and 30 days. A complete pig diet including restaurant food waste, bakery by-product, barley and wheat bran, and broiler poultry litter was amended with LAB at the levels of 0.1%, 0.2%, 0.5% and 1.0% and fermented anaerobically. These treatments were compared with intact FWM before storage and non-anaerobically stored FWM. Non-anaerobic storage of FWM showed microbial putrefaction with the loss (P < 0.05) of water and water soluble carbohydrate (WSC) and increases (P < 0.005) in protein and fiber. Anaerobic fermentation of FWM with or without LAB seemed effective in both 10- and 30-day-storage. The addition of LAB inoculants to FWM showed a linear trend (P < 0.05) toward an increase in the number of total and lactic acid bacteria and toward the nutritional improvement with WSC increased and fiber decreased. Long-term (30 days) storage resulted in consistent reduction (P < 0.05) in numbers of total and lactic acid bacteria and pH and showed little change in chemical components, compared with short-term (10 days) storage. On the basis of these results, LAB inoculation improved fermentative characteristics of FWM. Among anaerobic treatments, further WSC increase and NDF reduction did not occur (P > 0.05) when LAB-added levels were over 0.2%. Based on these observations the optimum level of LAB addition to FWM was 0.2%.

Cardiac Characteristics of Transgenic Mice Overexpressing Refsum Disease Gene-Associated Protein within the Heart.

Arrhythmia is a common cardiac symptom of Refsum disease. Recently, we identified a novel neuron-specific PAHX-associated protein (PAHX-AP1), which binds to the Refsum disease gene (PAHX). In this report, we developed heart-targeted transgenic (TG) mice under the control of alpha-myosin heavy chain promoter to determine whether cardiac overexpression of PAHX-AP1 provokes cardiac involvement symptoms. Northern and in situ hybridization analyses revealed PAHX-AP1 transcript was overexpressed in TG atrium, especially in the sinoatrial node. TG mice showed tachycardia, and tachyarrhythmia was observed in 20% of TG mice. Isolated TG atria showed higher frequency beating and were more sensitive to aconitine-induced tachyarrhythmia than the wild-type, and 40% of the TG atria showed irregular beating. Action potential duration in TG atrial fiber was shortened much more than the wild-type. Systemic administration of arrhythmogenic agents induced arrhythmia in TG mice, while no arrhythmia with the same dose in nonTG mice. Our results indicate that the chronic atrial tachycardia by overexpressed neuron-specific PAHX-AP1 transgene in atrium may be responsible for the increased susceptibility to arrhythmia.

Cyclosporine impairs the guanylyl cyclase activity of the natriuretic peptide receptor in the glomerulus.

In order to elucidate the involvement of the atrial natriuretic peptide (ANP) and its receptor (natriuretic peptide receptor; NPR) system in cyclosporine-induced nephrotoxicity, we investigated the cyclosporine A (CsA)-induced changes in characteristics of the NPR/guanylyl cyclase system in the glomerulus and inner medulla of the rat kidney. CsA was administered intramuscularly to rats for 2 weeks (CsA group). Particulate guanylyl cyclase activity was measured in glomerular and inner medullary membranes. For receptor characteristics, quantitative in vitro receptor autoradiography was performed. The guanylyl cyclase activity in the glomerulus from the CsA group was attenuated compared with that from the control. However, the activity in the inner medulla was not affected by CsA treatment. Direct application of CsA to normal glomerular membrane completely abolished the ANP-induced guanylyl cyclase activation. Binding studies, using(125)I-ANP, revealed that B(max)was decreased in the CsA group, while K(d)was not affected in the glomerulus. However, in the inner medulla, neither B(max)nor K(d)was affected by CsA treatment. CsA did not displace the(125)I-ANP bindings to NPRs in the normal rat kidney. Local tissue ANP as well as plasma ANP concentration in both groups was not significantly different. These results indicate that CsA impairs the guanylyl cyclase activity mainly in the glomerulus by the decrease in NPR population and/or by direct inhibition, suggesting that the ANP/NPR system might be involved in CsA-induced nephrotoxicity.

Perceived air quality, sick building syndrome (SBS) symptoms and productivity in an office with two different pollution loads.

Perceived air quality, Sick Building Syndrome (SBS) symptoms and productivity were studied in an existing office in which the air pollution level could be modified by introducing or removing a pollution source. This reversible intervention allowed the space to be classified as either non-low-polluting or low-polluting, as specified in the new European design criteria for the indoor environment CEN CR 1752 (1998). The pollution source was a 20-year-old used carpet which was introduced on a rack behind a screen so that it was invisible to the occupants. Five groups of six female subjects each were exposed to the conditions in the office twice, once with the pollution source present and once with the pollution source absent, each exposure being 265 min in the afternoon, one group at a time. They assessed the perceived air quality and SBS symptoms while performing simulated office work. The subject-rated acceptability of the perceived air quality in the office corresponded to 22% dissatisfied when the pollution source was present, and to 15% dissatisfied when the pollution source was absent. In the former condition there was a significantly increased prevalence of headaches (P = 0.04) and significantly lower levels of reported effort (p = 0.02) during the text typing and calculation tasks, both of which required a sustained level of concentration. In the text typing task, subjects worked significantly more slowly when the pollution source was present in the office (P = 0.003), typing 6.5% less text than when the pollution source was absent from the office Reducing the pollution load on indoor air proved to be an effective means of improving the comfort, health and productivity of building occupants.

Activation of particulate guanylyl cyclase by Vibrio vulnificus hemolysin.

Recently we reported that Vibrio vulnificus hemolysin, an exotoxin produced by V. vulnificus, dilates rat thoracic aorta via elevated cGMP levels without affecting nitric oxide synthase. We investigated the mechanism further by observing the guanylyl cyclase activities in cytosolic, membrane, unfractionated, or reconstituted preparations. Hemolysin did not activate guanylyl cyclase in the membrane or cytosolic fraction, while it activated guanylyl cyclase in unfractionated or reconstituted preparation. The increased activity was not inhibited by the HS-142-1, a microbial polysaccharide which antagonizes atrial natriuretic peptide receptor, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a soluble guanylyl cyclase inhibitor. However, it was attenuated by 6-(phenylamino)-5,8-quinolinedione (LY 83.583), which inhibits the catalytic domain of both guanylyl cyclases, and by cholesterol, which blocks hemolysin-incorporation into the membrane. Removing ATP, a cofactor of particulate guanylyl cyclase, attenuated the activation and ATPgammaS, a non-phosphorylating analog, restored it. These results suggest that V. vulnificus hemolysin activates particulate guanylyl cyclase via hemolysin incorporation into the vascular smooth muscle cell membrane in cooperation with certain unidentified cytosolic component(s).

Effects of calcium antagonists on contractions of chorionic arteries in normal and preeclampsia placenta.

This study was undertaken to observe the effects of organic or inorganic calcium antagonists and to investigate the involvement of cyclic nucleotides in regulating the vascular tone in the chorionic artery from normal or preeclamptic placenta. KCI and prostaglandin (PG) F2 alpha produced marked and constant contractions in chorionic arterial preparations of both normal and preeclamptic placentas. Nifedipine (NIF), verapamil (VER) and diltiazem (DIL) reduced the tension that had been produced by KCI and PGF2 alpha in a concentration-dependent fashion in both preparations, and the potency order of the three agents was NIF > VER > DIL. In preeclamptic arteries, however, the magnitudes of vasodilatation induced by NIF and DIL were much smaller than those in normal chorionic arteries. Mg2+ and Cd2+ also relaxed the tension induced by KCI and PGF2 alpha. In preeclamptic chorionic artery, the vasodilatation induced by Mg2+ was significantly potentiated, while that by Cd2+ was not. Removing endothelium did not alter cyclic GMP content in both preparations. In both preparations contracted by PGF2 alpha, nitroprusside markedly increased cyclic GMP content, but neither cyclic GMP nor cyclic AMP content was affected by acetylcholine, NIF, isopro-terenol, or Mg2+. The above results suggest that neither cyclic AMP nor cyclic GMP is involved in regulating the vascular tone of chorionic artery and that sensitivity of the artery in preeclampsia to the inhibitory action of calcium antagonist might be different from that in normal placenta.

Vibrio vulnificus hemolysin dilates rat thoracic aorta by activating guanylate cyclase.

Hemolysin produced by Vibrio vulnificus caused hypotension and tachycardia in rats and dilated rat thoracic aorta. Hemolysin-induced vasodilatation of the aorta was not affected by N omega-nitro-L-arginine methyl ester and aminoguanidine, NO synthase inhibitors, whereas the vasodilatation was inhibited by LY 83,583, a guanylate cyclase inhibitor. Hemolysin elevated cGMP levels, and the elevation was abolished by LY 83,583. These results suggest that V. vulnificus hemolysin activates guanylate cyclase independently of NO synthase, and the subsequent increase in cGMP levels results in vasodilatation.

Dihydropyridine Ca2+ channel agonists and antagonists potentiate ultraviolet light-induced relaxation through cyclic GMP formation in porcine coronary artery.

We investigated the mechanisms of dihydropyridine Ca2+ channel agonist potentiation of ultraviolet (UV) light-induced smooth muscle relaxation in porcine coronary artery rings. Rings contracted with the dihydropyridine Ca2+ channel agonist, (+)-S-202-791, were more sensitive to relaxation in response to UV light than were rings contracted with KCl or histamine. Relaxation of (+)-S-202-791-contracted rings was independent of the presence of endothelium and was associated with cyclic GMP formation. Methylene blue (MB) prevented UV light-induced relaxation and cyclic GMP formation. UV light-induced relaxation of histamine and KCl contracted rings and cyclic GMP formation were potentiated by (+)-S-202-791 or the Ca2+ channel antagonist, (-)-R-202-791. Exposure of (+)-S-202-791 to UV light decreased its contractile potency. The data suggest that UV light-induced relaxation of vascular smooth muscle (VSM) is mediated through cyclic GMP formation and that potentiation of UV light-induced relaxation by dihydropyridine Ca2+ channel agonists results from their breakdown to a compound(s) that activates guanylate cyclase.

Transient temperature responses of hydronic radiant floor heating system by different pipe embedding depth and water supply condition.

"Ondol" is a Korean unique heating system. It is a specific radiant floor heating system using combustion heat of briquette or timber in Korea. Such traditional "Ondol" is changed to radiant heating system with pipe-coil embedded in the floor or slab. This study has contributed to the understandings of the transient behaviours of Ondol-heated floor panels and enclosure exposed to this type of heating system. The result is that the water supply temperature had a large effect on the rate of increase in floor surface and room air temperature. But, in spite of a higher water supply temperature, the heat flow rate was not increased considerably. The shallow pipe embedding depths, of course, result in a low heat flow rate.

Effects of isosorbide dinitrate and diltiazem on Ca2+ flux and contraction in artery.

We studied the effects of isosorbide dinitrate and diltiazem on histamine-stimulated 45Ca fluxes and contractions of isolated porcine coronary artery. Isosorbide dinitrate was slightly more potent as an inhibitor of intracellular compared to extracellular calcium-dependent contraction. Isosorbide dinitrate inhibited histamine-stimulated calcium efflux and intracellular calcium-dependent contraction over similar concentration ranges. Isosorbide dinitrate partially inhibited histamine-stimulated calcium influx, but this effect was significant only at high concentration and correlated weakly with inhibition of contraction that was dependent on extracellular calcium. Diltiazem more potently inhibited extracellular vs. intracellular calcium-dependent contraction. Diltiazem partially inhibited histamine-stimulated calcium efflux and intracellular calcium-dependent contraction to similar extents (55-60%) and produced similar concentration-response relationships for inhibition of histamine-stimulated calcium influx and extracellular calcium-dependent contraction. The data suggest that alterations of cellular calcium metabolism are major mechanisms of vascular smooth muscle relaxation by isosorbide dinitrate and diltiazem, but that the specific alterations differ for the two drugs. Isosorbide dinitrate may inhibit contraction primarily by enhancing intracellular calcium sequestration, but possibly also by inhibiting agonist-stimulated calcium influx at high isosorbide dinitrate concentrations. Diltiazem primarily inhibits stimulated calcium influx, but may also inhibit intracellular calcium release.

A possible role for the endothelium in porcine coronary smooth muscle responses to dihydropyridine calcium channel modulators.

The role of the endothelium in contraction and relaxation produced by the dihydropyridine calcium channel modulators was examined in porcine coronary smooth muscle. The optically pure dihydropyridine calcium agonists (+)-S202-791 and (-)-Bay k 8644 both produced greater contractions in tissues without endothelium compared with tissues with intact endothelium. In contrast, histamine produced the same degree of contraction in tissues with and without endothelium. In the presence of KCl-induced active muscle tone, the optically pure calcium antagonists (-)-R202-791 and (+)-Bay k 8644 and the nitrovasodilator isosorbide dinitrate all produced the same degree of relaxation in tissues with and without endothelium. These results suggest that the endothelium plays an inhibitory role in dihydropyridine-induced contraction. When coronary rings with intact endothelium were pretreated for 60 min with 10 or 100 nM (-)-R202-791, the contraction to subsequent addition of (+)-S202-791 was significantly greater than in control tissues pretreated with only solvent. However, in rings with denuded endothelium, pretreatment with (-)-R202-791 resulted in a rightward shift of the dose-response curve to (+)-S202-791, and a depression of the maximal contraction compared with controls. Thus, the interaction between the calcium agonist [(+)-S202-791] and antagonist [(-)-R202-791] is more complex than competitive inhibition. We suggest that the calcium agonists produce two effects, a release of endothelium-derived relaxant factor and a direct contraction of smooth muscle; the calcium antagonists can inhibit both processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on the mode of action of isosorbide dinitrate: a physiologic and biochemical approach.

The action of isosorbide dinitrate (ISDN) and diltiazem on coronary artery diameter, vascular resistance, and coronary blood flow was determined in instrumented postoperative conscious dogs. Low doses of ISDN were found to increase the diameter of large arteries without affecting coronary blood flow. Higher doses of ISDN produced an increase in both coronary diameter and blood flow. Diltiazem, on the other hand, increased coronary artery diameter and blood flow at all doses tested. Coronary vascular resistance was more sensitive to diltiazem than to ISDN. In isolated canine cardiac Purkinje strands, ISDN produced a concentration-dependent decrease in force development and action-potential duration measured at 50% of repolarization (APD50). ISDN did not significantly affect action potentials recorded in Purkinje strands depolarized by potassium (22 mmol) and treated with isoproterenol (10(-6)M). Diltiazem also decreased Purkinje strand force development and APD50 in a concentration-dependent manner. Diltiazem, however, was several orders of magnitude more potent than ISDN and completely abolished action-potential genesis in potassium-depolarized, isoproterenol-restored Purkinje strands. Both diltiazem and ISDN were found to relax porcine coronary artery strips contracted by KCl or histamine. Studies on 45Ca flux, in isolated coronary artery rings, indicate that ISDN inhibited both histamine-induced Ca++ influx and efflux from intracellular sources. The inhibition of Ca++ efflux and intracellular Ca++-dependent contraction occurred over a similar ISDN concentration range. ISDN also relaxed bovine coronary artery strips contracted with KCl. No change in cyclic adenosine monophosphate levels occurred during ISDN-induced relaxation of bovine coronary arterial strips.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrendipine potentiates Bay k 8644-induced contraction of isolated porcine coronary artery: evidence for functionally distinct dihydropyridine receptor subtypes.

Bay k 8644 and nitrendipine, dihydropyridines classified as calcium channel agonist and antagonist, respectively, produced concentration-dependent biphasic responses (contraction and relaxation) in porcine coronary artery rings. Nitrendipine relaxed rings (IC50 = 60 nM) that were contracted with 100 nM Bay k 8644. Pretreatment of rings with 60 nM nitrendipine caused paradoxical potentiation of Bay k 8644-induced contraction. The data are consistent with a model that consists of two functionally-distinct dihydropyridine "receptors" with which Bay k 8644 and nitrendipine interact as partial agonists. We propose that these excitatory and inhibitory dihydropyridine receptor subtypes mediate contraction and relaxation, respectively, by dihydropyridines.