Using web analytics data to identify platforms and content that best engage high-priority HIV populations in online and social media marketing advertisements.

Background: Online advertisements on social media platforms are an important tool for engaging relevant populations in public health research. However, little is known about what platforms and ad characteristics are most effective in engaging high-priority HIV populations, including racial/ethnic and sexual minority individuals. Methods: Data from this study were drawn from advertising campaigns conducted on popular websites and social media platforms that recruited for several nationwide randomized controlled trials of various HIV prevention and testing strategies among sexual minority men (SMM) from December 2019 until March 2022. Descriptive statistics and LASSO regression models were used to determine which platforms and ad characteristics were associated with significantly higher odds of engagement. Results: Ads on Google search, Facebook, and Instagram yielded the most cost-effective engagement, while gay-oriented dating platforms and TrafficJunky yielded the highest percentage of users who appeared to meet basic eligibility criteria. The highest percentages of Black users were screened through ads on Jack'd, TrafficJunky, and Google search; for Hispanic/Latino users, Google search, Grindr, Facebook, and Instagram. Analyzing ad characteristics, we found ads that used suggestive content, animation, and included study or institution logos were associated with greater engagement. Ads that emphasized convenience of the research (e.g. mentioned participating "from home") and that depicted people of similar races/ethnicities were also associated with greater engagement among Black and Hispanic/Latino sexual minority men. Conclusions: We found that advertisements on mainstream social media sites are most cost effective. Although gay-oriented dating platforms were much more effective at reaching the target population, they were considerably more expensive. We also identified ad characteristics that were particularly effective in engaging users. These results could inform the design of online public health outreach campaigns for similar populations to improve their engagement and reach. Findings also demonstrated the value of conducting focused research on the effectiveness of various online marketing strategies.

Relationship between vision impairment and employment.

AIMS: To examine the relationship between vision impairment (VI) and employment outcomes in a multiethnic Asian population. METHODS: We included 7608 Asian individuals aged ≥40 years (mean (SD) age: 58.4 (10.3) years; 64.8% male) from the Singapore Epidemiology Eye Disease Study (response rate: 78.8%), a population-based cohort study (mean follow-up period: 6.2 years). Presenting visual acuity (VA) was assessed using a logarithm of the minimum angle of resolution (logMAR) chart, with VI defined as mild (VA >0.3 to <0.6 logMAR) and moderate to severe (VA ≥0.6 logMAR). Self-reported employment statuses at both baseline and follow-up were used as outcomes. Underemployment was defined as a decline in occupational skill level, categorised by International Standard Classification of Occupations, at follow-up compared with baseline. Multinomial logistic regression models were used to determine independent associations between VI and various employment outcomes, adjusted for variables that were found to significantly differ across employment statuses. RESULTS: Presenting VI was prevalent in 20.2% (N=1536) of participants. Compared with those without VI, participants with mild and moderate to severe VI were more likely to be unemployed at baseline (OR 1.47, 95% CI 1.15 to 1.87, p=0.002 and 2.74, 95% CI 1.94 to 3.89, p<0.001, respectively). At follow-up, participants with any VI at baseline were more likely to be underemployed (OR 1.46, 95% CI 1.03 to 2.05, p=0.033). CONCLUSION: VI, even when mild, is associated with unemployment and underemployment. Future studies should investigate whether visual interventions could be used as part of a multipronged strategy to improve employment outcomes for the population.

Evaluation of the Microbial Load and Heavy Metal Content of Two Polyherbal Antimalarial Products on the Ghanaian Market.

The use of herbal products has increased and become more popularized globally; however, limited studies coupled with questions related to the quality and safety of these herbal products have been raised. Herbal products with hope of their nontoxicity may play a role of alternative to overcome the problems of multi-drug resistant pathogens. Medicinal plants used as raw materials for production may have quality and safety issues due to proximity to wastewater application of fungicides and pesticides, which may be directly deposited superficially or absorbed by the plant system. Therefore, possible contamination of some Ghanaian herbal products cannot be ignored, as it may severely affect human life in the process of treatment. Aim. To evaluate the microbial load and the presence of toxic heavy metals in Mist Amen Fevermix and Edhec Malacure, two polyherbal products used in the treatment of uncomplicated malaria in Ghana. Methods. Thermo Elemental M5 Atomic Absorption Spectrophotometer (AAS) fitted with graphite furnace and an auto sampler was used to determine the heavy metal contents of the herbal products. The herbal samples were evaluated for the microbial load by using the appropriate culture media. Results and Analysis. Mist Amen Fevermix and Edhec Malacure complied with the safety limits evaluated for all different microbial counts and contamination. The following heavy metals were present in Mist Amen Fevermix and Edhec Malacure Mixture: Fe, Ni, K, Zn, Hg, Cu, Mn, Cr, Cd, Pb, Fe, Cu, K, and Na. Ni was below detectable limit in Edhec Malacure. Conclusion. Mist Amen Fevermix and Edhec Malacure may be assured of safety. The products contained heavy metals, but all were within acceptable limit established by the FAO/WHO. The levels of microbial contamination were below the maximum acceptable limit.

Leishmanicidal activity of the root bark of Erythrophleum Ivorense (Fabaceae) and identification of some of its compounds by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS/MS).

ETHNOPHARMACOLOGICAL RELEVANCE: Leishmaniasis is one of the neglected tropical disease caused by a protozoan of the genus Leishmania transmitted by sandflies. High cost and lack of oral formulation of existing drugs, rapid developments of resistance by the parasite coupled with serious side effects require new treatments to augment or replace currently available therapies. The major merits of herbal medicine seem to demonstrate perceived efficacy, low incidence of serious adverse effects and low cost. Erythrophleum plants possess beneficial biological properties and, as such, characterization of the bioactive components of these plants is imperative. Previous work has shown an overwhelming presence of cassaine alkaloids in these plants. However, amongst these plants, the African based specie (Erythrophleum ivorense) is the least studied. OBJECTIVE: In the current study, the in vitro anti-leishmanial activity of the crude extract, its fractions and isolated compounds were evaluated using direct counting assay of promastigotes of Leishmania donovani using amphotericin B as positive control. MATERIALS AND METHODS: The anti-leishmanial activity of E. ivorense extract was evaluated in vitro against the promastigote forms of Leishmania Donovani using a direct counting assay based on growth inhibition. Different crude extracts from ethyl acetate, pet-ether, and methanol as well as pure isolated compounds of E. ivorense: Erythroivorensin, Eriodictyol and Betulinic acid were screened. To know the possible components of the active methanolic extract, attempt was made to elucidate the extract using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS/MS). RESULTS: This afforded a weak pet-ether fraction, a moderately active ethyl acetate fraction and a significantly active methanol fraction (IC50 = 2.97µg/mL) compared to Amphotericin B (IC50 = 2.40±0.67µg/mL). The novel diterpene erythroivorensin, betulinic acid and the flavanone Eriodictyol, from the ethyl acetate fraction, showed weak activity. UPLC-QTOF-MS/MS was used to identify the cassaine diterpenoids from the active methanol fraction. Here, 10 compounds of this type were putatively identified from the ethanol crude extract. CONCLUSION: The fragmentation mechanism of these metabolites is also proposed and are expected to serve as reference template for identification of these and related compounds in future. The presence of these compounds is an indication that they are an inherited and evolutionary component of plants belonging to the Erythrophleum genus. Our results further present another dimension where these compounds and their relative abundances can be used as chemo-taxonomical bio-markers of the genus. The present study also successfully demonstrated/re-affirmed the use of UPLC-QTOF-MS/MS as a robust technique for the characterization of natural products.

Occupational noise exposure of traffic enforcers in selected streets in the City of Manila

@#<p style="text-align: justify;"><strong>OBJECTIVE:</strong> The study aimed to evaluate the sound pressure levels of selected traffic enforcer sites in the City of Manila.</p><p style="text-align: justify;"><strong>METHODOLOGY:</strong> A Brüel & Kjær Integrating Sound Level Meter type 2225 was used to measure sound pressure levels in dB(A) to estimate personal noise exposure of traffic enforcers designated at Quezon Boulevard near Quiapo Church and Recto - Rizal Avenue on a weekday and a weekend. Graphs were generated while appropriate measures were calculated for the noise exposure levels. The mean exposure levels were compared with the Philippine Occupational Safety and Health standards by computing the corresponding permissible exposure limit for each work shift using the Equal Energy Principle.17</p><p style="text-align: justify;"><strong>RESULTS:</strong> Noise exposure levels at Quezon Boulevard ranged from 75.0 dB(A) to 91.5 dB(A) with mean noise exposure level of 84.3 ± 3.7 dB(A) and 82.5 ± 2.6 dB(A) for the weekday AM and PM shift, respectively. The mean noise exposure level at Quezon Boulevard for the weekend AM shift was 82.4 ± 2.6, whereas 80.4 ± 2.8 for the PM shift. The noise exposure levels at Recto - Rizal Avenue ranged from 81.5 dB(A) to 99.3 dB(A) with mean noise exposure level of 86.7 ± 2.6 dB(A) and 86.0 ± 2.1 dB(A) for the weekday AM and PM shift, respectively. The mean noise exposure level at Recto - Rizal Avenue for the weekend AM shift was 86.7 ± 2.3, whereas 89.0 ± 4.0 for the PM shift.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> The study showed that traffic enforcers designated at Quezon Boulevard and Recto - Rizal Avenue are exposed to noise levels that do not exceed the Philippine Occupational Safety and Health standards.</p>

Mosquito larvicidal activity of Cassia tora seed extract and its key anthraquinones aurantio-obtusin and obtusin.

BACKGROUND: The edible and medicinal leguminous plant Cassia tora L. (Fabaceae) is known to possess insecticidal properties against a wide range of plant-feeding insects. However, the bioactivity of extracts of this plant and their constituents against vectors of medical importance has been largely unexplored. We investigated the mosquito larvicidal activity of the seed extract and its major anthraquinones against larvae of the African malaria vector Anopheles gambiae (s.s.). METHODS: Third-fourth instar larval mortality was observed after 24, 48, 72 and 96 h of exposure to varying doses of the extracts, and two anthraquinones isolates identified using liquid chromatography- quadrupole time of flight mass spectrometry (LC-QtoF-MS). The mosquito larval mortality was evaluated relative to the natural insecticide azadirachtin. RESULTS: Fractionation of the crude extract decreased mosquito larvicidal activity, however, larvicidal activity increased with increasing dose of the treatment and exposure time. The known anthraquinones aurantio-obtusin and obtusin were identified as key larvicidal compounds. Aurantio-obtusin and obtusin, exhibited similar toxicity to larvae of A. gambiae (s.s.) with LD50 values of 10 and 10.2 ppm, respectively. However, the two anthraquinones were four- and ~ six-fold less potent than that of the crude seed extract and azadirachtin, which had comparable LD50 values of 2.5 and 1.7 ppm, respectively. CONCLUSION: Both aurantio-obtusin and obtusin showed mosquito larvicidal activity which were comparable to their respective fractions although they were less potent relative to the crude extract and azadirachtin. Further studies need to be conducted on C. tora for its exploitation as a potential eco-friendly tool in mosquito larval source reduction.

Discovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway.

Pathogenic microorganisms often have the ability to attach to a surface, building a complex matrix where they colonize to form a biofilm. This cellular superstructure can display increased resistance to antibiotics and cause serious, persistent health problems in humans. Here we describe a high-throughput in vitro screen to identify inhibitors of Acinetobacter baumannii biofilms using a library of natural product extracts derived from marine microbes. Analysis of extracts derived from Streptomyces gandocaensis results in the discovery of three peptidic metabolites (cahuitamycins A-C), with cahuitamycin C being the most effective inhibitor (IC50=14.5 µM). Biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalysed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis lead to production of unnatural analogues cahuitamycins D and E of increased potency (IC50=8.4 and 10.5 µM).

Activation of Yap-Directed Transcription by Knockdown of Conserved Cellular Functions.

The Yap-Hippo pathway has a significant role in regulating cell proliferation and growth, thus controlling organ size and regeneration. The Hippo pathway regulates two highly conserved, transcription coactivators, YAP and TAZ. The upstream regulators of the Yap-Hippo pathway have not been fully characterized. The aim of this study was to use a siRNA screen, in a liver biliary cell line, to identify regulators of the Yap-Hippo pathway that allow activation of the YAP transcription coactivator at high cell density. Activation of the YAP transcription coactivator was monitored using a high-content, image-based assay that measured the intracellular localization of native YAP protein. Active siRNAs were identified and further validated by quantification of CYR61 mRNA levels (a known YAP target gene). The effect of compounds targeting the putative gene targets identified as hits was also used for further validation. A number of validated hits reveal basic aspects of Yap-Hippo biology, such as components of the nuclear pore, by which YAP cytoplasmic-nuclear shuttling occurs, or how proteasomal degradation regulates intracellular YAP concentrations, which then alter YAP localization and transcription. Such results highlight how targeting conserved cellular functions can lead to validated activity in phenotypic assays.

Erythroivorensin: A novel anti-inflammatory diterpene from the root-bark of Erythrophleum ivorense (A Chev.).

The stem- and root-bark of Erythrophleum ivorense (A Chev., family, Fabaceae) are routinely employed in the West African traditional medicine to treat inflammation and a variety of other disease conditions. Although the chemistry and pharmacology of cassaine-type diterpene alkaloids isolated from the stem-bark of the plant are fairly established, the root-bark has not yet been investigated. In the present study, the crude aqueous-alcohol extract of the root-bark was demonstrated to display a time- and dose (30-300 mg/kg p.o.)-dependent anti-inflammatory effect in chicks. Comprehensive chromatographic analysis coupled with spectroscopic and X-ray study further allowed the assignment of one of the major anti-inflammatory constituents as a novel cassaine-type diterpene, erythroivorensin. The other major constituents were known anti-inflammatory compounds: a triterpene, betulinic acid and a flavonoid, eriodictyol. The dose (10-100mg/kg p.o.)-dependent anti-inflammatory effects of the three compounds were either comparable or more significant than the positive control, diclofenac.

A novel triterpene from the roots of Paullinia pinnata: 6α-(3'-methoxy-4'-hydroxybenzoyl)-lup-20(29)-ene-3-one.

Paullinia pinnata L. (Sapindaceae) is an endemic West African plant that is extensively used in traditional medicine to treat various diseases. Previous phytochemical analysis by various groups led to the isolation of several novel lupene-based triterpenene derivatives along with other classes of compounds. As part of our continued phytochemical studies on the roots of this plant, we have now identified yet another novel triterpene, 6a-(3'-methoxy-4'-hydroxybenzoyl)-lup-20(29)-ene-3-one. The identification of the compound through comprehensive spectroscopic studies is discussed.

Antiinflammatory properties of the stem-bark of Anopyxis klaineana and its major constituent, methyl angolensate.

Anopyxis klaineana (Pierre) Engl. (Rhizophoraceae) is one of the reputed West African folkloric medicines that has never been investigated for its pharmacological effects or phytochemical constituents. In the present study, the antiinflammatory properties of the stem-bark extracts were evaluated using the carrageenan-induced paw oedema model in chicks. The petroleum ether, ethyl acetate and methanol extracts all showed a time and dose-dependent antiinflammatory effect over the 5-h observation period. Phytochemical analysis of the most active extract (methanol extract) yielded the principal constituent that was identified as methyl angolensate through extensive spectroscopic and X-ray analysis studies. Although slightly less potent (ED50 , 4.05 ± 0.0034 mg/kg, orally) than the positive control, diclofenac (ED50 , 2.49 ± 0.023, intraperitoneally n = 5), this first ever compound isolated from A. klaineana showed promising antiinflammatory activity that may account to some of the reported medicinal uses of the plant.

In vitro evaluation of effects of two Ghanaian plants relevant to wound healing.

Commelina diffusa and Spathodea campanulata are used as wound-healing agents in Ashanti traditional medicine in Ghana. The methanol extracts of Commelina diffusa herb and Spathodea campanulata bark showed some level of antimicrobial activity with C. diffusa exhibiting selective antifungal activity against Trichophyton species. The extracts reduced the peroxidation of bovine brain extract with an IC(50) value of 1.39 mg/mL and 0.24 mg/mL, respectively. In addition the extracts also exhibited significant antioxidant activity by protecting MRC-5 cells from hydrogen peroxide induced oxidant injury at concentrations between 1 microg/mL and 10 microg/mL. The extracts showed no inhibition of NF-kappaB at 100 microg/mL. The antioxidant activities and antimicrobial activities suggest that the use of the plants in wound healing may be based on antioxidant and antiseptic effects of its constituents.

Terpenoids in Buddleja: relevance to chemosystematics, chemical ecology and biological activity.

The terpenoids reported from Buddleja species are described. The antifungal activity of chloroform extracts of B. cordata and B. davidii stembark against the soil fungi Fusarium culmorum and Sordari fimicola is reported, with buddledin A shown to be the major compound responsible. The terpenoids present support the view that the Buddlejaceae should be classified in a taxon with Scrophulariaceae rather than Loganiaceae. Ecological aspects of the terpenoids are considered in relation to insects and soil fungi and the role of terpenoids in the chemical basis of the use of Buddleja in traditional medicine is also discussed, especially with regard to their anti-inflammatory properties.

Inter-current and nosocomial infections among visceral leishmaniasis patients in Ethiopia: an observational study.

From July 1989 up to September 1997, a total of 247 non-HIV associated visceral leishmaniasis (VL) patients were treated on outpatient basis in rural clinics (195 patients) and hospitalised in the Northern-Omo Regional Hospital (18 patients) and in Addis Ababa referral hospitals (34 patients). Patients treated in the rural clinics and in the Regional hospital originated from the same endemic area and had comparable baseline characteristics. Overall rates of complications (inter-current/concurrent infectious or non-infectious diseases or deaths) in the three categories were 10.7, 38.9 and 61.6%, while case fatality rates were 2.5, 5.6 and 11.7%, respectively. Nosocomial bacterial infections occurred in 16.6% of patients treated in the Regional hospital and 32.3% of patients treated in Addis Ababa referral hospitals, and these infections accounted for 42.8 and 52.4% of the complications seen in the respective categories. Among VL patients originating from the same endemic place and with comparable baseline clinical data, patients treated hospitalised had significantly higher rates of complications than patients treated on outpatient basis (P<0.001). Patients who had complications during the course of VL therapy had significantly lower pre-treatment haemoglobin levels. Considering the extra cost of hospitalisation and risk of nosocomial infections and petavalent antimonial therapy being fairly safe, we recommend that VL patients, unless with serious complications, should preferably be treated on ambulatory basis with follow-up to monitor response and inter-current infections if any.

Electrocardiographic findings in Ethiopians on pentavalent antimony therapy for visceral leishmaniasis.

BACKGROUND: The old short course regimens of pentavalent antimonial (sb(v)) therapy of visceral leishmaniasis (VL) have largely been abandoned worldwide as they are associated with increasing problems of relapse and unresponsiveness. In Ethiopia, some hospitals still use the old interrupted and short course regimen partly because of fear of drug toxicity. OBJECTIVE: To evaluate the safety of the WHO recommended uninterrupted therapy at a dose of 20 mg sb(v)/kg for up to thirty days. DESIGN: A prospective study. SETTING: Patients were recruited from Addis Ababa hospitals and from Konso VL endemic area in southern Ethiopia. SUBJECTS: Forty nine patients who included, ten HIV-positive and 39 HIV-negative, were enrolled for the study. RESULTS: Twenty three HIV-negative patients got treatment for 20 days and the rest, 16 HIV-negative and 10 HIV-positive, were treated for 28 to 30 days. Among HIV-seronegatives, the mean QT interval corrected for heart rate (QTc) at the end of therapy in patients treated for 20 days and 28-30 days was comparable (0.419 +/- 0.031 seconds versus 0.424 +/- 0.027 seconds, respectively). Among patients treated for 28-30 days, the mean QTc in HIV co-infected patients was comparable to that of HIV-negatives (0.416 +/- 0.018 seconds versus 0.424 +/- 0.027). Comparable rates of new ECG changes involving the T waves were observed in two HIV-positive (20%) and two HIV-negative (12.5%) patients treated for 28-30 days, and in seven (30.4%) HIV-negative patients treated for 20 days. Overall, only two (4.1%) patients (all HIV-negative males) had QTc interval > or = 0.50 seconds at the end of therapy. In one patient, the prolonged QTc was noted on the twentieth day with bradycardia of 44/minute. CONCLUSIONS: In Ethiopian VL patients with normal renal function, sb(v) therapy at a daily dose of 20 mg/kg for up to 30 days is safe and only rarely associated with clinically significant bradycardia which resolves after temporary cessation of therapy. Furthermore, in areas with limited facilities, monitoring the pulse rate during antimonial therapy may help detect impending cardiotoxicity.

A role for centrin 3 in centrosome reproduction.

Centrosome reproduction by duplication is essential for the bipolarity of cell division, but the molecular basis of this process is still unknown. Mutations in Saccharomyces cerevisiae CDC31 gene prevent the duplication of the spindle pole body (SPB). The product of this gene belongs to the calmodulin super-family and is concentrated at the half bridge of the SPB. We present a functional analysis of HsCEN3, a human centrin gene closely related to the CDC31 gene. Transient overexpression of wild-type or mutant forms of HsCen3p in human cells demonstrates that centriole localization depends on a functional fourth EF-hand, but does not produce mitotic phenotype. However, injection of recombinant HsCen3p or of RNA encoding HsCen3p in one blastomere of two-cell stage Xenopus laevis embryos resulted in undercleavage and inhibition of centrosome duplication. Furthermore, HsCEN3 does not complement mutations or deletion of CDC31 in S. cerevisiae, but specifically blocks SPB duplication, indicating that the human protein acts as a dominant negative mutant of CDC31. Several lines of evidence indicate that HsCen3p acts by titrating Cdc31p-binding protein(s). Our results demonstrate that, in spite of the large differences in centrosome structure among widely divergent species, the centrosome pathway of reproduction is conserved.

HIV viral load and response to antileishmanial chemotherapy in co-infected patients.

OBJECTIVE: To investigate whether clearance of Leishmania parasites from tissue aspirate smears in patients with HIV and visceral leishmaniasis (VL) co-infection treated with pentavalent antimonials is influenced by initial HIV viral load and to assess the effect of active VL on HIV viral load and replication in vivo. METHODS: Leishmania parasites were identified in Giemsa-stained smears prepared from tissue aspirates. Parasite index was determined by quantifying Leishmania donovani bodies in smears. HIV-1 RNA was quantitated by using the nucleic acid sequence-based amplification technique with a limit of detection of 500 copies/ml. All patients were treated with pentavalent antimonials at 20 mg pentavalent antimony (Sb(V))/kg daily for a total of 28 days. None of the patients received specific anti-retroviral therapy. RESULTS: Seventeen patients (73.9%) showed good initial response to anti-leishmanial treatment and the remaining six (26.1%) had very poor response. Among the good responders, 11 (64.7%) had no demonstrable Leishmania donovani bodies in post-therapy tissue aspirate smear preparations, and in the remaining six (35.3%) their parasite loads were reduced to very low levels. Patients with poor response had persistently high parasite index despite completion of anti-leishmanial chemotherapy. Poor responders had pre-treatment median HIV viral load that was >160-fold higher than responders to anti-leishmanial chemotherapy; [410000 copies/ml (quartile range, 33000-530000) and 2500 copies/ml (quartile range 500-297500), respectively]. Furthermore, compared with pre-treatment viral concentrations, patients with good response showed marked reduction in post-treatment viral load. In contrast, post-treatment HIV viral concentrations were markedly increased among patients with poor response to anti-leishmanial therapy. CONCLUSIONS: The results suggest that pre-treatment HIV viral load influences response to anti-leishmanial chemotherapy and active VL is associated with increased viral replication in vivo, supporting the notion that dual infection plays an important role in the pathogenesis and disease progression of either infection.

Retention control training in the treatment of younger versus older enuretic children.

This study compared the efficacy of retention control training (RCT) in two groups of children suffering from nocturnal enuresis: a younger group of 15 children aged 4 to 5 years and an older group of 15 children aged 7 to 8 years. To control for family history, frequency, and type of enuresis, only children with primary nocturnal enuresis who had a family history of enuresis and who wet the bed 4 to 7 nights per week were included. RCT was found to be an effective treatment for young children who were closer to the final stage of bladder development, but not for older children. RCT may be used for older children as a preliminary treatment to increase functional bladder capacity, after which treatment of enuresis should be continued by other methods, such as bell-and-pad reinforcement programs.