“To assess the impact of prebiotic supplementation during

“To assess the impact of prebiotic supplementation during gestation and fetal and early neonatal life, gestating BALB/cj dam mice were fed either a control or a prebiotic (galacto-oligosaccharides-inulin, 9:1 ratio)-enriched diet throughout pregnancy and lactation, and allowed to nurse their pups until weaning. At the time of weaning, male offspring mice were separated from their mothers, weaned to the same solid diet as their dam and their growth was monitored until killed 48 d after weaning. Prebiotic click here treatment affected neither the body-weight gain

nor the food intake of pregnant mice. In contrast, at the time of weaning, pups that had been nursed by prebiotic-fed dams had a higher body weight (11.0 (SE 1.2) g) than pups born from control dams (9.8 (SE 0.9) g). At 48 d after weaning, significantly higher values were observed for colon length and muscle mass in the offspring of prebiotic-fed dams (1.2 (SE 0.1) cm/cm and 5.7 (SE 1.8) mg/g, respectively), compared with Selleckchem DZNeP control offspring (1.1 (SE 0.1) cm/cm and 2.9 (SE 0.9) mg/g, respectively), without any difference in spleen and stomach weight, or serum leptin concentration. The present preliminary study suggests that altering the fibre content of the maternal diet during both pregnancy

and lactation enhances offspring growth, through an effect on intestinal and muscle mass rather than fat mass accretion.”
“Some Bantu languages spoken in southwestern Zambia and neighboring regions of Botswana, Namibia, and Angola are characterized by the presence of click consonants, whereas their closest linguistic relatives lack such clicks. As clicks are a typical feature not of the Bantu language family, but of Khoisan languages, it is highly probable that the Bantu languages in question borrowed the clicks from Khoisan languages. In this paper, we combine complete mitochondrial genome sequences from a representative sample of populations from the Western Province of Zambia speaking Bantu languages with and without

clicks, with fine-scaled analyses of Y-chromosomal single nucleotide polymorphisms and short tandem repeats to investigate the prehistoric RG-7112 in vivo contact that led to this borrowing of click consonants. Our results reveal complex population-specific histories, with female-biased admixture from Khoisan-speaking groups associated with the incorporation of click sounds in one Bantu-speaking population, while concomitant levels of potential Khoisan admixture did not result in sound change in another. Furthermore, the lack of sequence sharing between the Bantu-speaking groups from southwestern Zambia investigated here and extant Khoisan populations provides an indication that there must have been genetic substructure in the Khoisan-speaking indigenous groups of southern Africa that did not survive until the present or has been substantially reduced.

Mol Cancer Ther; 9(6); 1809-19 (C)2010 AACR “
“Objective E

Mol Cancer Ther; 9(6); 1809-19. (C)2010 AACR.”
“Objective. Extensive association analyses including genome-wide association studies (GWAS) and powerful metaanalysis studies have identified a long list of loci associated with rheumatoid arthritis (RA) in very large populations, but most of them established statistical associations of genetic markers and RA only at the DNA level, without supporting evidence of functional

MI-503 nmr relevance. Our study serves as’ a trial to detect the functional mechanisms underlying associations for RA by searching publicly available datasets and results.\n\nMethods. Based on publicly available datasets and results, we performed integrative analyses (gene relationships across implicated loci analysis, differential gene expression analysis, and functional annotation clustering analysis) and combined them LXH254 nmr with the expression quantitative trait locus (eQTL) results to dissect functional mechanisms underlying the associations for RA.\n\nResults. By searching 2 GWAS, Integrator and PheGenl, we selected 98 RA association results (p < 10(-5)). Among these associations, we found that 8 single-nucleotide polymorphisms (SNP; rs 1600249, rs2736340,

rs3093023, rs3093024, rs4810485, rs615672, rs660895, and rs9272219) serve as cis-effect regulators of the corresponding eQTL genes (BLK and CD4 in non-HLA region; CCR6, HLA-DQA1, and HLA-DQB1 in HLA region) that also were differentially expressed in RA-related cell groups. These 5 genes are closely related with immune response in function.\n\nConclusion. Our results showed the functional mechanisms underlying the associations of 8 SNP and the corresponding genes. This study is an example of mining publicly available datasets and results in validation of significant disease-association results. Using public data resources for integrative analyses

may provide insights into the molecular genetic mechanisms underlying human diseases.”
“J Clin Hypertens (Greenwich). 2012;00:0000 (c) 2012 Wiley Periodicals, Inc. The authors aim was to investigate the prognostic value of first-visit systolic and diastolic blood pressure (SBP/DBP) in hypertensive patients with stable coronary artery disease (sCAD) in conditions of contemporary daily clinical practice. From February Galardin in vitro 1, 2000, to January 31, 2004, 690 consecutive hypertensive patients with sCAD (mean age 68 +/- 10 years, 65% male) were prospectively followed in the outpatient cardiology clinic for major events (acute coronary syndrome, revascularization, stroke, heart failure, or death) and associations with baseline SBP/DBP were investigated. At first visit, median SBP/SDP were 130/75 mm Hg (interquartile range, 2575; 120140/7080 mm Hg). After 25 months of follow-up (median), 19 patients died (2.8%); 10 from cardiovascular causes (1.5%), 87 patients experienced a coronary event (13%), and 130 patients (19%) a major event.

Regular digital ano-rectal examination (DARE) is a type of screen

Regular digital ano-rectal examination (DARE) is a type of screening that has been recommended by some experts. How widely this forms part of HIV management guidelines is unclear. Methods: The protocol was registered

prospectively (CRD42013005188; www.crd.york.ac.uk/PROSPERO/). We systematically reviewed 121 regional and national HIV guidelines and searched for guidelines from http://hivinsite.ucsf.edu/global?page=cr-00-04#SauguidelineX, PubMed and Web of Science databases up to 5th August 2013 for recommendations of DARE as a means of anal cancer screening in HIV positive MSM. Guidelines were examined in detail if they were clinical guidelines, including both prevention and treatment protocols and were in English. Guidelines were excluded if they were restricted to limited areas (e. g. antiretroviral therapy only, children or pregnant women, strategies for prevention/testing). Information was extracted regarding recommendation of DARE STA-9090 Cytoskeletal Signaling inhibitor click here as a screening method,

the frequency of DARE recommended, target population for screening and the strength of evidence supporting this. Results: 30 regional and national guidelines were included and examined in detail. Only 2 recommended DARE. The ‘European AIDS Clinical Society Guidelines’ recommends DARE every 1-3 years for HIV positive MSM whilst the ‘US Guideline for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents’ recommends an annual DARE for the HIV + population in general. None of these guidelines specify the age of commencing screening. In each case, the highest level of evidence supporting these two recommendations selleck was expert opinion. Conclusions: Few HIV guidelines discuss or recommend DARE as a means of anal cancer screening. Studies of the efficacy,

acceptability and cost-effectiveness of DARE are needed to assess its role in anal cancer screening.”
“The care and outcome of patients with end stage renal disease (ESRD) on chronic hemodialysis is directly dependent on their hemodialysis access. A brachiocephalic fistula (BCF) is commonly placed in the elderly and in patients with a failed lower-arm, or radiocephalic, fistula. However, there are numerous complications such that the BCF has an average patency of only 3.6 years. A leading cause of BCF dysfunction and failure is stenosis in the arch of the cephalic vein near its junction with the axillary vein, which is called cephalic arch stenosis (CAS). Using a combined clinical and computational investigation, we seek to improve our understanding of the cause of CAS, and to develop a means of predicting CAS risk in patients with a planned BCF access. This paper details the methodology used to determine the hemodynamic consequences of the post-fistula environment and illustrates detailed results for a representative sample of patient-specific anatomies, including a single, bifurcated, and trifurcated arch.

“Background: It is generally understood that shorter Web s

“Background: It is generally understood that shorter Web surveys S63845 concentration and use of incentives result in higher response rates

in Web surveys directed to health care providers. Less is known about potential respondent preference for reduced burden as compared to increased reward.\n\nObjective: To help elicit preference for minimized burden compared to reward for completion of a survey, we observed physician preferences for shorter Web surveys compared to incentives as well as incentive preference (small guaranteed incentive compared to larger lottery incentive) accompanying an electronic request to complete a survey.\n\nMethods: This was an observational study that accompanied a large Web survey study of radiology staff, fellows, and residents at select academic medical centers in the United States. With the request to complete the survey, potential respondents were offered three options: (1) a 10-minute Web survey with the chance to win an iPad, (2) a 10-minute Web survey

with a guaranteed nominal incentive ($ Cyclopamine cell line 5 amazon. com gift card), or (3) a shorter (5-7 minute) Web survey with no incentive. A total of 254 individuals responded to the Web survey request.\n\nResults: Overwhelmingly, individuals chose a longer survey accompanied by an incentive compared to a shorter survey with no incentive (85% compared to 15%, P <. 001). Of those opting for an incentive, a small, but not selleck inhibitor significant majority chose the chance to win an iPad over a guaranteed $5 gift card (56% compared to 44%).\n\nConclusions: When given the choice, radiologists preferred a reward (either guaranteed or based on a lottery) to a less burdensome survey, indicating that researchers should focus more attention at increasing perceived benefits of completing a Web survey compared to decreasing perceived burden.”
“Objective: Accurate measurements of prevalence of “any” breastfeeding and “exclusive” breastfeeding help assess progress toward public health goals. We compared two commonly used data sources

for measuring breastfeeding rates to assess agreement.\n\nMethods: The National Immunization Survey (NIS) is used by the Centers for Disease Control and Prevention to measure progress toward national breastfeeding goals and obtains breastfeeding outcomes retrospectively at 1935 months. The California Newborn Screen (CNS) is a contemporaneous measure of breastfeeding during birth hospitalization and measures progress toward public health goals in California. We compared results for “any breastfeeding” and “exclusive breastfeeding” for California infants in the NIS to those in the CNS using descriptive statistics.\n\nResults: Our results show that the two methods produce similar results for “any” breastfeeding at <4 days: 82.7%, 95% confidence interval (79.6%, 85.

Results: Chronic

social instability during adolescenc

\n\nResults: Chronic

social instability during adolescence and early adulthood induces persistent behavioral alterations, including enhanced anxiety and social deficits that are transmitted predominantly to females across at least three generations. Both mothers and fathers can transmit all of these altered behaviors to their F1 offspring. However, only F1 fathers transmit all of them to their F2 and F3 daughters. In the F1 generation, enhanced anxiety and social deficits are associated with elevated serum corticosterone levels; however, in the F2 and F3 generations, they are not.\n\nConclusions: These findings support the idea that individual risk for psychiatric disorders that involve enhanced learn more anxiety and/or social dysfunction may be dependent not only on the specific alleles of genes that are inherited from one’s parents and on one’s own experiences, but also on the experiences of one’s parents when they were young.”
“Background. Traumatic tricuspid insufficiency (TTI) is uncommon

and surgical experience Galardin ic50 is limited. We report our surgical experience with TTI in 13 patients.\n\nMethods. From January 2000 through March 2008, we operated on 13 patients with TTI (10 men 3 women; mean age, 39.8 +/- 10.5 years). The intervals from trauma to diagnosis and from trauma to surgery averaged 37.4 and 54.4 months, respectively. At operation, the mechanism of TTI was due to anterior chordal rupture in 8, anterior papillary muscle rupture in 3, rupture of anterior papillary muscle and chordae in 1, and anterior leaflet defect in 1. In 7 patients the annulus was dilated. Valve repair was successful in 13 patients.\n\nResults. No early or late deaths occurred. Severe hemolysis occurred in 1 patient after tricuspid and mitral valve repairs. At follow-up extending

to 9.5 years, 9 patients were in New York Heart Association functional class I, and 4 were in class II. Transthoracic echocardiography demonstrated no or trivial residual regurgitation in 7 patients, mild regurgitation in 4, and mild-to-moderate regurgitation in 2. A significant decrease of the right ventricular end-diastolic dimension (37.7 +/- 9.7 vs 20.7 +/- 4.6 mm; p < 0.001) was observed. The mean transvalvular gradient was 2.5 +/- 0.8 mm Hg. Eleven patients were in sinus rhythm.\n\nConclusions. Satisfactory Vorinostat nmr early and midterm outcomes can be achieved for TTI by tricuspid valve repair. Early surgical intervention should be emphasized to achieve good functional results and preserve the right ventricular function. (Ann Thorac Surg 2010;90:1934-8) (C) 2010 by The Society of Thoracic Surgeons”
“OBJECTIVE: Although amphibians are known Salmonella carriers, no such outbreaks have been reported. We investigated a nationwide outbreak of human Salmonella Typhimurium infections occurring predominantly among children from 2008 to 2011.\n\nMETHODS: We conducted a matched case-control study.

The first nomograms to predict late urinary toxicity but also spe

The first nomograms to predict late urinary toxicity but also specific urinary symptoms after prostate RT were generated, contributing to prostate cancer treatment decision.”
“Background In West Africa, the principal vectors of lymphatic filariasis INCB28060 inhibitor (LF) are Anopheles

species with Culex species playing only a minor role in transmission, if any. Being a predominantly rural disease, the question remains whether conflict-related migration of rural populations into urban areas would be sufficient for active transmission of the parasite. Methodology/Principal Findings We examined LF transmission in urban areas in post-conflict Sierra Leone and Liberia that experienced significant rural-urban migration.

Mosquitoes from Freetown and Monrovia, were analyzed for infection with Wuchereria bancrofti. We also undertook a transmission assessment survey (TAS) in Bo and Pujehun districts in Sierra Leone. The majority of the mosquitoes collected were Culex species, while Anopheles species were present in low numbers. The mosquitoes were analyzed in pools, with a maximum of 20 mosquitoes per pool. In both countries, a total of 1731 An. gambiae and 14342 Culex were analyzed for W. bancrofti, using the PCR. Two pools of Culex mosquitoes and 1 pool of An. gambiae were found infected XMU-MP-1 molecular weight from one community in Freetown. Pool screening analysis indicated a maximum likelihood of infection of 0.004 (95% CI of 0.00012-0.021) and 0.015 (95% CI of 0.0018-0.052) for the An. gambiae and Culex respectively. The results indicate that An. gambiae is present in low numbers, with a microfilaria

prevalence breaking threshold value not sufficient to maintain transmission. The results of the TAS in Bo and Pujehun also indicated an antigen prevalence of 0.19% and 0.67% in children, respectively. This is well below the recommended 2% level for stopping MDA in Anopheles E1 Activating inhibitor transmission areas, according to WHO guidelines. Conclusions We found no evidence for active transmission of LF in cities, where internally displaced persons from rural areas lived for many years during the more than 10 years conflict in Sierra Leone and Liberia. Author Summary There have been many arguments regarding the implementation of Mass Drug Administration (MDA) activities for elephantiasis control in urban areas, and especially in countries where the disease is mostly found in rural settings. Blanket MDA in implementation units in big cities, may be costly and unnecessary, without evidence for active transmission in urban areas. Over 1 million people were treated in Freetown during the first MDA carried out in 2010. This represents hundreds of thousands dollars that may serve a better use in reducing the impact of elephantiasis in areas with established on-going transmission.

g , EPA and DHA) and/or biodiesel production However, lipid extr

g., EPA and DHA) and/or biodiesel production. However, lipid extraction methods

for microalgae cells are not well established, and there is currently no standard extraction method for the determination of the fatty acid content of microalgae. This has caused a few problems in microlagal biofuel research due to the bias derived from different extraction methods. Therefore, this study used several extraction methods for fatty acid analysis on marine microalga Tetraselmis sp. M8, aiming to assess the potential impact of different extractions on current microalgal lipid research. These methods included classical Bligh & Dyer lipid extraction, two other chemical extractions using different solvents and sonication, direct saponification and supercritical CO2 extraction. Soxhlet-based extraction YH25448 was used to weigh out the importance of solvent polarity in the algal oil extraction. Coupled with GC/MS, a Thermogravimetric Analyser was used to improve the quantification of microalgal lipid extractions. Among these extractions, significant differences were observed in both, extract yield and fatty acid composition. The supercritical extraction technique stood out most for effective extraction of microalgal lipids, especially 3-deazaneplanocin A cost for long chain unsaturated fatty acids. The results highlight the necessity for comparative analyses of microalgae fatty acids and careful

choice and validation of analytical methodology in microalgal lipid research.”

Shenzhen’s rapid growth and urbanisation has attracted a large, mobile, migrant working population. This article explores health protection through the means of social health insurance between migrants and registrants and their point of access to healthcare.\n\nMethods: A cross-sectional questionnaire survey was conducted in Shenzhen, with a random sample of 793 registered and 750 non-registered residents. Chi-square test and multivariate logistic regression were applied to analyse the association between health insurance coverage with Hukou registration status and healthcare utilisation.\n\nResults: Amongst 1543 respondents, 43.1% of non-registered residents were uninsured. Being non-registered strongly predicted for no insurance Tyrosine Kinase Inhibitor Library (OR = 5.00; CI 3.53,7.07) and have purchased additional/private insurance (OR = 2.99; CI 1.66,5.37). Migrants who self-reported chronic health conditions were also more likely to utilise health services in general (OR = 2.77; CI 1.18,6.52).\n\nConclusions: Inadequate health insurance coverage for migrants as observed in Shenzhen remains a challenge for the Chinese health reform. Our results suggest that the current insurance system must seek to include migrants in order to achieve universal coverage and improved health protection for its population.

Expression of VD metabolizing enzymes has not previously been inv

Expression of VD metabolizing enzymes has not previously been investigated in human testis and male reproductive tract. Therefore, we performed a comprehensive analysis of the expression of VDR, VD activating (CYP2R1, CYP27A1, CYP27B1) and inactivating (CYP24A1) enzymes in the testis, epididymis, seminal vesicle (SV), prostate and spermatozoa.\n\nTissue samples were obtained after orchiectomy (testis n = 13; epididymis n = 7), prostatectomy Navitoclax concentration (prostate n = 5 and SVs n = 3) and semen samples obtained after ejaculation (n = 13). mRNA was detected with RT-PCR and expression

of proteins was determined by immunohistochemistry.\n\nVDR and VD metabolizing enzymes were concomitantly expressed in round and elongated spermatids, vesicles within the caput epididymis, and glandular epithelium of cauda epididymis, SV and prostate. The expression pattern in ejaculated spermatozoa varied,

although, concomitant expression of VDR, CYP2R1, CYP27B1 and CYP24A1 was observed in neck and midpiece in a subpopulation of mature spermatozoa.\n\nOn the basis of the marked expression of VDR and the VD metabolizing enzymes in human testis, ejaculatory tract and mature spermatozoa, we suggest that VD is important for spermatogenesis and maturation of human spermatozoa.”
“Background: Small intestinal bacterial overgrowth (SIBO) may mimic a functional disorder such as irritable bowel syndrome (IBS) or functional bloating (FB). In this Study, 3 MA we buy LY2606368 aimed to assess the utility of glucose breath test (GBT) in patients with the above conditions.\n\nMethods: This study included 200 consecutive patients (130 with IBS and 70 with FB on the basis of Rome III criteria) and 70 controls with similar age and sex distribution. Patients and controls underwent 50g GBT and a H(2) peak of >= 12 ppm was considered diagnostic of SIBO. Positive patients received rifaximin of 1200 mg/day for 10 days and underwent a second GBT I month after the end of treatment. A symptom questionnaire was completed before and after therapy.\n\nResults:

GBT resulted to be altered in 21 out of 130 IRS patients and in 2 out of 70 FB patients with a significant difference of the former group compared with controls (3 out of 70, P = 0.0137). Most IRS patients with a positive GBT complained of diarrhea. GBT showed an increased methane excretion in 26% of patients. Who Were equally distributed among different bowel pattern subgroups. Previous abdominal surgery was more frequently seen in GBT-positive patients (P = 0.008). After antibiotic treatment, eradication of SIBO was achieved in 70% of patients, with a significant improvement of symptoms in eradicated patients compared with the not eradicated ones (P < 0.001).\n\nConclusions: GBT is useful to identify a subgroup of IBS-like patients, whose symptoms are owing to SIBO.

All rights reserved “
“Higher plasma copeptin levels correla

All rights reserved.”
“Higher plasma copeptin levels correlate with poor clinical outcomes after traumatic brain injury. Nevertheless, their links with acute traumatic coagulopathy and progressive LDN-193189 hemorrhagic injury are unknown. Therefore, we aimed to investigate the relationship between plasma copeptin levels, acute traumatic coagulopathy and progressive hemorrhagic injury in patients with severe traumatic brain injury. We prospectively studied

100 consecutive patients presenting within 6 h from head trauma. Progressive hemorrhagic injury was present when the follow-up computerized tomography scan reported any increase in size or number of the hemorrhagic lesion, including newly developed ones. Acute traumatic coagulopathy was defined as an activated partial thromboplastic time greater than 40s and/or international normalized ratio greater than 1.2 and/or a platelet count less than 120

x 10(9)/L. We measured plasma copeptin levels on admission using an enzyme-linked immunosorbent assay in a blinded fashion. In multivariate logistic regression www.selleckchem.com/products/SB-203580.html analysis, plasma copeptin level emerged as an independent predictor of progressive hemorrhagic injury and acute traumatic coagulopathy. Using receiver operating characteristic curves, we calculated areas under the curve for progressive hemorrhagic injury and acute traumatic coagulopathy. The predictive performance of copeptin was similar to that NSC23766 of Glasgow Coma Scale score. However, copeptin did not obviously improve the predictive

value of Glasgow Coma Scale score. Thus, copeptin may help in the prediction of progressive hemorrhagic injury and acute traumatic coagulopathy after traumatic brain injury. (C) 2014 Elsevier Inc. All rights reserved.”
“Background: Babesiosis threatens the development of the cattle and buffaloes industries in Egypt and improved control is needed. The main objectives of this study are surveying the presence of bovine babesiosis in distinct selected bovine and buffalo populations in Egypt using novel molecular and previously validated serological methods, while also comparing the occurrence of hematological alterations among Babesia infected cattle and buffalos. Methods: A total of 253 and 81 blood samples from apparently healthy cattle and buffaloes, respectively, were randomly collected from diverse locations in Egypt. All samples were tested for Babesia bovis and B. bigemina infection using blood film examination, competitive ELISA (cELISA) and PCR. Novel semi-nested and nested PCR assays for the detection of Babesia bovis and B. bigemina respectively, were developed and used to analyze DNA extracted from bovine and buffalo samples. Hematological profiles were studied using a hematological analyzer. Results: Blood films examination revealed 13.8 % and 7.4 % Babesia infection rates in cattle and buffaloes, respectively. However, in cattle, the cELISA detected 32.8 %, 21.3 % and 10.7 % infection rates with B.

In 2005, the channel water provoked a significantly greater numbe

In 2005, the channel water provoked a significantly greater number of anomalies than the control water. The number of anomalies increased in 2007. This suggests that there was an increase in toxic substances in the channel over the years.”
“In the field of so-called

chronic daily headache, it is not easy for migraine that worsens progressively until it becomes daily or almost daily to find a precise and universally recognized place within the current international headache classification systems. In line with the 2006 revision of the second edition of the International Classification of Headache Disorders (ICHD-2R), the current prevailing opinion is that this headache type should be named chronic migraine (CM) and be characterized by the presence of at least 15 days selleck chemical of headache per month for at least 3 consecutive months, with headache having

the same clinical features of migraine without HM781-36B aura for at least 8 of those 15 days. Based on much evidence, though, a CM with the above characteristics appears to be a heterogeneous entity and the obvious risk is that its definition may be extended to include a variety of different clinical entities. A proposal is advanced to consider CM a subtype of migraine without aura that is characterized by a high frequency of attacks (10-20 days of headache per month for at least 3 months) and is distinct from transformed migraine (TM), which in turn should be included in the classification as a complication of migraine. Therefore,

CM should be removed from its current coding position in the ICHD-2 and be replaced CCI-779 by TM, which has more restrictive diagnostic criteria (at least 20 days of headache per month for at least 1 year, with no more than 5 consecutive days free of symptoms; same clinical features of migraine without aura for at least 10 of those 20 days).”
“Women with bipolar disorder have a high risk for symptom exacerbation during pregnancy and the risk is elevated further when mood stabilizers are discontinued. This report describes a 31-year-old bipolar woman who discontinued medication before pregnancy but had to resume her pharmacotherapy due to manic episodes that recurred during the second trimester. Olanzapine, an atypical antipsychotic, was administered from week 25 of gestation and then replaced with quetiapine in week 35 of gestation. Even though a consensus on clinical interventions for pregnant patients with symptom relapse has not been reached, clinicians should still discuss pregnancy and therapeutic management with every female bipolar patient of childbearing age. This discussion is important because treatment can be managed most effectively in these individuals if pregnancy is planned. Ultimately, clinical decisions should be made on a case-by-case basis, weighing the risks to the mother and fetus between the disorder itself and the teratogenicity of pharmacotherapy.