A systematic review of relationships and sex education outcomes for students with intellectual disability reported in the international literature.

BACKGROUND: Little is known about how to evaluate relationships and sex education (RSE) delivered to students with intellectual disability and what stakeholders perceive are important outcomes. The present study aimed to systematically review existing studies on outcomes of RSE, as the first step in the development of a core outcome set (COS) for students with intellectual disability. METHOD: A systematic literature process included two stages: (1) searching for studies reporting on RSE outcomes for students with intellectual disability and (2) studies reporting on measurement properties (e.g. validity, reliability and responsiveness) of standardised instruments identified in stage 1. RESULTS: A total of 135 RSE outcomes were extracted from 42 studies: 43 outcomes for students in secondary education and 92 outcomes for students in further education. No RSE outcomes were reported for primary education. Outcomes referred to the human body, hygiene, relationships, sexuality, sex and its consequences, inappropriate and appropriate social and sexual behaviour, keeping safe, emotional vocabulary and positive self-esteem. Outcomes were predominantly knowledge-based, rather than relating to skills and attitudes development. Students with intellectual disability, parents and teachers perceive different RSE outcomes meaningful. Five instruments were used to measure the outcomes, but none have established psychometric properties with this population. CONCLUSIONS: The comprehensive list of RSE outcomes for students with intellectual disability will be used to inform the next steps of a Core Outcome Set needed for RSE evaluations in research and education settings. There is an urgent need to develop standardised instruments validated for students with intellectual disability.

Socio-economic determinants of COVID-19 in Mexico.

OBJECTIVES: This study aimed to identify and quantify the role that social and economic determinants play in the probability of dying from COVID-19, in the case of Mexico. STUDY DESIGN: This was a cross-sectional study based on secondary data. METHODS: In this study, COVID-19 contagion and mortality data were used, as well as socio-economic variables, from public databases and open access, with which an econometric model was estimated. RESULTS: It shows that the number of deaths can rise when variables related to vulnerable groups increase, such as poverty, lack of services, gender, and age. In addition, having pre-existing medical conditions or lacking access to water can be a significant factor in the increase in deaths. CONCLUSIONS: Therefore, this study suggests more policies be developed for vulnerable groups to reduce gaps in inequality, particularly given the current situation in which greater inequality can exacerbate the impact of a disease or an unforeseen situation, as is the case of COVID-19.

Colorimetric detection of residual quaternary ammonium compounds on dry surfaces and prediction of antimicrobial activity using bromophenol blue.

Controlling and monitoring the residual activity of quaternary ammonium compounds (QACs) are critical for maintaining safe yet effective levels of these agents in the environment. This study investigates the utility of bromophenol blue (BPB) as a safe, rapid and user-friendly indicator to detect in situ residual QACs dried on hard, non-porous surfaces, as well a means to assess their antimicrobial efficacy. At pH 7, BPB has a purple colour which turns blue upon its complexation with QACs such as didecyldimethylammonium chloride (DDAC). BPB itself has no antimicrobial properties up to 400 ppm. Within the range of 0-400 ppm, BPB colour change was tied to specific DDAC antimicrobial performances with a detection threshold of 100 ppm. BPB concentration and application volume could be adjusted such that a colour shift from purple to blue correlated with a set percent reduction (>99·9%) in test bacteria (Staphylococcus aureus and Klebsiella aerogenes). The BPB solutions developed in this study yielded similar colour shifts on polycarbonate and stainless steel surfaces and did not cross-react with chemical ingredients commonly found in sanitizers and disinfectant products. Overall, this study suggests that BPB provides a simple solution to safely monitor the post-application level and biocidal activity of residual dried QACs on surfaces.

Reducing risk of Type 2 diabetes in HIV: a mixed-methods investigation of the STOP-Diabetes diet and physical activity intervention.

AIM: To conduct a mixed-methods feasibility study of the effectiveness and acceptability of an individualized diet and physical activity intervention designed to reduce the risk of Type 2 diabetes experienced by people living with HIV. METHODS: Participants with impaired fasting glucose and HIV were invited to take part in a 6-month diet and physical activity intervention. Individualized advice to achieve 10 lifestyle goals was delivered monthly. Diabetes risk was assessed pre- and post-intervention by measurement of the glucose and insulin response to a 3-h meal tolerance test. Six-month change was analysed using paired t-tests. Research interviews exploring the acceptability of the intervention and factors influencing behaviour change were conducted with those who participated in the intervention, and those who declined participation. RESULTS: The intervention (n=28) significantly reduced the following: glucose and insulin, both fasting and postprandial incremental area under the curve (glucose 7.9% and 17.6%; insulin 22.7% and 31.4%, respectively); weight (4.6%); waist circumference (6.2%); systolic blood pressure (7.4%); and triglycerides (36.7%). Interview data demonstrated the acceptability of the intervention. However, participants expressed concern that deliberate weight loss might lead to disclosure of HIV status or association with AIDS-related illness. The belief that antiretroviral medications drove diabetes risk was associated with declining study participation or achieving fewer goals. CONCLUSIONS: We have demonstrated the beneficial effects of a lifestyle intervention in mitigating the increased risk of Type 2 diabetes associated with HIV. Future interventions should be designed to further reduce the unique barriers that prevent successful outcomes in this cohort.

Prevalence of Spasticity and Postural Patterns in the Upper Extremity Post Stroke.

INTRODUCTION: A high number of patients with stroke develop upper extremity spasticity, causing abnormal postures and patterns. These alterations limit the use of arm in functional activities and affect social participation. AIM: To determine the prevalence of spasticity and postural patterns of the upper extremity post stroke. MATERIALS AND METHODS: A cross-sectional descriptive design was used with a prospective follow-up. The sample included 136 patients. The study included 3 measuring times; at 10 days (T1), applying a record with sociodemographic-clinical data, the evaluation of muscle tone in the elbow and wrist and the postural patterns of the UE, and at 3 months (T2) and 12 months (T3) post stroke, re-evaluating tone and patterns. Prevalence was calculated through the one-sample chi-squared (χ2) test followed by inspection of the standardized residuals (z) in each cell. The Kappa coefficient evaluated the degree of agreement in elbow and wrist tone. RESULTS: The prevalence of spasticity in the elbow was 37.5% at T1, 57.4% at T2, and 57.4% at T3. At each time there was a high degree of agreement between elbow and wrist tone. Patients developed increased elbow tone between T1 and T2, with maintained tone between T2 and T3. Postural pattern III was the most prevalent according to Hefter's classification. CONCLUSION: The prevalence of spasticity in the elbow and wrist increases between 10 days and 3 months post stroke, and is maintained between 3 and 12 months. The onset of spasticity occurs in almost half of patients during the first 10 days post stroke. Postural pattern III according to Hefter's classification presented the greatest prevalence in the spastic UE.

Cognition and adaptive functioning in older people attending drug and alcohol services.

BACKGROUND: Substance use disorders in older adults are expected to increase dramatically in the coming years. Given the increased susceptibility to cognitive deficits in older substance users (defined here as aged 50+ years due to the accelerated health decline observed in this population), it is important to consider the functional correlates of cognitive impairment in these older adults. This study details the cognitive status of older individuals attending outpatient drug and alcohol (D&A) treatment services and seeks to determine of the association of cognitive impairment to self-reported daily functioning. METHODS: Ninety nine clients aged 50 years or over attending outpatient D&A treatment services in Sydney, Australia participated. Cognition was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R). Recent substance use (Australian Treatment Outcome Profile), physical and mental health (SF12, Geriatric Depression Scale), social isolation (Lubben Social Network Scale), and activities of daily living (Bayer ADL Scale) were also assessed. RESULTS: Nearly two-thirds of participants screened positive for cognitive impairment on the ACE-R; 41% and 65% of clients met the cut-off scores for mild cognitive impairment (MCI) and more severe cognitive impairment, respectively. Self-reported seizure history was a predictor of cognitive impairment. CONCLUSIONS: The results suggest that cognitive impairment in this group is common. The assessment of cognitive status for this older group of patients should not only include the identification of cognitive impairment but also encompass mental health and social functioning. A greater understanding of the needs of this cohort will also enable better co-ordination with other health and welfare services tailored to this population.

A qualitative metasynthesis exploring the impact of prostate cancer and its management on younger, unpartnered and gay men.

Prostate cancer (PCa) can negatively impact on men's sexual, urinary and emotional functioning, affecting quality of life. Most men with PCa are older (≥65 years), married and heterosexual and little is known about the impact on men who are younger, unpartnered or gay. We aimed to synthesise existing qualitative research on these three groups of men. A systematic metasynthesis was undertaken that included data on the unique impacts of PCa on younger (<65 years) (n = 7 papers), unpartnered (n = 17 papers) or gay or bisexual men (n = 11 papers) using a modified meta-ethnographic approach. The three overarching constructs illustrated the magnified disruption to men's biographies, that included: marginalisation, isolation and stigma-relating to men's sense of being "out of sync"; the burden of emotional and embodied vulnerabilities and the assault on identity-illustrating the multiple threats to men's work, sexual and social identities; shifting into different communities of practice-such as the shift from being part of a sexually active community to celibacy. These findings suggest that PCa can have a particular impact on the quality of life of younger, unpartnered and gay men. This has implications for the provision of tailored support and information to these potentially marginalised groups.

Methylglyoxal and methylglyoxal-modified collagen as inducers of cellular injury in gingival connective tissue cells.

BACKGROUND AND OBJECTIVES: Methylglyoxal is a toxic product derived from glucose metabolism that plays a role in inflammation, diabetes and aging. In addition, the periodontal pathogen Tannerella forsythensis may also generate this compound. However, the effects of methylglyoxal on gingival cells are still poorly understood. In the present study, we have explored whether methylglyoxal or methylglyoxal-treated collagen may modulate cell viability, death and proliferation in gingival connective tissue cells. In addition, we have searched for inflammatory mediators secreted by cells upon exposure to these conditions. MATERIAL AND METHODS: Primary cultures of human gingival fibroblasts were stimulated with soluble methylglyoxal or cultured over a collagen matrix glycated by this agent. Cell viability was evaluated through the MTS assay. Cell death was assessed through DAPI nuclear staining, annexin V and propidium iodide assays. Cell proliferation was evaluated through double immunofluorescence for DAPI and Ki67. Protein levels of matrix metalloproteinases and cytokines were assessed through antibody arrays, enzyme-linked immunosorbent assay, real-time reverse transcription polymerase chain reaction and immunofluorescence. Statistical analysis was performed using the Kruskall-Wallis and Mann-Whitney tests. RESULTS: Soluble methylglyoxal, but not culture of gingival fibroblasts over a methylglyoxal-modified collagen matrix, induced a reduction on cell viability. Moreover, soluble methylglyoxal induced apoptotic cell death as indicated by DAPI nuclear staining, annexin V and propidium iodide assays. Neither soluble methylglyoxal, nor methylglyoxal-modified collagen modified cell proliferation. Using an antibody array, enzyme-linked immunosorbent assay and immunofluorescence assays, we determined that both, soluble methylglyoxal and methylglyoxal-modified collagen stimulated an increase in tissue inhibitor of metalloproteinase (TIMP)-1 protein levels. CONCLUSIONS: Soluble methylglyoxal is a highly cytotoxic compound that induces cell death through apoptosis in gingival fibroblasts. TIMP-1 is induced in these cells upon direct exposure to methylglyoxal or after culture of gingival fibroblasts over methylglyoxal-treated collagen. As TIMP-1 has been implicated in cell survival and matrix remodeling, we propose that increased TIMP-1 protein levels may be part of a protective response of gingival connective tissue cells upon exposure to methylglyoxal or after the interaction with the collagen matrix that has been modified by this agent.

Influence of dietary grape pomace combined with linseed oil on fatty acid profile and milk composition.

Grape pomace is a by-product resulting from the winery industry that is rich in phenolic compounds. It could play a role as an antioxidant and, owing to its high fiber concentration, it would be an alternative ingredient to partially replace forage in the diet of small ruminants. The objective of this study was to evaluate the effect of dietary supplementation of vitamin E or different doses of grape pomace associated with linseed oil on milk fatty acid profile, composition, and yield. Forty-eight Churra ewes were fed with experimental diets consisting of a total mixed ration (TMR) containing 2.7% [on a dry matter (DM) basis] of linseed oil, forage, and concentrate at a 40:60 ratio. Ewes were assigned to 1 of 4 treatments: control (without grape pomace), vitamin E (with 500 mg/kg of TMR of vitamin E), grape pomace-5 (5 g/100 g of TMR of DM of grape pomace), and grape pomace-10 (10 g/100 g of TMR of DM of grape pomace). Experimental diets did not affect DM intake and milk yield and composition. The vitamin E supplementation had only a moderate effect on milk concentration of fatty acids (increase in α-linolenic acid and 16:0 and decrease in cis-9 18:1). Grape pomace supplementation did not affect the percentages of total saturated, monounsaturated, and polyunsaturated fatty acids. Levels of α-linolenic acid reached about 1% of total fatty acids as a consequence of the presence of linseed oil in the diets, were not modified with vitamin E, and remained unaltered in grape pomace-5 and -10 treatments. Linoleic acid was increased by the highest dose of grape pomace, but this ingredient did not modify the cis-9,trans-11 18:2 milk fat content. The concentration of total odd- and branched-chain fatty acids did not diminish in grape pomace-5 and pomace-10 treatments. The presence of grape residue did not modified the trans-11 18:1 and trans-10 18:1 contents, which might indicate that, under the conditions assayed, this winery by-product would not alter the pathways of rumen conversion of dietary unsaturated fatty acids.

Forensic evaluation of the AmpFℓSTR Identifiler kit in nine Mexican native populations from the pre-Columbian Mesoamerican region.

Allele frequency distribution and forensic parameters of the AmpFℓSTR Identifiler kit was determined in nine Mexican Amerindian populations based on 1,040 unrelated individuals from the pre-Columbian region known as Mesoamerica. Hardy-Weinberg equilibrium was demonstrated for most of the short tandem repeats (STRs) in all nine populations. The power of discrimination and exclusion were higher than 0.99999 and 0.997942, respectively. In addition, a brief overview of the genetic relatedness and structure (F st = 2.62 %; p = 0.00000) between these populations is presented.

Caspofungin for the treatment of invasive fungal disease in hematological patients (ProCAS Study).

Caspofungin is an echinocandin with proven efficacy in invasive candidiasis (IC) and invasive aspergillosis (IA). This multicenter, prospective, non-comparative, observational ProCAS study was aimed to assess the effectiveness and safety of caspofungin in adult hematological patients with IC or IA under everyday clinical conditions. Favorable outcomes included complete and partial responses on the last day of caspofungin therapy. Safety was assessed up to 14 days post-caspofungin. A total of 115 patients (69 male) with a median age of 52 years (range, 23-78 years) were analyzed. Underlying disease was acute myeloid leukemia in 45 patients (39%), and 21 (18%) were allogeneic stem cell transplant recipients. Thirty-four (29.5%) patients had a diagnosis of IA and 26 (22.6%) had IC (candidemia). The median duration of caspofungin therapy was 14 days (range, 1-100). The overall favorable response rate was 77% (20/26) for patients with IC (69% first-line) and 79% (27/34) for those with IA. Antifungal therapy with caspofungin was generally well tolerated, only two (1.7%) patients having a non-serious drug-related adverse reaction. These results suggest that caspofungin, either alone or in combination, should be considered an effective and safe option for the treatment of invasive mycoses in patients with severe hematological disorders.

RvE1 Promotes Axin2+ Cell Regeneration and Reduces Bacterial Invasion.

Vital pulp therapy and root canal therapy (RCT) are the dominant treatment for irreversible pulpitis. While the success rate of these procedures is favorable, they have some limitations. For instance, RCT leads to removing significant dentin in the coronal third of the tooth that increases root-fracture risk, which forces tooth removal. The ideal therapeutic goal is dental pulp regeneration, which is not achievable with RCT. Specialized proresolving mediators (SPMs) are well known for inflammatory resolution. The resolution of inflammation and tissue restoration or regeneration is a dynamic and continuous process. SPMs not only have potent immune-modulating functions but also effectively promote tissue homeostasis and regeneration. Resolvins have been shown to promote dental pulp regeneration. The purpose of this study was to explore further the cellular target of Resolvin E1 (RvE1) therapy in dental pulp regeneration and the impact of RvE1 in infected pulps. We investigated the actions of RvE1 on experimentally exposed pulps with or without microbial infection in an Axin2Cre-Dox;Ai14 genetically defined mouse model. Our results showed RvE1 promoted Axin2-tdTomato+ cell expansion and odontoblastic differentiation after direct pulp capping in the mouse, which we used to mimic reversible pulpitis cases in the clinic. In cultured mouse dental pulp stem cells (mDPSCs), RvE1 facilitated Axin2-tdTomato+ cell proliferation and odontoblastic differentiation and also rescued impaired functions after lipopolysaccharide stimulation. In infected pulps exposed to the oral environment for 24 h, RvE1 suppressed inflammatory infiltration, reduced bacterial invasion in root canals, and prevented the development of apical periodontitis, while its proregenerative impact was limited. Collectively, topical treatment with RvE1 facilitated dental pulp regenerative properties by promoting Axin2-expressing cell proliferation and differentiation. It also modulated the resolution of inflammation, reduced infection severity, and prevented apical periodontitis, presenting RvE1 as a novel therapeutic for treating endodontic diseases.

Modified Chevrel technique for abdominal closure in critically ill patients with abdominal hypertension and limited options for closure.

Abdominal compartment syndrome is a potentially life-threatening condition seen in critically ill patients, and most often caused by acute pancreatitis, postoperative abdominal vascular thrombosis or mesenteric ischemia. A decompressive laparotomy is sometimes required, often resulting in hernias, and subsequent definitive wall closure is challenging. AIM: This study aims to describe short term results after a modified Chevrel technique for midline laparotomies in patients witch abdominal hypertension. MATERIALS AND METHODS: We performed a modified Chevrel as an abdominal closure technique in 9 patients between January 2016 and January 2022. All patients presented varying degrees of abdominal hypertension. RESULTS: Nine patients were treated with new technique (6 male and 3 female), all of whom had conditions that precluded unfolding the contralateral side as a means for closure. The reasons for this were diverse, including presence of ileostomies, intraabdominal drainages, Kher tubes or an inverted T scar from previous transplant. The use of mesh was initially dismissed in 8 of the patients (88,9%) because they required subsequent abdominal surgeries or active infection. None of the patients developed a hernia, although two died 6 months after the procedure. Only one patient developed bulging. A decrease in intrabdominal pressure was achieved in all patients. CONCLUSION: The modified Chevrel technique can be used as a closure option for midline laparotomies in cases where the entire abdominal wall cannot be used.

Effects of grape pomace supplementation on the diet of lactating ewes as compared to vitamin E on the meat shelf life of suckling lambs.

Forty-eight Churra ewes and their suckling lambs were assigned to four dietary treatments: control (CTRL), VIT-E (500 mg kg-1 TMR vitamin E), GP-5 (5% grape pomace) and GP-10 (10% grape pomace). After slaughter (11.5 kg live weight), longissimus muscle of lambs was sliced, packaged under modified atmosphere (80,20%/O 2:CO 2) and stored in retail conditions. At each sampling point (0, 3, 7, 10, 14 days), microbiological, physicochemical and sensory characteristics were analysed. Vitamin E and GP-5 were found to be effective (p < 0.05) at preventing enterobacteria growth as of day 10. After day 10, vitamin E and grape pomace in the ewe's supplementation reduced metmyoglobin (p < 0.05) lipid oxidation (p < 0.05) and sensory spoilage throughout the storage period. An effect of the grape pomace dosage was observed, with the supplementation at 5% being more effective. Therefore, we can conclude that grape pomace was just as effective as vitamin E in preventing spoilage during retail storage.

Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action.

The double-stranded RNA-dependent protein kinase PKR is a critical mediator of the antiproliferative and antiviral effects exerted by interferons. Not only is PKR an effector molecule on the cellular response to double-stranded RNA, but it also integrates signals in response to Toll-like receptor activation, growth factors, and diverse cellular stresses. In this review, we provide a detailed picture on how signaling downstream of PKR unfolds and what are the ultimate consequences for the cell fate. PKR activation affects both transcription and translation. PKR phosphorylation of the alpha subunit of eukaryotic initiation factor 2 results in a blockade on translation initiation. However, PKR cannot avoid the translation of some cellular and viral mRNAs bearing special features in their 5' untranslated regions. In addition, PKR affects diverse transcriptional factors such as interferon regulatory factor 1, STATs, p53, activating transcription factor 3, and NF-kappaB. In particular, how PKR triggers a cascade of events involving IKK phosphorylation of IkappaB and NF-kappaB nuclear translocation has been intensively studied. At the cellular and organism levels PKR exerts antiproliferative effects, and it is a key antiviral agent. A point of convergence in both effects is that PKR activation results in apoptosis induction. The extent and strength of the antiviral action of PKR are clearly understood by the findings that unrelated viral proteins of animal viruses have evolved to inhibit PKR action by using diverse strategies. The case for the pathological consequences of the antiproliferative action of PKR is less understood, but therapeutic strategies aimed at targeting PKR are beginning to offer promising results.

Performance of the Ogawa-Kudoh method for isolation of mycobacteria in a laboratory with large-scale workload.

In Uruguay (population 3,323,906; notified tuberculosis incidence 18.4/100,000), virtually all 30,000 samples yearly collected for mycobacterial culture countrywide are processed in a central laboratory. An average of 110 samples are routinely shipped daily and maintained 48-96 hours at room temperature until cultured on Löwenstein-Jensen slants using the standard NALC-NaOH decontamination procedure. The much simpler Kudoh decontamination/culture method -swab and Ogawa (acidified) medium- was compared with NALC-NaOH/Löwenstein-Jensen for isolation of mycobacteria from sputa under routine conditions. To this aim, 784 sputum samples were cultured by both methods in the summertime. Gross agreement was 0.99, kappa: 1. Kudoh performance was as follows: sensitivity 100% and accuracy 98.9%. Assays using a modified culture medium, different decontamination times and NaOH concentrations showed the versatility of this procedure. Thus, the Kudoh method is suitable for culturing mycobacteria from naturally contaminated samples even when processing is deferred two to four days after collection.

Induction of paclitaxel resistance by the Kaposi's sarcoma-associated herpesvirus latent protein LANA2.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causal agent of both KS and primary effusion lymphoma (PEL). Although treatment with paclitaxel has significant antitumor activity in KS, drug resistance represents a major obstacle for improving the overall response and survival of PEL patients. The transcriptional pattern of KSHV is cell/tissue specific, as revealed by the fact that the viral latent protein LANA2 is detected exclusively in B cells. This paper focuses on the mechanism of paclitaxel resistance observed in PEL cells. Here we show that LANA2 protein modulates microtubule dynamics through its direct binding to polymerized microtubules, preventing microtubule stabilization induced by paclitaxel. This is the first demonstration of paclitaxel resistance induced by a viral protein and suggests a link between the expression of LANA2 and the resistance of PEL cells to paclitaxel.

Prevalence of ergot derivatives in natural ryegrass pastures: detection and pathogenicity in the horse.

In the present study, we determined the incidence and effects of season and weather on clinical manifestations of endophyte-infected ryegrass toxicity, performed chemical detection and pharmacological bioassays on ryegrass extracts, and conducted trials on: (i) effects of domperidone or metochlopramide on ovarian inactivity induced by endophyte-infected ryegrass; (ii) efficacy of buspirone or dihydrochloro phenyl piperazine (m-CPP) for preventing suppressed milk production induced by endophyte-infected ryegrass; and (iii) efficacy of domperidone to induce ovulation during winter anestrus. Mares with toxicosis had prolonged gestation, embryonic losses, dystocia, poor mammary gland development, low milk production, prolonged uterine involution, and suppressed ovarian activity. Foals had respiratory failure, abnormalities of the skin, umbilicus, bone, and muscle, failure to thrive, blindness, testicular atrophy, and decreased serum total immunoglobulin concentrations. Endophyte-infected ryegrass and the incidence of toxicosis were correlated (r=0.861, P=0.03). Ergot alkaloids were not detected in extracts of endophyte-infected ryegrass by either thin-layer chromatography or spectrophotometry, but their presence was inferred in bioassays of extracts (dose-related increases in the contractile response of rat uterus). Mares given metoclopropamide (0.6 mg/kg/d), given orally every 8h for up to 7d) ovulated earlier (4-7d vs. 15-18d, P<0.001) than those given domperidone (1.1mg/kg/d) orally for up to 18d). Although both metoclopropamide and domperidone induced milk production, the latter did not induce ovarian cyclicity in healthy mares during seasonal anestrus. Based on these findings, we inferred that endophyte-infected ryegrass is associated with ergot alkaloid intoxication in horse.

Effects of ascending buprenorphine doses on measures of experimental pain: A pilot study.

BACKGROUND: Buprenorphine is widely used in the treatment of opioid use disorder and pain management. Little is known about the analgesic effects of high-dose sublingual buprenorphine, particularly in doses of >8 mg. The aim of this study was to examine the effect of ascending doses of buprenorphine upon acute pain measures in patients stabilized on buprenorphine as treatment for opioid dependence. METHODS: The pilot study (n = 7) was a randomised, controlled, double-blind, double-dummy, within-subject crossover study examining cold-pressor threshold and tolerance testing under different buprenorphine dose conditions. Each participant attended three sessions to test the analgesic effect of buprenorphine in their usual dose (100%), 150% and 200% of their usual daily dose. RESULTS: No significant effects of increased dose were seen on experimental pain measures. Expected physiological effects on pupil size and pulse were observed with increasing dose. No effect of buprenorphine condition was seen on subjective ratings of drug strength, or self-reported sedation, though lower ratings drug liking were seen with 150% and 200% conditions, and lower ratings of 'bad effects' and intoxication were reported with the 200% buprenorphine dose condition. No safety concerns with the 150 and 200% buprenorphine dose condition were observed. DISCUSSION: This pilot study suggests that a ceiling effect on analgesia may be observed in people maintained on buprenorphine, though larger studies may confirm this finding. Clinical Trial Number: ACTRN12614001038684.

Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention.

To determine prognosis of acute promyelocytic leukemia (APL) failing to front-line therapy with all-trans retinoic acid (ATRA) and anthracyclines, outcome of 52 patients (32 M/20 F; age: 37, 3-72) included in PETHEMA trials LPA96 and LPA99 who presented with either molecular failure (MOLrel, n=16) or hematological relapse (HEMrel, n=36) was analyzed. Salvage therapy consisted of ATRA and high-dose ara-C-based chemotherapy (HDAC) in most cases (83%), followed by stem-cell transplantation (autologous, 18; allogeneic, 10; syngeneic, 1). Fourteen patients with MOLrel (88%) achieved second molecular complete response (molCR), whereas 81% HEMrel patients responded to second-line treatment, with 58% molCR. After median follow-up of 45 months, four MOLrel and 18 HEMrel patients, respectively, experienced a second relapse. Outcome after MOLrel compared favorably to HEMrel, with longer survival (5-year survival: 64+/-14 vs 24+/-8%, P=0.01) and lower relapse risk (5-year relapse risk: 30+/-13 vs 64+/-9%; P=0.044). Additionally, age