Group VII ethylene response factors, MtERF74 and MtERF75, sustain nitrogen fixation in Medicago truncatula microoxic nodules.

Group VII ethylene response factors (ERF-VII) are plant-specific transcription factors (TFs) known for their role in the activation of hypoxia-responsive genes under low oxygen stress but also in plant endogenous hypoxic niches. However, their function in the microaerophilic nitrogen-fixing nodules of legumes has not yet been investigated. We investigated regulation and the function of the two Medicago truncatula ERF-VII TFs (MtERF74 and MtERF75) in roots and nodules, MtERF74 and MtERF75 in response to hypoxia stress and during the nodulation process using an RNA interference strategy and targeted proteolysis of MtERF75. Knockdown of MtERF74 and MtERF75 partially blocked the induction of hypoxia-responsive genes in roots exposed to hypoxia stress. In addition, a significant reduction in nodulation capacity and nitrogen fixation activity was observed in mature nodules of double knockdown transgenic roots. Overall, the results indicate that MtERF74 and MtERF75 are involved in the induction of MtNR1 and Pgb1.1 expression for efficient Phytogb-nitric oxide respiration in the nodule.

A systematic review of the evidence on the effect of parental communication about health and health behaviours on children's health and wellbeing.

Parents report feeling unsure how best to talk with their children about sensitive health topics and may avoid such conversations; yet if children have questions or concerns about their health, talking to a parent could enhance their health and wellbeing. We investigated the effects of parental communications about health and health behaviours on children's health and wellbeing, and explored what strategies can encourage parents to communicate about health. We conducted a systematic review and narrative synthesis of research published between January 2008 and April 2020 from five databases. Of 14,007 articles identified, 16 met inclusion criteria focusing on five topics: diet and weight (n = 5), body image (n = 2), sexual health (n = 7), physical activity (n = 1) and bullying (n = 1). Positive child outcomes were associated with positive general parent-child communication characterised by warmth, openness and allowing children choice. Conversely, hostility, negative and inconsistent messaging were associated with poorer outcomes. Interventions to increase parent-child communication could be classified as providing single directive messages, media campaigns or intensive support. Single messages increased communication frequency; media campaigns and intensive interventions showed mixed outcomes. No differences in outcomes were found according to child's gender or socio-economic status. Generally, parents were less confident in initiating, rather than continuing, conversations and were more likely to initiate conversations when they felt they had good topic knowledge. While the relatively small, diverse sample limits the strength of these findings, this review provides provisional support for approaches to promote positive parent-child communication about health that are associated with better child health and wellbeing.

Effect of high-flow vs. low-flow nasal plus mouthguard oxygen therapy on hypoxaemia during sedation: a multicentre randomised controlled trial.

Whether high-flow vs. low-flow nasal oxygen reduces hypoxaemia for sedation during endoscopic retrograde cholangiopancreatography is currently unknown. In this multicentre trial, 132 patients ASA physical status 3 or higher, BMI > 30 kg.m-2 or with known or suspected obstructive sleep apnoea were randomly allocated to high-flow nasal oxygen up to 60 l.min-1 at 100% FI O2 or low-flow nasal oxygen at 4 l.min-1 . The low-flow nasal oxygen group also received oxygen at 4 l.min-1 through an oxygenating mouthguard, totalling 8 l.min-1 . Primary outcome was hypoxaemia, defined as Sp O2 < 90% regardless of duration. Hypoxaemia occurred in 7.7% (5/65) of patients with high-flow and 9.1% (6/66) with low-flow nasal oxygen (percentage point difference -1.4%, 95%CI -10.9 to 8.0; p = 0.77). Between the groups, there were no significant differences in frequency of hypoxaemic episodes; lowest Sp O2 ; peak transcutaneous carbon dioxide; hypercarbia (transcutaneous carbon dioxide > 2.66 kPa from baseline); requirement of chin lift/jaw thrust; nasopharyngeal airway insertion; bag-mask ventilation; or tracheal intubation. Following adjustment for duration of the procedure, the primary outcome remained non-significant. In high-risk patients undergoing endoscopic retrograde cholangiopancreatography, oxygen therapy with high-flow nasal oxygen did not reduce the rate of hypoxaemia, hypercarbia or the need for airway interventions, compared with combined oral and nasal low-flow oxygen.

Promoting the get healthy information and coaching service (GHS) in Australian-Chinese communities: facilitators and barriers.

Obesity and being overweight are major public health concerns that health coaching can assist people to manage through encouraging self-management and behaviour change. The Get Healthy Information and Coaching Service (GHS) is a telephone health coaching service in Australia that has effectively improved the health of the general population but has had less participation of culturally and linguistically diverse (CALD) populations. The Chinese population is the largest migrant group in Australia with increased risk of diabetes but had reduced access to the GHS program due to communication barriers. The GHS developed a pilot program for Chinese (Mandarin and Cantonese-speaking) communities using bilingual coaches and translated material to address these barriers. Qualitative research was undertaken with Chinese stakeholders (14 interviews) and 11 program participants from the group which had completed the program (2 focus groups in Mandarin and Cantonese) to understand their experiences and the success of promotional activities. This research does not contain the experiences of the people that withdrew from the program. The bilingual program was culturally and linguistically appropriate and addressed risk factors for chronic conditions. Participants formed positive relationships with bilingual coaches who they preferred to interpreters. They felt the program promoted healthy eating, weight and physical activity. Although Chinese stakeholders had concerns about participants' ability to goal set, participants said they met their health goals and were committed to the GHS program. Strategies to enhance the program included promoting the bilingual GHS to the communities and stakeholders. Factors to consider beyond language in adapting the program to the Australian Chinese communities include meeting the heterogenous needs of the older population, ensuring community engagement and addressing cultural beliefs and practices.

Obesity and being overweight are major public health concerns that health coaching can assist people to manage. The Get Healthy Information and Coaching Service (GHS) is a government telephone health coaching service that has improved the health of the general population but has had less participation of culturally and linguistically diverse populations. The Chinese population is the largest migrant group in Australia with increased risk of diabetes but had reduced access to the GHS program due to communication barriers. The GHS developed a pilot program for Chinese (Mandarin and Cantonese-speaking) communities using bilingual coaches and translated material. Findings from 14 interviews with Chinese stakeholders and two focus groups (in Mandarin and Cantonese) with program participants sought to understand their experiences and success of promotional activities. Results demonstrated the bilingual program was culturally and linguistically appropriate. Participants formed positive relationships with coaches and felt the service promoted healthy eating and weight, and physical activity. Although Chinese stakeholders had concerns about participants' cultural familiarity with goal setting and achieving long-term change, participants said that they met their goals and were committed to the program. Strategies to enhance the program will include promoting the bilingual GHS to the communities and stakeholders.

Scabies polymerase chain reaction with standardized dry swab sampling: an easy tool for cluster diagnosis of human scabies.

BACKGROUND: Expert visualization of Sarcoptes scabiei remains essential for diagnosing human scabies, but access to said experts can be difficult. Polymerase chain reaction (PCR) is a specific tool for the detection and confirmation of S. scabiei but has poor sensitivity. OBJECTIVES: To evaluate PCR as a diagnostic method for scabies using nonexpert-dependent standardized sampling. METHODS: The dry swab was systematically rubbed across the front of both wrists, the eight interdigital spaces and on any suspected scabies lesions in all patients referred for scabies. A new PCR-based diagnostic test was run on the samples. All patients underwent clinical and dermoscopic examination. Scabies diagnosis was confirmed when dermoscopic examination was positive or the patient had typical clinical signs of scabies. RESULTS: Of 183 suspected cases of scabies, 164 patients were sampled, 87 had confirmed scabies (dermoscopy positive n = 87, typical clinical signs n = 1) and 77 did not. Of the 87 patients with proved scabies, 33 patients had positive scabies PCR, resulting in a 37·9% [95% confidence interval (CI) 28·4-48·4%] sensitivity and a 61·7% (95% CI 52·4-72·7%) negative predictive value. None of the 77 patients ruled out for scabies had a positive PCR result. CONCLUSIONS: This method is nontraumatic, repeatable and non-expert-dependent. It shows sensitivity similar to previous studies involving expert skin scraping. However, this method facilitates the multiplication of sampling, which increased the sensitivity for cluster scabies diagnosis. This method may be suitable as a first-line diagnosis tool where a large cluster scabies outbreak is suspected. What's already known about this topic? Scabies diagnosis requires expertise. Scabies polymerase chain reaction (PCR) is specific but has poor sensitivity. Poor sensitivity is the consequence of the low efficiency of sampling methods. What does this study add? This PCR-based diagnostic method based on nontraumatic standardized skin sampling is not expert-dependent and is reproducible. This diagnostic method may be relevant as a non-expert sentinel diagnosis tool in large clusters where a scabies outbreak is suspected.

Population, general practitioner and practice characteristics are associated with screening procedures for microvascular complications in Type 2 diabetes care in Norway.

AIMS: To assess population, general practitioner (GP) and practice characteristics associated with the performance of microvascular screening procedures and to propose strategies to improve Type 2 diabetes care. METHODS: A cross-sectional survey in Norway (281 GPs from 77 practices) identified 8246 people with a Type 2 diabetes duration of 1 year or more. We used multilevel regression models with either the recording of at least two of three recommended screening procedures (albuminuria, monofilament, eye examination) or each procedure separately as dependent variable (yes/no), and characteristics related to the person with diabetes, GP or practice as independent variables. RESULTS: The performance of recommended screening procedures was recorded in the following percentages: albuminuria 31.5%, monofilament 27.5% and eye examination 60.0%. There was substantial heterogeneity between practices, and between GPs within practices for all procedures. Compared with people aged 60-69 years, those aged < 50 years were less likely to have an albuminuria test performed [odds ratio (OR) 0.75, 95% CI 0.61 to 0.93] and eye examination (OR 0.79, 95% CI 0.66 to 0.95). People with macrovascular disease had fewer screening procedures recorded (OR 0.68, 95% CI 0.59 to 0.78). Use of an electronic diabetes form was associated with improved screening  (OR 2.65, 95% CI 1.86 to 3.78). GPs with high workload recorded fewer procedures (OR 0.59, 95% CI 0.39 to 0.90). CONCLUSIONS: Performance of screening procedures was suboptimal overall, and in people who should be prioritized. Performance varied substantially between GPs and practices. The use of a structured diabetes form should be mandatory.

Host choice and fitness of anemonefish Amphiprion ocellaris (Perciformes: Pomacentridae) living with host anemones (Anthozoa: Actiniaria) in captive conditions.

In this study, we investigated the host choice of naïve Amphiprion ocellaris, a specialist, at two different stages of development (newly settling juveniles and post-settlement juveniles). The fish were exposed to their natural and unnatural host species in the laboratory and their fitness was assessed in terms of activity and growth rate. Newly settling juveniles exhibited little host preference, while post-settlement juveniles immediately associated with their most common host in the wild. The analysis of fish activity confirmed that A. ocellaris is diurnal; they are most active in the morning, less at midday and barely move at night. The average travelling distance of juveniles was shorter in the groups living with their natural host, increasing in the groups living with an unnatural host and was highest in groups that did not become associated with any other unnatural host species. Post-settlement juveniles living with the natural host species grew better than those living with unnatural hosts or without anemone contact. These results suggest that the welfare of A. ocellaris in captivity will be optimized by keeping them with their natural anemone host species, although more generalist Amphiprion species may survive in association with other hosts.

A systematic review and meta-analysis of utility estimates in melanoma.

BACKGROUND: Health-related quality of life (HRQOL) in melanoma is affected by cancer stage. Previous studies have reported limited data on utility-based HRQOL. OBJECTIVES: To determine pooled estimates of utility-based HRQOL (utilities) for people with American Joint Cancer Committee stage I/II, III or IV melanoma for use in economic evaluations. METHODS: We performed a systematic review, meta-analysis and metaregression of utilities for patients with melanoma. HRQOL scores reported with the QLQ-C30, SF-36, SF-12, FACT-G and FACT-M instruments were converted to utilities using published mapping algorithms. Meta-analysis was used to calculate mean utilities. Metaregression was used to examine the effects of baseline patient and study characteristics. RESULTS: We identified 33 studies reporting 213 utilities. From meta-analyses, the mean utility for stage I/II melanoma was 0·97 [95% confidence interval (CI) 0·90-0·98]; for stage III melanoma it was 0·77 (95% CI 0·70-0·83); for stage III/IV 0·76 (95% CI 0·76-0·77); and for stage IV melanoma 0·76 (95% CI 0·71-0·81). The difference in utility between stage III and stage IV was not statistically significant (P = 0·52). For patients with stage I/II, the utility estimate at the time of surgery was 0·77 (95% CI 0·75-0·79), and at 3-12 months postsurgery it was 0·85 (95% CI 0·84-0·86). Utility estimates for patients with stage IV melanoma were 0·65 (95% CI 0·62-0·69) during the first 3 months of treatment and 0·83 (95% CI 0·81-0·86) at 4-12 months on treatment. For patients with stage IV melanoma treated with chemotherapy, the utility estimate was 0·52 (95% CI 0·51-0·52), while for those treated with targeted therapy it was 0·83 (95% CI 0·82-0·85). CONCLUSIONS: These robust, evidence-based estimates of health state utility can be used in economic evaluations of new treatments for patients with early-stage or advanced-stage melanoma.

Observation of chemically protected polydimethylsiloxane: towards crack-free PDMS.

The current modification of polydimethylsiloxane (PDMS) substrates via oxygen plasma treatment causes surface cracks. Here, we demonstrate a method to prevent crack formation by chemical treatment. Chemical modification renders the surface hydrophilic for several days and is effective in preserving the elasticity of the PDMS surface at the nanoscale level.

A spatial and temporal analysis of paediatric central nervous system infections from 2005 to 2015 in Ho Chi Minh City, Vietnam.

Central nervous system infections (CNSI) are a leading cause of death and long-term disability in children. Using ICD-10 data from 2005 to 2015 from three central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized additive mixed models (GAMM) to examine the spatial-temporal distribution and spatial and climatic risk factors of paediatric CNSI, excluding tuberculous meningitis, in this setting. From 2005 to 2015, there were 9469 cases of paediatric CNSI; 33% were ⩽1 year old at admission and were mainly diagnosed with presumed bacterial CNSI (BI) (79%), the remainder were >1 year old and mainly diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of HCMC in proximity to the hospitals as well as some outer districts had the highest incidences of BI and non-BI; BI incidence was higher in the dry season. Monthly BI incidence exhibited a significant decreasing trend over the study. Both BI and non-BI were significantly associated with lags in monthly average temperature, rainfall, and river water level. Our findings add new insights into this important group of infections in Vietnam, and highlight where resources for the prevention and control of paediatric CNSI should be allocated.

A comparison of the effects of medical Qigong and standard exercise therapy on symptoms and quality of life in patients with advanced cancer.

PURPOSE: Patients with advanced cancer frequently experience anxiety, depression and poor quality of life (QOL), as well as physical symptoms such as fatigue and weakness. Physical exercise has potential to help control these symptoms but the optimal training prescription is still not clear. We performed a study comparing medical Qigong (QG) and standard endurance and strength training (SET) in patients with advanced stage non-small cell lung (NSCLC) and gastrointestinal (GI) cancers. METHODS: A randomized, cross-over study was performed in patients with advanced NSCLC and GI cancers receiving or eligible for chemotherapy. Patients received supervised QG or SET twice-weekly for 6 weeks. Psychological functioning, QOL, symptoms and physical functioning were assessed before and after each intervention period. RESULTS: Nineteen patients completed both interventions. Comparing interventions revealed no difference between QG and SET on change in anxiety or depression scores or QOL. However, SET treatment was better at improving perceived strength (P = 0.05) and walking distance (P = 0.02). The order in which interventions were performed had a significant impact on the improvement in certain symptoms (sleep quality, breathlessness, P < 0.05), QOL (P = 0.01) and walking distance (P = 0.008). In all cases, the beneficial effects of the exercise interventions were markedly reduced during the second interval. CONCLUSIONS: QG and SET are equivalent in their impact on many aspects of psychological function in cancer patients. However, SET leads to greater improvements in exercise capacity and helps reduce some symptoms. The reduction in beneficial effect of SET on exercise function when offered as the second intervention is a new finding that warrants further study.

Environmental factors and public health policy associated with human and rodent infection by leptospirosis: a land cover-based study in Nan province, Thailand.

Leptospirosis incidence has increased markedly since 1995 in Thailand, with the eastern and northern parts being the most affected regions, particularly during flooding events. Here, we attempt to overview the evolution of human prevalence during the past decade and identify the environmental factors that correlate with the incidence of leptospirosis and the clinical incidence in humans. We used an extensive survey of Leptospira infection in rodents conducted in 2008 and 2009 and the human incidence of the disease from 2003 to 2012 in 168 villages of two districts of Nan province in Northern Thailand. Using an ad-hoc developed land-use cover implemented in a geographical information system we showed that humans and rodents were not infected in the same environment/habitat in the land-use cover. High village prevalence was observed in open habitat near rivers for the whole decade, or in 2008-2009 mostly in rice fields prone to flooding, whereas infected rodents (2008-2009) were observed in patchy habitat with high forest cover, mostly situated on sloping ground areas. We also investigated the potential effects of public health campaigns conducted after the dramatic flood event of 2006. We showed that, before 2006, human incidence in villages was explained by the population size of the village according to the environmental source of infection of this disease, while as a result of the campaigns, human incidence in villages after 2006 appeared independent of their population size. This study confirms the role of the environment and particularly land use, in the transmission of bacteria, emphasized by the effects of the provincial public health campaigns on the epidemiological pattern of incidence, and questions the role of rodents as reservoirs.

Screening of pigmented Bacillus aquimaris SH6 from the intestinal tracts of shrimp to develop a novel feed supplement for shrimp.

AIMS: To develop a novel feed supplement for shrimp using pigmented spore-forming bacterial strains isolated from their gastrointestinal tracts. METHODS AND RESULTS: Eight pigmented Bacillus strains were selected from the isolates based on high production of heat-stable spores, typical UV-Vis spectra of produced carotenoids (400-550 nm), and free radical scavenging activity of their extracts. Of the eight strains, the red-orange pigmented Bacillus aquimaris SH6 was selected because it showed the highest abundance in shrimp guts (70% population). Whiteleg shrimp (n = 30 per group) fed with SH6 spores, at >3 × 106  CFU g-1  pellet for 4 weeks had redder colour (score of 21-23 vs 20-22), 2·7-fold higher astaxanthin level (0·69 vs 0·25 µg g-1 shrimp), 34% higher weight gain (7·18 vs 5·32 g shrimp-1 ), and 85% higher phenoloxidase activity (OD490  = 0·265 vs 0·143) than shrimp in the control group. CONCLUSIONS: The result supports the potential use of B. aquimaris SH6 as a feed supplement for promoting the colourization and weight gain, and for enhancing innate immunity of whiteleg shrimp. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates that carotenoids produced by B. aquimaris SH6 can be successfully absorbed and converted to astaxanthin in whiteleg shrimp.

2,3,7,8-Tetrachlorodibenzo-p-dioxin in breast milk increases autistic traits of 3-year-old children in Vietnam.

Dioxin levels in the breast milk of mothers residing near a contaminated former airbase in Vietnam remain much higher than in unsprayed areas, suggesting high perinatal dioxin exposure for their infants. The present study investigated the association of perinatal dioxin exposure with autistic traits in 153 3-year-old children living in a contaminated area in Vietnam. The children were followed up from birth using the neurodevelopmental battery Bayley-III. The high-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed groups (⩾3.5 pg per g fat) showed significantly higher Autism Spectrum Rating Scale (ASRS) scores for both boys and girls than the mild-TCDD exposed groups, without differences in neurodevelopmental scores. In contrast, the high total dioxin-exposed group, indicated by polychlorinated dibenzo-p-dioxins/furans (PCDDs/Fs)--the toxic equivalents (TEQ) levels⩾17.9 pg-TEQ per g fat, had significantly lower neurodevelopmental scores than the mild-exposed group in boys, but there was no difference in the ASRS scores. The present study demonstrates a specific impact of perinatal TCDD on autistic traits in childhood, which is different from the neurotoxicity of total dioxins (PCDDs/Fs).

A pilot comparison study of four clinician-rated atopic dermatitis severity scales.

BACKGROUND: There are multiple severity outcome measures for atopic dermatitis (AD). There is a need to compare the reliability of these measures. OBJECTIVES: To compare the inter-rater and intrarater reliability of the objective Scoring Atopic Dermatitis (oSCORAD), Eczema Area and Severity Index (EASI), Six Area, Six Sign Atopic Dermatitis (SASSAD) and Three Item Severity index (TIS); and to analyse the correlation between these outcome measures and the quality-of-life instruments Patient-Orientated Eczema Measurement, Dermatology Life Quality Index and Skindex-29. METHODS: Twelve patients with AD attended a 1-day scoring exercise by five trained dermatology clinicians. Inter-rater and intrarater reliability were assessed using the intraclass correlation coefficient (ICC). Correlation between clinician-rated and patient-reported measures was analysed using Spearman's rho. RESULTS: Regarding inter-rater reliability, EASI and SASSAD showed good reliabilities, with ICCs of 0·730 [95% confidence interval (CI) 0·500-0·900] and 0·680 (95% CI 0·440-0·880), respectively. However, the ICCs were poor for TIS and oSCORAD, with 0·497 (95% CI 0·233-0·785) and 0·498 (95% CI 0·234-0·785), respectively. Separate body surface area (BSA) component analyses showed that the oSCORAD BSA component contributed to its inter-rater variations. Regarding intrarater reliability, EASI and TIS showed excellent ICCs of 0·886 (95% CI 0·744-0·952) and 0·820 (0·614-0·923), respectively, while SASSAD showed a good reliability with an ICC of 0·720 (95% CI 0·424-0·878). However, the intrarater ICC was poor for oSCORAD, with 0·446 (95% CI 0·037-0·730). Regarding correlation with patient-reported measures, only SASSAD demonstrated moderate correlation with Skindex-29 (ρ = 0·611, P = 0·035). CONCLUSIONS: EASI demonstrated the highest inter-rater and intrarater reliability, supporting it as the optimal AD severity outcome measure.

γ-Aminoalcohol rearrangement applied to pentahydroxylated azepanes provides pyrrolidines epimeric to homoDMDP.

A series of pentahydroxylated pyrrolidines, displaying five contiguous stereogenic centres and epimeric to α-glucosidase inhibitor homoDMDP, have been synthesized. The key step involves a γ-aminoalcohol rearrangement applied to polyhydroxylated azepanes. These five-membered iminosugars demonstrate micromolar inhibition of glycosidases.

Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment.

This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4(+) T cell count, 104 cells/µl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid Cmax and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of rifampin and isoniazid when coadministered with nevirapine or efavirenz were not altered to a clinically significant extent in these severely immunosuppressed HIV-infected patients. Patients experienced favorable clinical outcomes. (This study has been registered at ClinicalTrials.gov under registration no. NCT00495326.).

Variability of fibrinolytic activity in pregnant patients exposed to tissue plasminogen activator: an in vitro study utilizing rotational thromboelastometry.

BACKGROUND: The investigation into the variability of fibrinolysis in obstetric patients is notably limited despite its relevance to postpartum hemorrhage. We investigate an in vitro model of fibrinolysis measured by rotational thromboelastrometry (ROTEM) in maternal blood samples with lysis stimulated by tissue plasminogen activator (tPA). METHODS: Written informed consent was obtained from 19 patients at term pregnancy during admission to the labor and delivery unit. Patients who were taking medication affecting coagulation were excluded. Tissue plasminogen activator was added to whole blood samples to a final concentration of 100 or 220 ng/mL prior to ROTEM testing. RESULTS: The addition of tPA produced high intra-individual fibrinolytic variability for clot firmness and lysis parameters. Patients responded differently to each tPA dose ranging from clot lysis within the range of 0 ng/mL tPA group to complete clot lysis. The coefficient of variation (CV) values for the 220 ng/mL tPA group were: EXTEM MCF 0.510, EXTEM LI30 1.601, FIBTEM MCF 0.349, FIBTEM LI30 2.097. CV values for the 100 ng/mL tPA group were: EXTEM MCF 0.144, EXTEM LI30 1.038, FIBTEM MCF 0.096, FIBTEM LI30 1.238. CONCLUSION: We demonstrate a wide range of fibrinolytic response in the obstetric population to exogeneous tPA. We found subgroups of patients that were very responsive to tPA and insensitive to tPA. This study represents a preliminary exploration into classifying the obstetric fibrinolytic phenotypes. Further research will integrate relevant coagulation factors to establish a predictive model for testing susceptibility to lysis that can be applied at the point of care.

A PTHrP Gradient Drives Mandibular Condylar Chondrogenesis via Runx2.

The mandibular condylar cartilage (MCC) is an essential component of the temporomandibular joint, which orchestrates the vertical growth of the mandibular ramus through endochondral ossification with distinctive modes of cell differentiation. Parathyroid hormone-related protein (PTHrP) is a master regulator of chondrogenesis; in the long bone epiphyseal growth plate, PTHrP expressed by resting zone chondrocytes promotes chondrocyte proliferation in the adjacent layer. However, how PTHrP regulates chondrogenesis in the MCC remains largely unclear. In this study, we used a Pthrp-mCherry knock-in reporter strain to map the localization of PTHrP+ cells in the MCC and define the function of PTHrP in the growing mandibular condyle. In the postnatal MCC of PthrpmCherry/+ mice, PTHrP-mCherry was specifically expressed by cells in the superficial layer immediately adjacent to RUNX2-expressing cells in the polymorphic layer. PTHrP ligands diffused across the polymorphic and chondrocyte layers where its cognate receptor PTH1R was abundantly expressed. We further analyzed the mandibular condyle of PthrpmCherry/mCherry mice lacking functional PTHrP protein (PTHrP-KO). At embryonic day (E) 18.5, the condylar process and MCC were significantly truncated in the PTHrP-KO mandible, which was associated with a significant reduction in cell proliferation across the polymorphic layer and a loss of SOX9+ cells in the chondrocyte layers. The PTHrP-KO MCC showed a transient increase in the number of Col10a1+ hypertrophic chondrocytes at E15.5, followed by a significant loss of these cells at E18.5, indicating that superficial layer-derived PTHrP prevents premature chondrocyte exhaustion in the MCC. The expression of Runx2, but not Sp7, was significantly reduced in the polymorphic layer of the PTHrP-KO MCC. Therefore, PTHrP released from cells in the superficial layer directly acts on cells in the polymorphic layer to promote proliferation of chondrocyte precursor cells and prevent their premature differentiation by maintaining Runx2 expression, revealing a unique PTHrP gradient-directed mechanism that regulates MCC chondrogenesis.

Oral health education strategies for patients living with cardiovascular disease within hospital settings: a scoping review.

Objective: To identify and describe the impact of current oral health education programmes provided to patients in cardiology hospital wards and outpatient clinics. Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews statement. Searches were conducted using electronic databases: Cochrane, Medline, and Scopus, as well as grey literature searching. Results: Three eligible studies were identified. All included studies reported generalised poor oral health in their participants at baseline, with significant improvement at follow-up. They all reported significant reductions in plaque deposits and gingival bleeding. One study reported significantly less bacteria on participant tongues, as well as fewer days with post-operative atrial fibrillation in the intervention group. Furthermore, in this study, one patient in the intervention group developed pneumonia, whilst four patients in the control group did. Conclusion: Oral health education for patients with cardiovascular disease is limited and many have poor oral health. Educational programmes to improve oral health behaviours in patients with cardiovascular disease can improve both oral and general health outcomes. Implications for public health: Oral disease is a modifiable risk factor for cardiovascular disease. Integrating oral health education into cardiology hospital settings is a simple strategy to improve access to oral health information and improve both oral and cardiovascular outcomes.