Patients requiring pediatric palliative care for advanced heart disease in France: A descriptive study.

INTRODUCTION: Pediatric palliative care (PPC) teams address unmet needs and improve the quality of life of patients with life-limiting conditions across pediatric subspecialties. However, little is known about the timing, reasons, and nature of PPC team interventions in advanced heart diseases (AHD). OBJECTIVES: Here we describe how, when, and why PPC teams interact with referred teams of children suffering from AHD. METHODS: We conducted a retrospective nationwide survey among PPC teams in France. All patients referred to participating PPC teams for a cardiologic disease in 2019 were studied. RESULTS: Among six PPC teams, 18 patients with AHD had a PPC consultation in 2019. Six of these patients had cardiomyopathy and 12 had congenital heart disease (CHD). The median age at referral was 0.9 months for CHD and 72 months for cardiomyopathy. An antenatal diagnosis had been made for six families with CHD, and two of them were referred to PPC before birth allowing for a prenatal palliative care plan. The main reason for referral was ethical considerations (50%) followed by organization for home-based palliative care (28%). PPC teams participated in ethical discussions when asked to but also provided family support (12/18), home-based PPC (9/18), coordination of care (5/18), support of the referred team (4/18), and symptoms management (3/18) CONCLUSION: The main reason for referral to PPC was ethical considerations, but PPC interventions followed a holistic model of care. Prospective outcomes measurement and partnerships should be further developed.

Use of an intragastric balloon for management of obesity in a dog.

While various bariatric surgeries are commonplace in obesity medicine for humans, these techniques have not been commonly used in veterinary medicine. A technique used in humans consists in endoscopically placing an intragastric balloon. The intragastric balloon takes volume in the stomach causing a feeling of satiety and reducing food intake. A 57.6 kg, 9-year-old neutered female Labrador dog with chronic hypothyroidism was presented for overweight management. Combined levothyroxine treatment and dietary management with specific alimentation for obesity had failed to control overweight. An intragastric balloon was placed endoscopically in the stomach to allow the reduction of the gastric capacity and resulted in effective weight loss. The dog weight decreased to 40.9 kg at the time of intragastric balloon removal 198 days after placement. Further research including a larger sample size and long term follow-up is required to establish safety and effectiveness of this procedure.

Analysis of radioprotection and antimutagenic effects of Ilex paraguariensis infusion and its component rutin.

DNA repair pathways, cell cycle checkpoints, and redox protection systems are essential factors for securing genomic stability. The aim of the present study was to analyze the effect of Ilex paraguariensis (Ip) infusion and one of its polyphenolic components rutin on cellular and molecular damage induced by ionizing radiation. Ip is a beverage drank by most inhabitants of Argentina, Paraguay, Southern Brazil, and Uruguay. The yeast Saccharomyces cerevisiae (SC7Klys 2-3) was used as the eukaryotic model. Exponentially growing cells were exposed to gamma rays (γ) in the presence or absence of Ip or rutin. The concentrations used simulated those found in the habitual infusion. Surviving fractions, mutation frequency, and DNA double-strand breaks (DSB) were determined after treatments. A significant increase in surviving fractions after gamma irradiation was observed following combined exposure to γ+R, or γ+Ip. Upon these concomitant treatments, mutation and DSB frequency decreased significantly. In the mutant strain deficient in MEC1, a significant increase in γ sensitivity and a low effect of rutin on γ-induced chromosomal fragmentation was observed. Results were interpreted in the framework of a model of interaction between radiation-induced free radicals, DNA repair pathways, and checkpoint controls, where the DNA damage that induced activation of MEC1 nodal point of the network could be modulated by Ip components including rutin. Furthermore, ionizing radiation-induced redox cascades can be interrupted by rutin potential and other protectors contained in Ip.

Analysis of radioprotection and antimutagenic effects of Ilex paraguariensis infusion and its component rutin

DNA repair pathways, cell cycle checkpoints, and redox protection systems are essential factors for securing genomic stability. The aim of the present study was to analyze the effect of Ilex paraguariensis (Ip) infusion and one of its polyphenolic components rutin on cellular and molecular damage induced by ionizing radiation. Ip is a beverage drank by most inhabitants of Argentina, Paraguay, Southern Brazil, and Uruguay. The yeast Saccharomyces cerevisiae (SC7Klys 2-3) was used as the eukaryotic model. Exponentially growing cells were exposed to gamma rays (γ) in the presence or absence of Ip or rutin. The concentrations used simulated those found in the habitual infusion. Surviving fractions, mutation frequency, and DNA double-strand breaks (DSB) were determined after treatments. A significant increase in surviving fractions after gamma irradiation was observed following combined exposure to γ+R, or γ+Ip. Upon these concomitant treatments, mutation and DSB frequency decreased significantly. In the mutant strain deficient in MEC1, a significant increase in γ sensitivity and a low effect of rutin on γ-induced chromosomal fragmentation was observed. Results were interpreted in the framework of a model of interaction between radiation-induced free radicals, DNA repair pathways, and checkpoint controls, where the DNA damage that induced activation of MEC1 nodal point of the network could be modulated by Ip components including rutin. Furthermore, ionizing radiation-induced redox cascades can be interrupted by rutin potential and other protectors contained in Ip.

Effects of forested floodplain soil properties on phosphorous concentrations in two Chesapeake Bay sub-watersheds, Virginia, USA.

Aquatic ecosystems are known to undergo fluctuations in nutrient levels as a result of both natural and anthropogenic processes. Changes in both extrinsic and intrinsic fluvial dynamics necessitate constant monitoring as anthropogenic alterations exert new pressures to previously stable river basins. In this study, we analyzed stream water and riparian zone soil phosphorous (P) dynamics in two third-order sub-watersheds of the lower Chesapeake Bay in Virginia, USA. The Ni River is predominantly forested (70 % forested), and Sugarland Run is a more human impacted (>45 % impervious surfaces) sub-watershed located in the suburbs of Washington D.C. Total stream P concentrations were measured during both high and low flows and Mehlich-3 methods were used to evaluate potential P fluxes in riparian soils. The results show total stream P concentrations in Sugarland Run ranged from 0.002 to 0.20 ppm, with an average of 0.054 ppm. In contrast, the forested Ni River had typical stream P concentrations <0.01 ppm. Total soil P was significantly higher in the more urbanized Sugarland Run basin (23.8 ± 2.1 ppm) compared to the Ni River basin (16 ± 3.7 ppm). Average stream bank erosion rates and corresponding cut-bank P flux rates were estimated to be 7.98 cm year(-1) and 361 kg P year(-1) for Ni River and 9.84 cm year(-1) and 11,600 kg P year(-1) for Sugarland Run, respectively. The significantly higher values of total P in the stream water and floodplain cut-banks of Sugarland Run suggests erosion and resuspension of previously deposited legacy sediments is an important processes in this human-impacted basin.

High sensitive mesoporous TiO2-coated love wave device for heavy metal detection.

This work deals with the design of a highly sensitive whole cell-based biosensor for heavy metal detection in liquid medium. The biosensor is constituted of a Love wave sensor coated with a polyelectrolyte multilayer (PEM). Escherichia coli bacteria are used as bioreceptors as their viscoelastic properties are influenced by toxic heavy metals. The acoustic sensor is constituted of a quartz substrate with interdigitated transducers and a SiO2 guiding layer. However, SiO2 shows some degradation when used in a saline medium. Mesoporous TiO2 presents good mechanical and chemical stability and offers a high active surface area. Then, the addition of a thin titania layer dip-coated onto the acoustic path of the sensor is proposed to overcome the silica degradation and to improve the mass effect sensitivity of the acoustic device. PEM and bacteria deposition, and heavy metal influence, are real time monitored through the resonance frequency variations of the acoustic device. The first polyelectrolyte layer is inserted through the titania mesoporosity, favouring rigid link of the PEM on the sensor and improving the device sensitivity. Also, the mesoporosity of surface increases the specific surface area which can be occupied and favors the formation of homogeneous PEM. It was found a frequency shift near -20±1 kHz for bacteria immobilization with titania film instead of -7±3 kHz with bare silica surface. The sensitivity is highlighted towards cadmium detection. Moreover, in this paper, particular attention is given to the immobilization of bacteria and to biosensor lifetime. Atomic Force Microscopy characterizations of the biosurface have been done for several weeks. They showed significant morphological differences depending on the bacterial life time. We noticed that the lifetime of the biosensor is longer in the case of using a mesoporous TiO2 layer.

HMGB1 mediates splenomegaly and expansion of splenic CD11b+ Ly-6C(high) inflammatory monocytes in murine sepsis survivors.

BACKGROUND: More than 500,000 hospitalized patients survive severe sepsis annually in the USA. Recent epidemiological evidence, however, demonstrated that these survivors have significant morbidity and mortality, with 3-year fatality rates higher than 70%. To investigate the mechanisms underlying persistent functional impairment in sepsis survivors, here we developed a model to study severe sepsis survivors following cecal ligation and puncture (CLP). METHODS: Sepsis was induced in mice by CLP and survivors were followed for twelve weeks. Spleen and blood were collected and analyzed at different time points post-sepsis. RESULTS: We observed that sepsis survivors developed significant splenomegaly. Analysis of the splenic cellular compartments revealed a major expansion of the inflammatory CD11b+ Ly-6CHigh pool. Serum high-mobility group box 1 (HMGB1) levels in the sepsis surviving mice were significantly elevated for 4-6 weeks after post-sepsis, and administration of an anti-HMGB1 monoclonal antibody significantly attenuated splenomegaly as well as splenocyte priming. Administration of recombinant HMGB1 to naive mice induced similar splenomegaly, leukocytosis and splenocyte priming as observed in sepsis survivors. Interestingly analysis of circulating HMGB1 from sepsis survivors by mass spectroscopy demonstrated a stepwise increase of reduced form of HMGB1 (with known chemo-attractant properties) during the first 3 weeks, followed by disulphide form (with known inflammatory properties) 4-8 weeks after CLP. DISCUSSION: Our results indicate that prolonged elevation of HMGB1 is a necessary and sufficient mediator of splenomegaly and splenocyte expansion, as well as splenocyte inflammatory priming in murine severe sepsis survivors.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

Tuberculosis and noncommunicable diseases: neglected links and missed opportunities.

Globally, the incidence of tuberculosis (TB) is declining very slowly, and the noncommunicable disease (NCD) burden for many countries is steadily increasing. Several NCDs, such as diabetes mellitus, alcohol use disorders and smoking-related conditions, are responsible for a significant proportion of TB cases globally, and in the European region, represent a larger attributable fraction for TB disease than HIV. Concrete steps are needed to address NCDs and their risk factors. We reviewed published studies involving TB and NCDs, and present a review and discussion of how they are linked, the implications for case detection and management, and how prevention efforts may be strengthened by integration of services. These NCDs put patients at increased risk for developing TB and at risk for poor treatment outcomes. However, they also present an opportunity to provide better care through increased case-detection activities, improved clinical management and better access to care for both TB and NCDs. Hastening the global decline in TB incidence may be assisted by strengthening these types of activities.

TB contact investigations: 12 years of experience in the National TB Programme, Morocco 1993-2004.

We reviewed data collected from 1993 to 2004 as part of the routine activities of the national tuberculosis (TB) control programme (NTP) in Morocco. More than 1 million household TB contacts were identified in approximately 200,000 investigations. On average, 77% of identified contacts were screened every year; overall prevalence was 2.5%. The proportion of TB cases identified in household contacts of registered cases was 5.6%. This was significantly higher in children under 10 years and in patients registered and diagnosed with symptomatic primary complex. Performing TB contact investigations as part of the routine activities of NTP services is feasible in low-middle-income countries.

Results of the feasibility test of the Practical Approach to Lung Health in the Syrian Arab Republic.

We assessed implementation of the Practical Approach to Lung Health (PAL) in primary care facilities in the Syrian Arab Republic and its short-term impact on respiratory care in patients aged 5+ years. After training on PAL for 76 general practitioners in 75 health centres, referrals and sputum smear examinations for patients increased. The mean number of drugs prescribed per patient decreased by 14.8% and that of antibiotics by 33.3%, while prescriptions for inhaled medications increased. The mean cost of drug prescriptions fell by 26.2%.

Training on the Practical Approach to Lung Health: effect on drug prescribing in PHC settings in Jordan.

This study assessed whether training physicians on the Practical Approach to Lung Health (PAL) reduces drug prescribing and the cost of drugs prescribed to respiratory patients in the primary health care setting. Data were compared before and after training general practitioners on standard guidelines for case management of respiratory conditions in primary care. A total of 56 general practitioners practising in 25 health centres in 3 out of 12 governorates of Jordan participated in both the baseline survey (n = 6260 respiratory patients) and the impact survey (n = 2709 patients). Training in PAL decreased by 12.2% the number of drugs prescribed per patient, increased the prescription of inhaled medications and reduced the mean cost of a drug prescription per patient by 8.7%.

Feasibility test results of the Practical Approach to Lung Health in Bishkek, Kyrgyzstan.

SETTING: Ambulatory health centres in Bishkek, Kyrgyzstan. OBJECTIVE: To assess the results of training family doctors in Practical Approach to Lung Health (PAL) techniques. DESIGN: Comparison of the results of two surveys, before (baseline) and after (impact) training on PAL guidelines. Both surveys were carried out according to the same protocol. RESULTS: A total of 86 family physicians working in three ambulatory health centres participated in both surveys. Respectively 893 and 992 respiratory patients were registered in the baseline and impact surveys. Baseline survey patients had longer duration of symptoms, were older and had more concomitant health conditions than impact survey patients. Findings suggest that PAL training has resulted in a decrease by one third in referrals to hospital or specialists or for diagnostic tests. Data do not show any improvement in tuberculosis case detection. However, in the impact survey, the number of drugs prescribed per patient decreased by 13.6% and the average cost of prescription of any drug per patient was reduced by 32.2%. CONCLUSION: The study suggests that training in standardised PAL guidelines is likely to reduce referral as well as drug prescription costs for respiratory patients. These findings need to be confirmed by further studies.

Results of the feasibility test of the Practical Approach to Lung Health in the Syrian Arab Republic

We assessed implementation of the Practical Approach to Lung Health [PAL] in primary care facilities in the Syrian Arab Republic and its short-term impact on respiratory care in patients aged 5+ years. After training on PAL for 76 general practitioners in 75 health centers, referrals and sputum smear examinations for patients increased. The mean number of drugs prescribed per patient decreased by 14.8% and that of antibiotics by 33.3%, while prescriptions for inhaled medications increased. The mean cost of drug prescriptions fell by 26.2%

TB contact investigations: 12 years of experience in the National TB Programme, Morocco 1993-2004

We reviewed data collected from 1993 to 2004 as part of the routine activities of the national tuberculosis [TB] control programme [NTP] in Morocco. More than 1 million household TB contacts were identified in approximately 200 000 investigations. On average, 77% of identified contacts were screened every year; overall prevalence was 2.5%. The proportion of TB cases identified in household contacts of registered cases was 5.6%. This was significantly higher in children under 10 years and in patients registered and diagnosed with symptomatic primary complex. Performing TB contact investigations as part of the routine activities of NTP services is feasible in low-middle-income countries

Training on the Practical Approach to Lung Health: effect on drug prescribing in PHC settings in Jordan

This study assessed whether training physicians on the Practical Approach to Lung Health [PAL] reduces drug prescribing and the cost of drugs prescribed to respiratory patients in the primary health care setting. Data were compared before and after training general practitioners on standard guidelines for case management of respiratory conditions in primary care. A total of 56 general practitioners practising in 25 health centres in 3 out of 12 governorates of Jordan participated in both the baseline survey [n = 6260 respiratory patients] and the impact survey [n = 2709 patients]. Training in PAL decreased by 12.2% the number of drugs prescribed per patient, increased the prescription of inhaled medications and reduced the mean cost of a drug prescription per patient by 8.7%

Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice.

TSAP6 (tumor suppressor-activated pathway 6), also known as Steap3, is a direct p53 transcriptional target gene. It regulates protein secretion, for example translationally controlled tumor protein (TCTP), which is implicated in tumor reversion. In keeping with the latter, we show herein that TSAP6 is a glycosylated protein present in the trans-Golgi network, endosomal-vesicular compartment and cytoplasmic membrane. To further investigate the physiological function of TSAP6, we have generated TSAP6-deficient mice. These mice exhibit microcytic anemia with abnormal reticulocyte maturation and deficient transferrin receptor downregulation, a process known to be dependent on exosomal secretion. Moreover, we provide direct evidence that exosome production is severely compromised in TSAP6-null cells. Finally, we show that the DNA damage-induced p53-dependent nonclassical exosomal secretory pathway is abrogated in TSAP6-null cells. Given the fact that exosomes are used as cell-free vaccines against cancer and that they could be involved in the biogenesis and spread of human immunodeficiency virus, it is important to understand their regulation. The results presented here provide the first genetic demonstration that exosome formation is a tightly controlled biological process dependent of TSAP6.

Improving the quality of cohort analysis by incorporating treatment outcomes of 'transferred in' TB cases.

Treatment outcomes of patients with tuberculosis (TB) who move between TB units ('transferred out') are often not incorporated in the annual cohort analysis. Experience from Morocco shows that using a simple method, the outcomes of these patients, notified as 'transferred in' cases, can be easily taken into account when compiling the annual report on treatment outcomes. With this method the treatment success rate increased in Morocco by a median of 5.8% (range 5.0-6.7), indicating that the country reached the global target of curing at least 85% of the new smear-positive TB cases detected during the period 1995-2003.