Preserved function and reduced angiogenesis potential of the quadriceps in patients with mild COPD.

BACKGROUND: Little is known about limb muscle abnormalities in mild COPD. Inactivity and systemic inflammation could play a role in the development of limb muscle dysfunction in COPD. The objective of the present study was to characterize quadriceps function, enzymatic activities and morphometry, levels of plasma inflammatory markers and physical activity levels in daily life (PAdl) in patients with mild COPD (GOLD 1). METHODS: Mid-thigh muscle cross-sectional area (MTCSA), quadriceps strength, endurance, fiber-type distribution, capillarity, pro-angiogenesis factors (VEGF-A, angiopoietin I and II) and muscle oxidative capacity were assessed in 37 patients with mild COPD and 19 controls. Systemic inflammatory markers (CRP, IL-6, TNF-α, Fibrinogen, SP-D) and PAdl were assessed. RESULTS: MTCSA, quadriceps strength and endurance were not different between COPD and controls. Capillarity and muscle oxidative capacity were all preserved in mild COPD. Reduced pro-angiogenesis factor mRNA expression was seen in COPD. The level of moderately active intensity (>3 METs) was significantly lower in mild COPD and, in multiple regression analyses, the level of physical activity was a determinant of muscle oxidative capacity and capillarization. No between-group differences were found regarding muscle oxidative stress while circulating IL-6 levels were elevated in mild COPD. CONCLUSIONS: The quadriceps muscle function was preserved in mild COPD although a reduced potential for angiogenesis was found. The reduced level of daily activities and evidence of systemic inflammation in these individuals suggest that these factors precede the development of overt limb muscle dysfunction in COPD.

Hypoxia acts through multiple signaling pathways to induce metallothionein transactivation by the metal-responsive transcription factor-1 (MTF-1).

Metal-responsive transcription factor-1 (MTF-1) is essential for the induction of genes encoding metallothionein by metals and hypoxia. Here, we studied the mechanism controlling the activation of MTF-1 by hypoxia. Hypoxia activation of Mt gene transcription is dependent on the presence of metal regulatory elements (MREs) in the promoter of Mt genes. We showed that MREa and MREd are the main elements controlling mouse Mt-1 gene induction by hypoxia. Transfection experiments in Mtf-1-null cells showed that MTF-1 is essential for induction by hypoxia. Chromatin immunoprecipitation analysis showed that MTF-1 DNA-binding activity was strongly enhanced in the presence of zinc but not by hypoxia. Notably, hypoxia inducible factor- (HIF) 1α was recruited to the Mt-1 promoter in response to hypoxia but not to zinc. MTF-1 activation was inhibited by PKC, JNK, and PI3K inhibitors and by the electron transport chain inhibitors rotenone and myxothiazol, but not by the antioxidant N-acetylcysteine. We showed that prolyl-hydroxylase inhibitors can activate MTF-1, but this activation requires the presence of HIF-1α. Finally, HIF-dependent transcription is enhanced in the presence of MTF-1 and induction of an MRE promoter is stimulated by HIF-1α, thus indicating cooperation between these 2 factors. However, coimmunoprecipitation experiments did not suggest direct interaction between MTF-1 and HIF-1α.

Childbirth-Associated Fistula and Perineal Tears Repaired on Outreach Campaigns in Remote Democratic Republic of Congo.

PURPOSE: To describe the demographics and evaluate the repair of childbirth-associated injuries leading to incontinence in patients in remote Democratic Republic of Congo (DRC). PATIENTS AND METHODS: Four surgical outreach campaigns were organised between March 2018 and October 2019. These campaigns specifically targeted women with incontinence secondary to childbirth-associated injuries. Patients were recruited on a voluntary basis, and locations included Katako-kombe (Sankuru province), Wamba (Haut Uelé province), Karawa (North Ubangi province) and Kipaka (Maniema province). Necessary care was provided along with informal teaching with local healthcare professionals. RESULTS: A total of 481 patients,14-71 years old with a mean of 32 years of age, were included in this study. The average duration of incontinence associated with a childbirth injury was 6.8 years. Vesicovaginal fistulas (277/481; 57.6%) and perineal tears (148/481; 30.8%) were predominant, while the combination of vesicovaginal and rectovaginal fistulas were seen in only 5 (1.0%) patients. Vaginal delivery (259/481; 53.9%), caesarean section (120/481; 25.0%) and laparotomy (hysterectomy) (102/481; 21.2%) were identified as the causes of the fistulas treated during the surgical campaign. Vesicovaginal fistulas were more likely to require complex repairs, as compared to rectovaginal fistulas and perineal tears (P-value <0.0001). As well, vesicovaginal fistulas were less likely to result in successful resolution of the incontinence when compared to rectovaginal fistulas and perineal tears (P-value < 0.0001). CONCLUSION: Vesicovaginal fistulas are predominant among childbirth injuries encountered in remote DRC with poorly managed vaginal deliveries being the leading cause. Cure rate of fistulas and perineal tears is high during outreach campaigns; however, long-term follow-up is limited. There remains a need to train and mentor rural medical professionals in the DRC on adequate management of obstetric emergencies.

Trends in sexual violence patterns and case management: a sex disaggregated analysis in Goma, Democratic Republic of Congo.

BACKGROUND: Both conflict and non-conflict sexual violence have been well described in the Democratic Republic of Congo (DRC). However, there is little empiric data comparing sexual violence patterns for males and females in the DRC, and little is known about how post-sexual assault care experiences may differ between the two sexes. METHODS: This was a retrospective, registry-based study at HEAL Africa Hospital. Researchers extracted and analyzed available data for all patients seeking post-sexual assault care between July 2013 and December 2017. Comparative analysis was conducted using SAS to document patterns of sexual violence among male and female survivors and to describe the clinical management of males and females seeking post-assault care. RESULTS: Between July 2013 and December 2017, the hospital provided post-sexual assault care to 1766 patients (1623 female and 93 male). Female survivors were more likely to be minors under the age 18 (p < 0.0001) with a mean age 16.5 years versus 22.3 years for males. For both sexes, approximately half of all perpetrators were civilians who were known to the survivor (friends, family members, colleagues or neighbors). After sexual assault, males (79.6%) were more likely than females (55.7%) to present to the hospital within 72 h (p-value < 0.0001). Among female patients, 12% had a positive pregnancy test at the time of presentation and another 43% received emergency contraception. Male survivors were more likely to test positive for HIV (p-value = 0.0032) and to receive HIV post-exposure prophylaxis as well as prophylactic antibiotics (p-value < 0.0001). CONCLUSIONS: In this single-centre registry, non-conflict-related sexual violence affected both women and girls as well as men and boys in North Kivu with civilian-perpetrated assaults being most common, and girls under the age of 18 being disproportionately affected. Overall, delays to seeking post-assault care appear to have decreased over time, although females presented later than males. These differences, as well as sex discrepancies in receiving HIV prophylaxis and prophylactic antibiotics, are not well understood. Additional research is needed to understand these phenomena such that equitable and optimal care can be ensured for both female and male sexual violence survivors.

Atrophy and hypertrophy signalling of the quadriceps and diaphragm in COPD.

BACKGROUND: Factors involved in the regulation of muscle mass in chronic obstructive pulmonary disease (COPD) are still poorly understood. Comparing the signalisation involved in muscle mass regulation between two muscles with different levels of activation within the same subjects is an interesting strategy to tease out the impact of local (muscle activity) versus systemic factors in the regulation of muscle mass. A study was undertaken to measure and compare the protein levels of p-AKT, AKT, Atrogin-1, p-p70S6K, p-4E-BP1, p-GSK3ß as well as the mRNA expression of Atrogin-1, MuRF1 and FoxO-1 in the quadriceps and the diaphragm of 12 patients with COPD and 7 controls with normal lung function. METHODS: Diaphragm biopsies were obtained during thoracic surgery and quadriceps samples were obtained from needle biopsies. Protein content and mRNA expression were measured by western blot and quantitative PCR, respectively. RESULTS: Increased mRNA expressions of Atrogin-1, MuRF1 and FoxO-1 were found in the quadriceps compared with the diaphragm only in patients with COPD. The quadriceps/diaphragm ratio for MuRF1 was higher in COPD. The protein level of p-p70S6K was decreased in the quadriceps compared with the diaphragm in patients with COPD. The quadriceps/diaphragm ratios of p-p70S6K and p-GSK3ß were lower in patients with COPD than in controls. CONCLUSIONS: These results indicate a greater susceptibility to a catabolic/anabolic imbalance favouring muscle atrophy in the quadriceps compared with the diaphragm in patients with COPD. The balance between the atrophy and hypertrophy signalling is inhomogeneous between respiratory and lower limb muscles, suggesting that local factors are likely to be involved in the regulation of muscle mass in COPD.

Health Outcomes for Children in Haiti Since the 2010 Earthquake: A Systematic Review.

BACKGROUND: Haiti remains the poorest country in the Americas and one of the poorest in the world. Children in Haiti face many health concerns, some of which were exacerbated by the 2010 earthquake. This systematic review summarizes published research conducted since the 2010 earthquake, focusing on health outcomes for children in Haiti, including physical, psychological, and socioeconomic well-being. METHODS: A literature search was conducted identifying articles published from January 2010 through May 2016 related to pediatric health outcomes in Haiti. Two reviewers screened articles independently. Included research articles described at least one physical health, psychological health, or socioeconomic outcome among children less than 18 years of age in Haiti since the January 2010 earthquake. RESULTS: Fifty-eight full-length research articles were reviewed, covering infectious diseases (non-cholera [N=12] and cholera [N=7]), nutrition (N=11), traumatic injuries (N=11), mental health (N=9), anemia (N=4), abuse and violence (N=5), and other topics (N=3). Many children were injured in the 2010 earthquake, and care of their injuries is described in the literature. Infectious diseases were a significant cause of morbidity and mortality among children following the earthquake, with cholera being one of the most important etiologies. The literature also revealed that large numbers of children in Haiti have significant symptoms of posttraumatic stress disorder (PTSD), peri-traumatic stress, depression, and anxiety, and that food insecurity and malnutrition continue to be important issues. CONCLUSIONS: Future health programs in Haiti should focus on provision of clean water, sanitation, and other measures to prevent infectious diseases. Mental health programming and services for children also appear to be greatly needed, and food insecurity/malnutrition must be addressed if children are to lead healthy, productive lives. Given the burden of injury after the 2010 earthquake, further research on long-term disabilities among children in Haiti is needed. Dube A , Moffatt M , Davison C , Bartels S . Health outcomes for children in Haiti since the 2010 earthquake: a systematic review. Prehosp Disaster Med. 2018;33(1):77-88.

The Chilcapamba-McGill Partnership: Exploring Access to Maternal and Newborn Care in Indigenous Communities of Ecuador.

BACKGROUND: Based on a participatory research (PR) partnership between Family Medicine at McGill University, Canada and the Andean community of Chilcapamba, Ecuador, a medical student study focused on maternal and newborn health. OBJECTIVES: To evaluate the access to maternal and newborn care and the occurrence of intrafamilial violence in women with children 5 years of age or less in three indigenous communities of Ecuador. METHODS: A semistructured survey explored the perinatal and intrapartum care as well as intrafamilial violence. RESULTS: All women (N = 30) received prenatal care, 29 received postnatal care from a physician and 77% gave birth at the hospital. Eighty percent of women experienced intrafamilial violence; 73% reported psychological and 53% physical violence. CONCLUSIONS: There is good access to maternal and newborn health care, although the reported level of violence is high. Results were shared with the community and will be used in a local community health worker (CHW) training program. Our project highlights the importance of PR to investigate sensitive health challenges.

Tolerance and physiological correlates of neuromuscular electrical stimulation in COPD: a pilot study.

RATIONALE: Neuromuscular electrical stimulation (NMES) of the lower limbs is an emerging training strategy in patients with COPD. The efficacy of this technique is related to the intensity of the stimulation that is applied during the training sessions. However, little is known about tolerance to stimulation current intensity and physiological factors that could determine it. Our goal was to find potential physiological predictors of the tolerance to increasing NMES stimulation intensity in patients with mild to severe COPD. METHODS: 20 patients with COPD (FEV1 = 54±14% pred.) completed 2 supervised NMES sessions followed by 5 self-directed sessions at home and one final supervised session. NMES was applied simultaneously to both quadriceps for 45 minutes, at a stimulation frequency of 50 Hz. Spirometry, body composition, muscle function and aerobic capacity were assessed at baseline. Cardiorespiratory responses, leg discomfort, muscle fatigue and markers of systemic inflammation were assessed during or after the last NMES session. Tolerance to NMES was quantified as the increase in current intensity from the initial to the final NMES session (ΔInt). RESULTS: Mean ΔInt was 12±10 mA. FEV1, fat-free-mass, quadriceps strength, aerobic capacity and leg discomfort during the last NMES session positively correlated with ΔInt (r = 0.42 to 0.64, all p≤0.06) while post/pre NMES IL-6 ratio negatively correlated with ΔInt (r = -0.57, p = 0.001). FEV1, leg discomfort during last NMES session and post/pre IL-6 ratio to NMES were independent factors of variance in ΔInt (r2 = 0.72, p = 0.001). CONCLUSION: Lower tolerance to NMES was associated with increasing airflow obstruction, low tolerance to leg discomfort during NMES and the magnitude of the IL-6 response after NMES. TRIAL REGISTRATION: ClinicalTrials.gov NCT00809120.

Emotion processing in women with schizophrenia is menstrual cycle phase and affective valence dependent: an FMRI study.

Despite a large number of functional neuroimaging investigations of emotion processing in schizophrenia, very few have included women. In the present study 21 schizophrenia and 23 healthy women underwent functional MRI (3T) on two occasions (during the follicular and luteal phase of their menstrual cycle) while viewing blocks of emotionally negative, positive and neutral images. During exposure to negatively charged images patients showed relatively less activations than controls during the luteal phase, but no between-group differences were observed during the follicular phase. In contrast, the exposure to positively valenced material produced no significant interaction, but the main effect of group; schizophrenia patients exhibited less activation than healthy controls during both phases of the menstrual cycle. This is the first study demonstrating that atypical neural activations associated with emotion processing in women diagnosed with schizophrenia depend on the menstrual cycle phase and on the affective valence of presented stimuli.

Functional and muscular effects of neuromuscular electrical stimulation in patients with severe COPD: a randomized clinical trial.

BACKGROUND: The mechanisms through which neuromuscular electrical stimulation (NMES) training may improve limb muscle function and exercise tolerance in COPD are poorly understood. We investigated the functional and muscular effects of NMES in advanced COPD. METHODS: Twenty of 22 patients with COPD were randomly assigned to NMES (n = 12) or sham (n = 8) training in a double-blind controlled study. NMES was performed on quadriceps and calf muscles, at home, 5 days per week for 6 weeks. Quadriceps and calf muscle cross-sectional area (CSA), quadriceps force and endurance, and the shuttle-walking distance with cardiorespiratory measurements were assessed before and after training. Quadriceps biopsy specimens were obtained to explore the insulin-like growth factor-1/AKT signaling pathway (70-kDa ribosomal S6 kinase [p70S6K] , atrogin-1). RESULTS: NMES training improved muscle CSA (P < .05), force, and endurance (P < .03) when compared with sham training. Phosphorylated p70S6K levels (anabolism) were increased after NMES as compared with sham (P = .03), whereas atrogin-1 levels (catabolism) were reduced (P = .01). Changes in quadriceps strength and ventilation during walking contributed independently to variations in walking distance after training (r = 0.77, P < .001). Gains in walking distance were related to the ability to tolerate increasing current intensities during training (r = 0.95, P < .001). CONCLUSIONS: In patients with severe COPD, NMES improved muscle CSA. This was associated with a more favorable muscle anabolic to catabolic balance. Improvement in walking distance after NMES training was associated with gains in muscle strength, reduced ventilation during walking, and the ability to tolerate higher stimulation intensity. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00874965; URL: www.clinicaltrials.gov.

MAPK signaling in the quadriceps of patients with chronic obstructive pulmonary disease.

Muscle atrophy in chronic obstructive pulmonary disease (COPD) is associated with reduced exercise tolerance, muscle strength, and survival. The molecular mechanisms leading to muscle atrophy in COPD remain elusive. The mitogen-activated protein kinases (MAPKs) such as p38 MAPK and ERK 1/2 can increase levels of MAFbx/Atrogin and MuRF1, which are specifically involved in muscle protein degradation and atrophy. Our aim was to investigate the level of activation of p38 MAPK, ERK 1/2, and JNK in the quadriceps of patients with COPD. A biopsy of the quadriceps was obtained in 18 patients with COPD as well as in 9 healthy controls. We evaluated the phosphorylated as well as total protein levels of p38 MAPK, ERK 1/2, and JNK as well as MAFbx/Atrogin and MuRF1 in these muscle samples. The corresponding mRNA expression was also assessed by RT-PCR. Ratios of phosphorylated to total level of p38 MAPK (P = 0.02) and ERK 1/2 (P = 0.01) were significantly elevated in patients with COPD compared with controls. Moreover, protein levels of MAFbx/Atrogin showed a tendency to be greater in patients with COPD (P = 0.08). mRNA expression of p38 MAPK (P = 0.03), ERK 1/2 (P = 0.02), and MAFbx/Atrogin (P = 0.04) were significantly elevated in patients with COPD. In addition, phosphorylated-to-total p38 MAPK ratio (Pearson's r = -0.45; P < 0.05) and phosphorylated-to-total ERK 1/2 ratio (Pearson's r = -0.47; P < 0.05) were negatively associated with the mid-thigh muscle cross-sectional area. These data support the hypothesis that the MAPKs might play a role in the development of muscle atrophy in COPD.