Percutaneous Embolization of Congenital Portosystemic Venous Fistula in an Infant with Down Syndrome

Congenital intrahepatic portosystemic venous shunts are rare vascular malformations often associated with severe complications. We describe a term male infant with Down syndrome with high output heart failure secondary to a congenital arterial to portal venous fistula that was diagnosed by Doppler ultrasound. Percutaneous embolizations of the left hepatic vein, portal vein, and communicating fistulas were performed without complications, resulting in clinical improvement. A subsequent hepatic ultrasound demonstrated resolution of the pathologic fistulous communication and shunting effects

Exploring the role of BMP7 gene expression in an In Vitro model of aging human skeletal muscle.

Sarcopenia is an age-related condition associated with rapid loss of skeletal muscle (SKM) tissue that affects mobility and quality of life of geriatric individuals. Mechanistic Target of Rapamycin (mTOR) and Protein Kinase B (AKT) have significant roles in SKM hypertrophy with responses to DNA damage and repair within SKM. However, mTOR and AKT expression is significantly decreased with age. Upstream of AKT, Bone Morphogenetic Protein (BMP7) is a member of the TGF-β signaling family that has been reported as a positive regulator of muscle hypertrophy through the Bmp–Smad1/5/8 signaling axis. PURPOSE: To use an in vitro model of aging muscle cells to investigate the role of BMP7 expression on protein synthesis. METHODS: Human SKM myoblasts were cultured and grown beyond mature myotube formation (typically day 6) to emulate aged SKM tissue (extracted on day 18). Groups included control cells (D6) and aged SKM myotubes (D18). Total RNA was extracted at the respective time points (days 6 & 18) and gene expression for BMP7, mTOR, and AKT was determined by qPCR. RESULTS: BMP7 expression was 7.73 fold greater for D18 compared to D6 (p \u3c 0.05). No differences were reported for AKT or mTOR. Data are expressed as fold changes. CONCLUSION: BMP7 expression, thought to be a positive regulator of muscle hypertrophy, was increased in the aging muscle cells of our model, despite our hypothesis that it would be decreased. However, BMP7’s downstream targets related to increased protein synthesis, mTOR and AKT, did not similarly increase from D6 to D18, which is constant with the phenomena of sarcopenia. This leads us to speculate that there may be additional mechanisms related to BMP7 activation and, despite increased signaling, may block protein synthesis at the level of AKT

Attitudes of Healthcare Providers towards Non-initiation and Withdrawal of Neonatal Resuscitation for Preterm Infants in Mongolia

Antenatal parental counselling by healthcare providers is recommended to inform parents and assist with decision-making before the birth of a child with anticipated poor prognosis. In the setting of a low-income country, like Mongolia, attitudes of healthcare providers towards resuscitation of high-risk newborns are unknown. The purpose of this study was to examine the attitudes of healthcare providers regarding ethical decisions pertaining to non-initiation and withdrawal of neonatal resuscitation in Mongolia. A questionnaire on attitudes towards decision-making for non-initiation and withdrawal of neonatal resuscitation was administered to 113 healthcare providers attending neonatal resuscitation training courses in 2009 in Ulaanbaatar, the capital and the largest city of Mongolia where ~40% of deliveries in the country occur. The questionnaire was developed in English and translated into Mongolian and included multiple choices and free-text responses. Participation was voluntary, and anonymity of the participants was strictly maintained. In total, 113 sets of questionnaire were completed by Mongolian healthcare providers, including neonatologists, paediatricians, neonatal and obstetrical nurses, and midwives, with 100% response rate. Ninety-six percent of respondents were women, with 73% of participants from Ulaanbaatar and 27% (all midwives) from the countryside. The majority (96%) of healthcare providers stated they attempt pre-delivery counselling to discuss potential poor outcomes when mothers present with preterm labour. However, most (90%) healthcare providers stated they feel uncomfortable discussing not initiating or withdrawing neonatal resuscitation for a baby born alive with little chance of survival. Religious beliefs and concerns about long-term pain for the baby were the most common reasons for not initiating neonatal resuscitation or withdrawing care for a baby born too premature or with congenital birth-defects. Most Mongolian healthcare providers provide antenatal counselling to parents regarding neonatal resuscitation. Additional research is needed to determine if the above-said difficulty with counselling stems from deficiencies in communication training and whether these same counselling-related issues exist in other countries. Future educational efforts in teaching neonatal resuscitation in Mongolia should incorporate culturally-sensitive training on antenatal counselling

Myogenic Regulatory Factor Expression is Downregulated Following Formoterol Stimulation in Thyroid Hormone Depleted Skeletal Muscle

In skeletal muscle (SKM), gene expression of transcription factors regulating myogenesis are dependent on Thyroid Hormone (TH) signal transduction. Expression of myogenic regulatory factors may be altered due to dysregulated TH metabolism, which may result in SKM dysfunction and intolerance to exercise in individuals with hypothyroidism. PURPOSE: Implement an in vitro model of hypothyroidism in SKM and determine the response of myogenic regulatory factor expression during several stages of myogenesis following TH depletion. Formoterol, an exercise mimetic, was also used to examine the effects of exercise signaling on myogenesis in TH depleted cells. METHODS: Human SKM myoblasts (n = 6 per group) were cultured and differentiated until mature myotube formation (Day 6). Groups included control cells (CON), TH depleted cells (ThD), and TH depleted cells plus formoterol stimulation (ThD+F; 30nm for 3h). Total RNA was extracted during mid-myogenesis (Day 4) and at terminal differentiation (Day 6). Gene expression for myogenic regulatory factors (Myf5, MyoD, MyoG) was determined by qPCR. RESULTS: ThD decreased Myf5 at both Day 4 and Day 6 compared to control (P\u3c0.001). Myf5 was increased following ThD + F compared to ThD at Day 4 (P\u3c0.05). MyoD decreased following ThD at both Day 4 and Day 6 (P\u3c0.001). Further, MyoD was decreased following ThD + F at both Day 4 and Day 6 compared to ThD (P\u3c0.001). ThD had no effect on MyoG at Day 4 and Day 6; however, MyoG was decreased following ThD + F compared to ThD and control at both time points (P\u3c0.001). Data are expressed as mean ± SEM. CONCLUSION: TH depletion had no effect on MyoG but did reduce the expression of both Myf5 and MyoD at both Day 4 and Day 6. Additionally, ThD+F resulted in the lowest expression of MyoG and MyoD for both time points. These results indicate TH depletion and formoterol stimulation may inhibit myotube maturation

Mitochondrial Biogenesis is Dysregulated in Thyroid Hormone Depleted Muscle Cells Despite Stimulatory Effects of Formoterol

Skeletal muscle (SKM) is an important regulator of metabolism and adaptations from exercise training influences mitochondrial function. Thyroid hormone (TH) is a regulator of SKM processes, including mitochondrial biogenesis. PURPOSE: To use an in vitro model of hypothyroidism to test the hypothesis that SKM cells will have dysregulated mitochondrial homeostasis. Additionally, the exercise mimetic, formoterol, was used to determine the effects of exercise signaling on mitochondrial biogenesis. METHODS: Human SKM myoblasts (n = 6 per group) were cultured and differentiated until mature myotube formation (Day 6). Groups included control cells (CON), TH depleted cells (ThD), and TH depleted cells plus formoterol stimulation (ThD+F; 30nM for 3h). Total RNA was extracted during mid-myogenesis (Day 4) and at terminal differentiation (Day 6). Gene expression for Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha (PGC-1α), Mitochondrial Transcription Factor A (TFAM), and Nuclear Respiratory Factor 1 (NRF1) was determined by qPCR. Data was analyzed by repeated measures ANOVA. RESULTS: PGC-1α: D4 ThD was decreased compared to D4 ThD+F (-4.6); D4 ThD+F was increased compared to D4 CON (4.6); D6 CON was decreased compared to D6 ThD+F (-2.9); D6 ThD was decreased compared to D6 ThD+F (-3.7). TFAM: D4 ThD+F was greater than D4 CON (3.6); D4 ThD+F was greater than D6 ThD+F (3.6); D6 ThD was decreased compared to D6 CON (-0.55); D6 ThD+F was decreased compared to D6 CON (-0.63). NRF1: D4 ThD was decreased compared to D4 CON (-0.31); D4 ThD was greater than D4 ThD+F (0.36); D4 ThD was greater than D6 ThD (0.17); ThD+F was decreased compared to D4 CON (-0.67); D6 CON was decreased compared to D4 CON (-0.18); D6 ThD was decreased compared to D6 CON (-0.3); D6 ThD+F was decreased compared to D6 CON (-0.42). All reported differences are significant (p \u3c 0.05). Data are expressed as fold changes. CONCLUSION: ThD media resulted in reduced NRF1 signaling in both D4 and D6 with a subsequent decrease in D6 only for TFAM. Formoterol resulted in the expected stimulation of PGC-1α at both D4 and D6, but subsequent signaling for genes associated with mitochondrial biogenesis common to PGC-1α stimulation were lost as a result of TH depletion at D6 only for TFAM and both D4 and D6 for NRF1

Formoterol Stimulation In Vitro Influences Myogenic Regulatory Factors During Myogenesis in Human Skeletal Muscle Cells

The process of myogenesis within skeletal muscle (SKM) is essential for growth and repair and is coordinated via the expression of myogenic regulatory genes. Previous animal studies have reported that formoterol, a beta-adrenergic receptor agonist, has stimulating effects on genes related to SKM mitochondrial function and biogenesis, similar to effects found for exercise. Lesser known is the potential “exercise mimetic” influence that formoterol stimulation may have during the stages of myogenesis, especially in human SKM cells. PURPOSE: To investigate the effects of formoterol stimulation on expression of myogenic regulatory genes during myogenesis in human SKM cells. METHODS: Human SKM myoblasts (n = 6 per group) were cultured and differentiated until mature myotube formation (Day 6). Groups included control cells (CON) and cells stimulated by 30nM formoterol for 3h prior to RNA extraction points (FORM). Total RNA was extracted during mid-myogenesis (Day 4) and at terminal differentiation (Day 6) (a cell culture model of investigating myogenesis). Gene expression for Myogenic factor 5 (Myf5), Myogenic differentiation 1(MyoD), and Myogenin (MyoG) was determined by qPCR. Data was analyzed using repeated measures ANOVA. RESULTS: Myf5: There was no change for either condition for D4. D6 CON was lower than D4 CON (-0.25). D6 FORM was greater than D4 FORM (0.65) and D6 CON (0.75). MyoD: D4 FORM was lower than D4 CON (-0.57). D6 FORM was greater than D4 FORM (0.85) and lower than D6 CON (-0.16). D6 CON was lower than D4 CON (-0.33). MyoG: D4 FORM was lower than D4 CON (-0.72). D6 CON was lower than D4 CON (-0.44). D6 FORM was lower than D6 CON (-0.24). All reported differences are significant (p \u3c 0.05). Data are expressed as fold changes. CONCLUSION: As expected, for the CON group, Myf5, MyoD, and MyoG expression all decreased from D4 mid-myogenesis to D6 terminal myogenesis, indicating finalization of the myogenic gene program. For the FORM group, Myf5 expression was elevated at D6 compared to CON while MyoG and MyoD expression was lower than CON for D4 and D6. The interpretation is that FORM stimulation increased stimulus of D4 myoblast proliferation and, thus, delayed initiation of differentiation. These results, coupled with other preliminary data from our lab showing increased mitochondrial biogenesis with this model of investigation, suggests that this exercise mimetic stimulation may cause shift in the cell towards bioenergetic preference rather than fusion of myotubes

Poor birth weight recovery among low birth weight/preterm infants following hospital discharge in Kampala, Uganda

<p>Abstract</p> <p>Background</p> <p>Healthy infants typically regain their birth weight by 21 days of age; however, failure to do so may be due to medical, nutritional or environmental factors. Globally, the incidence of low birth weight deliveries is high, but few studies have assessed the postnatal weight changes in this category of infants, especially in Africa. The aim was to determine what proportion of LBW infants had not regained their birth weight by 21 days of age after discharge from the Special Care Unit of Mulago hospital, Kampala.</p> <p>Methods</p> <p>A cross sectional study was conducted assessing weight recovery of 235 LBW infants attending the Kangaroo Clinic in the Special Care Unit of Mulago Hospital between January and April 2010. Infants aged 21 days with a documented birth weight and whose mothers gave consent to participate were included in the study. Baseline information was collected on demographic characteristics, history on pregnancy, delivery and postnatal outcome through interviews. Pertinent infant information like gestation age, diagnosis and management was obtained from the medical records and summarized in the case report forms.</p> <p>Results</p> <p>Of the 235 LBW infants, 113 (48.1%) had not regained their birth weight by 21 days. Duration of hospitalization for more than 7 days (AOR: 4.2; 95% CI: 2.3 - 7.6; p value < 0.001) and initiation of the first feed after 48 hours (AOR: 1.9; 95% CI 1.1 - 3.4 p value 0.034) were independently associated with failure to regain birth weight. Maternal factors and the infant's physical examination findings were not significantly associated with failure to regain birth weight by 21 days of age.</p> <p>Conclusion</p> <p>Failure to regain birth weight among LBW infants by 21 days of age is a common problem in Mulago Hospital occurring in almost half of the neonates attending the Kangaroo clinic. Currently, the burden of morbidity in this group of high-risk infants is undetected and unaddressed in many developing countries. Measures for consideration to improve care of these infants would include; discharge after regaining birth weight and use of total parenteral nutrition. However, due to the pressure of space, keeping the baby and mother is not feasible at the moment hence the need for a strong community system to boost care of the infant. Close networking with support groups within the child's environment could help alleviate this problem.</p

911 Calls for Emergency Medical Services in Heart Failure: A Descriptive Qualitative Study

Background Heart failure (HF) is a common condition leading to activation of emergency medical services (EMS). Objective The aim of this study was to describe reasons given by persons with HF, family members, or other caregivers for requesting EMS activation during 911 calls. Methods In this descriptive qualitative study, a content analysis was performed on transcribed audio files of 383 EMS requests involving 383 persons with HF in the community. Results One hundred forty-seven calls (38.4%) were placed by the family members, 75 (19.6%) were placed by the patients, 56 (14.6%) were placed by healthcare workers or personnel from living facilities, and the remaining calls (n = 105, 27.4%) were placed by others (eg, friends, neighbors, officers). Three broad categories of symptoms, signs, and events were identified as the reasons for an EMS request. Frequently reported symptoms were breathing problems (55.4%), chest pain (18.3%), and other pain (eg, head, extremities) (16.7%). Signs included decreased consciousness (15.4%), swelling (5.7%), and bleeding (5.0%). The reported events involved falls (8.1%), heart attack (6.3%), hypoxic episodes (6.0%), stroke (5.2%), and post–hospital-discharge complications (4.7%). In most calls (74.9%), multiple reasons were reported and a combination of symptoms, signs, and events were identified. Heart failure diagnosis was mentioned in fewer than 10% of the calls. Conclusions Overall, symptoms and signs of HF exacerbation were common reasons to activate 911 calls. Falls were frequently reported. Under the duress of the emergent situations surrounding the 911 call, callers rarely mentioned the existence of HF. Interventions are needed to guide patients with HF and their family members to promote the management of HF to reduce EMS activation as well as to activate EMS quickly for acute changes in HF conditions