Does speech improve after delayed palatal closure in Filipino adults? Effects of combined palatal repair, buccinator flaps and suspension pharyngeal flap.

Background: Adults presenting with unrepaired cleft palate are not a rare occurrence in middle-income countries. However, many surgeons are hesitant to operate on these individuals because of the challenges in repairing the wide adult cleft palate, as well as concerns regarding any improvement in speech in older patients. Unfortunately, the literature on the effect of delayed palatal closure is scarce.

Effects of Suspension Pharyngeal Flap on Speech in Filipino Individuals with Velopharyngeal Insufficiency.

Introduction: This study investigated the effects of suspension pharyngeal flap surgery for velopharyngeal insufficiency (VPI) due to cleft palate.

Methods: Ten Filipino individuals (mean age = 20.63 years, range = 8.

Better speech outcomes after very early palatal repair?-A longitudinal case-control study in Ugandan children with cleft palate.

Introduction: Children born with cleft palate with or without cleft lip (CP±L) tend to use less oral pressure consonants and more glottal sounds in their babbling. The purpose of very early palatal repair (i.e.

Metabolomic profiling of human pluripotent stem cell differentiation into lung progenitors.

Metabolism is vital to cellular function and tissue homeostasis during human lung development. , embryonic pluripotent stem cells undergo endodermal differentiation toward a lung progenitor cell fate that can be mimicked using induced human pluripotent stem cells (hiPSCs) to study genetic mutations. To identify differences between wild-type and surfactant protein B (deficient cell lines during endoderm specification toward lung, we used an untargeted metabolomics approach to evaluate the developmental changes in metabolites.

Vascularized fibula flap in the management of segmental bone loss following osteomyelitis in children at a Ugandan hospital.

: Hematogenous osteomyelitis is commonly observed in the pediatric population across sub-Saharan Africa. This retrospective case series was designed to evaluate the complications and outcomes of treatment using a vascularized fibula flap (VFF) to fill segmental bone defects secondary to osteomyelitis in children in a low-resource setting in CoRSU Rehabilitation Hospital, Uganda. : Clinical notes and radiographs of children with a diagnosis of osteomyelitis that subsequently underwent a VFF procedure between October 2013 and December 2017 were reviewed.

Perceptual Speech Outcomes After Early Primary Palatal Repair in Ugandan Patients With Cleft Palate.

Objective: To provide speech outcomes of English-speaking Ugandan patients with a cleft palate with or without cleft lip (CP±L).

Design: Prospective case-control study.

Setting: Referral hospital for patients with cleft lip and palate in Uganda.

Multi-omic comparison of Alzheimer's variants in human ESC-derived microglia reveals convergence at APOE.

Variations in many genes linked to sporadic Alzheimer's disease (AD) show abundant expression in microglia, but relationships among these genes remain largely elusive. Here, we establish isogenic human ESC-derived microglia-like cell lines (hMGLs) harboring AD variants in CD33, INPP5D, SORL1, and TREM2 loci and curate a comprehensive atlas comprising ATAC-seq, ChIP-seq, RNA-seq, and proteomics datasets. AD-like expression signatures are observed in AD mutant SORL1 and TREM2 hMGLs, while integrative multi-omic analysis of combined epigenetic and expression datasets indicates up-regulation of APOE as a convergent pathogenic node.

"Reprogram Enablement" as an Assay for Identifying Early Oncogenic Pathways by Their Ability to Allow Neoplastic Cells to Reacquire an Epiblast State.

One approach to understanding how tissue-specific cancers emerge is to determine the requirements for "reprograming" such neoplastic cells back to their developmentally normal primordial pre-malignant epiblast-like pluripotent state and then scrutinizing their spontaneous reconversion to a neoplasm, perhaps rendering salient the earliest pivotal oncogenic pathway(s) (before other aberrations accumulate in the adult tumor). For the prototypical malignancy anaplastic thyroid carcinoma (ATC), we found that tonic RAS reduction was obligatory for reprogramming cancer cells to a normal epiblast-emulating cells, confirmed by changes in their transcriptomic and epigenetic profiles, loss of neoplastic behavior, and ability to derive normal somatic cells from their "epiblast organoids." Without such suppression, ATCs re-emerged from the clones.

An improvement in skeletal muscle mitochondrial capacity with short-term aerobic training is associated with changes in Tribbles 1 expression.

Exercise training and physical activity are known to be associated with high mitochondrial content and oxidative capacity in skeletal muscle. Metabolic diseases including obesity and insulin resistance are associated with low mitochondrial capacity in skeletal muscle. Certain transcriptional factors such as PGC-1α are known to mediate the exercise response; however, the precise molecular mechanisms involved in the adaptation to exercise are not completely understood.

DNMT3B Oncogenic Activity in Human Intestinal Cancer Is Not Linked to CIMP or BRAFV600E Mutation.

Approximately 10% of human colorectal cancer (CRC) are associated with activated BRAFV600E mutation, typically in absence of APC mutation and often associated with a CpG island methylator (CIMP) phenotype. To protect from cancer, normal intestinal epithelial cells respond to oncogenic BRAFV600E by activation of intrinsic p53 and p16-dependent tumor suppressor mechanisms, such as cellular senescence. Conversely, CIMP is thought to contribute to bypass of these tumor suppressor mechanisms, e.

Endurance training remodels skeletal muscle phospholipid composition and increases intrinsic mitochondrial respiration in men with Type 2 diabetes.

The effects of exercise training on the skeletal muscle (SKM) lipidome and mitochondrial function have not been thoroughly explored in individuals with Type 2 diabetes (T2D). We hypothesize that 10 wk of supervised endurance training improves SKM mitochondrial function and insulin sensitivity that are related to alterations in lipid signatures within SKM of T2D (males = 8). We employed integrated multi-omics data analyses including ex vivo lipidomics (MS/MS-shotgun) and transcriptomics (RNA-Seq).

Myc and Loss of p53 Cooperate to Drive Formation of Choroid Plexus Carcinoma.

Choroid plexus carcinoma (CPC) is a rare brain tumor that occurs most commonly in very young children and has a dismal prognosis despite intensive therapy. Improved outcomes for patients with CPC depend on a deeper understanding of the mechanisms underlying the disease. Here we developed transgenic models of CPCs by activating the oncogene and deleting the tumor suppressor gene in murine neural stem cells or progenitors.

Challenges to achieving low palatal fistula rates following primary cleft palate repair: experience of an institution in Uganda.

Objective: To determine frequency of palatal fistula following primary cleft palate repair and the associated factors as a measure of cleft palate repair outcome and its challenges at a cleft centre in Uganda.

Results: Between May and December 2016, 54 children with cleft palate were followed up at Comprehensive Rehabilitation services of Uganda (CoRSU) hospital, from time of primary cleft palate repair until at least 3 months postoperative to determine whether they developed palatal fistula or not. Frequency of palatal fistula was 35%.

Delayed primary palatal closure in resource-poor countries: Speech results in Ugandan older children and young adults with cleft (lip and) palate.

Aims: Unrepaired clefts still regularly occur in resource-poor countries as a result of limited health-care access. The purpose of the present study was to report resonance, airflow and articulation characteristics following delayed (≥8years) primary palatal closure.

Methods: Fifteen Ugandan participants with cleft (lip and) palate (CP±L) were included as well as 15 age- and gender-matched Ugandan subjects without clefts.

The prevalence and factors associated with malnutrition among infants with cleft palate and/or lip at a hospital in Uganda: a cross-sectional study.

Background: To determine the prevalence and factors associated with malnutrition among infants with Cleft palate and/or cleft lip (CP+/-L) at Comprehensive Rehabilitation for Uganda Hospital (CoRSU) in Uganda.

Methods: This was a cross-sectional study done on infants with CP+/-L and their caretakers admitted between November 2013 and October 2014 at CoRSU hospital which was the study setting. A questionnaire was answered by the infants' caretakers.

Effects of 12 Months of Caloric Restriction on Muscle Mitochondrial Function in Healthy Individuals.

Context: The effects of caloric restriction (CR) on in vivo muscle mitochondrial function in humans are controversial.

Objective: We evaluated muscle mitochondrial function and associated transcriptional profiles in nonobese humans after 12 months of CR.

Design: Individuals from an ancillary study of the CALERIE 2 randomized controlled trial were assessed at baseline and 12 months after a 25% CR or ad libitum (control) diet.

Differences in Mitochondrial Coupling Reveal a Novel Signature of Mitohormesis in Muscle of Healthy Individuals.

Context: Reduced mitochondrial coupling (ATP/O [P/O]) is associated with sedentariness and insulin resistance. Interpreting the physiological relevance of P/O measured in vitro is challenging.

Objective: To evaluate muscle mitochondrial function and associated transcriptional profiles in nonobese healthy individuals distinguished by their in vivo P/O.

Neutralizing antibody affords comparable protection against vaginal and rectal simian/human immunodeficiency virus challenge in macaques.

Objective: Passive administration of broadly neutralizing antibodies has been shown to protect against both vaginal and rectal challenge in the simian/human immunodeficiency virus (SHIV)/macaque model of HIV transmission. However, the relative efficacy of antibody against the two modes of exposure is unknown and, given differences in the composition and immunology of the two tissue compartments, this is an important gap in knowledge. To investigate the significance of the challenge route for antibody-mediated protection, we performed a comparative protection study in macaques using the highly potent human monoclonal antibody, PGT126.

Challenges in global microsurgery: A six year review of outcomes at an East African hospital.

Background: Free tissue transfer is an invaluable resource for reconstruction of complex defects. There is very little evidence as to the feasibility and outcomes of microsurgery performed in East Africa. This study will analyse outcomes of 114 consecutive free flaps, performed over 6 years at a single plastic surgery unit in Uganda.

Bayesian network analysis of multi-compartmentalized immune responses in a murine model of sepsis and direct lung injury.

Background: Inflammatory disease processes involve complex and interrelated systems of mediators. Determining the causal relationships among these mediators becomes more complicated when two, concurrent inflammatory conditions occur. In those cases, the outcome may also be dependent upon the timing, severity and compartmentalization of the insults.

Twistors and amplitudes.

A brief review is given of why twistor geometry has taken a central place in the theory of scattering amplitudes for fundamental particles. The emphasis is on the twistor diagram formalism as originally proposed by Penrose, the development of which has now led to the definition by Arkani-Hamed et al. of the 'amplituhedron'.

Reconstruction of Punitive Ear Amputations in Uganda: A Unique Surgical Burden of Disease.

Over the course of 12 months, a plastic surgical team from Paris, France, undertook 2 intensive ear reconstruction missions with plastic surgeons from the CoRSU Rehabilitation Hospital in Uganda. A cohort of over 30 adult women was assessed having been subjected to ear amputations by members of the Lords Resistance Army in Northern Uganda in the 1990s. The patients were identified, mobilized, and transferred to Kampala for surgery by a charitable arm of the Watoto Church, known as Living Hope.

Identification of drug combinations containing imatinib for treatment of BCR-ABL+ leukemias.

The BCR-ABL translocation is found in chronic myeloid leukemia (CML) and in Ph+ acute lymphoblastic leukemia (ALL) patients. Although imatinib and its analogues have been used as front-line therapy to target this mutation and control the disease for over a decade, resistance to the therapy is still observed and most patients are not cured but need to continue the therapy indefinitely. It is therefore of great importance to find new therapies, possibly as drug combinations, which can overcome drug resistance.

Impact of early synchronous lip and palatal repair on speech.

Aims: The purpose of this study was to describe articulation and resonance characteristics of Ugandan English-speaking children with cleft lip and palate (CLP) after synchronous lip and palatal closure (Sommerlad technique) prior to the age of 6 months in comparison with an age- and gender-matched control group.

Methods: Eleven Ugandan patients with CLP (mean age 4;9 years), repaired during a synchronous lip and (soft and hard) palatal closure at a mean age of 3.4 months, were included as well as a control group (n = 22) consisting of 2 Ugandan age- and gender-matched noncleft children for each patient (mean age 4;10 years).