Stercoral perforation of the cecum: A case report.

Background: With less than 90 reported cases to date, stercoral perforation of the colon is a rare occurrence. Stercoral ulceration is thought to occur due to ischemic pressure necrosis of the bowel wall, which is caused by the presence of a stercoraceous mass. To underscore this urgent surgical situation concerning clinical presentation, surgical treatment, and results, we present the case of a 66-year-old man with a stercoral perforation.

The effect of medial calcar support on proximal humeral fractures treated with locking plates.

Background: Studies have reported mixed results on the importance of medial calcar support for the treatment of proximal humeral fractures. The purpose of this study was to compare radiographic and functional outcomes of patients who had displaced proximal humeral fractures with varying levels of medial support.

Methods: We performed a retrospective comparative cohort study.

Effect of Platelet-Rich Plasma Augmentation on Endoscopy-Assisted Percutaneous Achilles Tendon Repair.

Background: Achilles tendon ruptures are one of the most common sports injuries. Recently, platelet-rich plasma (PRP) has been widely used in tendon-related disorders to enhance tendon healing. However, studies regarding PRP treatment in Achilles tendon rupture show inconsistent results.

Whole-exome sequencing and adrenocorticotropic hormone therapy in individuals with infantile spasms.

Aim: To identify additional genes associated with infantile spasms using a cohort with defined infantile spasms.

Method: Whole-exome sequencing (WES) was performed on 21 consented individuals with infantile spasms and their unaffected parents (a trio-based study). Clinical history and imaging were reviewed.

Biocompatibility of NbTaTiVZr with Surface Modifications for Osteoblasts.

We report a potential biomedical material, NbTaTiVZr, and the impact of surface roughness on the osteoblast culture and later behavior based on in vitro tests of preosteoblasts. Cell activities such as adhesion, viability, and typical protein activity on NbTaTiVZr showed comparable results with that of commercially pure Ti (CP-Ti). In addition, NbTaTiVZr with a smooth surface exhibits better cell adhesion, viability, and typical protein activity which shows that surface modification can improve the biocompatibility of NbTaTiVZr.

Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu Africans.

Similarity in facial characteristics between relatives suggests a strong genetic component underlies facial variation. While there have been numerous studies of the genetics of facial abnormalities and, more recently, single nucleotide polymorphism (SNP) genome-wide association studies (GWASs) of normal facial variation, little is known about the role of genetic structural variation in determining facial shape. In a sample of Bantu African children, we found that only 9% of common copy number variants (CNVs) and 10-kb CNV analysis windows are well tagged by SNPs (r ≥ 0.

Genome-wide copy number variations in a large cohort of bantu African children.

Background: Copy number variations (CNVs) account for a substantial proportion of inter-individual genomic variation. However, a majority of genomic variation studies have focused on single-nucleotide variations (SNVs), with limited genome-wide analysis of CNVs in large cohorts, especially in populations that are under-represented in genetic studies including people of African descent.

Methods: We carried out a genome-wide copy number analysis in > 3400 healthy Bantu Africans from Tanzania.

Abnormal expression of GABA receptor subunits and hypomotility upon loss of in zebrafish.

We used whole-exome sequencing (WES) to determine the genetic etiology of a patient with a multi-system disorder characterized by a seizure phenotype. WES identified a heterozygous missense mutation in the gene (c.875C>T).

Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging.

Genome sequencing has established clinical utility for rare disease diagnosis. While increasing numbers of individuals have undergone elective genome sequencing, a comprehensive study surveying genome-wide disease-associated genes in adults with deep phenotyping has not been reported. Here we report the results of a 3-y precision medicine study with a goal to integrate whole-genome sequencing with deep phenotyping.

An unsupervised learning approach to identify novel signatures of health and disease from multimodal data.

Background: Modern medicine is rapidly moving towards a data-driven paradigm based on comprehensive multimodal health assessments. Integrated analysis of data from different modalities has the potential of uncovering novel biomarkers and disease signatures.

Methods: We collected 1385 data features from diverse modalities, including metabolome, microbiome, genetics, and advanced imaging, from 1253 individuals and from a longitudinal validation cohort of 1083 individuals.

Predictors for Unfavorable Early Outcomes in Elective Total Hip Arthroplasty: Does Extreme Body Mass Index Matter?

Background: Studies of previous cohorts have demonstrated a controversial association between extreme body mass index (BMI) and complication rates following total hip arthroplasty (THA). The purpose of this study was to compare 30-day perioperative complications in underweight (BMI <18.50 kg/m), normal-weight (BMI 18.

Production of functional peptides with inhibition ability against angiotensin I-Converting enzyme using P. pastoris expression system.

To obtain the angiotension-I converting enzyme inhibitor (ACEI), a fusion ACEI polypeptide encoded with 8 DNA sequences of GPL, GPM, IKW, IVY, IRPVQ, IWHHT, IYPRY and IAPG, which were selected and designed and cloned into pGAPZαC and then transformed into Pichia pastoris SMD1168H. After 3 days induction, the fraction with highest ACEI activity was expressed and purified using a Ni Sepharose™ 6 Fast Flow. The IC of recombinant ACEI polypeptide was 88.

Identification of Misclassified ClinVar Variants via Disease Population Prevalence.

There is a significant interest in the standardized classification of human genetic variants. We used whole-genome sequence data from 10,495 unrelated individuals to contrast population frequency of pathogenic variants to the expected population prevalence of the disease. Analyses included the ACMG-recommended 59 gene-condition sets for incidental findings and 463 genes associated with 265 OrphaNet conditions.

Mutations in PMPCB Encoding the Catalytic Subunit of the Mitochondrial Presequence Protease Cause Neurodegeneration in Early Childhood.

Mitochondrial disorders causing neurodegeneration in childhood are genetically heterogeneous, and the underlying genetic etiology remains unknown in many affected individuals. We identified biallelic variants in PMPCB in individuals of four families including one family with two affected siblings with neurodegeneration and cerebellar atrophy. PMPCB encodes the catalytic subunit of the essential mitochondrial processing protease (MPP), which is required for maturation of the majority of mitochondrial precursor proteins.

The human noncoding genome defined by genetic diversity.

Understanding the significance of genetic variants in the noncoding genome is emerging as the next challenge in human genomics. We used the power of 11,257 whole-genome sequences and 16,384 heptamers (7-nt motifs) to build a map of sequence constraint for the human species. This build differed substantially from traditional maps of interspecies conservation and identified regulatory elements among the most constrained regions of the genome.

Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities.

CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor.

X-Linked Cobalamin Disorder (HCFC1) Mimicking Nonketotic Hyperglycinemia With Increased Both Cerebrospinal Fluid Glycine and Methylmalonic Acid.

Background: Autosomal recessive or X-linked inborn errors of intracellular cobalamin metabolism can lead to methylmalonic aciduria and homocystinuria. In neonates, both increased cerebrospinal fluid glycine and cerebrospinal fluid/plasma glycine ratio are biochemical features of nonketotic hyperglycinemia.

Methods: We describe a boy presenting in the neonatal period with hypotonia, tonic, clonic, and later myoclonic seizures, subsequently evolving into refractory epilepsy and severe neurocognitive impairment.

Whole-genome sequencing identifies common-to-rare variants associated with human blood metabolites.

Genetic factors modifying the blood metabolome have been investigated through genome-wide association studies (GWAS) of common genetic variants and through exome sequencing. We conducted a whole-genome sequencing study of common, low-frequency and rare variants to associate genetic variations with blood metabolite levels using comprehensive metabolite profiling in 1,960 adults. We focused the analysis on 644 metabolites with consistent levels across three longitudinal data collections.

Discovery of a potentially deleterious variant in TMEM87B in a patient with a hemizygous 2q13 microdeletion suggests a recessive condition characterized by congenital heart disease and restrictive cardiomyopathy.

Restrictive cardiomyopathy (RCM) is a rare cause of heart muscle disease with the highest mortality rate among cardiomyopathy types. The etiology of RCM is poorly understood, although genetic causes have been implicated, and syndromic associations have been described. Here, we describe a patient with an atrial septal defect and restrictive cardiomyopathy along with craniofacial anomalies and intellectual disabilities.

Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder.

Background: Mitochondrial disease is often suspected in cases of severe epileptic encephalopathy especially when a complex movement disorder, liver involvement and progressive developmental regression are present. Although mutations in either mitochondrial DNA or POLG are often present, other nuclear defects in mitochondrial DNA replication and protein translation have been associated with a severe epileptic encephalopathy.

Methods And Results: We identified a proband with an epileptic encephalopathy, complex movement disorder and a combined mitochondrial respiratory chain enzyme deficiency.

Compound heterozygosity for a frame shift mutation and a likely pathogenic sequence variant in the planar cell polarity—ciliogenesis gene WDPCP in a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas.

We report on a young girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas. These features are similar to those reported in individuals with variant forms of orofaciodigital syndrome known as congenital heart defects, hamartomas of the tongue and polysyndactly (CHDHTP: OMIM 217085) [Örstavik et al., 1992] and orocardiodigital syndrome [Digilio et al.

Evaluating Familial Essential Tremor with Novel Genetic Approaches: Is it a Genotyping or Phenotyping Issue?

Background: Essential tremor is a common movement disorder with a strong heritable component. Large families with inherited forms of essential tremor have undergone genetic analyses by different approaches. However, our knowledge of genetic variants unequivocally linked to essential tremor is remarkably limited.