Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Intracerebral hemorrhage after IV tPA for stroke as early symptom of ANCA-associated vasculitis

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare diseases characterized by a necrotizing small-vessel vasculitis and circulating ANCA that comprise granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (EGPA). Acute ischemic stroke (AIS) can be a manifestation of central nervous system (CNS) involvement in these diseases. Furthermore, intracerebral hemorrhage (ICH) is a potential complication of these necrotizing vasculitides. We describe a case of AAV who presented with acute ischemic stroke and developed multiple ICHs after administration of IV tPA. We propose that patients with AAV are more prone to develop hemorrhage in the presence of IV tPA and discuss the possible underlying pathogenesis. We suggest that AAV should be considered a contraindication for administration of IV tPA. Keywords: ANCA associated vasculitis, Intracerebral hemorrhage, Ischemic stroke, IV tP

Microvascular Decompression and MRI Findings in Trigeminal Neuralgia and Hemifacial Spasm. A Single Center Experience.

OBJECTIVE: For patients with medically unresponsive trigeminal neuralgia (TIC) and hemifacial spasm (HS), surgical microvascular decompression (MVD) is the procedure of choice. The authors of this report sought to review their outcomes with MVD in patients with TIC and HS, and the success of preoperative magnetic resonance imaging (MRI) in identifying the offending vascular compression. METHODS: Since 2004, there were a total of 51 patients with TIC and 12 with HS with available MRI scans. All patients underwent preoperative MRI to rule out non-surgical etiologies for facial pain and facial spasm, and confirm vascular compression. Follow-up after surgery was 13 ± 22 months for the patients with TIC and 33 ± 27 months for the patients with HS. RESULTS: There were 45 responders to MVD in the TIC cohort (88%), with a Visual Analog Score (VAS) of 1 ± 3. All patients with HS responded to MVD between 25 and 100%, with a mean of 75 ± 22%. Wound complications occurred in 10% of patients with MVD for TIC, and 1 patient reported hearing loss after MVD for HS, documented by audiogram. The congruence rate between the preoperative MRI and operative findings of vascular compression was 84% in TIC and 75% in HS. CONCLUSION: MVD is an effective and safe modality of treatment for TIC and HS. In addition to ruling out structural lesions, MRI can offer additional information by highlighting vascular loops associated with compressions. On conventional scans as obtained here, the resolution of MRI was congruent with operative findings in 84% in TIC and 75% in HS. This review emphasizes that the decision to undertake MVD in TIC or HS should be based on clinical diagnosis and not visualization of a compressing vessel by MRI. Conversely, the presence of a compressing vessel by MRI demands perseverance by the surgeon until the nerve is decompressed

Brain Multimodality Monitoring: A New Tool in Neurocritical Care of Comatose Patients

Neurocritical care patients are at risk of developing secondary brain injury from inflammation, ischemia, and edema that follows the primary insult. Recognizing clinical deterioration due to secondary injury is frequently challenging in comatose patients. Multimodality monitoring (MMM) encompasses various tools to monitor cerebral metabolism, perfusion, and oxygenation aimed at detecting these changes to help modify therapies before irreversible injury sets in. These tools include intracranial pressure (ICP) monitors, transcranial Doppler (TCD), Hemedex6 (thermal diffusion probe used to measure regional cerebral blood flow), microdialysis catheter (used to measure cerebral metabolism), Licox6 (probe used to measure regional brain tissue oxygen tension), and continuous electroencephalography. Although further research is needed to demonstrate their impact on improving clinical outcomes, their contribution to illuminate the black box of the brain in comatose patients is indisputable. In this review, we further elaborate on commonly used MMM parameters, tools used to measure them, and the indications for monitoring per current consensus guidelines

Effect of Two-Year Caloric Restriction on Bone Metabolism and Bone Mineral Density in Non-obese Younger Adults: a Randomized Clinical Trial

Although caloric restriction (CR) could delay biologic aging in humans, it is unclear if this would occur at the cost of significant bone loss. We evaluated the effect of prolonged CR on bone metabolism and bone mineral density (BMD) in healthy younger adults. Two-hundred eighteen non-obese (body mass index [BMI] 25.1 ± 1.7 kg/m(2) ), younger (age 37.9 ± 7.2 years) adults were randomly assigned to 25% CR (CR group, n = 143) or ad libitum (AL group, n = 75) for 2 years. Main outcomes were BMD and markers of bone turnover. Other outcomes included body composition, bone-active hormones, nutrient intake, and physical activity. Body weight (-7.5 ± 0.4 versus 0.1 ± 0.5 kg), fat mass (-5.3 ± 0.3 versus 0.4 ± 0.4 kg), and fat-free mass (-2.2 ± 0.2 versus -0.2 ± 0.2 kg) decreased in the CR group compared with AL (all between group p < 0.001). Compared with AL, the CR group had greater changes in BMD at 24 months: lumbar spine (-0.013 ± 0.003 versus 0.007 ± 0.004 g/cm(2) ; p < 0.001), total hip (-0.017 ± 0.002 versus 0.001 ± 0.003 g/cm(2) ; p < 0.001), and femoral neck (-0.015 ± 0.003 versus -0.005 ± 0.004 g/cm(2) ; p = 0.03). Changes in bone markers were greater at 12 months for C-telopeptide (0.098 ± 0.012 versus 0.025 ± 0.015 μg/L; p < 0.001), tartrate-resistant acid phosphatase (0.4 ± 0.1 versus 0.2 ± 0.1 U/L; p = 0.004), and bone-specific alkaline phosphatase (BSAP) (-1.4 ± 0.4 versus -0.3 ± 0.5 U/L; p = 0.047) but not procollagen type 1 N-propeptide; at 24 months, only BSAP differed between groups (-1.5 ± 0.4 versus 0.9 ± 0.6 U/L; p = 0.001). The CR group had larger increases in 25-hydroxyvitamin D, cortisol, and adiponectin and decreases in leptin and insulin compared with AL. However, parathyroid hormone and IGF-1 levels did not differ between groups. The CR group also had lower levels of physical activity. Multiple regression analyses revealed that body composition, hormones, nutrients, and physical activity changes explained ∼31% of the variance in BMD and bone marker changes in the CR group. Therefore, bone loss at clinically important sites of osteoporotic fractures represents a potential limitation of prolonged CR for extending life span. Further long-term studies are needed to determine if CR-induced bone loss in healthy adults contributes to fracture risk and if bone loss can be prevented with exercise. © 2015 American Society for Bone and Mineral Research

Influence of Protein Intake, Race, and Age on Responses to a Weight-Reduction Intervention in Obese Women

BACKGROUND: Women have higher rates of obesity than men and develop more pronounced functional deficits as a result. Yet, little is known about how obesity reduction affects their functional status, including whether their responses differ when protein intake is enhanced. OBJECTIVE: The aim of this study was to confirm the feasibility of delivery of a higher-protein (balanced at each meal) calorie-restricted diet in obese women and determine its efficacy for influencing function and retention of lean mass. METHOD: Obese community-dwelling women [n = 80; body mass index (in kg/m2), in means ± SDs: 37.8 ± 5.9; aged 45–78 y; 58.8% white] were enrolled in a weight-loss (−500 kcal/d) study and randomly assigned to either a Control–Weight-Loss (C-WL; 0.8 g protein/kg body weight) group or a High-Protein–Weight-Loss (HP-WL; 1.2 g protein/kg body weight; 30 g protein 3 times/d) group in a 1:2 allocation. Primary outcomes were function by 6-min walk test (6MWT) and lean mass by using the BodPod (Life Measurement, Inc.) at 0, 4, and 6 mo. RESULTS: Both groups reduced calorie intakes and body weights (P &lt; 0.001), and the feasibility of the HP-WL intervention was confirmed. The 6MWT results improved (P &lt; 0.01) at 4 mo in the HP-WL group and at 6 mo in both groups (P &lt; 0.001). Both groups improved function by several other measures while slightly decreasing (P &lt; 0.01) lean mass (−1.0 kg, C-WL; −0.6 kg, HP-WL). Weight loss was greater in white than in black women at both 4 mo (6.0 ± 3.6 compared with 3.7 ± 3.4 kg; P &lt; 0.02) and 6 mo (7.2 ± 4.8 compared with 4.0 ± 4.7 kg; P &lt; 0.04) and tended to be positively related to age (P &lt; 0.06). CONCLUSIONS: A clinically important functional benefit of obesity reduction was confirmed in both study groups, with no significant group effect. Our findings of racial differences in response to the intervention and a potential influence of participant age lend support for further studies sufficiently powered to explore the interaction of race and age with functional responses to obesity reduction in women. This trial was registered at clinicaltrials.gov as NCT02033655