Bloom syndrome patients and mice display accelerated epigenetic aging.

Bloom syndrome (BSyn) is an autosomal recessive disorder caused by variants in the BLM gene, which is involved in genome stability. Patients with BSyn present with poor growth, sun sensitivity, mild immunodeficiency, diabetes, and increased risk of cancer, most commonly leukemias. Interestingly, patients with BSyn do not have other signs of premature aging such as early, progressive hair loss and cataracts. We set out to determine epigenetic age in BSyn, which can be a better predictor of health and disease over chronological age. Our results show for the first time that patients with BSyn have evidence of accelerated epigenetic aging across several measures in blood lymphocytes, as compared to carriers. Additionally, homozygous Blm mice exhibit accelerated methylation age in multiple tissues, including brain, blood, kidney, heart, and skin, according to the brain methylation clock. Overall, we find that Bloom syndrome is associated with accelerated epigenetic aging effects in multiple tissues and more generally a strong effect on CpG methylation levels.

A blended neurostimulation protocol to delineate cortico-muscular and spino-muscular dynamics following neuroplastic adaptation.

In this paper we propose a novel neurostimulation protocol that provides an intervention-based assessment to distinguish the contributions of different motor control networks in the cortico-spinal system. Specifically, we use a combination of non-invasive brain stimulation and neuromuscular stimulation to probe neuromuscular system behavior with targeted impulse-response system identification. In this protocol, we use an in-house developed human-machine interface (HMI) for an isotonic wrist movement task, where the user controls a cursor on-screen. During the task, we generate unique motor evoked potentials based on triggered cortical or spinal level perturbations. Externally applied brain-level perturbations are triggered through TMS to cause wrist flexion/extension during the volitional task. The resultant contraction output and related reflex responses are measured by the HMI. These movements also include neuromodulation in the excitability of the brain-muscle pathway via transcranial direct current stimulation. Colloquially, spinal-level perturbations are triggered through skin-surface neuromuscular stimulation of the wrist muscles. The resultant brain-muscle and spinal-muscle pathways perturbed by the TMS and NMES, respectively, demonstrate temporal and spatial differences as manifested through the human-machine interface. This then provides a template to measure the specific neural outcomes of the movement tasks, and in decoding differences in the contribution of cortical- (long-latency) and spinal-level (short-latency) motor control. This protocol is part of the development of a diagnostic tool that can be used to better understand how interaction between cortical and spinal motor centers changes with learning, or injury such as that experienced following stroke.

Robotic port-site hernias after general surgical procedures.

BACKGROUND: With the increasing use of the robotic platform in general surgery, whether 8-mm ports should be closed comes into question. We sought to characterize the incidence of port-site hernias (PSHs) among patients undergoing robotic-assisted general surgery. METHODS: A retrospective chart review of a single institutional database identified patients who underwent robotic-assisted general surgery from July 2010 to December 2016. For each patient, the number, type, location, and size of all ports were collected. Twelve-millimeter port sites were routinely closed, whereas 5-mm and 8-mm port sites were not. PSH was detected on review of documented physical examination and of postoperative cross-sectional imaging, when available, in which case it was defined as a disruption of the fascia with or without eventration of tissue at a site of prior port placement. RESULTS: One hundred and seventy-eight patients underwent robotic-assisted general surgery, with 725 total ports: 433 8-mm working ports, 72 12-mm working ports, 178 12-mm camera ports, and 42 5-mm assistant ports. Ninety-four percent of the patients were men, the mean age was 63 ± 12, body mass index was 29 ± 7 kg/m2, and the median American Society of Anesthesiologists score was 3. Types of cases included 68 rectal (38.2%), 36 colon (20.2%), 25 hepatopancreatobiliary (14.0%), 21 inguinal hernia (11.8%), and 28 "other" (15.7%) operations. At a median follow-up of 193 d, there were three PSHs through 8-mm port sites (0.7%), two PSHs through 12-mm port sites (0.8%), and no PSH through 5-mm port sites. Two of the three 8-mm PSHs occurred in the early postoperative period and required emergent repair due to small bowel incarceration. CONCLUSIONS: PSHs through 8-mm robotic port sites occur infrequently but can cause significant morbidity. Further investigation with longer follow-up is warranted to better understand the true incidence of robotic PSH.

Familial bilateral abductor vocal cord paralysis.

Familial bilateral abductor vocal cord paralysis is a rare entity with few prior descriptions in the literature. Modes of inheritance include X-linked, autosomal recessive, and autosomal dominant. A case of this condition in a father and son is presented. Signs and symptoms at presentation, diagnosis, therapeutic considerations, and modes of inheritance are discussed.

Single-gene disorders: what role could moonlighting enzymes play?

Single-gene disorders with "simple" Mendelian inheritance do not always imply that there will be an easy prediction of the phenotype from the genotype, which has been shown for a number of metabolic disorders. We propose that moonlighting enzymes (i.e., metabolic enzymes with additional functional activities) could contribute to the complexity of such disorders. The lack of knowledge about the additional functional activities of proteins could result in a lack of correlation between genotype and phenotype. In this review, we highlight some notable and recent examples of moonlighting enzymes and their possible contributions to human disease. Because knowledge and cataloging of the moonlighting activities of proteins are essential for the study of cellular function and human physiology, we also review recently reported and recommended methods for the discovery of moonlighting activities.