Epistatic hotspots organize antibody fitness landscape and boost evolvability.

The course of evolution is strongly shaped by interaction between mutations. Such epistasis can yield rugged sequence-function maps and constrain the availability of adaptive paths. While theoretical intuition is often built on global statistics of large, homogeneous model landscapes, mutagenesis measurements necessarily probe a limited neighborhood of a reference genotype.

Very early life microbiome and metabolome correlates with primary vaccination variability in children.

We show that simultaneous study of stool and nasopharyngeal microbiome reveals divergent timing and patterns of maturation, suggesting that local mucosal factors may influence microbiome composition in the gut and respiratory system. Antibiotic exposure in early life as occurs commonly, may have an adverse effect on vaccine responsiveness. Abundance of gut and/or nasopharyngeal bacteria with the machinery to produce lipopolysaccharide-a toll-like receptor 4 agonist-may positively affect future vaccine protection, potentially by acting as a natural adjuvant.

Evaluating hip disarticulation outcomes in a 51-patient series.

Background: Hip disarticulations are proximal lower extremity amputations with high postoperative complication and mortality rates. The purpose of the study was to evaluate hip disarticulation outcomes at our institution. Targeted Muscle Reinnervation (TMR) is an effective surgical technique shown to reduce pain in amputees.

Longitudinal Durability of Patient-Reported Pain Outcomes after Targeted Muscle Reinnervation at the Time of Major Limb Amputation.

Background: Phantom limb pain (PLP) and residual limb pain (RLP) are debilitating sequelae of major limb amputation. Targeted muscle reinnervation (TMR), when performed at the time of amputation, has been shown to be effective for management of this pain; however, its long-term effects and the longitudinal trend of patient-reported outcomes is unknown. The purpose of this study was to characterize the longitudinal patient-reported outcomes of pain and quality of life following TMR at the time of initial amputation.

Targeted Muscle Reinnervation in Partial Hand Amputations.

Targeted muscle reinnervation (TMR) surgery has been shown to aid in prevention and treatment of neuropathic pain. Technical and anatomical descriptions of TMR surgery for upper extremity amputees (including transradial, transhumeral, and forequarter amputations) have been reported, yet such descriptions of TMR surgery for partial hand amputations are currently lacking. Herein we outline the technique of different types of partial hand amputation TMR surgeries to serve as a reference and guide.

Factors influencing the detection of treatable epileptogenic lesions on MRI. A randomized prospective study.

Background: To prospectively analyze factors associated with detecting epileptogenic lesions on MRI within the work-sharing process of neurologists, epileptologists, radiologists and neuroradiologists.

Methods: We assembled four sets of six MRI scans, each set representing five typical epileptogenic lesions (hippocampal sclerosis or limbic encephalitis; focal cortical dysplasias; periventricular nodular or other heterotopias; long-term epilepsy associated tumors; gliotic scar, hemosiderin or cavernoma), and non - lesional epilepsy. At professional conferences, we invited neurologists, epileptologists, radiologists, and neuroradiologists to read two out of four MRI sets, one of which was presented with a clinical focus hypothesis.

Parameters and determinants of responses to selection in antibody libraries.

The sequences of antibodies from a given repertoire are highly diverse at few sites located on the surface of a genome-encoded larger scaffold. The scaffold is often considered to play a lesser role than highly diverse, non-genome-encoded sites in controlling binding affinity and specificity. To gauge the impact of the scaffold, we carried out quantitative phage display experiments where we compare the response to selection for binding to four different targets of three different antibody libraries based on distinct scaffolds but harboring the same diversity at randomized sites.

The application of indocyanine green (ICG) and near-infrared (NIR) fluorescence imaging for assessment of the lymphatic system in reconstructive lymphaticovenular anastomosis surgery.

Introduction: Lymphedema has traditionally been managed through noninvasive means with complete decongestive therapy. However, complete decongestive therapy is an intensive program that requires lifelong adherence by patients with lymphedema. More recently, reconstructive surgical procedures have shown promise in improving lymphedema by physiologically restoring lymphatic function.

Negative pressure wound therapy: device design, indications, and the evidence supporting its use.

Negative pressure wound therapy (NPWT) has become a mainstay in the armamentarium for wound care. Since the initial commercial vacuum-assisted closure device became available in 1995, subsequent research has confirmed the positive physiological effects of negative pressure on wound healing. Traditionally, NPWT has been used to improve healing of open nonsurgical wounds by secondary intention.

Residual breast tissue after robot-assisted nipple sparing mastectomy.

Introduction: While the long-term oncologic safety of robot-assisted nipple sparing mastectomy (RNSM) remains to be elucidated, histologically detected residual breast tissue (RBT) can be a surrogate for oncologically sound mastectomy. The objective of this study is to determine the presence of RBT after RNSM.

Methods: Between August 2019-January 2020, we completed 5 cadaveric RNSMs.

A multidisciplinary approach to complex oncological spine coverage in high-risk patients.

Objective: The consequences of failed spinal hardware secondary to wound complications can increase the burden on the patient while also significantly escalating the cost of care. The objective of this study was to demonstrate the effectiveness of a protocol-based multidisciplinary approach in optimizing wound outcome in complex oncological spine care patients.

Methods: A retrospective consecutive case series was performed from 2015 to 2019 of all patients who underwent oncological spine surgery.

Targeted muscle reinnervation for the management of pain in the setting of major limb amputation.

The life altering nature of major limb amputations may be further complicated by neuroma formation in up to 60% of the estimated 2 million major limb amputees in the United States. This can be a source of pain and functional limitation of the residual limb. Pain associated with neuromas may limit prosthetic limb use, require reoperation, lead to opioid dependence, and dramatically reduce quality of life.

Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase signaling in cardiac myocytes by oxidizing agents.

The contraction and relaxation of the heart is controlled by stimulation of the β1-adrenoreceptor (AR) signaling cascade, which leads to activation of cAMP-dependent protein kinase (PKA) and subsequent cardiac protein phosphorylation. Phosphorylation is counteracted by the main cardiac protein phosphatases, PP2A and PP1. Both kinase and phosphatases are sensitive to intramolecular disulfide formation in their catalytic subunits that inhibits their activity.

Targeted Muscle Reinnervation Combined with a Vascularized Pedicled Regenerative Peripheral Nerve Interface.

Symptomatic neuromas and pain caused by nerve transection injuries can adversely impact a patient's recovery, while also contributing to increased dependence on opioid and other pharmacotherapy. These sources of pain are magnified following amputation surgeries, inhibiting optimal prosthetic wear and function. Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI) represent modern advances in addressing amputated peripheral nerves.

Instillation negative pressure wound therapy: An effective approach for hardware salvage.

Wound infection involving hardware can be notoriously difficult to treat, often requiring the removal of the infected implant. The goal of this study was to determine the utility of instillation negative pressure wound therapy to help eradicate infection and allow for definitive wound closure in patients without removing the infected hardware. A retrospective review was performed on the outcomes of 28 patients who presented with open wounds with exposed or infected hardware and who were treated with a combination of surgical debridement and negative pressure wound therapy with instillation (NPWTi).

Incisional Negative Pressure Wound Therapy: An Effective Tool for Major Limb Amputation and Amputation Revision Site Closure.

To evaluate our institutional experience of incisional negative pressure wound therapy (iNPWT) applied immediately after major limb amputation closure or amputation revision closure. A retrospective review was performed on 25 patients who underwent major limb amputation or amputation revision and had iNPWT placed intraoperatively upon incision closure. Twenty-one patients underwent lower extremity amputation and four underwent upper extremity amputation.

Analysis of fibrosis in control or pressure overloaded rat hearts after mechanical unloading by heterotopic heart transplantation.

Mechanical unloading (MU) by implantation of left ventricular assist devices (LVAD) has become clinical routine. This procedure has been shown to reverse cardiac pathological remodeling, with the underlying molecular mechanisms incompletely understood. Most studies thus far were performed in non-standardized human specimens or MU of healthy animal hearts.

Comparison of Polypropylene and Bioabsorbable Mesh for Abdominal Wall Reinforcement following Microsurgical Breast Reconstruction.

Background:  Abdominal wall morbidity following microvascular breast reconstruction continues to be an area of interest due to both functional and aesthetic concerns. Donor-site closure technique has been shown to affect bulge and hernia rates and ranges from primary closure to various uses of mesh. Few studies to date have compared types of mesh.