Novel Approach for Umbilical Hernia Repair Using Mesh Strips.

Umbilical hernia repair is a common surgical procedure without a universally accepted means of repair. We introduce a novel surgical technique for open primary umbilical hernia repair, using strips of polypropylene mesh as sutures to achieve a repair. Methods: Two-centimeter-wide strips of macroporous polypropylene mesh were passed through the abdominal wall and tied as simple interrupted sutures to achieve umbilical hernia repair. A retrospective review of all elective umbilical hernia repairs performed by a single surgeon using the mesh strip technique between 2016 and 2021 was conducted, and patient-reported outcomes were assessed via a telephonic survey. Results: Thirty-three patients underwent an elective, open mesh strip repair of a primary umbilical hernia and met criteria for inclusion in the study. Of these patients, 60% responded to a patient-reported outcomes telephone survey. Ninety percent of survey responders reported a pain score of 0 of 10. Additionally, 90% reported being unable to feel or palpate the knot, and 80% reported an improvement in quality of life. Mean follow-up at 3 years revealed one recurrence in the setting of ascites, yielding a recurrence rate of 3%. Conclusion: Primary mesh strip repair of umbilical hernias combines the simplicity of suture repair with the advantageous force distribution properties of mesh, and constitutes a safe, efficient, and effective method of repair with a low recurrence rate at long-term follow-up that is comparable to planar mesh repair.

Targeted muscle reinnervation in above knee amputation: surgical technique.

In the United States, an estimated 185,000 individuals undergo amputation of their upper or lower limb. This results in residual limb pain in up to 85% of cases. Targeted muscle reinnervation (TMR) is a technique that has been shown to prevent symptomatic neuroma formation. In this video, the authors demonstrate their technique utilizing TMR at the time of above-the-knee amputation. Coaptations are made to provide motor targets for branches of the saphenous, tibial, and peroneal sensory nerves. At the featured patient's most recent follow-up visit 3 months postoperatively, she reported no stump pain or phantom limb pain. The video can be found here: https://stream.cadmore.media/r10.3171/2022.10.FOCVID2293.

Insight into human Miro1/2 domain organization based on the structure of its N-terminal GTPase.

Dysfunction in mitochondrial dynamics is believed to contribute to a host of neurological disorders and has recently been implicated in cancer metastasis. The outer mitochondrial membrane adapter protein Miro functions in the regulation of mitochondrial mobility and degradation, however, the structural basis for its roles in mitochondrial regulation remain unknown. Here, we report a 1.7Å crystal structure of N-terminal GTPase domain (nGTPase) of human Miro1 bound unexpectedly to GTP, thereby revealing a non-catalytic configuration of the putative GTPase active site. We identify two conserved surfaces of the nGTPase, the "SELFYY" and "ITIP" motifs, that are potentially positioned to mediate dimerization or interaction with binding partners. Additionally, we report small angle X-ray scattering (SAXS) data obtained from the intact soluble HsMiro1 and its paralog HsMiro2. Taken together, the data allow modeling of a crescent-shaped assembly of the soluble domain of HsMiro1/2. PDB RSEFERENCE: Crystal structure of the human Miro1 N-terminal GTPase bound to GTP, 6D71.

Mandibular Catch-Up Growth in Pierre Robin Sequence: A Systematic Review.

OBJECTIVE: The concept of mandibular catch-up growth is often quoted in the literature regarding Pierre Robin sequence (PRS). We endeavored to perform a systematic review of whether the literature supports this concept. DESIGN: Systematic review. INTERVENTIONS: A PubMed-based systematic review of the English literature was performed of articles objectively measuring mandibular growth or position after nonoperative management of PRS. MAIN OUTCOME MEASURES: Rate and end point of mandibular length, ramus length, gonial angle, and maxillomandibular discrepancy. RESULTS: The initial search delivered 607 English-language abstracts. Of these, 16 met inclusion criteria. Eight articles evaluating 143 patients followed longitudinal patient data and therefore allowed comparison of growth rates to controls. Ten articles evaluating 228 patients presented cross-sectional data and therefore could only evaluate a single time point. Two of the 8 longitudinal studies reported faster than normal growth of mandibular length in a significant portion of their cohort. Five of 8 reported equal growth rates. One of 16 studies reported that mandibular length of patients with PRS normalized compared to controls. Two of 16 studies reported no difference in maxillomandibular discrepancy between PRS and controls, whereas 10 reported a posteriorly displaced mandible relative to the maxilla in PRS. Significant differences in control groups, patients, and age existed between studies. CONCLUSIONS: While the concept of catch-up growth in PRS is often quoted, a minority of objective studies suggest increased mandibular growth rates in isolated PRS. Even fewer studies suggest that the maxillomandibular discrepancy in PRS completely resolves.

Mechanism of ubiquitin chain synthesis employed by a HECT domain ubiquitin ligase.

Homologous to E6AP C-terminal (HECT) ubiquitin (Ub) ligases (E3s) are a large class of enzymes that bind to their substrates and catalyze ubiquitination through the formation of a Ub thioester intermediate. The mechanisms by which these E3s assemble polyubiquitin chains on their substrates remain poorly defined. We report here that the Nedd4 family HECT E3, WWP1, assembles substrate-linked Ub chains containing Lys-63, Lys-48, and Lys-11 linkages (Lys-63 > Lys-48 > Lys-11). Our results demonstrate that WWP1 catalyzes the formation of Ub chains through a sequential addition mechanism, in which Ub monomers are transferred in a successive fashion to the substrate, and that ubiquitination by WWP1 requires the presence of a low-affinity, noncovalent Ub-binding site within the HECT domain. Unexpectedly, we find that the formation of Ub chains by WWP1 occurs in two distinct phases. In the first phase, chains are synthesized in a unidirectional manner and are linked exclusively through Lys-63 of Ub. In the second phase, chains are elongated in a multidirectional fashion characterized by the formation of mixed Ub linkages and branched structures. Our results provide new insight into the mechanism of Ub chain formation employed by Nedd4 family HECT E3s and suggest a framework for understanding how this family of E3s generates Ub signals that function in proteasome-independent and proteasome-dependent pathways.

Resolution of Cosmetic Buttock Injection-induced Inflammatory Reaction and Heart Failure after Excision of Filler Material.

We present a case of a 66-year-old woman who developed heart failure and severe inflammatory reaction after the illicit cosmetic injections of polymethyl-methacrylate or polyacrylamide hydrogel from a primary care provider. After medical optimization, an en bloc excision of all injectable materials and gluteus muscle was performed, which resulted in exposure of bilateral sciatic nerves. Within 10 days, the patient's heart failure resolved and inflammatory state improved. This is the first known report of heart failure due to buttock injections and subsequent improvement after surgery.

Structural insights into Parkin substrate lysine targeting from minimal Miro substrates.

Hereditary Parkinson's disease is commonly caused by mutations in the protein kinase PINK1 or the E3 ubiquitin ligase Parkin, which function together to eliminate damaged mitochondria. PINK1 phosphorylates both Parkin and ubiquitin to stimulate ubiquitination of dozens of proteins on the surface of the outer mitochondrial membrane. However, the mechanisms by which Parkin recognizes specific proteins for modification remain largely unexplored. Here, we show that the C-terminal GTPase (cGTPase) of the Parkin primary substrate human Miro is necessary and sufficient for efficient ubiquitination. We present several new X-ray crystal structures of both human Miro1 and Miro2 that reveal substrate recognition and ubiquitin transfer to be specific to particular protein domains and lysine residues. We also provide evidence that Parkin substrate recognition is functionally separate from substrate modification. Finally, we show that prioritization for modification of a specific lysine sidechain of the cGTPase (K572) within human Miro1 is dependent on both its location and chemical microenvironment. Activation of Parkin by phosphorylation or by binding of pUb is required for prioritization of K572 for modification, suggesting that Parkin activation and acquisition of substrate specificity are coupled.

Structural coupling of the EF hand and C-terminal GTPase domains in the mitochondrial protein Miro.

Miro is a highly conserved calcium-binding GTPase at the regulatory nexus of mitochondrial transport and autophagy. Here we present crystal structures comprising the tandem EF hand and carboxy terminal GTPase (cGTPase) domains of Drosophila Miro. The structures reveal two previously unidentified 'hidden' EF hands, each paired with a canonical EF hand. Each EF hand pair is bound to a helix that structurally mimics an EF hand ligand. A key nucleotide-sensing element and a Pink1 phosphorylation site both lie within an extensive EF hand-cGTPase interface. Our results indicate structural mechanisms for calcium, nucleotide and phosphorylation-dependent regulation of mitochondrial function by Miro.