Human Cytomegalovirus Enhances Placental Susceptibility and Replication of Human Immunodeficiency Virus Type 1 (HIV-1), Which May Facilitate In Utero HIV-1 Transmission.

Several co-pathogens that pose threats to the fetus during gestation, including human cytomegalovirus (HCMV), may also contribute to mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1). Within endemic settings, associations between maternal HCMV viral load and increased incidence of MTCT of HIV-1 are documented; however, the mechanisms that promote transmission are poorly characterized. Here we demonstrate that HCMV coinfection enhances susceptibility and viral replication of HIV-1 in placental macrophages (Hofbauer cells) in vitro. Consistent with enhanced viral susceptibility, HCMV exposure upregulates CCR5 and CD80 expression on Hofbauer cells. HCMV also significantly induces type I interferon (IFN), proinflammatory cytokines, and antiviral gene expression. Interestingly, we found that HCMV diminishes type I IFN-mediated phosphorylation of STAT2. Collectively, our data suggest that HCMV-induced activation, local inflammation, and antagonism of type I IFN responses in placental Hofbauer cells promote in utero transmission of HIV-1.

ACKR3-arrestin2/3 complexes reveal molecular consequences of GRK-dependent barcoding.

Atypical chemokine receptor 3 (ACKR3, also known as CXCR7) is a scavenger receptor that regulates extracellular levels of the chemokine CXCL12 to maintain responsiveness of its partner, the G protein-coupled receptor (GPCR), CXCR4. ACKR3 is notable because it does not couple to G proteins and instead is completely biased towards arrestins. Our previous studies revealed that GRK2 and GRK5 install distinct distributions of phosphates (or "barcodes") on the ACKR3 carboxy terminal tail, but how these unique barcodes drive different cellular outcomes is not understood. It is also not known if arrestin2 (Arr2) and 3 (Arr3) bind to these barcodes in distinct ways. Here we report cryo-electron microscopy structures of Arr2 and Arr3 in complex with ACKR3 phosphorylated by either GRK2 or GRK5. Unexpectedly, the finger loops of Arr2 and 3 directly insert into the detergent/membrane instead of the transmembrane core of ACKR3, in contrast to previously reported "core" GPCR-arrestin complexes. The distance between the phosphorylation barcode and the receptor transmembrane core regulates the interaction mode of arrestin, alternating between a tighter complex for GRK5 sites and heterogenous primarily "tail only" complexes for GRK2 sites. Arr2 and 3 bind at different angles relative to the core of ACKR3, likely due to differences in membrane/micelle anchoring at their C-edge loops. Our structural investigations were facilitated by Fab7, a novel Fab that binds both Arr2 and 3 in their activated states irrespective of receptor or phosphorylation status, rendering it a potentially useful tool to aid structure determination of any native GPCR-arrestin complex. The structures provide unprecedented insight into how different phosphorylation barcodes and arrestin isoforms can globally affect the configuration of receptor-arrestin complexes. These differences may promote unique downstream intracellular interactions and cellular responses. Our structures also suggest that the 100% bias of ACKR3 for arrestins is driven by the ability of arrestins, but not G proteins, to bind GRK-phosphorylated ACKR3 even when excluded from the receptor cytoplasmic binding pocket.

Arthroscopic meniscus repair and augmentation with autologous fibrin clot in Indian population: A 2-year prospective study.

Introduction: This study was proposed to evaluate the efficacy of fibrin clot augmentation in meniscal tear using inside-out meniscal repair. Methods: A total of 35 patients with meniscus tears were operated on with inside-out meniscus repair and fibrin clot augmentation. Patients were evaluated preoperatively and postoperatively with clinical criteria, Lysholm knee scoring system, and MRI. Results: Out of the total 35 cases, 5 cases were lost to follow-up. Clinical improvement was observed in 29 out of 30 patients (96.6%). The mean Lysholm score improved significantly from 67.63 ± 6.55 points preoperatively to 92.0 ± 2.9 points postoperatively (P < 0.05) in 3 years follow-up. Follow-up MRI in all patients revealed complete healing except in 1 case where the patient presented with recurrence of symptoms such as pain and locking which resolved with partial meniscectomy. Paraesthesia in the anterior part of the knee was observed in 2 cases. (6.6%). Conclusion: We conclude that fibrin clot augmentation is a good cost-effective modality of treatment for repairable meniscus tears to preserve the meniscus and decrease the point contact pressure on the condyles which may prevent the early occurrence of osteoarthritis.

Single-Cut Single-Screw Capitate-Shortening Osteotomy for Kienbock's Disease.

Background Kienbock's disease, in spite of an uncertain natural history, is known to cause lunate compromise, leading to central column collapse, carpal instability, and degenerative arthritis of the wrist. Joint leveling procedures are performed in the early stages of Kienbock's disease to "unload" the lunate. Capitate shortening is the preferred procedure in Kienbock's patients with positive ulnar variance. Description of Technique We describe the rationale and a simplified technique of capitate shortening in early Kienbock's disease. This is a single-cut osteotomy with single-screw stabilization. Patients and Methods We have performed this technique in three cases. We present a case of a 26-year-old male who presented with a 1-year history of pain in his right wrist. Radiology performed demonstrated lunate sclerosis. Diagnostic arthroscopy revealed healthy articular surfaces. Single osteotomy capitate shortening was performed with an oscillating saw and fixed with a single cannulated compression screw. A shortening of 1.5mm was obtained with this technique. Results At 1- to 2-year follow-up, all three patients had considerable pain relief but did not have a complete resolution of pain. There was a significant improvement in function and grip strength. There have been no cases with infection, nonunion, avascular necrosis or a need for a salvage procedure. Conclusion The simplified technique of capitate shortening is easy to perform, less traumatic to the capitate vascularity, and leads to good short-term functional results.

Evaluation of Functional Outcome of Arthroscopic Rotator Cuff Repair Using Southern California Orthopedic Institute Technique.

BACKGROUND: The number of anchors and modality of fixation to be used has been a point of debate in the arthroscopic management of rotator cuff repair. Southern California Orthopedic Institute (SCOI) technique has shown better anatomical healing of tendons using single-row anchors. In this study, we evaluated the functional outcomes of arthroscopic rotator cuff repair using the SCOI technique, in Indian population. MATERIALS AND METHODS: Thirty two patients (16 males and 16 females) were included in the study, and underwent an arthroscopic repair of small-to-medium-sized rotator cuff tear, at a single institution, for 12 months. Postoperatively, patients were evaluated using UCLA score and Constant-Murley score, and range of motion was analyzed and documented using photographs. RESULTS: Mean age was 57.06 years, and the most common cause of cuff tear was a traumatic degeneration. Mean UCLA score improved from preoperative 8.75 to postoperative 31.79, at 12 months, with the P < 0.001. Similarly, mean Constant-Murley score improved from preoperative 20.66 to postoperative 81.31, at 12 months, with P < 0.001. CONCLUSION: We conclude that the SCOI single-row technique proves to be a good and effective modality of treatment in the arthroscopic management of small-to-medium-sized rotator cuff tears. In Indian population, considering cost-effectiveness, single-row repair of rotator cuff tears using SCOI technique can be an interesting option in its management.

Increased Intracranial Pressure Damages Optic Nerve Structural Support.

Optic nerve sheath diameter (ONSD) is used clinically as a noninvasive measure for elevated intracranial pressure (ICP). This study had two purposes: to investigate the immediate effects optic nerve sheath (ONS) dilation post-ICP increase on trabecular fibers connecting the optic nerve to the ONS and to document any changes in these fibers 30 days post-increased ICP. In a swine model, ICP was increased by inflating a Foley catheter balloon in the epidural space. Three control pigs received the catheter insertion without inflation (no increase in ICP) and four experimental pigs received the catheter with inflation (increased ICP). The control and two randomly selected pigs with increased ICP were euthanized immediately after the procedure. The two other pigs were euthanized 30 days post-catheter inflation. For all pigs, the ONS was removed and imaged using a scanning electron microscope, calculating percent porosity values. Porosity values for the experimental groups (Immediately measured [IM] µ = 0.5749; Delayed measured [DM] µ = 0.5714) were larger than the control group (µ = 0.4336) and statistically significant (IM vs. Control, p = 0.0018; DM vs. Control, p = 0.0092). There was no significant difference (p = 0.9485) in porosity of the DM group when compared with the IM group. This study demonstrated that the trabecular fibers immediately post-increased ICP (ONS dilation) were more porous than the control and remained statistically different (more porous) after 30 days. These results suggest a structural change that occurs in the ONS with elevations in ICP.

Effect of History of Mild Traumatic Brain Injury on Optic Nerve Sheath Diameter Changes after Valsalva Maneuver.

Optic nerve sheath diameter (ONSD) measured by transocular ultrasound is a marker of real-time intracranial pressure (ICP). The objective of this study was to evaluate the association between optic nerve sheath (ONS) dilation after a Valsalva maneuver and a prior history of mild to moderate traumatic brain injury (mTBI) in a heterogeneous sample of participants. Participants were excluded if they had had a recent brain injury, were symptomatic from a prior brain injury, had a history consistent with severe TBI and/or had undergone intracranial surgery. Ninety-five participants with and without a history of mTBI were included in the study. Transocular ultrasound of the ONS was performed before and after a Valsalva maneuver. Differences in the ONSD before and after a Valsalva maneuver were analyzed and correlated to the participants' history of mTBI. Baseline ONSD measurements between groups were not statistically significant. Following Valsalva, participants with a history of mTBI had a statistically significant increase in the ONSD compared with participants with no history of mTBI. This significant difference persisted after controlling for age, race, and sex. This study demonstrated an association between a prior history of mTBI and dilation of the ONS after Valsalva maneuver in a sample of asymptomatic participants, which was not seen in participants without a history of mTBI.

Dyspnea in a case of shoulder dislocation - to beware of this rare life-threatening symptom.

Shoulder dislocation is a common injury in orthopedic practice. In an acute presentation, closed reduction of the shoulder joint leads to an uneventful recovery. However, in the developing world neglected shoulder dislocation and treatments from quacks are not uncommon. Improper treatment and neglect can rarely become life threatening. We present one such case, emphasizing the need to investigate the symptom of dyspnea in a patient with history of shoulder dislocation.