Virucidal activity of trehalose 6-monolaurate against dengue virus in vitro.

Dengue fever is an acute febrile disease caused by dengue virus (DENV) infection. Over the past 60 years, DENV has spread throughout tropical regions and currently affects more than 50% of the world's population; however, there are as of yet no effective anti-DENV drugs for clinical treatment. A number of research teams have investigated derivatives of glycolipids as possible agents for the inhibition of DENV. Our objective in this research was to study the antiviral effects of trehalose 6-caprate (TMC), trehalose 6-monolaurate (TML), and trehalose 6-monooleate (TMO), based on reports that the corresponding glycosyl, trehalose, reduces the transmission of Zika virus (ZIKV). We also sought to elucidate the molecular mechanisms underlying inhibition using the RNA isolation and reverse transcription-quantitative polymerase chain reaction, western blot analysis, median tissue culture infectious dose (TCID50 ) assay, and immunofluorescence assay and immunochemistry staining, in vitro. This is the first study to demonstrate the TML-induced inhibition of DENV serotype 2 (DENV-2) in a dose-dependent manner. The inhibitory effects of TML in the pretreated, cotreated, and full-treated groups were confirmed using time of addition assays. We determined that TML restricted viral binding, entry, replication, and release. We also confirmed the efficacy of TML against three clinical isolates of DENV serotypes 1, 3, and 4 (DENV-1, DENV-3, and DENV-4). The findings obtained in this study identify TML as a promising candidate for the development of drugs to treat DENV infection.

Surgical stabilization of the ipsilateral scapula and rib fractures using the mirror Judet approach: a preliminary result.

BACKGROUND: We report our preliminary results using a single approach, the mirror Judet approach, for patients with both ipsilateral scapula and multiple rib fractures. METHODS: Five consecutive patients [median age: 56 years (range: 44 ~ 60)] with ipsilateral scapula and multiple rib fractures that met the surgical indications were retrospectively reviewed. A single approach, the mirror Judet approach, was used for surgical stabilization of the scapula and targeted rib fractures. Thoracoscopic surgery was performed first for management of associated lung lesions and marking the targeted rib. All patients received the same rehabilitation protocol and a minimum 12-month follow-up. RESULTS: All surgically-fixed fractures eventually united without malunion. No complaints of intercostal neuralgia, infection, or other complications were seen. The mean range of motion in the injured shoulder returned to at least 90% of the contralateral side range. The mean Disabilities of the Arm, Shoulder, and Hand score at the 12th month was 2.0 (range: 0-7). All patients were able to return to their previous work. CONCLUSION: The mirror Judet approach allows for the surgical stabilization of the ipsilateral scapula and multiple rib fractures using the same approach and provides acceptable functional outcomes in well-selected patients. LEVEL OF EVIDENCE: Level IV.

Isolated and early-onset cerebral fat embolism syndrome in a multiply injured patient: a rare case.

BACKGROUND: Fat embolism syndrome (FES) is a rare complication that can occur between 12 and 72 h after the initial insult. Isolated cerebral FES without pulmonary symptoms is rarer. Early fracture fixation might prevent FES. We report a case of multiple-fracture with FES despite definite fixation three hours post-injury. CASE PRESENTATION: A 54-year-old man presented with multiple fractures: left femoral shaft (AO B2), left distal radius (AO C3), left comminuted patella, right comminuted 1st metatarsal base and left 2nd-4th metatarsal neck. Because he was stable, we gave him early total care and definite fixation, which required seven hours and yielded no complications. After he recovered from anesthesia, however, his eyes deviated right, his right upper arm was paralyzed, his consciousness level was poor, and his Glasgow Coma Scale score was E3VeM4. Chest X-rays showed clear lung fields, and brain computed tomography showed no intracranial hemorrhage. He did, however, have tachycardia, anemia, and thrombocytopenia. Brain magnetic resonance images showed a hyperintensive starfield pattern on diffuse weighted images, which suggested cerebral FES. After supportive care, his consciousness cleared on postoperative day 17, and he recovered full right upper arm muscle power after four months; however, he had a significant cognitive deficit. One-year post-injury, after regular rehabilitation therapy, he was able to independently perform his activities of daily living but still had a residual mild cognitive deficit. CONCLUSION: Early fixation can attenuate but not eliminate the incidence of FES. Early assessment and rehabilitation therapy might be required for patients with cerebral FES and cognitive deficits; however, such deficits are difficult to predict and need long-term follow-ups.

Synergistic in-vitro antiviral effects of combination treatment using anidulafungin and T-1105 against Zika virus infection.

Zika virus (ZIKV) has been the cause of some epidemics since 2007. The correlations of microcephaly and Guillain-Barré syndrome with ZIKV have been noticed. Unfortunately, researchers have yet to develop an effective vaccine or drug approved for ZIKV infection. Anidulafungin is a member of echinocandins that is used to treat candida infections. This study assessed the antiviral capability of anidulafungin against ZIKV. Anidulafungin was shown to significantly decrease viral RNA levels, protein expression levels, viral yields, and the rate of infection. In time of addition assays, anidulafungin exhibited inhibitory activities in the early stages of ZIKV infection. In binding and entry assays, administering anidulafungin did not lead to a corresponding decrease in quantity of viral RNA, but a significant decrease in ZIKV infectivity was observed in virucidal assays. This indicated that anidulafungin interferes directly with virions. T-1105 is a viral polymerase inhibitor, which functions in the late stage of ZIKV infection. When anidulafungin was administered in combination with T-1105, an obvious synergistic effect was observed, resulting in a combination index (CI) value of 0.85 ± 0.13. Finally, we evaluated the effects of echinocandins in terms of half-maximal inhibitory concentration (IC50), calculation of cytotoxicity concentration 50% (CC50), selectivity index (SI), and Patchdock score. Among the tests, anidulafungin bears the lowest IC50 and highest Patchdock score. Although anidulafungin is classified as a pregnancy category C agent; however, combination therapy of anidulafungin with a viral RNA replication inhibitor could expand treatment options for ZIKV infection.

A rare complication of ipsilateral femoral neck fracture after removal of the long Gamma nail in a healed intertrochanteric fracture.

Ipsilateral femoral neck fracture after hardware removal in healed trochanteric fracture is a rare complication. We reported a case of a 79-year-old woman who had undergone open reduction and internal fixation for her left intertrochanteric fracture with a long Gamma nail about 1 year ago. She asked for implants removal due to local irritation. However, 5 days after implants removal, left subcapital femoral neck fracture occurred. Removal of implants under elective indications could lead to high complication rate. Orthopedic surgeons should perform the removal of hardware in healed intertrochanteric fracture for very selected cases.