Cyclin D3 restricts SARS-CoV-2 envelope incorporation into virions and interferes with viral spread.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a great threat to human health. The interplay between the virus and host plays a crucial role in successful virus replication and transmission. Understanding host-virus interactions are essential for the development of new COVID-19 treatment strategies. Here, we show that SARS-CoV-2 infection triggers redistribution of cyclin D1 and cyclin D3 from the nucleus to the cytoplasm, followed by proteasomal degradation. No changes to other cyclins or cyclin-dependent kinases were observed. Further, cyclin D depletion was independent of SARS-CoV-2-mediated cell cycle arrest in the early S phase or S/G2/M phase. Cyclin D3 knockdown by small-interfering RNA specifically enhanced progeny virus titres in supernatants. Finally, cyclin D3 co-immunoprecipitated with SARS-CoV-2 envelope (E) and membrane (M) proteins. We propose that cyclin D3 impairs the efficient incorporation of envelope protein into virions during assembly and is depleted during SARS-CoV-2 infection to restore efficient assembly and release of newly produced virions.

Multifunctional Biomimetic Nanofibrous Scaffold Loaded with Asiaticoside for Rapid Diabetic Wound Healing.

Diabetes mellitus is a chronic disease with a high mortality rate and many complications. A non-healing diabetic foot ulcer (DFU) is one the most serious complications, leading to lower-extremity amputation in 15% of diabetic patients. Nanofibers are emerging as versatile wound dressing due to their unique wound healing properties, such as a high surface area to volume ratio, porosity, and ability to maintain a moist wound environment capable of delivering sustained drug release and oxygen supply to a wound. The present study was aimed to prepare and evaluate a polyvinyl alcohol (PVA)-sodium alginate (SA)-silk fibroin (SF)-based multifunctional nanofibrous scaffold loaded with asiaticoside (AT) in diabetic rats. The SEM findings showed that fibers' diameters ranged from 100-200 nm, and tensile strengths ranged from 12.41-16.80 MPa. The crosslinked nanofibers were sustained AT over an extended period. The MTT and scratch assay on HaCat cells confirmed low cytotoxicity and significant cell migration, respectively. Antimicrobial tests revealed an excellent anti-microbial efficacy against P. aeruginosa and S. aureus bacteria. In-vivo study demonstrated better wound healing efficacy in diabetic rats. In addition, the histopathological studies showed its ability to restore the normal structure of the skin. The present study concluded that developed multifunctional nanofibers have a great potential for diabetic wound healing applications.

Tramadol sparing effect of dexmedetomidine as an adjuvant with lignocaine in preoperative stellate ganglion block for postoperative pain relief following upper limb surgeries.

BACKGROUND: Recent literature has established the role of stellate ganglion block (SGB) for management of acute postoperative pain. The effects of dexmedetomidine as an adjuvant to lignocaine in a preoperative SGB for postoperative pain relief have not been evaluated so far. METHODS: The following randomised, double-blinded, control trail included 54 patients scheduled for upper limb orthopaedic surgery under general anaesthesia. Preoperative ultrasound-guided (USG) SGB was performed in all patients. Group I (n = 18) received 3.5 mL of a solution (3 mL 2% lignocaine + 0.5 µg/kg dexmedetomidine for SGB) and 15 mL of intravenous (IV) normal saline (NS). Group II (n = 18) received 3.5 mL of a solution (3 mL 2% lignocaine + 0.5 mL NS for SGB) and 15 mL of IV NS. Group III (n = 18) received 3.5 mL of a solution (3 mL 2% lignocaine + 0.5 mL of NS for SGB) and 0.5 µg/kg dexmedetomidine in 15 mL of IV NS. Postoperatively tramadol consumption and Visual Analogue Scale (VAS) score were recorded up to 48 hours. RESULTS: The cumulative tramadol consumption at the end of 48 hours (p = 0.01) was significantly reduced in the group I as compared to group II. In group I, postoperative VAS at rest was significantly reduced up to 12 hours postoperatively as compared to group II (p = 0.05). The cumulative tramadol consumption was not reduced significantly in group III compared to group II (p = 0.51). CONCLUSION: Dexmedetomidine as an adjuvant to SGB along with lignocaine produced a significant tramadol sparing effect and superior analgesia as compared to IV dexmedetomidine and control group.1.

Triceps tendon reconstruction using autologous semitendinosis graft in professional kabaddi player-A rare case report.

Triceps tendon rupture is a rare injury occurs due to sudden forceful contraction of triceps against flexed elbow. Though there are case reports describing various treatment options for this injury, including primary repair as well as reconstruction using different technique, no standardised technique has been defined. We present, for the first time, a case of five month old neglected triceps tendon rupture in a professional kabaddi player. Ruptured tendon was reconstructed using free autologous semitendinous graft with good functional outcome.

"Quadrangular-construct" modification of Sauve-Kapandji procedure.

BACKGROUND: Subluxation of ulna in distal radioulnar joint disorders causes pain on motion, loss of grip strength, and a restriction of forearm rotation. Several procedures have been described to salvage DRUJ disorders including the Darrach procedure, the matched distal ulnar resection, the hemiresection interposition arthroplasty (Bowers procedure) and the Sauve-Kapandji (S-K) procedure. All these procedures are associated with either loss of grip, pain over proximal ulnar stump or instability. We describe our modification of S-K procedure with good functional outcome. MATERIALS AND METHODS: Twenty patients, 12 male and 8 female, underwent S-K procedure, with our modification, were included in this study. Patients were evaluated preoperatively, postoperatively, and on followup visits using Modified Mayo Wrist Score and wrist radiographs. Average followup period was 34.55 months (range 24-64 months). RESULTS: Excellent results were found in one patient, good in 15 patients, and fair in four patients. Mean Modified Mayo Wrist Score improved from 32 to 79.75, which was statistically significant. CONCLUSIONS: Our modification of S-K procedure provides good functional outcome with stable ulnar stump and without significant procedure-related complications.

Rotary ultrasonic drilling on bone: A novel technique to put an end to thermal injury to bone.

Bone drilling is common in orthopedic procedures and the heat produced during conventional experimental drilling often exceeds critical temperature of 47 °C and induces thermal osteonecrosis. The osteonecrosis may be the reason for impaired healing, early loosening and implant failure. This study was undertaken to control the temperature rise by interrupted cutting and reduced friction effects at the interface of drill tool and the bone surface. In this work, rotary ultrasonic drilling technique with diamond abrasive particles coated on the hollow drill tool without any internal or external cooling assistance was used. Experiments were performed at room temperature on the mid-diaphysis sections of fresh pig bones, which were harvested immediately after sacrifice of the animal. Both rotary ultrasonic drilling on bone and conventional surgical drilling on bone were performed in a five set of experiments on each process using identical constant process parameters. The maximum temperature of each trial was recorded by K-type thermocouple device. Ethylenediaminetetraacetic acid decalcification was done for microscopic examination of bone. In this comparative procedure, rotary ultrasonic drilling on bone produced much lower temperature, that is, 40.2 °C ± 0.4 °C and 40.3 °C ± 0.2 °C as compared to that of conventional surgical drilling on bone, that is, 74.9 °C ± 0.8 °C and 74.9 °C ± 0.6 °C with respect to thermocouples fixed at first and second position, respectively. The conventional surgical drilling on bone specimens revealed gross tissue burn, microscopic evidence of thermal osteonecrosis and tissue injury in the form of cracks due to the generated force during drilling. But our novel technique showed no such features. Rotary ultrasonic drilling on bone technique is robust and superior to other methods for drilling as it induces no thermal osteonecrosis and does not damage the bone by generating undue forces during drilling.

Sports injury pattern in school going children in Union Territory of Chandigarh.

OBJECTIVE: To determine incidence of various types of sport injuries and other associated factors, among competitive sports playing school children of Chandigarh. DESIGN: This study is a survey based study, and spanned for a period of one year. School going students in age group 11-18 years of Chandigarh (Union Territory) India, who were in competitive sports, were included for this survey after taking informed consent from concerned school authorities. 33 schools consisting of 36.165 students were analysed in the study, 7230 students were found to participate in 40 different categories of sports. RESULTS: Total of 246 filled questionnaires were analyzed making it an injury frequency of 3.40% among 7230 participating young athletes in 12 months study duration. Estimated incidence rate, considering hours of exposure in practice, came out to be 48.07 injuries per 1000 h of exposure in practice among 246 injured cases. 40.2% of the injured children (99/246) attributed their injury to poor ground condition while other 30.5% (75/246) to faulty techniques. Rest attributed their injuries to poor fitness levels, improper use of equipment and other reasons. Of the 33 schools surveyed, 27.3% (9/33) had a doctor as health professional, 9.1% (2/33) had a physiotherapist while 66.6% of the schools (22/33) had no health care professional. CONCLUSION: The incidence of sports injuries in the region is high as compared to the global data. The findings has highlighted the need for a nationwide surveillance system and then taking appropriate measures for future injury prevention and appropriate management.

Leaf extract of Azadirachta indica (neem): a potential antibiofilm agent for Pseudomonas aeruginosa.

Pseudomonas aeruginosa is well known for its ability to form biofilm on indwelling medical devices. These biofilms are difficult to remove because of their high tolerance to conventional antibiotics. Therefore, there is a need to look for alternative agents such as medicinal plants, which can eradicate or inhibit biofilm effectively. This study evaluated the role of neem in inhibiting biofilm formation by P aeruginosa Factors contributing to adherence and biofilm formation were also studied. Results demonstrated that neem leaves extract was quite effective in disrupting formation and structure of biofilms. Moreover, the level of exopolysaccharide, alginate, hydrophobic interactions and uroepithelial cell attachment, which contributes to biofilm formation, was also affected significantly. Results confirm the effectiveness of neem extract in inhibiting biofilm formation. Such studies can lead to the discovery of safe antimicrobial drugs from natural sources without the risk of resistance.

Supratentorial primitive neuroectodermal tumor in an adult: a case report and review of the literature.

INTRODUCTION: Supratentorial primitive neuroectodermal tumors predominantly occur in children, and are rare in the adult population. Less than 100 cases of supratentorial primitive neuroectodermal tumor have been reported in adults internationally. Our case study reports this rare incident. CASE PRESENTATION: A 22-year-old Hispanic man presented with headaches, blurry vision, diplopia, intermittent vomiting, and grossly decreased vision. A magnetic resonance image showed a left posterior parietal heterogeneously enhancing mass measuring 4.2cm × 7.2cm × 7.0cm. After craniotomy for resection and decompression, the mass was histologically revealed to be a supratentorial primitive neuroectodermal tumor. Standardized immunohistochemical studies for this mass were carried out. CONCLUSION: We have concluded that immunohistochemical and genetic workup should be included in the standardized pathological workup for primitive neuroectodermal tumors in order to provide more prognostic information. Based on our current literature review, we propose an immunohistochemical panel.

Repair of the torn distal biceps tendon by endobutton fixation.

BACKGROUND: A number of techniques have been described to reattach the torn distal biceps tendon to the bicipital tuberosity. We report a retrospective analysis of single incision technique using an endobutton fixation in sports persons. MATERIALS AND METHODS: The present series include nine torn distal biceps tendons in eight patients, fixed anatomically to the radial tuberosity with an endobutton by using a single incision surgical technique; seven patients had suffered the injuries during contact sports. The passage of the endobutton was facilitated by using a blunt tipped pin in order to avoid injury to the posterior interosseous nerve. The patients were evaluated by Disabilities of the Arm, Shoulder and Hand (DASH) score and Mayo elbow score. RESULTS: The average age of the patients was 27.35 years (range 21-42 years). Average follow-up was 41.5 months (range 24-102 months). The final average flexion extension arc was 0°-143°, while the average pronation and supination angles were 77° (range 70°-82°) and 81° (range 78°-85°), respectively at the last followup. All the patients had a Disabilities of the Arm, Shoulder and Hand (DASH) score of 0 and a Mayo elbow score of 100 each. All the seven active sports persons were able to get back to their respective game. There was no nerve injury or any other complication. CONCLUSIONS: The surgical procedure used by us is a simple, safe and reproducible technique giving minimal morbidity and better cosmetic results.

Evaluation of analgesic efficacy of intra-articular bupivacaine, bupivacaine plus fentanyl, and bupivacaine plus tramadol after arthroscopic knee surgery.

PURPOSE: To compare the efficacy of intra-articular (IA) bupivacaine, bupivacaine-fentanyl, and bupivacaine-tramadol for relief of postoperative pain after arthroscopic knee surgery. METHODS: In a randomized double-blind design, 60 adult American Society of Anesthesiologists class I or class II patients undergoing elective arthroscopic knee surgery under general anesthesia were randomized to 3 groups: all received 30 mL of 0.25% bupivacaine, plus either 1 mL of normal saline solution (group I), 1 mL (50 µg) of fentanyl (group II), or 1 mL (50 mg) of tramadol (group III). Pain was assessed by use of a 100-mm visual analog scale (VAS) at 0, 1, 2, 4, 6, and 8 hours postoperatively. Intramuscular diclofenac sodium was used as rescue analgesic. Postoperative adverse effects were noted. RESULTS: The mean VAS pain scores were the lowest for group II, intermediate for group III, and highest for group I. There was a significant main effect for group differences on pain scores (F = 41.138, P < .001). The main effect for the time factor was also significant (F = 6.097, P < .001). However, both group II and group III were comparable and both were superior to group I with regard to supplementary analgesia in terms of (1) number of patients receiving it, (2) total consumption during the study period, and (3) time to first supplementary analgesic requirement. The incidence of adverse event was comparable among the 3 groups. CONCLUSIONS: On the primary outcome measure (VAS pain score), both bupivacaine with fentanyl and bupivacaine with tramadol were better than IA bupivacaine, and bupivacaine with fentanyl was better than that with tramadol. However, both the combinations were comparable to each other with regard to the secondary outcome measure (supplementary analgesic requirement). Thus IA bupivacaine-fentanyl appears to be the best combination for relief of postoperative pain in patients undergoing arthroscopic knee surgery, followed by IA bupivacaine-tramadol. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains.

BACKGROUND: The Q151M multi-drug resistance (MDR) pathway in HIV-1 reverse transcriptase (RT) confers reduced susceptibility to all nucleoside reverse transcriptase inhibitors (NRTIs) excluding tenofovir (TDF). This pathway emerges after long term failure of therapy, and is increasingly observed in the resource poor world, where antiretroviral therapy is rarely accompanied by intensive virological monitoring. In this study we examined the genotypic, phenotypic and fitness correlates associated with the development of Q151M MDR in the absence of viral load monitoring. RESULTS: Single-genome sequencing (SGS) of full-length RT was carried out on sequential samples from an HIV-infected individual enrolled in ART rollout. The emergence of Q151M MDR occurred in the order A62V, V75I, and finally Q151M on the same genome at 4, 17 and 37 months after initiation of therapy, respectively. This was accompanied by a parallel cumulative acquisition of mutations at 20 other codon positions; seven of which were located in the connection subdomain. We established that fourteen of these mutations are also observed in Q151M-containing sequences submitted to the Stanford University HIV database. Phenotypic drug susceptibility testing demonstrated that the Q151M-containing RT had reduced susceptibility to all NRTIs except for TDF. RT domain-swapping of patient and wild-type RTs showed that patient-derived connection subdomains were not associated with reduced NRTI susceptibility. However, the virus expressing patient-derived Q151M RT at 37 months demonstrated ~44% replicative capacity of that at 4 months. This was further reduced to ~22% when the Q151M-containing DNA pol domain was expressed with wild-type C-terminal domain, but was then fully compensated by coexpression of the coevolved connection subdomain. CONCLUSIONS: We demonstrate a complex interplay between drug susceptibility and replicative fitness in the acquisition Q151M MDR with serious implications for second-line regimen options. The acquisition of the Q151M pathway occurred sequentially over a long period of failing NRTI therapy, and was associated with mutations in multiple RT domains.

Papillary carcinoma of the breast: an overview.

Papillary carcinoma of the breast represents approximately 0.5% of all newly diagnosed cases of breast cancer. The prevalence of both invasive and in situ papillary carcinoma seems to be greater in older postmenopausal women and, in relative terms, in males. Histologic features of the tumor include cellular proliferations surrounding fibrovascular cores, with or without invasion. In this review, characteristics of both in situ and invasive disease are outlined. Immunohistochemical analyses of papillary carcinoma suggest the utility of markers such as smooth muscle myosin heavy chain, calponin, p63, and high molecular weight keratins, which can characterize the myoepithelial cell layer. With respect to radiographic evaluation of papillary carcinoma, ultrasonography is the most extensively studied imaging modality, though magnetic resonance mammography has potential utility. Available data suggest improved outcome for papillary carcinoma as compared to invasive ductal carcinoma. Treatment-related information for patients with papillary carcinoma is limited, and patterns noted in available series suggest a variable approach to this disease. The scarcity of information underscores the need for further treatment- and outcome-related studies in papillary carcinoma of the breast.

Non-union scaphoid: Four-corner fusion of the wrist.

BACKGROUND: Four-corner fusion of the wrist is an option for management of non-union scaphoid with painful arthritis of the wrist. Various surgical techniques have been devised for four-corner fusion, with inconsistent results. We present our experience of four-corner fusion achieved using a standard H-plate, designed originally for anterior cervical plating. MATERIALS AND METHODS: The study is a retrospective analysis of six cases of painful wrist arthritis resulting from nonunion of scaphoid treated by four-corner fusion, between 1996 and 2004. The average duration of follow-up was 5.8 years. Each patient was evaluated clinically according to the rating scales described by Bach. RESULTS: The mean grip-strength calculated as a percentage of the uninvolved side was 47% pre-operatively, and 74% post- operatively at the final follow-up. The difference between the preoperative and postoperative 'pain ratings' and 'activity ratings' was found to be statistically significant (P<0.001). Mean time to fusion was 16.1 weeks. Dorsal impingement was the most common associated problem. CONCLUSIONS: H-plate, used for four-corner fusion, provides rigid fixation, ensures fusion, and is a good alternative to the available options.

Late arthroscopic retrieval of a bullet from hip joint.

We describe a case of arthroscopic retrieval of a bullet from the hip joint of an 18-year-old boy, who sustained the injury four months back, accidentally, while bird hunting with a country made shotgun. The surgery was performed with the standard ordinary instrumentation of knee arthroscopy. The patient became pain-free the same evening and started partial weight bearing on the next day of surgery. At 13 months follow-up, the patient had returned to normal activity without any functional limitations.

Results of operative treatment of acetabular fractures from the Third World--how local factors affect the outcome.

The objective of this study was to assess the outcome of operations on acetabular fractures from a developing country in the presence of locally available facilities. Sixty-three acetabular fractures were assessed at an average follow up of 52.94 months after operation. Twenty-six patients operated upon in the first three years and 37 operated thereafter were separately studied to discover the effect of the learning curve. Regarding the fractures, 47 of 63 (74.6%) had excellent/good results (Harris Hip Score>80). The complications included broken drill bit in eight patients (12.69%), deep infection and heterotopic ossification in five patients (7.93%), avascular necrosis and sciatic nerve palsy in two patients (3.17%) and implant failure in one patient (1.58%). The results collected during the learning curve were inferior in the complex fractures (p value<0.001). Complications were common in patients opting for local implants and in those operated after over 2 weeks delay.