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HIV-associated neurocognitive disorders (HAND) is a syndrome defined by neurocognitive deficits that are driven by viral neurotoxins, cytokines, free radicals, and proteases expressed in the brain. This neurological disease has also been linked to activation of Protease-Activated Receptors 1 and 2 (PAR1,2). These receptors are highly expressed in the central nervous system and are upregulated in HAND. Secretory basic-amino-acid-specific Proprotein Convertases (PCs), which cleave precursor proteins at basic residues, are also induced in HAND. They are vital for many biological processes including HIV-1 entry into cells. The cytoprotective role of Furin, PC5, and PACE4 has been linked to the presence of a potential PC-cleavage site R 41 XXXXR 46 ↓ in PAR1. Furthermore, Furin binds PAR1 and both are trapped in the trans-Golgi-network (TGN) as inactive proteins, likely due to the intermediary trafficking role of phospho-Furin acidic cluster sorting protein 1 (PACS1). Nothing is known about PAR2 and its possible recognition by PCs at its putative R 31 XXXXR 36 ↓ processing site. The present study implicates PACS1 in the retrograde trafficking of PAR1 to the TGN and demonstrates that the cytosolic extreme C-terminal tail of PAR1 contains an acidic phosphorylatable PACS1-sensitive domain. We further show the requirement of Asn 47 in PAR1 for its Furin-dependent TGN localization. Our data revealed that Furin is the only convertase that efficiently cleaves PAR2 at Arg 36 ↓. N-glycosylation of PAR2 at Asn 30 reduces the efficacy, but enhances selectivity of the Furin cleavage. Finally, in co-cultures comprised of human neuroblastoma SK-N-SH cells (stably expressing PAR1/2 and/or Furin) and HIV-1-infected primary macrophages, we demonstrate that the expression of Furin enhances neuronal cell viability in the context of PAR1- or PAR2-induced neuronal cytotoxicity. The present study provides insights into early stages of HIV-1 induced neuronal injury and the protective role of Furin in neurons co-expressing PAR1 and/or PAR2, as observed in HAND.

Primary neuroendocrine carcinoma of breast is a very rare malignancy and preoperative diagnosis is difficult by clinical examination alone.Most oftenly, histopathological examination (HPE) and immunohistochemistry (IHC) studies are required to establish the diagnosis. We describe here a case of a primary neuroendocrine carcinoma of right breast in a 32-year-old woman. The patient underwent a right modified radical mastectomy, and the diagnosis was conclusively established postoperatively by the HPE and IHC reports. The IHC report revealed positive status of oestrogen, progesterone and Herceptin receptors., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Competing Interests: There are no conflicts of interest.

Introduction: Wide awake surgery of the hand (WASH) is a well-accepted technique in hand surgery which allows the surgeon to identify and rectify on the table of some of the inadvertent shortcomings in the surgical procedures to optimise the final outcome. The advantage, however, precludes the use of tourniquet. We describe a modified method which preserves all the advantages of WASH and allows the surgeon to use tourniquet., Patients and Methods: Thirty-one cases of hand surgeries were carried out using the modified technique where a wrist block was supplemented with the ultra-short acting intravenous propofol which allowed the surgeon to use the upper arm tourniquet. The propofol infusion was stopped, and the tourniquet was released after the important surgical step. Within an average of 10 min of stoppage of the infusion, all the patients were awake for active intraoperative painless movements to aid the surgeon to identify, rectify and fine tune the procedure to optimise the results., Results: Five of the 31 patients needed correction based on the intraoperative movements. All the 31 patients were pain free at the surgical site during surgery. All the 31 patients were cooperative enough to perform full range of pain-free intraoperative movements. No patient experienced significant tourniquet pain during the procedure. Patient's and surgeon's satisfaction at the end of the procedure has been quite satisfactory., Conclusion: Timed wake-up anaesthesia, an improvement over the original WASH, has been suggested where the surgeon can add without subtracting the benefits of the procedure in the form of usage of the tourniquet providing the clear tissue plane and haemostasis during the surgery. However, an additional cost is incurred for the use of anaesthesia and equipment should be kept in mind., Competing Interests: There are no conflicts of interest.

Mesenchymal Stem Cells or Marrow Stromal Cells (MSCs) have long been viewed as a potent tool for regenerative cell therapy. MSCs are easily accessible from both healthy donor and patient tissue and expandable in vitro on a therapeutic scale without posing significant ethical or procedural problems. MSC based therapies have proven to be effective in preclinical studies for graft versus host disease, stroke, myocardial infarction, pulmonary fibrosis, autoimmune disorders and many other conditions and are currently undergoing clinical trials at a number of centers all over the world. MSCs are also being extensively researched as a therapeutic tool against neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Huntington's disease (HD) and Multiple Sclerosis (MS). MSCs have been discussed with regard to two aspects in the context of neurodegenerative diseases: their ability to transdifferentiate into neural cells under specific conditions and their neuroprotective and immunomodulatory effects. When transplanted into the brain, MSCs produce neurotrophic and growth factors that protect and induce regeneration of damaged tissue. Additionally, MSCs have also been explored as gene delivery vehicles, for example being genetically engineered to over express glial-derived or brain-derived neurotrophic factor in the brain. Clinical trials involving MSCs are currently underway for MS, ALS, traumatic brain injuries, spinal cord injuries and stroke. In the present review, we explore the potential that MSCs hold with regard to the aforementioned neurodegenerative diseases and the current scenario with reference to the same.

Purpose: To perform a prospective randomized study to evaluate aspiration and sclerotherapy vs. laparoscopic deroofing in the management of symptomatic simple renal cysts., Patients and Methods: Forty patients with symptomatic simple renal cysts were randomized to treatment either by ultrasonography-guided aspiration and sclerotherapy (group A-20 patients) or by laparoscopic deroofing (group B-20 patients). Two patients in group A and one patient in group B had a parapelvic cyst. Patients were evaluated by urine analysis, serum creatinine level, coagulation profile, ultrasonography, and CT urography. In group A patients, after aspiration, 1% polidocanol in a volume equivalent to 10% of cyst volume was instilled. In group B patients, laparoscopic deroofing was performed. All patients were followed up by ultrasonography up to 1 year after treatment., Results: In group A, aspiration and sclerotherapy was performed on an outpatient basis, and none of the patients needed postoperative analgesia. Eighteen of 20 patients had complete regression; two of these had parapelvic cyst. Partial regression with relief of pain was noted in one patient, whereas treatment failed in one patient. None of the patients had any significant complication and none required analgesia. All the patients were discharged two hours after the procedure. In group B, laparoscopic deroofing was successfully performed in 19 of 20 patients. Laparoscopic deroofing could not be performed in one patient with parapelvic cyst because of failure of access. The mean analgesic requirement was 285 ± 57.98 (200-400) mg tramadol, and average hospital stay was 2.1 ± 0.32 (2-3) days., Conclusion: Percutaneous aspiration and sclerotherapy with polidocanol is an effective, safe, and minimally invasive therapeutic option for symptomatic simple renal cysts, with equal efficacy and lower morbidity and hospital stay in comparison with laparoscopic deroofing.