Safety and efficacy of superior calyceal access versus inferior calyceal access for pelvic and/or lower calyceal renal calculi- a prospective observational comparative study.

OBJECTIVE: To compare efficacy and safety between superior calyceal access and inferior calyceal access for pelvic and/or lower calyceal renal stones. METHODS: Consecutive patients presenting with Pelvic and/or inferior calyceal renal calculi were allocated to the superior calyceal access (group 1) or inferior calyceal access (group 2) treatment arm. Allocation of treatment access was based on the surgeon's preference. Variables studied included stone free rate, operating time, intraoperative and postoperative complications. Statistical analysis was executed using SPSS, Version 16.0. The statistical significance was evaluated at 5% level of significance (p value < 0.05). RESULTS: Between July 2018 and February 2019, 63 patients were included in each group. The percutaneous inserted guidewire entered the ureter in 92% in group1 and 74.6% in group 2 (p = 0.034). Stone fragments migrated to the middle calyx in 3.2% in group1 and 9.5% in group 2 (p = 0.033). A second puncture was required in one patient in group 1 and in 5 patients in group 2 (p = 0.04). The operative duration (minutes) was 13.46 ± 1.09 in the group 1 while 16.58 ± 1.44 in the group 2 (p = 0.002). Thoracic complications (hydropneumothorax) occurred to 2 patients in superior calyceal access group managed with intercostal tube drainage (p = 0.243).Post operatively blood transfusion was required in two patients in group 2 (p = 0.169). Angioembolization was done in one patient among the inferior calyceal access approach (p = 0.683). Complete stone clearance assessed at 3 months was 96.8% in group 1 and 85.7% in group 2 (p = 0.046). CONCLUSIONS: Superior calyceal access is a safe and most efficacious in terms of achieving complete stone clearance rate with reduced operative time, minimal blood loss, less need for a second puncture and auxiliary procedures at minimal complications. STUDY REGISTRATION: Clinical trials registry - INDIA; CTRI/2018/07/014,687.

Endodontic implications of a patient with arteriovenous malformation: a case report and literature review.

AIM: To present the endodontic management of a patient diagnosed with a high-flow arteriovenous malformation (AVM) requiring root canal treatment and to discuss the relevant endodontic literature for this rare but significant problem. SUMMARY: AVM is a complex communication of an artery and a vein in which the oxygenated blood is forced away from the intended tissue. The incidence of its occurrence in the face and neck is rare, and when present, the most common sign is gingival bleeding. Arteriovenous malformation is both a diagnostic and therapeutic challenge for dentists. Also, there is ambiguity regarding the precautions to be taken whilst doing endodontic procedures in such cases. Hence, there is a need to understand the disease process and its implications in order to prevent life-threatening complications during treatment. This case report highlights the successful endodontic management of a cariously exposed right maxillary second premolar in a patient diagnosed with high-flow AVM. On an orthopantomogram, the AVM was spreading in the left submandibular space involving the left ramus area. The clinical findings of limited mouth opening with inter-appointment swelling and trismus during treatment made the case unusual and challenging. This paper addresses the current understanding of the classification, diagnosis, clinical features and endodontic management, together with specific guidelines and recommendations whilst performing endodontic procedures in AVM cases. KEY LEARNING POINTS: The classification and oral manifestations of AVM must be known and understood. Practitioners should be aware of the radiographic appearance of AVM. Recommended precautions should be taken when carrying out restorative and endodontic procedures in a patient with AVM. Antibiotic prophylaxis may be considered before endodontic treatment in a patient with AVM. Multidisciplinary treatment planning may be required.

Association between concentration of active MMP-9 in pulpal blood and pulpotomy outcome in permanent mature teeth with irreversible pulpitis - a preliminary study.

AIM: To investigate the correlation between the concentration of active-matrix metalloproteinases-9 (aMMP-9) in pulpal blood and the outcome of pulpotomy in mature permanent teeth with symptomatic irreversible pulpitis (SIP). METHODOLOGY: Forty permanent molar teeth with a clinical diagnosis of SIP and normal apical tissues with periapical index (PAI) score ≤ 2 and ten permanent teeth (8 molars and two premolars) with a diagnosis of normal pulp that required root canal treatment for prosthetic reasons from patients between the ages of 15-35 years were recruited. All clinical procedures were performed under local anaesthesia and rubber dam isolation. After access opening, the coronal pulp tissue was amputated up to the canal orifice. A 100 µL volume of the pulpal blood was collected using a micropipette and transported to the laboratory. Sodium hypochlorite (2.5 %) was used as a haemostatic agent, and mineral trioxide aggregate (MTA) was used as the pulp capping material. The tooth was restored with composite at the same visit. Teeth with normal pulps were treated with single-visit root canal treatment. Patients with pulpotomy were recalled at 6 and 12 months. Outcome assessment of teeth with pulpotomy was carried out at 12 months and was categorized as success (asymptomatic patients with PAI score ≤ 2) or failure (symptomatic patients or PAI score ≥ 3). Quantification of aMMP-9 in pulpal blood was achieved using a fluorometric assay. The following statistical analyses were performed to assess the data: t-test, Fisher's exact test, kappa coefficient, non-parametric test, Wilcoxon rank-sum test, Spearman rank correlation test and receiver operating characteristic curve (ROC). RESULT: The success rate of pulpotomy was 88 % at 12-months. There was a significant difference between the median concentrations of aMMP-9 in pulpal blood of teeth with normal pulps (52 (12-96) ng mL-1 :) and SIP (193.3 (25.8-607.7) ng mL-1 :) (P = 0.0003) and successful (132.3 (25.8-548.3) ng mL-1 :) and failed cases (512.4 (334.8-607.7 ng mL-1 :) (P = 0.0015) of MTA pulpotomy. A significant association was established between aMMP-9 concentration and outcome of pulpotomy. The area under the receiver operating characteristics curve (0.9484, 95%CI) suggested excellent discriminatory power of aMMP-9 concentration in pulpal blood to predict the pulpotomy outcome. CONCLUSION: The pulpal blood concentration of aMMP-9 was significantly associated with the outcome of pulpotomy in teeth with symptomatic irreversible pulpitis, where it may be used as a potential prognostic biomarker.

Exploration of a new model of care in a psychiatry unit.

The model established at Orillia Soldiers Memorial Hospital involves family physicians as the most responsible physician. They act as "admission gatekeeper" for all unattached patients who are admitted to the psychiatry in-patient unit. A PubMed, EBSCO, OVID Medline, Embase, CINAHL, and Web of Science database review of the last 10 years (2006-2016) was undertaken. A satisfaction survey was undertaken. An intensive literature review found this model to be unique. The model has proved to be extremely efficient and cost-effective.

Do Congenitally Blind Individuals have Better Haptic Object Perception Compared to Blindfolded Sighted Individuals?

Objective: Haptic perceptual enhancement in congenitally blind people is a subject of intense debate. There is no consensus whether the congenitally blind get the benefit of their haptic experience or the sighted get the benefit of previous visual experience when it comes to recognizing objects by manual exploration using different constraints. The present study compared haptic object perception between congenitally blind and blindfolded sighted participants in a situation where manual exploration of objects was constrained. Methods: Thirty congenitally blind braille readers and 30 age and gender matched controls were studied. All participants were required to identify the objects haptically, without the aid of vision. Manual exploration of the objects was constrained by permitting touching of the object with only the exposed tip of the index finger with the aim to limit cues about material information. Performance was evaluated in terms of speed and accuracy with which objects were identified. Result: The recognition time analysis showed that congenitally blind participants recognize objects much faster than blindfolded sighted participants. The analysis of haptic recognition rates showed that congenitally blind participants identified the objects more accurately compared to blindfolded normal sighted individuals. Conclusion: Congenitally blind individuals appear to possess a definite enhanced haptic perceptual ability allowing for faster and more accurate recognition of objects even when manual exploration is constrained.

MRI of perianal fistulae: a pictorial kaleidoscope.

Perianal fistulae are an abnormal communication between the anorectum and the perianal skin. A seemingly benign condition, it can be a cause of considerable distress to the patient if it is not mapped out adequately before embarking upon surgical correction. The persistence of residual disease complicates and up-stages the grade of the remnant fistula with increased risk of anal incontinence following surgery secondary to damage to the anal sphincter complex. Magnetic resonance imaging (MRI) can play a critical role in mapping the fistulae tract in relation to the anal sphincter complex and hence, act as a reliable guide for the surgeon to chart the optimised management of perianal fistulae. This review illustrates the role of MRI in the imaging evaluation of perianal fistulae, to facilitate a well-planned surgical course.

Tell tale of tablets in bronchus.

Foreign body (FB) aspiration is an emergency of concern at all ages. However, in adults, it can present with atypical symptoms such as shortness of breath, wheezing or rarely cyanosis. Aspiration of oral medications is seen in the elderly population with impairment of protective airway mechanism. Treatment of choice is endoscopic removal of the foreign body. We report such a case of foreign body aspiration (potassium chloride tablet), diagnosed on imaging and subsequently developed bronchostenosis. There are a very few reported cases of oral potassium supplement aspiration and associated complications in the literature.

Evaluating the cost implications of integrating SARS-CoV-2 genome sequencing for infection prevention and control investigation of nosocomial transmission within hospitals.

BACKGROUND: The COG-UK hospital-onset COVID-19 infection (HOCI) trial evaluated the impact of SARS-CoV-2 whole-genome sequencing (WGS) on acute infection, prevention, and control (IPC) investigation of nosocomial transmission within hospitals. AIM: To estimate the cost implications of using the information from the sequencing reporting tool (SRT), used to determine likelihood of nosocomial infection in IPC practice. METHODS: A micro-costing approach for SARS-CoV-2 WGS was conducted. Data on IPC management resource use and costs were collected from interviews with IPC teams from 14 participating sites and used to assign cost estimates for IPC activities as collected in the trial. Activities included IPC-specific actions following a suspicion of healthcare-associated infection (HAI) or outbreak, as well as changes to practice following the return of data via SRT. FINDINGS: The mean per-sample costs of SARS-CoV-2 sequencing were estimated at £77.10 for rapid and £66.94 for longer turnaround phases. Over the three-month interventional phases, the total management costs of IPC-defined HAIs and outbreak events across the sites were estimated at £225,070 and £416,447, respectively. The main cost drivers were bed-days lost due to ward closures because of outbreaks, followed by outbreak meetings and bed-days lost due to cohorting contacts. Actioning SRTs, the cost of HAIs increased by £5,178 due to unidentified cases and the cost of outbreaks decreased by £11,246 as SRTs excluded hospital outbreaks. CONCLUSION: Although SARS-CoV-2 WGS adds to the total IPC management cost, additional information provided could balance out the additional cost, depending on identified design improvements and effective deployment.

Epididymal and prostatic histoplasmosis in a renal transplant recipient from southern India.

An unusual case of epididymal and prostatic histoplasmosis is reported from Karnataka State of southern India, in a 37-year-old male renal transplant recipient, who had presented with gastrointestinal histoplasmosis a year before the second presentation and had responded successfully to 9 months' treatment with itraconazole. The patient presented a second time with high-grade fever and pain in the scrotum and the lower abdomen. Ultrasound of the abdomen revealed a retrotrigonal abscess, which was confirmed on computed tomography scan of the pelvis. Pus was drained via transrectal route and biopsy specimens were taken from the epididymis and the prostate. Histopathology revealed the picture suggestive of histoplasmosis, and the pus on culture confirmed the infection with Histoplasma capsulatum. To our knowledge, only 5 cases of epididymal histoplasmosis have been reported in the literature, our case being the second report from India and sixth in the world; prostatic histoplasmosis is also a rare occurrence.

PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is highly expressed in lipid-accumulating macrophages of the coronary artery. In light of this, the wide-spread clinical use of thiazolidinediones (TZDs) in the treatment of type II diabetes raises concerns about the role of PPAR-gamma in macrophage function and disease progression. To define the role of PPAR-gamma in macrophage biology, we used homologous recombination to create embryonic stem cells that were homozygous for a null mutation in the PPAR-gamma gene. We demonstrate here that PPAR-gamma is neither essential for nor substantially affects the development of the macrophage lineage both in vitro and in vivo. In contrast, we show it is an important regulator of the scavenger receptor CD36, which has been genetically linked to lipid accumulation in macrophages. Both 15-deoxy-Delta12,14prostaglandin J2 and thiazolidinediones have anti-inflammatory effects that are independent of PPAR-gamma. We show that PPAR-gamma is required for positive effects of its ligands in modulating macrophage lipid metabolism, but that inhibitory effects on cytokine production and inflammation may be receptor independent.

Behavioral and spermatogenic hybrid male breakdown in Nasonia.

Several reproductive barriers exist within the Nasonia species complex, including allopatry, premating behavioral isolation, postzygotic inviability and Wolbachia-induced cytoplasmic incompatibility. Here we show that hybrid males suffer two additional reproductive disadvantages, an inability to properly court females and decreased sperm production. Hybrid behavioral sterility, characterized by a reduced ability of hybrids to perform necessary courtship behaviors, occurs in hybrids between two species of Nasonia. Hybrid males produced in crosses between N. vitripennis and N. giraulti courted females at a reduced frequency (23-69%), compared with wild-type N. vitripennis and N. giraulti males (>93%). Reduced courtship frequency was not a simple function of inactivity among hybrids. A strong effect of cytoplasmic (mitochondrial) background was also found in N. vitripennis and N. giraulti crosses; F2 hybrids with giraulti cytoplasm showing reduced ability at most stages of courtship. Hybrids produced between a younger species pair, N. giraulti and N. longicornis, were behaviorally fertile. All males possessed motile sperm, but sperm production is greatly reduced in hybrids between the older species pair, N. vitripennis and N. giraulti. This effect on hybrid males, lowered sperm counts rather than nonfunctional sperm, is different from most described cases of hybrid male sterility, and may represent an earlier stage of hybrid sperm breakdown. The results add to previous studies of F2 hybrid inviability and behavioral sterility, and indicate that Wolbachia-induced hybrid incompatibility has arisen early in species divergence, relative to behavioral sterility and spermatogenic infertility.

A double leucine within the GLUT4 glucose transporter COOH-terminal domain functions as an endocytosis signal.

The unique COOH-terminal 30-amino acid region of the adipocyte/skeletal muscle glucose transporter (GLUT4) appears to be a major structural determinant of this protein's perinuclear localization, from where it is redistributed to the cell surface in response to insulin. To test whether an underlying mechanism of this domain's function involves glucose transporter endocytosis rates, transfected cells were generated expressing exofacial hemagglutinin epitope (HA)-tagged erythrocyte/brain glucose transporter (GLUT1) or a chimera containing the COOH-terminal 30 amino acids of GLUT4 substituted onto this GLUT1 construct. Incubation of COS-7 or CHO cells expressing the HA-tagged chimera with anti-HA antibody at 37 degrees resulted in an increased rate of antibody internalization compared to cells expressing similar levels of HA-tagged GLUT1, which displays a cell surface disposition. Colocalization of the internalized anti-HA antibody in vesicular structures with internalized transferrin and with total transporters was established by digital imaging microscopy, suggesting the total cellular pool of transporters are continuously recycling through the coated pit endocytosis pathway. Mutation of the unique double leucines 489 and 490 in the rat GLUT4 COOH-terminal domain to alanines caused the HA-tagged chimera to revert to the slow endocytosis rate and steady-state cell surface display characteristic of GLUT1. These results support the hypothesis that the double leucine motif in the GLUT4 COOH terminus operates as a rapid endocytosis and retention signal in the GLUT4 transporter, causing its localization to intracellular compartments in the absence of insulin.

Exofacial epitope-tagged glucose transporter chimeras reveal COOH-terminal sequences governing cellular localization.

The insulin-regulated adipocyte/skeletal muscle glucose transporter (GLUT4) displays a characteristic steady-state intracellular localization under basal conditions, whereas the erythrocyte/brain transporter isoform (GLUT1) distributes mostly to the cell surface. To identify possible structural elements in these transporter proteins that determine their cellular localization, GLUT1/GLUT4 chimera cDNA constructs that contain the hemagglutinin epitope YPYDVPDYA (HA) in their major exofacial loops were engineered. Binding of monoclonal anti-HA antibody to non-permeabilized COS-7 cells expressing HA-tagged transporter chimeras revealed that expression of transporters on the cell surface was strongly influenced by their cytoplasmic COOH-terminal domain. This method also revealed a less marked, but significant effect on cellular localization of amino acid residues between transporter exofacial and middle loops. The subcellular distribution of expressed chimeras was confirmed by immunofluorescence microscopy of permeabilized COS-7 cells. Thus, HA-tagged native GLUT4 was concentrated in the perinuclear region, whereas a chimera containing the COOH-terminal 29 residues of GLUT1 substituted onto GLUT4 distributed to the plasma membrane, as did native GLUT1. Furthermore, a chimera composed of GLUT1 with a GLUT4 COOH-terminal 30-residue substitution exhibited a predominantly intracellular localization. Similar data was obtained in CHO cells stably expressing these chimeras. Taken together, these results define the unique COOH-terminal cytoplasmic sequences of the GLUT1 and GLUT4 glucose transporters as important determinants of cellular localization in COS-7 and CHO cells.

Nuclear receptors and lipid physiology: opening the X-files.

Cholesterol, fatty acids, fat-soluble vitamins, and other lipids present in our diets are not only nutritionally important but serve as precursors for ligands that bind to receptors in the nucleus. To become biologically active, these lipids must first be absorbed by the intestine and transformed by metabolic enzymes before they are delivered to their sites of action in the body. Ultimately, the lipids must be eliminated to maintain a normal physiological state. The need to coordinate this entire lipid-based metabolic signaling cascade raises important questions regarding the mechanisms that govern these pathways. Specifically, what is the nature of communication between these bioactive lipids and their receptors, binding proteins, transporters, and metabolizing enzymes that links them physiologically and speaks to a higher level of metabolic control? Some general principles that govern the actions of this class of bioactive lipids and their nuclear receptors are considered here, and the scheme that emerges reveals a complex molecular script at work.

Binding of the Ras activator son of sevenless to insulin receptor substrate-1 signaling complexes.

Signal transmission by insulin involves tyrosine phosphorylation of a major insulin receptor substrate (IRS-1) and exchange of Ras-bound guanosine diphosphate for guanosine triphosphate. Proteins containing Src homology 2 and 3 (SH2 and SH3) domains, such as the p85 regulatory subunit of phosphatidylinositol-3 kinase and growth factor receptor-bound protein 2 (GRB2), bind tyrosine phosphate sites on IRS-1 through their SH2 regions. Such complexes in COS cells were found to contain the heterologously expressed putative guanine nucleotide exchange factor encoded by the Drosophila son of sevenless gene (dSos). Thus, GRB2, p85, or other proteins with SH2-SH3 adapter sequences may link Sos proteins to IRS-1 signaling complexes as part of the mechanism by which insulin activates Ras.

Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains.

Signal transmission by many cell surface receptors results in the activation of phosphoinositide (PI) 3-kinases that phosphorylate the 3' position of polyphosphoinositides. From a screen for mouse proteins that bind phosphoinositides, the protein GRP1was identified. GRP1 binds phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4, 5)P3] through a pleckstrin homology (PH) domain and displays a region of high sequence similarity to the yeast Sec7 protein. The PH domain of the closely related protein cytohesin-1, which, through its Sec7 homology domain, regulates integrin beta2 and catalyzes guanine nucleotide exchange of the small guanine nucleotide-binding protein ARF1, was also found to specifically bind PtdIns(3,4,5)P3. GRP1 and cytohesin-1 appear to connect receptor-activated PI 3-kinase signaling pathways with proteins that mediate biological responses such as cell adhesion and membrane trafficking.