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Objective: Alteration in somatosensory function has been linked to pain experience in individuals with joint pain. In this systematic review we aimed to establish the level of evidence of associations between psychological, social, physical activity, and sleep measures and somatosensory function that were assessed via quantitative sensory testing (QST) among individuals with joint pain., Methods: A comprehensive literature search was conducted in 6 electronic databases from their inception to July 2019. Two reviewers independently assessed the methodological quality using a modified Quality in Prognostic Studies (QUIPS) tool and supplemented with recommendations from the Critical Appraisal and Data Extraction for Systematic Review of Prediction Modelling Studies (CHARMS) checklist and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The level of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Data were pooled to evaluate the strength of the relationships of interest., Results: Seventeen studies related to joint pain were included. Pain catastrophizing, depression, anxiety, and physical activity level have been shown to have a significant (small to fair) association with several QST measures. Pressure pain threshold (PPT) is the only measure that was found to be consistently correlated with all the domains. The overall quality of evidence for all factors ranged from very low to moderate. Subgroup analysis revealed a stronger association for depression and pain catastrophizing and PPT and temporal pain summation in individuals with shoulder pain., Conclusion: Psychological factors and physical activity levels are associated with somatosensory function in people with joint pain. These factors need to be adjusted when establishing predictive relationships between somatosensory function and pain outcomes in individuals with joint pain., (© 2020 World Institute of Pain.)

Chickpea ( Cicer arietinum L.) is an important food legume crop grown in arid and semi-arid regions of the world. In India, kabuli chickpea is grown in central India in ~0.5 million ha, predominantly under short winter (<110 days). Efforts are underway to select promising genotypes at the Food Legume Research Platform (FLRP), Amlaha, located in intensive kabuli chickpea growing area of India. Sixty-four kabuli chickpea lines were evaluated for agronomic traits during 2017-2018 and 2018-2019 crop seasons at FLRP following simple 8 X 8 lattice design with two replications. The analysis of variance over two years revealed significant variation exists for days to flowering, plant height, maturity period, biomass, seed size and seed yield. It was observed that with similar maturity time (106 days), FLIP09-432C produced 2273 kg/ha, which out-yielded the popular variety in central India, JGK-3 by 15%. The breeding lines, FLIP09- 436C, FLIP09-171C, FLIP09-373C and FLIP09-247C were also found promising for earliness (104-110 days), and high yielding with the good yield ability (1003-2273 kg/ha). These promising genotypes for a short duration with good yield have been selected and can be used for various chickpea breeding programmes to develop high yielding varieties in central India.

Faba bean ( Vicia faba L.) is one of the earliest domesticated food legumes after chickpea and pea in the world. It is been produced in many countries including China, Ethiopia, Egypt, northern Europe, the Mediterranean region, central Asia, East Asia, Latin America and as a minor crop in India. The crop is affected by many diseases and alternaria leaf blight ( Alternaria spp.) is one of the serious threat to faba bean production. Twenty-five lines of faba bean were selected from three international nurseries and were evaluated at ICARDA-FLRP-Amlaha during 2016-2017 and 2017-2018, to identify resistant lines against alternaria blight disease. A wide range of variation to disease reaction was observed among faba bean genotypes. One faba bean line (S2011-134) found tolerant, six genotypes (S2011-116, FLIP15-139, FLIP15-156, FLIP15-159, FLIP15-164-S2 and FLIP15-169) were found moderately tolerant and 16 genotypes were found susceptible to alternaria blight. The faba bean genotypes showed resistance to the disease scoring (0-9) with high yield as compared to the checks, Giza and Gwalior local. The identified sources of resistance can be utilized in faba bean breeding programmes for the development of disease tolerant cultivars with high yield.

Aim: To analyze the morphological parameters of palatal rugae in a population of Maharashtrian ancestry., Material and Methods: This study was conducted on 1000 subjects of Maharashtrian ancestry with at least 3 generations on the mother's and father's side. Their palatal impressions were obtained with alginate and the casts were analyzed for length, shape and direction of palatal rugae., Results: Our results showed that the most predominant rugae were primary followed by secondary and fragmentary with significant differences between them. The most prevalent rugae shapes found were straight followed by wavy followed by curved with significant differences between them. According to direction, forward rugae were significantly higher than perpendicular rugae and backward rugae., Conclusion: The rugae are considered to have population specific configurations. This baseline data of patterns of palatal rugae in a sample of Maharashtrian ancestry may serve `as an accessory tool' for population identification in Forensic Dentistry.

Objectives: In the past few years, herbal medicines have gained popularity over synthetic drugs because of their natural source and minimal side effects which has led to a tremendous growth of phytopharmaceuticals usage. With the development of nanotechnology, it provides alternative approaches to overcome several limitations using nano-formulations. In spite of considerable quantity of antianemic preparations with different iron forms available, currently additives are used and represented in modern pharmaceutical market. Iron deficiency anemia is a major global public health problem which particularly affects pregnant women, children and elderly persons. The situation is complicated because of disadvantages and drug side effects from existing antianemic medicines. There is a great demand for the development of new antianemic preparations. Green synthesis of iron oxide nanoparticles, possess high potential in this field., Methods: Our study focuses on developing green synthesis of iron oxide nanoparticles (IONPs) of 10-50 nm with spherical shape where different dosages were used -1 mg/kg, 10 mg/kg and 100 mg/kg for exposure in Wistar albino female rats for 28 days. The toxicity was assessed using various parameters such as measurements of the rat body and organ mass, hematology, biochemical evaluation and histopathological examinations., Results: No significant differences were observed in body and organ weights. Hematological indices also indicated no significant differences whereas biochemical factors showed increase in levels of direct bilirubin and globulin of medium as well as high dose and SGPT levels were increased only in high dose. The major organs (heart, kidney and liver) showed histopathological alterations in 10 and 100 mg/kg whereas brain showed only in 100 mg/kg., Conclusion: The toxicity of IONPs was found to be more significant when the concentration was increased; however, low doses can be used for further investigation as an antianemic preparation., Competing Interests: CONFLICT OF INTEREST The author declares no conflict of interest., (© 2020 Korean Pharmacopuncture Institute.)

Embryonic stem cells provide their major contribution to embryogenesis through formation of germ layers as they have pluripotency potential and capacity for self-renewal. Retention of pluripotency of these stem cells depends on expression/level of transcription factors, i.e., SOX2, OCT4 and NANOG. During organogenesis, the altered expression of the molecules also influences these stem cells to lose their pluripotency and turn toward the lineage selection. As the differentiation progresses, the maintenance of the somatic cells including the oral squamous cells also depends on differential expression of the transcription factors to some extent. Recently, many experimental and observational studies documented the significant contribution in carcinogenesis of various human cancers. In this review, we have attempted to summarize the evidences indicating about the putative role of these master pluripotency regulators in various phases of oral carcinogenesis i.e. initiation , progression and prognosis of oral squamous cell carcinoma., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Oral and Maxillofacial Pathology.)

Aims: To understand the molecular pathways involved in oxidative stress (OS)-mediated sperm dysfunction against a hypoxic and hyperthermic microenvironment backdrop of varicocele through a proteomic approach. Results: Protein selection (261) based on their role in redox homeostasis and/or oxidative/hyperthermic/hypoxic stress response from the sperm proteome data set of unilateral varicocele (UV) in comparison with fertile control displayed 85 to be differentially expressed. Upregulation of cellular oxidant detoxification and glutathione and reduced nicotinamide adenine dinucleotide (NADH) metabolism accompanied with downregulation of protein folding, energy metabolism, and heat stress responses were observed in the UV group. Ingenuity pathway analysis (IPA) predicted suppression of oxidative phosphorylation (OXPHOS) (validated by Western blotting [WB]) along with augmentation in OS and mitochondrial dysfunction in UV. The top affected networks indicated by IPA involved heat shock proteins (HSPs: HSPA2 and HSP90B1). Their expression profile was corroborated by immunocytochemistry and WB. Hypoxia-inducible factor 1A as an upstream regulator of HSPs was predicted by MetaCore. Occurrence of reductive stress in UV spermatozoa was corroborated by thiol redox status. Innovation: This is the first evidence of a novel pathway showing aberrant redox homeostasis against chronic hypoxic insult in varicocele leading to sperm dysfunction. Conclusions: Upregulation of antioxidant system and dysfunctional OXPHOS would have shifted the redox balance of biological redox couples (GSH/GSSG, NAD + /NADH, and NADP + /NADPH) to a more reducing state leading to reductive stress. Chronic reductive stress-induced OS may be involved in sperm dysfunction in infertile men with UV, where the role of HSPs cannot be ignored. Intervention with antioxidant therapy warrants proper prior investigation.

A simple two-step approach has been employed to synthesize a cobalt-nickel-copper ternary metal oxide, involving electrochemical precipitation/deposition followed by calcination. The ternary metal hydroxide gets precipitated/deposited from a nitrate bath at the cathode in the catholyte chamber of a two-compartment diaphragm cell at room temperature having a pH ≈ 3. The microstructure of the ternary hydroxides was modified in situ by two different surfactants such as cetyltrimethylammonium bromide and dodecyltrimethylammonium bromide in the bath aiming for enhanced storage performance in the electrochemical devices. The effect of the surfactant produces a transition from microspheres to nanosheets, and the effect of micelle concentration produces nanospheres at a higher ion concentration. The ternary hydroxides were calcined at 300 °C to obtain the desired ternary mixed oxide materials as the electrode for hybrid supercapacitors. X-ray diffraction analysis confirmed the formation of the ternary metal oxide product. The scanning electron microscopy images associated with energy-dispersive analysis suggest the formation of a nanostructured porous composite. Ternary metal oxide in the absence and presence of a surfactant served as the cathode and activated carbon served as the anode for supercapacitor application. DTAB-added metal oxide showed 95.1% capacitance retention after 1000 cycles, achieving 188 F/g at a current density of 0.1 A/g, and thereafter stable until 5000 cycles, inferring that more transition metals in the oxide along with suitable surfactants at an appropriate micellar concentration may be better for redox reactions and achieving higher electrical conductivity and smaller charge transfer resistance. The role of various metal cations and surfactants as additives in the electrolytic bath has been discussed., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Objective: Somatosensory abnormalities are linked to clinical pain outcomes in individuals with spinal pain. However, a range of factors might confound the relationship between altered somatosensory function and clinical pain outcomes. This systematic review aimed to evaluate the literature to assess the level of evidence of associations between psychological, social, physical activity, and sleep measures and somatosensory function (assessed via sensory psychophysical testing) among individuals with spinal pain., Methods: A comprehensive literature search was performed in 6 electronic databases from their inception to June 2018. Two reviewers independently assessed the methodological quality using a modified Quality in Prognostic Studies (QUIPS) tool and supplemented with recommendations from the Critical Appraisal and Data Extraction for the Systematic Review of Prediction Modelling Studies (CHARMS) checklist and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The level of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Data were pooled to evaluate the strength of the relationships of interest., Results: Among the 17 factors identified in the included studies, pain catastrophizing, depression, and pain-related fear have significant negative (small to fair) associations with pain thresholds. A "very low" to "moderate" quality of evidence was found for all the investigated factors. Subgroup analysis showed a smaller effect size for pain catastrophizing/fear of movement and pain thresholds in individuals with low back pain., Conclusions: Psychological factors are associated negatively with pain thresholds and they need to be adjusted when establishing predictive relationships between somatosensory function and pain outcomes in individuals with spinal pain.

Context: Candida is a yeast-like fungus, and it causes candidiasis. Since it is commonly encountered in many cases, the need of the hour is for rapid and reliable method for identification of these fungi in tissue sections., Aim: The aim of this study was to evaluate and compare the staining efficacy of calcofluor white (CFW) and acridine orange (AO) for the detection of Candida species in formalin-fixed paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC) using fluorescence microscopy., Settings and Design: Sample size comprised forty cases of OSCC., Materials and Methods: Before tissue sampling, a swab of the area was taken, it was immediately inoculated on Sabouraud's dextrose agar media and germ tube test was performed for positive cultures for species identification. Tissue sections were obtained from cases of OSCC from the formalin-fixed paraffin-embedded tissue blocks of the same cases in which microbiological assessment was done at the time of tissue sampling, were stained with CFW and AO stain, respectively, and were examined using a fluorescent microscope., Statistical Analysis: Descriptive statistics were expressed in numbers and percentage. Independent t -test (unpaired t -test) and Chi-square test were used. P ≤0.05 was taken to be statistically significant., Results: The mean number of microorganisms per high-power field stained by CFW and AO was 6.35 and 2.57, respectively, and a statistically significant difference ( P ≤ 0.001) was observed. CFW compared to swab culture gave P = 0.018, which showed a statistically significant association., Conclusions: CFW is a better fluorescent stain when compared to AO to detect Candida species in tissue sections of OSCC cases., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Oral and Maxillofacial Pathology.)

Healthcare support workers face challenging situations in their day-to-day work but may have minimal training on how to deal with such incidents. Although staff training is often recommended as an essential part of any comprehensive approach for preventing and managing workplace violence, there is paucity of evidence on the content and effectiveness of such training. This study aimed to evaluate the effect of an intervention (communication skills training) to reduce the experience of aggression for healthcare support workers. A two arm, cluster randomised, single-blinded, controlled trial among healthcare support workers in nongovernmental organisations (NGOs) and District Health Boards (DHBs) in New Zealand was conducted. The trial was conducted across 14 NGOs and DHB in Otago, Southland, and Auckland regions of New Zealand. One hundred and twenty-seven participants were randomised to one of two groups. Both the intervention (communication skills) and control condition (mindfulness) were group-based, fully scripted, and structured training interventions that consisted of four once weekly workshops that were facilitated by one of two nonclinical facilitators. Measurements of perceived aggression, psychological well-being, and distress and communication competence were taken pre-, post-, 3 months' post-, and 6 months' postintervention. There was a significant drop in the rate of aggression over time with a mean score and standard deviation of 10.37 (9.169) at baseline dropping to 6.07 (6.923) for the Perception of Patient Aggression Scale-New Zealand across both intervention and control. Equivalent results were noted with increased psychological well-being and communication competence and decreased distress with both interventions. This was sustained at 6 months' follow-up. However, the between groups effect did not demonstrate a statistically significant difference between the intervention and control groups. Both mindfulness and communication skills training can reduce the experience of aggression reported by healthcare support workers., (© 2018 John Wiley & Sons Ltd.)

Aims: Informal care, which is unpaid and often provided by family and friends, is the primary source of aged care in New Zealand. In addition to financial costs there are known psychological costs of being a carer, including poor mental health., Methods: This research aimed to interview a group of New Zealand carers and describe their rates of depression and anxiety, their motivations for providing care, costs of care and their experience of aggression. Interviews used standardised questions and were conducted over the phone., Results: Results are reported from interviews of 48 carers and suggest this group have elevated symptoms of depression and anxiety. Most of the carers are partners or children of the carees and likely do the caring out of love. Unpaid family carers experience low levels of aggression. Carers reported personal and social restriction, and physical and emotional health the most burdensome aspect of being a carer., Conclusions: Carers of the elderly in New Zealand show elevated levels of distress. Higher levels of emotional support are needed for New Zealand carers. If the health system continues to rely on unpaid carers more should be done to support them., Competing Interests: Nil.

Objective: To compare the percentage of sacral lateral branches (LBs) that would be captured if lesions were created by seven current sacroiliac joint (SIJ) radiofrequency ablation (RFA) techniques: three monopolar and four bipolar., Design: Cadaveric fluoroscopy study., Setting: Anatomy and surgical skills laboratories., Subjects: Forty cadaveric SIJs., Methods: LBs were exposed, radiopaque wires were sutured to LBs, and anterior-posterior fluoroscopic images through the S1 superior endplate were obtained. Lesions that would be created by 17 versions of seven current SIJ RFA techniques were mapped on the fluoroscopic images. These 17 versions were compared: 1) percentage of LBs that would be captured; 2) percentage of SIJ specimens in which 100% of LBs would be captured; and 3) percentage of LBs that would not be captured at each level (S1-S4)., Results: Both the mean LB and 100% capture rates were greater for the bipolar techniques (93.4-99.7% and 62.5-97.5%, respectively) than for the monopolar techniques (49.6-99.1% and 2.5-92.5%, respectively) evaluated. For the bipolar techniques, 1.5-29.2% of LBs would not be captured at S1 and 0% at S2-S4 vs 0-29.2% at S1-S4 for the cooled monopolar techniques vs 36.9-100% at S1-S4 for the conventional monopolar technique., Conclusions: The findings suggest that, if lesions were created, the RFA needle placement locations of the bipolar techniques evaluated may be capable of capturing all LBs, but those of the current monopolar techniques evaluated may not. Future in vivo imaging studies are required to compare the lesion morphology generated by different SIJ RFA techniques and correlate the findings with clinical outcomes.

Background: Current sacroiliac joint (SIJ) cooled radiofrequency (RF) is based on fluoroscopic anatomy of lateral branches (LBs) in three specimens. Recent studies confirm significant variation in LB positions., Objectives: To determine if common fluoroscopic needle placements for cooled SIJ RF are adequate to lesion all S1-3 LBs. If not, would different targets improve lesion accuracy?, Methods: The LBs of 20 cadavers were dissected bilaterally (40 SIJs), and 26 G radiopaque wires were sutured to the LBs. With a 10-mm radius ruler centered at each foramen, standard targets were assessed, as judged by a clockface on the right, for S1 and S2 at 2:30, 4:00, and 5:30 positions and at S3 at 2:30 and 4:00. Mirror image targets were assessed on the left. Assuming an 8-mm lesion diameter, the percentage of LBs that would not be ablated for each level was determined. Imaging through the superior end plate of S1 was compared against segment specific (SS) imaging., Results: Nine point four percent of LBs would not be ablated at S1 vs 0.99% at S2 vs 35% at S3, and 60% of the 40 SIJs would be completely denervated using current targets. SS imaging did not improve results. Alternate target locations could improve the miss rate to 2.8% at S1 and 0% at S3 and would ablate all LBs in 95% of SIJs., Conclusions: Using a conservative 8-mm lesion measurement, contemporary cooled RF needle targets are inadequate to lesion all target LBs. Modifications to current targets are recommended to increase the effectiveness of the procedure.

Purpose: Varicocele may disrupt testicular microcirculation and induce hypoxia-ischemia related degenerative changes in testicular cells and spermatozoa. Superoxide production at low oxygen concentration exacerbates oxidative stress in men with varicocele. Therefore, the current study was designed to study the role of mitochondrial redox regulation and its possible involvement in sperm dysfunction in varicocele associated infertility., Materials and Methods: We identified differentially expressed mitochondrial proteins in 50 infertile men with varicocele and in 10 fertile controls by secondary liquid chromatography-tandem mass spectroscopy data driven in silico analysis. Identified proteins were validated by Western blot and immunofluorescence. Seminal oxidation-reduction potential was measured., Results: We identified 22 differentially expressed proteins related to mitochondrial structure (LETM1, EFHC, MIC60, PGAM5, ISOC2 and import TOM22) and function (NDFSU1, UQCRC2 and COX5B, and the core enzymes of carbohydrate and lipid metabolism). Cluster analysis and 3-dimensional principal component analysis revealed a significant difference between the groups. All proteins studied were under expressed in infertile men with varicocele. Liquid chromatography-tandem mass spectroscopy data were corroborated by Western blot and immunofluorescence. Impaired mitochondrial function was associated with decreased expression of the proteins (ATPase1A4, HSPA2, SPA17 and APOA1) responsible for proper sperm function, concomitant with elevated seminal oxidation-reduction potential in the semen of infertile patients with varicocele., Conclusions: Impaired mitochondrial structure and function in varicocele may lead to oxidative stress, reduced ATP synthesis and sperm dysfunction. Mitochondrial differentially expressed proteins should be explored for the development of biomarkers as a predictor of infertility in patients with varicocele. Antioxidant therapy targeting sperm mitochondria may help improve the fertility status of these patients., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Early postnatal-life malnutrition remains prevalent globally, and about 45% of all child deaths are linked to malnutrition. It is not clear whether survivors of childhood malnutrition suffer from long-term metabolic effects, especially when they are later in life exposed to a fat and carbohydrate rich obesogenic diet. The lack of knowledge around this dietary "double burden" warrants studies to understand the long-term consequences of children previously exposed to malnutrition. We hypothesized that an early-life nutritional insult of low protein consumption in mice would lead to long-term metabolic disturbances that would exacerbate the development of diet-induced insulin resistance and non-alcoholic fatty liver disease (NAFLD). We investigated the effects of feeding a low protein diet (4% wt/wt) immediately after weaning for four weeks and subsequent feeding of a high carbohydrate high fat feeding for 16 weeks on metabolic function and development of NAFLD. Mice exposed to early-life protein restriction demonstrated a transient glucose intolerance upon recovery by regular chow diet feeding. However, protein restriction after weaning in mice did not exacerbate an obesogenic diet-induced insulin resistance or progression to NAFLD. These data suggest that transient protein restriction in early-life does not exacerbate an obesogenic diet-induced NAFLD and insulin resistance., Competing Interests: The authors have declared that no competing interests exist.

Research suggests that transgender young offenders are a uniquely vulnerable caseload that may benefit from speech pathology intervention to help bring their voice into alignment with their gender identity. However, no previous studies have investigated treatment efficacy in this population. This study investigated the impact of intensive voice feminisation therapy targeting fundamental frequency and oral resonance in a 17 year old transgender individual within a youth justice institution. Acoustic analysis, listener and self-ratings of vocal femininity, self-ratings of vocal satisfaction, a post-treatment structured interview, and pre- and post- treatment completion of the Transsexual Voice Questionnaire (TVQ MtF ) were utilised to determine treatment impact. Outcome measures indicated therapy was effective at increasing the client's vocal pitch and perceptually femininity without compromising vocal quality. However, the client was still not consistently perceived as female post-intervention and had difficulty implementing feminine speech strategies in discourse. This case study provides preliminary evidence for the effectiveness of intensive voice feminisation therapy in a youth offending population. This research also highlights the potential utility of speech pathologists working in youth justice settings, even when the timeframe for intervention is limited. Furthermore, this research paper validates the use of perceptual outcome measures in transgender voice work, by replicating previous findings in which significant correlations were found between perceptual ratings of vocal gender and client satisfaction., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Malnutrition contributes significantly to death and illness worldwide and especially to the deaths of children younger than 5 years. The relation between intestinal changes in malnutrition and morbidity and mortality has not been well characterized; however, recent research indicates that the functional and morphologic changes of the intestine secondary to malnutrition itself contribute significantly to these negative clinical outcomes and may be potent targets of intervention. The aim of this review was to summarize current knowledge of experimental and clinically observed changes in the intestine from malnutrition preclinical models and human studies. Limited clinical studies have shown villous blunting, intestinal inflammation, and changes in the intestinal microbiome of malnourished children. In addition to these findings, experimental data using various animal models of malnutrition have found evidence of increased intestinal permeability, upregulated intestinal inflammation, and loss of goblet cells. More mechanistic studies are urgently needed to improve our understanding of malnutrition-related intestinal dysfunction and to identify potential novel targets for intervention.

Background: While the prevalence of language and communication difficulties among young people in custody is well established, holistic understanding of the complexity and co-occurrence of additional vulnerabilities among this population are rare., Methods: Ninety-three young people in a young offenders institution in England were assessed using the Comprehensive Health Assessment Tool, the Test of Word Knowledge, and a range of additional assessments of communication, cognition, and neurodevelopmental difficulties., Results: Forty-seven percent of the young people demonstrated an aspect of language skills significantly below the population average, with more than one in four identified as having impairment. Only one in four of those with an impairment had previously accessed speech and language services. Language needs were associated with difficulties with social communication and nonverbal cognition, as well as higher risk of self-harm and substance misuse., Conclusions: Earlier identification of language difficulties requires routine assessment of young people at risk of engagement in offending behavior. Where language difficulties are identified, holistic assessments of needs should be undertaken. There is a need for speech and language therapy provision within youth justice services, as well as in other services accessed by young people at risk of engagement in offending., (© 2017 Association for Child and Adolescent Mental Health.)

In this article, we describe the discovery of an aryl ether series of potent and selective Na v 1.3 inhibitors. Based on structural analogy to a similar series of compounds we have previously shown bind to the domain IV voltage sensor region of Na v channels, we propose this series binds in the same location. We describe the development of this series from a published starting point, highlighting key selectivity and potency data, and several studies designed to validate Na v 1.3 as a target for pain.

A bloom of the non-toxic cyanobacterium Romeria elegans in waste stabilisation ponds (WSPs) within Angaston waste water treatment plant (WWTP) has posed an unprecedented treatment challenge for the local water utility. The water from the WSPs is chlorinated for safety prior to reuse on nearby farmland. Cyanobacteria concentrations of approximately 1.2 × 106 cells mL -1 increased the chlorine demand dramatically. Operators continuously increased the disinfectant dose up to 50 mg L -1 to achieve operational guideline values for combined chlorine (0.5-1.0 mg L -1 ) prior to reuse. Despite this, attempts to achieve targeted combined chlorine residual (CCR) failed. In this study, samples from the waste stabilisation pond at Angaston WWTP were chlorinated over a range of doses. Combined chlorine, disinfection by-product formation, cyanobacteria cell concentration, Escherichia coli inactivation, as well as dissolved organic carbon and free ammonia were monitored. This study shows that, in the occurrence of cyanobacterial blooms, CCR does not directly suggest pathogen removal efficiency and is therefore not an ideal parameter to evaluate the effectiveness of disinfection process in WWTP. Instead, E. coli removal is a more direct and practical parameter for the determination of the efficiency of the disinfection process.

The checkerboard lattice, with alternating 'crossed' plaquettes, serves as the two dimensional analog of the pyrochlore lattice. The corner sharing plaquette structure leads to a hugely degenerate ground state, and no magnetic order, for classical spins with short range antiferromagnetic interaction. For the half-filled Hubbard model on this structure, however, we find that the Mott insulating phase involves virtual electronic processes that generate longer range and multispin couplings. These couplings lift the degeneracy, selecting a 'flux like' state in the Mott insulator. Increasing temperature leads, strangely, to a sharp crossover from this state to a '120 degree' correlated state and then a paramagnet. Decrease in the Hubbard repulsion drives the system towards an insulator-metal transition-the moments reduce, and a spin disordered state wins over the flux state. Near the insulator-metal transition the electron system displays a pseudogap extending over a large temperature window.

Objective: Our laboratory has shown that insulin's effect to decrease neointimal thickness after arterial injury is greatly diminished in insulin resistant conditions. Thus, in these conditions, a better alternative to insulin could be to use an insulin sensitizing agent. Metformin, the most commonly prescribed insulin sensitizer, has a cardiovascular protective role. Therefore, the objective of this study was to investigate the potential benefit of metformin on neointimal area after arterial injury in a rat model of restenosis., Methods: Rats fed with either normal or high fat diet and treated with or without oral metformin (420mg/kg daily) underwent carotid balloon injury. Effects of metformin on clamp-determined insulin sensitivity, vessel AMPK (AMP-activated protein kinase) phosphorylation (activation marker) and neointimal area were evaluated., Results: Metformin increased insulin sensitivity, but did not affect neointimal thickness in either the normal fat or high fat diet-fed rats. Furthermore, metformin activated AMPK in uninjured but not in injured vessels. Similarly, 10mmol/L metformin inhibited proliferation and activated AMPK in smooth muscle cells of uninjured but not injured vessels, whereas 2mmol/L metformin did not have any effect., Conclusion: In rats, metformin does not decrease neointimal growth after arterial injury, despite increasing whole body insulin sensitivity., (Copyright © 2016. Published by Elsevier Inc.)

The aim of this study was to conduct an in-depth investigation of experiences with pain before knee and hip replacement surgery. A total of 20 patients were interviewed, and interpretative phenomenological analysis was used to identify themes. These were as follows: living with pain, pain conceptualised, pain treatments and healthcare system. Pre-surgical pain is very disabling and is viewed as biological. There was an associated loss of independence. Pharmaceutical management is used by all but not entirely effective, psychological therapies are underutilised. Patients were frustrated, angry, and confused about qualifying for surgery. Many areas of care could be improved to help these pre-surgical patients.

Patient or client aggression towards staff is a risk in healthcare. Healthcare takes place in a variety of settings, including hospitals, community, and Aged Care facilities. A minimal amount is known regarding the existence of safety and training measures available throughout the broad range of hospital and community healthcare services. A web-based survey of the type and frequency of violence experienced by healthcare staff was sent to unit managers working in mental health and older peoples' services of District Health Boards, Non-Governmental Organisations, and Aged Care facilities across New Zealand. One hundred and forty-one managers responded to the survey with a response rate of 79.21%. Managers reported high rates of verbal aggression and assaults against staff within their services. A total of 60% of respondents stated that an increase in assaults against staff was due to an increase in violent events and 43.1% related this to increased staff awareness and reporting of violent events to management. Communication skills and de-escalation training were provided across approximately 95% of organisations. The availability of safety measures including panic buttons, personal alarms, use of security personnel, and police assistance were more widely available and accessible within hospital settings and the community sector was found to mostly rely on police for assistance when violence occurs. The perception of violence is high in healthcare. Prevention and management training is provided in public hospital and aged care setting but not so much in NGOs. All areas of healthcare provision could benefit from increased evidence based aggression prevention programmes.

Background: The spermatozoa undergo a series of changes in the epididymis to mature after their release from the testis and subsequently in the female reproductive tract after ejaculation to get capacitated and achieve fertilization potential. Despite having a silenced protein synthesis machinery, the dynamic change in protein profile of the spermatozoa is attributed either to acquisition of new proteins via vescicular transport or to several post-translational modifications (PTMs) occurring on the already expressed protein complement., Scope of Review: In this review emphasis is given on the PTMs already reported on the human sperm proteins under normal and pathologic conditions with particular reference to sperm function such as motility and fertilization. An attempt has been made to summarize different protocols and methods used for analysis of PTMs on sperm proteins and the newer trends those were emerging., Major Conclusions: Deciphering the differential occurrence of PTM on protein at ultrastructural level would give us a better insight of structure-function relationship of the particular protein. Protein with multiple PTMs could be used to generate the complex interaction network involved in a physiological function of a sperm. It can be speculated that crosstalk between different PTMs occurring either on same/ other proteins actually regulate the protein stability and activity both in physiological and pathological states., General Significance: The analytical prospective of various PTMs reported in human spermatozoa and their relevance to sperm function particularly in various pathophysiological states, would pave way for development of biomarkers for diagnosis, prognosis and therapeutic intervention of male infertility., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Contribution from a defective paternal genome has been attributed to be an important cause for spontaneous recurrent pregnancy loss (RPL). Increased oxidative stress results in decreased detoxification and is a cause for damage to chromatin, proteins, and membrane lipids. The present study aimed to explore if there is a significant relationship between retained histones due to defective packaging of DNA in spermatozoa and oxidative stress. RPL patients (n=16) with a history of ≥2 embryo losses before the 20th week of gestation and no female factor abnormality, and fertile healthy volunteers (n=20) as controls were included in the study. A significant difference in the levels of protein carbonylation and lipid peroxidation together with an increased retention of histones in the experimental groups was noticed. Histone carrying sites for oxidative modification such as arginine and lysine might be responsible for disturbing the paternal epigenomic control during early stages of embryonic differentiation leading to abortion.

An asymptomatic, blue, dome-shaped lesion on the buccal mucosa can include a plethora of entities clinically as well as histopathologically. Its clinical presentation may mimic reactive, developmental, benign or malignant conditions. This emphasizes the need on histopathological assessment of every docile looking lesion to explore its exact biological behavior., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Transient Receptor Potential Vanilloid sub-type 4 (TRPV4) is a non-selective cationic channel involved in regulation of temperature, osmolality and different ligand-dependent Ca(2+)-influx. Recently, we have demonstrated that TRPV4 is conserved in all vertebrates. Now we demonstrate that TRPV4 is endogenously expressed in all vertebrate sperm cells ranging from fish to mammals. In human sperm, TRPV4 is present as N-glycosylated protein and its activation induces Ca(2+)-influx. Its expression and localization differs in swim-up and swim-down cells suggesting that TRPV4 is an important determining factor for sperm motility. We demonstrate that pharmacological activation or inhibition of TRPV4 regulates Ca(2+)-wave propagation from head to tail. Such findings may have wide application in male fertility-infertility, contraception and conservation of endangered species as well., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The number of patients with oral cancer in India is increasing gradually (especially in younger people). Although the diagnostic modalities and therapeutic management of oral cancer are improving, the treatment outcome and prognosis of oral cancer remain poor. The absence of definite early warning symptoms for most head and neck cancers suggests that sensitive and specific biomarkers are likely to be important in screening for high-risk patients., Aims: To analyze serum adenosine deaminase (ADA) levels in oral squamous cell carcinoma (OSCC) cases who reported to our institute., Materials and Methods: A prospective study was performed on 100 histopathologically proven cases of OSCC (study group) and 100 normal healthy individuals (control group). Independent sample and one sample t-tests and one way ANOVA followed by Tuckey's POST HOC test were conducted for analysis., Results: Statistically significant increase in serum ADA levels was observed in OSCC cases compared to the control group. Also serum ADA level increased significantly with the histopathological grade., Conclusions: Serum ADA levels in OSCC may be a useful diagnostic and prognostic biomarkers in clinical practice and our findings suggest that a large-scale study is warranted to confirm clinical utility as a prognostic and diagnostic biomarker.

Transient Receptor Potential cation channel, subfamily Melastatin, member 8 (TRPM8) is involved in detection of cold temperature, different noxious compounds and in execution of thermo- as well as chemo-sensitive responses at cellular levels. Here we explored the molecular evolution of TRPM8 by analyzing sequences from various species. We elucidate that several regions of TRPM8 had different levels of selection pressure but the 4th-5th transmembrane regions remain highly conserved. Analysis of synteny suggests that since vertebrate origin, TRPM8 gene is linked with SPP2, a bone morphogen. TRPM8, especially the N-terminal region of it, seems to be highly variable in human population. We found 16,656 TRPM8 variants in 1092 human genomes with top variations being SNPs, insertions and deletions. A total of 692 missense mutations are also mapped to human TRPM8 protein of which 509 seem to be delateroiours in nature as supported by Polyphen V2, SIFT and Grantham deviation score. Using a highly specific antibody, we demonstrate that TRPM8 is expressed endogenously in the testis of rat and sperm cells of different vertebrates ranging from fish to higher mammals. We hypothesize that TRPM8 had emerged during vertebrate evolution (ca 450 MYA). We propose that expression of TRPM8 in sperm cell and its role in regulating sperm function are important factors that have guided its molecular evolution, and that these understandings may have medical importance.

While effects of different steroids on the gene expression and regulation are well established, it is proven that steroids can also exert rapid non-genomic actions in several tissues and cells. In most cases, these non-genomic rapid effects of steroids are actually due to intracellular mobilization of Ca(2+)- and other ions suggesting that Ca(2+) channels are involved in such effects. Transient Receptor Potential (TRP) ion channels or TRPs are the largest group of non-selective and polymodal ion channels which cause Ca(2+)-influx in response to different physical and chemical stimuli. While non-genomic actions of different steroids on different ion channels have been established to some extent, involvement of TRPs in such functions is largely unexplored. In this review, we critically analyze the literature and summarize how different steroids as well as their metabolic precursors and derivatives can exert non-genomic effects by acting on different TRPs qualitatively and/or quantitatively. Such effects have physiological repercussion on systems such as in sperm cells, immune cells, bone cells, neuronal cells and many others. Different TRPs are also endogenously expressed in diverse steroid-producing tissues and thus may have importance in steroid synthesis as well, a process which is tightly controlled by the intracellular Ca(2+) concentrations. Tissue and cell-specific expression of TRP channels are also regulated by different steroids. Understanding of the crosstalk between TRP channels and different steroids may have strong significance in physiological, endocrinological and pharmacological context and in future these compounds can also be used as potential biomedicine., (Copyright © 2014 Elsevier Inc. All rights reserved.)

As the mammalian spermatozoa transcends from the testis to the end of the epididymal tubule, the functionally incompetent spermatozoa acquires its fertilizing capability. Molecular changes in the spermatozoa at the posttesticular level concern qualitative and quantitative modifications of proteins along with their sugar moieties and membranous lipids mostly associated with motility, egg binding, and penetration processes. Proteomic studies have identified numerous sperm-specific proteins, and recent reports have provided a further understanding of their function with respect to male fertility. High-throughput techniques such as mass spectrometry have shown drastic potential for the identification and study of sperm proteins. In fact, compelling evidence has provided that proteins are critically important in cellular remodeling event and that aberrant expression is associated with pronounced defects in sperm function. This review highlights the posttesticular functional transformation in the epididymis and female reproductive tract with due emphasis on proteomics., (© The Author(s) 2014.)

Fibrous dysplasia (FD) is a benign skeletal lesion occurring due to mutation of Gs α gene and involves one or multiple bones. We present a case of a 30-year-old female patient, with a 1-year history of swelling under her right eye that had gradually increased in size. Extraoral examination revealed a diffuse swelling extending anteroposteriorly from preauricular region to nasolabial fold, frontonasal region and superoinferiorly from zygoma to body of mandible, causing ipsilateral proptosis and contralateral deviation of nose. Intraoral examination showed obliteration of right upper and lower buccal vestibule. CT disclosed expansile lytic lesions involving multiple skull bones, jaws, sternum, rib and thoracic vertebrae. Histopathology displayed broad and interconnected trabeculae connected to the host bone exhibiting reversal lines resembling the mosaic pattern of Paget's disease. These features suggested pagetoid polyostotic FD. The patient underwent cosmetic recontouring and is under regular follow-up postoperatively., (2015 BMJ Publishing Group Ltd.)

Introduction: Tuberculosis (TB) is still a major public health problem in India. This study was aimed to know the awareness and impact of Information, Education, Communication (IEC) activities about TB and RNTCP & DOTS among general population around Bathinda area of Malwa region of Punjab through patients attending chest OPD of a tertiary care hospital attached to a medical college of this region., Material & Methods: A cross-sectional study was conducted in above stated hospital from 1st June, 2012 to 31st May 2013, for a period of one year using a questionnaire and a pictorial poster, which was pilot-tested and results were included in the main study., Results: A total Of 19,259 patients attended chest OPD in the given time period. It included 11412 (59%) male and 7847(41%) female patients. Average age of the patients was 46.8 years. Majority of patients were in the age-group of 26-50 years which is a most active and economically productive age group., Conclusion: Although this study shows that knowledge about symptoms, mode of transmission of infection, treatment under RNTCP by DOTS is satisfactory but still IEC activities for RNTCP and DOTS need more and more and repeated sensitization of the general population. It is recommended that such, studies are to be conducted for better implementation of RNTCP and DOTS programme in the country, particularly in the light of HIV and drug resistant Tuberculosis.

Podoplanin, a transmembrane sialoglycoprotein, is a specific marker for lymphatic endothelial cells which in recent years has gained prominent notoriety for its role in tumor progression and metastasis. It is an extensively studied biomarker for predictive assessment of malignant transformation as well as biologic behavior in both human precancer and cancer, respectively. This review summarizes the association of podoplanin overexpression in oral potentially malignant disorders and oral cancer with special emphasis on its putative role in carcinogenesis as well as its prospective use in targeted therapy.

Background: Previous studies have shown that healthcare workers experience high levels of aggression from patients. Prevention packages to address this have received little research support. Communication skills have been shown to influence individuals' experience of aggression and are also amenable to training., Objectives: This study aims to deliver a communication skills training package that will reduce the experience of aggression in the workplace for healthcare workers., Design: An interactive, multimedia communication skills package was developed that would be suitable for community healthcare workers. The training consisted of four workshops, including teaching, discussion and DVD illustrative examples. These were based on research and clinical experience., Settings: This intervention was delivered in two community care organisations over several months., Participants: Fifty-six community healthcare workers took part in the trial in small groups. There were 46 females and 10 males with a median age of 45-54 years., Methods: For each group a series of four communication skills workshops were given. Measurements of perceived aggression and wellbeing were taken before the workshops, at the end of the workshops, one month after and two months after., Results: Results show statistically significant reductions in perceived aggression one and two months after baseline measures (p<0.01). Results also suggest reductions in distress and increases in general mental wellness (p<0.01). Evaluation of the programme by participants was positive., Conclusions: A brief communication skills training programme is both enjoyable and shows decreases in perceived aggression, distress, and increases in general mental wellness. A full RCT of this intervention is warranted., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aims: Working in a healthcare environment is a known risk factor for violence. Patient aggression towards staff is often present in a hospital setting but the extent, type and variation among various occupations and roles are not known., Method: This research examines the type and frequency of aggression experienced by healthcare staff, using a previously used measure the POPAS-NZ, which is a short pen and paper survey. Responses were gathered from 227 people working in a single district health board., Results: Responses showed verbal anger was experienced by 93% of healthcare workers in the previous year and physical aggression was experienced by 65% of respondents. Also, 38% of staff reported experiencing a physical assault in the previous year. When analysed by role it was found that nurses and support staff experienced the greatest number of aggressive incidents compared to doctors and allied health staff. No effects of gender of the healthcare worker were found. Psychiatric units showed greater levels of destructive behaviour and attempted assaults but were similar to other areas of the hospital on all other measures., Conclusion: These results demonstrate many hospital staff, of all roles and workplaces experience aggression on a frequent basis. Implications for staff training are discussed.

Adenomatoid odontogenic tumor (AOT) has a limited biological profile and been an attention-grabbing tumor for a century for its origin. Though described earlier, it was widely accepted after Harbitz from Norway reported about this uncommon benign tumor in 1915. There has been a long debate as whether this tumor is a hamartoma or a neoplasm. Here, we present a case of AOT in a 20-year-old female with details of clinical, radiological and histological features along with clear cell changes, signifying AOT to be more aggressive in nature than assessed from earlier literature. Thus, we did an extensive search of PubMed literature on AOT with all its histopathological features associated until date to find the report of clear cell changes yet.

Aim: The 2010 New Zealand Chronic Pain Survey aimed to gather information from people who experience chronic pain about their pain, mental health, disabilities, and acceptance of pain., Methods: In December 2010, surveys were distributed in paper or online to GPs, hospitals, pain clinics asking for people with chronic pain to respond. The survey was open for 6 weeks., Results: There were 142 responses to the survey. Most people reported more than one cause of their pain, and pain in more than one site. Although respondents reported a wide range of causes of their pain, most people were unsure of the cause, or endorsed injury or arthritis as the cause. The most common site of pain was the lower back, followed by the pelvis and joints. Levels of disability were high. Pain was significantly correlated with depression and anxiety, and negatively correlated with acceptance., Conclusion: New Zealanders experience chronic pain stemming from multiple origins, with multiple causes. Consistent with international data, the experience of pain causes high levels of mental health issues and disability, but can be modulated by acceptance. Future studies should examine treatment availability and effectiveness.

There is increasing evidence that the growth and spread of cancers is driven by a small subpopulation of cancer stem cells (CSCs)--the only cells that are capable of long-term self-renewal and generation of the phenotypically diverse tumor cell population. CSCs have been identified and isolated in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). The concept of cancer stem cells may have profound implications for our understanding of tumor biology and for the design of novel treatments targeted toward these cells. The present review is an attempt to conceptualize the role of CSCs in HNSCC--its implication in tumorigenesis and the possible additional approach in current treatment strategies.

Sperm cells exhibit extremely high sensitivity in response to slight changes in temperature, osmotic pressure and/or presence of various chemical stimuli. In most cases throughout the evolution, these physico-chemical stimuli trigger Ca (2+)-signaling and subsequently alter structure, cellular function, motility and survival of the sperm cells. Few reports have recently demonstrated the presence of Transient Receptor Potential (TRP) channels in the sperm cells from higher eukaryotes, mainly from higher mammals. In this work, we have explored if the sperm cells from lower vertebrates can also have thermo-sensitive TRP channels. In this paper, we demonstrate the endogenous presence of one specific thermo-sensitive ion channel, namely Transient Receptor Potential Vanilloid family member sub type 1 (TRPV1) in the sperm cells collected from fresh water teleost fish, Labeo rohita. By using western blot analysis, fluorescence assisted cell sorting (FACS) and confocal microscopy; we confirm the presence of this non-selective cation channel. Activation of TRPV1 by an endogenous activator NADA significantly increases the quality as well as the duration of fish sperm movement. The sperm cell specific expression of TRPV1 matches well with our in silico sequence analysis. The results demonstrate that TRPV1 gene is conserved in various fishes, ranging from 1-3 in copy number, and it originated by fish-specific duplication events within the last 320 million years (MY). To the best of our knowledge, this is the first report demonstrating the presence of any thermo-sensitive TRP channels in the sperm cells of early vertebrates as well as of aquatic animals, which undergo external fertilization in fresh water. This observation may have implications in the aquaculture, breeding of several fresh water and marine fish species and cryopreservation of fish sperms.