"Factors influencing sedentary time and physical activity early after stroke: a qualitative study".

Abstract:
PURPOSE
We aimed to understand from the perspective of stroke survivors and their carers (1) factors contributing to sedentary time and physical activity during inpatient rehabilitation and the transition home, and (2) actual and perceived opportunities to reduce sedentary time and increase physical activity.

MATERIAL AND METHODS
Qualitative study with 7 stroke survivor/carer dyads and 8 stroke survivors. Semi-structured interviews were conducted 2-4 weeks after hospital discharge, audio recorded and transcribed prior to thematic analysis.

RESULTS
Stroke survivors were mean age 69 [SD15] years (53% male). Carers were mean age 62 [SD15] years (86% were female). Five themes were identified: (1) Education and guidance about physical activity and sedentary behaviour after stroke is important to build understanding of recovery and secondary prevention, (2) Stroke survivors need clear communication about safety and risk, (3) Return to life participation supports motivation for and engagement in physical activity, 4) Social and professional influences and 5) Opportunities to be physically active.

CONCLUSION
Stroke survivors and their carers need a clearer understanding of the role of physical activity and risks of sedentary time during stroke recovery. Physical activity enablers included consistent communication, building confidence and skills to self-manage activity before discharge.Implications for RehabilitationInpatient rehabilitation and early after discharge may be an important time-point to support stroke survivors to establish long term physical activity behaviours before contact with healthcare professionals reduces.To reduce sedentary behaviour, people need to understand the health benefits of breaking up sedentary time and people who need physical support to stand up will need greater support from health professionals.Being able to imagine a future post-stroke self is important motivation to get up and move. Rehabilitation should help develop a person's vision of their post-stroke self.Managing potential risks in hospital without overly restricting physical activity is important and requires consistent communication from the multi-disciplinary team.Building a person's confidence and skills to self-manage physical activity in the community prior to discharge home may be another key enabler for activity.

physical activity
stroke
Qualitative
rehabilitation
transition home


Hexavalent chromium bioreduction and chemical precipitation of sulphate as a treatment of site-specific fly ash leachates.

Abstract: Most of the power generation globally is by coal-fired power plants resulting in large stockpiles of fly ash. The trace elements associated with the ash particles are subjected to the leaching effects of precipitation which may lead to the subsequent contamination of surface and groundwater systems. In this study, we successfully demonstrate an efficient and sustainable dual treatment remediation strategy for the removal of high levels of Cr6+ and SO42- introduced by fly ash leachate generated by a power station situation in Mpumalanga, South Africa. The treatment consisted of a primary fixed-bed bioreactor kept at a reduction potential for Cr6+ reduction. Metagenome sequencing clearly indicated a diverse bacterial community containing various bacteria, predominantly of the phylum Proteobacteria which includes numerous species known for their ability to detoxify metals such as Cr6+. This was followed by a secondary BaCO3/dispersed alkaline substrate column for SO42- removal. The combination of these two systems resulted in the removal of 99% Cr6+ and 90% SO42-. This is the first effective demonstration of an integrated system combining a biological and chemical strategy for the remediation of multi-contaminants present in fly ash leachate in South Africa.

Cason|Errol D|ED|
Williams|Peter J|PJ|
Ojo|Elizabeth|E|
Castillo|Julio|J|
DeFlaun|Mary F|MF|
van Heerden|Esta|E|

Hexavalent chromium
Sulphate
Fly ash leachate
Remediation


From conventional sensors to fibre optic sensors for strain and force measurements in biomechanics applications: a review.

Abstract: In vivo measurement, not only in animals but also in humans, is a demanding task and is the ultimate goal in experimental biomechanics. For that purpose, measurements in vivo must be performed, under physiological conditions, to obtain a database and contribute for the development of analytical models, used to describe human biomechanics. The knowledge and control of the mechanisms involved in biomechanics will allow the optimization of the performance in different topics like in clinical procedures and rehabilitation, medical devices and sports, among others. Strain gages were first applied to bone in a live animal in 40's and in 80's for the first time were applied fibre optic sensors to perform in vivo measurements of Achilles tendon forces in man. Fibre optic sensors proven to have advantages compare to conventional sensors and a great potential for biomechanical and biomedical applications. Compared to them, they are smaller, easier to implement, minimally invasive, with lower risk of infection, highly accurate, well correlated, inexpensive and multiplexable. The aim of this review article is to give an overview about the evolution of the experimental techniques applied in biomechanics, from conventional to fibre optic sensors. In the next sections the most relevant contributions of these sensors, for strain and force in biomechanical applications, will be presented. Emphasis was given to report of in vivo experiments and clinical applications.

Roriz|Paulo|P|
Carvalho|Lídia|L|
Frazão|Orlando|O|
Santos|José Luís|JL|
Simões|José António|JA|

Fibre optical sensors
Strain
Force
Biomechanics
In vivo sensing


Avoiding disease mongering: A checklist for vascular physicians and researchers.

Abstract: Disease mongering is an expression created in 1992 by a medical journalist, Lynn Payer, to qualify the "selling of sickness that widens the boundaries of treatable illness in order to expand markets for those who sell and deliver treatments". This interesting concept led us to question whether, as researchers with publication and career interests in superficial vein thrombosis, we were not shaping a benign condition into a disease. Since the publication of the CALISTO trial in 2010, anticoagulant management of superficial vein thrombosis remains debated. Issues raised, such as the cost-effectiveness of the treatment strategy, the use of a composite endpoint including death, the low event rate without mortality reduction and conflict of interest due to industrial funding. We searched Embase, Medline, Web of science, and Opengrey databases to review all aspects about disease mongering raised in the literature and created a checklist with seventeen items. We used this checklist as support for a narrative review, questioning known literature on superficial vein thrombosis. The main issues pointing towards disease mongering concerned definition and promotion; whereas management seemed rather spared. Many arguments could be counterbalanced, but researchers should pay particular attention to three major points: exaggeration of the severity of the disease and potential adverse outcomes without treatment, promotion by opinion leaders, and an openly declared, yet undoubtedly present, conflict of interest situation.

Frappé|Paul|P|
Haller|Dagmar M|DM|
Roméas|Andrea|A|
Bertoletti|Laurent|L|
François|Mathilde|M|
Robert-Ebadi|Helia|H|
Righini|Marc|M|

Awareness
Disease management
Medical ethics
Saphenous vein
Venous thromboembolism


Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance by suppressing NLRP3 inflammasome-mediated inflammation in type 2 diabetes rats.

Abstract:
BACKGROUND
Insulin resistance is one of the most common and important pathological features of type 2 diabetes (T2D). Recently, insulin resistance is increasingly considered to be associated with systemic chronic inflammation. Elevated levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in blood are predictive indicators of the development of T2D. Mesenchymal stem cell (MSC)-based therapies have been proven to have potential immunomodulation and anti-inflammatory properties through their paracrine effects; however, the mechanism for the anti-inflammatory effect of MSCs in enhancing insulin sensitivity is still uncertain.

METHODS
In the present experiment, we used HepG2 cells, a human hepatoma cell line, and a MSC-HepG2 transwell culturing system to investigate the anti-inflammatory mechanism of human umbilical cord-derived MSCs (UC-MSCs) under palmitic acid (PA) and lipopolysaccharide (LPS)-induced insulin resistance in vitro. Insulin resistance was confirmed by glycogen assay kit and glucose assay kit. Inflammatory factor release was detected by ELISA, gene expression was tested by quantitative real-time PCR, and insulin signaling activation was determined by western blotting analysis. The changes of inflammatory factors and insulin signaling protein were also tested in T2D rats injected with UC-MSCs.

RESULTS
Treating HepG2 cells with PA-LPS caused NLRP3 inflammation activation, including overexpression of NLRP3 and caspase-1, and overproduction of IL-1β and IL-18 as well as TNF-α from HepG2 cells. The elevated levels of these inflammatory cytokines impaired insulin receptor action and thereby prevented downstream signaling pathways, exacerbating insulin resistance in HepG2 cells. Importantly, UC-MSCs cocultured with HepG2 could effectively alleviate PA and LPS-induced insulin resistance by blocking the NLRP3 inflammasome activation and inflammatory agents. Furthermore, knockdown of NLRP3 or IL-1β partially improved PA and LPS-induced insulin signaling impairments in the presence of UC-MSCs. Similarly, UC-MSC infusion significantly ameliorated hyperglycemia in T2D rats and decreased inflammatory activity, which resulted in improved insulin sensitivity in insulin target tissues.

CONCLUSIONS
Our results indicated that UC-MSCs could attenuate insulin resistance and this regulation was correlated with their anti-inflammatory activity. Thus, MSCs might become a novel therapeutic strategy for insulin resistance and T2D in the near future.

D045164:Mesenchymal Stem Cell Transplantation

D000071199:NLR Family, Pyrin Domain-Containing 3 Protein

Mesenchymal stem cells
Insulin resistance
Inflammation
Type 2 diabetes
Palmitic acid
Lipopolysaccharide
NLRP3 inflammasome


Correction and response to: Grommets in HBOT patients: GA vs. LA, unanswered questions.

Abstract: We thank Gibbs and Commons for their interest in our paper. There is a key difference between the datasets for Commons et al and our study. Our data set, has grouped ﬁve years of data according to the calendar year. This is different from Commons et al's study population recruited between 01 June 2009 and 31 May 2010. We feel this may explain the difference of one case between the two papers in 2010. Our data collection used the standard clinic and operating theatre databases, and we were advised that there was no searchable clinical code for grommet procedures undertaken with local anaesthetic (LA) in the outpatient clinic. The alternative, to review many hundreds of patients, was considered beyond the study's scope. Instead, the TTH Hyperbaric Medicine Unit (HMU) database was used to recruit cases and cross checked with operating theatre data. We have since re-investigated the operating theatre database to identify any additional bilateral grommet procedures during 2008 to 2012 and cross checked these with the HMU database. This has identiﬁed one to four additional patients per year in the general anaesthesia (GA) group and one additional LA patient that meet the criteria for recruitment into the study. There was one further unconﬁrmed patient from each of 2008 and 2010, whose charts were unavailable for this response, and have not been included in this amendment. The corrected Figure 1 reﬂects these changes. Despite the additional cases, the frequency spike during 2010 remains. A published audit of the number of middle ear barotrauma (MEBT) cases between 2007-2010 also reports an increased incidence of MEBT in 2009-2010 compared with previous years at our unit. Possible reasons for this may be the introduction of new technology at the unit, in the form of the digital Macro View™ otoscope during this period, leading to a possible change in clinical practice and an increased detection of MEBT, or a lower threshold for ENT referral for grommet placement. Alternatively, a 'Hawthorne effect' from the conduct of a prospective study within the TTH HMU, during 2009-2010 may be considered. With the outliers removed using ROUT's test, the signiﬁcant difference in the delay time to surgery remains (LA median 1, IQR 2, range 0-5 days; GA median 7.5, IQR 6, range 0-24 days; P < 0.0001; Figure 2). The data values of 98 days and 86 days from the GA group published in our paper are corrected to six days and 12 days respectively. On review, the ﬁrst individual was found to have had two HBOT courses, and it was only in the second round of HBOT that an ENT referral for grommets was made. The second individual was found to have been offered two ENT referrals after experiencing MEBT, the ﬁrst was followed by the patient declining further HBOT until representing to TTH HMU four months later and receiving prophylactic grommets before recommencing HBOT; this second ENT referral date has been used in the amended data. These corrections have not been found to change the primary outcome of statistical signiﬁcance between the LA and GA groups. A delay of seven days may not be considered clinically relevant in the most common cases requiring HBOT, aside from affecting patient convenience and logistics as well as hospital efﬁciency and resources. In emergency cases, knowledge of factors able to reduce the delay for grommet insertion is clinically relevant. In centres where a long wait for GA is the norm, LA may convey a clinically important lesser waiting time. As a retrospective study, only data documented in the patient records could be studied, and patient discomfort was not consistently recorded in the charts. We would liken this to undertaking other surgical procedures, where clinicians often do not routinely document pain scores for the beneﬁt of retrospective research. Several studies have examined patients' tolerance of grommets under LA, ﬁnding the technique tolerable.

Lamprell|Laura|L| Vangaveti|Venkat|V| Young|Derelle|D| Orton|John|J|

Corrections
middle ear
ear barotrauma
ENT
hyperbaric oxygen therapy


Screening and early detection of chronic kidney disease at primary healthcare.

Abstract: Chronic kidney disease (CKD) represents a global public health concern and results in poor health outcomes. While the burden of CKD is accurately well defined in developed countries, increasing evidence indicates that the CKD burden may be even greater in developing countries. Primary care has an essential role in the early identification of CKD and the prompt integrated management between primary and secondary CKD care, with participation of the patient, should be done in high quality. Systematic screening for CKD in at-risk individuals is strongly indicated for timely intervention when needed and to perceive the impact of such policies on CKD incidence. Furthermore, failure to recognize a patient in stages 1-3 of CKD may result in high incidence of CKD complications and kidney failure, often leaving the patient unsuitable for different renal replacement therapies, such as dialysis and transplantation. Therefore, primary care early referral and consultation with a nephrologist can give a better chance for different dialysis procedures and minimize the rate of hospitalization and mortality.

D042241:Early Diagnosis
D006760:Hospitalization
D006801:Humans
D008403:Mass Screening
D058007:Physicians, Primary Care
D011320:Primary Health Care
D051436:Renal Insufficiency, Chronic

Screening
chronic kidney disease
health programmes
primary healthcare centers


Association of the anti-angiogenic factor secreted protein and rich in cysteine (SPARC) with vascular complications among Chinese type 2 diabetic patients in Singapore.

Abstract:
AIMS
This study evaluated the association of the anti-angiogenic SPARC with known angiogenesis-associated factors and diabetes-related micro- and macro-vascular complications in a Singapore Chinese cohort with type 2 diabetes (T2DM).

METHODS
Plasma SPARC was measured by immunoassay in 438 T2DM adults (mean age:58±11years).

RESULTS
Higher SPARC levels in subjects stratified by SPARC tertiles displayed decreased pro-angiogenic adiponectin, osteopontin, vascular cell adhesion molecule (VCAM)-1 and matrix metalloproteinase (MMP)-2 concentrations (all p<0.05). The anti-angiogenic pigment epithelium-derived factor (PEDF) level was not statistically different among the SPARC tertiles. Age-adjusted partial correlation revealed significant associations of SPARC with adiponectin, osteopontin, VCAM-1, MMP-2, and PEDF (all p<0.05). Lower SPARC was accompanied by less favorable estimated glomerular filtration rate (eGFR) and carotid-femoral pulse wave velocity (PWV) readings (all p<0.05). Conversely, ankle-brachial index (ABI) reduced with increasing SPARC (p=0.048). The eGFR (B=0.834, p=0.019), PWV (B=-7.925, p=0.009), and ABI (B=-142.160, p=0.010) remained as determinants of SPARC after confounder adjustment. Moreover, individuals in the lowest SPARC tertile had increased odds of aortic stiffness (OR=1.900, 95% CI=1.103-3.274) but reduced odds of peripheral arterial disease (OR=0.400, 95% CI=0.175-0.919). However, SPARC was not independently associated with chronic kidney disease.

CONCLUSIONS
The anti-angiogenic SPARC may be associated with the pathophysiology of diabetes-related macrovascular complications.

Moh|Mei Chung|MC|
Sum|Chee Fang|CF|
Tavintharan|Subramaniam|S|
Pek|Sharon Li Ting|SLT|
Yeoh|Lee Ying|LY|
Ng|Xiaowei|X|
Lee|Simon Biing Ming|SBM|
Tang|Wern Ee|WE|
Lim|Su Chi|SC|

SPARC
Type 2 diabetes
Aortic stiffness
Peripheral arterial disease
Chronic kidney disease
Angiogenesis


Intravenous Thrombolysis for Stroke and Presumed Stroke in Human Immunodeficiency Virus-Infected Adults: A Retrospective, Multicenter US Study.

Abstract:
BACKGROUND AND PURPOSE
Human immunodeficiency virus (HIV) infection has been shown to increase both ischemic and hemorrhagic stroke risks, but there are limited data on the safety and outcomes of intravenous thrombolysis with tPA (tissue-type plasminogen activator) for acute ischemic stroke in HIV-infected patients.

METHODS
A retrospective chart review of intravenous tPA-treated HIV patients who presented with acute stroke symptoms was performed in 7 large inner-city US academic centers (various search years between 2000 and 2017). We collected data on HIV, National Institutes of Health Stroke Scale score, ischemic stroke risk factors, opportunistic infections, intravenous drug abuse, neuroimaging findings, and modified Rankin Scale score at last follow-up.

RESULTS
We identified 33 HIV-infected patients treated with intravenous tPA (mean age, 51 years; 24 men), 10 of whom were stroke mimics. Sixteen of 33 (48%) patients had an HIV viral load less than the limit of detection while 10 of 33 (30%) had a CD4 count <200/mm3. The median National Institutes of Health Stroke Scale score at presentation was 9, and mean time from symptom onset to tPA was 144 minutes (median, 159). The median modified Rankin Scale score for the 33-patient cohort was 1 and for the 23-patient actual stroke cohort was 2, measured at a median of 90 days poststroke symptom onset. Two patients had nonfatal hemorrhagic transformation (6%; 95% confidence interval, 1%-20%), both in the actual stroke group. Two patients had varicella zoster virus vasculitis of the central nervous system, 1 had meningovascular syphilis, and 7 other patients were actively using intravenous drugs (3 cocaine, 1 heroin, and 3 unspecified), none of whom had hemorrhagic transformation.

CONCLUSIONS
Most HIV-infected patients treated with intravenous tPA for presumed and actual acute ischemic stroke had no complications, and we observed no fatalities. Stroke mimics were common, and thrombolysis seems safe in this group. We found no data to suggest an increased risk of intravenous tPA-related complications because of concomitant opportunistic infections or intravenous drug abuse.

AbdelRazek|Mahmoud A|MA|
Gutierrez|Jose|J|
Mampre|David|D|
Cervantes-Arslanian|Anna|A|
Ormseth|Cora|C|
Haussen|Diogo|D|
Thakur|Kiran T|KT|
Lyons|Jennifer L|JL|
Smith|Bryan R|BR|
O'Connor|Owen|O|
Willey|Joshua Z|JZ|
Mateen|Farrah J|FJ|

D000073618:Varicella Zoster Virus Infection

stroke
tissue-type plasminogen activator
CD4 lymphocyte count
CVA (cerebrovascular accident)
HIV infections
intracranial hemorrhages


Maternal 'near miss' at Royal Darwin Hospital: An analysis of severe maternal morbidity at an Australian regional tertiary maternity unit.

Abstract:
BACKGROUND
Assessment of severe maternal morbidity using World Health Organization (WHO) 'near-miss' criteria is gaining in importance as a valuable tool in the assessment of maternity care of women. Identification of cases allows an understanding of aetiology of severe morbidity and factors contributing to poor maternal outcomes.

AIM
The aim of this study is to determine the rate of maternal 'near miss' at Royal Darwin Hospital (RDH) and the utility of the WHO near-miss criteria as a tool for data collection in a regional Australian context.

METHODS AND MATERIALS
Cases of maternal 'near miss' and deaths were prospectively identified over a period of 12 months using the WHO criteria.

RESULTS
During the audit period, there were 2080 live births at Royal Darwin Hospital (RDH): 10 women presented with a 'near miss' and there was one maternal death. The maternal mortality ratio for the hospital was 48/100 000 live births, the maternal 'near-miss' index ratio was 4.8/1000 live births, and the combination of maternal deaths and near misses gave a severe maternal outcome (SMO) ratio of 5.3/1000 live births. The main cause of obstetric 'near miss' was obstetric haemorrhage. Indigenous women and women from remote areas comprised a significant portion of 'near-miss' cases.

CONCLUSION
The rates of maternal 'near miss' at RDH are consistent with other studies in the developed world. The WHO maternal 'near-miss' audit tool helps health professionals understand and anticipate severe maternal morbidities, with the aim of improving maternal and perinatal outcomes.

Jayaratnam|Skandarupan|S|
Burton|Alice|A|
Connan|Kirsten Fiona|KF|
de Costa|Caroline|C|

D005260:Female
D006757:Hospital Units
D006801:Humans
D008428:Maternal Mortality
D008485:Medical Audit
D000067491:Near Miss, Healthcare
D015876:Northern Territory
D011247:Pregnancy
D011248:Pregnancy Complications
D011446:Prospective Studies
D019984:Quality Indicators, Health Care
D062606:Tertiary Care Centers
D014592:Uterine Hemorrhage
D014944:World Health Organization


Endogenous production of n-3 polyunsaturated fatty acids protects mice from carbon tetrachloride-induced liver fibrosis by regulating mTOR and Bcl-2/Bax signalling pathways.

Abstract:
NEW FINDINGS
What is the central question of this study? What is the protective benefit of n-3 polyunsaturated fatty acids (PUFAs) on liver fibrosis and what are the relevant signalling pathways in a transgenic mouse model overexpressing the mfat-1 enzyme? What is the main finding and its importance? n-3 PUFA elevation strongly prevented carbon tetrachloride (CCl4 )-induced hepatic damage and inhibited the activation of hepatic stellate cells. n-3 PUFAs suppressed CCl4 -induced activation of mTOR, elevated Bcl-2 expression, and reduced Bax level, suggesting that n-3 PUFAs can render strong protective effects against liver fibrosis and point to the potential of mfat-1 gene therapy as a treatment modality.

ABSTRACT
Liver fibrosis is a reversible wound healing response with excessive accumulation of extracellular matrix proteins. It is a globally prevalent disease with ultimately severe pathological consequences. However, very few current clinical therapeutic options are available. Nutritional addition of n-3 polyunsaturated fatty acids (PUFAs) can delay and lessen the development of liver fibrosis. Herein, this study examined the protective benefit of n-3 PUFAs on liver fibrosis and the relevant signalling pathways using a transgenic mouse model overexpressing the mfat-1 enzyme that converts n-6 to n-3 PUFAs. Male C57BL/6 wild-type and mfat-1 transgenic mice were administered carbon tetrachloride (CCl4 ) or control corn oil by intraperitoneal injection. Blood alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were subsequently measured. CCl4 -induced hepatic damage and fibrosis were assessed using haematoxylin-eosin and Masson's trichrome staining. Western blot assays were used to detect and quantify fibrosis-related proteins and mechanistic target of rapamycin (mTOR) and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) signalling components. The direct effect of docosahexaenoic acid (DHA) on primary hepatic stellate cells (HSCs) was also investigated in a co-culture experiment. n-3 PUFAs, as a result of mfat-1 activity, had a strong protective effect on liver fibrosis. The elevation of ALT and AST induced by CCl4 was significantly lessened in the mfat-1 mice. Histological determination revealed the protective effects of n-3 PUFAs on liver inflammation and collagen deposition. Co-incubation with DHA reduced the expression of profibrogenic factors in the primary HSCs. Moreover, mfat-1 transgenic mice showed significant reduction of proteins that are involved in mTOR and Bcl-2/Bax signalling pathways. Collectively, these results suggest that n-3 PUFA elevation strongly prevents CCl4 -induced hepatic damage by directly inhibiting the activation of HSCs and regulating the basal activity of the mTOR and Bcl-2/Bax signalling pathways. Gene therapy applying mfat-1 and elevating n-3 PUFAs represents a promising treatment strategy to prevent liver fibrosis.

liver fibrosis
mTOR
Bcl-2/Bax
hepatic stellate cells
n−3 PUFAs
transgenic mfat-1 mice


Genetic markers for antimony resistant clinical isolates differentiation from Indian Kala-azar.

Abstract: Visceral Leishmaniasis or Kala-azar is caused by the protozoan parasites belonging to the Genus Leishmania. Once thought eradicated from the Indian subcontinent, the disease came back with drug resistance to almost all prevalent drugs. Molecular epidemiological studies revealed the polymorphic nature of the population of the main player of the disease, Leishmania donovani and involvement of other species (L. tropica) and other genus (Leptomonas) with the disease. This makes control measures almost futile. It also strongly demands the characterization of each and every isolate mandatory which is not done. In this background, the present study has been carried out to assess the genetic attributes of each clinical isolates (n=26) of KA and PKDL patients from India and Bangladesh. All the isolates were characterized through Restriction Fragment Length Polymorphism (RFLP) analysis to ascertain their species identity. 46.2% of the isolates were found to be Sodium Stibogluconate (SSG) resistant by amastigote-macrophage model. When the clinical isolates were subjected to Single Stranded Conformation Polymorphism (SSCP) of Internal Transcribed Spacer 1 (ITS1), Internal Transcribed Spacer 2 (ITS2) and some anonymous markers, the drug resistant Leishmania isolates of SSG can be distinguished from the sensitive isolates distinctly. This study showed for the first time, the genetic markers for SSG drug resistance of Indian Kala-azar clinical isolates.

Khanra|Supriya|S|
Sarraf|Nibedeeta Rani|NR|
Das|Shantanabha|S|
Das|Anjan Kumar|AK|
Roy|Syamal|S|
Manna|Madhumita|M|

D012150:Polymorphism, Restriction Fragment Length

Single stranded conformation polymorphism


Evidence for Policy Making: Clinical Appropriateness Study of Lumbar Spine MRI Prescriptions Using RAND Appropriateness Method.

Abstract:
BACKGROUND
MRI is a new and expensive diagnostic technology, which has been used increasingly all over the world. Low back pain is a worldwide prevalent disorder and MRI technique is one of the several ways to diagnose it. This paper aims to identify the appropriateness of lumbar spine MRI prescriptions in Shiraz teaching hospitals using standardized RAND Appropriateness Method (RAM) criteria in 2012.

METHODS
This study consisted of two phases. The first phase involved a qualitative enquiry and the second phase had a quantitative cross-sectional nature. In the first phase RAM was used for developing lumbar spine MRI indications and scenarios. In the second phase, the finalized scenarios were compared with the history and physical examination of 300 patients with low back pain. The rate of appropriateness of lumbar spine MRI prescription was then calculated.

RESULTS
Of 300 cases of lumbar spine MRI prescriptions, approximately 167 (56%) were considered inappropriate, 72 (24%) were uncertain, and 61 (20%) were deemed to be appropriate. The economic burden of inappropriate prescriptions was calculated at 88,009,000 Rials. In addition, the types of expertise and physical examination were considered as related factors to appropriateness of prescriptions.

CONCLUSION
In conclusion, a large proportion of lumbar spine MRI prescriptions, which result in financial burden on the insurance companies and the patients alike is unnecessary. This study suggests that policy makers consider this evidence while decision-making. Our findings highlight the imperative role of Health Technology Assessment (HTA) and Clinical Practice Guidelines (CPGs). As a result, developing local clinical guidelines may create the commitment needed in physicians in prescribing appropriate prescriptions within the health sector. The study further recommends that appropriate scenarios should be considered as a criterion for payment and reimbursement.

Salari|Hedayat|H|
Ostovar|Rahim|R|
Esfandiari|Atefeh|A|
Keshtkaran|Ali|A|
Akbari Sari|Ali|A|
Yousefi Manesh|Hossein|H|
Rakhshan|Amir|A|

Evidence
Lumbar Spine
MRI Prescription
RAND Appropriateness Method
Shiraz
Clinical Practice Guideline


Synthesis and biological evaluation of heterocyclic 1,2,4-triazole scaffolds as promising pharmacological agents.

Abstract:
BACKGROUND
Triazole is an important heterocyclic moiety that occupies a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms i.e. 1,2,4-triazole and 1,2,3-triazole and is used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, anti-urease, anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic and antimigraine agents.

METHODS
The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards.

RESULTS, DISCUSSION AND CONCLUSION
The biological screening results reveal that the compounds T5 (MICBS, EC = 24.7 µM, MICPA, CA = 12.3 µM) and T17 (MICAN = 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MICCipro = 18.1 µM, MICAmo = 17.1 µM) and fluconazole (MICFlu = 20.4 µM), respectively. The antioxidant evaluation showed that compounds T2 (IC50 = 34.83 µg/ml) and T3 (IC50 = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC50 = 35.44 µg/ml). Compounds T3 (IC50 = 54.01 µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC50 = 54.25 µg/ml). The most potent anticancer activity was shown by compounds T2 (IC50 = 3.84 μM) and T7 (IC50 = 3.25 μM) against HCT116 cell lines as compared to standard 5-FU (IC50 = 25.36 μM).

Kumari|Mukesh|M|
Tahlan|Sumit|S|
Narasimhan|Balasubramanian|B|
Ramasamy|Kalavathy|K|
Lim|Siong Meng|SM|
Shah|Syed Adnan Ali|SAA|
Mani|Vasudevan|V|
Kakkar|Saloni|S|

1,2,4-Triazole Antimicrobial Antioxidant Anti-urease Anticancer SAR


Do children with dyslexia present a handwriting deficit? Impact of word orthographic and graphic complexity on handwriting and spelling performance.

Abstract: Several studies have demonstrated that children with dyslexia frequently show poor and slow handwriting skills. It is not clear whether these difficulties are a consequence of their spelling deficit or if they arise from graphomotor difficulties. The present study aims to test the hypothesis of the presence of handwriting difficulties in dyslexia, through the investigation of the impact of graphic and orthographic complexity of words on writing. Participants were all monolingual French-speaking children. Twenty-three children with dyslexia (DYS) were compared to two groups of typically developing children: 23 chronological-age (CA) matched children and 23 spelling-age (SA) matched children. They were assessed on a single-word dictation task of 40 words on a digital tablet. The target words varied in orthographic complexity and in graphic complexity (simple vs. difficult). This task was scored on spelling accuracy, handwriting quality and handwriting speed. General Linear Mixed Model analyses revealed no global differences between the three groups for handwriting quality. However, the DYS children were more impacted by the graphic complexity of words than both the CA and SA children. These findings support the idea that children with dyslexia struggle with the graphomotor aspects of writing and have potential implications for educational and clinical supports.

Dyslexia
Handwriting
Spelling
Graphomotor abilities
Learning disability
Writing development


Broncho-Vaxom® (OM-85 BV) soluble components stimulate sinonasal innate immunity.

Abstract:
BACKGROUND
Broncho-Vaxom® (OM-85 BV) is an extract of infectious respiratory bacteria that is used as an immunostimulant outside of the United States for the prevention and treatment of bronchitis and rhinosinusitis. Prior studies have shown that use of OM-85 BV is associated with reduction in frequency of respiratory infection and decreased duration of antibiotic usage. However, the effects of OM-85 BV on respiratory mucosal innate immunity are unknown.

METHODS
Human sinonasal epithelial cells were grown at an air-liquid interface (ALI). Ciliary beat frequency (CBF) and nitric oxide (NO) production in response to stimulation with OM-85 BV was measured in vitro. Pharmacologic inhibitors of bitter taste receptor (T2R) signaling were used to determine if this pathway was taste-receptor-mediated.

RESULTS
Apical application of OM-85 BV resulted in an NO-mediated increase in CBF (p < 0.05) and increased NO production (p < 0.0001) when compared to saline-stimulated control cultures. ALI pretreatment with taste receptor pathway inhibitors blocked OM-85 BV-induced increases in NO.

CONCLUSION
OM-85 BV has ciliostimulatory and immunogenic properties that may be partially responsible for its observed efficacy as a respiratory therapeutic. These responses were NO-dependent and consistent with T2R activation. Further work is necessary to elucidate specific component-receptor signaling relationships.

D000276:Adjuvants, Immunologic
D002457:Cell Extracts
D002478:Cells, Cultured
D002923:Cilia
D004847:Epithelial Cells
D006801:Humans
D007113:Immunity, Innate
D009297:Nasal Mucosa
D009569:Nitric Oxide

innate immunity
rhinosinusitis
therapeutics
ciliary motility
immunotherapy
sinusitis


Transglutaminase type 2 affects cell migration through post-translational modification of platelet-derived growth factor-BB.

Abstract: Migration is a key cellular function with important implications in cell physiology. Impairment of such function is observed in angiogenesis, cancer, central nervous system development, and many other physiological and pathological events. Serum is considered among the most potent physiological chemotactic stimuli. Transglutaminase 2 (TG2) is involved in most of the mentioned processes, suggesting the hypothesis that TG2 may modulate cell movement and chemotaxis by acting on serum factors. Cell biology and biochemistry studies confirmed this hypothesis, showing that human serum contains potent chemotactic signals significantly impaired by activated TG2. Bioinformatics studies indicated that one potent serum factor potential substrate of TG2-dependent transamidation is platelet-derived growth factor-BB (PDGF-BB). Cell biology and immunometric experiments carried out with U87MG human glioma cell line showed that human recombinant PDGF-BB pre-incubated with calcium-activated TG2 lost about 70 % of its chemotactic activity and antigenicity. These data indicate that PDGF-BB is a substrate of TG2-transamidating activity, and such modification may play a key role in the modulation of PDGF's chemotactic features. Further, these findings suggest a novel point of view to study the extracellular functions of TG2 and to understand how protein signals, such as growth factors and cytokines, act in the extracellular space to reach their specific targets.

Cordella|Martina|M|
Tabolacci|Claudio|C|
Rossi|Stefania|S|
Senatore|Cinzia|C|
Facchiano|Angelo M|AM|
D'Arcangelo|Daniela|D|
Facchiano|Antonio|A|
Facchiano|Francesco|F|

D061307:Human Umbilical Vein Endothelial Cells

D000091345:Protein Glutamine gamma Glutamyltransferase 2

Transglutaminase type 2
Migration
Angiogenesis
Cancer
Serum
PDGF


Isolation and characterization of a novel, T7-like phage against Aeromonas veronii.

Abstract: A virulent Aeromonas veronii biovar sobria and the corresponding novel, lytic bacteriophage (VTCCBPA5) were isolated from village pond water. The phage was found to belong to family Podoviridae. PCR analysis of major capsid protein gene confirmed its classification to T7-like genus. The protein profiling by SDS-PAGE indicated the major structural protein to be ~ 45 kDa. The phage (VTCCBPA5) is host specific and is stable over a range of pH (6-10) and temperatures (4-45 °C). On the basis of restriction endonuclease analysis combined with prediction mapping, it was observed to vary significantly from previously reported podophages of Aeromonas sp., viz. phiAS7 and Ahp1. The phylogenetic analysis on the basis of PCR-amplified segment of DNA polymerase gene of phage revealed it being an outgroup from podophages of Klebsiella sp. and Pseudomonas sp. though a small internal fragment (359 bp) showed the highest identity (77%) with Vibrio sp. phages. Thus, this is the first report of a novel Podoviridae phage against A. veronii. It expands the assemblage of podophages against Aeromonas sp. and BPA5 could be potentially useful in biocontrol of environmentally acquired Aeromonas veronii infections.

Characterization
Aeromonas veronii
Podoviridae
DNA polymerase gene
TEM


Down Regulation of KAI1/CD82 in Lymph Node Positive and Advanced T-Stage Group in Breast Cancer Patients.

Abstract:
BACKGROUND
Metastasis represents a deadly aspect of any cancer including breast cancer, given its high prevalence; treatment of metastatic breast cancer remains a clinically unmet need, which necessitates the exploration of metastasis suppressor genes (MSGs). KAI-1/CD82 is an important member of MSGs; the role of KAI1 has been well explored in prostate cancer, however its role in breast cancer is not fully explored and in fact the results of breast cancer studies are contentious. Thus, the present study aimed to investigate expression of KAI1 at both transcriptional and translational levels in the tissue of breast cancer patients and benign breast disease. Further, we analysed the relationship between expression levels of KAI1 and clinicopathological parameters in breast cancer patients.

MATERIALS AND METHODS
mRNA expression was studied by Real time PCR and protein expression was analyzed by both Western blot and Immunohistochemistry.

RESULTS
The results of the study indicate that KAI1 expression was remarkably decreased in breast cancer both at the gene and the protein levels (P < 0.05) compared to benign breast disease. In addition, KAI1 expression levels were strongly associated with axillary lymph node status and advanced T stage (p < 0.05), however no association was found with tumor grade, age, menopausal status and receptor status like ER, PR and Her2.

CONCLUSION
Low expression of KAI1 might be helpful for predicting the lymph node metastasis and T staging, thus predicts malignant prognosis of breast cancer.<br />.

Krishna Latha|Thammineni|T|
Verma|Ankur|A|
Thakur|Gaurav Kumar|GK|
Banerjee|Basudev|B|0000000283483989
Kaur|Navneet|N|
Singh|Usha Rani|UR|
Sharma|Sonal|S|

D000328:Adult
D014408:Biomarkers, Tumor
D001943:Breast Neoplasms
D016022:Case-Control Studies
D005260:Female
D005500:Follow-Up Studies
D006801:Humans
D051861:Kangai-1 Protein
D008198:Lymph Nodes
D008207:Lymphatic Metastasis
D009367:Neoplasm Staging

breast cancer
KAI-1/CD82
Lymph node metastasis


Primary peritoneal carcinoma presenting as a case of ascites.

Abstract: Primary peritoneal carcinoma (PPC) was first described in 1959 by Swerdlow. It is a rare malignant tumor of the peritoneal cavity. Clinically and histologically it is similar to advanced-stage serous ovarian carcinoma that develops from the peritoneum lining the pelvis and abdomen and is characterized by abdominal carcinomatosis, uninvolved or minimally involved ovaries, and no identifiable primary tumor. This cancer spreads widely inside the peritoneal cavity and mostly involves the omentum. There is some thought that the peritoneal cells that give rise to peritoneal cancer may actually be leftover ovarian cells that remained in the abdomen during development. It is almost exclusively found in women. Clinical features include abdominal swelling, constipation, gastrointestinal disorders, nausea, vomiting, anorexia, and weight loss.

Jha|Ajay K|AK|
Sunder|Ashok|A|
Kumari|Shweta|S|
Dubey|Keertee|K|

Primary peritoneal carcinoma
Abdominal carcinomatosis
Immunohistochemistry


Mechanisms Associated to Nitroxyl (HNO)-Induced Relaxation in the Intestinal Smooth Muscle.

Abstract: The pharmacological properties of nitroxyl (HNO) donors in the gastrointestinal tract are unknown. We investigated the properties of this molecule in the regulation of gastrointestinal contractility focusing on its possible interaction with other gaseous signaling molecules such as NO and H2S. Organ bath, Ca2+ imaging, and microelectrode recordings were performed on rat intestinal samples, using Angeli's salt as HNO donor. Angeli's salt caused a concentration-dependent relaxation of longitudinal or circular muscle strips of the ileum and the proximal colon. This relaxation was strongly inhibited by the Rho-kinase inhibitor Y-27632 (10 μM), by the reducing agent DTT or by the inhibitor of soluble guanylate cyclase (sGC) ODQ (10 μM) alone or in combination with the inhibitors of the endogenous synthesis of H2S β-cyano-L-alanine (5 mM) and amino-oxyacetate (5 mM). Preventing endogenous synthesis of NO by the NO synthase inhibitor L-NAME (200 μM) did not affect the relaxation induced by HNO. HNO induced an increase in cytosolic Ca2+ concentration in colonic myocytes. It also elicited myocyte membrane hyperpolarization that amounted to -10.6 ± 1.1 mV. ODQ (10 μM) and Apamin (1 μM), a selective inhibitor of small conductance Ca2+-activated K+ channels (SKca), strongly antagonized this effect. We conclude that HNO relaxes the gastrointestinal tract musculature by hyperpolarizing myocytes via activation of the sGC/cGMP pathway similarly to NO, not only inhibiting the RhoK and activating MLCP as do both NO and H2S but also increasing cytosolic Ca2+ for activation of SK   contributing to hyperpolarization.


The surgical technique of the convergent procedure.

Abstract: The convergent procedure is a newly developed hybrid ablation procedure that involves extensive epicardial ablation of the posterior left atrial wall followed by endocardial mapping and addition of pulmonary vein isolation. It is a team-based approach that provides a promising option for patients with persistent and permanent atrial fibrillation. In this manuscript, we present a detailed description of the surgical component of this procedure and include potential pitfalls based on our experience in performing it.

convergent procedure
epicardial ablation
atrial fibrillation
endocardial ablation
minimally invasive


Abstract:
Background and aims
To determine the incidence of upper and lower limb deep vein thrombosis (DVT) using ultrasonography (USG) in adult patients admitted to neuro-medical and neurosurgical intensive care unit (ICU).

Materials and methods
In this prospective observational study, patients admitted to the medical and surgical neuro-ICU and remained in the ICU for more than 48 hours were recruited. All patients were clinically examined for DVT. Basilic and axillary veins in the upper limbs and popliteal and femoral veins in the lower limbs were screened for DVT using USG. USG examination was performed on the day of admission to ICU and thereafter every 3rd day till discharge from ICU or death. Intermittent pneumatic compression (IPC) stockings were applied to the lower limbs to all the patients in both ICUs. Unfractionated heparin (UFH) was given subcutaneously to neuromedical ICU patients, while in surgical ICU, it was left to the discretion of the neurosurgeons.

Results
A total of 130 adult patients were admitted to the ICU during the 8 month study period. Thirty patients were excluded and the remaining 98 patients' (38 in medical and 60 in surgical ICU) data were analyzed. None of the 38 medical ICU patients developed DVT, while in neurosurgical ICU, 4 out of 60 patients developed DVT.

Conclusion
A combination of UFH and IPC stockings were effective in minimizing the DVT in neuromedical ICU patients. In surgical patients, through IPC stockings were effective, UFH can be considered for patients with intracranial malignancy.

How to cite this article
Behera SS, Krishnakumar M, Muthuchellappan R, Philip M. Incidence of Deep Vein Thrombosis in Neurointensive Care Unit Patients-Does Prophylaxis Modality Make Any Difference? Indian Journal of Critical Care Medicine, January 2019;23(1):43-46.

Behera|Shailaja S|SS|
Krishnakumar|Mathangi|M|
Muthuchellappan|Radhakrishnan|R|
Philip|Mariamma|M|

Deep vein thrombosis
Heparin
Intracranial malignancy
Neurocritical care
Thromboprophylaxis


Does a combination of ≥2 abnormal tests vs. the ERC-ESICM stepwise algorithm improve prediction of poor neurological outcome after cardiac arrest? A post-hoc analysis of the ProNeCA multicentre study.

Abstract:
BACKGROUND
Bilaterally absent pupillary light reflexes (PLR) or N20 waves of short-latency evoked potentials (SSEPs) are recommended by the 2015 ERC-ESICM guidelines as robust, first-line predictors of poor neurological outcome after cardiac arrest. However, recent evidence shows that the false positive rates (FPRs) of these tests may be higher than previously reported. We investigated if testing accuracy is improved when combining PLR/SSEPs with malignant electroencephalogram (EEG), oedema on brain computed tomography (CT), or early status myoclonus (SM).

METHODS
Post-hoc analysis of ProNeCA multicentre prognostication study. We compared the prognostic accuracy of the ERC-ESICM prognostication strategy vs. that of a new strategy combining ≥2 abnormal results from any of PLR, SSEPs, EEG, CT and SM. We also investigated if using alternative classifications for abnormal SSEPs (absent-pathological vs. bilaterally-absent N20) or malignant EEG (ACNS-defined suppression or burst-suppression vs. unreactive burst-suppression or status epilepticus) improved test sensitivity.

RESULTS
We assessed 210 adult comatose resuscitated patients of whom 164 (78%) had poor neurological outcome (CPC 3-5) at six months. FPRs and sensitivities of the ≥2 abnormal test strategy vs. the ERC-ESICM algorithm were 0[0-8]% vs. 7 [1-18]% and 49[41-57]% vs. 63[56-71]%, respectively (p < .0001). Using alternative SSEP/EEG definitions increased the number of patients with ≥2 concordant test results and the sensitivity of both strategies (67[59-74]% and 54[46-61]% respectively), with no loss of specificity.

CONCLUSIONS
In comatose resuscitated patients, a prognostication strategy combining ≥2 among PLR, SSEPs, EEG, CT and SM was more specific than the 2015 ERC-ESICM prognostication algorithm for predicting 6-month poor neurological outcome.

Scarpino|Maenia|M|
Lolli|Francesco|F|
Lanzo|Giovanni|G|
Carrai|Riccardo|R|
Spalletti|Maddalena|M|
Valzania|Franco|F|
Lombardi|Maria|M|
Audenino|Daniela|D|
Celani|Maria Grazia|MG|
Marrelli|Alfonso|A|
Contardi|Sara|S|
Peris|Adriano|A|
Amantini|Aldo|A|
Grippo|Antonello|A|
Sandroni|Claudio|C|


Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging: earlier administration of chelating therapy can reduce the damage to the brain.

Abstract: The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson's disease during the long-term chelating therapy using magnetic resonance imaging and a possible significance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson's disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into: group A, where chelating therapy was initiated < 24 months from the first symptoms and group B, where the therapy started ≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a significant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions (P = 0.005 and P = 0.024, respectively). If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be expected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.

Kozić|Duško B|DB|
Petrović|Igor|I|
Svetel|Marina|M|
Pekmezović|Tatjana|T|
Ragaji|Aleksandar|A|
Kostić|Vladimir S|VS|

Wilson's disease
magnetic resonance imaging
chelating therapy
copper toxicity
cirrhosis
delayed diagnosis
diagnostic imaging
hepatic encephalopathy
metabolic disorders
nerve regeneration
neural regeneration
pontine myelinolysis


A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux.

Abstract: Lipid accumulation within the lumen of endolysosomal vesicles is observed in various pathologies including atherosclerosis, liver disease, neurological disorders, lysosomal storage disorders, and cancer. Current methods cannot measure lipid flux specifically within the lysosomal lumen of live cells. We developed an optical reporter, composed of a photoluminescent carbon nanotube of a single chirality, that responds to lipid accumulation via modulation of the nanotube's optical band gap. The engineered nanomaterial, composed of short, single-stranded DNA and a single nanotube chirality, localizes exclusively to the lumen of endolysosomal organelles without adversely affecting cell viability or proliferation or organelle morphology, integrity, or function. The emission wavelength of the reporter can be spatially resolved from within the endolysosomal lumen to generate quantitative maps of lipid content in live cells. Endolysosomal lipid accumulation in cell lines, an example of drug-induced phospholipidosis, was observed for multiple drugs in macrophages, and measurements of patient-derived Niemann-Pick type C fibroblasts identified lipid accumulation and phenotypic reversal of this lysosomal storage disease. Single-cell measurements using the reporter discerned subcellular differences in equilibrium lipid content, illuminating significant intracellular heterogeneity among endolysosomal organelles of differentiating bone-marrow-derived monocytes. Single-cell kinetics of lipoprotein-derived cholesterol accumulation within macrophages revealed rates that differed among cells by an order of magnitude. This carbon nanotube optical reporter of endolysosomal lipid content in live cells confers additional capabilities for drug development processes and the investigation of lipid-linked diseases.

hyperspectral microscopy
live-cell imaging
near-infrared fluorescence
single-cell sensing
single-walled carbon nanotubes


Anticoagulant protein S in COVID-19: low activity, and associated with outcome.

Abstract: Introduction. COVID-19 disease was associated with both thrombo-embolic events and in-situ thrombi formation in small vessels. Antiphospholipidic antibodies were found in some studies.Aim. Assessment of protein S activity in patients with COVID-19 as a cause of this prothrombotic state, and of the association of protein S activity with worse outcome.Methods. All patients admitted for COVID-19 disease in a university hospital between 15th of May and 15th of July 2020 were prospectively enrolled into this cohort study. Patients treated with antivitamin K anticoagulants and with liver disease were excluded. All patients had protein S activity determined at admission. The main outcome was survival, while secondary outcomes were clinical severity and lung damage.Results. 91 patients were included, of which 21 (23.3%) died. Protein S activity was decreased in 65% of the patients. Death was associated with lower activity of protein S (median 42% vs. 58%, p < 0.001), and the association remained after adjustment for age, inflammation markers and ALAT. There was a dose-response relationship between protein S activity and clinical severity (Kendall_tau coefficient = -0.320, p < 0.001; Jonckheere-Terpstra for trend: p < 0.001) or pulmonary damage on CT scan (Kendall_tau coefficient = -0.290, p < 0.001; Jonckheere-Terpstra for trend: p < 0.001). High neutrophil count was also independently associated with death (p = 0.002).Conclusion. Protein S activity was lower in COVID-19 patients, and its level was associated with survival and disease severity, suggesting that it may have a role in the thrombotic manifestations of the disease.

Stoichitoiu|Laura Elena|LE|
Pinte|Larisa|L|
Balea|Marius Ioan|MI|
Nedelcu|Valentin|V|
Badea|Camelia|C|
Baicus|Cristian|C|

protein S
COVID-19
neutrophilia
thrombophilia
thrombosis


Ten-year results of mesenchymal stromal cell transplantation augmented with vascularised bone grafts for advanced osteonecrosis of the femoral head.

Abstract:
Background
A prospective, open-label clinical trial, in which transplantation of cultured autologous bone marrow-derived multipotent mesenchymal stromal cells in combination with vascularised bone grafts for the treatment of post-collapse extensive osteonecrosis of the femoral head in ten patients, was conducted previously. The aim of this study was to assess the 10-year clinical and radiographic results of that study.

Methods
Patients were evaluated for radiographic progression of osteonecrosis of the femoral head using anteroposterior radiographs at 10 years postoperatively. Clinical score and hip function, including the timed up and go test, were also estimated.

Results
Osteoarthritic changes in the affected hip were found in five of the ten patients, two of whom had undergone total hip arthroplasty at 7 and 9 years postoperatively. Five of the six cases (83.3%) in which pre-operative femoral head collapse was less than 3 mm, had no further collapse. On the other hand, all four cases in which pre-operative femoral head collapse was ≥3 mm, showed osteoarthritic changes within 10 years. The average clinical score significantly improved postoperatively and was maintained at 10 years.

Conclusions
Considering that eight of 10 post-collapse cases could avoid total hip arthroplasty conversion with good clinical results for 10 years and five of 6 post-collapse cases (collapse <3 mm) could avoid further collapse and osteoarthritic changes for 10 years, mesenchymal stromal cell transplantation in combination with vascularised bone grafts could be an effective treatment for post-collapse osteonecrosis of the femoral head.

Goto|Koji|K| Aoyama|Tomoki|T| Toguchida|Junya|J| Kuroda|Yutaka|Y| Kawai|Toshiyuki|T| Okuzu|Yaichiro|Y| Matsuda|Shuichi|S|

Mesenchymal stromal cell
Vascularised bone graft
Osteonecrosis of the femoral head
Post-collapse


Spectacle: An interactive resource for ocular single-cell RNA sequencing data analysis.

Abstract: Single-cell RNA sequencing has revolutionized ocular gene expression studies. This technology has enabled researchers to identify expression signatures for rare cell types and characterize how gene expression changes across biological conditions, such as topographic region or disease status. However, sharing single-cell RNA sequencing results remains a major obstacle, particular for individuals without a computational background. To address these limitations, we developed Spectacle, an interactive web-based resource for exploring previously published single-cell RNA sequencing data from ocular studies. Spectacle is powered by a locally developed R package, cellcuratoR, which utilizes the Shiny framework in R to generate interactive visualizations for single-cell expression data. Spectacle contains five pre-processed ocular single-cell RNA sequencing data sets and is accessible via the web at OcularGeneExpression.org/singlecell. With Spectacle, users can interactively identify which cell types express a gene of interest, detect transcriptomic subpopulations within a cell type, and perform highly flexible differential expression analyses. The freely-available Spectacle system reduces the bioinformatic barrier for interacting with rich single-cell RNA sequencing studies from ocular tissues, making it easy to quickly identify cell types that express a gene of interest.

Voigt|Andrew P|AP|
Whitmore|S Scott|SS|
Lessing|Nicholas D|ND|
DeLuca|Adam P|AP|
Tucker|Budd A|BA|
Stone|Edwin M|EM|
Mullins|Robert F|RF|
Scheetz|Todd E|TE|

Interactive
Single-cell RNA sequencing
Gene expression
Choroid
RPE
Retina


Tracheal Capillary Hemangioma Successfully Treated With Combined Bronchoscopic Cryotherapy and Argon-Plasma Coagulation.

Abstract: We report a 43-year-old female who presented with recurrent non-massive hemoptysis for four months. Chest radiograph was normal. Thoracic computed tomography (CT) scan revealed a 0.8-centimeter intraluminal polypoid mass abutting the middle part of trachea. A fiber-optic bronchoscopy demonstrated a lobulated reddish mass at dorsolateral aspect of the right side of tracheal wall. Cryotherapy to remove the mass and argon plasma coagulation to stop bleeding at the stump was performed. The histological evaluation conﬁrmed the diagnosis of a tracheal lobular capillary hemangioma. There was no recurrence hemoptysis nor the recurrence of tumor during a one-year follow-up.

Ruenwilai|Parinya|P| Liwsrisakun|Chalerm|C| Limsukon|Atikun|A| Bumroongkit|Chaiwat|C| Lertprasertsuk|Nirush|N|

cryotherapy
bronchoscopy
argon plasma coagulation
tracheal lobular capillary hemangioma
primary tracheal tumor


SU-E-J-35: A Model for the Simulation of EPID Measurements in the BeamNRC Monte Carlo Package.

Abstract:
PURPOSE
The intent of this study was to create a virtual model of a simple Electronic Portal Image Device (EPID) in the BeamNRC Monte Carlo package which would simulate EPID measurements taken in vivo.

METHODS
A typical accelerator was created in the BeamNRC software using published 6MV spectra from Mohan, et. al. and the basic head design of a Varian accelerator head. The particle fluence at the level of the mylar window was output into a planar 'phase space' file. The output of this accelerator was delivered to a phantom with a 1 mm thick slab of water acting as the detector array using the DosXYZ package. Additionally, the fluence from the same geometry was computed at the level of the virtualEPID (vEPID). The simulations were run for 2×2, 5×5, 10×10, 20×20, and 25×25 field sizes, as well as a simple IMRT field. The results of the open field simulations were then used for the parameterization of a deconvolution kernel using the form described by Renner, et. al.

RESULTS
The simulations were run with sufficient histories to produce a 1% uncertainty in the resulting fluence and dose matrices in the high dose/fluence region of the output. Additional software was created to convert 'phase space' files to fluence in the same grid as the vEPID. A final software package was written to iteratively determine the exponential fitting parameters described in Ritter, et. al. to deconvolve the detector function from the fluence measurements.

CONCLUSIONS
The system will allow one to simulate both EPID measurements, as well as remove the detector function from vEPIDsimulations for further use in fluence studies using BeamNRC. This will allow one to simulate a system for in vivo patient measurements using an EPID to study without the need for time on a medical accelerator, and without contributing additional radiation fatigue to the EPID device.

Detector arrays
Field size
Deconvolution
Medical accelerators
Computer software
Image guided radiation therapy
Intensity modulated radiation therapy
Medical imaging
Monte Carlo methods
Particle beam detectors


Measurements of body surface area and volume in male Japanese White rabbits using a computed tomography scanner: comparison with male New Zealand White rabbits.

Abstract: The body surface area (BSA) of animals has generally been estimated by multiplying the k value by the measured body weight (BW) raised to the power of 2/3 (Meeh's formula). In mathematical terms, the assumption that the density and body shape of animals are essentially constant means that the BSA is proportional to BW2/3. In this study, we measured the BSA and volume of 50 male Japanese White rabbits (JW) at 10 to 54 weeks of age using a computed tomography scanner, then calculated the k value, density, and sphericity. The variations in these parameters were then analyzed in relation to growth. The obtained results indicated that the k value was negatively correlated to BW, and that this negative correlation was mainly due to the variation in density. Based on the regression analysis, we propose the following linear regression equation for calculating the k value in male JW at 10-54 weeks of age: the k value = 14.602 - 0.959 × BW [kg]. The calculated values ranged from 10.9 to 12.7 (working BW range: 1.98 to 3.81 kg). The k value of male New Zealand White rabbits (NZW) determined in our previous study and that of male JW in the present study were compared. It was revealed that the k value of male JW was larger than that of male NZW. We concluded that different breeds of rabbits express different k values.

Itoh|Tadashi|T| Kawabe|Mifumi|M| Nagase|Takahiko|T| Endo|Katsumi|K| Miyoshi|Masafumi|M| Miyahara|Kazuro|K|

D015898:Tomography Scanners, X-Ray Computed

body surface area
Japanese White rabbit
rabbit
computed tomography
CT scanner


Adenoid Cystic Carcinoma of Bartholin's Gland: Case Report.

Abstract: Primary adenoid cystic carcinoma (ACC) of Bartholin's gland is a rare gynecologic malignancy. We report a case of locally advanced ACC of Bartholin's gland. A 62-year-old presented with left Bartholin's gland carcinoma and underwent left radical vulvectomy, left-sided inguinal-femoral lymph node dissection, posterior pelvic exenteration, and pedicle abdominal muscle flap. On her 3 months follow-up exam she was disease free.Pelvic exenteration for thetreatment of this rare disease in the vulva is a potential curative option.

Momeni|Mazdak|M| Korotkaya|Yelena|Y| Carrasco|Gonzalo|G| Prasad-Hayes|Monica|M|

D001472:Bartholin's Glands
D003528:Carcinoma, Adenoid Cystic
D005260:Female
D013509:Gynecologic Surgical Procedures
D006801:Humans
D008875:Middle Aged
D013524:Surgical Flaps
D016896:Treatment Outcome
D014844:Vulva
D014846:Vulvar Neoplasms

Adenoid cystic carcinoma
Pelvic exenteration


Activation of RhoA/Rho-kinase pathway accounts for pulmonary endothelial dysfunction in patients with chronic obstructive pulmonary disease.

Abstract: Recent evidence suggests that activation of RhoA/Rho-kinase accounts for systemic and pulmonary endothelial dysfunction in smokers with normal lung function. However, its role in patients with chronic obstructive pulmonary disease (COPD) has not yet been investigated. The aim of this study was to evaluate the regulation of RhoA/Rho-kinase pathway and pulmonary endothelial dysfunction in patients with COPD. Pulmonary arteries were obtained from nonsmokers (control subjects) and patients with nonhypoxemic and hypoxemic COPD (n = 6-7/group). Endothelium-dependent and -independent relaxations were evaluated by acetylcholine and sodium nitroprusside, respectively. Gene and protein expressions of endothelial nitric oxide synthase (eNOS) were measured by RT-PCR, Western blot, and immunohistochemistry. Nitrate, cGMP, and endothelin-1 (ET-1) concentrations, as well as Rho-kinase activity were measured by ELISA. Protein expressions of total RhoA and GTP-RhoA were measured by Western blot and pull-down assay, respectively. Endothelium-dependent relaxation, and nitrate and cGMP levels were significantly reduced in pulmonary arteries of COPD patients as compared with control subjects. Conversely, activity of RhoA/Rho-kinase was increased in pulmonary arteries of COPD patients as compared with control subjects. In patients with COPD, pulmonary endothelial dysfunction was related to the downregulation of eNOS activity and upregulation of RhoA/Rho-kinase activity.

Bei|Yihua|Y|
Duong-Quy|Sy|S|
Hua-Huy|Thong|T|
Dao|Pierre|P|
Le-Dong|Nhat-Nam|NN|
Dinh-Xuan|Anh Tuan|AT|

RhoA
Rho-kinases
endothelial dysfunction
COPD
eNOS


Carnitine palmitoyltransferase 1C negatively regulates the endocannabinoid hydrolase ABHD6 in mice, depending on nutritional status.

Abstract:
BACKGROUND AND PURPOSE
The enzyme α/β-hydrolase domain containing 6 (ABHD6), a new member of the endocannabinoid system, is a promising therapeutic target against neuronal-related diseases. However, how ABHD6 activity is regulated is not known. ABHD6 coexists in protein complexes with the brain-specific carnitine palmitoyltransferase 1C (CPT1C). CPT1C is involved in neuro-metabolic functions, depending on brain malonyl-CoA levels. Our aim was to study CPT1C-ABHD6 interaction and determine whether CPT1C is a key regulator of ABHD6 activity depending on nutritional status.

EXPERIMENTAL APPROACH
Co-immunoprecipitation and FRET assays were used to explore ABHD6 interaction with CPT1C or modified malonyl-CoA-insensitive or C-terminal truncated CPT1C forms. Cannabinoid CB1 receptor-mediated signalling was investigated by determining cAMP levels. A novel highly sensitive fluorescent method was optimized to measure ABHD6 activity in non-neuronal and neuronal cells and in brain tissues from wild-type (WT) and CPT1C-KO mice.

KEY RESULTS
CPT1C interacted with ABHD6 and negatively regulated its hydrolase activity, thereby regulating 2-AG downstream signalling. Accordingly, brain tissues of CPT1C-KO mice showed increased ABHD6 activity. CPT1C malonyl-CoA sensing was key to the regulatory role on ABHD6 activity and CB1 receptor signalling. Fasting, which attenuates brain malonyl-CoA, significantly increased ABHD6 activity in hypothalamus from WT, but not CPT1C-KO, mice.

CONCLUSIONS AND IMPLICATIONS
Our finding that negative regulation of ABHD6 activity, particularly in the hypothalamus, is sensitive to nutritional status throws new light on the characterization and the importance of the proteins involved as potential targets against diseases affecting the CNS.

ABHD6
CPT1C
malonyl-CoA
fasting
hypothalamus
endocannabinoid signalling
hippocampus


A Case of Cushing's Syndrome with Multiple Adrenocortical Adenomas Composed of Compact Cells and Clear Cells.

Abstract: A 58-year-old woman was referred to our hospital for Cushingoid features and diagnosed as adrenal Cushing's syndrome due to a right adrenocortical mass (60 × 55 mm). The mass was composed of three different tumors; the first one was homogeneously lipid-poor neoplasm measuring 20 × 13 mm located at the most dorsal region, the second one was heterogeneous and lipid-rich tumor containing multiple foci of calcification measuring 50 × 32 mm located at the central region, and the last one was heterogeneous harboring dilated and tortuous vessels and lipid-poor one measuring 35 × 18 mm at the most ventral region of the adrenal gland. A right adrenalectomy was subsequently performed by open surgery. Macroscopic and microscopic analyses revealed that all three tumors were adrenocortical adenomas; the first one represents a pigmented adrenocortical adenoma, the second one adrenocortical adenoma associated with degeneration, and the third one adrenocortical adenoma harboring extensive degeneration. Immunohistochemical analysis of the steroidogenic enzymes also revealed that all of the tumors had the capacity of synthesizing cortisol. This is a very rare case of Cushing's syndrome caused by multiple adrenocortical adenomas including a pigmented adenoma. Immunohistochemical analysis of steroidogenic enzymes contributed to understanding of steroidogenesis in each of these three different adrenocortical adenomas in this case.

Multiple adrenocortical adenomas
Steroidogenic enzymes
Pigmented adenoma
Cushing’s syndrome
Immunohistochemistry


Adjunctive Non-Surgical Therapy of Inflamed Periodontal Pockets During Maintenance Therapy Using Diode Laser: A Randomized Clinical Trial.

Abstract:
BACKGROUND
Numerous studies have documented the clinical outcomes of laser therapy for untreated periodontitis, but very few have reported on lasers treating inflamed pockets during maintenance therapy. The aim of this study is to compare the effectiveness of scaling and root planing (SRP) plus the adjunctive use of diode laser therapy to SRP alone on changes in the clinical parameters of disease and on the gingival crevicular fluid (GCF) inflammatory mediator interleukin-1β (IL-1β) in patients receiving regular periodontal maintenance therapy.

METHODS
This single-masked and randomized, controlled, prospective study includes 22 patients receiving regular periodontal maintenance therapy who had one or more periodontal sites with a probing depth (PD) ≥ 5 mm with bleeding on probing (BOP). Fifty-six sites were treated with SRP and adjunctive laser therapy (SRP + L). Fifty-eight sites were treated with SRP alone. Clinical parameters, including PD, clinical attachment level (CAL), and BOP, and GCF IL-1β levels were measured immediately before treatment (baseline) and 3 months after treatment.

RESULTS
Sites treated with SRP + L and SRP alone resulted in statistically significant reductions in PD and BOP and gains in CAL. These changes were not significantly different between the two therapies. Similarly, differences in GCF IL-1β levels between SRP + L and SRP alone were not statistically significant.

CONCLUSION
In periodontal maintenance patients, SRP + L did not enhance clinical outcomes compared to SRP alone in the treatment of inflamed sites with ≥ 5 mm PD.

Nguyen|Naomi-Trang|NT|
Byarlay|Matthew R|MR|
Reinhardt|Richard A|RA|
Marx|David B|DB|
Meinberg|Trudy A|TA|
Kaldahl|Wayne B|WB|

D000368:Aged
D000369:Aged, 80 and over
D003131:Combined Modality Therapy
D012534:Dental Scaling
D005260:Female
D005500:Follow-Up Studies
D005883:Gingival Crevicular Fluid
D005884:Gingival Hemorrhage
D006801:Humans
D053583:Interleukin-1beta
D054023:Lasers, Semiconductor
D028022:Low-Level Light Therapy
D008297:Male
D008875:Middle Aged
D017622:Periodontal Attachment Loss
D010514:Periodontal Pocket
D010518:Periodontitis
D011446:Prospective Studies
D016745:Root Planing
D016037:Single-Blind Method
D016896:Treatment Outcome

periodontitis
lasers
Clinical trial
root planing
recurrence
therapeutics


p38 mitogen-activated protein kinase and pain.

Abstract: Inflammatory and neuropathic pain is initiated by tissue inflammation and nerve injury, respectively. Both are characterized by increased activity in the peripheral and central nervous system, where multiple inflammatory cytokines and other active molecules activate different signaling pathways that involve in the development and/or maintenance of pain. P38 mitogen-activated protein kinase (MAPK) is one member of the MAPK family, which is activated in neurons and glia and contributes importantly to inflammatory and neuropathic pain. The aim of this review is to summarize the latest advances made about the implication of p38 MAPK signaling cascade in pain. It can deepen our understanding of the molecular mechanisms of pain and may help to offer new targets for pain treatment.

Mai|Lijia|L| Zhu|Xiao|X| Huang|Fang|F| He|Hongwen|H| Fan|Wenguo|W|

D048051:p38 Mitogen-Activated Protein Kinases


Strategies to Care for Patients Being Treated in the Emergency Department After Self-harm: Perspectives of Frontline Staff.

Abstract:
INTRODUCTION
Every year, approximately 500 000 patients in the United States present to emergency departments for treatment after an episode of self-harm. Evidence-based practices such as designing safer ED environments, safety planning, and discharge planning are effective for improving the care of these patients but are not always implemented with fidelity because of resource constraints. The aim of this study was to provide insight into how ED staff innovate processes of care and services by leveraging what is available on-site or in their communities.

METHODS
A total of 34 semi-structured qualitative phone interviews were conducted with 12 nursing directors, 11 medical directors, and 11 social workers from 17 emergency departments. Respondents comprised a purposive stratified sample recruited from a large national survey in the US. Interview transcripts were coded and analyzed using a directed content analysis approach to identify categories of strategies used by ED staff to care for patients being treated after self-harm.

RESULTS
Although respondents characterized the emergency department as an environment that was not well-suited to meet patient mental health needs, they nevertheless described 4 categories of strategies to improve the care of patients seen in the emergency department after an episode of self-harm. These included: adapting the ED environment, improving efficiencies to provide mental health care, supporting the staff who provide direct care for patients, and leveraging community resources to improve access to mental health resources postdischarge.

DISCUSSION
Despite significant challenges in meeting the mental health needs of patients treated in the emergency department after self-harm, the staff identified opportunities to provide mental health care and services within the emergency department and leverage community resources to support patients after discharge.

True|Gala|G|
Pollock|Miranda|M|
Bowden|Cadence F|CF|
Cullen|Sara Wiesel|SW|
Ross|Abigail M|AM|
Doupnik|Stephanie K|SK|
Caterino|Jeffrey M|JM|
Olfson|Mark|M|
Marcus|Steven C|SC|

D000359:Aftercare
D004636:Emergency Service, Hospital
D006801:Humans
D008603:Mental Health
D010351:Patient Discharge
D016728:Self-Injurious Behavior
D014481:United States

Evidence-based practice
Mental health
Emergency service
Hospital
Self-injurious Behavior


Equine Mx1 Restricts Influenza A Virus Replication by Targeting at Distinct Site of its Nucleoprotein.

Abstract: Interferon-mediated host factors myxovirus (Mx) proteins are key features in regulating influenza A virus (IAV) infections. Viral polymerases are essential for viral replication. The Mx1 protein has been known to interact with viral nucleoprotein (NP) and PB2, resulting in the influence of polymerase activity and providing interspecies restriction. The equine influenza virus has evolved as an independent lineage to influenza viruses from other species. We estimated the differences in antiviral activities between human MxA (huMxA) and equine Mx1 (eqMx1) against a broad range of IAV strains. We found that huMxA has antiviral potential against IAV strains from non-human species, whereas eqMx1 could only inhibit the polymerase activity of non-equine species. Here, we demonstrated that NP is the main target of eqMx1. Subsequently, we found adaptive mutations in the NP of strains A/equine/Jilin/1/1989 (H3N8JL89) and A/chicken/Zhejiang/DTID-ZJU01/2013 (H7N9ZJ13) that confer eqMx1 resistance and sensitivity respectively. A substantial reduction in Mx1 resistance was observed for the two mutations G34S and H52N in H3N8JL89 NP. Thus, eqMx1 is an important dynamic force in IAV nucleoprotein evolution. We, therefore, suggest that the amino acids responsible for Mx1 resistance should be regarded as a robust indicator for the pandemic potential of lately evolving IAVs.

Fatima|Urooj|U| Zhang|Zhenyu|Z| Zhang|Haili|H| Wang|Xue-Feng|XF| Xu|Ling|L| Chu|Xiaoyu|X| Ji|Shuang|S| Wang|Xiaojun|X|

D000818:Animals
D004285:Dogs
D019143:Evolution, Molecular
D057809:HEK293 Cells
D006734:Horse Diseases
D006736:Horses
D054884:Host-Pathogen Interactions
D006801:Humans
D009980:Influenza A virus
D007251:Influenza, Human
D061985:Madin Darby Canine Kidney Cells
D009154:Mutation
D064547:Myxovirus Resistance Proteins
D019590:Nucleocapsid Proteins
D009976:Orthomyxoviridae Infections
D010802:Phylogeny
D011485:Protein Binding
D016601:RNA-Binding Proteins
D013045:Species Specificity
D014758:Viral Core Proteins
D014779:Virus Replication

equine Mx1
nucleoprotein
polymerase activity
equine influenza
MxA
influenza A viruses
interspecies transmission


Digital Videokymography: Analysis of Glottal Closure in Adults.

Abstract:
INTRODUCTION
High-speed videolaryngoscopy and quantitative analysis of laryngeal images are relevant in accurately diagnosing vocal fold closure patterns.

OBJECTIVE
To analyze the parameters of digital videokymography obtained through high-speed videolaryngoscopy in women and men with complete and incomplete glottal closure, and posterior glottal chink.

METHODS
We conducted an observational, analytical, cross-sectional study with data from 65 adults, which we divided into groups according to sex and glottal closure. Digital videokymography parameters were analyzed using an image-processing program. The Anderson-Darling and Mann-Whitney U tests were used to verify sample normality and compare videokymography parameters between groups, respectively. The significance level was set at 5%.

RESULTS
Among 65 laryngeal images, 20 each were from women with complete and incomplete glottal closure, and 20 and 5 were from men with complete and incomplete glottal closure, respectively. Considering the clinical relevance of the evaluated data, groups of 11 women and 4 men with posterior glottal chink were compared with sex-similar groups with complete glottal closure. Digital videokymography showed a lower maximum and mean vocal fold opening in women with incomplete glottal closure, and a lower dominant left vocal fold-opening amplitude and higher dominant frequency of bilateral vocal fold opening in men with incomplete glottal closure. It also showed a lower closed phase percentage in the posterior region for women and men, with higher closed phase percentage in the anterior and middle regions in women. Both groups with posterior glottal chink showed similar results.

CONCLUSION
Incomplete glottal closure may interfere with the results of the digital videokymography parameters, with higher impact on the posterior vocal fold region in males and the middle and anterior vocal fold regions in females.

Nogueira do Nascimento|Ualisson|U|
Santos|Marco Aurélio Rocha|MAR|
Gama|Ana Cristina Côrtes|ACC|

Vocal fold
Digital kymography
Glottis
Kymography
Laryngoscopy


Technical design of a new bone conduction implant (BCI) system.

Abstract:
OBJECTIVE
The objective of this study is to describe the technical design and verify the technical performance of a new bone conduction implant (BCI) system.

DESIGN
The BCI consists of an external audio processor and an implanted unit called the bridging bone conductor. These two units use an inductive link to communicate with each other through the intact skin in order to drive an implanted transducer.

STUDY SAMPLE
In this study, the design of the full BCI system has been described and verified on a skull simulator and on real patients.

RESULTS
It was found that the maximum output force (peak 107 dB re 1 μN) of the BCI is robust for skin thickness range of 2-8 mm and that the total harmonic distortion is below 8% in the speech frequency range for 70 dB input sound pressure level. The current consumption is 7.5 mA, which corresponds to 5-7 days use with a single battery.

CONCLUSIONS
This study shows that the BCI is a robust design that gives a sufficiently high output and an excellent sound quality for the hearing rehabilitation of indicated patients.

Taghavi|Hamidreza|H|
Håkansson|Bo|B|
Reinfeldt|Sabine|S|
Eeg-Olofsson|Måns|M|
Jansson|Karl-Johan Fredén|KJ|
Håkansson|Emil|E|
Nasri|Bayan|B|

D019986:Persons With Hearing Impairments

Bone conduction implant
inductive links
implanted transducer
bone anchored hearing aid
long-term implantation


Whole Genome Sequencing and Re-sequencing of the Sable Antelope (Hippotragus niger): A Resource for Monitoring Diversity in ex Situ and in Situ Populations.

Abstract: Genome-wide assessment of genetic diversity has the potential to increase the ability to understand admixture, inbreeding, kinship and erosion of genetic diversity affecting both captive (ex situ) and wild (in situ) populations of threatened species. The sable antelope (Hippotragus niger), native to the savannah woodlands of sub-Saharan Africa, is a species that is being managed ex situ in both public (zoo) and private (ranch) collections in the United States. Our objective was to develop whole genome sequence resources that will serve as a foundation for characterizing the genetic status of ex situ populations of sable antelope relative to populations in the wild. Here we report the draft genome assembly of a male sable antelope, a member of the subfamily Hippotraginae (Bovidae, Cetartiodactyla, Mammalia). The 2.596 Gb draft genome consists of 136,528 contigs with an N50 of 45.5 Kbp and 16,927 scaffolds with an N50 of 4.59 Mbp. De novo annotation identified 18,828 protein-coding genes and repetitive sequences encompassing 46.97% of the genome. The discovery of single nucleotide variants (SNVs) was assisted by the re-sequencing of seven additional captive and wild individuals, representing two different subspecies, leading to the identification of 1,987,710 bi-allelic SNVs. Assembly of the mitochondrial genomes revealed that each individual was defined by a unique haplotype and these data were used to infer the mitochondrial gene tree relative to other hippotragine species. The sable antelope genome constitutes a valuable resource for assessing genome-wide diversity and evolutionary potential, thereby facilitating long-term conservation of this charismatic species.

sable antelope
Hippotragus niger
genome assembly
Bovidae
conservation genetics


Isotope dilution mass spectrometry for the quantification of sulfane sulfurs.

Abstract: Sulfane sulfurs are one type of important reactive sulfur species. These molecules have unique reactivity that allows them to attach reversibly to other sulfur atoms and exhibit regulatory effects in diverse biological systems. Recent studies have suggested that sulfane sulfurs are involved in signal transduction processes regulated by hydrogen sulfide (H2S). Accurate and reliable measurements of sulfane sulfurs in biological samples are thus needed to reveal their production and mechanisms of actions. Herein we report a convenient and accurate method for the determination of sulfane sulfur concentrations. The method employs a triphenylphosphine derivative (P2) to capture sulfane sulfurs as a stable phosphine sulfide product, PS2. The concentration of PS2 was then determined by isotope dilution mass spectrometry, using a (13)C3-labeled phosphine sulfide, PS1, as the internal standard. The specificity and efficiency of the method were proven by model reactions. It was also applied to the measurement of sulfane sulfurs in mouse tissues including brain, kidney, lung, liver, heart, spleen, and blood.

Liu|Chunrong|C| Zhang|Faya|F| Munske|Gerhard|G| Zhang|Hui|H| Xian|Ming|M|

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Mass
Sulfane sulfur
Reactive sulfur species
Free radicals
Isotope dilution assay


Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension.

Abstract: Ubiquitination is a representative, reversible biological process of the post-translational modification of various proteins with multiple catalytic reaction sequences, including ubiquitin itself, in addition to E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, E3 ubiquitin ligase, deubiquitinating enzymes, and proteasome degradation. The ubiquitin-proteasome system is known to play a pivotal role in various molecular life phenomena, including the cell cycle, protein quality, and cell surface expressions of ion-transporters. As such, the failure of this system can lead to cancer, neurodegenerative diseases, cardiovascular diseases, and hypertension. This review article discusses Nedd4-2/NEDD4L, an E3-ubiquitin ligase involved in salt-sensitive hypertension, drawing from detailed genetic dissection analysis and the development of genetically engineered mice model. Based on our analyses, targeting therapeutic regulations of ubiquitination in the fields of cardio-vascular medicine might be a promising strategy in future. Although the clinical applications of this strategy are limited, compared to those of kinase systems, many compounds with a high pharmacological activity were identified at the basic research level. Therefore, future development could be expected.

Ishigami|Tomoaki|T| Kino|Tabito|T| Minegishi|Shintaro|S| Araki|Naomi|N| Umemura|Masanari|M|0000-0002-1812-5720 Ushio|Hisako|H| Saigoh|Sae|S| Sugiyama|Michiko|M|

D000075702:Nedd4 Ubiquitin Protein Ligases

epithelial sodium channel
Nedd4L/Nedd4-2
salt-sensitive hypertension
ubiquitination
aldosterone sensitive distal nephron
excitation-transcription coupling


Reduction in Short- and Long-term Pneumonia Rate With Laryngoplasty for Unilateral Vocal Fold Paralysis.

Abstract:
OBJECTIVE
To examine the association of laryngoplasty, voice therapy, and pneumonia rate in patients with unilateral vocal fold paralysis (UVFP).

STUDY DESIGN
Population-based retrospective cohort study.

SETTING
Data were collected from the LHID2000 (Longitudinal Health Insurance Database 2000), containing the information of 1 million randomly selected patients in Taiwan.

METHODS
In the LHID2000, we identified 439 patients having new diagnoses of UVFP from 1997 to 2013. We grouped the aforementioned patients according to UVFP treatment and probed the occurrence of pneumonia: 305 patients underwent laryngoplasty or voice therapy, and 134 patients did not undergo treatment. Follow-up procedures were executed for the enrollees until death or December 31, 2013, representing the end of the study period. We assessed the association of UVFP treatment and pneumonia by executing Cox proportional hazards regression.

RESULTS
The pneumonia cumulative incidence was significantly higher among enrolled patients without treatment than in those receiving treatment (P < .001). The pneumonia incidence was significantly lower in patients receiving UVFP treatment (hazard ratio, 0.49; 95% CI, 0.27-0.88; P = .018), as validated by the Cox proportional hazards model after adjustment. Patients undergoing laryngoplasty with or without voice therapy had a significantly lower incidence of pneumonia at 6 months and 1, 3, and 5 years, whereas those undergoing voice therapy alone did not.

CONCLUSION
Laryngoplasty was associated with a lower incidence of short- and long-term pneumonia in patients with UVFP. Physicians should encourage patients with UVFP at risk of aspiration to receive prompt evaluation as well as treatment.

Hsu|Cheng-Ming|CM| Tsai|Yao-Te|YT| Chang|Geng-He|GH| Yang|Yao-Hsu|YH| Fang|Tuan-Jen|TJ| Lee|Yi-Chan|YC| Liu|Chia-Yen|CY| Lin|Meng-Hung|MH| Wang|Yun-Ting|YT| Tsai|Ming-Shao|MS|

pneumonia
unilateral vocal fold paralysis
voice therapy
phonosurgery
risk factor


Concepts, Practices and Advantages of Spirituality Among People with a Chronic Mental Illness in Melbourne.

Abstract: There is a relative paucity of literature in the field of spirituality among people who have a lived experience of severe mental illness from Australia. Sixteen individuals with a severe mental illness were interviewed on their experiences of spirituality. The three themes that emerged from the data were concepts of spirituality, benefits of intentional spiritual practices and perceived spiritual benefits of recreational pursuits and physical activity. This paper adds to the relatively sparse literature on spirituality among persons with a mental illness in Australia.

Spirituality
Mental disorder
Mental health services
Recovery
Religion


Identification of the first in Poland CACNA1A gene mutation in familial hemiplegic migraine. Case report.

Abstract:
INTRODUCTION
Migraine is a common neurological disorder characterized by a particular phenotype, complex pathophysiology and a heterogeneous genetic background. Among several heritable forms, familial hemiplegic migraine is the best described one. In the majority of cases it is caused by mutations in one of three different genes.

CASE REPORT
Clinical symptoms of a 47 year old proband (and independently described in his 20 year old son) as well as differential diagnosis are discussed in the presented report. The most characteristic were recurrent attacks of blurred vision, paresthesias and hemiparesis often accompanied by speech disturbances and followed by severe headache with vomiting. Advanced morphological and genetic procedures were required to exclude MELAS, CADASIL and Call-Fleming syndrome. Finally, the definite diagnosis was possible after the application of the whole exome sequencing technique. It confirmed, for the first time in the Polish population, a heterozygous T666M mutation (c.1997C>T; p.Thr666Met) in the CACNA1A gene in the proband, the proband's son and in several other family members.

CONCLUSION
The presented report provides clinical and genetic insight into familial hemiplegic migraine 1 resulting from a mutation in the CACNA1A gene.

Kierdaszuk|Biruta|B|
Dziewulska|Dorota|D|
Pronicka|Ewa|E|
Trubicka|Joanna|J|
Rokicki|Dariusz|D|
Piekutowska-Abramczuk|Dorota|D|
Kaliszewska|Magdalena|M|
Tonska|Katarzyna|K|
Bartnik|Ewa|E|
Ploski|Rafal|R|
Kaminska|Anna M|AM|

CACNA1A
Familial hemiplegic migraine
Migraine
Calcium channel


Rehabilitation - a new approach. Part three: the implications of the theories.

Abstract: The last editorial suggested that rehabilitation needed to involve the patient in learning, and depended upon a group of professionals to identify what actions might help the patient, and to undertake or arrange the necessary actions. In many cases there will be both a wide variety of actions needed from a reasonably large number of people and organisations, and the process is likely to be extended over weeks, months or occasionally years. This editorial shows that these features characterise the rehabilitation process as complex and therefore it needs to be managed by a trans-disciplinary team. Some of the characteristics of teamwork are discussed. This leads to a discussion of teams in rehabilitation, showing that there are currently many different types of teams organised around different areas of interest and that a patient might need access to several specialised teams. It is then argued that the complexity of team coordination is best resolved by formal rehabilitation planning meetings, held early in a patient's involvement with rehabilitation; this should increase effectiveness and efficiency. Finally the editorial argues that rehabilitation would be improved by having rehabilitation teams that mirror the existing medical specialities, ensuring that all patients thereby have easy and early access to rehabilitation planning.

D004185:Disability Evaluation
D006233:Disabled Persons
D005260:Female
D006040:Goals
D006801:Humans
D008297:Male
D009936:Organizational Innovation
D017063:Outcome Assessment, Health Care
D010347:Patient Care Planning
D010348:Patient Care Team
D012047:Rehabilitation Centers
D014481:United States

rehabilitation Process
Biopsychosocial model
Goal setting


Automated fiducial marker detection and localization in volumetric computed tomography images: a three-step hybrid approach with deep learning.

Abstract: Purpose: Automating fiducial detection and localization in the patient's pre-operative images can lead to better registration accuracy, reduced human errors, and shorter intervention time. Most current approaches are optimized for a single marker type, mainly spherical adhesive markers. A fully automated algorithm is proposed and evaluated for screw and spherical titanium fiducials, typically used in high-accurate frameless surgical navigation. Approach: The algorithm builds on previous approaches with morphological functions and pose estimation algorithms. A 3D convolutional neural network (CNN) is proposed for the fiducial classification task and evaluated for both traditional closed-set and emerging open-set classifiers. A proposed digital ground-truth experiment, with cone-beam computed tomography (CBCT) imaging software, is performed to determine the localization accuracy of the algorithm. The localized fiducial positions in the CBCT images by the presented algorithm were compared to the actual known positions in the virtual phantom models. The difference represents the fiducial localization error (FLE). Results: A total of 241 screws, 151 spherical fiducials, and 1550 other structures are identified with the best true positive rate 95.9% for screw and 99.3% for spherical fiducials at 8.7% and 3.4% false positive rate, respectively. The best achieved FLE mean and its standard deviation for a screw and spherical marker are 58 (14) and  , respectively. Conclusions: Accurate marker detection and localization were achieved, with spherical fiducials being superior to screws. Large marker volume and smaller voxel size yield significantly smaller FLEs. Attenuating noise by mesh smoothing has a minor effect on FLE. Future work will focus on expanding the CNN for image segmentation.

fiducial markers
convolutional neural network
phantom models
image-guided surgery
open-set recognition
virtual computed tomography


Photodynamic therapy with smart nanomedicine.

Abstract: For several decades, clinical demands for utilization of photodynamic therapy (PDT) have been increasing. Notably, PDT was mainly applied for cancer therapy, and most photosensitizers (PSs) were developed to treat cancer. The advantages of PDT, such as minimal invasiveness and local treatment by topical light irradiation, have made it possible to widen the range of target diseases. Thus, PDT has been clinically used for treatment of various diseases (e.g., cancer, acne, and age-related macular degeneration). However, PS, which is the main component of PDT, exhibits several shortcomings such as low solubility, low bioavailability, and lack of lesion selectivity for use as a therapeutic agent. Therefore, many research projects have been performed to develop smart PS. To increase therapeutic efficacy and to decrease adverse effects in normal tissue at the same time, PS incorporation within nanoscaled delivery systems is evolving. This review provides a comprehensive explanation of PDT in smart nanomedicine, which is academically and clinically utilized in the treatment of various diseases.

Photodynamic therapy
Nanomedicine
Photosensitizer
Drug delivery
Nanotechnology


Apolipoprotein E Gene Polymorphisms in Saudi Patients with Systemic Lupus Erythematosus.

Abstract: Apolipoprotein E (APOE) is a glycosylated protein with multiple biological properties. APOE gene polymorphism plays a central role in lipid metabolism and has recently been suggested to regulate inflammation. Our objective is to evaluate whether APOE polymorphism affects susceptibility to SLE. APOE genotyping was performed using ApoE StripAssay™ kit. Results indicated significantly higher frequencies of allele ε4 and genotype ε3/ε4 and lower frequencies of allele ε3 and genotype ε3/ε3 in SLE patients than controls. APOE ε2 allele was found in three patients, whereas it was absent in controls. The frequencies of allele ε4 and genotype ε3/ε4 were significantly higher in SLE patients with renal involvement and those of alleles ε2, ε4 and genotypes ε2/ε3, ε3/ε4 were higher in patients with neuropsychiatric symptoms. It is concluded that APOE allele ε4 is associated with susceptibility risk/clinical manifestations of SLE and ε2 may increase its severity while ε3 is protective for SLE in Saudis.

Al-Rayes|Hannan|H| Huraib|Ghaleb|G| Julkhuf|Saeed|S| Arfin|Misbahul|M| Tariq|Mohammad|M| Al-Asmari|Abdulrahman|A|

apolipoprotein E
polymorphism
Saudi
systemic lupus erythematosus