SNTG1, the gene encoding gamma1-syntrophin: a candidate gene for idiopathic scoliosis.
Idiopathic scoliosis (IS) affects approximately 2%-3% of the population and has a heritable component. The genetics of this disorder are complex. Here, we describe a family in which a pericentric inversion of chromosome 8 co-segregates with IS. We have used fluorescence in situ hybridization to identify cloned DNAs that span the breakpoints on the two arms of the chromosome. We have identified a bacterial artificial chromosome (BAC) of 150 kb that crosses the q-arm breakpoint and a BAC of 120 kb that crosses the p-arm breakpoint. The complete genomic DNA sequence of these BACs has been analyzed to identify candidate genes and to localize further the precise breakpoints. This has revealed that the p-arm break does not interrupt any known gene and occurs in a region of highly repetitive sequence elements. On the q-arm, the break occurs between exons 10 and 11 of the gamma-1 syntrophin (SNTG1) gene. Syntrophins are a group of cytoplasmic peripheral membrane proteins that associate directly with dystrophin, the Duchenne muscular dystrophy gene; gamma1-syntrophin has been shown to be a neuronal cell-specific protein. Mutational analysis of SNTG1 exons in 152 sporadic IS patients has revealed a 6-bp deletion in exon 10 of SNTG1 in one patient and a 2-bp insertion/deletion mutation occurring in a polypyrimidine tract of intronic sequence 20 bases upstream of the SNTG1 exon 5 splice site in two patients. These changes were not seen in a screen of 480 control chromosomes. Genomic DNAs from seven affected individuals within the family of a patient carrying the 6-bp deletion were typed to determine whether the alteration co-segregated with IS. The deletion was only observed in five out of these seven individuals. Thus, although genetic heterogeneity or multiple alleles cannot be ruled out, the 6-bp deletion does not consistently co-segregate with the disease in this family.


Dilute topical proparacaine for pain relief after photorefractive keratectomy.
The purpose of the study is to determine whether there is a nonanesthetic and nontoxic concentration of topical proparacaine that can be applied repeatedly to the cornea to reduce pain after photorefractive keratectomy (PRK). Part I: To determine a nonanesthetic concentration, the corneal sensitivity of 50 healthy volunteers was assessed using aesthesiometry before and after a drop of either 0.01%, 0.025%, 0.05%, 0.1%, or 0.2% topical proparacaine. Ten volunteers similarly were tested with multiple doses of 0.05% proparacaine. To evaluate toxicity, ten healthy volunteers self-administered 0.05% proparacaine to one eye and placebo to the other eye every 15 minutes for 12 hours on day 1 and every hour for 12 hours on days 2 through 7. Subjects were assessed throughout the week using visual acuity, slitlamp examination, aesthesiometry, and ultrasonic pachometry. Part II: In a prospective, double-masked study, 34 patients who underwent PRK (48 eyes) self-administered either topical 0.05% proparacaine or placebo for 1 week after PRK as needed to reduce pain. Patients recorded their pain score before and after drop use and answered a pain-relief questionnaire. Part I: Proparacaine concentrations greater than or equal to 0.1% eliminated sensation from some corneas; concentrations of less than or equal to 0.05% were never fully anesthetic. No corneal toxicity was observed except for some minimal punctate staining in both treatment and placebo eyes. Part II: Patients in the treatment group had significantly more pain relief (P < 0.001) for a longer period (P < 0.001) than did patients in the control group. Average change in pain score was significantly greater in the treatment group (P < 0.002). No significant difference in the number of days needed to reach complete epithelial healing was found between the two groups (P < 0.18). Dilute (0.05%) topical proparacaine is nonanesthetic and nontoxic, and can be used safely for at least 1 week to reduce pain after PRK.


Financing of pediatric home health care. Committee on Child Health Financing, Section on Home Care, American Academy of Pediatrics.
In certain situations, home health care has been shown to be a cost-effective alternative to inpatient hospital care. National health expenditures reveal that pediatric home health costs totaled $5.3 billion in 2000. Medicaid is the major payer for pediatric home health care (77%), followed by other public sources (22%). Private health insurance and families each paid less than 1% of pediatric home health expenses. The most important factors affecting access to home health care are the inadequate supply of clinicians and ancillary personnel, shortages of home health nurses with pediatric expertise, inadequate payment, and restrictive insurance and managed care policies. Many children must stay in the NICU, PICU, and other pediatric wards and intermediate care areas at a much higher cost because of inadequate pediatric home health care services. The main financing problem pertaining to Medicaid is low payment to home health agencies at rates that are insufficient to provide beneficiaries access to home health services. Although home care services may be a covered benefit under private health plans, most do not cover private-duty nursing (83%), home health aides (45%), or home physical, occupational, or speech therapy (33%) and/or impose visit or monetary limits or caps. To advocate for improvements in financing of pediatric home health care, the American Academy of Pediatrics has developed several recommendations for public policy makers, federal and state Medicaid offices, private insurers, managed care plans, Title V officials, and home health care professionals. These recommendations will improve licensing, payment, coverage, and research related to pediatric home health services.


A Propensity Score-Matched Analysis of Inflammatory Response With Endovascular Aneurysm Sealing vs Endovascular Aneurysm Repair.
To evaluate the risk of postimplantation syndrome associated with endovascular aneurysm sealing (EVAS) and endovascular aneurysm repair (EVAR) in patients treated for abdominal aortic aneurysm (AAA). From December 2013 to May 2015, 41 AAA patients treated with EVAS (mean age 72±9 years; 38 men) and 63 with EVAR (mean age 74±10 years; 55 men) at a single center were retrospectively reviewed. To control for treatment selection bias, propensity score matching was used to compare outcomes by treatment mode. Main outcomes were postimplantation syndrome (defined as temperature >38°C and leukocyte count >12,000/µL), inflammatory response markers [platelets and high-sensitivity C-reactive protein (hs-CRP)], and clinical complications through 30 days. In 39 matched patients per group, the incidences of postimplantation syndrome (p=0.07), mean body temperature (p=0.05), mean leukocyte count (p=0.003), and mean hs-CRP (p<0.001) were proportionally lower with EVAS vs EVAR. Serious adverse events (0% vs 12.8%, p=0.05) and endoleaks (0% vs 10.3%, p=0.13) through 30 days were less frequent with EVAS, but the group differences were not significantly different. The choice of endovascular graft material influenced postoperative and 30-day clinical outcomes, with greater overall risk observed with polyester stent-grafts. Endovascular aneurysm sealing is associated with a blunted systematic inflammatory response compared with EVAR. Polyester stent-grafts induce the greatest periprocedural inflammatory response.


Estimation of External Dose Rates to Hotel Workers from bed linens Contaminated by 131I Patients.
Iodine-131 is commonly used in medical diagnosis and therapy for patients with hyperthyroidism or differentiated thyroid cancer. Following treatment, patients may recuperate in a hotel room to avoid exposing family members. The main purpose of this study was to estimate external effective dose rate coefficients to a hotel worker who handles potentially contaminated bed linens due to secretions from I patients as sweat or urine. The external dose rate estimates were derived using Monte Carlo radiation transport code and the phantom with movable arms and legs to model a housekeeper standing in an upright position holding a pile of bed linens. Simulations further integrated the body burden of time-dependent biokinetic metabolism of I in the patient's body, differentiating between biokinetic excretion models of hyperthyroid vs. cancer patients. Organ absorbed dose rate and effective dose rate coefficients were calculated for three scenarios of bed linen contamination and estimated out to 5 d postadministration and compared to past I patient contamination measurements.


Role of T cells in resistance to Theiler's virus infection.
Intracerebral infection of C57BL/10SNJ mice with Theiler's virus results in acute encephalitis with subsequent virus clearance and absence of spinal cord demyelination. In contrast, infection of SJL/J mice results in acute encephalitis, virus persistence, and immune-mediated demyelination. These experiments examined the role of T-cell subsets in the in vivo immune response to Theiler's virus in resistant C57BL/10SNJ mice. Depletion of T-cell subsets with monoclonal antibodies (mAbs) directed at CD3 (pan-T-cell marker), CD4+ (class II-restricted) or CD8+ (class I-restricted) T cells resulted in increased frequency of paralysis and death as a result of acute encephalitis. Neuropathologic studies 10 days after infection demonstrated prominent necrosis, primarily in the pyramidal layer of hippocampus and in the thalamus of mice depleted of T-cell subsets. In immunosuppressed and infected C57BL/10SNJ mice, analysis of spinal cord sections 35 days after infection demonstrated small demyelinated lesions relatively devoid of inflammatory cells even though virus antigen could be detected by immunocytochemistry. Both CD4+ and CD8+ T cells are important in the resistance to infection with Theiler's virus in C57BL/10SNJ mice. However, subsequent spinal cord demyelination, to the extent observed in susceptible mice, depends on the presence of virus antigen persistence and a competent cellular immune response.


Topical retinoic acid inhibits changes in Langerhans cell density during carcinogenesis.
Ultraviolet radiation (UVR), chemical carcinogens and contact sensitisers all reduce the density of Langerhans cells (LC) in murine epidermis; UVR also lowers the number of Thy-1 dendritic epidermal cells (Thy-1+ dEC). Topical application of all-trans retinoic acid (RA) renders these cells insensitive to UVR and the tumour promoter 12-0-tetradecanoylphorbol 13-acetate (TPA) but does not inhibit LC migration from the epidermis in response to a contact sensitiser. Additionally, when the diet of mice was supplemented with the retinoid temarotene, UVR was unable to reduce the number of LC or Thy-1+ dEC. Hence one of the anti-carcinogenic mechanisms of retinoids may be to protect LC from carcinogens.


Stimulation of ornithine decarboxylase activity and inhibition of S-adenosyl-L-methionine decarboxylase activity in leukaemic mice by methylglyoxal bis(guanylhydrazone).
Administration of methylglyoxal bis(guanylhydrazone) to leukaemic mice results in an early depression followed by a marked elevation of S-adenosyl-l-methionine decarboxylase activity. Further, there is an early prolonged increase in the activity of ornithine decarboxylase, the initial enzyme in the polyamine biosynthetic pathway. Because of the profound effects of methylglyoxal bis(guanylhydrazone) in vivo on the polyamine biosynthetic pathway, the drug can no longer be considered a specific inhibitor of spermidine synthesis.


Evaluation of pH of Bathing Soaps and Shampoos for Skin and Hair Care.
Normal healthy skin has potential of hydrogen (pH) range of 5.4-5.9 and a normal bacterial flora. Use of soap with high pH causes an increase in skin pH, which in turn causes an increase in dehydrative effect, irritability and alteration in bacterial flora. The majority of soaps and shampoos available in the market do not disclose their pH. The aim of this study was to assess the pH of different brands of bathing soaps and shampoos available in the market. The samples of soaps and shampoos were collected from shops in the locality. The samples of different brands are coded before the analysis of the pH. Solution of each sample was made and pH was measured using pH meter. Majority of the soaps have a pH within the range of 9-10. Majority of the shampoos have a pH within the range of 6-7. The soaps and shampoos commonly used by the population at large have a pH outside the range of normal skin and hair pH values. Therefore, it is hoped that before recommending soap to patient especially those who have sensitive and acne prone skin, due consideration is given to the pH factor and also that manufacturers will give a thought to pH of soaps and shampoos manufactured by them, so that their products will be more skin and hair friendly.


Recent advances in retromer biology.
The endosomal network is an organized array of intracellular, membranous compartments that function as sorting sites for endosomal and biosynthetic cargo. The fate of endocytic cargo is reliant upon interactions with a number of molecularly distinct sorting complexes, which tightly control the relationship between sorting of their respective cargo and the physical process of membrane re-scuplturing required for the formation of transport carries. One such complex, retromer, mediates retrograde transport from endosomes to the trans-Golgi network (TGN). Disregulation of retromer has been implicated in a host of disease states including late-onset Alzheimer's. Rather than give a broad overview of retromer biology, here we aim to outline the recent advances in understanding this complex, focussing on the involvement of both clathrin and the cytoskeleton in retromer function.


[Venous reservoirs: the late complications according to the route of implantation. The Interhospital Group of Valencia (GIHV)].
The aim of the study which we present is to analyze the incidence of late complications, clinical and sub-clinical, of venous reservoirs implanted through two access routes, subclavian (group A), and brachial (group B). It is a multi-centric clinical study, initiated in 1992, in which the general surgery departments of three general hospitals of the Valencian Community were involved. It is made up of 87 patients, 48 men and 39 women, with a mean age (SD) of 57.1 (12.6) years, of whom we made a late review of 41 patients (29 from group A and 12 from group B). They were subjected to a physical examination, bacterial cultures of the entrance, and phlebograms of the upper extremities through the dorsal veins of the hands. The incidence of clinical complications was 39% in group A and 77% in group B (p = 0.0507). The main clinical complications were minimally symptomatic venous thrombosis, catheter thrombosis, infection, and miscellaneous (migration, paresthesias, articular movement alterations, etc.). And the prevalence of phlebographic venous thrombosis was 18% in group A and 40% in group B (p = 0.051). The subclavian access for the implantation of venous reservoirs has a lower incidence (with a tendency towards clinical significance) of clinical complications and subclinical venous thrombosis (Phlebogram) than the brachial access.


Food Stamp Program participation but not food insecurity is associated with higher adult BMI in Massachusetts residents living in low-income neighbourhoods.
Food-insecure populations employ multiple strategies to ensure adequate household food supplies. These strategies may increase the risk of overweight and obesity. However, existing literature reports conflicting associations between these strategies and BMI. The objective of the present study was to examine whether food insecurity and strategies for managing food insecurity are associated with BMI in adults. In 2005, RTI International and Project Bread conducted a representative survey of 435 adult residents of low-income census tracts in Massachusetts. Food insecurity was assessed using the US Department of Agriculture's eighteen-item Household Food Security Module. The prevalence of overweight and obesity was 51 % and 25 %, respectively. After adjusting for age, sex, sociodemographic characteristics and food insecurity, both participation in the Food Stamp Program (FSP) and participation in any federal nutrition programme 12 months prior to the survey were each associated with an approximate 3.0 kg/m2 higher adult BMI. In the subset of current FSP participants (n 77), participation for >or=6 months was associated with an 11.3 kg/m2 lower BMI compared with participation for <6 months. Respondents who consumed fast foods in the previous month had a mean BMI that was 2.4 kg/m2 higher than those who did not. Food insecurity was not associated with BMI after adjustment for sociodemographic characteristics and FSP participation. Participation in federal nutrition programmes and consumption of fast food were each associated with higher adult BMI independent of food insecurity and other sociodemographic factors. However, prolonged participation in the FSP was associated with lower BMI.


Exercise stress testing for the family physician: Part II. Interpretation of the results.
Information gained from exercise stress testing includes the heart rate and blood pressure response, the presence of symptoms or dysrhythmias, functional aerobic capacity and evidence of myocardial ischemia. Certain ST-segment patterns correlate with various degrees of ischemia. Overall, stress testing has a sensitivity and a specificity of about 70 and 75 percent, respectively, but the results are even more useful than this when considered in light of the pre- and post-test probability of coronary artery disease. Use of the exercise test score and decision-tree algorithms is helpful in clinical decision making.


[Occupational exposure to nitrous oxide and sevoflurane during pediatric anesthesia: evaluation of an anesthetic gas extractor].
To determine the level of occupational exposure to anesthetic gases in the absence of an extractor during pediatric anesthesia and to assess the efficacy of a purpose-built extraction system. The patients were 24 children undergoing tonsillectomy and adenoidectomy. Gases were extracted from the room for 1 group and were not extracted for the other group (n=12 in each group). Induction was with 8% sevoflurane, 60% nitrous oxide (N2O), 40% oxygen at a flow rate of 8 L x min(-1) through a Mapleson C circuit. Maintenance was with 2% sevoflurane at the same flow rate and gas mixture under spontaneous ventilation with an endotracheal tube and a Mapleson D circuit. The circuits were equipped with an airway pressure-limiting valve to allow connection to an anesthetic gas extractor. Ambient levels of sevoflurane and N2O were measured in the breathing area around the anesthesiologist. The surgeon and the nurse were asked about symptoms related to occupational exposure. The mean (SD) exposure to N2O and sevoflurane in the group without an extractor was 423 (290) and 12 (10.9) parts per million (ppm), respectively. In the group working with the extractor, exposure was 94% and 91% lower: 24.7 (26) and 1.1 (1) ppm (P<.001). A higher incidence of noticing a "smell of gas" was registered for the group without an extractor (87% vs 11% in the extractor group, P=.003). Higher rates were also found for general discomfort (62% vs 11%, P=.05), nausea (62% vs 0%, P=.009), and headache (62% vs 0%, P=.009) in the absence of the extractor. Gas extraction decreased the level of exposure by up to 94%, achieving levels that were below the recommended limits and greatly reducing occupational risk.


Evaluation of Primary Stability of Cylindrical and Tapered Implants in Different Bone Types by Measuring Implant Displacement: An In vitro Study.
The purposes of this study were to investigate the primary stability of cylindrical and tapered implants in different bone types by measuring implant displacement and to examine the relationship between insertion torque value (ITV) and implant displacement. Four different polyurethane bone models consisted of low-density or low-to-medium-density cancellous bone with or without a cortical bone layer. A total of 120 cylindrical and tapered implants were placed into bone blocks (n = 15 in each group), and the ITV was measured. A lateral load of 15 N was applied to the top of the abutment, and implant displacement was recorded. Implant displacement was significantly affected by cancellous bone density and to a lesser degree by cortical bone thickness. The displacement of tapered implants was significantly smaller than that of cylindrical implants in the presence of cortical bone. However, both implant groups showed similar ITV in the low-density cancellous bone model with the cortical bone layer. There was a correlation between ITV and displacement in the cylindrical and tapered implants. However, no correlation was observed between ITV and displacement within each bone type. Implant stability depended mainly on the bone type, whereas implant design had a limited influence on primary stability. The use of tapered implants may be advantageous for improving primary stability in patients with low-density cancellous bone only when crestal cortical bone exists. The same ITV of cylindrical and tapered implants did not necessarily represent similar primary stability in the bone type.


[Improving efficacy of fluorescent diagnostics of skin and mucosal tumors in ocular oncology].
Developed in 2006 by our institute, the method of primary detection of skin and mucosal tumors based on non-induced fluorescence of endogenous protoporphyrin IX is used to estimate proliferative activity of tumor and its probable progression. This study was aimed to improve method efficacy by means of additional parameter which would quantitatively describe the interpenetration of tumor and surrounding tissues. The authors analyzed autofluorescent data of 97 patients and determined medico-biological factors which could cause controversal results (all cases were histologically controlled). The coefficient of interpenetration K(dith) was proposed as a solution. It is calculated as averaged reciprocal to tumor border probability. Repeated analysis of the autofluorescent images using both the proliferative factor and coefficient of interposition revealed improvement of method specificity from 69% to 85% while sensitivity of method remained 70%. In authors' opinion, the method can be recommended for use in general oncology and dermatology.


Robotic-assisted laparoscopic donor nephrectomies: early experience and review of the literature.
With over 80,000 patients in the United States awaiting kidney transplantation, renal transplant surgery continues to evolve with attractive surgical options for living donation, which include laparoscopic donor nephrectomy (LDN) and robotic-assisted laparoscopic donor nephrectomy (RALDN). LDN is currently accepted as the gold standard procedure for living donor nephrectomy; RALDN is an evolving technique and may emerge as a preferred procedure over time. We present our initial experience with RALDN from December 2007 to August 2008. Thirty-five patients who underwent RALND were retrospectively analyzed and compared with 35 age- and time (year)-matched patients who underwent LDN. The parameters analyzed were length of hospital stay (3.2 ± 0.9 days, P < 0.59), estimated blood loss (146 ± 363 ml, P < 0.36), operating time (149 ± 44 min, P < 0.23), cold ischemic time (135 ± 202 min, P < 0.19), preoperative creatinine (0.82 ± 0.26 mg/dl, P < 0.46) and postoperative creatinine (1.44 ± 1.03 mg/dl, P < 0.20). There was no statistical difference between RALDN patients with single renal artery (n = 27) and those with more than one renal artery (n = 8) kidneys. There was one serious complication requiring conversion to open laparotomy to control a bleeding renal artery stump following extraction of the kidney. One-year graft survival for the 35 recipients of RALDN was 97.1%. RALDN is feasible and compares favorably to the standard LDN procedure with good graft survival. Robotic-assisted transplant surgery is an emerging technique with potential benefits to both surgeon and patient.


Long-term insulin independence following repeated islet transplantation in totally pancreatectomized diabetic pigs.
Clinical islet transplantation (Tx) in type I diabetic patients has been successful so far only in a minority of cases, probably because of multiple factors, partly immunologic and partly nonimmunologic in nature. Preclinical studies of islet Tx in large animals are still needed to clarify the reasons and find possible solutions. In this study, we tested the feasibility of noninvasive, repeated intrahepatic allo-Tx of porcine pancreatic islets obtained from multiple donors, in pigs rendered diabetic by total pancreatectomy (Pct). In group I Yucatan miniature swine (n = 6), after induction of diabetes by Pct, repeated islet allo-Tx of > or = 80% pure islets was performed. Islets obtained from two pigs of the Hanford breed were injected twice a week, half freshly isolated and half 48-h cultured, over a period of 11 days, for a total of 23,647 +/- 1617 islet equivalents (IE)/kg recipient body weight (BW). In group II Yucatan miniature swine (n = 3), after Pct, a single allo-Tx of > or = 80% pure islets, previously obtained from two donors of the Hanford breed, was performed, using a total of 22,416 +/- 1124 IE/kg BW. In group III Yucatan miniature swine (n = 3), auto-Tx of 60-75% pure islets, averaging 2980 +/- 424 IE/kg BW, was performed a few hours after Pct. Group IV Yucatan mini pigs (n = 3) underwent Pct and were used as diabetic controls. Group V animals (n = 3) were normal control Yucatan mini pigs. Porcine islets were isolated by a modification of the standard collagenase digestion and Ficoll gradient purification method. Donors and recipients were chosen on the basis of moderate to high mutual alloreactivity in mixed lymphocyte culture (MLC). In groups I and II, cyclosporine A (CsA) was started 4 days before allo-Tx, at the dose of 15 mg/kg IM, and then gradually reduced to 4 mg/kg IM. In all group I animals, normal fasting blood glucose (FBG) was restored within 2-3 weeks. Two normoglycemic pigs died of acute pneumonia at 33 and 112 days, respectively, and one animal became progressively hyperglycemic at 100 days. After 3 months, discontinuation of CsA treatment resulted in FBG increase in two group I animals. In one pig, CsA was stopped after 151 days, and normoglycemia persisted until euthanasia, after 8 months. In group II pigs, normoglycemia lasted 4-20 days, with a progressive increase of insulin requirement thereafter. In group III animals, after islet auto-Tx, normoglycemia lasted 7-10 days, while insulin daily requirement progressively increased thereafter, stabilizing at 0.4 IU/kg/day, corresponding to about one third of the amount required in diabetic controls. The single most important result in this series of experiments is that intraportal allo-Tx of a sufficient islet mass, divided in multiple subtherapeutic doses, produced a better metabolic long-term control in comparison to a single injection of the same amount of islets. The technique of multiple-donor repeated islet Tx may prove useful to overcome the problem of primary nonfunction or early graft failure, currently limiting the success of clinical islet Tx in most cases.


Predominance of M1 subtype among tumor-associated macrophages in phenotypically aggressive sporadic vestibular schwannoma.
Tumor-associated macrophages (TAMs) have been implicated as pathologic actors in phenotypically aggressive vestibular schwannoma (VS), potentially mediated via programmed death-ligand 1 (PD-L1). The authors hypothesized that PD-L1 is a key regulator of the VS immune microenvironment. Forty-six consecutive, radiation-naïve, sporadic VSs that were subtotally resected at primary surgery were assessed via immunohistochemical analysis, including analysis of CD163 and PD-L1 expression. Pathologic data were correlated with clinical endpoints, including tumor control, facial nerve function, and complications. Baseline parameters were equivalent between stable and progressive post-subtotal resection (STR) VS. CD163 percent positivity and M2 index were significantly increased among tumors that remained stable (34% vs 21%, p = 0.02; 1.13 vs 0.99, p = 0.0008), as well as patients with favorable House-Brackmann grade I or II facial nerve function (31% vs 13%, p = 0.04; 1.11 vs 0.97, p = 0.05). PD-L1 percent positivity was significantly associated with tumor progression (1% vs 11%, p = 0.01) and unfavorable House-Brackmann grade III-VI facial nerve function (1% vs 38%, p = 0.02). On multivariate analysis, PD-L1 was independently significant in all models (likelihood ratio 4.4, p = 0.04), while CD163 was dependent in all iterations. In contrast to prior reports, in this study, the authors observed significantly increased levels of M1, CD163+ TAMs in association with VS that progressed after STR. Progressive tumors are characterized by increased PD-L1, potentially highlighting a mechanism of immune evasion that results in TAM deactivation, tumor growth, and further infiltration of anti-tumor immune cells. Targeting PD-1/PD-L1 may offer therapeutic promise, particularly in the setting of disease control after STR.


Comparisons of zinc with cadmium in N2S2 coordination and as S-bonded adducts to tungsten carbonyls.
The synthesis and characterization of bis-mercaptoethanediazaheptane cadmium(II) is reported and compared to the analogous zinc complex. Of significance is the dimeric form of the [Zn(N(2)S(2))](2) complex achieves penta-coordination about zinc through a bridging thiolate whereas cadmium engages two thiolate as S-bridges resulting in hexa-coordination about cadmium within a coordination polymer whose X-ray crystal structure is reported here. In the presence of W(CO)(5), this polymer breaks up, generating dimeric [Cd(N(2)S(2))](2) with two W(CO)(5) units appended to the terminal thiolates, a feat that is not observed for the zinc dimer analogue. The greater thiophilicity of cadmium over zinc is noted in several features of these complexes.


Topology of IEP110, a component of the chloroplastic protein import machinery present in the inner envelope membrane.
Proteins from both the inner and outer envelope membranes are engaged in the recognition and translocation of precursor proteins into chloroplasts. A 110 kDa protein of the chloroplastic inner envelope membrane was identified as a component of the protein import apparatus by two methods. First, this protein was part of a 600 kDa complex generated by cross-linking of precursors trapped in the translocation process. Second, solubilization with detergents of chloroplasts containing trapped precursors resulted in the identification of a complex containing both radiolabeled precursor and IEP110. Trypsin treatment of intact purified chloroplasts was used to study the topology of IEP110. The protease treatment left the inner membrane intact while simultaneously degrading domains of inner envelope proteins exposed to the intermembrane space. About 90 kDa of IEP110 was proteolitically removed, indicating that large portions protrude into the intermembrane space. Hydropathy analysis of the protein sequence deduced from the isolated cDNA clone in addition to Western blot analysis using an antiserum of IEP110 specific to the N-terminal 20 kDa, suggests that the N-terminus serves to anchor the protein in the membrane. We speculate that IEP110 could be involved in the formation of translocation contact sites due to its specific topology.


Pancreatic pseudocyst drainage guided by endoscopic ultrasound.
Pancreatic pseudocysts can be managed conservatively in the majority of patients but some of them will require surgical, endoscopic or percutaneous drainage. Endoscopic drainage represents an efficient modality of drainage with a high resolution rate and lower morbidity and mortality than the surgical or percutaneous approach. In this article we review the endoscopic pseudocyst drainage procedure with special emphasis on technical details.


The c-kit ligand, stem cell factor, can enhance innate immunity through effects on mast cells.
Mast cells are thought to contribute significantly to the pathology and mortality associated with anaphylaxis and other allergic disorders. However, studies using genetically mast cell-deficient WBB6F1-KitW/KitW-v and congenic wild-type (WBB6F1-+/+) mice indicate that mast cells can also promote health, by participating in natural immune responses to bacterial infection. We previously reported that repetitive administration of the c-kit ligand, stem cell factor (SCF), can increase mast cell numbers in normal mice in vivo. In vitro studies have indicated that SCF can also modulate mast cell effector function. We now report that treatment with SCF can significantly improve the survival of normal C57BL/6 mice in a model of acute bacterial peritonitis, cecal ligation and puncture (CLP). Experiments in mast cell-reconstituted WBB6F1-KitW/KitW-v mice indicate that this effect of SCF treatment reflects, at least in part, the actions of SCF on mast cells. Repetitive administration of SCF also can enhance survival in mice that genetically lack tumor necrosis factor (TNF)-alpha, demonstrating that the ability of SCF treatment to improve survival after CLP does not solely reflect effects of SCF on mast cell- dependent (or -independent) production of TNF-alpha. These findings identify c-kit and mast cells as potential therapeutic targets for enhancing innate immune responses.


Dietary 9-cis-β,β-carotene fails to rescue vision in mouse models of leber congenital amaurosis.
Synthetic 9-cis-stereoisomers of vitamin A (all-trans-retinol) are especially promising agents for the fight against blinding diseases. Several studies suggested that 9-cis-β,β-carotene (9-cis-BC), a natural and abundant β-carotene isomer in the diet, could be the precursor of 9-cis-retinoids and thus could have therapeutic applications. Here we showed that 9-cis-BC is metabolized both in vitro and in vivo by two types of mouse carotenoid oxygenases, β,β-Carotene monooxygenase 1 (BCMO1), and β,β-carotene dioxygenase 2 (BCDO2). In the symmetric oxidative cleavage reaction at C15,C15' position by BCMO1, part of the 9-cis-double bond was isomerized to the all-trans-stereoisomer, yielding all-trans-retinal and 9-cis-retinal in a molar ratio of 3:1. The asymmetric cleaving enzyme BCDO2 preferentially removed the 9-cis-ring site at the C9,C10 double bond from this substrate, providing an all-trans-β-10'-apocarotenal product that can be further metabolized to all-trans-retinal by BCMO1. Studies in knockout mouse models confirmed that each carotenoid oxygenase can metabolize 9-cis-BC. Therefore, treatment of mouse models of Leber congenital amaurosis with 9-cis-BC and 9-cis-retinyl-acetate, a well established 9-cis-retinal precursor, showed that the cis-carotenoid was far less effective than the cis-retinoid in rescuing vision. Thus, our in vitro and in vivo studies revealed that 9-cis-BC is not a major source for mouse 9-cis-retinoid production but is mainly converted to all-trans-retinoids to support canonical vitamin A action.


Allograft airway fibrosis in the pulmonary milieu: a disorder of tissue remodeling.
Obliterative bronchiolitis (OB) is thought to be a form of chronic allograft rejection. However, immunosuppressive therapy is not effective once fibrosis has developed. We hypothesize that disordered tissue remodeling is a mechanism for the pathogenesis of OB. We examined allograft airway fibrosis in an intrapulmonary tracheal transplant model of OB. Allograft airways were completely obliterated at day 21 by fibrotic tissue; however, tissue remodeling continued thereafter, as demonstrated by the change of collagen deposition density, shift from type I to type III collagen, shift from fibroblasts to myofibroblasts and shift of expression profiles and activities of matrix metalloproteinases (MMPs). We then used a broad-spectrum MMP inhibitor, SC080, to attempt to manipulate tissue remodeling. Administration of the MMP inhibitor from day 0 to day 28 reduced airway obliteration, without inhibiting T-cell activation. MMP inhibition from day 14 to day 28 showed similar effects on airway obliteration. MMP inhibition from day 21 to day 35 did not reverse the airway obliteration, but significantly reduced the collagen deposition, type III collagen and myofibroblasts in the lumen. We conclude that tissue remodeling plays a critical role in the development and maintenance of fibrosis after transplantation.


Transforming growth factor alpha, but not epidermal growth factor, promotes the survival of sensory neurons in vitro.
Transforming growth factor alpha (TGF alpha) is a mitogenic polypeptide that is structurally homologous to epidermal growth factor (EGF) and appears to bind to the same receptor in all systems tested previously. In the present study, TGF alpha was found to enhance survival and neurite outgrowth of cultured neonatal rat dorsal root ganglion (DRG) neurons in a dose-dependent manner. This effect was observed with TGF alpha concentrations as low as 17.8 pM. By contrast, EGF at concentrations up to 83 nM was ineffective. Moreover, EGF did not antagonize the TGF alpha survival-promoting effect unless present in large excess (500-fold the concentration for which TGF alpha is effective); even in this case, only partial antagonism was achieved. Survival of neurons from nodose, trigeminal, and sympathetic ganglia was not increased by TGF alpha. Both a subpopulation of DRG neurons and of macrophages in the cultures bound iodinated TGF alpha. This binding was inhibited by excess unlabeled TGF alpha but not EGF. Our data are consistent with the possibilities that the actions of TGF alpha on DRG neurons occur indirectly via unidentified neurotrophic molecules other than NGF as well as directly on the neurons themselves. Thus, TGF alpha, in contrast to EGF, may act as a survival or maintenance factor for a subset of rat sensory neurons. Mediation of this neurotrophic effect appears to occur via a new form of TGF alpha receptor.


Cocaine adulteration with the anthelminthic tetramisole (levamisole/dexamisole): Long-term monitoring of its intake by chiral LC-MS/MS analysis of cocaine-positive hair samples.
Recent studies indicate that not only the anthelminthic levamisole but also the racemate tetramisole (R-/S-phenyltetraimidazothiazole, PTHIT) was found as an adulterant for cocaine. We herein report on the investigation of the prevalence of PTHIT among cocaine-positive hair samples and the discrimination of the presence of its stereoisomers levamisole and dexamisole. Cocaine-positive hair samples were collected in a forensic context in 2015 and mainly 2017 (n = 724). Cocaine and PTHIT concentrations have been determined by achiral liquid chromatography-tandem mass spectrometry (LC-MS/MS). For distinction of levamisole/dexamisole chiral LC-MS/MS was performed. Cocaine hair concentrations ranged from 500 (cut-off) to approximately 800 000 pg/mg. The study demonstrates a strong prevalence of PTHIT in cocaine users' hair (87%, n = 627). PTHIT hair concentrations ranged from below LLOQ 3.5 to approximately 61 000 pg/mg (median: 260 pg/mg). Surprisingly, enantiomeric ratios of levamisole/dexamisole ranged from 0.17 to 1.34 (median: 0.63). Therefore, PTHIT-adulterated street cocaine samples (n = 24) seized between 2013 and 2016 were tested. Samples mainly contained racemic tetramisole (87.5%), only one sample contained levamisole only and two samples contained non-racemic PTHIT. Our experiments suggest that the presence of tetramisole in biological samples may have hitherto been underestimated. Most probably higher dexamisole than levamisole concentrations in hair specimens arise from stereoselective metabolism and/or elimination. This is particularly important in light of the different pharmacological activities of the two enantiomers and potentially different adverse effects. Toxicological interpretations in intoxication cases with adulterated cocaine should not only consider levamisole but also tetramisole and terminology in scientific contributions should be used accordingly.


The Central Complex as a Potential Substrate for Vector Based Navigation.
Insects use path integration (PI) to maintain a home vector, but can also store and recall vector-memories that take them from home to a food location, and even allow them to take novel shortcuts between food locations. The neural circuit of the Central Complex (a brain area that receives compass and optic flow information) forms a plausible substrate for these behaviors. A recent model, grounded in neurophysiological and neuroanatomical data, can account for PI during outbound exploratory routes and the control of steering to return home. Here, we show that minor, hypothetical but neurally plausible, extensions of this model can additionally explain how insects could store and recall PI vectors to follow food-ward paths, take shortcuts, search at the feeder and re-calibrate their vector-memories with experience. In addition, a simple assumption about how one of multiple vector-memories might be chosen at any point in time can produce the development and maintenance of efficient routes between multiple locations, as observed in bees. The central complex circuitry is therefore well-suited to allow for a rich vector-based navigational repertoire.


Anti-fatigue activity of a triterpenoid-rich extract from Chinese bamboo shavings (Caulis bamfusae in taeniam).
The anti-fatigue activity of a pentacyclic triterpenoid extract from bamboo shavings (EBS) from the bark of bamboo (Bambusa tuldoides Munro), was evaluated in BALB/c mice. EBS, isolated by the supercritical CO(2) fluid extraction (SFE) technique, was given to mice at concentrations of 0.04 (low-dose group), 0.08 (middle-dose group) and 0.25 g/kg body weight (high-dose group). The anti-fatigue activity of EBS was estimated by the change in body weight, weight-loaded swimming test and climbing test, and corresponding parameters including serum urea nitrogen, hepatic glycogen and blood lactic acid were measured. The results showed that an appropriate level of EBS could prolong the weight-loaded swimming and climbing time, and had an active effect on the serum urea nitrogen, hepatic glycogen and blood lactic acid level in BALB/c mice, which significantly embodied the anti-fatigue activity of EBS. Overall, it is predicted that EBS, being a composition mainly containing a group of pentacyclic triterpenoids, and its main triterpenoid components have great potential for application in relevant fields for its anti-fatigue activity.


Cyclosporine versus tacrolimus: cost-effectiveness analysis for renal transplantation in Brazil.
OBJECTIVE To analyze the cost-effectiveness of treatment regimens with cyclosporine or tacrolimus, five years after renal transplantation. METHODS This cost-effectiveness analysis was based on historical cohort data obtained between 2000 and 2004 and involved 2,022 patients treated with cyclosporine or tacrolimus, matched 1:1 for gender, age, and type and year of transplantation. Graft survival and the direct costs of medical care obtained from the National Health System (SUS) databases were used as outcome results. RESULTS Most of the patients were women, with a mean age of 36.6 years. The most frequent diagnosis of chronic renal failure was glomerulonephritis/nephritis (27.7%). In five years, the tacrolimus group had an average life expectancy gain of 3.96 years at an annual cost of R$78,360.57 compared with the cyclosporine group with a gain of 4.05 years and an annual cost of R$61,350.44. CONCLUSIONS After matching, the study indicated better survival of patients treated with regimens using tacrolimus. Moreover, regimens containing cyclosporine were more cost-effective [corrected].


Understanding the Role of Fathers in Children's Physical Activity: A Qualitative Study.
Parents are influential in supporting children's physical activity, but relatively little is known about the role of fathers in children's physical activity. Semi-structured interviews (n = 24) were conducted with low-active and active fathers of children 3-11 years old. Deductive thematic analysis was used to identify fathers' physical activity practices and understand how fathers interact with their children around physical activity. All fathers demonstrated coparticipation in physical activity with their children. Other physical activity practices commonly used by fathers included as follows: facilitation of active opportunities, modeling, involvement through coaching or teaching, and encouragement. In addition, fathers viewed physical activity as an opportunity to spend time with their children to bond and develop shared interests. Finally, fathers perceived their role in children's physical activity to be different compared with mothers. Regarding father activity level, active fathers discussed modeling more frequently and tended to engage in a variety of different activities compared with low-active fathers. Fathers play an important role in their children's physical activity, suggesting that physical activity may be one context in which to prompt paternal involvement, foster father-child relationships, and strengthen paternal parenting.


Membrane processing of fruit juices and beverages: a review.
Membrane technology for the processing of fruit juices and beverages has been applied mainly for clarification using ultrafiltration and microfiltration, and for concentration using reverse osmosis. The effects of product preparation, membrane selection, and operating parameters are important factors influencing filtration rate and product quality. Technological advances related to the development of new membranes, improvement in process engineering, and better understanding of fruit beverage constituents have expanded the range of membrane separation processes. Developments in novel membrane processes, including electrodialysis and pervaporation, increased the array of applications in combination with other technologies for alternate uses in fruit juices and beverages.


Antimitochondrial effects of thioacetamide and ethylenethiourea in human and yeast cell cultures.
Cytological studies in the light microscope showed that thioacetamide (TAA) depressed the mitotic index in cultures of skin fibroblasts at the lowest concentrations used (100 μg/ml). At high concentration (1 mg/ml), TAA tended to cause aberration in nuclear morphology. Ethylenethiourea (ETU) had no effect on either mitotic index or nuclear morphology at 1 mg/ml. Fibroblast cultures treated with 1 mg/ml TAA and cultures grown in the presence of 2 mg/ml ETU were studied by electron microscopy. In some TAA-treated cells there was unfolding of the nuclear membrane and enlargement and granulation of the nucleolus, but these effects were not correlated. In all cells, TAA caused severe and characteristic damage to the majority of mitochondria, whether or not there were nuclear aberrations. The organelle showed extensive swelling of the cristae of the inner membrane and an increase in matrix density. Ultrastructure of other cell components appeared to be unaffected by this treatment. In ETU-treated cells some less severe swelling of inner mitochondrial membranes was seen and only in a minority of cells, whilst all other cell structures appeared normal. Similar membrane swelling and increase in matrix density was seen in isolated rat liver mitochondria after incubation with TAA, indicating a direct antimitochondrial effect of the carcinogen.When yeast cells were treated with TAA and ETU, primary antimitochondrial activity of these compounds was apparent from (1) inhibition of growth in non-fermentable medium, (2) selective blockage of mitochondrial protein synthesis and (3) induction of mitochondrial mutations. TAA was much more effective than ETU in all these respects.


Comparative Analysis of Topical Evolution Patterns and Temporal Trends of Hypertension Research.
Exploring the topical evolution patterns and temporal trends of hypertension can promote knowledge communication among experts, and is of great significance to understand the profile and frontiers of chronic disease. Current popular topic detection mainly focuses on two directions: one is based on social network analysis (SNA), the other is based on the topic models. Aiming at distinguishing their similarities and differences, this paper adopts the community detection method and expanded topic model Dirichlet-multinomial regression (DMR) respectively to detect the topic distribution and evolution trends of hypertension research. A total of 26,717 articles in the PubMed database were used as examples to construct the MeSH Terms co-occurrence matrix. It is found that hypertension literature is mainly concentrated on three communities and five research topics. MeSH Terms obtained from SNA are more specific and clearer, while the DMR has an advantage in exploring the evolution patterns of various themes.


What Motivates Us for Work? Intricate Web of Factors beyond Money and Prestige.
Efficiency at doing a certain task, at the workplace or otherwise, is strongly influenced by how motivated individuals are. Exploring new ways to motivate employees is often at the top of a company's agenda. Traditionally identified motivators in Western economies primarily include salary and prestige, often complemented by meaning, creation, challenge, ownership, identity, etc. We report the results of a survey conducted in Slovenia, involving an ensemble of highly educated employees from various public and private organizations. Employing new methodologies such as network analysis, we find that Slovenians are stimulated by an intricate web of interdependent factors, largely in contrast to the traditional understanding that mainly emphasizes money and prestige. In fact, these key motivators only weakly correlate with the demographic parameters. Unexpectedly, we found the evidence of a general optimism in Slovenian professional life - a tendency of the employees to look at the "bright side of things", thus seeing more clearly the benefits of having something than the drawbacks of not having it. We attribute these particularities to Slovenian recent history, which revolves around gradually embracing the Western (economic) values.


[Sociodemographics, health, and social support to senior users of emergency services].
The aim of this study was to characterize the sociodemographic aspects, health issues and social support offered to the senior users of the Emergency Department of the Hospital de Clinicas in Porto Alegre. A cross-sectional survey was conducted with a random sample of 220 seniors. A structured data form was used to collect data related to the sociodemographic and health characteristics and social support. The majority of subjects were women, married retired,from Porto Alegre, and aged from 60 to 69 years. Almost half reported having poor or very poor health and the prevalent self-reported morbidities were cardiovascular diseases. Differently from other studies with seniors from the community, the majority reported receiving support from family and few provided support. Social support from the formal network was small. Health care must occur in a comprehensive network to provide support to the seniors and their families and to prevent the frequent use of emergency services and to qualify assistance.


Hurdles in tissue engineering/regenerative medicine product commercialization: a pilot survey of governmental funding agencies and the financial industry.
The Tissue Engineering and Regenerative Medicine International Society of the Americas (TERMIS-AM) Industry Committee conducted a semiquantitative opinion survey in 2010 to delineate potential hurdles to commercialization perceived by the TERMIS constituency groups that participate in the stream of technology commercialization (academia, start-up companies, development-stage companies, and established companies). A significant hurdle identified consistently by each group was access to capital for advancing potential technologies into development pathways leading to commercialization. A follow-on survey was developed by the TERMIS-AM Industry Committee to evaluate the financial industry's perspectives on investing in regenerative medical technologies. The survey, composed of 15 questions, was developed and provided to 37 investment organizations in one of three sectors (governmental, private, and public investors). The survey was anonymous and confidential with sector designation the only identifying feature of each respondent's organization. Approximately 80% of the survey was composed of respondents from the public (n=14) and private (n=15) sectors. Each respondent represents one investment organization with the potential of multiple participants participating to form the organization's response. The remaining organizations represented governmental agencies (n=8). Results from this survey indicate that a high percentage (<60%) of respondents (governmental, private, and public) were willing to invest >$2MM into regenerative medical companies at the different stages of a company's life cycle. Investors recognized major hurdles to this emerging industry, including regulatory pathway, clinical translation, and reimbursement of these new products. Investments in regenerative technologies have been cyclical over the past 10-15 years, but investors recognized a 1-5-year investment period before the exit via Merger and Acquisition (M&A). Investors considered musculoskeletal products and their top technology choice with companies in the clinical stage of development being the most preferred investment targets. All sectors indicated a limited interest in early-stage start-up companies potentially explaining why start-up companies have struggled to access to capital and investors based their investment on the stage of a company's life cycle, reflecting each sector's risk tolerance, exit strategy, time of holding an investment, and investment strategy priorities. Investors highlighted the limited number of regenerative medical companies that have achieved commercial status as a basis for why public investors have been approached by so few companies. Based on respondents to this survey, regenerative medical sponsors seeking capital from the financial industry must keep the explanation of their technology simple, since all sectors considered regenerative medical technology as difficult to evaluate. This survey's results indicate that under the current financial environment, many regenerative medical companies must consider codevelopment or even M&A as nondilutive means of raising capital. The overall summary for this survey highlights the highly varied goals and motivations for the various sectors of the government and financial industries.


Endothelin type A and B receptors in the control of afferent and efferent arterioles in mice.
Endothelin 1 contributes to renal blood flow control and pathogenesis of kidney diseases. The differential effects, however, of endothelin 1 (ET-1) on afferent (AA) and efferent arterioles (EA) remain to be established. We investigated endothelin type A and B receptor (ETA-R, ETB-R) functions in the control of AA and EA. Arterioles of ETB-R deficient, rescued mice [ETB(-/-)] and wild types [ETB(+/+)] were microperfused. ET-1 constricted AA stronger than EA in ETB(-/-) and ETB(+/+) mice. Results in AA: ET-1 induced similar constrictions in ETB(-/-) and ETB(+/+) mice. BQ-123 (ETA-R antagonist) inhibited this response in both groups. ALA-ET-1 and IRL1620 (ETB-R agonists) had no effect on arteriolar diameter. L-NAME did neither affect basal diameters nor ET-1 responses. Results in EA: ET-1 constricted EA stronger in ETB(+/+) compared to ETB(-/-). BQ-123 inhibited the constriction completely only in ETB(-/-). ALA-ET-1 and IRL1620 constricted only arterioles of ETB(+/+) mice. L-NAME decreased basal diameter in ETB(+/+), but not in ETB(-/-) mice and increased the ET-1 response similarly in both groups. The L-NAME actions indicate a contribution of ETB-R in basal nitric oxide (NO) release in EA and suggest dilatory action of ETA-R in EA. ETA-R mediates vasoconstriction in AA and contributes to vasoconstriction in EA in this mouse model. ETB-R has no effect in AA but mediates basal NO release and constriction in EA. The stronger effect of ET-1 on AA supports observations of decreased glomerular filtration rate to ET-1 and indicates a potential contribution of ET-1 to the pathogenesis of kidney diseases.


Oral squamous cell carcinomas and oral potentially malignant disorders: A Latin American study.
To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America. A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential-OSCC versus OSCC-de novo (OSCC-dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t-test, and qualitative variables with chi-square. In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC-dn, while s-OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD. In Latin America, OSCC-dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon.


Personality disorder and parietal lobe dysfunction.
An inability to relate transitionally is a major feature of personality disorder. The developmental independence of transitional relatedness from verbal-symbolic growth, its orienting function, and the nature of its visual and tactile components support the conclusion that it is a function of the nondominant parietal lobe. Therefore it can be hypothesized that dysfunction of this area is the cerebral analogue of personality disorder. The fact that unawareness of illness ("anosognosia") in conjunction with grossly intact intellectual function is common to both personality disorder and minor parietal lobe dysfunction further supports this hypothesis.


Clinical and Imaging Outcomes of Plantar Fasciotomy Using Microdebrider Coblation Wand.
A plantar fasciotomy using a microdebrider coblation wand may be an effective treatment for treating chronic plantar fasciitis. The objective of this prospective study was to determine the success rate of performing a plantar fasciotomy using a microdebrider coblation wand to treat plantar fasciitis and determine utility of ultrasonographic imaging to evaluate for recovery after treatment. Patients with plantar fasciitis treated with a plantar fasciotomy using a microdebrider coblation wand were prospectively followed for 1 year. Outcome measures included numeric rating scale (NRS) for pain, Foot and Ankle Disability Index (FADI), the Foot and Ankle Ability Measure for activities of daily living (FAAMA) and for sports (FAAMS), and plantar fascia thickness evaluated with ultrasonographic imaging. Forty patients were included. Average patient age was 53.4 ± 9.9 years. Average symptom duration prior to the procedure was 20 ± 26 months. Five patients dropped out of the study at various points, most due to the COVID quarantine. The mean preoperative NRS score was 4.7 and at 3 and 6 months postprocedure was ≤2. At 1 year, the outcomes were all improved compared to the preoperative status: NRS 0.7±1.3 (P < .001), FADI 107±16 (P < .001), FAAMA 95%±10% (P < .001), FAAMS 84%±19% (P < .001), and plantar fascia thickness 6.8 ± 1.2 mm (P = .014). Furthermore, 86% of patients had clinically successful outcome in pain, defined as NRS score ≤ 2 (95% CI 0, 2), and 91% of patients had a clinically successful outcome in their function, defined as having an FAAMA score ≥75%. There were no complications at the operative site either during or after the procedure. In this study of 40 patients followed prospectively, we found percutaneous plantar fasciotomy using a microdebrider coblation wand to be an effective treatment for plantar fasciitis, with a low incidence of complications. Ultrasonographic imaging may help evaluate for interval healing.Level of Evidence: Level IV, prospective case series.


Complete genome sequence of the ammonia-oxidizing bacterium and obligate chemolithoautotroph Nitrosomonas europaea.
Nitrosomonas europaea (ATCC 19718) is a gram-negative obligate chemolithoautotroph that can derive all its energy and reductant for growth from the oxidation of ammonia to nitrite. Nitrosomonas europaea participates in the biogeochemical N cycle in the process of nitrification. Its genome consists of a single circular chromosome of 2,812,094 bp. The GC skew analysis indicates that the genome is divided into two unequal replichores. Genes are distributed evenly around the genome, with approximately 47% transcribed from one strand and approximately 53% transcribed from the complementary strand. A total of 2,460 protein-encoding genes emerged from the modeling effort, averaging 1,011 bp in length, with intergenic regions averaging 117 bp. Genes necessary for the catabolism of ammonia, energy and reductant generation, biosynthesis, and CO(2) and NH(3) assimilation were identified. In contrast, genes for catabolism of organic compounds are limited. Genes encoding transporters for inorganic ions were plentiful, whereas genes encoding transporters for organic molecules were scant. Complex repetitive elements constitute ca. 5% of the genome. Among these are 85 predicted insertion sequence elements in eight different families. The strategy of N. europaea to accumulate Fe from the environment involves several classes of Fe receptors with more than 20 genes devoted to these receptors. However, genes for the synthesis of only one siderophore, citrate, were identified in the genome. This genome has provided new insights into the growth and metabolism of ammonia-oxidizing bacteria.


Cardiovascular Manifestations of Systemic Sclerosis: A Danish Nationwide Cohort Study.
Background Cardiovascular involvement in systemic sclerosis (SSc) comprises a wide range of manifestations with prevalence and incidence that remain uncertain. Methods and Results In the Danish administrative registries between 1995 and 2015, all patients aged ≥18 years with a first diagnosis of SSc were matched by age and sex with controls (1:5) from the general population. Prevalence of cardiovascular diseases at the time of the SSc diagnosis and incidence during follow-up were assessed by in- and outpatient discharge diagnoses. Conditional logistic and Cox proportional hazards regression models were used respectively to calculate odds ratios for prevalent cardiovascular diseases and hazard ratios (HRs) for incident diseases associated with SSc. Patients with SSc (n=2778; 76% women; mean±SD age: 55±15 years) had more established cardiovascular risk factors than their respective controls at baseline, including greater prevalence of hypertension (31.2% versus 21.0%, P<0.0001) and treated dyslipidemia (9.8% versus 8.5%, P=0.02). SSc was associated with an increased relative risk of developing most cardiovascular diseases, including myocardial infarction (HR: 2.08; 95% CI, 1.65-2.64), peripheral vascular disease (HR: 5.73; 95% CI, 4.63-7.09), pulmonary hypertension (HR: 21.18; 95% CI, 14.73-30.45), mitral regurgitation (HR: 4.60; 95% CI, 3.12-6.79), aortic regurgitation (HR: 3.78; 95% CI, 2.55-5.58), aortic stenosis (HR: 2.99; 95% CI, 2.25-3.97), pericarditis (HR: 8.78; 95% CI, 4.84-15.93), heart failure (HR: 2.86; 95% CI, 2.43-3.37), atrial fibrillation (HR: 1.75; 95% CI, 1.51-2.04), and venous thromboembolism (HR: 2.10; 95% CI, 1.65-2.67). Additional adjustment for medications and comorbidities yielded results similar to the main analyses. Conclusions In this nationwide study, SSc was associated with greater risks of distinct cardiovascular diseases for patients than for matched controls, suggesting a significant disease-related adverse impact across the vascular bed and specific cardiac structures.


Emerging Heterogeneities in Italian Customs and Comparison with Nearby Countries.
In this work we apply techniques and modus operandi typical of Statistical Mechanics to a large dataset about key social quantifiers and compare the resulting behaviors of five European nations, namely France, Germany, Italy, Spain and Switzerland. The social quantifiers considered are i. the evolution of the number of autochthonous marriages (i.e., between two natives) within a given territorial district and ii. the evolution of the number of mixed marriages (i.e., between a native and an immigrant) within a given territorial district. Our investigations are twofold. From a theoretical perspective, we develop novel techniques, complementary to classical methods (e.g., historical series and logistic regression), in order to detect possible collective features underlying the empirical behaviors; from an experimental perspective, we evidence a clear outline for the evolution of the social quantifiers considered. The comparison between experimental results and theoretical predictions is excellent and allows speculating that France, Italy and Spain display a certain degree of internal heterogeneity, that is not found in Germany and Switzerland; such heterogeneity, quite mild in France and in Spain, is not negligible in Italy and highlights quantitative differences in the habits of Northern and Southern regions. These findings may suggest the persistence of two culturally distinct communities, long-term lasting heritages of different and well-established customs. Also, we find qualitative differences between the evolution of autochthonous and of mixed marriages: for the former imitation in decisional mechanisms seems to play a key role (and this results in a square root relation between the number of autochthonous marriages versus the percentage of possible couples inside that country), while for the latter the emerging behavior can be recovered (in most cases) with elementary models with no interactions, suggesting weak imitation patterns between natives and migrants (and this translates in a linear growth for the number of mixed marriages versus the percentage of possible mixed couples in the country). However, the case of mixed marriages displays a more complex phenomenology, where further details (e.g., the provenance and the status of migrants, linguistic barriers, etc.) should also be accounted for.


Skin and soft tissue infection caused by Achromobacter xylosoxidans: report of 14 cases.
Skin and soft tissue infections (SSTIs) caused by Achromobacter xylosoxidans are very infrequent. The aim of the present study was to investigate the clinical and microbiological characteristics of this infection. We carried out a retrospective review of 14 cases of SSTI due to A. xylosoxidans that occurred at the University Hospital of Guadalajara (Spain) from January 2007 to December 2012. The infection was secondary to vascular diseases, trauma, and recent surgery in 12 patients (85.7%). The most frequent clinical presentation was infection of a vascular ulcer (5 cases). The infection was monomicrobial in 7 patients (50%) and 9 cases were community-acquired (64.2%). The clinical outcome of the patients was uniformly good after antibiotic treatment, except in 4 patients who suffered recurrence of the infection. A. xylosoxidans should be considered a potential pathogen in patients with SSTIs, especially in patients with vascular diseases or after surgery or trauma. A history of contact with water should be investigated in all cases. Treatment can be difficult due to the high level of antibiotic resistance. Trimethoprim-sulfamethoxazole may be useful for treatment in outpatients with community-acquired infections.


Interoception in emotional experience.
Many theories of emotion have postulated a close relationship of the feedback of physiological changes and their perception with emotional experience. This paper reviews recent advances in theory and brain-imaging research on this topic of interoception and describes a hypothetical model of the potential mechanisms. Research from patients with spinal-cord injuries and pure autonomic failure suggests that emotion-related peripheral autonomic changes are not necessary for emotional experience. However, in support of a role for centrally integrated feedback from the whole body, imaging studies found that activations in areas commonly associated with interoception and emotion (anterior insula and anterior cingulate) were correlated with individual differences in interoception (heartbeat detection) and trait measures of emotion. Because recent theory distinguishes between two levels of emotional experience (phenomenology and awareness), this paper proposes a hypothetical model of the effects of interoception on phenomenology and awareness. This model classifies interoception into the central representation of feedback from the whole body, the perception of actual physiological changes as well as the perception of illusory changes. Consistent with recent theories of emotion, evidence from brain imaging supports the notion that centrally integrated feedback from the whole body plays a role in emotional experience. Because research on neural correlates of emotional experience is at an early stage, the hypothesized model of potential causal links between interoception and emotional experience might serve as a helpful guide to future research.


Distinct Dominant Lineage from In Vitro Expanded Adipose-Derived Stem Cells (ASCs) Exhibits Enhanced Wound Healing Properties.
It has been suggested that immunophenotypically defined lineages within the in vitro expanded adipose-derived stem cell (ASC) may play a beneficial role from the perspective of a personalized intervention. Therefore, to better understand the implications of different surface marker profiles for the functionality, we set out to examine the evolution of ASC-variants based on the co-expression of five bright or eight dim epitopes. At passages P1, P4, and P8, the co-localization of five bright markers (CD73, CD90, CD105, CD166, and CD201), or eight dim markers (CD34, CD36, CD200, CD248, CD271, CD274, CD146, and the Stro-1), was investigated by flow cytometry. Selected subpopulations were isolated using the fluorescence-activated cells sorting from the cryopreserved P4 and analyzed in terms of proliferative and clonogenic properties, trilineage differentiation, and wound healing potential. Only two of the dim epitopes were found in representative subpopulations (SP), and from the P4 onwards, two major combinations featuring the CD274+ (SP1) or the CD274+ CD146+ (SP2) emerged. Upon sorting and growth, both subpopulations assumed new but highly similar clonal profiles, consisting of the CD274+ CD146+ and the CD274+ CD146+ CD248+ phenotypes. The functional analysis revealed that the SP2 surpassed SP1 and the unfractionated cells regarding the growth rate, clonogenic activity, and the wound closure and endothelial tube formation potential. The surface epitopes may be considered a tool to enrich specific functionality and thus improve therapeutic outcomes in dedicated circumstances.


Latent Class Analysis of E-cigarette Use Sessions in Their Natural Environments.
Delivery of nicotine and substances from electronic nicotine delivery systems, or e-cigarettes, depends in part on how users puff on the devices. Little is known about variation in puffing behavior to inform testing protocols or understand whether puffing behaviors result in increased exposure to emissions. We analyzed puff topography data collected using a wireless portable use monitor (wPUM) continuously over 2 weeks among 34 current second-generation e-cigarette users in their everyday lives. For each puff, the wPUM recorded date, time, duration, volume, flow rate, and inter-puff interval. We defined use session and classes at the session level using multilevel latent profile analysis, resulting in two session classes and three person types. Session class 1 ("light") was characterized by 14.7 puffs per session (PPS), low puff volume (59.9 ml), flow rate (28.7 ml/s), and puff duration (202.7 s × 100). Session class 2 ("heavy") was characterized by 16.7 PPS with a high puff volume (290.9 ml), flow rate (71.5 ml/s), and puff duration (441.1 s × 100). Person class 1 had almost exclusively "light" sessions (98.0%), whereas person class 2 had a majority of "heavy" sessions (60.7%) and person class 3 had a majority of "light" sessions (75.3%) but some "heavy" sessions (24.7%). Results suggest there are different session topography patterns among e-cigarette users. Further assessment is needed to determine whether some users have increased exposure to constituents and/or health risks because of e-cigarettes. Our study examines topography characteristics in a users' natural setting to identify two classes of e-cigarette session behavior and three classes of users. These results suggest that it is important for studies on the health effects of e-cigarettes to take variation in user topography into account. It is crucial to accurately understand the topography profiles of session and user types to determine whether some users are at greater exposure to harmful or potentially harmful constituents and risks from e-cigarettes as they are used by consumers.


Biology of immunoglobulins.
Intravenous Immunoglobulins (IvIg) are often administered to critically ill patients more as an act of faith than on the basis of relevant clinical studies. This particularly applies to the treatment of sepsis in adult patients, in whom the current guidelines even recommend against their use, despite that many studies demonstrated either their beneficial effects in different subsets of patients and that some preparations of IvIg are more effective than other. The biology of Ig are reviewed, aiming to a more in-depth understanding of their properties in order to clarify their possible indications in different clinical settings.


Prioritization of pharmaceuticals based on risks to aquatic environments in Kazakhstan.
Over the last 20 years, there has been increasing interest in the occurrence, fate, effects, and risk of pharmaceuticals in the natural environment. However, we still have only limited or no data on ecotoxicological risks of many of the active pharmaceutical ingredients (APIs) currently in use. This is partly due to the fact that the environmental assessment of an API is an expensive, time-consuming, and complicated process. Prioritization methodologies, which aim to identify APIs of most concern in a particular situation, could therefore be invaluable in focusing experimental work on APIs that really matter. The majority of approaches for prioritizing APIs require annual pharmaceutical usage data. These methods cannot therefore be applied to countries, such as Kazakhstan, that have very limited data on API usage. The present paper therefore offers an approach for prioritizing APIs in surface waters in information-poor regions such as Kazakhstan. Initially data were collected on the number of products and active ingredients for different therapeutic classes in use in Kazakhstan and on the typical doses. These data were then used alongside simple exposure modeling approaches to estimate exposure indices for active ingredients (about 240 APIs) in surface waters in the country. Ecotoxicological effects data were obtained from the literature or predicted. Risk quotients were then calculated for each pharmaceutical based on the exposure and the substances were ranked in order of risk quotient. Highest exposure indices were obtained for benzylpenicillin, metronidazole, sulbactam, ceftriaxone, and sulfamethoxazole. The highest risk was estimated for amoxicillin, clarithromycin, azithromycin, ketoconazole, and benzylpenicillin. In the future, the approach could be employed in other regions where usage information is limited. Integr Environ Assess Manag 2017;13:832-839. © 2017 SETAC.


[Catamnesis of patients with Kanner's early infantile autism syndrome].
By means of a follow-up study the author studied 28 patients who at the age of 3-6 years were diagnosed as suffering from early infantile autism. In 6 cases the mental state of patients was characterized by traits of dissociated oligophrenic-like defect with preserved autistic forms of contacts, residual disorders of the syndrome of Kanners early autism, simbiotical dependency from the parents. In 15 cases there was a personality distortion, with traits of autism, emotional poorness, motor insufficiency, indifferent negativistic forms of contacts, mental retardation of the pseudooligophrenic type. In 7 cases there was a formation of a psychopathic state of a schizoid type.


Pterostilbene inhibits colorectal aberrant crypt foci (ACF) and colon carcinogenesis via suppression of multiple signal transduction pathways in azoxymethane-treated mice.
Pterostilbene (PS), a natural dimethylated analogue of resveratrol, is known to have diverse pharmacologic activities including anticancer, anti-inflammation, antioxidant, apoptosis, antiproliferation, and analgesic potential. This paper reports the inhibitory effect of dietary administration of pterostilbene against the formation of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) preneoplastic lesions and adenomas in male ICR mice and delineates its possible molecular mechanisms. ICR mice were given two AOM injections intraperitoneal and continuously fed a 50 or 250 ppm pterostilbene diet for 6 or 23 weeks. It was found that the dietary administration of pterostilbene effectively reduced AOM-induced formation of ACF and adenomas and inhibited the transcriptional activation of iNOS and COX-2 mRNA and proteins in mouse colon stimulated by AOM. Treatment with pterostilbene resulted in the induction of apoptosis in mouse colon. Moreover, administration of pterostilbene for 23 weeks significantly suppressed AOM-induced GSK3beta phosphorylation and Wnt/beta-catenin signaling. It was also found that pterostilbene significantly inhibited AOM-induced expression of VEGF, cyclin D1, and MMPs in mouse colon. Furthermore, pterostilbene markedly inhibited AOM-induced activation of Ras, phosphatidylinositol 3 kinase/Akt, and EGFR signaling pathways. All of these results revealed that pterostilbene is an effective antitumor agent as well as its inhibitory effect through the down-regulation of inflammatory iNOS and COX-2 gene expression and up-regulation of apoptosis in mouse colon, suggesting that pterostilbene is a novel functional agent capable of preventing inflammation-associated colon tumorigenesis.


Variations in Trochlear Morphology of Contemporary and Legacy Total Knee Arthroplasty Prostheses - A Review of 22 Designs.
The morphology of the trochlear compartment of total knee arthroplasty (TKA) prostheses is a major determinant of postoperative patello-femoral kinematics, particularly with unresurfaced patellae. The objective of this study was to quantify and compare the trochlear morphology of a large series of contemporary and legacy TKA designs. The three-dimensional surface models of twenty-two femoral components (13 contemporary and 9 legacy) were created using high-resolution laser scanning. The trochlear profile of each component was analyzed from proximal to distal in 15° increments around the trochlear axis. In each profile, the following variables were measured: sulcus angle, medio-lateral deviation of the sulcus, the height and width of the facets, and the trochlear groove orientation. In the contemporary group, the sulcus angle decreased progressively along the trochlear arc to varying degrees, except for two symmetrical designs, whereas the sulcus angle of the legacy designs showed significant variability. The height of the medial facet was very strongly correlated with that of the lateral facet in the contemporary group (R2=0.89), whereas the correlation was weak for the legacy designs (R2=0.36). Moreover, the trochlear sulcus deviated laterally from distal to proximal in ten contemporary designs and seven legacy designs, resulting in a trochlear groove orientation of 4.2 to 11.1°, and 4.3 to 10.5°, respectively. In the remaining five designs (3 contemporary and 2 legacy), the sulcus was vertical. There is more consistency in trochlear morphology of contemporary TKA designs compared to legacy designs, yet the variations between different designs are still significant.


Public health education at the University of California, Davis: past, present, and future programs.
This article reviews the history of public-health education at the University of California, Davis, from the inception of the Master of Preventive Veterinary Medicine Program in the School of Veterinary Medicine through the creation of the Master of Public Health Program offered jointly by the Schools of Medicine and Veterinary Medicine. The long history of collaborative teaching and research between the schools, as well as the university's close proximity to and relationship with numerous university-affiliated and state public-health agencies, has created remarkable opportunities for novel and creative public-health education. The university is already anticipating the approval of a School of Public Health on its campus, which will create even more educational opportunities in both human and veterinary public-health disciplines. Given the projected shortfall of veterinarians entering such fields, the opportunity of a novel Doctor of Public Health degree program specifically suited to the needs of veterinary medicine is also discussed as a means of addressing this shortage.


Adrenal suppression following a single dose of etomidate for rapid sequence induction: a prospective randomized study.
The administration of etomidate for rapid sequence induction (RSI) has been linked to subsequent adrenocortical insufficiency in nontrauma patients. However, etomidate-related adrenocortical insufficiency has not been well studied in the trauma population. We performed a prospective, randomized, controlled study to assess the effect of one dose of etomidate for RSI on adrenal function and its clinical significance during and after resuscitation in trauma patients. Adult trauma patients admitted to our Level I trauma center requiring RSI were randomized to receive etomidate 0.3 mg/kg and succinylcholine 1 mg/kg (E group) or fentanyl 100 microg, midazolam 5 mg, and succinylcholine 1 mg/kg (FM group) for induction. A baseline serum cortisol level was drawn before RSI. Four to six hours after RSI, a postintubation serum cortisol level was drawn. An ACTH stimulation test was performed. Thirty patients were enrolled: 18 E group patients and 12 FM group patients. No statistical difference was detected between the two groups with respect to age, injury severity score, and baseline serum cortisol. Mean serum cortisol levels were significantly lower in E group patients than in FM group patients 4 to 6 hours after intubation (18.2 vs. 27.8 mug/dL, p < 0.05). Change in serum cortisol between baseline and postintubation levels was different (-12.8 mg/dL +/- 9.6 microg/dL vs. 1.1 microg/dL +/- 7.6 microg/dL, p < 0.01). Patients in the E group had an average increase in cortisol after ACTH administration of 4.2 microg/dL +/- 4.9 microg/dL vs. 11.2 microg/dL +/- 6.1 microg/dL in the FM group, p < 0.001. Patients in the E group required longer ICU lengths of stay (mean, 6.3 days vs. 1.5 days, p < 0.05), more ventilator days (mean, 28 days vs. 17 days, p < 0.01), and longer hospital lengths of stay (mean, 11.6 days vs. 6.4 days, p < 0.01). The use of etomidate for RSI in trauma patients led to chemical evidence of adrenocortical insufficiency and may have contributed to increased hospital and ICU lengths of stay and increased ventilator days. Further studies should be considered to evaluate the safety profile of this drug in trauma patients.


Wrist and forearm posture from typing on split and vertically inclined computer keyboards.
A study was conducted on 90 experienced office workers to determine how commercially available alternative computer keyboards affected wrist and forearm posture. The alternative keyboards tested had the QWERTY layout of keys and were of three designs: split fixed angle, split adjustable angle, and vertically inclined (tilted or tented). When set up correctly, commercially available split keyboards reduced mean ulnar deviation of the right and left wrists from 12 degrees to within 5 degrees of a neutral position compared with a conventional keyboard. The finding that split keyboards place the wrist closer to a neutral posture in the radial/ulnar plane substantially reduces one occupational risk factor of work-related musculoskeletal disorders (WMSDs): ulnar deviation of the wrist. Applications of this research include commercially available computer keyboard designs that typists can use and ergonomists can recommend to their clients in order to minimize wrist ulnar deviation from typing.


Melanoma miRNA trafficking controls tumour primary niche formation.
Melanoma originates in the epidermis and becomes metastatic after invasion into the dermis. Prior interactions between melanoma cells and dermis are poorly studied. Here, we show that melanoma cells directly affect the formation of the dermal tumour niche by microRNA trafficking before invasion. Melanocytes, cells of melanoma origin, are specialized in releasing pigment vesicles, termed melanosomes. In melanoma in situ, we found melanosome markers in distal fibroblasts before melanoma invasion. The melanosomes carry microRNAs into primary fibroblasts triggering changes, including increased proliferation, migration and pro-inflammatory gene expression, all known features of cancer-associated fibroblasts (CAFs). Specifically, melanosomal microRNA-211 directly targets IGF2R and leads to MAPK signalling activation, which reciprocally encourages melanoma growth. Melanosome release inhibitor prevented CAF formation. Since the first interaction of melanoma cells with blood vessels occurs in the dermis, our data suggest an opportunity to block melanoma invasion by preventing the formation of the dermal tumour niche.


Tumor necrosis factor alpha enhances nicotinic receptor up-regulation via a p38MAPK-dependent pathway.
A response by key neuronal nicotinic acetylcholine receptors (nAChRs) to sustained nicotine exposure is up-regulation. Although this unusual receptor characteristic contributes to processes ranging from aging to addiction, the normal physiologic reason for this response is unknown. We find that up-regulation of [(3)H]epibatidine binding and function in HEK293 cells stably expressing alpha4beta2-nAChR is significantly enhanced by co-application of the proinflammatory cytokine, tumor necrosis factor alpha. The mechanism of tumor necrosis factor alpha-enhanced up-regulation requires transcription, new protein synthesis, and signaling through p38(MAPK) as demonstrated by complete inhibition using SB 202190. This finding extends the possibilities for nAChR-inflammatory interactions in normal physiological processes and offers novel insights into endogenous mechanisms that can modify up-regulation.


Experiential avoidance and excessive smartphone use: a Bayesian approach.
The smartphone is a common tool in our everyday lives. However, recent research suggests that using the smartphone has both positive and negative consequences. Although there is no agreement on the concept or the term to label it, researchers and clinical practitioners are worried about the negative consequences derived from excessive smartphone usage. This study aims to analyse the relationship between smartphone addiction and experiential avoidance. A sample of 1176 participants (828 women) with ages ranging from 16 to 82 (M = 30.97; SD = 12.05) was used. The SAS-SV scale was used to measure smartphone addiction and the AAQ-II to assess experiential avoidance. To model the relationship between variables, Bayesian inference and Bayesian networks were used. The results show that experiential avoidance and social networks usage are directly related to smartphone addiction. Additionally, the data suggests that sex is playing a mediating role in the observed relationship between these variables. These results are useful for understanding healthy and pathological interaction with smartphones and could be helpful in orienting or planning future psychological interventions to treat smartphone addiction.


Recent perspective on CAR and Fcγ-CR T cell immunotherapy for cancers: Preclinical evidence versus clinical outcomes.
The chimeric antigen receptor T cell (CAR-T cell) immunotherapy currently represents a hot research trend and it is expected to revolutionize the field of cancer therapy. Promising outcomes have been achieved using CAR-T cell therapy for haematological malignancies. Despite encouraging results, several challenges still pose eminent hurdles before being fully recognized. Directing CAR-T cells to target a single tumour associated antigen (TAA) as the case in haematological malignancies might be much simpler than targeting the extensive inhibitory microenvironments associated with solid tumours. This review focuses on the basic principles involved in development of CAR-T cells, emphasizing the differences between humoral IgG, T-cell receptors, CAR and Fcγ-CR constructs. It also highlights the complex inhibitory network that is usually associated with solid tumours, and tackles recent advances in the clinical studies that have provided great hope for the future use of CAR-T cell immunotherapy. While current Fcγ-CR T cell immunotherapy is in pre-clinical stage, is expected to provide a sound therapeutic approach to add to existing classical chemo- and radio-therapeutic modalities.


Antimicrobial susceptibility and clinical characteristics of Nocardia isolates from a tertiary care centre diagnostic laboratory in Pakistan.
Nocardiosis is an opportunistic infection that can present as cutaneous, pulmonary and/or disseminated disease depending on the host immunity. Treatment choices include trimethoprim/sulfamethoxazole (co-trimoxazole; SXT) and imipenem along with some other antibiotics. The Clinical and Laboratory Standards Institute (CLSI) recommends the broth microdilution (BMD) method to determine antimicrobial susceptibility, however there is a lack of susceptibility data using this method in Pakistan. Therefore, this study was undertaken to outline the susceptibility profile of Nocardia isolates in Pakistan. From November 2014 to June 2016, 52 consecutive isolates of Nocardia obtained from clinical specimens cultured at the clinical microbiology laboratory of Aga Khan University Hospital (Karachi, Pakistan) were tested for susceptibility to recommended antibiotics using the CLSI-recommended BMD method. The frequency and percentage of susceptibility and resistance of Nocardia to antimicrobials recommended by CLSI were calculated. The susceptibility profiles of pulmonary and extrapulmonary specimens were compared by χ2 test. Of the 52 isolates, 47 (90.4%) were susceptible to SXT, 20 (38.5%) to imipenem, 49 (94.2%) to amikacin and 52 (100%) to linezolid. No significant differences were found when susceptibilities were compared between pulmonary and extrapulmonary isolates. This study highlights the importance of using the gold-standard BMD method for susceptibility testing of Nocardia isolates. Larger studies are needed in the region to establish susceptibility profiles of Nocardia spp. using the BMD method in order to monitor resistance trends and to inform empirical therapy choices.


Antimalarial activity of some novel derivatives of 2,4-diamino-5(p-chlorophenyl)-6-ethylpyrimidine (pyrimethamine).
Thirteen new analogs of 2,4-diamino-5(p-chlorophenyl)-6-ethylpyrimidine (Daraprim, pyrimethamine) in which the alph position of the 6-ethyl substituent was modified were prepared. The respective oxygens analogs (ketals, ketone, alcohol), the dimethyl hydrazone, and the nitrone displayed activities in the range of 1/4 to 1/16 that of pyrimethamine toward Plasmodium berghei in mice. The therapeutic ratios of some of these compounds may be slightly better than that of pyrimethamine.


Endoscopic treatment of esophageal varices in patients with liver cirrhosis.
Variceal bleeding is a life-threatening complication of portal hypertension with a six-week mortality rate of approximately 20%. Patients with medium- or large-sized varices can be treated for primary prophylaxis of variceal bleeding using two strategies: non-selective beta-blockers (NSBBs) or endoscopic variceal ligation (EVL). Both treatments are equally effective. Patients with acute variceal bleeding are critically ill patients. The available data suggest that vasoactive drugs, combined with endoscopic therapy and antibiotics, are the best treatment strategy with EVL being the endoscopic procedure of choice. In cases of uncontrolled bleeding, transjugular intrahepatic portosystemic shunt (TIPS) with polytetrafluoroethylene (PTFE)-covered stents are recommended. Approximately 60% of the patients experience rebleeding, with a mortality rate of 30%. Secondary prophylaxis should start on day six following the initial bleeding episode. The combination of NSBBs and EVL is the recommended management, whereas TIPS with PTFE-covered stents are the preferred option in patients who fail endoscopic and pharmacologic treatment. Apart from injection sclerotherapy and EVL, other endoscopic procedures, including tissue adhesives, endoloops, endoscopic clipping and argon plasma coagulation, have been used in the management of esophageal varices. However, their efficacy and safety, compared to standard endoscopic treatment, remain to be further elucidated. There are safety issues accompanying endoscopic techniques with aspiration pneumonia occurring at a rate of approximately 2.5%. In conclusion, future research is needed to improve treatment strategies, including novel endoscopic techniques with better efficacy, lower cost, and fewer adverse events.


Acute P. falciparum malaria induces a loss of CD28- T IFN-gamma producing cells.
P. falciparum malaria is associated with increased activation among peripheral lymphocytes. In the present study, we investigated markers of susceptibility to apoptosis and expression of IFN-gamma and IL-4 by CD28-and CD28+T cells in West African children with acute P. falciparum malaria. The study showed increased susceptibility to apoptosis and cytokine production among T lymphocytes during acute malaria but also that T cells, in particular IFN-gamma producing CD28-T cells, were substantially reduced. These results are in line with previous studies suggesting that certain T cell subsets are sequestered away from the peripheral blood during P. falciparum malaria.


Mediterranean Diet, Brain and Muscle: Olive Polyphenols and Resveratrol Protection in Neurodegenerative and Neuromuscular Disorders.
The Mediterranean diet is worldwide recognized as a good prototype of nutrition due to the conspicuous intake of olive oil, nuts, red wine, legumes, fruit, and vegetables, all fundamental elements rich in antioxidant substances and polyphenols. Polyphenols are a wide range of phytochemicals and/or synthetic chemical compounds with proven beneficial properties for human health. In the present review, we critically summarize the wellcharacterized antioxidant and anti-inflammatory properties of polyphenols contained in the olives and extra virgin olive oil and of resveratrol, a non-flavonoid phenolic compound. We discuss the potential use of these polyphenols as pharmaceutical formulations for the treatment of human diseases. We also show the emerging importance of their consumption in the prevention and management of crucial neurodegenerative conditions (alcohol-related brain disorders and aging) and in neuromuscular disorders (Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis and Duchenne Muscular Dystrophy), where oxidative stress plays a predominant role.


A prospective comparison of robotic and laparoscopic pyeloplasty.
To determine whether robotic-assisted pyeloplasty (RLP) has any significant clinical or cost advantages over laparoscopic pyeloplasty (LP) for surgeons already facile with intracorporeal suturing. LP has become an established management approach for primary ureteropelvic junction obstruction. More recently, the da Vinci robot has been applied to this procedure (RLP) in an attempt to shorten the learning curve. Whether RLP provides any significant advantage over LP for the experienced laparoscopist remains unclear. Ten consecutive cases each of transperitoneal RLP and LP performed by a single surgeon were compared prospectively with respect to surgical times and perioperative outcomes. Cost assessment was performed by sensitivity analysis using a mathematical cost model incorporating operative time, anesthesia fees, consumables, and capital equipment depreciation. The RLP and LP groups had statistically indistinguishable demographics, pathology, and similar perioperative outcomes. Mean operative and total room time for RLP was significantly longer than LP by 19.5 and 39.0 minutes, respectively. RLP was much more costly than LP (2.7 times), due to longer operative time, increased consumables costs, and depreciation of the costly da Vinci system. However, even if depreciation was eliminated, RLP was still 1.7 times as costly as LP. One-way sensitivity analysis showed that LP operative time must increase to almost 6.5 hours for it to become cost equivalent to RLP. For the experienced laparoscopist, application of the da Vinci robot resulted in no significant clinical advantage and added substantial cost to transperitoneal laparoscopic dismembered pyeloplasty.