Clinical and radiological outcomes of two implants with different prosthetic interfaces and neck configurations: randomized, controlled, split-mouth clinical trial.
Peri-implant bone loss seems to occur following implant placement/loading regardless of all the efforts to eliminate it. Several factors, including surgical trauma, biologic width establishment, lack of passive fit of the superstructures, implant-abutment microgap, and occlusal overloading, may increase peri-implant bone loss. Over the years, new interface designs were introduced and clinical studies suggest that internal conical connection and platform shifting may be advantageous for marginal bone preservation. To compare clinical and radiological outcomes of two implant designs with different prosthetic interfaces and neck configurations in a randomized, controlled, split-mouth clinical trial. Thirty-four partially edentate patients randomly received at least one internal conical connection with back-tapered collar and platform shifting design or external-hexagon implants with flat-to-flat implant-abutment interface. Primary end point was peri-implant bone level changes at different time points, failures of implants and/or prosthesis, any complications, implant stability quotient (ISQ) values, and periodontal parameters. No dropout occurred. Marginal bone changes were statistically significantly different with better results for the internal conical connection. No implants and prosthesis failures have been observed, yielding a cumulative survival rate of 100%. A high ISQ value was found for both implants, and no statistically significant difference was found for ISQ mean values between interventions at each time point (p > .05). All implants showed no bleeding on probing and a very slight amount of plaque at the 1-year-in-function visit. Both implant designs investigated performed similarly in terms of failure rates, providing successful results up to 1 year after loading. The back-tapered neck configuration with conical connection and built-in platform shifting showed statistically lower marginal bone loss than straight neck configuration with flat-to-flat implant-abutment interface and external-hexagonal connection.


Impact of maternal desvenlafaxine exposure on brain development in pregnant albino rats and their fetuses.
Depression during pregnancy adversely affects fetal development. Desvenlafaxine drug is used for the treatment of gestational depression. In light of the well-established role of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in regulating neurogenesis and neural survival, the role of S100b in nerve cell energetic metabolism, differentiation of neurons and glial cells, an aberrant increase in NGF, BDNF and S100b expression in the fetal brain may contribute to desvenlafaxine cognitive disorders by altering brain development. This study is trying to determine the effect of desvenlafaxine on brain development. Thirty timed pregnant rats (from the 5th to the 20th day) were divided into three groups: control, low dose (5.14 mg/kg/day) and high dose (10.28 mg/kg/day) of desvenlafaxine where all animals received the corresponding doses by gavage. Maternal and fetal brain samples were fixed for histological, immunohistochemical (IHC) study of NGF and evaluated for BDNF and S100b genes expression. Desvenlafaxine induced some of the histopathological alterations in maternal and fetal rat brains. Moreover, IHC analysis of maternal and fetal rat brains showed that groups treated with desvenlafaxine demonstrated a significant increase of NGF protein immunoreactivity compared with that in the controls. Gene expression results revealed upregulation of messenger RNA BDNF and S100B expression. According to developmental changes in the brain, desvenlafaxine affects neonatal growth during pregnancy, which may lead to delay of brain development. So, it is essential to survey the roles of antidepressant drugs on neonatal development during pregnancy.


Intense 18F-Flourodeoxyglucose Uptake in Brachial Plexus of Patients with Brachial Plexopathy.
Brachial plexopathy is a significant cause of pain and disability in patients with breast cancer. Major causes of brachial plexopathy in patients with breast cancer are metastatic invasion or radiation damage to the plexus. Differentiation between the two pathologies is important for appropriate treatment planning. The complicated anatomy of the plexus makes this a difficult area to image accurately. Magnetic resonance imaging (MRI) is the imaging modality of choice for diagnostic evaluation of these cases. We presented a case to demonstrate the role of 18F-flourodeoxyglucose positron emission tomography/computerized tomography for confirming metastatic brachial plexopathy when MRI findings were suspicious and for differentiating radiation-induced brachial plexopathy from metastatic plexopathy.


Vitamin A Deficiency Impairs Mucin Expression and Suppresses the Mucosal Immune Function of the Respiratory Tract in Chicks.
The chicken immune system is immature at the time of hatching. The development of the respiratory immune system after hatching is vital to young chicks. The aim of this study was to investigate the effect of dietary vitamin A supplement levels on respiratory mucin and IgA production in chicks. In this study, 120 one-day-old broiler chicks were randomly divided into 4 groups consisting of three replicates of 10 broilers and subjected to dietary vitamin A supplement levels of 0, 1,500, 6,000, or 12,000 IU/kg for seven days. Compared with control birds, vitamin A supplementation significantly increased the mucin and IgA levels in the bronchoalveolar lavage fluid (BALF) as well as the IgA level in serum. In the lungs, vitamin A supplementation downregulated TNF-α and EGFR mRNA expression. The TGF-β and MUC5AC mRNA expression levels were upregulated by vitamin A supplementation at a dose of 6,000 IU/kg, and the IL-13 mRNA expression level was increased at the 12,000 IU/kg supplement level. Vitamin A deficiency (control) significantly decreased the mRNA expression levels of MUC2, IgA, EGFR, IL-13 and TGF-β in trachea tissue. Histological section analysis revealed that the number of goblet cells in the tracheal epithelium was less in the 0 and 12,000 IU/kg vitamin A supplement groups than in the other groups. In conclusion, vitamin A deficiency suppressed the immunity of the airway by decreasing the IgA and mucin concentrations in neonatal chicks. This study suggested that a suitable level of vitamin A is essential for the secretion of IgA and mucin in the respiratory tract by regulating the gene expression of cytokines and epithelial growth factors.


Second-Order Perturbation Theory for Generalized Active Space Self-Consistent-Field Wave Functions.
A multireference second-order perturbation theory approach based on the generalized active space self-consistent-field (GASSCF) wave function is presented. Compared with the complete active space (CAS) and restricted active space (RAS) wave functions, GAS wave functions are more flexible and can employ larger active spaces and/or different truncations of the configuration interaction expansion. With GASSCF, one can explore chemical systems that are not affordable with either CASSCF or RASSCF. Perturbation theory to second order on top of GAS wave functions (GASPT2) has been implemented to recover the remaining electron correlation. The method has been benchmarked by computing the chromium dimer ground-state potential energy curve. These calculations show that GASPT2 gives results similar to CASPT2 even with a configuration interaction expansion much smaller than the corresponding CAS expansion.


Gene Deregulation and Underlying Mechanisms in Spinocerebellar Ataxias With Polyglutamine Expansion.
Polyglutamine spinocerebellar ataxias (polyQ SCAs) include SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17 and constitute a group of adult onset neurodegenerative disorders caused by the expansion of a CAG repeat sequence located within the coding region of specific genes, which translates into polyglutamine tract in the corresponding proteins. PolyQ SCAs are characterized by degeneration of the cerebellum and its associated structures and lead to progressive ataxia and other diverse symptoms. In recent years, gene and epigenetic deregulations have been shown to play a critical role in the pathogenesis of polyQ SCAs. Here, we provide an overview of the functions of wild type and pathogenic polyQ SCA proteins in gene regulation, describe the extent and nature of gene expression changes and their pathological consequences in diseases, and discuss potential avenues to further investigate converging and distinct disease pathways and to develop therapeutic strategies.


Factors affecting patients' ratings of health-care satisfaction.
Surveys that include rating scales are commonly used to collect data about patients' experiences. We studied how patients associated their ratings with their experiences of care. A survey and a qualitative study were conducted at a Danish hospital. Initially, 19 female patients completed a questionnaire using the response categories from very good to very bad; and subsequently they participated in a semi-structured interview held within two days after they completed the questionnaire. Additionally, 44 female patients participated in an interview within six weeks of completing a questionnaire. A phenomenological-hermeneutical approach was used in the analysis and interpretation. Two major themes emerged: experienced versus expected clinical quality and health-care professional attitude. Patients responded to each question by combining their experiences of both themes, e.g. a "very good" experience required that clinical service was provided at the expected level, at the very least, and that it was provided with recognition and respect. The female patients associated their experiences with their ratings, and two types of relation seemed to be at play: a care relation and a human relation. This finding can inform health-care practice, but department-specific examples may be needed to initiate improvements. The study received funding from the Centre for Patient Experience and Evaluation, Copenhagen, Denmark. The Danish Scientific Ethical Committees deemed it unnecessary to be involved in this project. The Danish Data Protection Agency number of this study is 2008-58-0035.


Relation between lymphocyte to monocyte ratio and survival in patients with hypertrophic cardiomyopathy: a retrospective cohort study.
The lymphocyte-to-monocyte ratio (LMR) has been proposed as a novel prognostic factor in malignancies and cardiovascular diseases. Our study aimed to ascertain whether LMR is a useful biomarker in discriminating the hypertrophic cardiomyopathy (HCM) patients at higher risk of all-cause mortality. This retrospective study consisted of 354 adult HCM patients. Cox's proportional hazards regression models were used to analyze the association between LMR and all-cause mortality. Smooth curve fitting was conducted to explore the linear relationship between LMR and all-cause mortality. During the follow-up, 44 patients reached the study endpoint. The all-cause mortality rate was 7.3 per 100 person-years in the first tertile and decreased across the three tertiles of LMR. With the first tertile as reference, adjusted hazard ratios (HR) for all-cause mortality were 0.43 for the second tertile (95% CI [0.20-0.91], p = 0.027) and 0.39 for the third tertile (95% CI [0.17-0.90], p = 0.028), respectively. Smooth curve fitting exhibited a nonlinear relationship between LMR values and all-cause mortality. For LMR < 6.5, per SD increase resulted in a significantly decreased risk of all-cause mortality by 62% (HR: 0.38, 95% CI [0.21-0.68]). For LMR ≥ 6.5, the all-cause mortality risk did not progressively increase. Stratified and subgroup analyses revealed similar results to the main analyses,andE-value analysis suggested robustness to unmeasured confounding. The study demonstrated that LMR was an independent predictor of all-cause mortality in HCM patients, and LMR may be useful for identifying HCM patients at high mortality risk.


The dichotomy between herpes simplex virus type 1-induced ocular pathology and systemic immunity.
Herpes simplex virus Type 1 (HSV-1) was injected into the mouse eye by the intravitreal (into the vitreous chamber; VC) or translimbal (across the limbus into the anterior chamber; TxL) route. These routes were compared for ocular pathology and systemic immunity. After VC inoculation, the virus-injected eye developed a viral infection, with the majority of opposite, uninjected eyes remaining intact and free of virus over the 4 week period of observation. In contrast, following translimbal inoculation, the entire virus-injected eye developed infection and inflammation together with subsequent chorioretinitis in the opposite uninjected eye. Systemic immunity induced by VC or TxL virus inoculation was similar to the effects of anterior chamber (AC) inoculation of the same dose of HSV-1: T cell-mediated DTH responses were suppressed while levels of anti-HSV neutralizing antibody were enhanced, compared to subcutaneously primed positive control mice. These findings demonstrate that HSV-1-induced ocular pathology does not necessarily correlate directly with systemic immunity.


Increased urinary excretion of transferrin in children with type 1 diabetes mellitus.
Urinary transferrin excretion was measured by radioimmunoassay in 74 children with Type 1 diabetes mellitus and in 40 normal children, and compared with urinary excretion of albumin, alpha-1-microglobulin, and N-acetyl-beta-D-glucosaminidase. Urinary transferrin excretion was significantly elevated in diabetic (median (range) 186 (18-1671) mg mol-creatinine-1) compared with normal (85 (27-668) mg mol-creatinine-1) children (p less than 0.001). Seventeen diabetic children had transferrin excretion above the 95th centile for normal children. In contrast there was no significant increase in urinary albumin excretion in the diabetic children although 8 had urinary albumin excretion which exceeded the 95th centile for normal children (6 of these 8 patients having coexistent urinary hyperexcretion of transferrin). Urinary transferrin excretion correlated significantly with urinary albumin excretion in both normal (rs = 0.62, p less than 0.001) and diabetic (rs = 0.61, p less than 0.001) children. The indices of proximal renal tubular function (urinary excretion of alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase) correlated significantly with transferrin excretion in both diabetic (rs = 0.43 and rs = 0.41, p less than 0.001) and normal (rs = 0.40, p less than 0.02 and rs = 0.53, p less than 0.001) children, but not with albumin excretion (rs = 0.20, p greater than 0.05 and rs = 0.22, p greater than 0.05). In addition urinary transferrin excretion significantly correlated with urinary glucose concentration (rs = 0.34, p less than 0.007) in Type 1 diabetic children. The discrepancy in urinary excretion of transferrin and albumin may reflect impaired proximal renal tubular reabsorption of transferrin and/or altered glomerular basement membrane selectivity for the two proteins.


A new species of Polyamia DeLong (Hemiptera: Cicadellidae: Deltocephalinae: Deltocephalini) representing the first record of the genus from South America.
Polyamia (Polyamia) choromorica sp. n., representing the first record of the genus Polyamia DeLong from South America, is described and illustrated. Previously described species of Polyamia DeLong appear to be restricted to North America. Color illustrations of Polyamia (Copolyamia) caperata (Ball), Polyamia (Copolyamia) similaris DeLong Davidson and Polyamia (Polyamia) weedi Van Duzee are also provided for comparison. A species checklist and distribution summary for the genus is provided. Notes on other South American species of Deltocephalini with supernumerary forewing crossveins are also provided.


A procedure using immobilized antibody for the isolation of the beta-subunit of human chorionic gonadotropin from the culture fluid of a beta-subunit-secreting nontrophoblastic cell line.
Antibody produced against the beta-subunit of hCG was linked to Sepharose 4B and used to isolate ectopic hCG beta secreted by DoT cervical cancer cells in culture. beta-Subunit was eluted with 3 M guanidine-hydrochloride, pH 3.0 (three treatments, 15 min each, at 20 C). The eluted hCG beta was desalted with Sephadex G-25 and concentrated by lyophilization. A single batch of antibody-bound Sepharose was used repeatedly to adsorb hCG beta from liter quantities of spent culture fluid containing 10% fetal bovine serum. The material recovered from 15.75 liters of fluid was pooled and treated a second time with immobilized antibody. Using only immobilized antibody, purification of more than 200,000-fold was achieved, with an overall recovery of about 28%.


Cutaneous exposure to lewisite causes acute kidney injury by invoking DNA damage and autophagic response.
Lewisite (2-chlorovinyldichloroarsine) is an organic arsenical chemical warfare agent that was developed and weaponized during World Wars I/II. Stockpiles of lewisite still exist in many parts of the world and pose potential environmental and human health threat. Exposure to lewisite and similar chemicals causes intense cutaneous inflammatory response. However, morbidity and mortality in the exposed population is not only the result of cutaneous damage but is also a result of systemic injury. Here, we provide data delineating the pathogenesis of acute kidney injury (AKI) following cutaneous exposure to lewisite and its analog phenylarsine oxide (PAO) in a murine model. Both agents caused renal tubular injury, characterized by loss of brush border in proximal tubules and tubular cell apoptosis accompanied by increases in serum creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Interestingly, lewisite exposure enhanced production of reactive oxygen species (ROS) in the kidney and resulted in the activation of autophagic and DNA damage response (DDR) signaling pathways with increased expression of beclin-1, autophagy-related gene 7, and LC-3A/B-II and increased phosphorylation of γ-H2A.X and checkpoint kinase 1/2, respectively. Terminal deoxyribonucleotide-transferase-mediated dUTP nick-end labeling-positive cells were detected in renal tubules along with enhanced proapoptotic BAX/cleaved caspase-3 and reduced antiapoptotic BCL2. Scavenging ROS by cutaneous postexposure application of the antioxidant N-acetyl-l-cysteine reduced lewisite-induced autophagy and DNA damage. In summary, we provide evidence that topical exposure to lewisite causes AKI. The molecular mechanism underlying these changes involves ROS-dependent activation of autophagy and DDR pathway associated with the induction of apoptosis.


Distribution and antimicrobial resistance profile of bacteria recovered from sewage system of health institutions found in Hawassa, Sidama Regional State, Ethiopia: A descriptive study.
The aim of the study was to determine the distribution and antimicrobial susceptibility profile of bacteria recovered from the sewage systems of health institutions found in Hawassa, Sidama Regional State, Ethiopia. A cross-sectional study was conducted from 20 October 2020 to 1 December 2020. A total of 27 sewage samples were collected at two points, namely, before entering the septic tank and from the septic tank of seven health institutions. Samples were inoculated onto Mannitol salt agar, Blood agar, and MacConkey agar, and incubated for 24 h at 37°C. Bacteria were identified using colony morphology, Gram staining, and biochemical tests. An antimicrobial susceptibility test was performed using the Kirby-Bauer disk diffusion method. Data were analyzed by SPSS, version 25, and results were presented in text and tables. All sewage samples (n = 27) examined in the current study contained potential pathogenic bacteria. Overall, 129 different types of bacteria were identified. Of isolated bacteria, 14 (10.8%) were Gram positive, while 115 (89.2%) were Gram negative. The most prevalent bacteria were Escherichia coli (n = 27, 20.9%) followed by Shigella species (n = 26, 20.2%), Pseudomonas species (n = 25, 19.4%), Salmonella species (n = 25, 19.4%), Staphylococcus aureus (n = 14, 10.9%), and Klebsiella species (n = 12, 9.3%). All bacteria were susceptible to azithromycin. About 80% of bacteria were resistant to ampicillin, whereas greater than 80% of bacteria were susceptible to norfloxacin, ciprofloxacin, and gentamicin. All sewage systems of health institutions included in the current study contained different types of pathogenic bacteria, which are resistant to commonly prescribed antibiotics.


PCSK9 inhibitors: A new era of lipid lowering therapy.
Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein (LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsin-kexin type 9 (PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.


Structure of a short-chain dehydrogenase/reductase from Bacillus anthracis.
The crystal structure of a short-chain dehydrogenase/reductase from Bacillus anthracis strain `Ames Ancestor' complexed with NADP has been determined and refined to 1.87 Å resolution. The structure of the enzyme consists of a Rossmann fold composed of seven parallel β-strands sandwiched by three α-helices on each side. An NADP molecule from an endogenous source is bound in the conserved binding pocket in the syn conformation. The loop region responsible for binding another substrate forms two perpendicular short helices connected by a sharp turn.


Volar melanotic macules in a gardener: a case report and review of the literature.
Volar melanotic macules are asymptomatic, tan-brown to brownish-black macules found on the palms, fingers, soles, and/or toes of dark-skinned individuals and are infrequently reported in light-skinned individuals. Herein, we report the acquisition of multiple, brownish-black volar digital macules in a 63-year-old white woman and avid gardener that were noted after the onset of pruritic, chronic hand dermatitis over a 10-month period. She was healthy without any medical conditions or medications. No family history of intestinal polyposis or mucosal melanosis existed. At presentation, she had less than 20 brownish-black, 2- to 10-mm irregular macules over the volar aspect of the thumbs and index fingers, left greater than right hand, associated with erythema, scale, and a negative potassium hydroxide examination. In addition, she had melanotic macules of her lips, buccal mucosa, and conjuctiva. No nail or anogenital macules were found. Biopsy demonstrated a region of epidermal hyperplasia, hyperkeratosis, and interface dermatitis associated with melanophages and sparse lymphocytic infiltrate. Melanin staining revealed diffuse pan-epidermal hypermelanization, dermal melanin, and dendritic melanocytes, which expressed HMB-45. After 1-year follow-up and treatment with topical corticosteroid, the volar macules have faded to tan brown. Based on the location, avocation, and coexisting mucosal melanotic macules, an irritant phytodermatitis with postinflammatory hyperpigmentation was diagnosed in the setting of Laugier-Hunziker syndrome-a disorder denoted by macular hyperpigmentation of nail, volar, and/or mucosal surfaces in healthy adults. Volar melanotic macules can also complicate 5-flourouracil therapy, tinea pedis, and other inflammatory disorders; be associated with acral melanomas; or represent a cutaneous manifestation of systemic disease such as Addison disease, Peutz-Jegher syndrome, Leopard syndrome, Carney syndrome, AIDS, and neurofibromatosis.


A Lipid-Anchored NAC Transcription Factor Is Translocated into the Nucleus and Activates Glyoxalase I Expression during Drought Stress.
The plant-specific NAC (NAM, ATAF1/2, and CUC2) transcription factors (TFs) play a vital role in the response to drought stress. Here, we report a lipid-anchored NACsa TF in Medicago falcata MfNACsa is an essential regulator of plant tolerance to drought stress, resulting in the differential expression of genes involved in oxidation reduction and lipid transport and localization. MfNACsa is associated with membranes under unstressed conditions and, more specifically, is targeted to the plasma membrane through S-palmitoylation. However, a Cys26-to-Ser mutation or inhibition of S-palmitoylation results in MfNACsa retention in the endoplasmic reticulum/Golgi. Under drought stress, MfNACsa translocates to the nucleus through de-S-palmitoylation mediated by the thioesterase MtAPT1, as coexpression of APT1 results in the nuclear translocation of MfNACsa, whereas mutation of the catalytic site of APT1 results in colocalization with MfNACsa and membrane retention of MfNACsa. Specifically, the nuclear MfNACsa binds the glyoxalase I (MtGlyl) promoter under drought stress, resulting in drought tolerance by maintaining the glutathione pool in a reduced state, and the process is dependent on the APT1-NACsa regulatory module. Our findings reveal a novel mechanism for the nuclear translocation of an S-palmitoylated NAC in response to stress.


Integrated biomarker responses of the submerged macrophyte Vallisneria spiralis via hydrological processes from Lake Poyang, China.
Vallisneria spiralis, a widely distributed wetland plant, was used to reveal how the light intensity at the top of the plant, plant morphology and antioxidant enzyme activity respond to different hydrologic conditions from Lake Poyang, China. By designing a laboratory experiment simulating historical water levels of low, normal and high wetland plant submersion, this study aimed to elucidate the effects of different levels of flooding on growth and antioxidant enzyme activity for V. spiralis. The results showed that the plant crown light intensity of the treated group and control group (CG) first decreased and then increased along with the seasonal variation of the water level. The maximum and minimum values of the plant crown light intensity were observed in April and July, respectively. Similar to the CG, V. spiralis from the normal and low water level (LWL) groups was measured and had higher plant height growth in the flooding period from May to June, and the entire plant biomass also showed a steady growth trend in the same period. However, the plant growth of the high water level (HWL) group was lower during the whole simulation period, with negative growth in July. Antioxidant enzyme activities changed with the seasonal temperature, and the activity of the CG showed a rising trend. Compared with those of the CG, the antioxidant enzyme activities of the HWL group showed a 'bell shaped' trend, which was first significantly induced and then significantly inhibited. In addition, the peroxidase (POD) and catalase (CAT) activities from the LWL group in April were also significantly induced. The integrated biomarker response (IBR) index showed that a comprehensive biological index could well reflect the effects of seasonal water levels in Poyang Lake on the growth of the wetland plant V. spiralis. This study indicated that high flooding levels had the strongest negative effect on the growth and enzyme activity of the submerged plant V. spiralis.


Paradental cysts: a role for food impaction in the pathogenesis? A review of cases from Northern Ireland.
We present the clinical, radiographic and histological findings of 15 paradental cysts. These were the second most common type of cyst associated with mandibular third molars, comprising 25% of all lesions at this site. Ten patients were aged 30 years or younger and 13 gave a history of pericoronitis. There was a close relationship between the site of the cyst and the angle of the impacted tooth; the cyst lay mesially to two mesioangularly impacted teeth, buccal to two vertically impacted teeth and distal/distobuccal to the remainder, all but one of which were distoangular in impaction. The pericoronal follicular space was preserved in nine cases, a useful diagnostic sign. Most cysts were lined with epithelium that resembled that seen in radicular cysts, although the lining of three cysts resembled that of unicystic ameloblastoma, a potential diagnostic pitfall. We propose that the relation between location of cyst and angle of impaction points to a role for food impaction in the pathogenesis of paradental cysts.


Report of the 2003 pan-Canadian forum on cervical cancer prevention and control.
To develop evidence-based consensus recommendations on the delivery of cervical cancer screening, human papillomavirus (HPV) education, HPV testing, and the optimal tool for cervical cytology within the Canadian health system. Leading up to a forum held in Ottawa on November 21 and 22, 2003, 254 registrants reviewed position papers through a Web-based discussion group. Experts in program management, clinical practice, epidemiology, public health, economics, and women's health, representing 48 organizations, then participated in the 2-day forum to develop consensus recommendations. Writing groups prepared position papers on optimal methods for cervical cytology; education concerning HPV; HPV testing in primary screening; HPV testing as a triage tool in cytopathology; and delivery mechanisms for cervical screening. Systematic reviews were the primary source of evidence supplemented by literature searches. Feedback from Web-based discussions was incorporated into consecutive drafts of position papers. At the forum, recommendations and supporting evidence were presented, further debated in small-group sessions, and discussed in a plenary session. Despite divergent professional mandates and opinions, consensus was achieved on 15 recommendations across all areas. Final recommendations were posted to the Web for further input and circulated for written consensus by participants. The recommendations cover the use of new evidence and technologies in cervical cancer prevention in Canada and provide a framework for provision of HPV education, planning the implementation of new cervical screening technologies in Canada, the development of evaluation plans, and new research areas.


NIDR funding related to the presence of oral biology departments and source of basic science instruction.
The amount of research funds awarded to American dental schools by the National Institute of Dental Research (NIDR) in 1976 and 1977 was analyzed according to the schools' oral biology and basic science deparmental status. Four categories of schools were identified based on the presence or absence of oral biology programs (the ORB and NOB schools, respectively) and on medical school (-M) or dental school (-D) source of basic science instruction. This breakdown yielded 20 ORB-M schools, 7 ORB-D schools, 12 NOB-M schools, and 15 NOB-D schools. The ORB schools generated more than twice as much mean National Institute of Dental Research (NIDR) research funding per school as did the NOB schools. The rank order of funding in the four subgroups was ORB-M, NOB-D, ORB-D, and NOB-M. The rank order of NIDR research funding among these four subgroups was quite similar to the previously reported rank order of student National Board performance in the same subgroups.


Prevention of tick-borne diseases.
Tick-borne diseases are on the rise. Lyme borreliosis is prevalent throughout the Northern Hemisphere, and the same Ixodes tick species transmitting the etiologic agents of this disease also serve as vectors of pathogens causing human babesiosis, human granulocytic anaplasmosis, and tick-borne encephalitis. Recently, several novel agents of rickettsial diseases have been described. Despite an explosion of knowledge in the fields of tick biology, genetics, molecular biology, and immunology, transitional research leading to widely applied public health measures to combat tick-borne diseases has not been successful. Except for the vaccine against tick-borne encephalitis virus, and a brief campaign to reduce this disease in the former Soviet Union through widespread application of DDT, success stories in the fight against tick-borne diseases are lacking. Both new approaches to tick and pathogen control and novel ways of translating research findings into practical control measures are needed to prevent tick-borne diseases in the twenty-first century.


CD4+ T cells in inflammatory diseases: pathogenic T-helper cells and the CD69-Myl9 system.
CD4+ T cells not only direct immune responses against infectious micro-organisms but are also involved in the pathogenesis of inflammatory diseases. In the last two to three decades, various researchers have identified and characterized several functional CD4+ T-cell subsets, including T-helper 1 (Th1), Th2, Th9 and Th17 cells and regulatory T (Treg) cells. In this mini-review, we introduce the concept of pathogenic Th cells that induce inflammatory diseases with a model of disease induction by a population of pathogenic Th cells: the 'pathogenic Th population disease-induction model'. We will focus on Th2 cells that induce allergic airway inflammation-pathogenic Th2 cells (Tpath2 cells)-and discuss the nature of Tpath2 cells that shape the pathology of chronic inflammatory diseases. Various Tpath2-cell subsets have been identified and their unique features are summarized in mouse and human systems. Second, we will discuss how Th cells migrate and are maintained in chronic inflammatory lesions. We propose a model known as the 'CD69-Myl9 system'. CD69 is a cell surface molecule expressed on activated T cells and interaction with its ligand myosin light chain 9 (Myl9) is required for the induction of inflammatory diseases. Myl9 molecules in the small vessels of inflamed lungs may play a crucial role in the migration of activated T cells into inflammatory lesions. Emerging evidence may provide new insight into the pathogenesis of chronic inflammatory diseases and contribute to the development of new therapeutic strategies for intractable inflammatory disorders.


Residency Program Directors' Interview Methods and Satisfaction With Resident Selection Across Multiple Specialties.
Competition for postdoctoral training positions is at an all-time high, and residency program directors continue to have little direction when it comes to structuring an effective interview process. To examine whether a relationship existed between interview methods used and program director satisfaction with resident selection decisions and whether programs that used methods designed to assess candidate personal characteristics were more satisfied with their decisions. Residency directors from the Statewide Campus System at the Michigan State University College of Osteopathic Medicine were invited to complete a 20-item survey regarding their recent interview methods and proportion of resident selections later regretted. Data analyses examined relationships between interview methods used, frequency of personal characteristics evaluated, and subsequent satisfaction with selected residents. Of the 186 program director surveys distributed, 83 (44.6%) were returned, representing 11 clinical specialty areas. In total, 69 responses (83.1%) were from programs accredited by the American Osteopathic Association only, and 14 (16.9%) were from programs accredited dually by the American Osteopathic Association and Accreditation Council for Graduate Medical Education. The most frequent interview method reported was faculty or peer resident interview. No statistically significant correlational relationships were found between type of interview methods used and subsequent satisfaction with selected residents, either within or across clinical specialties. Although program directors rated ethical behavior/honesty as the most highly prioritized characteristic in residents, 27 (32.5%) reported using a specific interview method to assess this trait. Program directors reported later regrets concerning nearly 1 of every 12 resident selection decisions. The perceived success of an osteopathic residency program's interview process does not appear to be related to methods used and is not distinctively different from that of programs dually accredited. The findings suggest that it may not be realistic to aim for standardization of a common set of best interview methods or ideal personal characteristics for all programs. Each residency program's optimal interview process is likely unique, more dependent on analyzing why some resident selections are regretted and developing an interview process designed to assess for specific desirable and unwanted characteristics.


Omidenepag isopropyl for the treatment of glaucoma and ocular hypertension.
Glaucoma is a main cause of irreversible vision impairment and its prevalence is expected to rise significantly in the near future. Among the current medications, prostaglandin analogues (PGAs) are widely used and considered as a first-line strategy in the management of glaucoma and ocular hypertension (OHT). However, given the non-negligible incidence of adverse ocular effects (conjunctival hyperemia, increase of iris pigmentation and eyelash changes) due to the use of this class of drugs, novel PGAs are being investigated. Omidenepag isopropyl is a selective prostaglandin EP2 receptor agonist which was approved on September 21, 2018, in Japan for the treatment of glaucoma and OHT. In this review, we will discuss its pharmacokinetics, pharmacodynamics and clinical efficacy, focusing also on its safety and tolerability profile.


Phytoremediation potential of water caltrop (Trapa natans L.) using municipal wastewater of the activated sludge process-based municipal wastewater treatment plant.
Phytoremediation experiments were carried out to assess the phytoremediation potential of water caltrop (Trapa natans L.) using municipal wastewater collected from the activated sludge process- (ASP) based municipal wastewater treatment plant. The results revealed that T. natans significantly (P ≤ .05/P ≤ .01/P ≤ .001) reduced the contents of total dissolved solids (TDS), electrical conductivity (EC), biochemical oxygen demand (BOD5), chemical oxygen demand, total Kjeldahl nitrogen, phosphate ([Formula: see text]), sodium (Na+), potassium (K+), calcium (Ca2+), magnesium (Mg2+), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), lead (Pb), zinc (Zn), standard plate count, and most probable number of the municipal wastewater after phytoremediation experiments. The maximum removal of these parameters was obtained at 60 days of the phytoremediation experiments, but the removal rate of these parameters was gradually increased from 15 to 45 days and it was slightly decreased at 60 days. Most contents of Cd, Cu, Fe, Mn and Zn were translocated in the leaves of T. natans, whereas most contents of Cr and Pb were accumulated in the root of T. natans after phytoremediation experiments. The contents of different biochemical components were recorded in the order of total sugar > crude protein > total ash > crude fiber > total fat in T. natans after phytoremediation of municipal wastewater. Therefore, T. natans was found to be effective for the removal of different parameters of municipal wastewater and can be used effectively to reduce the pollution load of municipal wastewater drained from the ASP-based treatment plants.


The patient care evaluation system: patients' perception of anesthetic care.
Our department's Patient Care Evaluation Survey was developed to measure the patients' perception of the care they received by our anesthesia caregivers (attending physicians, residents, and certified registered nurse anesthetists [CRNAs]), and identify those areas of patient contact which might require improvement in the delivery of anesthesia. The survey instrument (a personal letter sent by the chairman), is mailed to randomly selected patients two weeks following discharge from the hospital or ambulatory surgery center. Patients rated the anesthesia care they received from one (poor) to 10 (excellent) in three areas: the preoperative visit, the postoperative visit, and overall satisfaction. From October 1986 to October 1991, a total of 2,374 (n = 2,374) questionnaires representing a random sample of 99,964 anesthetics, were sent to patients. Fifty-four percent or 1,291/2,374 patients returned the survey. A high degree of patient satisfaction is seen for all categories: the preoperative visit, (mean score of 9.17 +/- 1.6); the postoperative visit (8.33 +/- 2.7); and overall satisfaction (9.15 +/- 1.7). Of the responses returned, 0.9% of the patients surveyed rated their interaction with the department as unsatisfactory in all three areas; 2.6% in two areas; 10.8% in at least one area. The Patient Care Evaluation system has served as an important means of feedback for medical, educational, and administrative goals of the department.


[The art of touch. Elisabeth Caland and the physio-aesthetics of piano playing].
The issue of how it is possible to play the piano without striking it was raised by Chopin: one must 'caresser' and not 'frapper' the piano. In her teachings on the art of piano playing, Elisabeth Caland (1862-1929) attempts to articulate a scientifically grounded solution to this complex (kin-)aesthetic problem. The solution turns on her intuitively discovered 'lowering of the shoulderblades' which was documented in 1904, through X-rays, by the Berlin physiologist René du Bois-Reymond, and recorded as a way of coordinating movement which had been unknown to physiology up to that time. Caland's physio-aesthetic of piano playing, which she worked out on the basis of du Bois-Reymond's observations, turns on the ideal of 'floating sound' put forward by her teacher Ludwig Deppe, and on Ferruccio Busoni's technique of piano playing. Her method makes essential use of what Feldenkrais would later call the 'sixth sense' (i.e. proprioceptive perception); in fact, it represents the first modern kinaesthetically based conception of piano playing. Caland's doctrine of touch was ahead of its time and it virtually disappeared from discussions of piano technique after 1930. But it has become accessible again through reprints of her most important writings: Deppe's doctrine of piano playing (1897), Sources of power in piano playing (1904), and Artistic piano playing (1910).


Reducing the Energy Band Gap of Cobalt Hydroxide Nanosheets with Silver Atoms and Enhancing Their Electrical Conductivity with Silver Nanoparticles.
Although cobalt hydroxide (Co(OH)2) has been attracting attention in several applications, its photoelectrochemical property has not yet been fully investigated. In this work, tuning the energy band gap of Co(OH)2 nanosheets with silver atoms and enhancing their electrical conductivity with silver nanoparticles were then focused. A Ag-doped α-Co(OH)2 thin film was successfully synthesized via an electrodeposition method. The optical properties of the as-prepared materials were characterized by UV-vis and fluorescence lifetime spectroscopies and further confirmed by density functional theoretical calculation. It was found that Ag atoms between adjacent layers of Co(OH)2 can reduce its electronic band gap to 2.45 eV (α-Co(OH)2) as compared to 2.85 eV of β-Co(OH)2. In terms of electrochemical properties, silver nanoparticles (AgNPs) can enhance the electrical conductivity of Co(OH)2 nanosheets, leading to faster charge transfer reducing the internal resistance and significantly increasing the overall charge storage performance. Interestingly, under light illumination, Ag-doped α-Co(OH)2 exhibits ca. 0.8 times lower charge storage capacity as compared to that under the dark condition. This is because the photoelectrons can be recombined with the generated holes in the conduction band. The charge storage mechanisms of Ag-doped α-Co(OH)2 operated under dark conditions and light irradiation were further studied and confirmed using in situ electrochemical X-ray absorption spectroscopy (XAS). Overall, the in situ XAS supports the electrochemical result. This finding may pave a way to further develop photoactive advanced functional materials of metal hydroxides and oxides.


Divergence-free WKB method.
A new semiclassical approach to the linear and nonlinear one-dimensional Schrödinger equation is presented. For both equations our zeroth-order solutions include nonperturbative quantum corrections to the WKB solution and the Thomas-Fermi solution, thereby allowing us to make uniformly converging perturbative expansions of the wave functions. Our method leads to a new quantization condition that yields exact eigenenergies for the harmonic-oscillator and Morse potentials.


Regioselective Ring Opening of Di-isopropylsilylenes Derived from 1,3-Diols with Alkyl Lithium Reagents.
The selective alkyl lithium-induced ring opening of 1,3-di-isopropylsilylenes is described. The reaction affords a differentially substituted 1,3-diol bearing a silane that resides at the oxygen in the more sterically demanding position. The reaction can be highly selective with a regiochemical preference up to >50:1 and likely proceeds via an alkoxy-silane intermediate. This intermediate can by trapped by methyl iodide to provide the corresponding silyl methyl ether, wherein the silane again resides at the oxygen in the more sterically demanding position.


[Association of polymorphism of 1800255 COL3A1 gene with pelvic organ prolapse and urinary incontinence in women: preliminary data].
Collagen type I and III have a significant role in the development of pelvic organ prolapse (POP) and urinary incontinence in women. The role of the COL3A1 gene polymorphism remains debatable. Some studies and meta-analyzes have found a direct correlation between genetic defects and POP, while other researchers have not confirmed this association. This study aimed to investigate the association of the 1800255 COL3A1 gene polymorphism with the development of POP and urinary incontinence in women. The study group comprised 52 patients (mean age 64.4 years) with verified POP and stress urinary incontinence. The control group included 21 patients without pelvic floor dysfunction. Patients were comparable in age and had at least one or more risk factors for developing pelvic floor dysfunction. Exclusion criteria for both groups were Marfan and Ehlers-Danlos syndromes and a history of surgery for POP or incontinence (for the control group). In all women, saliva samples were collected to detect polymorphism at the rs1800255 locus of the COL3A1 gene. Genotyping was conducted by Sanger sequencing. In patients with isolated genital prolapse, homozygous polymorphism (AA) had a low sensitivity (0.06) but an extremely high specificity (0.95). Heterozygote (GA) had the sensitivity of 0.35, the specificity of 0.53, and the AUC of 0.44. For urinary incontinence by homozygote (AA), sensitivity was 0.08, specificity 0.96, and by heterozygote (GA) 0.45 and 0.63, respectively. For the combination of pelvic prolapse and urinary incontinence by homozygote (AA), sensitivity was 0.07, specificity 1.0, and heterozygote (GA) 0.41 and 0.62, respectively. Given the high specificity of the polymorphism at the rs1800255 locus of the COL3A1 gene, determined by the Sanger sequencing, it can be concluded that there is an association between this polymorphism and urinary incontinence and POP in women.


Sus scrofa miR-204 and miR-4331 Negatively Regulate Swine H1N1/2009 Influenza A Virus Replication by Targeting Viral HA and NS, Respectively.
The prevalence of swine pandemic H1N1/2009 influenza A virus (SIV-H1N1/2009) in pigs has the potential to generate novel reassortant viruses, posing a great threat to human health. Cellular microRNAs (miRNAs) have been proven as promising small molecules for regulating influenza A virus replication by directly targeting viral genomic RNA. In this study, we predicted potential Sus scrofa (ssc-, swine) miRNAs targeting the genomic RNA of SIV-H1N1/2009 by RegRNA 2.0, and identified ssc-miR-204 and ssc-miR-4331 to target viral HA and NS respectively through dual-luciferase reporter assays. The messenger RNA (mRNA) levels of viral HA and NS were significantly suppressed when newborn pig trachea (NPTr) cells respectively overexpressed ssc-miR-204 and ssc-miR-4331 and were infected with SIV-H1N1/2009, whereas the suppression effect could be restored when respectively decreasing endogenous ssc-miR-204 and ssc-miR-4331 with inhibitors. Because of the importance of viral HA and NS in the life cycle of influenza A virus, ssc-miR-204 and ssc-miR-4331 exhibited an inhibition effect on SIV-H1N1/2009 replication. The antiviral effect was sequence-specific of SIV-H1N1/2009, for the target sites in HA and NS of H5N1 or H9N2 influenza A virus were not conserved. Furthermore, SIV-H1N1/2009 infection reversely downregulated the expression of ssc-miR-204 and ssc-miR-4331, which might facilitate the virus replication in the host. In summary, this work will provide us some important clues for controlling the prevalence of SIV-H1N1/2009 in pig populations.


Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients.
We report the findings from 4437 individuals (3219 patients and 1218 relatives) who have been analyzed by whole genome sequencing (WGS) at the Genomic Medicine Center Karolinska-Rare Diseases (GMCK-RD) since mid-2015. GMCK-RD represents a long-term collaborative initiative between Karolinska University Hospital and Science for Life Laboratory to establish advanced, genomics-based diagnostics in the Stockholm healthcare setting. Our analysis covers detection and interpretation of SNVs, INDELs, uniparental disomy, CNVs, balanced structural variants, and short tandem repeat expansions. Visualization of results for clinical interpretation is carried out in Scout-a custom-developed decision support system. Results from both singleton (84%) and trio/family (16%) analyses are reported. Variant interpretation is done by 15 expert teams at the hospital involving staff from three clinics. For patients with complex phenotypes, data is shared between the teams. Overall, 40% of the patients received a molecular diagnosis ranging from 19 to 54% for specific disease groups. There was heterogeneity regarding causative genes (n = 754) with some of the most common ones being COL2A1 (n = 12; skeletal dysplasia), SCN1A (n = 8; epilepsy), and TNFRSF13B (n = 4; inborn errors of immunity). Some causative variants were recurrent, including previously known founder mutations, some novel mutations, and recurrent de novo mutations. Overall, GMCK-RD has resulted in a large number of patients receiving specific molecular diagnoses. Furthermore, negative cases have been included in research studies that have resulted in the discovery of 17 published, novel disease-causing genes. To facilitate the discovery of new disease genes, GMCK-RD has joined international data sharing initiatives, including ClinVar, UDNI, Beacon, and MatchMaker Exchange. Clinical WGS at GMCK-RD has provided molecular diagnoses to over 1200 individuals with a broad range of rare diseases. Consolidation and spread of this clinical-academic partnership will enable large-scale national collaboration.


Physician Perceptions of Disposition Decision-making for Older Adults in the Emergency Department: A Preliminary Analysis.
Disposition decision-making in the emergency department (ED) is critical to patient safety and quality of care. Disposition decision-making has particularly important implications for older adults who comprise a significant portion of ED visits annually and are vulnerable to suboptimal outcomes throughout ED care transitions. We conducted a secondary inductive content analysis of interviews with ED physicians (N= 11) to explore their perceptions of who they involve in disposition decision-making and what information they use to make disposition decisions for older adults. ED physicians cited 7 roles (5 types of clinicians, patients and families) and 11 information types, both clinical (e.g. test/lab results) and non-clinical (e.g. family's preference). Our preliminary findings represent a key first step toward the development of interventions that promote patient safety and quality of care for older adults in the ED by supporting the cognitive and communicative aspects of disposition decision-making.


Wheat Albumin Increases the Ratio of Fat to Carbohydrate Oxidation during the Night in Healthy Participants: A Randomized Controlled Trial.
Not only are energy expenditure (EE) and the respiratory quotient (RQ) parameters of the energy nutrient utilization and energy balance, they are also related to the development of obesity. In this study, post-meal night-time energy metabolism was investigated following the oral ingestion of wheat albumin (WA) with a late evening meal. A randomly assigned, double-blind, placebo-controlled crossover trial for a single oral ingestion in healthy participants was completed. The participants ingested the placebo (PL) or WA (1.5 g) containing tablets 3 minutes before the late evening meal at 22:00 hour, and energy metabolism was measured using a whole-room indirect calorie meter until wake-up. The participants were in bed from 00:00 hour until 06:30 hour. Twenty healthy participants completed the trial and were included in the analyses. Night-time RQ and carbohydrate oxidation were significantly lower following the WA treatment as compared with the PL treatment. Although the total EE was not significantly different between treatments, postprandial fat oxidation was significantly higher following the WA treatment as compared with the PL treatment. In conclusion, WA has the potential to shift the energy balance to a higher ratio of fat to carbohydrate oxidation during the night.


Conditions during adulthood affect cohort-specific reproductive success in an Arctic-nesting goose population.
Variation in fitness between individuals in populations may be attributed to differing environmental conditions experienced among birth (or hatch) years (i.e., between cohorts). In this study, we tested whether cohort fitness could also be explained by environmental conditions experienced in years post-hatch, using 736 lifelong resighting histories of Greenland white-fronted geese (Anser albifrons flavirostris) marked in their first winter. Specifically, we tested whether variation in age at first successful reproduction, the size of the first successful brood and the proportion of successful breeders by cohort was explained by environmental conditions experienced on breeding areas in west Greenland during hatch year, those in adulthood prior to successful reproduction and those in the year of successful reproduction, using North Atlantic Oscillation indices as proxies for environmental conditions during these periods. Fifty-nine (8%) of all marked birds reproduced successfully (i.e., were observed on wintering areas with young) only once in their lifetime and 15 (2%) reproduced successfully twice or thrice. Variation in age at first successful reproduction was explained by the environmental conditions experienced during adulthood in the years prior to successful reproduction. Birds bred earliest (mean age 4) when environmental conditions were 'good' prior to the year of successful reproduction. Conversely, birds successfully reproduced at older ages (mean age 7) if they experienced adverse conditions prior to the year of successful reproduction. Hatch year conditions and an interaction between those experienced prior to and during the year of successful reproduction explained less (marginally significant) variation in age at first successful reproduction. Environmental conditions did not explain variation in the size of the first successful brood or the proportion of successful breeders. These findings show that conditions during adulthood prior to the year of successful reproduction are most important in determining the age at first successful reproduction in Greenland white-fronted geese. Very few birds bred successfully at all (most only once), which suggests that May environmental conditions on breeding areas have cohort effects that influence lifetime (and not just annual) reproductive success.


Contrasting immunological effects of two disparate dusts - preliminary observations.
Modern lifestyle and urbanization have been associated with a raised risk for atopic diseases whereas early and long-term exposure to a farm environment confers protection against atopic sensitization. Immunomodulatory potential and microbiological characteristics of settled airborne dust from an urban house and a barn were examined. Pulmonary inflammation was induced in mice by repeated intranasal administration of dusts. Monocyte-derived human dendritic cells (moDCs) were exposed to dusts followed by coculture with purified naïve T cells. Cytokine/chemokine mRNA and protein levels were analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry. The dusts were analyzed by cloning and sequencing of 16S rRNA genes (290 sequences) for DNA, lipids, endotoxin and beta-glucan, by live-dead staining, viable counting, isolation and identification of pure cultures (n = 76). Repeated exposure to house dust elicited pulmonary eosinophilia in mice whereas exposure to barn dust elicited neutrophilic and lymphocytic airway inflammation. Stimulation of moDCs with urban house dust elicited expression of Th2-promoting OX40L and Jagged-1 costimulatory molecules. Dendritic cells (DCs) exposed to house dust directed naïve T cells towards Th2 responses. Exposure of DCs to barn dust elicited the development of Th1-dominated immune responses. Urban house dust contained bacterial debris almost exclusively of human commensal species (corynebacteria, streptococci) whereas barn dust comprised mainly intact, viable bacteria of high diversity and no commensal species. Contact to debris originating from human commensal bacteria in urban house dust elicited a Th2-type response whereas barn dust with high bacterial diversity directed the cells towards a Th1 response.


Safety and Tolerability of Intravenous Push Lacosamide and Levetiracetam.
Background: Lacosamide and levetiracetam are antiseizure medications (ASMs) commonly utilized in the treatment and prevention of seizures. Historically, these agents have been administered as slow IV infusions after further dilution. Recent literature suggests that rapid administration via undiluted IV push may be safe and may increase efficiency of administration. Objective: This study aimed to evaluate the safety and tolerability of undiluted IV push lacosamide and levetiracetam over 5 min. Methods: This study was conducted as a single-centered, retrospective, observational cohort that analyzed the rapid administration of undiluted lacosamide and levetiracetam. Adult patients admitted from September 1st, 2019, to May 31st, 2020, receiving at least one administration of IV push lacosamide at any dose or levetiracetam at doses ≤ 1500 mg were evaluated. The primary safety outcomes were the incidence of hypotension and bradycardia. Results: A total of 86 subjects were evaluated; 36 patients were administered lacosamide, and 50 patients were administered levetiracetam. Hypotension or bradycardia occurred in 6 patients in the lacosamide group (16.6%) and 6 patients in the levetiracetam group (12.0%). There were no reported infusion site reactions. Among the subjects who received lacosamide and had a 12-lead electrocardiogram (EKG), there were no reported incidences of a prolonged PR interval. Conclusions: In this safety-analysis cohort, undiluted lacosamide and levetiracetam were not associated with significant adverse events when administered via IV push over 5 min. This seems to be a safe alternative method of administration to intermittent infusion. A larger, prospective cohort is needed to confirm these findings.


Molecular changes and signaling events occurring in spermatozoa during epididymal maturation.
After leaving the testis, spermatozoa have not yet acquired the ability to move progressively and are unable to fertilize oocytes. To become fertilization competent, they must go through an epididymal maturation process in the male, and capacitation in the female tract. Epididymal maturation can be defined as those changes occurring to spermatozoa in the epididymis that render the spermatozoa the ability to capacitate in the female tract. As part of this process, sperm cells undergo a series of biochemical and physiological changes that require incorporation of new molecules derived from the epididymal epithelium, as well as post-translational modifications of endogenous proteins synthesized during spermiogenesis in the testis. This review will focus on epididymal maturation events, with emphasis in recent advances in the understanding of the molecular basis of this process.


Transbronchial needle aspiration in the diagnosis of bronchogenic carcinoma.
Transbronchial needle aspiration (TBNA) was performed as a diagnostic procedure in 91 consecutive patients ultimately proven to have bronchogenic carcinoma. Results of TBNA were compared, in the same patients, to the diagnostic yield of cytologic examination of sputum, endobronchial brushings and washings, and endobronchial/transbronchial biopsy. The diagnostic yield for sputum was 13 percent (10 of 75); brushings, 40 percent (34 of 84); washings, 29 percent (26 of 89); biopsy, 56 percent (42 of 75); and TBNA, 45 percent (41 of 91). Aspirates were positive in 35 percent of patients with adenocarcinoma, 41 percent with squamous cell carcinoma, 52 percent with large cell undifferentiated carcinoma, and 55 percent of patients with small cell carcinoma. Carinal aspirates were positive in 54 percent (6 of 11); paratracheal aspirates, 57 percent (13 of 23); parabronchial aspirates, 39 percent (11 of 28); endobronchial, 78 percent (7 of 9), and peripheral mass or solitary pulmonary nodule, 40 percent (17 of 42). The overall diagnostic yield for brushings, washings, and biopsy was 64 percent. The addition of TBNA increased the yield to 71 percent. Bronchogenic carcinoma was diagnosed solely by TBNA in six patients, all with extrabronchial or extratracheal lesions. We conclude that TBNA increases the diagnostic yield of bronchoscopy, particularly in patients with extratracheal and extrabronchial lesions. An equally important observation is that TBNA fails to contribute significantly to the diagnosis of cancer in patients with lesions readily accessible by conventional bronchoscopic techniques. Exceptions to this observation include occasional patients with necrotic endobronchial tumors, submucosal lesions, and rarely patients with peripheral lung nodules or masses.


Pseudorotaxane capped mesoporous silica nanoparticles for 3,4-methylenedioxymethamphetamine (MDMA) detection in water.
Mesoporous silica nanoparticles loaded with fluorescein and capped by a pseudorotaxane, formed between a naphthalene derivative and cyclobis(paraquat-p-phenylene) (CBPQT4+), were used for the selective and sensitive fluorogenic detection of 3,4-methylenedioxymethamphetamine (MDMA).


Strain-dependent production of interleukin-17/interferon-γ and matrix remodeling-associated genes in experimental Candida albicans keratitis.
The aim of this study was to investigate the role of genetic background in determining the development or prognosis of experimental fungal keratitis by comparing the disease courses and related molecules of experimental Candida albicans in two common mouse strains. After intrastromal inoculation of 1 × 10(5)C. albicans blastospores into corneas of Balb/c and C57BL/6 mice, all mice developed typical keratitis. The disease was monitored using a slit lamp microscope and scored for comparison of symptoms. At desired time points, blood was collected and corneal homogenates were prepared for enzyme-linked immunosorbent assay measurement of interferon (IFN)γ or interleukin (IL)17. Other corneas were processed for histological evaluation, pathogen load measurement, or total RNA extraction, the last of which was subjected to reverse transcription in conjunction with real-time PCR to measure genes of interest in terms of collagens, matrix metalloproteinases (MMPs), and the tissue inhibitors of MMPs (TIMPs). The infected corneas from the two strains presented different manifestations. Corneal transparency was less affected in Balb/c mice than in C57BL/6 mice, and Balb/c corneas contained fewer pathogens than C57BL/6 corneas during the measured period (10 days). In both strains, keratitis started to resolve around days 7-10, but C57BL/6 mice healed slower than Balb/c mice as indicated by disease presentation, histology, and pathogen burden assay. By day 7 post infection, pseudohyphae were rare but cellular infiltration remained intensive in both strains. The surface of the Balb/c corneas remained relatively intact and smooth, and C57BL/6 corneal lesions produced open erosion areas. Perforation was never seen in the current study setting. In both sera and corneas, IL17 expression increased earlier than IFNγ, and C57BL/6 mice produced higher IL17 levels and lower IFNγ levels than Balb/c mice. Compared with C57BL/6 mice, Balb/c corneas produced more MMP-2, Col3a1, and Col4a1, and less or equivalent TIMP-2 at all detected time points. They also produced more MMP-13, less MMP-8, MMP-9, and TIMP-1 at day 3 post infection, but less MMP-13, basically equivalent MMP-8, and more MMP-9 at later time points. The disease course of experimental C. albicans keratitis depends on the genetic background of the host animals. The balance between IL17 and IFNγ, as well as among the common injury- and wound healing-related proteins, may contribute to the pathogenesis of C. albicans keratitis. This study suggests that great variance of disease presentation should be expected for human subjects with Candida keratitis.


Identification of novel dual acting ligands targeting the adenosine A2A and serotonin 5-HT1A receptors.
GPCRs are a family of transmembrane receptors that are profoundly linked to various neurological disorders, among which is Parkinson's disease (PD). PD is the second most ubiquitous neurological disorder after Alzheimer's disease, characterized by the depletion of dopamine in the central nervous system due to the impairment of dopaminergic neurons, leading to involuntary movements or dyskinesia. The current standard of care for PD is Levodopa, a dopamine precursor, yet the chronic use of this agent can exacerbate motor symptoms. Recent studies have investigated the effects of combining A2AR antagonist and 5-HT1A agonist on dyskinesia and motor complications in animal models of PD. It has been proved that the drug combination has significantly improved involuntary movements while maintaining motor activity, highlighting as a result new lines of therapy for PD treatments, through the regulation of both receptors. Using a combination of ligand-based pharmacophore modelling, virtual screening, and molecular dynamics simulation, this study intends on identifying potential dual-target compounds from IBScreen. Results showed that the selected models displayed good enrichment metrics with a near perfect receiver operator characteristic (ROC) and Area under the accumulation curve (AUAC) values, signifying that the models are both specific and sensitive. Molecular docking and ADMET analysis revealed that STOCK2N-00171 could be potentially active against A2AR and 5-HT1A. Post-MD analysis confirmed that the ligand exhibits a stable behavior throughout the simulation while maintaining crucial interactions. These results imply that STOCK2N-00171 can serve as a blueprint for the design of novel and effective dual-acting ligands targeting A2AR and 5-HT1A.Communicated by Ramaswamy H. Sarma.


Central nervous system decompression sickness: latency of 1070 human cases.
Many aspects of central nervous system (CNS) decompression sickness (DCS) are poorly understood, including the temporal pattern of its presentation and the pathogenic mechanisms involved in the development of the disease. Using case histories and clinical series published in the literature and retrieved from treatment center records, this study is an attempt to define the interval between surfacing from a hyperbaric exposure and the onset of symptoms of CNS DCS. The results of 1070 cases of human CNS DCS were included in the study. The results show that the disease generally occurs rapidly: over 50% became symptomatic within 10 min of returning to 1 ATA, and in only 15% of cases was the onset of symptoms delayed for more than 1 h. Cerebral DCS had a more rapid onset than spinal cord disease: 50% of cerebral cases became apparent within about 3 min and a similar proportion of spinal cord cases within about 9 min from surfacing. The influence of these results on the diagnosis and treatment of dysbaric illness, on the safety of certain diving practices, and on possible pathogenic mechanisms is discussed.


Measurement of surface temperature and emissivity of different materials by two-colour pyrometry.
An experimental investigation is performed to substantiate the capability of a charge coupled device camera to measure local temperature and emissivity of different materials heated to temperatures above 500 °C by two-colour pyrometric technique using colorimetric method. Materials investigated are Inconel 718 with pyromark (high temperature paint), Inconel 718, stainless steel SS 304 and SS 316. Centerline temperature and emissivity distribution is obtained for target plates maintained at constant temperature by AC heating while complete temperature and emissivity distribution is provided for plates heated by flame impingement. The obtained results are compared with a calibrated infrared camera and thermocouples and the temperature distribution is found to be in close agreement. These results pertain to partially oxidized metal alloys covered in this study. Deviation in the measurement of emissivity can be attributed to its dependence on wavelength range, oxidation, and sensitivity of the image detector.


Current status and future challenges of chlorobenzenes pollution in soil and groundwater (CBsPSG) in the twenty-first century: a bibliometric analysis.
The global industrial structure had undertaken significant changes since the twenty-first century, making a severe problem of chlorobenzene pollution in soil and groundwater (CBsPSG). CBsPSG receives increasing attention due to the high toxicity, persistence, and bioaccumulation of chlorobenzenes. To date, despite the gravity of this issue, no bibliometric analysis (BA) of CBsPSG does exist. This study fills up the gap by conducting a BA of 395 articles related to CBsPSG from the Web of Science Core Collection database using CiteSpace. Based on a comprehensive analysis of various aspects, including time-related, related disciplines, keywords, journal contribution, author productivity, and institute and country distribution, the status, development, and hotspots of research in the field were shown visually and statistically. Moreover, this study has also delved into the environmental behavior and remediation techniques of CBsPSG. In addition, four challenges (unequal research development, insufficient cooperation, deeply mechanism research, and developing new technologies) have been identified, and corresponding suggestions have been proposed for the future development of research in the field. Afterwards, the limitations of BA were discussed. This work provides a powerful insight into CBsPSG, enabling to quickly identify the hotspot and direction of future studies by relevant researchers.


A variable-radius measure of local hospital market structure.
To provide a radius measure of the structure of local hospital markets that varies with hospital characteristics and is available for all hospitals in the United States. 1982 American Hospital Association (AHA) Survey of Hospitals, 1982 Area Resource File (ARF), and 1983 California Office of Statewide Health Planning and Development (OSHPD) discharge abstracts. The OSHPD data were used to measure the radii necessary to capture 75 percent and 90 percent of each hospital's admissions. These radii were used as the dependent variables in regression models in which the independent variables were from the AHA and ARF. To estimate predicted market radii, the estimated parameters from the California models were applied to all nonfederal, short-term, general hospitals in the continental United States. These radii were used to define each hospital's service area, and all other hospitals within the calculated radii were considered potential competitors. Using this definition, we calculated two measures of local market structure: the number of other hospitals within the radius and a Herfindahl-Hirschman Index based on the distribution of hospital bed shares in the market. These measures were calculated for all nonfederal, short-term, acute care hospitals in the continental United States for whom complete data were available (N = 4,884). These measures are available from the authors on computer-readable diskette, matched to hospital identifiers.


Concurrent 2009 pandemic influenza A (H1N1) virus infection in ferrets and in a community in Pennsylvania.
We report a fall 2010 cluster of pandemic influenza A/H1N1 (pH1N1) infections in pet ferrets in Lehigh Valley region of Pennsylvania. The ferrets were associated with one pet shop. The influenza cluster occurred during a period when the existing human surveillance systems had identified little to no pH1N1 in humans in the Lehigh Valley, and there were no routine influenza surveillance systems for exotic pets. The index case was a 2.5-month-old neutered male ferret that was presented to a veterinary clinic with severe influenza-like illness (ILI). In response to laboratory notification of a positive influenza test result, and upon request from the Pennsylvania Department of Health (PADOH), the Pennsylvania Department of Agriculture (PDA) conducted an investigation to identify other ill ferrets and to identify the source and extent of infection. PDA notified the PADOH of the pH1N1 infection in the ferrets, leading to enhanced human surveillance and the detection of pH1N1 human infections in the surrounding community. Five additional ferrets with ILI linked to the pet shop were identified. This simultaneous outbreak of ferret and human pH1N1 demonstrates the important link between animal health and public health and highlights the potential use of veterinary clinics for sentinel surveillance of diseases shared between animals and humans.


Preliminary use of a hydrogel containing enzymes in the treatment of stage II and stage III pressure ulcers.
Considerable progress has been made in the prevention and treatment of pressure ulcers but they remain a significant healthcare problem, particularly among the elderly. Treatment may include the use of wound dressings such as hydrogels as well as debridement products that contain relatively high concentrations of various enzymes. Unlike enzymes found in debridement products, low concentrations of endopeptidase enzymes can cleave to denatured proteins. Many endopeptidases have been reported to enhance the healing process. To evaluate the effect of a hydrogel wound dressing containing a combination of endopeptidases on pressure ulcers, a 12-week prospective preliminary study was conducted involving 10 nursing home patients with Stage II (n = 3) or Stage III (n = 7) ulcers that had failed to respond to previous treatments. Seven subjects (three with Stage II ulcers and four with Stage III ulcers) completed the study. Healing was based on wound closure by re-epithelialization as determined by area measurement and clinical assessment. All three Stage II ulcers and two of the Stage III ulcers healed completely; four Stage III ulcers were categorized as healing (>60% improvement) after 12 weeks of care. No dressing-related adverse events occurred and subject acceptance of the product, including comfort, was high. These results suggest that additional studies designed to define the possible contribution of endopeptidase enzymes in wound healing are warranted.


Common and distinct modulation of electrophysiological indices of feedback processing by autistic and psychopathic traits.
Both autism spectrum disorder (ASD) and psychopathy are primarily characterized by social dysfunction; overlapping phenotypic features may reflect altered function in common brain mechanisms. The current study examined the degree to which neural response to social and nonsocial feedback is modulated by autistic versus psychopathic traits in a sample of typically developing adults (N = 31, 11 males, 18-52 years). Event-related potentials were recorded whilst participants completed a behavioral task and received feedback on task performance. Both autistic and psychopathic traits were associated with alterations in the neural correlates of feedback processing. Sensitivity to specific forms of feedback (social, nonsocial, positively valenced, negatively valenced) differed between the two traits. Autistic traits were associated with decreased sensitivity to social feedback. In contrast, the antisocial domain of psychopathic traits was associated with an overall decrease in sensitivity to feedback, and the interpersonal manipulation domain was associated with preserved processing of positively valenced feedback. Results suggest distinct alterations within specific mechanisms of feedback processing may underlie similar difficulties in social behavior.


Non-invasive brain stimulation in neurological diseases.
Non-invasive brain stimulation has shown its potential to modulate brain plasticity in humans. Endeavour has been made to utilize brain stimulation in neurological diseases to enhance adaptive processes and prevent potential maladaptive ones. In stroke for instance both sensorimotor and higher cognitive impairment, such as aphasia and neglect, has been addressed to facilitate functional recovery. In Parkinson's disease, brain stimulation has been evaluated to improve motor and non-motor symptoms. In the present review we provide an update of the field of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) as non-invasive brain stimulation techniques to improve motor and higher cognitive functions in patients suffering from stroke and Parkinson's disease. Rather than attempting to be comprehensive in regard of the reviewed scientific field, this article may be considered as a present day's framework of the application of non-invasive brain stimulation on selected examples of common neurological diseases. At the end we will briefly discuss open controversies and future directions of the field which has to be addressed in upcoming studies. This article is part of a Special Issue entitled 'Cognitive Enhancers'.


Highly Sensitive, Flexible, and Wearable Pressure Sensor Based on a Giant Piezocapacitive Effect of Three-Dimensional Microporous Elastomeric Dielectric Layer.
We report a flexible and wearable pressure sensor based on the giant piezocapacitive effect of a three-dimensional (3-D) microporous dielectric elastomer, which is capable of highly sensitive and stable pressure sensing over a large tactile pressure range. Due to the presence of micropores within the elastomeric dielectric layer, our piezocapacitive pressure sensor is highly deformable by even very small amounts of pressure, leading to a dramatic increase in its sensitivity. Moreover, the gradual closure of micropores under compression increases the effective dielectric constant, thereby further enhancing the sensitivity of the sensor. The 3-D microporous dielectric layer with serially stacked springs of elastomer bridges can cover a much wider pressure range than those of previously reported micro-/nanostructured sensing materials. We also investigate the applicability of our sensor to wearable pressure-sensing devices as an electronic pressure-sensing skin in robotic fingers as well as a bandage-type pressure-sensing device for pulse monitoring at the human wrist. Finally, we demonstrate a pressure sensor array pad for the recognition of spatially distributed pressure information on a plane. Our sensor, with its excellent pressure-sensing performance, marks the realization of a true tactile pressure sensor presenting highly sensitive responses to the entire tactile pressure range, from ultralow-force detection to high weights generated by human activity.


Isolation and Characterization of the Colletotrichum acutatum ABC Transporter CaABC1.
Fungi tolerate exposure to various abiotic stresses, including cytotoxic compounds and fungicides, via their ATP-driven efflux pumps belonging to ATP-binding cassette (ABC) transporters. To clarify the molecular basis of interaction between the fungus and various abiotic stresses including fungicides, we constructed a cDNA library from germinated conidia of Colletotrichum acutatum, a major anthracnose pathogen of pepper (Capsicum annum L.). Over 1,000 cDNA clones were sequenced, of which single clone exhibited significant nucleotide sequence homology to ABC transporter genes. We isolated three fosmid clones containing the C. acutatum ABC1 (CaABC1) gene in full-length from genomic DNA library screening. The CaABC1 gene consists of 4,059 bp transcript, predicting a 1,353-aa protein. The gene contains the typical ABC signature and Walker A and B motifs. The 5'-flanking region contains a CAAT motif, a TATA box, and a Kozak region. Phylogenetic and structural analysis suggested that the CaABC1 is a typical ABC transporter gene highly conserved in various fungal species, as well as in Chromista, Metazoans, and Viridiplantae. We also found that CaABC1 was up-regulated during conidiation and a minimal medium condition. Moreover, CaABC1 was induced in iprobenfos, kresoxim-methyl, thiophanate-methyl, and hygromycin B. These results demonstrate that CaABC1 is necessary for conidiation, abiotic stress, and various fungicide resistances. These results will provide the basis for further study on the function of ABC transporter genes in C. acutatum.


Lixisenatide as add-on treatment among patients with different β-cell function levels as assessed by HOMA-β index.
The effect of lixisenatide-a prandial once-daily glucagon-like peptide-1 receptor agonist-on glycaemic control in patients with inadequately controlled type 2 diabetes mellitus (T2DM), stratified by baseline β-cell function, was assessed. The 24-week GetGoal-M, -P and -S trials evaluated the efficacy and safety of lixisenatide in combination with oral antidiabetic agents. This post hoc analysis used data from patients receiving lixisenatide in these trials, divided into matched cohorts by propensity scoring, and stratified according to baseline homeostasis model assessment of β-cell function (HOMA-β) index levels, high HOMA-β: > median HOMA-β (28.49%); low HOMA-β: ≤ median. The matched "low" and "high" HOMA-β index cohorts (N = 546 patients) had comparable baseline parameters. Mean change from baseline in glycated haemoglobin (HbA1c ) was -0.85% and -0.94% for low and high HOMA-β cohorts, respectively (P = .2607). Reductions from baseline in fasting plasma glucose (FPG; -0.77 vs -1.04 mmol/L; P = .1496) and postprandial plasma glucose (PPG; -5.82 vs -5.61 mmol/L; P = .7511) were similar in the low versus high HOMA-β index cohorts. Reduction in body weight was significantly greater in the low versus high HOMA-β index cohort (-2.06 vs -1.13 kg, respectively; P = .0006). In patients with T2DM, lixisenatide was associated with reduction in HbA1c and improvements in both FPG and PPG, regardless of β-cell function, indicating that lixisenatide is effective in reducing hyperglycaemia, even in patients with more advanced stages of T2DM and poor residual β-cell function.


Experimental approaches to chronic wounds.
The pathogenesis of most chronic wounds is unknown. In this report, we summarize several areas of investigation which appear ready for further progress and which were discussed at a recent National Institutes of Health workshop on this subject. Of note were presentations of research on the role of fibrosis in wound healing, interaction of cytokines, hypoxia, extracellular matrix formation, keratinocyte migration, and involvement of proteases and neuropeptides in chronic wounds.


Iron oxide magnetic nanoparticles as antimicrobials for therapeutics.
The use of iron oxide magnetic nanoparticles (IMNP) in medical and pharmaceutical areas dates to the beginning of the 1970s, as carriers. Some other uses to these nanoparticles are in vitro separation, magnetic resonance imaging and drug targeting agent. Many preparations containing IMNP have been described and used in drug delivery, hyperthermia, in vitro separation, tissue repair, cellular therapy, for magnetic separation, magnetic resonance imaging, as spoilers for magnetic resonance spectroscopy, and more recently as sensors for metabolites and other biomolecules. The use of these nanostructures as antibacterial agents has also been reported, which could kill some bacteria species causing no damage to the human host cells. Recently, they have been used as hyperthermia agents to treat infections or cancer, which are more susceptible than the healthy host's cells. Engineering designs, physiochemical characteristics, biomedical applications of IMNP, toxicity and magnetic nanotoxicology have been discussed. However, the application of IMNP as antimicrobials is very important. Thus, this review explores the therapeutic activities of IMNP and their use as antimicrobial agents. These nanoparticles can be efficient for the treatment of microbial infections, probably acting as membrane permeability enhancer, damaging the cell wall or by generating reactive oxygen species.


Transfer of dynamic motor skills acquired during isometric training to free motion.
Recent studies have explored the prospects of learning to move without moving, by displaying virtual arm movement related to exerted force. However, it has yet to be tested whether learning the dynamics of moving can transfer to the corresponding movement. Here we present a series of experiments that investigate this isometric training paradigm. Subjects were asked to hold a handle and generate forces as their arms were constrained to a static position. A precise simulation of reaching was used to make a graphic rendering of an arm moving realistically in response to the measured interaction forces and simulated environmental forces. Such graphic rendering was displayed on a horizontal display that blocked their view to their actual (statically constrained) arm and encouraged them to believe they were moving. We studied adaptation of horizontal, planar, goal-directed arm movements in a velocity-dependent force field. Our results show that individuals can learn to compensate for such a force field in a virtual environment and transfer their new skills to the actual free motion condition, with performance comparable to practice while moving. Such nonmoving techniques should impact various training conditions when moving may not be possible.NEW & NOTEWORTHY This study provided early evidence supporting that training movement skills without moving is possible. In contrast to previous studies, our study involves 1) exploiting cross-modal sensory interactions between vision and proprioception in a motionless setting to teach motor skills that could be transferable to a corresponding physical task, and 2) evaluates the movement skill of controlling muscle-generated forces to execute arm movements in the presence of external forces that were only virtually present during training.


Electromagnetic hypersensitivity: a critical review of explanatory hypotheses.
Electromagnetic hypersensitivity (EHS) is a condition defined by the attribution of non-specific symptoms to electromagnetic fields (EMF) of anthropogenic origin. Despite its repercussions on the lives of its sufferers, and its potential to become a significant public health issue, it remains of a contested nature. Different hypotheses have been proposed to explain the origin of symptoms experienced by self-declared EHS persons, which this article aims to review. As EHS is a multi-dimensional problem, and its explanatory hypotheses have far-reaching implications, a broad view was adopted, not restricted to EHS literature but encompassing all relevant bodies of research on related topics. This could only be achieved through a narrative approach. Two strategies were used to identify pertinent references. Concerning EHS, a complete bibliography was extracted from a 2018 report from the French Agency for Food, Environmental and Occupational Health & Safety and updated with more recent studies. Concerning related topics, the appropriate databases were searched. Systematic reviews and expert reports were favored when available. Three main explanatory hypotheses appear in the literature: (1) the electromagnetic hypothesis, attributing EHS to EMF exposure; (2) the cognitive hypothesis, assuming that EHS results from false beliefs in EMF harmfulness, promoting nocebo responses to perceived EMF exposure; (3) the attributive hypothesis, conceiving EHS as a coping strategy for pre-existing conditions. These hypotheses are successively assessed, considering both their strengths and limitations, by comparing their theoretical, experimental, and ecological value. No hypothesis proves totally satisfying. Avenues of research are suggested to help decide between them and reach a better understanding of EHS.


Migration patterns of HIV-1 subtype B virus in Northern Italy.
Gene flow analysis is used to identify the migration patterns of viruses within a geographical area and /or in different populations. 883 HIV-1 B subtype pol gene sequences were analyzed. The gene analysis among different geographical areas of the Bergamo district and from different transmission risk groups showed 25% of the observed gene flow was from people living in the north valleys to lowland and 40.5% from a heterosexual risk group to injecting drug users. Injecting drug users seem to be the central link, mercenary sex being the common route of transmission (and gene flow) between this group and both heterosexual and homosexual individuals.


Rosiglitazone Reverses Inflammation in Epididymal White Adipose Tissue in Hormone-Sensitive Lipase-Knockout Mice.
Hormone-sensitive lipase (HSL) plays a crucial role in intracellular lipolysis, and loss of HSL leads to diacylglycerol (DAG) accumulation, reduced FA mobilization, and impaired PPARγ signaling. Hsl knockout mice exhibit adipose tissue inflammation, but the underlying mechanisms are still not clear. Here, we investigated if and to what extent HSL loss contributes to endoplasmic reticulum (ER) stress and adipose tissue inflammation in Hsl knockout mice. Furthermore, we were interested in how impaired PPARγ signaling affects the development of inflammation in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT) of Hsl knockout mice and if DAG and ceramide accumulation contribute to adipose tissue inflammation and ER stress. Ultrastructural analysis showed a markedly dilated ER in both eWAT and iWAT upon loss of HSL. In addition, Hsl knockout mice exhibited macrophage infiltration and increased F4/80 mRNA expression, a marker of macrophage activation, in eWAT, but not in iWAT. We show that treatment with rosiglitazone, a PPARγ agonist, attenuated macrophage infiltration and ameliorated inflammation of eWAT, but expression of ER stress markers remained unchanged, as did DAG and ceramide levels in eWAT. Taken together, we show that HSL loss promoted ER stress in both eWAT and iWAT of Hsl knockout mice, but inflammation and macrophage infiltration occurred mainly in eWAT. Also, PPARγ activation reversed inflammation but not ER stress and DAG accumulation. These data indicate that neither reduction of DAG levels nor ER stress contribute to the reversal of eWAT inflammation in Hsl knockout mice.


ATG4A promotes tumor metastasis by inducing the epithelial-mesenchymal transition and stem-like properties in gastric cells.
The metastasis of tumor cells to distant organs is an ominous feature of gastric cancer. However, the molecular mechanisms underlying the invasion and metastasis of gastric cancer cells remain elusive. In this study, we found that the expression of ATG4A, an autophagy-regulating molecule, was significantly increased in gastric cancer tissues and was significantlycorrelated with the gastric cancer differentiation degree, tumor invasion and lymph node metastasis. ATG4A over-expression significantly promoted gastric cancer cell migration and invasion in vitro and metastasis in vivo, as well as promoted gastric cancer cell stem-like properties and the epithelial-mesenchymal transition (EMT) phenotype. By contrast, ATG4A knockdown inhibited the migration, invasion and metastasis of cancer cells, as well as the stem-like properties and EMT phenotype. Mechanistically, ATG4A promotes gastric cancer cell stem-like properties and the EMT phenotype through the activation of Notch signaling not via autophagy, and using the Notch signaling inhibitor DAPT attenuated the effects of ATG4A on gastric cancer cells. Taken together, these findings demonstrated that ATG4A promotes the metastasis of gastric cancer cells via the Notch signaling pathway, which is an autophagy-independent mechanism.


Thermal modulation of anthropogenic estrogen exposure on a freshwater fish at two life stages.
Human-mediated environmental change can induce changes in the expression of complex behaviors within individuals and alter the outcomes of interactions between individuals. Although the independent effects of numerous stressors on aquatic biota are well documented (e.g., exposure to environmental contaminants), fewer studies have examined how natural variation in the ambient environment modulates these effects. In this study, we exposed reproductively mature and larval fathead minnows (Pimephales promelas) to three environmentally relevant concentrations (14, 22, and 65ng/L) of a common environmental estrogen, estrone (E1), at four water temperatures (15, 18, 21, and 24°C) reflecting natural spring and summer variation. We then conducted a series of behavioral experiments to assess the independent and interactive effects of temperature and estrogen exposure on intra- and interspecific interactions in three contexts with important fitness consequences; reproduction, foraging, and predator evasion. Our data demonstrated significant independent effects of temperature and/or estrogen exposure on the physiology, survival, and behavior of larval and adult fish. We also found evidence suggesting that thermal regime can modulate the effects of exposure on larval survival and predator-prey interactions, even within a relatively narrow range of seasonally fluctuating temperatures. These findings improve our understanding of the outcomes of interactions between anthropogenic stressors and natural abiotic environmental factors, and suggest that such interactions can have ecological and evolutionary implications for freshwater populations and communities.


Advanced and rapidly progressing head and neck cancer: good palliation following intralesional bleomycin.
The authors herein report the case of a 61-year-old man undergoing adjuvant therapy for locally advanced laryngeal cancer, who developed parastomal recurrence in his radiation field around his tracheotomy site, while he was undergoing radiation therapy, and compromised the secure placement of his tracheotomy tube and maintenance of his upper airway. MRI restaging and biopsy confirmed recurrence and progressive disease in his mediastinum. He underwent local therapy with intralesional bleomycin with good palliation, and ability to maintain the patency of his upper airway.


Impact of traumatic dental injuries and malocclusions on quality of life of preschool children: a population-based study.
Few studies assessed the impact of traumatic dental injuries (TDI) and malocclusions on the oral health-related quality of life (OHRQoL) in preschool children. To assess the impact of the presence of TDI and malocclusions, as well as its severity and types, respectively, on the OHRQoL of preschool children. The study was conducted in 1215 children aged 1-4 years old who attended the National Day of Children Vaccination in Diadema, Brazil. Parents answered the Brazilian version of the Early Childhood Oral Health Impact Scale (B-ECOHIS) and socio-demographic conditions. Calibrated dental examiners performed the oral examinations for TDI and malocclusions. Poisson regression models adjusted by dental caries associated the clinical and socio-demographic conditions with the outcome. The multivariate adjusted models showed associations between some individual domains of the B-ECOHIS and clinical and socio-demographic conditions (P < 0.05). The severity of TDI showed a negative impact on the symptoms domain and self-image/social interaction domain (P < 0.05). Children with complicated TDI were more likely to experience a negative impact on total B-ECOHIS scores (PR = 2.10; P = 0.048). The presence of complicated TDI and dental caries were associated with worse OHRQoL of Brazilian preschool children, whereas malocclusions do not.