Effectiveness of a support program for balancing treatment and work in small and medium-sized enterprises promoted by occupational health nurses using a web meeting system: A cluster randomized controlled trial.
In this study, we conducted a cluster randomized control trial to verify the effectiveness of a treatment work balance support (TWBS) program promoted by occupational health nurses (OHNs) in small and medium-sized enterprises (SMEs) using a web meeting system. We analyzed data from 64 managers (32 each in the control and intervention groups) and 541 workers (246 and 295 in the control and intervention groups, respectively) from 22 SMEs (11 in each group) with less than 200 workers. The TWBS program comprised online consultations for managers and seminars for workers by an OHN. TWBS leaflets were distributed among both groups. The "Recognition and Attitude Scale toward TWBS" was administered and workplace climate, psychological safety (PS), and work engagement (WE) scores were measured at baseline and endpoint. The increase in scores of each group was analyzed using a linear mixed-effects model. Increases in managers' scores on all three recognition and attitude subscales were significantly greater in the intervention than in the control group (P = .048, .003, and .032, respectively). Workers' score increases were significantly higher on two subscales-recognition of workplace initiatives and understanding of professionals' roles-in the intervention than in the control group (P = .043 and .001, respectively). There was no difference between the two groups in the amount of increase in PS and WE, as perceived by managers and workers. The TWBS program by OHNs increased recognition and attitude among SME managers and workers, indicating the usability of promoting TWBS in SMEs.


[The male factor in the incidence and persistence of condyloma of the cervix and intraepithelial cervical neoplasms].
From 1988 to 1990, prospectively, were studied 113 masculine couples (males), and 113 women, treated for intraepithelial cervical neoplasia, alone, or associated to viral infection by human papilloma virus-80 males were asymptomatic (70.7%). Colposcopy and local application of acetic acid, were needed for the diagnosis of 69.9% of lesions, which presented with a gray color to a brilliant white color. Papulous lesion, (56.70%) was most frequent; and the classical lesions as condyloma acuminatum, were 15.52%; urethral cytology was positive for condyloma (one condyloma in 30%), and biopsies in 91.66%. There were persistence and recidiva, nonsignificant, when the man had received treatment suggesting that the treatment does not alter the appearance of condyloma, nor cervical intraepithelial, neoplasia.


Staphylococcus aureus nasal carriage in rheumatoid arthritis: antibody response to toxic shock syndrome toxin-1.
To determine the prevalence of Staphylococcus aureus nasal carriage and to compare antibody responses to two superantigens, staphylococcal toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA), in rheumatoid arthritis patients and normal subjects. 88 rheumatoid arthritis patients and 110 control subjects were cultured for nasal carriage of S aureus; 62 isolates were bacteriophage typed. Twenty five patients and 11 spouses were tested for antibodies to TSST-1, SEA, and sonicate extracts of Bacteroides fragilis and Escherichia coli; 19 patients were HLA-DR typed. 50% of patients and 33% of normal subjects were S aureus carriers. Bacteriophage typing of isolates suggested significant differences between strains isolated from the two groups. Patients showed higher IgG (P = 0.0025) and IgA (P = 0.0372) antibody levels to TSST-1 than normal spouses and these responses were not related to rheumatoid factor titres or HLA-DR type. When compared to normals, rheumatoid arthritis patients more often carry S aureus in their nasal vestibule, carry a distinct subpopulation of S aureus strains, and have higher average antibody levels to TSST-1.


Recent Advances and Challenges in the Design of Organic Photoacid and Photobase Generators for Polymerizations.
Photopolymerization, or the use of light to trigger polymerization, is one of the most exciting technologies for advanced manufacturing of polymers. One of the key components in the photopolymerization processes is the photoactive compound that absorbs the light, generating the active species that promotes the polymerization and largely determines the final properties of the material. The field of photopolymerization has been dominated by photoradical generators to mediate radical reactions. In the last decade, to expand the number of polymers that can be prepared by photopolymerization, intensive research has been devoted to the synthesis and utilization of photoactive molecules that are able to generate a base or an acid upon irradiation. These organic compounds are known to promote not only the ring-opening polymerization of various heterocyclic monomers such as lactones, carbonates, or epoxides but also to trigger the step-growth synthesis of polyurethanes. This Minireview highlights the recent advances in the development of organic photobase and photoacid generators, with the aim of encouraging the wider application of these photoactive compounds in the photopolymerization area and to expand the use of these polymers in advanced manufacturing processes.


Small-cell carcinoma of the lung: a five-year experience with combined modality therapy.
In the past five years, we have treated 89 patients with small-cell carcinoma of the lung with radiotherapy plus one of three chemotherapy programs. The 24 patients with disease confined to the chest (Stage IIIMO) had an 87% response rate to the combined modalities (79% complete responses) and a median survival of 18 months; 13 patients with disease confined to the chest and ipsilateral supraclavicular nodes (Stage IIIMOSCN +) had an 84% response rate (69% complete responses) and 11-month median survival; the 52 patients with distant metastases (Stage IIIMI) had a 71% response rate (15% complete responses) and eight-month median survival. Survival was not affected by adding prophylactic cranial irradiation to the latest regimen, although the CNS relapse rate was reduced. We conclude that our three chemotherapy programs to date differ very little in their effect on survival of patients with metastatic disease. New and more vigorous approaches, possibly including surgery, need to be tested for the management of disease confined to the chest. The designation of patients as Stage IIIMOSCN + is valid because such patients have better survival rates than patients with distant metastatic disease.


The mobility of single-file water molecules is governed by the number of H-bonds they may form with channel-lining residues.
Channel geometry governs the unitary osmotic water channel permeability, pf, according to classical hydrodynamics. Yet, pf varies by several orders of magnitude for membrane channels with a constriction zone that is one water molecule in width and four to eight molecules in length. We show that both the pf of those channels and the diffusion coefficient of the single-file waters within them are determined by the number NH of residues in the channel wall that may form a hydrogen bond with the single-file waters. The logarithmic dependence of water diffusivity on NH is in line with the multiplicity of binding options at higher NH densities. We obtained high-precision pf values by (i) having measured the abundance of the reconstituted aquaporins in the vesicular membrane via fluorescence correlation spectroscopy and via high-speed atomic force microscopy, and (ii) having acquired the vesicular water efflux from scattered light intensities via our new adaptation of the Rayleigh-Gans-Debye equation.


Psychotic experiences and subjective cognitive complaints among 224 842 people in 48 low- and middle-income countries.
Cognitive deficits are an important factor in the pathogenesis of psychosis. Subjective cognitive complaints (SCCs) are often considered to be a precursor of objective cognitive deficits, but there are no studies specifically on SCC and psychotic experiences (PE). Thus, we assessed the association between SCC and PE using data from 48 low- and middle-income countries. Community-based cross-sectional data of the World Health Survey were analysed. Two questions on subjective memory and learning complaints in the past 30 days were used to create a SCC scale ranging from 0 to 10 with higher scores representing more severe SCC. The Composite International Diagnostic Interview was used to identify past 12-month PE. Multivariable logistic regression and mediation analyses were performed. The final sample consisted of 224 842 adults aged ⩾18 years [mean (SD) age 38.3 (16.0) years; 49.3% males]. After adjustment for sociodemographic factors, a one-unit increase in the SCC scale was associated with a 1.17 (95% CI 1.16-1.18) times higher odds for PE in the overall sample, with this association being more pronounced in younger individuals: age 18-44 years OR = 1.19 (95% CI 1.17-1.20); 45-64 years OR = 1.15 (95% CI 1.12-1.17); ⩾65 years OR = 1.14 (95% CI 1.09-1.19). Collectively, other mental health conditions (perceived stress, depression, anxiety, sleep problems) explained 43.4% of this association, and chronic physical conditions partially explained the association but to a lesser extent (11.8%). SCC were associated with PE. Future longitudinal studies are needed to understand temporal associations and causal inferences, while the utility of SCC as a risk marker for psychosis especially for young adults should be scrutinised.


Automated in vivo drug screen in zebrafish identifies synapse-stabilising drugs with relevance to spinal muscular atrophy.
Synapses are particularly vulnerable in many neurodegenerative diseases and often the first to degenerate, for example in the motor neuron disease spinal muscular atrophy (SMA). Compounds that can counteract synaptic destabilisation are rare. Here, we describe an automated screening paradigm in zebrafish for small-molecule compounds that stabilize the neuromuscular synapse in vivo. We make use of a mutant for the axonal C-type lectin chondrolectin (chodl), one of the main genes dysregulated in SMA. In chodl-/- mutants, neuromuscular synapses that are formed at the first synaptic site by growing axons are not fully mature, causing axons to stall, thereby impeding further axon growth beyond that synaptic site. This makes axon length a convenient read-out for synapse stability. We screened 982 small-molecule compounds in chodl chodl-/- mutants and found four that strongly rescued motor axon length. Aberrant presynaptic neuromuscular synapse morphology was also corrected. The most-effective compound, the adenosine uptake inhibitor drug dipyridamole, also rescued axon growth defects in the UBA1-dependent zebrafish model of SMA. Hence, we describe an automated screening pipeline that can detect compounds with relevance to SMA. This versatile platform can be used for drug and genetic screens, with wider relevance to synapse formation and stabilisation.


Endothelium-dependent vasodilation and oxidative stress in chronic renal failure: impact on cardiovascular disease.
Despite significant progress in renal replacement therapy, the mortality from cardiovascular disease (CVD) in patients with chronic renal failure (CRF) is many times higher than in the general population. The traditional risk factors are frequently present in CRF patients. However, based upon conventional risk factor analysis, these factors do not fully explain the extraordinary increase in morbidity and mortality in CVD among patients with CRF. Accumulating evidence suggests that CRF is associated with impaired endothelial cell function. In recent years, the role of endothelial dysfunction (ED) and excessive oxidative stress (OS) in the development of CVD has been highlighted. ED is an early feature of vascular disease in different diseases such diabetes, hypertension, hypercholesterolemia, and coronary heart disease. The precise mechanism which induces ED is not clear. Several factors however, including OS-related accumulation of uremic toxins, hypertension and shear stress, dyslipidemia with cytotoxic lipoprotein species such as small, dense low-density lipoprotein (LDL) particles, competitive inhibition of endothelial nitric oxide (NO) by increased production by asymmetrical dimethylarginine (ADMA) are pathogenic. In addition, it is known that excessive OS causes ED. An overproduction of reactive oxygen species (ROS) may injure the endothelial cell membrane, inactivate NO, and cause oxidation of an essential cofactor of nitric oxide synthase (NOS). Recent studies have demonstrated that an impaired endothelium-dependent vasodilation and OS are closely related to each other in patients with CRF.


Endothelin A receptor is necessary for O(2) constriction but not closure of ductus arteriosus.
In vitro and in vivo techniques were developed with genetically modified mice to determine whether endothelin-1 (ET-1) functions as an O(2) mediator in closure of the ductus arteriosus (DA) at birth. Wild-type CD-1 and 129/SvEv mice with ET(A) receptor -/-, +/-, and +/+ genotypes were used. Isolated DA from term ET(A) +/+ fetuses contracted to O(2) (5-95%) and a thromboxane A(2) analog (ONO-11113, 0.1 microM). Instead, ET-1 elicited a dual response with weak relaxation (0.1 nM) preceding contraction (1-100 nM). Indomethacin (2.8 microM) was also a constrictor. ET(A) -/- DA, unlike ET(A) +/+ DA, contracted marginally to O(2) and ET-1 but responded to ONO-11113. O(2) contraction was also reduced in ET(A) +/- DA. In vivo, DA constricted equally in tracheotomized ET(A) -/- and ET(A) +/+ newborns. Conversely, no DA constriction was seen in hyperoxic ET(A) -/- fetuses in utero, although it occurred in ET(A) +/+ and +/- littermates. We conclude that ET-1 mediates the DA constrictor response to O(2). Without ET-1, however, the vessel still closes postnatally, conceivably caused by the withdrawal of relaxing influence(s).


Experimental and computational studies of the neutral and reduced states of indeno[1,2-b]fluorene.
This study examines the intrinsic structural and optoelectronic properties of the neutral indeno[1,2-b]fluorene skeleton as well as those of the corresponding anion radical and dianion. We report their characterization by analysis of solid-state structures and EPR, NMR, and absorbance spectra. Additionally, 20 popular density functional theory methods are used to evaluate their performance for predicting NMR chemical shifts, EPR hyperfine coupling constants, and low-energy transitions of the absorbance spectrum to act as a guide for future studies. This information can be used for a better understanding and tuning of the electron-transporting/accepting ability of the indenofluorene core for use in organic photovoltaics and organic field effect transistors.


Depth distributions of coral reef fishes: the influence of microhabitat structure, settlement, and post-settlement processes.
Many coral reef fishes have restricted depth ranges that are established at settlement or soon after, but the factors limiting these distributions are largely unknown. This study examines whether the availability of microhabitats (reef substrata) explains depth limits, and evaluates whether juvenile growth and survival are lower beyond these limits. Depth-stratified surveys of reef fishes at Kimbe Bay (Papua New Guinea) showed that the abundance of new settlers and the cover of coral substrata differed significantly among depths. A field experiment investigated whether settling coral reef fishes preferred particular depths, and whether these depth preferences were dependent on microhabitat. Small patch reefs composed of identical coral substrata were set up at five depths (3, 6, 10, 15 and 20 m), and settlement patterns were compared to those on unmanipulated reef habitat at the same five depths. For all species, settlement on patch reefs differed significantly among depths despite uniform substratum composition. For four of the six species tested, depth-related settlement patterns on unmanipulated habitat and on patch reefs did not differ, while for the other two, depth ranges were greater on the patch reefs than on unmanipulated habitat. A second experiment examined whether depth preferences reflected variation in growth and survival when microhabitat was similar. Newly settled individuals of Chrysiptera parasema and Dascyllus melanurus were placed, separately, on patch reefs at five depths (as above) and their survival and growth monitored. D. melanurus, which is restricted to shallow depths, had highest survival and growth at the shallowest depth. Depth did not affect either survival or growth of C. parasema, which has a broader depth range than D. melanurus (between 6 and 15 m). This suggests that the fitness costs potentially incurred by settling outside a preferred depth range may depend on the strength of the depth preference.


Transthoracic Ultrasound Improves Cardiac Function in Mice.
Cardiac dysfunction is a severe complication that is as-sociated with an increased risk of mortality in multiple diseases. One potential solution that has been researched is the electrical stimulation of the vagus nerve to exert cardioprotection. This method has been shown to reduce the systemic inflammatory response and maintain im-mune homeostasis of the heart. However, the invasive procedure of electrode implantation poses a risk of nerve or fiber damage. Here, we propose transthoracic ultrasound stimulation of vagus nerve to allevi-ate cardiac dysfunction caused by lipopolysaccharide. We developed a noninvasive transthoracic ultrasound stimulation system and exposed anesthetized mice to ultrasound protocol or sham stimulation 24 hours after lipopolysaccharide treatment. Results showed that daily heart tar-geting ultrasound stimulation for 4 days significantly increased left ventricular systolic function (p = 0.01) and improved ejection fraction (p = 0.03) and shortening fraction (p = 0.04). Furthermore, ultrasound stimulation significantly reduced inflammation cytokines, including IL-6 (p = 0.03) and IL-1β (p = 0.04). In addition, cervical vagotomy abrogated the effect of ultrasound stimulation, suggesting the involve-ment of the vagus nerve anti-inflammatory effect. Finally, the same ultrasound treatment but for a longer period (14 days) also significantly increased cardiac function in naturally aged mice. Collectively, these findings suggest that the potential of transthoracic ultrasound stimula-tion as a possible novel noninvasive approach in the context of cardiac dysfunction with reduced systolic function, and provide new targets for rehabilitation of peripheral organ function.


Malignant Insulinoma: A Rare Form of Neuroendocrine Tumor.
Due to the rarity of malignant insulinoma, a lack of the literature describing factors affecting outcomes exists. Our aim was to review malignant insulinoma incidence, characteristics and survival trends. We identified all patients with malignant insulinoma in the SEER registries from 1973 to 2015. Incidence, neoplasm characteristics and factors affecting cancer-specific survival (CSS) were described. A total of 121 patients were identified. The crude annual overall incidence was low (range 0.0-0.27 cases per million person years). The largest proportion had localized disease (40%), while 16% had regional disease, 39% distant metastatic disease, and stage was unreported in 5%. Most neoplasms were in the body/tail of the pancreas, followed by the head of the pancreas. Grade was reported in 40% of patients; only a single patient reported as having grade IV with the remainder all grades I/II. Surgical resection was performed in 64% of patients. Within surgical patients, the median primary neoplasm size was 1.8 cm. Regional lymph nodes were examined in 57.1% of surgical patients, while 34% of examined nodes were positive. The median CSS was 183 months. On multivariable analysis, surgical resection, male sex and absence of metastatic disease were associated with superior survival. While the greatest proportion of patients with malignant insulinoma present with localized disease, regional lymph node involvement was found in 34% of whose nodes were tested. Further studies are needed to assess the role of lymph node dissection in improving survival and preventing recurrence given the observed frequency of lymph node involvement.


The Clinical Significance of the Failure to Perceive Vertigo in the Postcaloric Period Despite a Robust Caloric Response.
Purpose The purpose of this project was to explore the association between the perception of motion during caloric testing and two tasks associated with central vestibular processing: postural stability and visuospatial memory. Method This was a prospective study of 25 patients who were found to have nonvestibular etiologies of their symptoms and normal vestibular function test results and who underwent caloric testing with a mean maximum slow phase eye velocity for each irrigation of 15° or greater. Following each caloric irrigation, patients were asked whether they had any sensation of movement. Patients were grouped based on the presence or absence of motion during the caloric exam (motion perception vs. absent perception). Postural stability was assessed using computerized dynamic posturography, and visuospatial memory was assessed using a memory match card game application. Results There were no significant differences between groups on any measures of peripheral vestibular function. However, the Absent Perception Group showed greater postural instability during Condition 5 of posturography and performed significantly worse on a task of visuospatial working memory. Both age and absence of motion perception predicted abnormal performance on measures of postural stability and visuospatial working memory. Conclusions There appears to be clinical implications to a lack of motion perception during the caloric exam in patients with an otherwise normal peripheral vestibular system. Based on the current findings, we are unable to determine whether differences in postural stability and visuospatial memory were due to age or a central vestibular processing deficit.


Multi-scale computational study of the Warburg effect, reverse Warburg effect and glutamine addiction in solid tumors.
Cancer metabolism has received renewed interest as a potential target for cancer therapy. In this study, we use a multi-scale modeling approach to interrogate the implications of three metabolic scenarios of potential clinical relevance: the Warburg effect, the reverse Warburg effect and glutamine addiction. At the intracellular level, we construct a network of central metabolism and perform flux balance analysis (FBA) to estimate metabolic fluxes; at the cellular level, we exploit this metabolic network to calculate parameters for a coarse-grained description of cellular growth kinetics; and at the multicellular level, we incorporate these kinetic schemes into the cellular automata of an agent-based model (ABM), iDynoMiCS. This ABM evaluates the reaction-diffusion of the metabolites, cellular division and motion over a simulation domain. Our multi-scale simulations suggest that the Warburg effect provides a growth advantage to the tumor cells under resource limitation. However, we identify a non-monotonic dependence of growth rate on the strength of glycolytic pathway. On the other hand, the reverse Warburg scenario provides an initial growth advantage in tumors that originate deeper in the tissue. The metabolic profile of stromal cells considered in this scenario allows more oxygen to reach the tumor cells in the deeper tissue and thus promotes tumor growth at earlier stages. Lastly, we suggest that glutamine addiction does not confer a selective advantage to tumor growth with glutamine acting as a carbon source in the tricarboxylic acid (TCA) cycle, any advantage of glutamine uptake must come through other pathways not included in our model (e.g., as a nitrogen donor). Our analysis illustrates the importance of accounting explicitly for spatial and temporal evolution of tumor microenvironment in the interpretation of metabolic scenarios and hence provides a basis for further studies, including evaluation of specific therapeutic strategies that target metabolism.


HIV-1 induces renal epithelial dedifferentiation in a transgenic model of HIV-associated nephropathy.
Human immunodeficiency virus-associated nephropathy (HIVAN) is the most common cause of renal failure in HIV-1-seropositive patients. Recent studies using an HIV-1 transgenic mouse model have demonstrated that expression of HIV-1 in the kidney is required for the development of HIVAN. What has remained unclear, however, is the renal cell type responsible for pathogenesis and the essential pathological process. To address these issues, we used a transgenic murine model of HIVAN. We identified the cell types in kidney in which HIV transgene expression occurs using in situ hybridization. We evaluated evidence of proliferation by immunocytochemical analysis using an antibody to Ki-67 and cell type-specific markers, including WT-1, synaptopodin, Na+,K+-ATPase, adducin, and desmin. TUNEL assay was used to evaluate apoptosis. We found that glomerular and tubular epithelial cells express the HIV-1 transgene early in the disease process when renal architecture is well preserved. Transgene expression is lost, however, in tubular epithelial cells when they lose their differentiated cuboidal phenotype. In glomerular epithelial cells, dedifferentiation occurs with reduced expression of WT-1 and synaptopodin, in association with activation of desmin expression. Tubular microcysts also form with mislocalization of Na+,K+-ATPase expression to the lateral and apical cellular membranes. These studies support the hypothesis that the glomerular and renal epithelial cells are the primary targets of HIV-1 pathogenesis in the kidney. The essential pathologic process is dysregulation of the epithelial cell cycle with increased proliferation, apoptosis, cellular dedifferentiation, and altered cellular polarity.


Systematics and biology of some species of Micrurapteryx Spuler (Lepidoptera, Gracillariidae) from the Holarctic Region, with re-description of M. caraganella (Hering) from Siberia.
During a DNA barcoding campaign of leaf-mining insects from Siberia, a genetically divergent lineage of a gracillariid belonging to the genus Micrurapteryx was discovered, whose larvae developed on Caragana Fabr. and Medicago L. (Fabaceae). Specimens from Siberia showed similar external morphology to the Palearctic Micrurapteryx gradatella and the Nearctic Parectopa occulta but differed in male genitalia, DNA barcodes, and nuclear genes histone H3 and 28S. Members of this lineage are re-described here as Micrurapteryx caraganella (Hering, 1957), comb. n., an available name published with only a brief description of its larva and leaf mine. Micrurapteryx caraganella is widely distributed throughout Siberia, from Tyumen oblast in the West to Transbaikalia in the East. Occasionally it may severely affect its main host, Caragana arborescens Lam. This species has been confused in the past with Micrurapteryx gradatella in Siberia, but field observations confirm that Micrurapteryx gradatella exists in Siberia and is sympatric with Micrurapteryx caraganella, at least in the Krasnoyarsk region, where it feeds on different host plants (Vicia amoena Fisch. and Vicia sp.). In addition, based on both morphological and molecular evidence as well as examination of type specimens, the North American Parectopa occulta Braun, 1922 and Parectopa albicostella Braun, 1925 are transferred to Micrurapteryx as Micrurapteryx occulta (Braun, 1922), comb. n. with albicostella as its junior synonym (syn. n.). Characters used to distinguish Micrurapteryx from Parectopa are presented and illustrated. These findings provide another example of the potential of DNA barcoding to reveal overlooked species and illuminate nomenclatural problems.


Early Blood Lead Levels and Sleep Disturbance in Preadolescence.
Little is known about the effect of lead exposure on children's sleep. This study examined the association between blood lead levels (BLL) and sleep problems in a longitudinal study of children. Four community-based elementary schools in Jintan City, China. 1,419 Chinese children. BLL were measured when children were aged 3-5 y, and sleep was assessed at ages 9-13 y. Sleep was assessed by both parents' report, using the Children's Sleep Habits Questionnaire (CSHQ), and children's report, using an adolescent sleep questionnaire. A total of 665 children with complete data on BLL and sleep at both ages were included in the current study. Mean age of the sample at BLL assessment was 4.74 y (standard deviation [SD] = 0.89) and at sleep assessment was 11.05 y (SD = 0.88). Mean BLL was 6.26 μg/dL (SD = 2.54). There were significant positive correlations between BLL and 3 CSHQ subscales: Sleep onset delay (r = 0.113, P < 0.01), sleep duration (r = 0.139, P < 0.001), and night waking (r = 0.089, P < 0.05). Excessive daytime sleepiness (EDS) (26.1% versus 9.0%, P < 0.001) and use of sleeping pills (6.5% versus 1.8%, P = 0.03) were more prevalent in children BLL ≥ 10.0 μg/dL than in those children BLL < 10.0 μg/dL. After adjusting for demographics, BLL ≥ 10.0 μg/dL was significantly associated with increased risk for insomnia symptoms (odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.03-3.95) and EDS (OR = 2.90, 95% CI = 1.27-6.61). The findings indicate that elevated blood lead levels in early childhood are associated with increased risk for sleep problems and excessive daytime sleepiness in later childhood.


Powder properties and their influence on dry powder inhaler delivery of an antitubercular drug.
The purpose of this study was to determine if aerosol delivery of drug loaded microparticles to lungs infected with Mycobacterium tuberculosis may be achieved by predicting dispersion of dry powders through knowledge of particle surface properties. Particle sizes of rifampicin-loaded poly(lactide-co-glycolide) microparticles (R-PLGA), rifampicin alone, and lactose and maltodextrin carrier particles (bulk and 75-125- microm sieved fractions) were determined by electron microscopy for the projected area diameter (D(p)) and laser diffraction for the volume diameter (D(v)). Surface energies (gamma) of R-PLGA, rifampicin alone, lactose, and maltodextrin were obtained by inverse phase gas chromatography, surface areas (S(a)) by N2 adsorption, and cohesive energy densities by calculation. Particle dispersion was evaluated (Andersen nonviable impactor) for 10% blends of R-PLGA and rifampicin alone with bulk and sieved fractions of the carriers. D(p) for R-PLGA and rifampicin alone was 3.02 and 2.83 microm, respectively. D(v) was 13 +/- 1 and 2 +/- 1 microm for R-PLGA and rifampicin alone, respectively, indicating that R-PLGA was more aggregated. This was evident in gamma of 35 +/- 1 and 19 +/- 6 mJ/m2 for R-PLGA and rifampicin alone. D(p) for lactose and maltodextrin (sieved and bulk) was approximately 40 mm. Bulk maltodextrin (D(v) = 119 +/- 6 microm) was more aggregated than bulk lactose (D(v) = 54 +/- 2 microm). This was a result of the higher S(a) for maltodextrin (0.54 m2/g) than for lactose (0.21 m2/g). The gamma of bulk lactose and maltodextrin was 40 +/- 4 and 60 +/- 6 mJ/m2 and of sieved lactose and maltodextrin was 39 +/- 1 and 50 +/- 1 mJ/m2. Impaction studies yielded higher fine particle fractions of R-PLGA from sieved lactose, 13% +/- 3%, than from sieved maltodextrin, 7% +/- 1%, at 90 L/min. An expression, based on these data, is proposed as a predictor of drug dispersion from carrier particles. Delivery of dry powder formulations can be achieved by characterizing particle surfaces and predicting impact on dispersion.


Expanding the NUIG MOF family: synthesis and characterization of new MOFs for selective CO2 adsorption, metal ion removal from aqueous systems, and drug delivery applications.
Metal organic frameworks (MOFs) have attracted considerable attention in recent years due to their use in a wide range of environmental, industrial and biomedical applications. The employment of benzophenone-4,4'-dicarboxylic acid (bphdcH2) in MOF chemistry provided access to the 3D mixed metal MOFs [CoNa2(bphdc)2(DMF)2]n (NUIG2) and [ZnK2(bphdc)2(DMF)2]n (NUIG3), and the 2D homometallic MOF [Co2(OH)(bphdcH)2(DMF)2(H2O)2]n(OH)·DMF (1·DMF). 1·DMF is based on a dinuclear SBU and consists of interpenetrating networks with an sql topology. Dc magnetic susceptibility studies were carried out in 1·DMF and revealed the presence of weak antiferomagnetic exchange interactions between the metal centres. NUIG2 and NUIG3 are structural analogues of [ZnNa2(bphdc)2(DMF)2]n (NUIG1), which has shown an exceptionally high encapsulation for ibuprophen (Ibu), NO and metal ions. Both NUIG2 and NUIG3 display high metal ion (CoII, NiII, CuII) adsorption capacity, comparable to that of NUIG1, with NUIG2 exhibiting good performance in Ibu uptake (780 mg Ibu per g NUIG2). Monte Carlo simulations were conducted in NUIG1 in order to assess its adsorption capacity for other guest molecules, and revealed that it possesses an outstanding CO2 uptake at ambient pressure, which is larger than that of the previously reported best functioning species (104 vs. 100 cm3 (stp) per cm3). Furthermore, NUIG1 exhibits high selectivity for CO2 over CH4.


Giant congenital melanocytic nevus: report from 30 years of experience in a single department.
Giant congenital melanocytic nevi (GCMN) occur in 1:20,000 livebirths and are associated with increased risk of malignant transformation. The treatment of GCMN from 1981 to 2010 in a tertiary referral center was reviewed evaluating the modalities used, cosmetic results, associated complications, and malignant transformation. Of 35 patients, 25 underwent surgery. Curettage was most frequently used (64%) followed by excision and tissue expansion (20%). Six percent of the patients treated with curettage, and 78% of the patients who received excision surgery required more than 1 planned procedure, and 25% versus 44% required unplanned additional surgery, respectively. Complications were noted in 25% and 67% of the patients, respectively. Cosmetic result was satisfying in 76% of patients without difference between the groups. No malignant transformation was found during a mean follow-up of 11 years. Curettage is a gentle alternative to excision with a lower complication rate and good cosmetic outcome.


Practical Management of Cardiovascular Comorbidities in Rheumatoid Arthritis.
Cardiovascular (CV) comorbidities are a frequent extra-articular manifestation of rheumatoid arthritis (RA). Cardiovascular disease (CVD) with accelerated atherosclerosis is a major cause of morbidity and mortality in patients with RA. Subclinical CVD may be present since the early phase of RA. Not only traditional but also non-traditional CV risk factors are involved in the pathogenesis of RA-related CVD. Due to the lack of specifically designed randomized clinical trials, it is still unclear which tools to use to perform CV risk assessment, how to interpret the results and which interventions are appropriate in RA patients both to prevent and to manage CVD. Based on the available evidence, we propose a practical approach.


Association between periodontal diseases and chronic obstructive pulmonary disease: Evidence from sequential cross-sectional and prospective cohort studies based on UK Biobank.
To investigate the association between periodontal diseases, airflow limitation and incident chronic obstructive pulmonary disease (COPD) in a large-scale prospective UK Biobank cohort. Our approach comprised a cross-sectional study and a prospective cohort. Periodontal diseases were determined based on the participants' self-reported dental symptoms, including painful gums, bleeding gums and loose teeth. Logistic regression and Cox proportional hazards models were used to evaluate the association of periodontal diseases with airflow limitation and incident COPD in the cross-sectional study and the prospective cohort, respectively. The cross-sectional study involved 495,610 participants. Multivariable analysis found that periodontal diseases were significantly associated with airflow limitation (odds ratio = 1.036, 95% confidence interval [CI]: 1.015-1.059). The cohort study included 379,266 participants with a median follow-up period of 12.68 years. An elevated risk of incident COPD was associated with the presence of periodontal diseases (hazard ratio: 1.248, 95% CI: 1.174-1.326). The effect was consistent among subgroups, including baseline age (≤65 or >65 years), sex, smoking status and diabetes mellitus. Periodontal diseases are associated with airflow limitation and elevated COPD incidence. Maintaining good periodontal health in patients with chronic bronchitis and emphysema may help prevent the onset of COPD.


Costs associated with acute respiratory illness and select virus infections in hospitalized children, El Salvador and Panama, 2012-2013.
Although acute respiratory illness (ARI) is a leading cause of hospitalization among young children, few data are available about cost of hospitalization in middle-income countries. We estimated direct and indirect costs associated with severe ARI resulting in hospitalization among children aged <10 years in El Salvador and Panama through the societal perspective. During 2012 and 2013, we surveyed caregivers of children hospitalized with ARI about their direct medical (i.e., outpatient consultation, medications, hospital fees), non-medical (transportation, childcare), and indirect costs (lost wages) at discharge and 7 days after discharge. We multiplied subsidized hospital bed costs derived from administrative data by hospitalization days to estimate provider costs. Overall, 638 children were enrolled with a median age of 12 months (IQR 6-23). Their median length of hospitalization was 4 days (IQR 3-6). In El Salvador, caregivers incurred a median of US$38 (IQR 22-72) in direct and indirect costs per illness episode, while the median government-paid hospitalization cost was US$118 (IQR 59-384) generating an overall societal cost of US$219 (IQR 101-416) per severe ARI episode. In Panama, caregivers incurred a median of US$75 (IQR 39-135) in direct and indirect costs, and the health-care system paid US$280 (IQR 150-420) per hospitalization producing an overall societal cost of US$393 (IQR 258-552). The cost of severe ARI to caregivers and the health care system was substantive. Our estimates will inform models to estimate national costs of severe ARI and cost-benefit of prevention and treatment strategies.


Use of rabbit antithymocyte globulin in cardiac transplantation. Relationship of serum clearance rates to clinical outcome.
Serum rabbit globulin (RG) clearance rates were determined in 30 consecutive cardiac transplant recipients by radioimmune assay of serum RG levels after completion of an initial postoperative course of rabbit anti-human antithymocyte globulin (RATG). Twenty patients, who exhibited rapid RG elimination rates (average half-life, 1.6 days), had a rejection onset time of 16.2 days rejection frequency of 3.9 episodes/100 patient days, and a 1-year survival rate of 59%, respectively, as compared with 28.3 days, 1.9 episodes/100 patient days, and 80%, respectively, for the 10 patients with more prolonged initial RG elimination rates (average half-life, 11.4 days); Nineteen patients received one or more repeat courses of RATG. In 16 of these a progressive increase in RG half-life during subsequent RATG administration could be demonstrated. A close correlation was observed between total RATG doses given in the initial course and peak serum levels of RG obtained (r = 0.82) and between onset of rejection and initial t1/2 RG (r = 0.69). This latter correlation was improved by the elimination of one of the 30 patients (r = 0.81) or by considering only those patients treated from a single RATG batch (r = 0.85; n = 15). No significant relationship was detected between any of the parameters assayed and (1) total RATG dose, or (2) rosette inhibition titers of RATG administered. Survival and rejection parameters of the first 30 patients receiving RATG were compared with the previous 20 receiving equine antithymocyte globulin; these 50 comprising the entire population in which rejection was confirmed by cardiac biopsy. Rejection onset was 20 versus 12 days, rejection frequency was 3.1 versus 5.0 episodes/100 patient days, and graft survival at 1 year was 66 versus 41% for the RATG-equine antithymocyte globulin-treated patients, respectively. From these data it was concluded that (1) RATG administration favorably affects transplantation outcome; (2) RATG half-life, as reflected by RG clearance rates, was the most important variable governing RATG effectiveness, (3) variation in rosette inhibition titers within RATG batches made in the same fashion from large rabbit pools were of minimal clinical importance; and (4) monitoring of serum RG levels provided a necessary and rational basis for effective modulation of immunosuppressive therapy.


Mapping the pharmaceutical design space by amorphous ionic liquid strategies.
Poor water solubility of drugs fuels complex formulations and jeopardizes patient access to medication. Simplifying these complexities we systematically synthesized a library of 36 sterically demanding counterions and mapped the pharmaceutical design space for amorphous ionic liquid strategies for Selurampanel, a poorly water soluble drug used against migraine. Patients would benefit from a rapid uptake after oral administration to alleviate migraine symptoms. Therefore, we probed the ionic liquids for the flux, supersaturation period and hygroscopicity leading to algorithms linking molecular counterion descriptors to predicted pharmaceutical outcome. By that, 30- or 800-fold improvements of the supersaturation period and fluxes were achieved as were immediate to sustained release profiles through structural counterions' optimization compared to the crystalline free acid of Selurampanel. Guided by ionic liquid structure, in vivo profiles ranged from rapid bioavailability and high maximal plasma concentrations to sustained patterns. In conclusion, the study outlined and predicted the accessible pharmaceutical design space of amorphous ionic liquid based and excipient-free formulations pointing to the enormous pharmaceutical potential of ionic liquid designs.


Antiapoptotic and proliferative activity of curcumin on ovarian follicles in mice exposed to whole body ionizing radiation.
The aim of this study was to evaluate the antiapoptotic and proliferative activity of curcumin (Cur) on the ovarian follicles in mice exposed to whole body ionizing radiation (Rd). The mice were exposed to 8.3 gray whole body Rd, and Cur groups were given as a daily dose of 100 mg/kg of Cur for 10 days (10 days before Rd). The ovaries were collected 3 and 12 h after irradiation. To date, no such studies have been performed on antiapoptotic and proliferative activity of Cur on the ovarian follicles in mice exposed to whole body Rd. Analysis of mice ovary after exposure to Rd by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling showed that there were apoptotic cells both in the follicular wall and the antrum, and that the number of follicles showing early atresic features was high 3 h after Rd. On the other hand, analysis of mice ovary 12 h after exposure to Rd showed that the number of follicles containing apoptotic cells with advanced atresic features was significantly higher when compared to the 3-h Rd exposure group. The proliferating cell nuclear antigen -positive granulosa cells were decreased in association with follicular atresia. The groups given treatment were observed to have some benefit from Cur against the damage caused by Rd. The results of this study demonstrate that Cur prevents follicular atresia in Rd-induced apoptosis in ovarian follicles.


Genetic encoding of DNA nanostructures and their self-assembly in living bacteria.
The field of DNA nanotechnology has harnessed the programmability of DNA base pairing to direct single-stranded DNAs (ssDNAs) to assemble into desired 3D structures. Here, we show the ability to express ssDNAs in Escherichia coli (32-205 nt), which can form structures in vivo or be purified for in vitro assembly. Each ssDNA is encoded by a gene that is transcribed into non-coding RNA containing a 3'-hairpin (HTBS). HTBS recruits HIV reverse transcriptase, which nucleates DNA synthesis and is aided in elongation by murine leukemia reverse transcriptase. Purified ssDNA that is produced in vivo is used to assemble large 1D wires (300 nm) and 2D sheets (5.8 μm(2)) in vitro. Intracellular assembly is demonstrated using a four-ssDNA crossover nanostructure that recruits split YFP when properly assembled. Genetically encoding DNA nanostructures provides a route for their production as well as applications in living cells.


Improved utilization of waist-to-height ratio in cardiometabolic risk counselling in children: Application of DMAIC strategy.
Waist circumference (WC) and waist-to-height ratio (WHtR) are superior surrogate markers of central obesity than body mass index. However, WC is not measured routinely in paediatric clinics. The objective of this study was to implement measurement of WC during routine assessment of children in an ambulatory outpatient clinic setting and subsequent dissemination of cardiometabolic risk counselling in children with central obesity (defined as WHtR ≥0.5). Prospective cohort of patients aged 6 to 20 years. Study period was divided into three phases: baseline (3 months), process improvement (2 months), and implementation (6 months). Define-Measure-Analyse-Improve-Control (DMAIC) strategy was applied. Measurement of WC was implemented as a component of the physical examination in patients. Outcome measures were (1) improvement in frequency of WC measurement and (2) utilization of WHtR in cardiometabolic risk counselling. Waist circumference was not measured in any patient during baseline phase (n = 551). During process improvement phase, of the total 347 patients, WC was measured in 35% vs target of 30%. In the implementation phase, WC was measured in 37% patients (365 out of 964). Of these 365 patients, 175 (48%) had elevated WHtR, and 73% of them (n = 128) were counselled about their increased cardiometabolic risk. Application of an evidence-based DMAIC protocol led to significant improvement in assessment for central obesity in an ambulatory clinic practice and appropriate counselling regarding cardiometabolic risk reduction in children and adolescents with central obesity over an 8-month period. Meticulous planning and execution, frequent reinforcement, and integrating feedback from the involved multi-disciplinary team were important factors in successful implementation of this quality improvement project.


[Production of spheroplasts from Pseudomonas aeruginosa].
The spheroplasts were prepared from the gram-negative bacterium Pseudomonas aeruginosa IBFM-13 upon incubation with lysozyme, but without EDTA. The following conditions were found to be optimal: 20 percent sucrose; lysozyme, 54 mcg/mg protein of the cells; pH 7.6. The spheroplasts, as well as the cells, have a high rate of malate oxidation, but do not oxidize NADH2, the latter fact suggesting that the cytoplasmic membrane remains intact.


Lessons from across the pond: Student perspectives on the Internal Medicine clerkship experience at an Irish and Canadian medical school.
This article was migrated. The article was marked as recommended. There is an increasing number of Canadians studying medicine outside of Canada, with a large cohort studying in Ireland. Studying abroad often means different foci in medical training which may make transitioning to residency in a different system more challenging. Students often enter North American elective rotations with little knowledge of student roles and responsibilities. This paper provides insight into the differences in learning objectives and student experiences in an Internal Medicine clerkship at a medical school in Canada and Ireland. Learning objectives are similar between systems; but there is an experiential discordance. In Ireland, clerks see many different patients, gaining exposure to a breadth of topics and clinical signs, but medical student presentations rarely inform decisions around patient care. In Canada, clerks have more direct patient responsibilities, performing physical examinations, reviewing investigations, writing progress notes, and devising management plans as part of their professional development. Overall, the Irish system places emphasis on the mastery of core clinical skills and maximizing breadth of patient exposure whereas the Canadian clerkship is more focused on graduated responsibility and formulating management plans, at the expense of some breadth of exposure. Such discrepancies may not affect the quality of residents, but are important considerations for Canadians studying abroad when repatriating for electives and residencies.


Current and emerging treatment options for Graves' hyperthyroidism.
Radioiodine, antithyroid drugs and surgery have been well established therapies for Graves' hyperthyroidism for several decades. However there remain large variations in practice among physicians in the preferred modality and the method of administration. Patient choice and perceptions also play a big role in the choice of treatment. Radioiodine may be given using fixed high doses or by calculated doses following uptake studies. The risks of radioiodine including eye disease and the role of prophylactic steroid therapy are discussed. The commonly used antithyroid drugs include carbimazole, methimazole and propylthiouracil; however a number of other agents have been tried in special situations or in combination with these drugs. The antithyroid drugs may be given in high (using additional levothyroxine in a block-replace regimen) or low doses (in a titration regimen). This review examines the current evidence and relative benefits for these options as well as looking at emerging therapies including immunomodulatory treatments such as rituximab which have come into early clinical trials. The use of antithyroid therapies in special situations is also discussed as well as clinical practice issues which may influence the choices.


Na2M2(SO4)3 (M = Fe, Mn, Co and Ni): towards high-voltage sodium battery applications.
Sodium-ion-based batteries have evolved as excellent alternatives to their lithium-ion-based counterparts due to the abundance, uniform geographical distribution and low price of Na resources. In the pursuit of sodium chemistry, recently the alluaudite framework Na2M2(SO4)3 has been unveiled as a high-voltage sodium insertion system. In this context, the framework of density functional theory has been applied to systematically investigate the crystal structure evolution, density of states and charge transfer with sodium ions insertion, and the corresponding average redox potential, for Na2M2(SO4)3 (M = Fe, Mn, Co and Ni). It is shown that full removal of sodium atoms from the Fe-based device is not a favorable process due to the 8% volume shrinkage. The imaginary frequencies obtained in the phonon dispersion also reflect this instability and the possible phase transition. This high volume change has not been observed in the cases of the Co- and Ni-based compounds. This is because the redox reaction assumes a different mechanism for each of the compounds investigated. For the polyanion with Fe, the removal of sodium ions induces a charge reorganization at the Fe centers. For the Mn case, the redox process induces a charge reorganization of the Mn centers with a small participation of the oxygen atoms. The Co and Ni compounds present a distinct trend with the redox reaction occurring with a strong participation of the oxygen sublattice, resulting in a very small volume change upon desodiation. Moreover, the average deintercalation potential for each of the compounds has been computed. The implications of our findings have been discussed both from the scientific perspective and in terms of technological aspects.


Structural valve deterioration in the Mitroflow biological heart valve prosthesis.
Concern has been raised regarding the long-term durability of the Mitroflow biological heart valve prosthesis. Our aim was to assess the incidence of structural valve degeneration (SVD) for the Mitroflow bioprosthesis in a nationwide study in Denmark including all patients alive in Denmark who had received a Mitroflow aortic bioprosthesis since 2000. Patients alive in Denmark with a Mitroflow bioprosthesis implanted since January 2000 were invited to participate in a nationwide cross-sectional study with a predefined definition of SVD. Of 1552 patients, 861 patients had died and 47 patients had been reoperated with 40 reoperations due to SVD. The remaining 644 patients were invited for evaluation; 574 patients accepted and were evaluated for SVD. The incidence of SVD was calculated using competing risk regression analysis with death as the competing event. A total of 173 patients were diagnosed with SVD by echocardiography. Of these, 64 (11%) patients had severe SVD and 109 (19%) patients moderate SVD. Severe SVD was associated with the age of the prosthesis and small prosthesis size [Size 21: hazard ratio (95% confidence interval, CI) 2.72 (0.97-8.56), P = 0.06; Size 19: 6.26 (1.63-24.06), P = 0.008]. The cumulative incidences of reoperation or severe SVD at Year 9 were 12.5% for Size 19, 7.6% for Size 21 and 3.1 (1.2-6.4)% for Size 23. Median survival in patients with prosthesis Sizes 23-29 was 6.4 (95% CI 5.7-7.0) years, with Size 21 it was 6.5 (95% CI 5.9-7.1) years and with Size 19 it was 6.9 (95% CI 5.7-8.2) years (P = 0.78). The incidence of undetected severe SVD was as high as the incidence of operated SVD. The overall risk for SVD is high for the Mitroflow bioprosthesis, especially if the prosthesis is small and older than 5 years.


Pharmacodynamics and dermatopharmacokinetics of betamethasone 17-valerate: assessment of topical bioavailability.
The bioavailability of most topically delivered drugs is difficult to quantify, but is generally believed to be very low. With the exception of the vasoconstrictor assay for corticosteroids, no methodology to quantify the rate and extent of drug delivery to the skin has been validated. Recent research has examined the dermatopharmacokinetic (DPK) technique, which is based on stratum corneum (SC) tape-stripping. To compare the in vivo bioavailability of different topical formulations of betamethasone 17-valerate (BMV) using the vasoconstrictor assay and the DPK method. BMV was formulated in different vehicles and the drug concentration was adjusted to either (i) equal thermodynamic activity, or (ii) a range of values up to that corresponding to 80% of maximum thermodynamic activity. Vasoconstriction, an accepted and widely used method to determine bioavailability and bioequivalence of topical steroids, was quantified with a chromameter over 24 h post-removal of the formulation. Drug uptake into the SC was assessed by tape-stripping. BMV at the same thermodynamic activity in different vehicles provoked similar skin blanching responses, while DPK profiles distinguished between the formulations. Further, skin blanching responses and drug uptake into the SC clearly depended upon the absolute BMV concentration applied. However, while the saturable nature of the pharmacodynamic response was clear, the tape-stripping method distinguished unequivocally between the different formulations and different concentrations. The DPK approach offers a reliable metric with which to quantify transfer of drug from the vehicle to the SC, and may be useful for topical bioavailability and bioequivalence determinations.


Inferior vena cava leiomyosarcoma: is reconstruction necessary after resection?
Leiomyosarcomas of the inferior vena cava represent a rare form of soft-tissue sarcomas. Management strategies necessarily vary because of limited experience. Questions about necessity of multimodality therapy and IVC reconstruction remain. Six patients were referred to our institution during a period of 6 years for leiomyosarcomas of the IVC. Demographic data, imaging results, pathology reports, preoperative radiation regimen, and postoperative outcomes were reviewed. Outcomes were compared with those of other published institutional experiences. After preoperative external-beam radiation (4,500 to 5,000 cGy), all patients underwent en bloc resection of the primary malignancy. Four patients (66%) had an R0 resection. All tumors were high grade. No reconstruction of the IVC was undertaken. Lower-extremity edema developed in 3 patients (50%), but this was well tolerated and did not lead to any long-term sequelae. Pulmonary metastasis developed postoperatively in 1 patient (17%) and was successfully treated with chemotherapy and metastectomy. Acute renal failure developed in 3 patients, but all recovered full function. Chylous leak developed in 2 patients (34%). Leiomyosarcoma of the IVC is a treatable malignancy. Preoperative external-beam radiation facilitates marginally negative resection, although our study is too small to demonstrate a survival benefit. Reconstruction of the IVC is not necessary for resection of tumors below the level of the hepatic veins in most if not all cases. Lower-extremity edema after ligation of the IVC is well tolerated. Acute renal failure can be a common, albeit transient, early postoperative complication. Extensive periaortic dissection can be associated with chylous leak, which can be managed with internal or external drainage.


Racial Differences and Injury Pattern Variation: Impact of COVID-19 on a Bronx Trauma Center.
New York City (NYC) became the epicenter of the COVID-19 pandemic in 2020. The Bronx, with the highest rates of poverty and violent crime of all NYC boroughs and a large Black and Hispanic population, was at increased risk of COVID-19 and its sequelae. We aimed to identify temporal associations among COVID-19 and trauma admission volume, demographics, and mechanism of injury (MOI). A retrospective review of prospectively collected data was conducted from a Level II trauma center in the Bronx. January 1st-September 30th for both 2019 (Pre-COVID) and 2020 (COVID) were compared. Pre-COVID and COVID cohorts were subdivided into EARLY (March-May) and LATE (June-September) subgroups. Demographics and trauma outcomes were compared. Trauma admissions were similar between Pre-COVID and COVID. During COVID, there was an increased percentage of Black patients (Black Hispanic 20.1% vs 15.2% and Black Non-Hispanic 39.4% vs 34.1%, P < .05), younger patients (26-35 years old: 22.6% vs 17.6%, P < .05), and out-of-pocket payors (6.0% vs 1.6%, P < .05). Trauma severity outcomes were mixed-some measures supported increased severity; others showed no difference or decreased severity. During COVID, there was a rise in total penetrating injuries (27.4% vs 20.8%, P < .05), MVC (13.2% vs 7.1, P < .05), and firearm injuries (11.6% vs 6.0%, P < .05). Additionally, during LATE COVID, there was a resurgence of total penetrating, total blunt, MVC, falls, cyclists/pedestrians struck, and firearm injuries. Our results emphasize MOI variations and racial differences of trauma admissions to a Level II trauma center in the Bronx during COVID-19. These findings may help trauma centers plan during pandemics and encourage outreach between trauma centers and community level organizations following future healthcare disasters.


Supra-additive growth inhibition by a celecoxib analogue and carboxyamido-triazole is primarily mediated through apoptosis.
Combination studies of celecoxib and chemotherapeutic agents suggest that combining cyclooxygenase-2 inhibitors with other agents may have supra-additive or synergistic effects on tumor growth inhibition. Carboxyamido-triazole (CAI), a voltage-independent calcium channel inhibitor, has been shown to induce growth inhibition and apoptosis in cancer cells. We found that continuous exposure to cytostatic doses of CAI and LM-1685, a celecoxib analogue, reduced the proliferation and survival of seven human cancer cell lines by at least one log (P < or = 0.001) over either agent alone. To explore the mechanism of action of this combination, we further studied the effects of LM-1685/CAI on CCL-250 colorectal carcinoma cells. We found that the supra-additive antiproliferative effects occurred throughout a range of LM-1685 doses (5-25 micromol/L) and paralleled a decrease in COX-2 activity as measured by prostaglandin E2 production. In these cells, treatment with LM-1685/CAI suppressed the extracellular signal-regulated kinase pathway within the first hour but ultimately results in high, sustained activation of ERK over a 9-day period (P = 0.0005). Suppression of cyclin D1 and phospho-AKT, and cleavage of caspase-3 and PARP were concomitant with persistent ERK activation. Addition of PD98059, a MEK-1 inhibitor, suppressed ERK activation and significantly but incompletely reversed these signaling events and apoptosis. Flow cytometry experiments revealed that the CAI/LM-1685 combination induced a 3-fold increase in apoptosis over control (P = 0.005) in 3 days. We show that the combination of CAI and LM-1685 produces a cytotoxic effect by suppressing proliferation and triggering apoptosis.


Headset-related sensory and motor neuropathies in image-guided sinus surgery.
Complications related to the use of image-guided systems in sinus surgery are fortunately rare. We report a case series of 6 patients who experienced facial neuropathies (both sensory and motor) related to the use of a headset for electromagnetic-based image-guided surgery. The auriculotemporal nerve was the most common sensory nerve involved, and the buccal branch of the facial nerve was implicated in a case of motor weakness. The cause of the complication appears to be a pressure neuropathy caused by a tight-fitting headset against the external auditory meatus and temporomandibular joint. Additional risk factors for headset-related neuropathy may relate to body habitus, length of surgical procedure, and patient positioning. All patients' neuropathies resolved completely without intervention. Headset-related complications appear to be uncommon but may be an important consideration in counseling patients who are candidates for image-guided sinus surgery.


Bidirectional association between hypothyroidism and myasthenia gravis: a Mendelian randomized study.
Although observational studies have suggested a link between hypothyroidism and myasthenia gravis (MG), a causal relationship has not been established. We aimed to investigate the causal association using a two-sample Mendelian randomization (MR) study. Using summary statistics from genome-wide association studies involving 494,577 and 38,243 individuals, single-nucleotide polymorphisms exhibiting no linkage disequilibrium (r2 ≤ 0.001) and displaying significant differences (p ≤ 5 × 10-8) were selected for hypothyroidism and MG. To assess the potential causality relationship between hypothyroidism and MG, MR analysis was conducted using inverse variance weighted (IVW), weighted median method, and MR-Egger. The MR-Egger regression, heterogeneity test, pleiotropy test, and leave-one-out sensitivity test were employed to examine sensitivity analyses. In addition, validation datasets were used to validate the relevant results. Genetic liability to hypothyroidism was positively associated with MG (IVW, OR: 1.36, 95% CI: 1.17-1.58, p = 7.53 × 10-05; weighted median, OR: 1.19, 95% CI: 0.70-2.02, p = 0.522; MR-Egger, OR: 1.19, 95% CI: 0.98-1.45, p = 0.080). Among the three MR methods, the correlation between hypothyroidism and MG genetic prediction was consistent. The independent validation set (IVW, OR: 466.47, 95% CI: 4.70 -46,285.95, p = 0.01) further supported this. Additionally, bidirectional studies showed that using IVW, there was no reverse causality (OR: 1.104, 95%CI: 0.96-1.27, p = 0.170). This MR study showed that hypothyroidism can increase the risk of MG. Further investigation into the underlying mechanisms of this potential causality is warranted to offer novel therapeutic options for MG in the future.


Premilitary tobacco use by male Marine Corps recruits.
Recognizing both the medical and operational costs of tobacco use, the Department of Defense has made tobacco cessation a top health promotion priority. Military tobacco rates remain high, however, especially among younger personnel and, particularly, in the Marine Corps. Tobacco is prohibited during basic training, but relapse is common following boot camp graduation. The objective of this study was to determine patterns and prevalence of tobacco use among Marine Corps recruits before entering basic training. Over a period of 14 months, 15,689 graduating male recruits completed a survey of their preservice tobacco use. Approximately 81% reported having tried tobacco at least once and 57% were classified as at-risk users. Compared to their civilian peers, more recruits were daily users and many more used smokeless tobacco. Approximately 67% of users evidenced at least one indicator of dependence. There is a clear need for additional tobacco cessation efforts to target this high-risk population.


The role of thalamic population synchrony in the emergence of cortical feature selectivity.
In a wide range of studies, the emergence of orientation selectivity in primary visual cortex has been attributed to a complex interaction between feed-forward thalamic input and inhibitory mechanisms at the level of cortex. Although it is well known that layer 4 cortical neurons are highly sensitive to the timing of thalamic inputs, the role of the stimulus-driven timing of thalamic inputs in cortical orientation selectivity is not well understood. Here we show that the synchronization of thalamic firing contributes directly to the orientation tuned responses of primary visual cortex in a way that optimizes the stimulus information per cortical spike. From the recorded responses of geniculate X-cells in the anesthetized cat, we synthesized thalamic sub-populations that would likely serve as the synaptic input to a common layer 4 cortical neuron based on anatomical constraints. We used this synchronized input as the driving input to an integrate-and-fire model of cortical responses and demonstrated that the tuning properties match closely to those measured in primary visual cortex. By modulating the overall level of synchronization at the preferred orientation, we show that efficiency of information transmission in the cortex is maximized for levels of synchronization which match those reported in thalamic recordings in response to naturalistic stimuli, a property which is relatively invariant to the orientation tuning width. These findings indicate evidence for a more prominent role of the feed-forward thalamic input in cortical feature selectivity based on thalamic synchronization.


Effect of testicular capsulotomy on fertility of rats.
To demonstrate the effect of capsulotomy on the fertility of male rats. Testicular capsulotomy was carried out in immature (21 days) and adult (60 days) male rats. The fertility of them was assessed by cohabitation with proestrus females overnight and 20 days later, the females were examined for impregnation. Morphological changes at the site of the capsulotomy were observed under light microscope. In rats capsulotomized at Day 60, the fertility was gradually depressed and all the rats completely lost their fertility 2 months post-operation. At that time, a partial regeneration of the capsule at the site of capsulotomy was observed. Immature rats capsulotomized at Day 21 were found to possess normal fertility at maturity. The capsulotomy site was almost completely recovered 60 days post-operation. In male rats, testicular capsulotomy at the age of Day 60 will damage fertility. However, when capsulotomy is performed at Day 21, fertility is preserve.


SARS-CoV-2 Detection: Radiology based Multi-modal Multi-task Framework.
The global community is still grappling with the SARS-CoV-2 pandemic, declared by the World Health Organization in March 2020. Radiology is an important screening method for the early detection of SARS-CoV-2. Doctors typically recommend that patients undergo one of the radiology procedures during the early stages of diagnosis. Recent research has focused on developing deep learning-based architectures that use either X-Rays or CT-Scans, but not both. This paper presents a multi-modal, multi-task learning framework that uses either the X-Rays or CT-Scans to identify SARS-CoV-2 patients. The framework employs a shared feature embedding that utilizes common information from both X-Rays and CT-Scans, as well as task-specific feature embeddings that are independent of the type of chest screening. The shared and task-specific embeddings are combined to obtain the final classification results, which have been shown to have an accuracy of 98.23% and 98.83% in detecting SARS-CoV-2 using X-Rays and CT-Scans, respectively.


IL-33 signalling in liver immune cells enhances drug-induced liver injury and inflammation.
The aim of this study was to investigate the contribution of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice model of drug-induced liver injury (DILI). DILI was induced by overdose administration of acetaminophen (APAP) by oral gavage in wild-type BALB/c, ST2-deficient mice and in different bone marrow chimeras. Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes (CLL). Blood and liver were collected for biochemical, immunologic and genetic analyses. Mice were imaged by confocal intravital microscopy and liver non-parenchymal cells and hepatocytes were isolated for flow cytometry, genetic and immunofluorescence studies. Acetaminophen overdose caused a massive necrosis and accumulation of immune cells within the liver, concomitantly with IL-33 and chemokine release. Liver non-parenchymal cells were the major sensors for IL-33, and amongst them, neutrophils were the major players in amplification of the inflammatory response triggered by IL-33/ST2 signalling pathway. Blockage of IL-33/ST2 axis reduces APAP-mediated organ injury by dampening liver chemokine release and activation of resident and infiltrating liver non-parenchymal cells.


Cortical and trabecular bone microarchitecture and turnover in alcohol-induced chronic pancreatitis: a histomorphometric study.
Alcohol-induced chronic pancreatitis is associated with bone loss, but bone histomorphometric data describing the mechanism of cortical (Ct) and trabecular (Tb) bone loss are scarce. In this case-control study, we investigated 13 black male patients aged 41.2 +/- 8.9 years with alcohol-induced chronic pancreatitis by routine iliac crest cortical and trabecular histomorphometry and by biochemistry relevant to bone, liver function, and iron overload. Patients showed lower values for Ct thickness (P = 0.018), endocortical (Ec) wall thickness (P = 0.0002), Tb bone volume (0.019), Tb thickness (0.001), Tb wall thickness (P < 0.0001), Ec osteoid thickness (P = 0.001), Ec mineral apposition rate (P = 0.011), and Ec bone formation rate (P = 0.035). Ec eroded surface (P = 0.004) was elevated compared to controls. Tb osteoid thickness (P = 0.14) and Tb mineral apposition rate (P = 0.195) tended to be lower than in controls. Levels of 25-hydroxyvitamin D (P < 0.005), serum magnesium (P = 0.02), and ascorbic acid (P = 0.049) were lower and urine calcium/creatinine ratios higher than in controls. Alkaline phosphatase and gamma-glutamyl transpeptidase (GGT) were negatively correlated but iron markers were positively correlated with bone structural and formation variables. The histomorphometric data were found to be consistent with alcohol bone disease. Osteomalacia was not a feature. Secondary pathogenetic factors were liver disease, hypovitaminosis D and C, diabetes mellitus, and possibly chronic pancreatitis.


Phototoxic maculopathy due to extreme usage of infrared illuminator-assembled night-vision handheld scope.
Night-vision handheld scopes are of wide use in military operations at dark conditions. In some cases in the battlefield, as in our case report, if there is no light coming from any source (neither from Moon nor from Stars), infrared light-emitting diode illumination can be coupled with night-vision goggles. Reflected illumination from the target is mostly blue filtered through the night-vision goggles objective lens. Retinal damage induced by unfiltered blue light and visible light has been previously reported. We described a phototoxic maculopathy induced by night-vision handheld scope assembled with infrared light-emitting diode illuminator in two soldiers who are on duty at nights for nearly two-thirds of the last year. The phototoxic maculopathy can represent with typical optical coherence tomography findings such as intraretinal hyperreflective accumulation particularly located on the surface of outer retinal segments defect or presumably in the vicinity of the light passageway. Here, we presented a unique factor causing phototoxic maculopathy.


Training pathologists in mouse pathology.
Expertise in the pathology of mice has expanded from traditional regulatory and drug safety screening (toxicologic pathology) primarily performed by veterinary pathologists to the highly specialized area of mouse research pathobiology performed by veterinary and medical pathologists encompassing phenotyping of mutant mice and analysis of research experiments exploiting inbred mouse strains and genetically engineered lines. With increasing use of genetically modified mice in research, mouse pathobiology and, by extension, expert mouse research-oriented pathologists have become integral to the success of basic and translational biomedical research. Training for today's research-oriented mouse pathologist must go beyond knowledge of anatomic features of mice and strain-specific background diseases to the specialized genetic nomenclature, husbandry, and genetics, including the methodology of genetic engineering and complex trait analysis. While training can be accomplished through apprenticeships in formal programs, these are often heavily service related and do not provide the necessary comprehensive training. Specialty courses and short-term mentoring with expert specialists are opportunities that, when combined with active practice and publication, will lead to acquisition of the skills required for cutting-edge mouse-based experimental science.


Responsiveness and Internal Validity of Common Patient-Reported Outcome Measures Following Total Shoulder Arthroplasty.
The Constant-Murley (Constant) score, Western Ontario Osteoarthritis of the Shoulder (WOOS) index, American Shoulder and Elbow Surgeons (ASES) score, and Single Assessment Numeric Evaluation (SANE) score are commonly used to assess patient-reported function following shoulder surgery. However, psychometric properties for these tools are mostly unknown for patients with primary glenohumeral arthritis who have undergone anatomic total shoulder arthroplasty (TSA). The purposes of this study were to (1) compare the responsiveness and internal validity between the 4 patient-reported outcomes (PROs) and (2) identify PRO score values associated with patient satisfaction after TSA. A total of 234 primary TSAs were performed for primary glenohumeral osteoarthritis with a 2-year or greater follow-up. The Constant score, WOOS index, ASES score, SANE score, and patient satisfaction were assessed preoperatively and 2 to 5 years postoperatively. Effect sizes, standardized response means, and relative efficiency were calculated to determine responsiveness, and internal validity was determined via the presence of floor and/or ceiling effects. Receiver operator characteristic (ROC) curves were constructed to identify the minimum outcome score that could correctly identify a satisfied patient. At final follow-up, 88% of patients were satisfied. The PROs had large effect sizes and standardized response means (≥0.83). The minimum score that most correctly identified a patient as satisfied was 78 for ASES score, 18 for WOOS index, 73 for Constant score, and 58 for SANE score. However, the ASES score, WOOS index, and SANE score had marked postoperative ceiling effects, whereas the Constant score was the most responsive and internally valid tool. These results suggest that the Constant score should serve as the primary PRO for patients with primary glenohumeral arthritis, whereas the WOOS index, ASES score, and SANE score could be supplementary assessments. [Orthopedics. 2017; 40(3):e513-e519.].


Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping.
THOC6 is a part of the THO complex, which is involved in coordinating mRNA processing with export. The THO complex interacts with additional components to form the larger TREX complex (transcription export complex). Previously, a homozygous missense mutation in THOC6 in the Hutterite population was reported in association with syndromic intellectual disability. Using exome sequencing, we identified three unrelated patients with bi-allelic mutations in THOC6 associated with intellectual disability and additional clinical features. Two of the patients were compound heterozygous for a stop and a missense mutation, and the third was homozygous for a missense mutation; the missense mutations were predicted to be pathogenic by in silico analysis and modeling. Clinical features of the three newly identified patients and those previously reported are reviewed; intellectual disability is moderate to severe, and malformations are variable including renal and heart defects, cleft palate, microcephaly, and corpus callosum dysgenesis. Facial features are variable and include tall forehead, short upslanting palpebral fissures +/- deep set eyes, and a long nose with overhanging columella. These subtle facial features render the diagnosis difficult to make in isolation with certainty. Our results expand the mutational and clinical spectrum of this rare disease, confirm that THOC6 is an intellectual disability causing gene, while providing insight into the importance of the THO complex in neurodevelopment.


Diabetic retinopathy in Victoria, Australia: the Visual Impairment Project.
To establish the prevalence, severity, and risk factors for diabetic retinopathy in a representative sample of Victorian residents aged 40 years and older. A population based, cluster sampling method was used to recruit 4744 participants (86% participation rate). Nine randomly selected, suburban Melbourne clusters and four randomly selected, rural Victorian clusters were used. Participants provided a detailed medical and personal history and underwent an ocular examination including funduscopy and fundus photography. Rural participants provided a blood sample, from which the glycosylated haemoglobin percentage was measured. The diagnosis of diabetic retinopathy was based on fundus photographs from participants with self reported diabetes. The prevalence of diabetic retinopathy among people with self reported diabetes was 29. 1%. The prevalence of untreated, vision threatening retinopathy was 2.8%. Retinopathy was positively associated with a longer reported duration of diabetes diagnosis (p<0.01) and with higher fractions of glycosylated haemoglobin (p<0.01). Retinopathy was not significantly associated with age, ethnicity, body mass index, glaucoma, myopia or intake of alcohol, tobacco, or aspirin (all p > 0.05). Most people in Victoria with proliferative diabetic retinopathy or clinically significant macular oedema have received laser treatment. There remains however, a small but important group who have not received treatment and whose vision is threatened. People with diabetes should be encouraged to maintain strict glycaemic control and to undergo regular screening to delay or prevent the development of retinopathy.


Crystallization and preliminary X-ray analysis of Escherichia coli methionyl-tRNAMet(f) formyltransferase complexed with formyl-methionyl-tRNAMet(f).
The structure of methionyl-tRNAfMet(f) formyltransferase from E. coli, a monomeric protein of 34 kDa, has previously been determined at 2.0 A resolution. In the present work, this enzyme was crystallized as a complex with its macromolecular product, the initiator formyl-methionyl-tRNAfMet(f) (25 kDa). Polyethylene glycol 5000 monomethylether was used as a precipitating agent. The crystals are orthorhombic and have unit-cell parameters a = 201.7, b = 68.1, c = 86.4 A. They belong to space group P21212 and diffract to 2.8 A resolution. The structure is being solved with the help of a mercury derivative.


Preoperative selective portal vein embolization in two-step hepatectomy for hepatocellular carcinoma in injured livers: a preliminary report.
To study the effect of preoperative selective portal vein embolization (SPVE) in the two-step hepatectomy for patients with primary hepatocellular carcinoma (HCC) in injured livers. Twenty-six patients with HCC and cirrhosis who were not suitable for curative hepatectomy were treated by ultrasound-guided percutaneous transhepatic SPVE with a fine needle. The success rate, side-effects and complications of SPVE, serial changes of hepatic lobe volume and rate of two-step curative hepatectomy after SPVE were observed. SPVE was performed in 24 patients (92.3%). In patients whose right portal vein branches were embolized, the right hepatic volume decreased but the left hepatic volume increased gradually. The ratio of the right hepatic volume to the total hepatic volume decreased from 64.0% before SPVE to 60.8% after l week, 55.1% after 2 weeks and 52.7% after 3 weeks, respectively. The side-effects included different degree of pain in the liver quandrant (17 patients), lower fever (9), and nausea and vomiting (7). The levels of aspartate alanine transaminase (AST), alanine transaminase (ALT) and total bilirubin (TBIL) increased after SPVE, but returned to the preoperative levels in 1 week. After 2-4 weeks, two-step curative hepatectomy for HCC was performed in 13 patients (54.2%). Ultrasound-guided percutaneous transhepatic SPVE with a fine needle is feasible and safe. It can extend the indications of curative hepatectomy for HCC in injured livers, and increase the safety of two-step hepatectomy.


Facial palsy and Lyme borreliosis: long-term follow-up of children with antibiotically untreated "idiopathic" facial palsy.
We report on the follow-up of 28 patients, who were admitted to our hospitals between 1968 and 1984, and who, at that time, were diagnosed as having idiopathic facial palsy. These children were neither tested for Lyme borreliosis (LB) nor did they receive antibiotic treatment. In those days LB was an unfamiliar infection. Today we can assume that approximately 30%-50% of the patients we studied represent actual cases of neuroborreliosis. We, therefore, considered them an appropriate model in studying the spontaneous course of LB in children. the analysis of the questionnaire designed for our study as well as the supplementary clinical and serological reexaminations in some cases provided no evidence that neuroborreliosis led to relevant health disorders in any of the children (follow-up 10 to 26 years, mean 17). The results of our retrospective study led us to conclude that tick-borne facial palsy is relatively benign in children and that neuroborreliosis is insignificantly related to late complications.


FLIMX: A Software Package to Determine and Analyze the Fluorescence Lifetime in Time-Resolved Fluorescence Data from the Human Eye.
Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a new technique for measuring the in vivo autofluorescence intensity decays generated by endogenous fluorophores in the ocular fundus. Here, we present a software package called FLIM eXplorer (FLIMX) for analyzing FLIO data. Specifically, we introduce a new adaptive binning approach as an optimal tradeoff between the spatial resolution and the number of photons required per pixel. We also expand existing decay models (multi-exponential, stretched exponential, spectral global analysis, incomplete decay) to account for the layered structure of the eye and present a method to correct for the influence of the crystalline lens fluorescence on the retina fluorescence. Subsequently, the Holm-Bonferroni method is applied to FLIO measurements to allow for group comparisons between patients and controls on the basis of fluorescence lifetime parameters. The performance of the new approaches was evaluated in five experiments. Specifically, we evaluated static and adaptive binning in a diabetes mellitus patient, we compared the different decay models in a healthy volunteer and performed a group comparison between diabetes patients and controls. An overview of the visualization capabilities and a comparison of static and adaptive binning is shown for a patient with macular hole. FLIMX's applicability to fluorescence lifetime imaging microscopy is shown in the ganglion cell layer of a porcine retina sample, obtained by a laser scanning microscope using two-photon excitation.


Mosses as biomonitors of atmospheric heavy metal deposition: spatial patterns and temporal trends in Europe.
In recent decades, mosses have been used successfully as biomonitors of atmospheric deposition of heavy metals. Since 1990, the European moss survey has been repeated at five-yearly intervals. Although spatial patterns were metal-specific, in 2005 the lowest concentrations of metals in mosses were generally found in Scandinavia, the Baltic States and northern parts of the UK; the highest concentrations were generally found in Belgium and south-eastern Europe. The recent decline in emission and subsequent deposition of heavy metals across Europe has resulted in a decrease in the heavy metal concentration in mosses for the majority of metals. Since 1990, the concentration in mosses has declined the most for arsenic, cadmium, iron, lead and vanadium (52-72%), followed by copper, nickel and zinc (20-30%), with no significant reduction being observed for mercury (12% since 1995) and chromium (2%). However, temporal trends were country-specific with sometimes increases being found.


A genetically encoded multifunctional unnatural amino acid for versatile protein manipulations in living cells.
The genetic code expansion strategy allowed incorporation of unnatural amino acids (UAAs) bearing diverse functional groups into proteins, providing a powerful toolkit for protein manipulation in living cells. We report a multifunctional UAA, Nε-p-azidobenzyloxycarbonyl lysine (PABK), that possesses a panel of unique properties capable of fulfilling various protein manipulation purposes. In addition to being used as a bioorthogonal ligation handle, an infrared probe and a photo-affinity reagent, PABK was shown to be chemically decaged by trans-cyclooctenols via a strain-promoted 1,3-dipolar cycloaddition, which provides a new bioorthogonal cleavage strategy for intracellular protein activation. The biocompatibility and efficiency of this method were demonstrated by decaging of a PABK-caged firefly luciferase under living conditions. We further extended this method to chemically rescue a bacterial toxin OspF inside mammalian host cells.


An earlier age of breast cancer diagnosis related to more frequent use of antiperspirants/deodorants and underarm shaving.
Breast cancer incidence suggests a lifestyle cause. A lifestyle factor used near the breast is the application of antiperspirants/deodorants accompanied by axillary shaving. A previous study did not support a link with breast cancer. If these habits have a role in breast cancer development, women using antiperspirants/deodorants and shaving their underarms frequently would be expected to have an earlier age of diagnosis than those doing so less often. An earlier age of diagnosis would also be expected in those starting to use deodorants and shaving at an earlier age. This is the first study to investigate the intensity of underarm exposure in a cohort of breast cancer survivors. Four hundred and thirty-seven females diagnosed with breast cancer were surveyed. Once grouped by their frequency of underarm hygiene habits, the mean age of diagnosis was the primary end point. Secondary end points included the overall frequency of these habits, and potential usage group confounding variables were evaluated. All statistical tests were two-sided. Frequency and earlier onset of antiperspirant/deodorant usage with underarm shaving were associated with an earlier age of breast cancer diagnosis. Combined habits are likely for this earlier age of diagnosis. In conclusion, underarm shaving with antiperspirant/deodorant use may play a role in breast cancer. It is not clear which of these components are involved. Reviewed literature insinuates absorption of aluminium salts facilitated by dermal barrier disruption. Case-controlled investigations are needed before alternative underarm hygiene habits are suggested.


Wound healing potential of Spirulina platensis extracts on human dermal fibroblast cells.
Blue-green alga (Spirulina platensis) is a well renowned nutri-supplement due to its high nutritional and medicinal properties. The aim of this study was to examine the wound healing efficiency of Spirulina platensis at various solvent extracts using in vitro scratch assay on human dermal fibroblast cells (HDF). Various gradient solvent extracts (50 μg/ml of methanolic, ethanolic and aqueous extracts) from Spirulina platensis were treated on HDF cells to acquire its wound healing properties through scratch assay and in this investigation we have used allantoin, as a positive control to compare efficacy among the phytoextracts. Interestingly, aqueous extract were found to stimulate proliferation and migration of HDF cells at given concentrations and enhanced closure rate of wound area within 24 hours after treatment. Methanolic and ethanolic extracts have shown proliferative effect, however these extracts did not aid in the migration and closure of wound area when compared to aqueous extract. Based on phytochemical profile of the plant extracts analyzed by LC-MS/MS, it was shown that compounds supposedly involved in accelerating wound healing are cinnamic acid, narigenin, kaempferol, temsirolimus, phosphatidylserine isomeric derivatives and sulphoquinovosyl diacylglycerol. Our findings concluded that blue-green algae may pose potential biomedical application to treat various chronic wounds especially in diabetes mellitus patients.


Fabrication of an ideal nanoring from a black phosphorus nanoribbon upon movable bundling carbon nanotubes.
As a low dimensional material, black phosphorus (BP) continues to attract much attention from researchers due to its excellent electric properties. In particular, the one-dimensional material, in the form of a ring or tube formed from BP, has been extensively studied and found to be a perfect semiconductor. But the BP ring has never been reported in laboratories. To form an ideal ring from a rectangular BP ribbon, we choose a carbon nanotube (CNT) bundle to attract the ribbon and move one or more CNTs in the bundle to induce the unsaturated ends of the BP ribbon to become covalently bonded. Numerical experiments are applied to BP ribbons with lengths either equal to, shorter, or longer than the perimeter of the CNT bundle, to investigate the formation of a BP ring. Experiments show that if one end of the BP ribbon is attracted by a CNT, moving the other CNTs away endows the ribbon with high probability of forming an ideal ring. The conclusions drawn from these results will benefit future in situ experiments involving forming a ring from a BP ribbon.


Non-Vascular Considerations When Interpreting Extremity Arterial and Venous Examinations.
Peripheral arterial and venous examinations are performed regularly in vascular labs and interpreted by physicians of different specialities. Many vascular examinations have nonvascular pathology that is either inadvertently imaged by the sonographer or imaged with intent as it relates to patient's symptoms. It is prudent for every reader of vascular studies to be acquainted with the sonographic appearance of these non-vascular lesions to enable appropriate and optimal interpretation that has a direct bearing on patient's clinical care. Our review includes a discussion of the nonvascular pathologies like lymph nodes, soft tissue edema, soft tissue fluid collections, musculotendinous injuries, soft tissue masses, and joint and bursal pathologies that may be encountered during interpretation of vascular exams. The pictorial essay includes a discussion of their sonographic appearances and pitfalls in interpretation. Multiple illustrative examples and sonographic images of the non-vascular pathologies found during interpretation of vascular studies have been utilized to highlight their appearances.


Do early symptoms of pancreatic cancer exist that can allow an earlier diagnosis?
Diagnosis of pancreatic cancer is made late, and prognosis remains extremely poor. This study was carried out to investigate whether symptoms exist before pain or jaundice that could suggest pancreatic cancer and favor earlier diagnosis. The study involved 305 patients with confirmed pancreatic cancer and 305 controls. All subjects were interviewed personally at least twice about their clinical history; pancreatic cancer patients were asked about any disturbances before abdominal pain or jaundice. Of the 305 pancreatic cancer patients, 151 (49.5%) had some prior disturbances, 108 (35.4%) 6 months or less before pain or jaundice and 43 (14.1%) more than 6 months before. Among the latter, 14 (4.6% of all patients) had had anorexia and/or early satiety and/or asthenia (7-20 months before pain or jaundice), 11 (3.6%) had disgust for coffee and/or smoking and/or wine (7-20 months before), 14 (4.6%) had diabetes (7-24 months before), and four (1.3%) had acute pancreatitis (8-26 months before). Among the controls, the only reports of these symptoms were two (0.7%) cases of asthenia (4 and 6 years earlier), 22 (7.2%) cases of diabetes (of which only two [0.7%] were diagnosed 7-24 months before the interview), and one (0.33%) case of acute pancreatitis (10 years earlier). Apart from acute pancreatitis, all the other differences between patients and controls were statistically significant. In approximately 15% of patients, disturbances existed more than 6 months before pain or jaundice, which, although not specific, could raise suspicion of the possibility of pancreatic cancer. These disturbances could represent the one current opportunity for an earlier diagnosis in a significant minority of pancreatic cancer patients.


Presynaptic GABA(B) receptors regulate experience-dependent development of inhibitory short-term plasticity.
Short-term changes in synaptic gain support information processing throughout the CNS, yet we know little about the developmental regulation of such plasticity. Here we report that auditory experience is necessary for the normal maturation of synaptic inhibitory short-term plasticity (iSTP) in the auditory cortex, and that presynaptic GABA(B) receptors regulate this development. Moderate or severe hearing loss was induced in gerbils, and iSTP was characterized by measuring inhibitory synaptic current amplitudes in response to repetitive stimuli. We reveal a profound developmental shift of iSTP from depressing to facilitating after the onset of hearing. Even moderate hearing loss prevented this shift. This iSTP change was mediated by a specific class of inhibitory interneurons, the low-threshold spiking cells. Further, using paired recordings, we reveal that presynaptic GABA(B) receptors at interneuron-pyramidal connections regulate iSTP in an experience-dependent manner. This novel synaptic mechanism may support the emergence of mature temporal processing in the auditory cortex.


Structural and dynamic properties of monoclonal antibodies immobilized on CNTs: a computational study.
Due to the widespread application of carbon nanotube (CNT)-based materials in nanomedicine, it is nowadays of paramount importance to unravel at the atomistic level of detail the structural properties of such bioconjugates in order to rationalize and predict the effect exerted by the graphitic framework on the bio-active counterpart. In this paper, we report for the first time all-atom explicit solvent molecular dynamics (MD) simulations investigating the structural and dynamic properties of a noncovalent bioconjugate in which the monoclonal Cetuximab antibody (Ctx) is adsorbed on a CNT surface. Upon selection of the three most representative adsorption modes as obtained by docking studies, force-field MD and DFT simulations unambiguously showed that hydrophobic interactions mainly govern the adsorption of the protein on the graphitic surface. Two main adsorption poses have been predicted: a pose-fab (p-fab) and pose-fc (p-fc) (fab = fragment antigen binding region; fc = fragment crystallizable region), the former being favored with small-diameter tubes (≤40 Å). In all the predicted poses, the secondary structure of Ctx is largely unaffected by the presence of the graphitic surface and, consistently with previous literature studies, our simulations reveal that positively charged amino acidic residues, such as Lys and Arg, predominantly contribute to the stabilization of the CNT⋅Ctx complex acting like surfactants. The predicted structural models are consistent with the experimental data, for which the immobilization of the antibody on CNTs does not disrupt the structural and recognition properties of the Ctx, consequently supporting the reliability of the used bioconjugation strategy for engineering stable and responsive hybrid nanomaterials for therapeutic applications. Moreover, a remarkable structural similarity of Ctx with antibodies of different isotypes suggests that in principle the CNT framework can interact in the same manner with all antibodies currently used in clinical applications.