Nanoparticles induce platelet activation in vitro through stimulation of canonical signalling pathways.
Nanomaterials are attracting growing interest for their potential use in several applications as nanomedicine; therefore, the analysis of their potential toxic effects on various cellular models, including circulating blood cells, is mandatory. This study aimed to investigate the effect of three unrelated nanomaterials, namely nanoscale silica, multiwalled carbon nanotubes, and carbon black, on platelet activation and aggregation. We found that these nanomaterials stimulate some of the typical biochemical pathways involved in canonical platelet activation, such as the stimulation of phospholipase C and Rap1b, resulting in the integrin α(IIb)β3-mediated platelet aggregation, through a mechanism largely dependent on the release of the extracellular second messengers ADP and thromboxane A2. Importantly, we found that doses of nanoparticles unable to trigger appreciable responses can synergize with subthreshold amounts of physiological agonists to mediate platelet aggregation, indicating that even small amounts of nanomaterials in the bloodstream might contribute to the development of thrombosis. In this study, nanosized particles of three virtually unrelated materials (silica, multi-walled carbon nanotubes and carbon black) were investigated regarding their effects on platelet activation and aggregation. All were found to stimulate some of the typical biochemical pathways involved in canonical platelet activation, and were found to have synergistic effects with physiologic platelet activator agonists.


Practice Pattern of Hepatitis B Testing in Rheumatoid Arthritis Patients: A Cross-National Comparison Between the US and Taiwan.
The hepatitis B virus (HBV) testing rates and patterns in rheumatoid arthritis (RA) patients starting disease-modifying antirheumatic drugs (DMARDs) have not been well studied. We describe and compare the practice patterns of HBV testing among RA patients in the US and Taiwan. We conducted a retrospective cohort study, including RA patients starting a first DMARD in the US or Taiwan. The first date patients newly received any DMARD was defined as the index date, and the 1-year period before the index date was the baseline period. HBV testing was defined as any of the following tests 1 year before or after the index date: hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, hepatitis B envelope antigen, hepatitis B envelope antibody, or HBV DNA. We calculated the HBV testing rate by year and used Poisson regression to calculate the testing rate ratio. We identified 14,568 RA patients in the US and 46,265 in Taiwan. The overall testing rate was 20.3% in the US and 24.5% in Taiwan, and gradually increased over the study period from 13.1-23.0% in the US and 16.8-30.0% in Taiwan. More than one type of HBV test was used in 43.4% of patients in the US and 16.3% of patients in Taiwan receiving tests. Results of Poisson regression found Taiwan had a 17% higher testing rate over the US during the followup period (crude rate ratio 1.17 [95% confidence interval 1.12-1.22]). We found small differences in the HBV testing rates across the US and Taiwan. Although the rate gradually increased in the past decade, it remained low in both countries.


Chronic Nodular Prurigo: A Retrospective Study of 74 Cases.
Chronic nodular prurigo (CNPG) is a recently defined and currently underdiagnosed disease with a variety of causes. It is associated with multiple comorbidities, and its management and treatment have improved with a better understanding of its pathogenesis. The aim of this study was to describe our experience with a series of patients with CNPG. Single-center, observational, retrospective study of the sociodemographic and clinical characteristics of patients with CNPG seen at the dermatology department of a tertiary care hospital between 2009 and 2021. We included 74 patients, mostly women (63.5%), with a mean age of 57 years. Overall, 39.2% of patients had a concomitant skin condition, mainly atopic dermatitis (62%). Other comorbidities included endocrine disorders (54.1%), cardiovascular disease (44.4%), and psychiatric disorders (36.5%). Skin biopsy helped confirm the clinical diagnosis in 70% of cases. The mean immunoglobulin E level was higher than normal (516 IU/mL), regardless of atopic predisposition. On average, patients received 3 treatments, the most common choices being methotrexate, antihistamines, and topical and oral corticosteroids. Methotrexate was among the most effective options. CNPG is a complex disease associated with multiple comorbidities. It requires a multidisciplinary approach, with the dermatologist at the center. Classical treatment approaches are probably insufficient.


The association of prokaryotic antiviral systems and symbiotic phage communities in drinking water microbiomes.
Prokaryotic antiviral systems are important mediators for prokaryote-phage interactions, which have significant implications for the survival of prokaryotic community. However, the prokaryotic antiviral systems under environmental stress are poorly understood, limiting the understanding of microbial adaptability. Here, we systematically investigated the profile of the prokaryotic antiviral systems at the community level and prokaryote-phage interactions in the drinking water microbiome. Chlorine disinfectant was revealed as the main ecological driver for the difference in prokaryotic antiviral systems and prokaryote-phage interactions. Specifically, the prokaryotic antiviral systems in the microbiome exhibited a higher abundance, broader antiviral spectrum, and lower metabolic burden under disinfectant stress. Moreover, significant positive correlations were observed between phage lysogenicity and enrichment of antiviral systems (e.g., Type IIG and IV restriction-modification (RM) systems, and Type II CRISPR-Cas system) in the presence of disinfection, indicating these antiviral systems might be more compatible with lysogenic phages and prophages. Accordingly, there was a stronger prokaryote-phage symbiosis in disinfected microbiome, and the symbiotic phages carried more auxiliary metabolic genes (AMGs) related to prokaryotic adaptability as well as antiviral systems, which might further enhance prokaryote survival in drinking water distribution systems. Overall, this study demonstrates that the prokaryotic antiviral systems had a close association with their symbiotic phages, which provides novel insights into prokaryote-phage interactions and microbial environmental adaptation.


Radiation therapy: a radiation oncologist's point of view.
This article is intended as a clinical introduction to radiation therapy as a treatment modality. It discusses the indications and contraindications for radiotherapy. Additionally, it attempts to cover the expected response of a wide variety of tumors to radiation. It should be remembered that veterinary radiotherapy is still in its infancy, and that much of the information presented in this article is, unfortunately, anecdotal in nature.


Clinical and radiographic outcomes of metacarpophalangeal joint pyrolytic carbon arthroplasty for osteoarthritis.
To determine the effectiveness of pyrolytic carbon arthroplasty for the management of primary osteoarthritis of the metacarpophalangeal joint. A retrospective review of 11 pyrolytic carbon arthroplasties for osteoarthritis of the metacarpophalangeal joint, performed by a single surgeon, was conducted. All patients returned for clinical assessment at a minimum of 2 years after surgery. Evaluation included range of motion, pain and functional scores, and patient satisfaction. Validated outcome measures included the Michigan Hand Questionnaire and Quick Disabilities of the Arm, Shoulder, and Hand. Radiographs were assessed for implant failure, loosening, migration, and subsidence. The average follow-up was 4 years (minimum 2 y). The arc of motion significantly improved from 62° before surgery to 76° after surgery. Grip strength decreased slightly compared to the contralateral side (average, 3 kg). The average pain score was 1 on a 10-point visual analog scale. All but 1 patient were fully satisfied at final follow-up. All patients who were working before surgery returned to work after surgery. The Michigan Hand Questionnaire average score was 80, and the Quick Disabilities of the Arm, Shoulder, and Hand average score was 22. Two patients experienced persistent, asymptomatic squeaking and clicking, and 1 patient reported extensor tendon subluxation. One joint had conversion to arthrodesis for continued, unexplained pain. All surviving implants had a surrounding lucency on radiographs. The average subsidence was 3 mm; there was no implant migration, fracture, or dislocation. Pyrolytic carbon arthroplasties of the metacarpophalangeal joint resulted in satisfactory outcomes at average 4-year follow-up, with improved joint motion, good pain relief and satisfaction, and few complications. Radiographic outcomes revealed a consistent, asymptomatic surrounding lucency with no evidence of implant failure or migration.


Pituitary suppression with GnRH agonists before ART may be insufficient to treat women with severe adenomyosis.
Does aromatase inhibitor improve IVF outcomes by reducing local oestrogen production in patients with adenomyosis undergoing long-term gonadotrophin-releasing hormone agonist (GnRHa) treatment? Four patients with severe adenomyosis who failed to improve after long-term treatment (≥3 months) with depot GnRHa received treatment with an aromatase inhibitor for 21 days. Blood oestradiol concentrations were monitored after GnRHa treatment both before and after treatment with an aromatase inhibitor. Women received a transfer of IVF autologous or donor oocytes. Pregnancy and ongoing pregnancy rates were the primary outcomes. Blood oestradiol concentration after treatment with an aromatase inhibitor was a secondary outcome. Patients with severe adenomyosis presented with hyperestrogenism due to local production from the lesions even after long-term treatment with GnRHa. Treatment with an aromatase inhibitor reduced hyperestrogenism and improved clinical outcomes in adenomyosis patients who have experienced previous embryo transfer failures. Women with severe adenomyosis would benefit from letrozole or a combination of GnRHa plus letrozole before receipt of treatment with assisted reproductive technology. For women with severe adenomyosis, GnRHa treatment alone may be insufficient to suppress oestrogen production by adenomyotic lesions. Thus, it should be mandatory to test for oestradiol concentrations in patients with severe adenomyosis who have received long-term GnRHa treatment. Also, GnRHa may not always be the sole strategy for medical management of adenomyotic lesions. Letrozole is safe and can improve IVF outcomes for patients with adenomyosis.


A live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden Syrian hamsters.
The immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (SARS) coronavirus lacking the E gene (rSARS-CoV-DeltaE) were studied using hamsters. Hamsters immunized with rSARS-CoV-DeltaE developed high serum-neutralizing antibody titers and were protected from replication of homologous (SARS-CoV Urbani) and heterologous (GD03) SARS-CoV in the upper and lower respiratory tract. rSARS-CoV-DeltaE-immunized hamsters remained active following wild-type virus challenge, while mock-immunized hamsters displayed decreased activity. Despite being attenuated in replication in the respiratory tract, rSARS-CoV-DeltaE is an immunogenic and efficacious vaccine in hamsters.


Open Source Digital Health Software for Resilient, Accessible and Equitable Healthcare Systems.
To assess the impact of open-source projects on making healthcare systems more resilient, accessible and equitable. In response to the International Medical Informatics Association (IMIA) call for working group contributions for the IMIA Yearbook, the Open Source Working Group (OSWG) conducted a rapid review of current open source digital health projects to illustrate how they can contribute to making healthcare systems more resilient, accessible and equitable. We sought case studies from the OSWG membership to illustrate these three concepts and how open source software (OSS) addresses these concepts in the real world. These case studies are discussed against the background of literature identified through the rapid review. To illustrate the concept of resilience, we present case studies from the adoption of District Health Information Software version 2 (DHIS2) for managing the Covid pandemic in Rwanda, and the adoption of the OpenEHR open Health IT standard. To illustrate accessibility, we show how open source design systems for user interface design have been used by governments to ensure accessibility of digital health services for patients and healthy individuals, and by the OpenMRS community to standardise their user interface design. Finally, to illustrate the concept of equity, we describe the OpenWHO framework and two open source digital health projects, GNU Health and openIMIS, that both aim to reduce health inequities through the use of open source digital health software. This review has demonstrated that open source software addresses many of the challenges involved in making healthcare more accessible, equitable and resilient in high and low income settings.


Screening for breast and cervical cancer: understanding the different recommendations.
Evidence-based screening guidelines issued by national organizations sometimes contradict each other, leading to confusion among health care providers and the women they care for. This article summarizes the most recent guidelines for breast and cervical cancer screening and notes where they concur and where they diverge.


Preliminary hemodynamic report of the efficacy and safety of quinapril in acute and chronic treatment of patients with congestive heart failure.
A two-part hemodynamic trial of the efficacy and safety of quinapril hydrochloride was conducted in 26 patients with congestive heart failure (NYHA Class III or IV) who had not optimally responded to treatment with diuretics and digitalis. A total of 25 patients had evaluable data after receiving single doses (2.5, 5, or 10 mg) of quinapril. Following acute dosing, favorable hemodynamic changes began within thirty minutes to one hour and usually reached a maximum within four hours post-dose. Nineteen evaluable patients who had responded to acute therapy received an additional sixteen weeks of chronic treatment with quinapril in individualized dosage regimens. Hemodynamic responses did not differ markedly between acute and chronic therapy. Favorable hemodynamic responses were maintained or enhanced following chronic doses of 5 to 30 mg/day (given either once daily or in divided doses). The most frequent doses were 10-15 mg/day in divided doses. The mean maximum percent changes in four primary hemodynamic parameters after chronic dosing (compared with baseline) were: mean arterial blood pressure, -3.9%; pulmonary capillary wedge pressure, -39.7%; cardiac output, +31.7%; and systemic vascular resistance, -25.2%. Changes in heart rate and mean arterial blood pressure did not result in clinically significant bradycardia or hypotention. Overall, quinapril produced both acute and sustained beneficial hemodynamic effects in patients whose congestive heart failure was not clinically controlled with diuretics and digitalis.


P62 accumulates through neuroanatomical circuits in response to tauopathy propagation.
In Alzheimer's disease and related tauopathies, trans-synaptic transfer and accumulation of pathological tau from donor to recipient neurons is thought to contribute to disease progression, but the underlying mechanisms are poorly understood. Using complementary in vivo and in vitro models, we examined the relationship between these two processes and neuronal clearance. Accumulation of p62 (a marker of defective protein clearance) correlated with pathological tau accumulation in two mouse models of tauopathy spread; Entorhinal Cortex-tau (EC-Tau) mice where tau pathology progresses in time from EC to other brain regions, and PS19 mice injected with tau seeds. In both models and in several brain regions, p62 colocalized with human tau in a pathological conformation (MC1 antibody). In EC-Tau mice, p62 accumulated before overt tau pathology had developed and was associated with the presence of aggregation-competent tau seeds identified using a FRET-based assay. Furthermore, p62 accumulated in the cytoplasm of neurons in the dentate gyrus of EC-Tau mice prior to the appearance of MC1 positive tauopathy. However, MC1 positive tau was shown to be present at the synapse and to colocalize with p62 as shown by immuno electron microscopy. In vitro, p62 colocalized with tau inclusions in two primary cortical neuron models of tau pathology. In a three-chamber microfluidic device containing neurons overexpressing fluorescent tau, seeding of tau in the donor chamber led to tau pathology spread and p62 accumulation in both the donor and the recipient chamber. Overall, these data are in accordance with the hypothesis that the accumulation and trans-synaptic spread of pathological tau disrupts clearance mechanisms, preceding the appearance of obvious tau aggregation. A vicious cycle of tau accumulation and clearance deficit would be expected to feed-forward and exacerbate disease progression across neuronal circuits in human tauopathies.


Non-smokers' and smokers' support for smoke-free legislation in 14 indoor and outdoor settings across 12 European countries.
European countries differ considerably in the scope and the extent of their policies to protect people from the harms of secondhand smoke exposure. Public opinion may have a substantial influence on several stages of policy development, implementation, and compliance. For this reason, we aimed to evaluate the population level of support for smoke-free policies and its correlates. We used data from the TackSHS Survey (2017-2018), a cross-sectional study with representative samples of the general population aged ≥15 years from 12 European countries. We described the proportion of non-smokers' and smokers' support for the implementation of smoke-free legislation in 14 indoor and outdoor settings and the country-level characteristics associated with it. In the total sample (n = 11,902), support for smoke-free legislation were the lowest for restaurants/bar patios (non-smokers = 53.0%; smokers = 29.2%) and the highest for workplaces (non-smokers = 78.5%; smokers = 66.5%). In the country-level analysis, the highest support among non-smokers was for workplaces in Bulgaria (93.1%) and the lowest for restaurants/bars patios in Greece (39.4%). Among smokers, the corresponding estimates were for children's playgrounds in Latvia (88.9%) and for cars in Portugal (21%). For most settings, support for smoke-free legislation was directly related with the countries' prevalence of secondhand smoke presence and reported smoking in each setting. Our results show that the majority of European adults (including a large proportion of smokers) are supportive of implementing smoke-free legislation in indoor settings and extending it to selected outdoor settings. Such expressive support can be seen as an opportunity to advance legislation and protect the European population from secondhand smoke exposure.


Fetal nuchal translucency screening in 12495 pregnancies in Sardinia.
To examine the distribution of fetal nuchal translucency thickness in normal and chromosomally abnormal fetuses in Sardinia and to determine the effectiveness of screening by a combination of fetal nuchal translucency and maternal age. Fetal nuchal translucency thickness and crown-rump length were measured at 10-14 weeks of gestation in 12 495 pregnancies. A reference range of fetal nuchal translucency thickness for crown-rump length was determined from the 10 001 singleton pregnancies with known normal pregnancy outcome. The median nuchal translucency thickness for crown-rump length was determined by regression analysis of the calculated median values of nuchal translucency thickness for each 0.1 mm interval in crown-rump length. The proportions of unaffected fetuses and those with trisomy 21 or other chromosomal defects with nuchal translucency thickness > 1.5 and 2.0 multiples of the regressed normal median for crown-rump length were calculated. The distribution of estimated risks based on maternal age and fetal nuchal translucency thickness according to The Fetal Medicine Foundation software were also determined and the sensitivity and false-positive rates were calculated. In the 10 001 normal pregnancies, the median fetal nuchal translucency thickness increased with crown-rump length (median nuchal translucency thickness = 0.3496 + 0.018 x crown-rump length) (r2 = 0.4411). In the singleton pregnancies, there were 64 fetuses with trisomy 21 and 46 with other chromosomal defects. The fetal nuchal translucency thickness was > 1.5 multiples of the median in 510 (5%) of the normal fetuses, in 52 (81%) of the trisomy 21 fetuses and in 33 (72%) of those with other chromosomal defects. The respective values for nuchal translucency thickness > 2.0 multiples of the median were 195 (2%), 41 (64%) and 32 (70%). In 184 multiple pregnancies, there were four fetuses with chromosomal abnormalities and in three of these the nuchal translucency thickness was > 1.5 multiples of the median. Screening by a combination of maternal age and fetal nuchal translucency thickness with a risk cut-off of 1 in 300 identified 90% of trisomy 21 pregnancies and 85% of all other chromosomal defects for a false-positive rate of 9%. Screening for chromosomal defects by measurement of nuchal translucency thickness identifies 80% of fetuses with trisomy 21 for a false-positive rate of 5%. In our population with a median maternal age of 33 years, screening by a combination of maternal age and fetal nuchal translucency thickness with a risk cut-off of 1 in 300 identified 90% of trisomy 21 pregnancies for a false-positive rate of 9%.


Peptidic degron in EID1 is recognized by an SCF E3 ligase complex containing the orphan F-box protein FBXO21.
EP300-interacting inhibitor of differentiation 1 (EID1) belongs to a protein family implicated in the control of transcription, differentiation, DNA repair, and chromosomal maintenance. EID1 has a very short half-life, especially in G0 cells. We discovered that EID1 contains a peptidic, modular degron that is necessary and sufficient for its polyubiquitylation and proteasomal degradation. We found that this degron is recognized by an Skp1, Cullin, and F-box (SCF)-containing ubiquitin ligase complex that uses the F-box Only Protein 21 (FBXO21) as its substrate recognition subunit. SCF(FBXO21) polyubiquitylates EID1 both in vitro and in vivo and is required for the efficient degradation of EID1 in both cycling and quiescent cells. The EID1 degron partially overlaps with its retinoblastoma tumor suppressor protein-binding domain and is congruent with a previously defined melanoma-associated antigen-binding motif shared by EID family members, suggesting that binding to retinoblastoma tumor suppressor and melanoma-associated antigen family proteins could affect the polyubiquitylation and turnover of EID family members in cells.


Alteration of transbilayer phospholipid compositions is involved in cell adhesion, cell spreading, and focal adhesion formation.
We previously showed that P4-ATPases, ATP10A/ATP8B1, and ATP11A/ATP11C have flippase activities toward phosphatidylcholine (PC), and aminophospholipids [phosphatidylserine (PS) and phosphatidylethanolamine], respectively. Here, we investigate the effect of PC-specific flippases versus aminophospholipid-specific flippases in cell spreading on the extracellular matrix. Expression of PC-flippases, but not PS-flippases, delayed cell adhesion, cell spreading and inhibited formation of focal adhesions. In addition, overexpression of a PS-binding probe that sequesters PS in the cytoplasmic leaflet delayed cell spreading and inhibited formation of focal adhesions. These results suggest that elevation of PC at the cytoplasmic leaflet of the plasma membrane by expression of PC-flippases may reduce the local concentration of PS or phosphoinositides, required for efficient cell adhesion, focal adhesion formation, and cell spreading.


Children and Adolescents' Behavioral Patterns in Response to Escalating COVID-19 Restriction Reveal Sex and Age Differences.
The COVID-19 pandemic affects students in a myriad of different ways. Our prospective, longitudinal study in a cohort of students in Hannover, Germany explores behavioral patterns during escalating COVID-19 restrictions. In total, 777 students between the age of 9 and 20 were assessed for their activity engagement, travel patterns, and self-assessed compliance with protective recommendations at six time points between June 2020 and June 2021 (3,564 observations) and were monitored for severe acute respiratory syndrome coronavirus 2 infection by nasal swab polymerase chain reaction and serum antibody titers. Activity engagement decreased, but self-assessed compliance with measures such as mask wearing and social distancing was stable during escalating restrictions. Although we found no sex difference during the summer break, when incidence was lowest, females engaged in a higher variety of activities than males for all other time points. Older students engaged in more activities and self-assigned themselves lower compliance values than younger ones. Greater involvement in different activities was seen in households which traveled more frequently. Infection rate in our cohort was low (0.03% acute infections, 1.94% positive seroprevalence). Our study supports the view that, overall, students show high compliance with COVID-19 recommendations and restrictions. The identification of subsets, such as female and older students, with higher risk behavioral patterns should be considered when implementing public information campaigns. In light of the low infection rate in our cohort, we conclude that in-person learning can occur safely if extensive protective measures are in place and the incidence in the general population remains moderate.


Surgical treatment outcome on a national cohort of 176 patients with cervical manifestation of rheumatoid arthritis.
Rheumatoid arthritis (RA) affecting the cervical spine results in instability and deformity that can be divided into the subtypes C1-C2 horizontal (atlantoaxial instability), C0-C2 vertical (basilar invagination), subaxial, and combined instabilities. The aim of this study was to compare the surgical treatments and outcomes of RA-related deformity and instability in a population-based setting. All patients with RA in the national Swespine register from January 1, 2006, to March 20, 2019, were assessed. Baseline characteristics, surgical treatments, European Myelopathy Scale (EMS), Neck Disability Index, the Visual Analog Scale for neck and arm pain as well as pre- and postoperative imaging were analyzed. The follow-up time points were at 1-, 2-, and 5 years after surgery. A total of 176 patients were included. There were 62 (35%) patients with C1-C2 horizontal instability, 48 (27%) with C0-C2 vertical instability, 19 (11%) patients with subaxial instability, 43 (24%) patients with combined instability, and 4 patients without instability served as controls. The EMS improved in the C1-C2 horizontal instability group after fusion surgery (Δ =2.6 p) but remained within baseline confidence intervals in the other groups. All patients regardless of instability improved in pain. The subaxial instability had the highest risk of death within 5 years after surgery (11/19, 58%). The most dangerous complications due to implant failure were seen in patients instrumented with laminar hooks. The neurological outcome after fusion surgery is poor and the death rate is high in patients with cervical RA-related instability and deformity.


Hsp40 proteins phase separate to chaperone the assembly and maintenance of membraneless organelles.
Membraneless organelles contain a wide spectrum of molecular chaperones, indicating their important roles in modulating the metastable conformation and biological function of membraneless organelles. Here we report that class I and II Hsp40 (DNAJ) proteins possess a high ability of phase separation rendered by the flexible G/F-rich region. Different Hsp40 proteins localize in different membraneless organelles. Specifically, human Hdj1 (DNAJB1), a class II Hsp40 protein, condenses in ubiquitin (Ub)-rich nuclear bodies, while Hdj2 (DNAJA1), a class I Hsp40 protein, condenses in nucleoli. Upon stress, both Hsp40 proteins incorporate into stress granules (SGs). Mutations of the G/F-rich region not only markedly impaired Hdj1 phase separation and SG involvement and disrupted the synergistic phase separation and colocalization of Hdj1 and fused in sarcoma (FUS) in cells. Being cophase separated with FUS, Hdj1 stabilized the liquid phase of FUS against proceeding into amyloid aggregation in vitro and alleviated abnormal FUS aggregation in cells. Moreover, Hdj1 uses different domains to chaperone FUS phase separation and amyloid aggregation. This paper suggests that phase separation is an intrinsic property of Hsp40 proteins, which enables efficient incorporation and function of Hsp40 in membraneless organelles and may further mediate the buildup of chaperone network in membraneless organelles.


Can videolaryngoscopy be a first option in a patient with laryngeal amyloidosis?
Amyloidosis is a term that involves a group of diseases characterised by deposition of extracellular monoclonal light-chain fibrillar immunoglobulin aggregates in the body, including many organs, with the larynx among them. A case is presented of a 78 year-old man who was referred to our institution for strangulated umbilical hernia treatment. He suffered from progressive hoarseness and dysphagia for 5months. He had a history of primary laryngeal amyloidosis. Awake intubation was performed successful with the King Vision® video-laryngoscopy. Sedation was achieved using a remifentanil infusion and midazolam. Haemorrhagic lesions are caused by deposition of amyloid in and around vessels, resulting in increased vascular fragility. Therefore, anaesthetists should take care in intubating the tracheas of these patients.


Selective adhesion and proliferation of cells on ion-implanted polymer domains.
We have found that the adhesion and proliferation of endothelial cells can be drastically improved when cultivated on an ion-implanted polymer surface. When the surface of segmented polyurethane, where endothelial cells are not capable of proliferating, is modified by Ne+ or Na+ ion implantation with a fluence of 1 x 10(15) ions/cm2 at an energy of 150 keV, cell adhesion and proliferation occurred selectively on the ion-implanted region irrespective of the ion species. The cells did not proliferate at ion fluences below 1 x 10(14) ions/cm2. Most cells migrated into the ion-implanted domain within 1-2 h, but some of the cells attached outside of the region and then slowly migrated into the region. Ion implantation of polystyrene, on which cells are capable of proliferating, further promoted cell spreading and proliferation, and increased resistance to detachment when the cells were exposed to trypsin.


Measurement of urinary advanced glycation end-products (AGEs) using a fluorescence assay for metabolic syndrome-related screening tests.
The simple screening test of advanced glycation end-products (AGEs) has not been established yet. We aimed to clarify the usefulness of simple measurement of AGEs for screening tests. The subjects were healthy participants and patients with metabolic syndrome. Urine samples were diluted from 1:10 to 1:200 using phosphate-buffered saline, and the fluorescence intensity was measured at 440nm after excitation at 370nm in a 96-well microplate spectrophotometer. The obtained intensities were adjusted according to the urinary creatinine levels. In patients with metabolic syndrome, urinary AGE levels were significantly higher than in healthy individuals (median [range], 168.25 [82.51-1276.15] AU/g creatinine [n=37] versus 134.67 [37.86-776.31] AU/g creatinine [n=350], respectively; p=0.0066). We found significant positive correlations between urinary AGEs and systolic and diastolic blood pressures (Spearman's correlation r=0.119 [p=0.019] and r=0.128 [p=0.012], respectively). There was no significant correlation between estimated glomerular filtration rate and urinary AGEs (r=0.018 [p=0.744]), confirming that renal dysfunction did not influence results of urinary AGE measurements. When all of the participants in the study were classified into four groups according to the numbers of components of metabolic syndrome, we found a significant tendency (p=0.0127) for urinary AGE levels to be higher with the increasing number of metabolic syndrome components. These results suggested that measurement of urinary AGE levels may be useful for evaluating the risk of metabolic syndrome.


Large variations in ocular dimensions in a multiethnic population with similar genetic background.
We aimed to describe the ethnic variations in ocular dimensions among three ethnic groups with similar genetic ancestry from mainland of China. We included 2119 ethnic Bai, 2202 ethnic Yi and 2183 ethnic Han adults aged 50 years or older in the study. Ocular dimensions including axial length (AL), anterior chamber depth (ACD), vitreous chamber depth (VCD) and lens thickness (LT) were measured using A-scan ultrasonography. Bai Chinese had longer ALs (P < 0.001), deeper ACDs (P < 0.001) but shallower VCDs (P < 0.001) compared with the other two ethnic groups. There were no ethnic variations in LTs. Diabetes was associated with shallower ACDs and this association was stronger in Bai Chinese compared with Yi or Han Chinese (P for interaction = 0.02). Thicker lenses were associated with younger age (P = 0.04), male gender (P < 0.001), smoking history (P = 0.01), alcohol intake (P = 0.03), the presence of cataract (P < 0.001), and the presence of diabetes (P < 0.001). There were significant differences in ocular dimensions among different ethnic groups with small differences in genetics but large variations in cultures and lifestyles.


Staying in aerobic shape: how the structural integrity of mitochondria and mitochondrial DNA is maintained.
The structure and integrity of the mitochondrial compartment are features essential for it to function efficiently. The maintenance of mitochondrial structure in cells ranging from yeast to humans has been shown to require both ongoing fission and fusion. Recent characterization of many of the molecular components that direct mitochondrial fission and fusion events have led to a more complete understanding of how these processes take place. Further, mitochondrial fragmentation observed when cells undergo apoptosis requires mitochondrial fission, underlying the importance of mitochondrial dynamics in cellular homeostasis. Mitochondrial structure also impacts mitochondrial DNA inheritance. Recent studies suggest that faithful transmission of mitochondrial DNA to daughter cells might require a mitochondrial membrane tethering apparatus.


Effectiveness of surgical fixation for rib fractures in relation to its timing: a retrospective Japanese nationwide study.
The effectiveness of surgical rib fixation is currently controversial, partly because of differences in timing. We used a Japanese nationwide database to investigate the effectiveness of surgical rib fixation in relation to its timing. We used the Japanese Diagnosis Procedure Combination database to identify patients with rib fractures who underwent mechanical ventilation from 1 July 2010 to 31 March 2018. We performed overlap weight analysis to compare in-hospital outcomes between patients who had and had not undergone surgical rib fixation within 3, 6 or 10 days after admission. The primary outcomes were duration of mechanical ventilation and post-rib fixation length of hospital stay. The secondary outcomes were tracheostomy, post-admission pneumonia and all-cause 28-day in-hospital mortality. We identified 8922 eligible patients. Surgical rib fixation within 3 days after admission was associated with shorter duration of mechanical ventilation (percent difference, - 42.9%; 95% confidence interval, - 57.4 to - 23.3) and shorter hospital stay (percent difference, - 19.6%; 95% confidence interval, - 31.8 to - 5.2). There were no significant differences between the groups in tracheostomy (risk difference, - 0.04; 95% confidence interval, - 0.15 to 0.07), post-admission pneumonia (risk difference, - 0.04; 95% confidence interval, - 0.13 to 0.05) or all-cause 28-day in-hospital mortality (risk difference, - 0.02; 95% confidence interval, - 0.07 to 0.03). However, there were no significant differences in any in-hospital outcomes between those who had and had not undergone rib fixation within 6 or 10 days after admission. Early surgical rib fixation was associated with better in-hospital outcomes, whereas later surgical rib fixation was not.


Accumulation of polyubiquitinated proteins: A consequence of early inactivation of the 26S proteasome.
The proteasomal degradation system is one of the most important protein degradation systems in the cytosol and nucleus. This system is present in two major forms: the ATP-stimulated 26S/30 S proteasome or the ATP-independent 20S core proteasome. While the first recognize ubiquitin-tagged target proteins and degrade them, the 20S proteasome works also independent from ATP, but requires partially unfolded substrates. While the role of the proteasome in the selective removal of oxidized proteins is undoubted, the debate about a selective ubiquitination of oxidized proteins is still ongoing. Here we demonstrate, that under some conditions of oxidative stress an accumulation of oxidized and of K48-ubiquitinated proteins occurs. However, the removal of oxidized proteins seems not to be linked to ubiquitination. In further experiments, we could show that the accumulation of ubiquitinated proteins under certain oxidative stress conditions is rather a result of a different sensitivity of the 26S proteasome and the ubiquitination machinery towards oxidants.


Ovarian metastases from colorectal cancer: a clinicopathological analysis of 103 patients.
To improve management of ovarian metastasis through assessment of clinicopathological features and treatment outcomes associated with ovarian metastasis from colorectal cancer. We recruited 103 subjects who were diagnosed with ovarian metastasis and subjected to surgery between June 1989 and December 2005. Clinical and pathological variables were evaluated. Survival and its associated factors were analysed with a median follow-up of 31 months after ovarian surgery (range 1-129 months). The mean age at diagnosis was 46 years (range 14-72 years), synchronous ovarian metastasis occurred in 74 patients and metachronous in 29 patients. The primary tumour was more commonly associated with the colon rather than the rectum (84/1608, 5.2%vs 19/1534, 1.2%, P < 0.001). Combined metastases occurred in 69 patients (67%). Complete resection was achieved in 34 (33%) patients without other metastases. The estimated 5-year disease free survival and overall survival rate were 40.1% and 26.6%, respectively. From univariate analysis, lymphovascular invasion (35.6%vs 12.8%, P = 0.034), combined metastasis (50.9%vs 15.6%, P = 0.0035) and bilaterale ovarian metastasis (36.4%vs 10.6%, P = 0.015) were identified as significant poor prognosis factors, and from multivariate analysis combined metastasis and bilaterale ovarian metastasis were significant (P = 0.034 and P = 0.015, respectively). This study suggests a role for regular follow-up computed tomography scans within 6 months postoperatively and tumour marker assays for the early detection of ovarian metastasis in premenopausal women after primary surgery, especially in colonic patients with poor prognostic factors.


Severe complications of circumcision: an analysis of 48 cases.
Circumcision is still the most commonly performed surgery in Islamic and Jewish societies. We report the findings of 48 cases referred for serious complications after circumcision that needed secondary surgical interventions. The aim of this study is to emphasize the important problem of circumcision complications. The 48 cases (mean age 14 years, range 5 months-24 years) with complications of circumcision were reviewed retrospectively. Circumcisions were performed at various medical centers or during religious ceremonies in environments other than health facilities. The most commonly observed complication was preputio-glandular fusion, seen in 25 cases (52%). The other complications were: meatal stenosis in 11 (23%), urethral fistula in five (10.4%), partial glandular amputation in four (8%) and opening distal urethra in three (6%). Adhesion freeing and revision were performed in all cases of preputio-glandular fusion, patients with meatal stenosis underwent meatotomy, urethral fistulae were repaired by simple closure, partial glans amputations were patched with buccal mucosa, and patients with complete open distal urethra were repaired by Mathieu (one patient) and tubularized incised plate urethroplasty techniques. Circumcision may be associated with many serious complications. To prevent these complications, the operation should be performed by educated and experienced personnel.


L-carnitine Modulates Cognitive Impairment Induced by Doxorubicin and Cyclophosphamide in Rats; Insights to Oxidative Stress, Inflammation, Synaptic Plasticity, Liver/brain, and Kidney/brain Axes.
Chemotherapy-induced cognitive impairment in cancer patients is known as "chemobrain". Doxorubicin and Cyclophosphamide are two chemotherapeutic agents used in combination to treat solid tumors. L-carnitine was reported for its anti-oxidant and anti-inflammatory activities. The goal of the present study was to elucidate the neuroprotective effect of L-carnitine against chemobrain induced by Doxorubicin and Cyclophosphamide in rats. Rats were divided into five groups: Control group; Doxorubicin (4mg/kg, IV) and Cyclophosphamide (40mg/kg, IV)-treated group; two L-carnitine-treated groups (150 and 300mg/kg, ip) with Doxorubicin and Cyclophosphamide; and L-carnitine alone-treated group (300mg/kg). Doxorubicin and Cyclophosphamide induced histopathological changes in rats' hippocampi and prefrontal cortices, as well as reduced memory as evidenced by behavioural testing. L-carnitine treatment showed opposite effects. In addition, chemotherapy treatment enhanced oxidative stress via reducing catalase and glutathione levels, and inducing lipid peroxidation. By contrast, L-carnitine treatment showed powerful antioxidant effects reversing chemotherapy-induced oxidative damage. Moreover, chemotherapy combination induced inflammation via their effect on nuclear factor kappa B (p65), interleukin-1β, and tumor necrosis factor-α. However, L-carnitine treatment corrected such inflammatory responses. Furthermore, Doxorubicin and Cyclophosphamide reduced synaptic plasticity via hindering expression of brain-derived neurotrophic factor, phosphorylated cyclase response element binding protein, synaptophysin, and postsynaptic density protein 95 whereas protein expression of such synaptic plasticity biomarkers was enhanced by L-carnitine treatment. Finally, acetylcholinesterase activity was found to be enhanced by chemotherapy treatment affecting rats' memory while L-carnitine treatment reduced acetylcholinesterase activity. L-carnitine also showed hepatoprotective and renal protective effects suggesting liver/brain and kidney/brain axes as possible mechanisms for its neuroprotective effects.


Activation and signaling mechanism revealed by GPR119-Gs complex structures.
Agonists selectively targeting cannabinoid receptor-like G-protein-coupled receptor (GPCR) GPR119 hold promise for treating metabolic disorders while avoiding unwanted side effects. Here we present the cryo-electron microscopy (cryo-EM) structures of the human GPR119-Gs signaling complexes bound to AR231453 and MBX-2982, two representative agonists reported for GPR119. The structures reveal a one-amino acid shift of the conserved proline residue of TM5 that forms an outward bulge, opening up a hydrophobic cavity between TM4 and TM5 at the middle of the membrane for its endogenous ligands-monounsaturated lipid metabolites. In addition, we observed a salt bridge between ICL1 of GPR119 and Gβs. Disruption of the salt bridge eliminates the cAMP production of GPR119, indicating an important role of Gβs in GPR119-mediated signaling. Our structures, together with mutagenesis studies, illustrate the conserved binding mode of the chemically different agonists, and provide insights into the conformational changes in receptor activation and G protein coupling.


Glucocorticoid receptor is involved in the neuroprotective effect of ginsenoside Rg1 against inflammation-induced dopaminergic neuronal degeneration in substantia nigra.
Accumulating clinical and experimental evidence suggests that chronic neuroinflammation is associated with dopaminergic neuronal death in Parkinson's disease (PD). Ginsenoside Rg1, the most active components of ginseng, possesses a variety of biological effects on the central nervous system, cardiovascular system and immune system. The present study aimed to evaluate the protective effects of ginsenoside Rg1 on lipopolysaccharide (LPS)-induced microglia activation and dopaminergic neuronal degeneration in rat substantia nigra (SN) and its potential mechanisms. Treatment with Rg1 could ameliorate the apomorphine-induced rotational behavior in LPS-lesioned rats. GR antagonist RU486 partly abolished the protective effect of Rg1. Rg1 treatment significantly attenuated LPS-induced loss of tyrosin hydroxlase (TH) positive neurons in substantial nigra par compacta (SNpc) and decreased content of dopamine (DA) and its metabolites in striatum of the lesioned side. Meanwhile, Rg1 significantly inhibited LPS-induced microglial activation and production of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and nitric oxide (NO). These effects were abolished by co-treatment with RU486. In addition, Rg1 treatment significantly inhibited the LPS-induced phosphorylation of IκB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) in the lesioned side of substantial nigra. These effect could be also partly blocked by RU486. Taken together, these data indicate that Rg1 has protective effects on mesencephalic dopaminergic neurons from LPS-induced microglia inflammation. GR signaling pathway might be involved in the anti-inflammatory effect of Rg1.


Disparities in outpatient and inpatient utilization by rural-urban areas among older Mongolians based on a modified WHO-SAGE instrument.
Mongolia has made significant progress towards achieving Universal Health Coverage (UHC), but there are still challenges ahead with population ageing and non-communicable diseases (NCDs). The purpose of this study was to investigate patterns and determinants of outpatient and inpatient health service use amongst older people in Mongolia. Data were collected using a questionnaire developed for the World Health Organization's Study on global AGEing and adult health (WHO SAGE). There were 478 participants from rural areas and 497 participants from Ulaanbaatar (further divided into 255 ger/yurt district and 242 apartment district residents). Multivariable logistic regression analyses were used to investigate determinants of outpatient and inpatient health service use with reported adjusted Odds Ratios (AORs) and 95 % Confidence Intervals (CIs). Participants were aged 60 to 93 years. About 55 % of respondents used outpatient services in the past 12 months and 51 % used inpatient services in the past three years. Hypertension was the most common reason for health service use. Rural residents had longer travel times and were more likely to incur out-of-pocket expenditure (OOP). Multivariable logistic regression revealed that women were more likely to use outpatient services (AOR 1.88; 1.34-2.63). Compared to apartment residents in urban areas, ger residents in urban areas were less likely to use outpatient services (AOR 0.54; 0.36-0.83). There was no statistically significant differences in inpatient service by location. Increasing numbers of chronic conditions (1 and 2+ compared to none) were associated with both outpatient (AORs 2.59 and 2.78) and inpatient (AORs 1.97 and 3.01) service use. This study highlights the needs to address disparities in outpatient service use for rural and urban ger populations. Compared with other WHO-SAGE countries, older Mongolians have relatively higher use of inpatient health care services. With a high prevalence of hypertension and an ageing population, efforts to achieve UHC would benefit from reorienting care services towards prevention and primary care management of NCDs to reduce the costs from hospital-based care.


Bronchial and vascular effects of Paf in the rat isolated lung are completely blocked by WEB 2086, a novel specific Paf antagonist.
1 The effect of the platelet-activating factor (Paf) antagonist, WEB 2086, on Paf-induced increase of pulmonary artery perfusion pressure (Pp), bronchial inflation pressure (Pi) and wet-to-dry lung weight ratios (W/D) was investigated in the rat isolated lung. 2 Lungs were perfused with Krebs-Ringer solution (KRS) as controls or with KRS containing WEB 2086 (0.1, 1.0, 10.0 or 100 micrograms ml-1) and then injected with a bolus of 20 micrograms Paf. 3 A dose-related inhibition of the Paf-induced increase of Pp, Pi and W/D was observed, being almost maximal for the 10.0 micrograms ml-1 and complete for the 100 micrograms ml-1 doses of WEB 2086 when compared to controls. 4 It is concluded that WEB 2086 is a highly effective and specific Paf antagonist in the pulmonary vasculature and bronchial tract.


Implementation of an Ultraviolet Phototherapy Service at a National Referral Hospital in Western Kenya: Reflections on Challenges and Lessons Learned.
In order to manage skin conditions at a national referral hospital level in Kenya, specialized dermatology services, such as dermatologic surgery, dermatopathology, phototherapy, and sub-specialty care, should be offered, as is typically available in referral hospitals around the world. A Kenyan patient with prurigo nodularis, whose severe itch remitted after phototherapy treatment at the University of California, San Francisco (UCSF), inspired the development of a phototherapy service at Academic Model Providing Access to Healthcare (AMPATH), a partnership in Western Kenya between Moi Teaching and Referral Hospital, Moi University College of Health Sciences, and a consortium of North American academic medical centers. Initial project funds were raised through a crowdfunding campaign and fundraising events. A new narrowband ultraviolet B phototherapy unit and replacement bulbs were donated and air shipped to Eldoret, Kenya. A team of dermatologists and phototherapy nurses from UCSF conducted a 2-day training session. US-based dermatologists affiliated with AMPATH provide ongoing support through regular communication and on-site visits. Early in implementation, challenges faced included training clinical staff with limited experience in phototherapy and improving communication between nurses and clinicians. More recent challenges include frequent rotation of specialty clinic nurses in the dermatology clinic, adaptation of phototherapy guidelines to balance patient volume with service delivery capacity, and training assessment of disease activity in darkly pigmented skin. Strategies that have been helpful in addressing implementation challenges include: increasing on-site and remote training opportunities for clinicians and nurses, developing a tiered payment schema, educating patients to combat misconceptions about phototherapy, dynamic phototherapy referral guidelines to accommodate service delivery capacity, and prioritizing the engagement of a multidisciplinary team.


Successful therapeutic management of canine Isosporosis in puppies.
Four labrador male puppies were confirmed for the Isospora spp infection by direct smear and flotation method following complains of anorexia, haematemesis and haematochezia. The puppies were treated with trimethoprime and sulphamethoxazole @ 40 mg/kg body weight in combination with metronidazole @ 10 mg/kg body weight twice daily for 5 days which was supported with fluid therapy, aniemetics and plasma expanders. All the animals showed completed clinical recovery along with clearing of faecal oocyst.


Dose dependent behavioral effects of acute alcohol administration in zebrafish fry.
The zebrafish is becoming increasingly utilized in behavioral neuroscience as it appears to strike a good compromise between practical simplicity and system complexity. Particularly in alcohol (ethanol) research, the zebrafish has been employed as a translationally relevant model organism. However, the majority of studies investigating the effects of alcohol on brain function and behavior has used adult zebrafish. In the current study, we utilize 6-8 post-fertilization day old larval zebrafish (fry) to investigate the effects of a 40 min-long, acute, immersion into the alcohol bath. We measure the behavioral responses of the fry during the immersion session in relatively large arenas, the petri dish, instead of the often employed 96 well plate, and report on significant modification of behavior induced by alcohol. For example, we found the intermediate dose of alcohol (0.5%, vol/vol) to exert a stimulant effect manifesting as slight elevation of swim speed, robust increase of turning, temporal variability of swim speed and turning, and diminished frequency of staying immobile. We also found the high dose of 1% alcohol to elicit an opposite response, a sedative effect. This biphasic dose response of alcohol mimics what has been found in mammals, including humans, and thus we conclude that a few day-old zebrafish fry may be a cost effective and efficient tool with which one can screen for small molecules or mutations with alcohol-effect modifying properties.


Antihyperglycemic activity of 2-methyl-3,4,5-triaryl-1H-pyrroles in SLM and STZ models.
Various 3,4,5-triarylpyrroles were synthesized and evaluated for their in vivo antihyperglycemic activity in sucrose-loaded (SLM) and/or streptozotocin-induced (STZ) diabetic rat models. Three of the test compounds, 2-methyl-4,5-diphenyl-3-substituted-phenyl-1H-pyrroles (3c, d and h) showed significant inhibition on postprandial hyperglycemia in normal rats post sucrose loaded. These compounds also showed lowering of plasma glucose level in STZ-induced diabetic rat model.


Isolation of herbicide-resistant mutants of Botryococcus braunii.
Aiming at herbicide-assisted cultivation of Botryococcus braunii for prevention of algal contamination, herbicide-tolerant mutant lines of B. braunii were established for two widely used herbicides, methyl viologen and glufosinate. Some established mutant lines exhibited vigorous oil production and growth in herbicide-containing media. Because the two herbicides were effective in controlling the growth of the algal competitors of B. braunii, these mutants can be directly used in industrial attempts for cost-effective oil production in herbicide-assisted non-axenic systems. This is the first report of mutagenesis of B. braunii.


Tissue protection mediated by mitochondrial K+ channels.
Two distinct K+ uniporters have been described in mitochondria, ATP-sensitive and Ca2+-activated. Both are capable of protecting tissues against ischemia and other forms of injury when active. These findings indicate a central role for mitochondrial K+ uptake in tissue protection. This review describes the characteristics of mitochondrial K+ uniport, physiological consequences of this transport, forms of tissue damage in which K+ channels are implicated and possible mechanisms through which protection occurs.


[Eye and corticosteroid's use].
Most common side effects of systemic corticosteroids are posterior subcapsular cataract and glaucoma. There is no way to prevent corticosteroid-induced cataract. The risk of these complications varies (cataract 11 to 15%; glaucoma 12.8%), and it depends on the dose, duration of administration and terrain. The discontinuation of corticosteroid therapy is required in cases of uncontrolled glaucoma by hypotonic treatment. Long-term topical or general steroids prescription has to be done after an ophthalmological examination. Indications of ophthalmic general corticosteroids are acute orbital and ocular inflammations. affecting the middle and posterior segments of the eye, or sclera when topical treatment is ineffective. When administered topically, only 5% of the delivered dose is absorbed by the anterior segment, distribution is almost zero in the middle and posterior segments of the eye.


Interactions between the associations of parity, lactation length, and weaning-to-conception interval with subsequent litter size in swine herds using early weaning.
Sixteen farms having an average lactation length between 14.9 and 18.9 days were selected based upon producers' willingness to keep records of production and lactation feed intake. Data contained 9162 subsequent litter-size records abstracted from computerized production information-system files and lactation feed-intake records. Two-way interactions between the associations of parity and lactation length, and parity and weaning-to-conception interval with subsequent litter size were found in the same statistical model. Subsequent litter size did not increase in parities 1 and 2 as lactation length increased--but subsequent litter size in sows of parities 3-6 increased. In only parity 1, sows with weaning-to-conception interval 6-12 days produced 0.5 fewer pigs at subsequent farrowing than those with weaning-to-conception interval 1-5 days. However, in multiparous sows, no difference in subsequent litter size was found between weaning-to-conception intervals 1-5 and 6-12 days.


ALDH3B1 protects interfollicular epidermal cells against lipid peroxidation via the NRF2 pathway.
Reactive oxygen species (ROS) production is critical for the initiation of wound repair; however, persistently high levels of ROS can lead to lipid peroxidation in cells and thus affect wound healing. Iron is a transition metal that is an essential component of almost all living cells and organisms. When present in excess in cells and tissues, iron disrupts redox homeostasis and catalyzes the generation of ROS, leading to increased lipid peroxidation. In this study, we found that after treating interfollicular epidermal (IFE) cells with different concentrations of holotransferrin (0 µg/ml, 1 µg/ml, 10 µg/ml, 100 µg/ml, and 1 mg/ml), the intracellular iron content increased, and cell viability and function did not differ significantly among the treatment groups of cells. In addition, the level of lipid peroxidation in IFE cells did not increase following holotransferrin treatment. We speculated that there is a protective mechanism within IFE cells that reduces the occurrence of intracellular lipid peroxidation. We also found that the elevated intracellular iron content of IFE cells was accompanied by elevated ALDH3B1 expression. We investigated the effect of ALDH3B1 on the level of lipid peroxidation in IFE cells and found that elevated ALDH3B1 expression decreased the damage to IFE cells induced by lipid peroxidation. In addition, the NRF2 pathway was found to affect the expression of ALDH3B1, which in turn affected lipid peroxidation in IFE cells. These findings suggest that in IFE cells, activation of the NRF2 pathway can increase the expression of ALDH3B1 and thus reduce the production of intracellular ROS and the occurrence of intracellular lipid peroxidation. Therefore, ALDH3B1 may be a potential target for the treatment of chronic wounds.


Heterotrimeric G proteins and microtubules.
Microtubules, major components of the cytoskeleton, play important roles in a variety of cellular functions including mitosis, intracellular transport, and the modulation of cell morphology. Several studies have demonstrated that specific G-protein alpha subunits bind to tubulin with a high affinity (~130 nM) and elicit various functional effects on tubulin and microtubules. In this chapter, we present a description of the protocols for several methods that are used to determine the interaction between heterotrimeric G proteins and tubulin, as well as functional consequences of the interactions including protocols for protein purification, binding assays, tubulin GTPase assays, microtubule dynamics assays, and assays for cytoskeletal consequences of G-protein-coupled receptor signaling.


Multiple active forms of a novel serine protease from Bacillus subtilis.
We have cloned and sequenced a gene (epr) encoding a novel serine protease from Bacillus subtilis. Several active forms of the enzyme with molecular masses between 40 and 34 kDa were found in the medium of B. subtilis cultures containing the epr gene cloned on a plasmid. Deletions at the 3' end of the gene, removing up to 240 amino acids of the reading frame, abolished the expression of the larger species but did not affect the expression of the 34 kDa enzyme. The C-terminal third of the protein is therefore not required for protease activity. The size variation of the active forms expressed by the complete epr gene appears to be the result of partial removal of the C-terminus either by processing or degradation. Thus, the epr gene consists of two domains, one encoding a serine protease homologous to subtilisin and the other a C-terminus of unknown function.


[Highly Frequent Regeneration System Establishment of Lycium ruthenicum].
To establish a rapid regeneration system of Lycium ruthenicum in order to produce large-scale commodity seedlings. Cotyledon, hypocotyl and radicle of Lycium ruthenicum seedlings were used as explants to produce plantlets by depending on MS basal medium mixed with the different kinds and different concentration of hormones. The desirable hormone composition for the inducement was MS + 6-BA 1.0 mg/L + NAA 0.5 mg/L, and the callus induction rate was as high as 100%, the optimum medium for the buds sprouting and regeneration was that of MS + 6-BA 0.5 mg/L + NAA 0.5 mg/L, with a propagation coefficient of 7.73, and the suitable medium for the roots induction was 1/2MS + IBA 1.0 mg/L, 90% of the regenerated plantlets transferred to an open field survive and grow well. The callus can be induced by cotyledon, hypocotyls and radicle of Lycium ruthenicum seedlings, and hypocotyls is the best explants for callus induced. The formulations suitable for callus induction, differentiation, bud proliferation and rooting are screened out to establish the rapid regeneration system for Lycium ruthenicum.


Modeling Tumor Evolutionary Dynamics to Predict Clinical Outcomes for Patients with Metastatic Colorectal Cancer: A Retrospective Analysis.
Over 50% of colorectal cancer patients develop resistance after a transient response to therapy. Understanding tumor resistance from an evolutionary perspective leads to better predictions of treatment outcomes. The objectives of this study were to develop a computational framework to analyze tumor longitudinal measurements and recapitulate the individual evolutionary dynamics in metastatic colorectal cancer (mCRC) patients. A stochastic modeling framework was developed to depict the whole spectrum of tumor evolution prior to diagnosis and during and after therapy. The evolutionary model was optimized using a nonlinear mixed effect (NLME) method based on the longitudinal measurements of liver metastatic lesions from 599 mCRC patients. The deterministic limits in the NLME model were applied to optimize the stochastic model for each patient. Cox proportional hazards models coupled with the least absolute shrinkage and selection operator (LASSO) algorithm were applied to predict patients' progression-free survival (PFS) and overall survival (OS). The stochastic evolutionary model well described the longitudinal profiles of tumor sizes. The evolutionary parameters optimized for each patient indicated substantial interpatient variability. The number of resistant subclones at diagnosis was found to be a significant predictor to survival, and the hazard ratios with 95% CI were 1.09 (0.79-1.49) and 1.54 (1.01-2.34) for patients with three or more resistant subclones. Coupled with several patient characteristics, evolutionary parameters strongly predict patients' PFS and OS. A stochastic computational framework was successfully developed to recapitulate individual patient evolutionary dynamics, which could predict clinical survival outcomes in mCRC patients. SIGNIFICANCE: A data analysis framework depicts the individual evolutionary dynamics of mCRC patients and can be generalized to project patient survival outcomes.


Sterol-side chain cleavage by fusants ofAlkaligenes foecalis andArthrobacter oxydans.
Protoplasts of a strain ofA. foecalis incapable of utilizing beta-sitosterol as carbon source for growth were fused with protoplasts ofA. oxydans - a strain capable of complete degradation of beta-sitosterol. Five fusants showing morphology and pattern of transformation of C-19 steroids identical toA. Foecalis were selected. Analysis of the fermentation broth containing beta-sitosterol showed that the fusants were capable of utilizing beta-sitosterol for growth but their pattern of metabolite formation from beta-sitosterol was different from that ofA. oxydans. The study revealed that the protoplast fusion technique could be used for intergeneric transfer of genetic determinants linked to partial cleavage of beta-sitosterol side chain toA. foecalis fromA. oxydans.


Differential DNA methylation profile of key genes in malignant prostate epithelial cells transformed by inorganic arsenic or cadmium.
Previous work shows altered methylation patterns in inorganic arsenic (iAs)- or cadmium (Cd)-transformed epithelial cells. Here, the methylation status near the transcriptional start site was assessed in the normal human prostate epithelial cell line (RWPE-1) that was malignantly transformed by 10μM Cd for 11weeks (CTPE) or 5μM iAs for 29weeks (CAsE-PE), at which time cells showed multiple markers of acquired cancer phenotype. Next generation sequencing of the transcriptome of CAsE-PE cells identified multiple dysregulated genes. Of the most highly dysregulated genes, five genes that can be relevant to the carcinogenic process (S100P, HYAL1, NTM, NES, ALDH1A1) were chosen for an in-depth analysis of the DNA methylation profile. DNA was isolated, bisulfite converted, and combined bisulfite restriction analysis was used to identify differentially methylated CpG sites, which was confirmed with bisulfite sequencing. Four of the five genes showed differential methylation in transformants relative to control cells that was inversely related to altered gene expression. Increased expression of HYAL1 (>25-fold) and S100P (>40-fold) in transformants was correlated with hypomethylation near the transcriptional start site. Decreased expression of NES (>15-fold) and NTM (>1000-fold) in transformants was correlated with hypermethylation near the transcriptional start site. ALDH1A1 expression was differentially expressed in transformed cells but was not differentially methylated relative to control. In conclusion, altered gene expression observed in Cd and iAs transformed cells may result from altered DNA methylation status.


Applying a relative ranking model to the self-assessment of extended performances.
Accurate self-assessment is an important but underdeveloped skill in medicine that, in the past, has received little formal attention from educators. Following an orthopedic rotation, twenty-five orthopedic surgery residents performed a self-assessment task for ten skills using a new relative ranking method, in which an individual's skills are ranked relative to each other rather than being compared to the individual's peers. Supervising faculty assessed residents using the same instrument. Faculty inter-rater reliability was measured and comparisons were made between each resident's self-assessment and the faculty assessments using Spearman rank order correlation coefficients. The mean correlation between faculty rating the same resident was 0.27 (sd = 0.49). The mean correlation between resident and faculty rankings was 0.20 (sd = 0.38), but was higher for junior residents (0.33) than for senior residents (0.12), apparently because senior residents do not alter their self-assessments while faculty change their assessments of senior residents. Consistent with the literature in other fields, we find that self-assessment is poor among surgical trainees when they are asked to assess their own performance over an extended time period.


Analysis by Age Group of Disease Outcomes in Patients with Psoriatic Arthritis: A Cross-Sectional Multicentre Study.
Elderly psoriatic arthritis (PsA) patients may show greater inflammatory activity and worse prognoses than patients of other ages. However, these patients may be at risk of receiving fewer systemic treatments. In this report, we have analysed disease outcomes in PsA by age groups. This cross-sectional, multicentre study included 227 PsA patients under biological and non-biological systemic therapies. The study population was divided into four categories by age: < 40, 40‒49, 50‒65 and > 65 years. Physical functioning, disease activity, remission rates and disease impact were compared. Thirty-one patients (13.7%) were under 40 years, 26.9% (n = 61) were 40-49 years, 26.4% (n = 60) were 50-65 years and 33.0% (n = 75) were patients > 65 years. Compared with the other age groups, disease duration was significantly higher in subjects older than 65 years (p < 0.001). Only 8% of patients older than 65 years received corticosteroids compared with 29% of patients aged < 40 years, 13.1% of patients aged 40-49 years and 26.7% of patients aged 50-65 years (p = 0.007). Similarly, only 36% of patients over 65 years of age received a biological therapy compared with between 51.6 and 59% for the other age groups (p = 0.036). However, remission rates were not statistically different between groups. Disease-associated physical disability was similar among groups. Compared with patients aged < 40 years, more patients > 65 years achieved low disease impact (10.7% vs 37.7%, respectively; p < 0.05). Fewer older patients received corticosteroids and biological therapy. However, disease outcomes were similar or even better compared with those observed in younger patients. Therefore, treatment strategies for older patients with PsA should be similar to those offered to younger individuals.


Optimizing screening for tuberculosis and hepatitis B prior to starting tumor necrosis factor-α inhibitors in Crohn's disease.
Treatment with tumor necrosis factor-α (TNF-α) inhibitors in patients with Crohn's disease (CD) is associated with potentially serious infections, including tuberculosis (TB) and hepatitis B virus (HBV). We assessed the cost-effectiveness of extensive TB screening and HBV screening prior to initiating TNF-α inhibitors in CD. We constructed two Markov models: (1) comparing tuberculin skin test (TST) combined with chest X-ray (conventional TB screening) versus TST and chest X-ray followed by the interferon-gamma release assay (extensive TB screening) in diagnosing TB; and (2) HBV screening versus no HBV screening. Our base-case included an adult CD patient starting with infliximab treatment. Input parameters were extracted from the literature. Direct medical costs were assessed and discounted following a third-party payer perspective. The main outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity and Monte Carlo analyses were performed over wide ranges of probability and cost estimates. At base-case, the ICERs of extensive screening and HBV screening were €64,340 and €75,760 respectively to gain one quality-adjusted life year. Sensitivity analyses concluded that extensive TB screening was a cost-effective strategy if the latent TB prevalence is more than 12 % or if the false positivity rate of TST is more than 20 %. HBV screening became cost-effective if HBV reactivation or HBV-related mortality is higher than 37 and 62 %, respectively. Extensive TB screening and HBV screening are not cost-effective compared with conventional TB screening and no HBV screening, respectively. However, when targeted at high-risk patient groups, these screening strategies are likely to become cost-effective.


Metacognitive monitoring of attention performance and its influencing factors.
Metacognitive monitoring is a central element of metacognitive processing exerting widespread influences on information processing. Albeit being subject to numerous empirical investigations referring to memory performance, there is little research investigating metacognitive monitoring in other cognitive domains. The present study investigated in 45 healthy students whether factors that are known to influence monitoring of memory performance, i.e., task difficulty, time of assessment, and practice, also exhibit a significant impact on monitoring of attention performance. A multivariate analysis of variance with three within-subject repeated measures factors on two dependent variables (monitoring of (a) time, and (b) errors in an attention task) was conducted. Results showed that monitoring ability significantly decreased with increasing task difficulty, was significantly better for post than for pre-assessment, and significantly increased with practice. Therefore, results suggest that the examined factors influenced monitoring of attention performance equivalent to the influence of these factors found in metamemory research.


The identification of material basis of Si Miao Formula effective for attenuating non-alcoholic fatty liver disease.
The Si Miao Formula (SMF), a traditional Chinese medicine, originated from the "Cheng Fang Bian Du" during the Qing Dynasty and is commonly employed for the treatment of gout and hyperuricemia. We have demonstrated the anti-NAFLD effect of SMF by regulating hepatic lipid metabolism in high fat and high sucrose (HFHS) feeding mice in our previous report. However, the material basis of SMF for its anti-NAFLD effect remains unknown. To compare the effeciacy of different components of SMF and identify the material basis for its anti-NAFLD effect. In the present study, a "Leave-one out" strategy was adopted by removing one herb from SMF each time, and the anti-NAFLD effects of four decomposed recipes containing three herbs were evaluated in C57BL/6J mice fed with an HFHS diet for 16 weeks. The chemical components of SMF and the absorbed entities in serum were assayed using UHPLC-Q-Exactive-Orbitrap HRMS. Finally, a new chemical combination with four compounds (berberine, betaine, caffeic acid, p-coumaric acid, 2:2:1:1) were generated (SMF component composition, SMF_CC), and its anti-NAFLD effect was evaluated by comparing with the original SMF in the mouse model. Varified effects on NAFLD mice were observed among the decomposed recipes of SMF, while the original SMF showed advantages over its decomposed recipes. A total of 111 chemicals were identified from SMF, and 21 of them were detected in serum after oral administration of SMF. Comparing to SMF, SMF_CC showed comparable anti-NAFLD effect in HFHS-diet-fed mice, which was associated with the inhibition of hepatic fatty acid synthesis and transport, as well as inflammation. Our current results suggested that the original SMF was better than its decomposed recipes in NAFLD management, and the derived SMF_CC was also effective in inhibiting NAFLD formation, highlighting its potential of being a novel natural agent for NAFLD therapy.


The clinical utility of image-guided iodine-125 seed in patients with unresectable pancreatic cancer.
In the present study, we investigated the clinical effects of image-guided iodine-125 ((125)I) seed on unresectable pancreatic cancer. Twenty-five patients with unresectable pancreatic cancer were enrolled in this study, including 13 patients with seed implantation and 12 patients as control. The survival status, clinical benefits, objective curative effects, and relevant tumor markers were analyzed to assess the feasibility and safety of interstitial (125)I seed implantation. We found that the clinical benefit rate of the seed implantation group is 92.3 % (12/13), compared with 41.7 % (5/12) in the control, and the difference was statistically significant (p < 0.01). Compared with control, patients with seed implantation had significantly shorter operative time, less bleeding, higher albumin, shorter periods to bowel movement, and normal diet as well as lower risk of complications (p < 0.001). The differences of objective curative effects adverse effects, complications, and median survival between these two groups were not significant statistically (p > 0.05). In conclusion, (125)I seed implantation provides a safe and effective method to inhibit the tumor development, relieve pain, and improve quality of life for unresectable pancreatic cancer. These findings need to be validated by conducting further studies with larger cohorts.


Kinetics of the substitution reaction of thiocyanate with tetrakis (3-N-methylphyridyl)porphinecobalt(III).
The equilibrium constant for the first thiocyanate addition to Co(III)-tetra(3-N-methylpyridyl)porphine is a factor of two smaller than for the less basic 4-N-methylporphine isomer. This effect is primarily due to a larger Co-SCN dissociation rate constant for the 3-isomer.


Heparin-associated antibody with pregnancy: discussion of two cases.
Heparin-associated thrombocytopenia may be a potentially devastating event when linked with thrombosis. Two cases of heparin-associated thrombocytopenia are presented, one with thrombosis that culminated in maternal death. Heparin-associated platelet antibody was seen in both patients. The incidence and management of heparin-associated thrombocytopenia are discussed.


Accelerated methanogenesis from effluents of hydrogen-producing stage in anaerobic digestion by mixed cultures enriched with acetate and nano-sized magnetite particles.
Potential for paddy soil enrichments obtained in the presence of nano-sized magnetite particles (named as PSEM) to promote methane production from effluents of hydrogen-producing stage in two-stage anaerobic digestion was investigated. The results showed that the addition of magnetite significantly accelerated methane production from acetate in a dose-independent manner. The results from high-throughput sequencing analysis revealed that Rhodocyclaceae-related species were selectively enriched, which were likely the key players for conversion of acetate to methane in PSEM. Compared to the paddy soil enrichments obtained in the absence of magnetite (named as PSEC), the maximum methane production rate in PSEM was significantly higher (1.5-5.5times higher for the artificial medium and 0.2-1.7times higher for the effluents). The accelerated methane production from the effluents indicated remarkably application potential of PSEM for improving performance of anaerobic digestion.


Inflammation induced loss of skeletal muscle.
Inflammation is an important contributor to the pathology of diseases implicated in skeletal muscle dysfunction. A number of diseases and disorders including inflammatory myopathies and Chronic Obstructive Pulmonary Disorder (COPD) are characterized by chronic inflammation or elevation of the inflammatory mediators. While these disease states exhibit different pathologies, all have in common the loss of skeletal muscle mass and a deregulated skeletal muscle physiology. Pro-inflammatory cytokines are key contributors to chronic inflammation found in many of these diseases. This section of the review focuses on some of the known inflammatory disorders like COPD, Rheumatoid Arthritis (RA) and inflammatory myopathies that display skeletal muscle atrophy and also provides the reader an overview of the mediators of inflammation, their signaling pathways, and mechanisms of action. This article is part of a Special Issue entitled "Muscle Bone Interactions".


Onconase dimerization through 3D domain swapping: structural investigations and increase in the apoptotic effect in cancer cells.
Onconase® (ONC), a protein extracted from the oocytes of the Rana pipiens frog, is a monomeric member of the secretory 'pancreatic-type' RNase superfamily. Interestingly, ONC is the only monomeric ribonuclease endowed with a high cytotoxic activity. In contrast with other monomeric RNases, ONC displays a high cytotoxic activity. In this work, we found that ONC spontaneously forms dimeric traces and that the dimer amount increases about four times after lyophilization from acetic acid solutions. Differently from RNase A (bovine pancreatic ribonuclease) and the bovine seminal ribonuclease, which produce N- and C-terminal domain-swapped conformers, ONC forms only one dimer, here named ONC-D. Cross-linking with divinylsulfone reveals that this dimer forms through the three-dimensional domain swapping of its N-termini, being the C-terminus blocked by a disulfide bond. Also, a homology model is proposed for ONC-D, starting from the well-known structure of RNase A N-swapped dimer and taking into account the results obtained from spectroscopic and stability analyses. Finally, we show that ONC is more cytotoxic and exerts a higher apoptotic effect in its dimeric rather than in its monomeric form, either when administered alone or when accompanied by the chemotherapeutic drug gemcitabine. These results suggest new promising implications in cancer treatment.


The relationship between the cholinergic mechanism of toxicity and oxidative stress in rats during subacute diazinon poisoning.
Diazinon is an organophosphate pesticide (OP) that has significant potential for accidental and intentional poisoning of wildlife, domestic animals and humans. The aim of the study is to investigate the correlation between cholinesterase activity and oxidative stress parameters in liver and diaphragm by continuous monitoring as a function of time during prolonged use of diazinon. Wistar rats were treated orally with diazinon (55 mg/kg/day): 7, 14, 21 and 28 days. At the end of each period, blood, liver and diaphragm were collected to examine cholinesterase activity and enzymatic/non-enzymatic oxidative stress parameters: superoxide dismutase 1 (SOD1), catalase (CAT), thiobarbituric acid substances (TBARS), protein carbonyl groups. In all four time periods, there was a significant change in acetylcholinesterase (AChE) in erythrocytes and butyrylcholinesterase (BuChE) in blood plasma, CAT in liver and diaphragm and SOD1 in diaphragm. Parameters significantly altered during the cholinergic crisis included: cholinesterases and TBARS in liver and diaphragm and partially SOD1 in liver. Protein carbonyl groups in liver and diaphragm were significantly altered outside the cholinergic crisis. In the liver, there was a very strong negative correlation between BuChE and TBARS in all four time periods and BuChE and CAT on day 7. In the diaphragm, a very strong negative correlation was found between AChE and TBARS at days 7 and 14, and a very strong positive correlation between AChE and SOD1 at days 14, 21 and 28. A better understanding of the relationship between cholinergic overstimulation and oxidative stress may help to better assess health status in prolonged OPs intoxication.


Keeping an eye on the rest of the body.
The health problems of the elderly are multiplying exponentially with the demographic changes in our aging population. Visual impairment represents one of the most significant of these problems, not only in terms of eye diseases, but because of the associated dangers affecting the rest of the body. The gradual loss of vision, especially if it first affects one eye, is often ignored or denied until it is far advanced with marked functional impairment or causes serious accident. A high percentage of falls, often with resulting fractures, is a direct result of poor vision, but in the elderly this risk is frequently compounded by unsteady gait, osteoporosis, and poor lighting. Misuse of medication, especially with overdose is frequent when directions are in small print. Misuse can be exacerbated by poor memory. The risk of driving accidents is increased. Although notable progress has been made in technical approaches to ophthalmology, many serious problems such as macular and retinal degeneration remain unsolved. The American Federation for Aging Research, which is dedicated to the support of research in all biomedical changes associated with aging, has an active interest in basic research in the field of visual impairment with other changes and diseases in our elderly population.


Detection of carcinogen-induced DNA breaks by nick translation in permeable cells.
A nick-translation reaction with E. coli DNA polymerase I (pol. I) was used to detect in situ DNA breaks produced by chemical carcinogens. Normal human fibroblasts treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in various doses were permeabilized with lysolecithin, and were nick translated in the presence of [3H]dCTP and pol. I. The radioactivity incorporated increased with MNNG concentration, and was directly proportional to the poly(ADP-ribose) synthetase activity. Other DNA-damaging agents such as bleomycin or 4-nitroquinoline 1-oxide also caused the nick translation rate to increase. When MNNG-treated cells were cultured in fresh medium containing no MNNG, the increase in the rate of nick translation in permeable cells became less and this decrease was abolished by addition of aphidicolin or cytosine arabinoside. The nick translation method described here may be a useful means for estimating intrinsic DNA breaks in cells treated with carcinogens.


The microcirculation image quality score: development and preliminary evaluation of a proposed approach to grading quality of image acquisition for bedside videomicroscopy.
Side-stream dark-field microscopy is currently used to directly visualize sublingual microcirculation at the bedside. Our experience has found inherent technical challenges in the image acquisition process. This article presents and assesses a quality assurance method to rate image acquisition quality before analysis. We identified 6 common image capture and analysis problem areas in sublingual side-stream dark-field videos: illumination, duration, focus, content, stability, and pressure. We created the "Microcirculation Image Quality Score" by assigning a score of optimal (0 points), suboptimal but acceptable (1 point), or unacceptable (10 points) to each category (for further details, go to http://www.MicroscanAnalysis.blogspot.com). We evaluated 59 videos from a convenience sample of 34 unselected, noncritically ill emergency department patients to create a test set. Two raters, blinded to each other, implemented the score. Any video with a cumulative score of 10 or higher (range, 0-60) was considered unacceptable for further analysis. We created the Microcirculation Image Quality Score and applied it to 59 videos. For this particular set of 59 videos, the mean (SD) passing quality score was 1.68 (0.90), and the mean (SD) failing quality score was 15.74 (6.19), with 27 of 59 passing the quality score less than 10. Highest failure occurred from pressure artifact. The interrater agreement for acceptability was assessed using Cohen κ for each category: illumination (κ = 1.0), duration (κ = 1.0), focus (κ = 0.91), content (κ = 0.76), stability (κ = 0.71), and pressure (κ = 0.82) and overall pass-fail rates (score >10) (κ = 0.66). Our Microcirculation Image Quality Score addresses many of the common areas where video quality can degrade. The criteria introduced are an objective way to assess the quality of image acquisition, with the goal of selecting videos of adequate quality for analysis. The interrater reliability results in our preliminary study suggest that the Microcirculation Image Quality Score is reasonably repeatable between reviewers. Further assessment is warranted.


Routine patch testing in a dermatology clinic of a teaching hospital in Nigeria.
Allergic Contact Dermatitis (ACD) poses a great diagnostic challenge to the dermatologist as it mimics many common dermatoses. Patch test (PT) is used to establish the diagnosis of ACD and to exclude suspected allergens. This study reviewed the clinical presentations and patch test results of consecutive patients with the diagnosis of allergic contact dermatitis seen at the skin clinic of the Lagos University Teaching Hospital (LUTH). This was a prospective study of all patients that presented with features of allergic contact dermatitis at the skin clinic of LUTH between September 2003 and October 2004. One hundred and two patients with ACD and 100 controls were patch tested and included in the sample size. Allergic contact dermatitis accounted for 7.7% of patients that presented at the dermatology clinic of LUTH during the study period. There was a slight female preponderance and the highest number of patients presented between the ages of 21 and 40. Features of chronic eczema were found in 71.4% of patients. Sixty patients (58.3%) and 26 controls (26%) had positive patch test responses. There was a statistically significant difference between the patch test responses in patients and controls. The specificity of the patch test procedure was 74% and the sensitivity was 58.8%. Patients with allergic contact dermatitis will benefit from routine patch test for aetiological diagnosis and to prevent chronicity.


Measurement of grip strength in the diagnosis of wrist pain.
Grip strength was assessed in patients with chronic wrist pain and correlated with the results of subsequent bone scans and pathology. The results showed a highly significant decrease of grip strength in patients with positive bone scans or confirmed wrist pathology compared with those with negative bone scans (p less than 0.01). We conclude that the detection of weakness of grip is a simple indicator of true pathology in "obscure" wrist pain.


Clinical characteristics of fatal patients with severe acute respiratory syndrome in a medical center in Taipei.
The clinical spectrum of severe acute respiratory syndrome (SARS) varies widely in the way that asymptomatic carriers are believed to exist in the community. Still there are severe forms of illness in which the patients deteriorate unexpectedly within hours. This study delineates clinical characteristics of such fatal cases of SARS for the purpose of identifying patients with poor outcome. Patients with the diagnosis of probable or suspected SARS admitted to the Taipei Veterans General Hospital during the period from March 26, 2003 to May 25, 2003 were included. The medical records of fatal cases were retrospectively reviewed. During the study period, thirty-six probable cases and 17 suspected cases of SARS were identified. Eight probable but none of the suspected cases died from acute respiratory distress syndrome (ARDS) with multiple organ dysfunction after a median of 6-day hospital stay (range, 1-30 days). All but 2 patients acquired the infection nosocomially. Of the fatal cases, four were males and 4 females, with the median age of 65 years (range, 29-76 yrs). All except 3 had co-morbid conditions, such as hypertension, diabetes mellitus, coronary artery disease or chronic obstructive pulmonary disease. The lactate dehydrogenase (LDH) values were abnormal (> 200 U/L) in all patients. The chest radiograph of these fatal cases consistently showed multifocal infiltration over the unilateral or bilateral lobe of the lung. Patients of SARS who had advanced age, co-morbid conditions, highly elevated LDH and multifocal infiltration over chest radiograph should be closely monitored and actively treated.


Photofunctionalization as a suitable approach to improve the osseointegration of implants in animal models-A systematic review and meta-analysis.
To determine whether photofunctionalization influences dental implant osseointegration. Data on osseointegration rates were extracted from 8 databases, based on bone-to-implant contact (BIC) and pushout tests. Internal validity was accessed through the SYRCLE risk of bias tool for animal experimental studies. Meta-analyses were performed for investigation of the influence of photofunctionalization on implant osseointegration, with a random effect and a confidence interval of 95%. The certainty of evidence was accessed through the GRADE approach. Thirty-four records were identified, and 10 were included in the meta-analysis. Photofunctionalized implants showed higher mean values for BIC in rabbits (MD 6.92 [1.01, 12.82], p = .02), dogs (MD 23.70 [10.23, 37.16], p = .001), rats (MD 20.93 [12.91, 28.95], p < .0001), and in the pooled BIC analyses (MD 14.23 [7.80, 20.66], p < .0001) compared to those in control implants in the overall assay. Conversely, at late healing periods, the pooled BIC meta-analyses showed no statistically significant differences (p > .05) for photofunctionalized and control implants at 12 weeks of follow-up. For pushout analysis, photofunctionalized implants presented greater bone strength integration (MD 19.92 [13.88, 25.96], p < .0001) compared to that of control implants. The heterogeneity between studies ranged from "not important" to "moderate" for rabbits I2 = 24%, dogs I2 = 0%, rats I2 = 0%, and pooled BIC (I2 = 49%), while considerable heterogeneity was observed for pushouts (I2 = 90%). Photofunctionalization improves osseointegration in the initial healing period of implants, as summarized from available data from rabbit, dog, and rat in vivo models.


Dexamethasone for delayed edema after intracerebral hemorrhage: To be or not to be?
The pathogenesis of delayed cerebral edema after intracerebral hemorrhage is still unclear. In this case report, we speculate that the formation of subdural effusion or hemorrhage is associated with delayed cerebral edema. By referring to the treatment plan of chronic subdural hematoma, adding dexamethasone to routine medication, certain therapeutic effect has been achieved. Dexamethasone may maintain the stability of blood-brain barrier by directly increasing the expression of ZO-1, and reduce the neuroinflammatory response caused by NF-κB pathway by upregulating KLF2 expression, ultimately reducing nerve injury through multiple pathways.


Radiofrequency sinus excision: better alternative to marsupialization technique in sacrococcygeal pilonidal sinus disease.
A number of techniques have been described for treatment of patients with sacrococcygeal pilonidal sinus disease. The author reports his experience in the surgical management of pilonidal sinus using radiofrequency sinus excision technique. The results are compared with those obtained after excision and marsupialization procedure. Seventeen patients were operated by radiofrequency sinus excision and 18 with excision and marsupialization. An Ellman radiofrequency device was used. The two groups were matched for age, gender and presentation symptoms. The median follow-up was two years. The patient's satisfaction on the outcome of the procedure was also evaluated. In the radiofrequency sinus excision group, we found on average a shorter operation time (10 vs. 36 minutes, p < 0.001), shorter hospitalization (nine vs. 30 hours, p < 0.001), significantly less postoperative pain, fewer cumulatve requests for analgesia by the patients (14 vs. 25 tablets, p < 0.001), and earlier return to work (six vs. 16 days, p < 0.001) The wounds with marsupialization did heal faster than those with sinus excision; however, the difference was not significant. At two year follow-up, one patient from each group had a recurrence. This pilot study shows that this new technique can be performed as a day care surgery. With reduced postoperative pain and early resumption to work, patient satisfaction is better in comparison to excision and marsupialization technique.


Secular trends in longevity among people with Down syndrome in Japan, 1995-2016.
Life expectancy in Japan has increased dramatically and is one of the longest in the world. However, the changes in lifespan in Japanese individuals with congenital diseases remain unknown. We investigated secular changes in the lifespan of people with Down syndrome over the last 20 years. We observed secular trends in the number of stillbirths, deaths and the mortality rates at ages 20, 40, and 60 among all deaths registered with Down syndrome as the cause of death (ICD10 code: Q90) in the Japan national death registry database between 1995 and 2016. Changes in the median age at death between 1995-2005 and 2006-2016 were investigated based on sex and history of surgery. We identified 240 stillbirths and 1,099 deaths in this period. The annual number of stillbirths and deaths above the age of 1 year increased, whereas the number of deaths below 1 year did not change. The proportional mortality indicator at ages 20, 40, and 60 increased from 21.7%, 11.7%, and 1.7% in 1995 to 69.9%, 66.7%, and 36.6% in 2016, respectively. The median age at death was higher in females, individuals without a surgical history, and deaths occurring in 2006-2016. The median age at death increased over the period in those without a surgical history. The age at death among people with Down syndrome has increased over the last 20 years, with currently 1 in 3 persons living over 60 years, necessitating adequate social welfare services in this aging population.


A BASIC program for the estimation of Michaelis-Menten parameters by the direct linear plot.
The use of manual graphical methods for the estimation of Michaelis-Menten kinetic parameters as recommended by Eisenthal and Cornish-Bowden (Biochem. J. 139 (1974) 715-720) was found to be impractical for large (n greater than 5) sample numbers. A BASIC program providing the rank ordered coordinates of intersections, which correspond to estimates of Km and Vmax in the direct linear plot method, is described.