Prevalence and predictive factors of diabetes in hepatitis virus positive liver cirrhosis with fasting plasma glucose level of <126 mg/dL.
The aim of this study was to evaluate the prevalence and predictive factors of diabetes in hepatitis virus positive liver cirrhotic patients with fasting plasma glucose (FPG) level of <126 mg/dL. A total of 263 patients with hepatitis C virus (HCV) or hepatitis B virus (HBV) positive liver cirrhosis, FPG level of <126 mg/dL, and had diabetes status evaluated by the use of 75-g oral glucose tolerance test (OGTT), were enrolled in this study. Plasma glucose and insulin levels were analyzed periodically for 3 h after oral glucose loading. Diabetes was defined as a 2-h post-load glucose on the OGTT of ≥200 mg/dL. The prevalence of diabetes by use of OGTT and predictive factors for diabetes were evaluated by the use of the Mann-Whitney U-test, Fisher's exact probability test or multivariate analysis by logistic regression. Hypoalbuminemia was defined as serum albumin level of <3.9 g/dL. Elevated indocyanine green retention rate at 15 min (ICG( R) 15) was regarded as ≥ 25%. Out of 263 patients, 44 (16.7%) were diagnosed as having diabetes. Multivariate analysis showed that diabetes occurred when patients had hypoalbuminemia of <3.9 g/dL (odds ratio [OR] 2.33; 95% confidential interval [CI] = 1.04-5.24; P = 0.040) and ICG( R) 15 of <25% (OR 2.36; 95%CI = 1.01-5.58). Hypoalbuminemia and elevated ICG( R) 15 in hepatitis virus related cirrhotic patients with FPG level of <126 mg/day enhance diabetes pattern after OGTT with significant difference.


Altered stress field of the human lens capsule after cataract surgery.
The lens capsule of the eye is important in focusing light onto the retina during the process of accommodation and, in later life, housing a prosthetic lens implanted during cataract surgery. Though considerable modeling work has characterized the mechanics of accommodation, little has been done to understand the mechanics of the lens capsule after cataract surgery. As such, we present the first 3-D finite element model of the post-surgical human lens capsule with an implanted tension ring and, separately, an intraocular lens to characterize the altered stress field compared to that in a model of the native lens capsule. All finite element models employed a Holzapfel hyperelastic constitutive model with regional variations in anisotropy. The post-surgical lens capsule demonstrated a dramatic perturbation to the stress field with mostly large reductions in stresses (except at the equator where the implant contacts the capsule) compared to native, wherein maximal changes in Cauchy stress were -100% and -145% for the tension ring and intraocular lens, respectively. However, implantation of the tension ring produced a more uniform stress field compared to the IOL. The magnitudes and distribution of the perturbed stress field may be an important driver of the fibrotic response of inhabiting lens epithelial cells and associated lens capsule remodeling after cataract surgery. Thus, the mechanical effects of an implant on the lens capsule could be an essential consideration in the design of intraocular lenses, particularly those with an accommodative feature.


Side effects of chronic lithium therapy in Hong Kong Chinese: an ethnopsychiatric perspective.
A biocultural study of the side effects of chronic lithium treatment among 70 Hong Kong Chinese psychiatric patients, using a self-report 33-item checklist and semi-structured interviews, revealed an imperfect correspondence between biomedically prescribed and culturally endorsed psychotropic side effects. Although polydipsia and polyuria (47%) were the biomedically most 'real' side effects, they were not usually regarded as bothersome or translated into metaphors to express undesirable side effects. Complaints such as tiredness (38%), drowsiness (36%) and poor memory (31%) were also common but their frequency was significantly lower than that of normal control subjects. The item 'loss of creativity' had no conceptual equivalent in Chinese and was usually misinterpreted. As no patient was aware that lithium was a metal, the side effect 'metallic taste' was variously labelled. Contrary to Western findings, complaints of 'missing of highs', loss of assertiveness and fear of weight gain were rarely encountered. Active elicitation was required for indigenous complaints, with 38% of patients considering lithium to cause mild "hotness." This was readily neutralized by drinking more water which had a "cooling" effect. Expectedly, concurrent neuroleptics and antidepressants amplified most lithium side effects. This study affirms Western data on the biomedically universalizable effects of chronic lithium treatment, but also supports the thesis that culturally constituted cognitive styles affect patients' recognition, labelling, experiencing and reporting the total drug effect. Further, it demonstrates that the lived experience and clinical negotiation of lithium associated side effects reproduce, authenticate, and at times critique, core cultural and moral premises of Western and Chinese societies.


Focus on sex differences in grant applications submitted to the Netherlands Organization for Health Research and Development.
Several measures have been implemented at international level to ensure that there is a greater focus on sex differences in health research. This study evaluates the effect of various formal incentives that were introduced by a Dutch financer of health research to encourage applicants to include sex differences in research proposals. We sampled 213 health research proposals submitted in 2003 to the programmes Prevention (N = 104) and Innovation (N = 109) by the Netherlands Organization for Health Research and Development (ZonMw). These proposals were analysed and categorized with regard to the expressed intention to take sex differences into consideration. Furthermore, those proposals in which such intention was absent were appraised by researchers to determine whether an intention of this kind would have been relevant. We found that 23 % of proposals submitted to Prevention (incentive: programme specific instructions) and 10% of those submitted to Innovation (general set of guidelines) took account of sex differences (difference 13%; 95% CI: 3.1-22.9). Conversely, 66% of the research proposals in Prevention, and 20% in Innovation, failed to take sex differences into consideration, even though this might well have been relevant. There is still insufficient incentive for those submitting research proposals to ZonMw to systematically incorporate sex differences when drafting such documents. The provisions in ZonMw's policy need to be amended and better monitored. For this, we formulated some recommendations.


DNA copy number changes in lung adenocarcinoma in younger patients.
We performed a comparative genomic hybridization study on 25 lung adenocarcinoma samples from younger patients (<41 y of age) and compared the results with a previous comparative genomic hybridization analysis of lung adenocarcinoma samples from older patients (50-81 y of age). Twenty of the 25 tumor samples from younger patients had DNA copy number changes. Gains, losses, and high-level amplifications were seen more frequently in the specimens from the younger group. The most striking difference between the two groups was the high frequency of gains and/or high-level amplifications in the long arm of chromosome 20 in the samples from the younger patients (14/25, 56%) compared with that in the samples from the older patients (2/24, 8%, P <.001). Gains in the long arm of chromosome 22 and of the chromosomal band 11q13 were also detected significantly more often in the younger group. No correlation was found between DNA copy number changes and clinical parameters. Our results suggest that amplification of genes in the long arm of chromosome 20 may be important in the tumorigenesis of lung adenocarcinoma in young adults. Several candidate genes have already been described in the long arm of chromosome 20, particularly in breast cancer.


Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration.
To determine whether levodopa (L-DOPA) is associated with a reduced likelihood of developing neovascular age-related macular degeneration (AMD). Three studies were performed: retrospective analyses in the Vestrum Health Retina Database (#1-2) and case-control analysis in the Merative MarketScan Research Databases (#3). Eyes with neovascular AMD and 2 years of follow-up (#1). Eyes with non-neovascular AMD and 1 to 5 years of follow-up (#2). Patients aged ≥ 55 years with newly diagnosed neovascular AMD matched to controls without neovascular AMD (#3). Eyes were divided into 2 groups (#1-2): exposed to L-DOPA before or on the date of neovascular (#1) or nonneovascular (#2) AMD diagnosis, and eyes not exposed to L-DOPA. We extracted AMD risk factors, number of intravitreal injections (#1), and conversion rate to neovascular AMD (#2). We calculated the percentage of newly diagnosed neovascular AMD cases and matched controls exposed to any L-DOPA and determined the cumulative 2-year dose in grams by tertiles (< 100 mg, approximately 100-300 mg, and approximately > 300 mg per day, #3). Number of intravitreal injections (#1) and detection of new-onset neovascular AMD (#2-3) after adjusting for AMD risk factors. In the Vestrum database, eyes with neovascular AMD that were exposed to L-DOPA underwent 1 fewer intravitreal injection over 2 years (N = 84 088 control vs. 530 L-DOPA eyes, P = 0.006). In eyes with nonneovascular AMD (N = 42 081-203 155 control vs. 314-1525 L-DOPA eyes), L-DOPA exposure was associated with a reduced risk of conversion to neovascular AMD by 21% at year 2 (P = 0.029), 35% at years 3 to 4 (P < 0.001), and 28% at year 5 (P = 0.024). In the MarketScan databases (N = 86 900 per group), cumulative 2-year doses of L-DOPA between approximately 100 to 300 mg per day and approximately > 300 mg were associated with decreased odds of developing neovascular AMD by 15% (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.75-0.97) and 23% (OR, 0.77; 95% CI, 0.67-0.87), respectively. Levodopa use was associated with reduced detection of new-onset neovascular AMD. A prospective, randomized clinical trial should be considered to investigate whether low-dose L-DOPA reduces neovascular AMD conversion. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Hybrid Closed-Loop Insulin Pump Technology Can Be Safely Used in the Inpatient Setting.
Hybrid closed-loop (HCL) systems, also known as automated insulin delivery systems, are a rapidly growing technology in diabetes management. Because more patients are using these systems in the outpatient setting, it is important to also assess inpatient safety to determine whether HCL use can be continued when those patients become hospitalized. The records of patients using HCL technology on admission to our hospital between June 1, 2020, and June 30, 2021, were analyzed. The final analysis included 71 patients divided into 3 categories based on their pump use as an inpatient: (1) HCL users; (2) manual pump users; and (3) pump removed. All cohorts were similar in age, sex, race, hemoglobin A1C at admission, and in Medicare Severity Diagnosis Related Group. Pairwise comparisons indicated that patient-stay mean glucose levels, frequency of patient-specific hyperglycemic measurements, and frequency of hypoglycemic events were similar between all groups. No adverse events, particularly occurrences of diabetic ketoacidosis, pump site complications or infection, or equipment malfunction, were reported. This preliminary case series review indicates that continued use of HCL technology in the hospital is safe. Moreover, glycemic control in HCL users was comparable with that in those using insulin pump with manual settings and those converted to basal-bolus insulin therapy.


Localization of mRNAs for subfamily of guanine nucleotide-exchange proteins (GEP) for ARFs (ADP-ribosylation factors) in the brain of developing and mature rats under normal and postaxotomy conditions.
ADP-ribosylation factors (ARFs) play important roles in vesicular trafficking and cytoskeletal regulation and its activation depends on guanine nucleotide-exchange proteins (GEPs). By way of in situ hybridization histochemistry, the localization of mRNAs for subfamily members of low-molecular-weight ARF-GEPs in the rat brain was studied at embryonic and postnatal stages. In the embryonic brain, the gene expression for msec7-1 was distinct in the ventricular zone while that for msec7-1, -3 and EFA6 in the mantle zone. In early postnatal brain, the expression for msec7-1, -2, -3 and EFA6 was seen widely in various loci of the gray matter with different intensity, and the expression of msec7-1 and -2 mRNAs was evident in the cerebellar external granule cell layer. In the adult brain, the gene expression for the four ARF-GEPs decreased more or less in most gray matter and the distinct expression was maintained mainly in the hippocampal and dentate neuronal layers and cerebellar cortex. The expression of EFA6 mRNA was also evident in the molecular layer of the hippocampus and dentate gyrus. No obvious gene expression for cytohesin-4 and ARF-GEP100 was detected in the brain at any stages of development. The present findings suggest that ARF-GEPs are differentially involved in some processes essential to neuronal differentiation and maturation in association with ARFs.


Clinical spectrum of oral candidosis and its role in HIV-infected patients.
Oral candidosis is a very frequent diseased state occurring mainly together with severe underlying disease. Clinical manifestation is variable. One can distinguish between oral thrush, denture stomatitis, angular cheilitis, leukoplakia and midline glossitis. Nowadays oral candidosis is also important in connection with HIV-infection. Here the clinical spectrum does not seem to be totally different. Apart from oral thrush (or pseudomembraneous type) a chronic atrophic type, a chronic hyperplastic type, papillary hyperplasia and angular cheilitis are distinguished. Oral candidosis is the most frequent opportunistic infection in HIV-infected patients. Frequency of overt disease is linked to the T4/T8 ratio. In patients with AIDS-related complex oral candidosis seems to be indicative of rapid progression. Candida albicans is the prevailing microorganism. There is, however, a change of biotypes during the course of HIV-infection. There seems to be a selection of certain phenotypes as can be judged from the increasing resistance to 5-fluorocytosine.


Puerperal acquired factor VIII inhibitor causing a von Willebrand-like syndrome in a patient with anti-DNA antibodies.
A 30-year-old Malay lady, with no previous or family history of bleeding, presented with severe gum bleeding 25 days post-partum. The factor VIII:c was 0.03 iu/ml with evidence of a slow-acting factor VIII inhibitor. Von Willebrand factor antigen (VWF:age) varied from less that 0.05 to 0.17 iu/ml, and there was absent ristocetin-induced platelet aggregation. Anti-nuclear and anti-DNA antibodies were present, but there were no other features of systemic lupus erythematosus. There was some clinical response to cryoprecipitate and tranexamic acid, and slight improvement with corticosteroid. Fifteen months later, the patient has no active bleeding problem, and her VWF-ag is increasing spontaneously. However, factor VIII:c is less than 0.01 iu/ml and her factor VIII inhibitor titre is still > 20 Bethesda units/ml.


Reducing inappropriate hospital use on a general pediatric inpatient unit.
Studies have documented high rates of inappropriate hospital use in children. We assessed the effectiveness of an audit-and-feedback intervention at reducing inappropriate hospital days on a general pediatric inpatient unit. A prospective observational study, using a before-and-after design, was conducted at a tertiary care pediatric hospital in Canada between March 2005 and August 2006. The appropriateness of all hospital days for all admissions was evaluated by a nurse trained in using a utilization review tool. This tool classifies hospital days as "qualified" or "nonqualified" on the basis of the nature of the inpatient services that are used. Reasons for nonqualified days were classified. The intervention consisted of (1) weekly feedback to attending physicians of which patients were nonqualified and (2) dissemination of summary reports to attending physicians. Comparisons were made between the preintervention (March 2005 to August 2005) and intervention (March 2006 to August 2006) phases. The intervention was associated with a significantly lower risk of inappropriate hospital days. Of the 7246 hospital days in the 6-month intervention phase, 2413 (33%) were nonqualified versus 3859 (47%) of 8228 hospital days in the 6-month preintervention phase. A total of 7.35 hospital days would have to be reviewed, combined with weekly feedback, to prevent 1 nonqualified hospital day. The 48-hour readmission rate in the intervention phase and preintervention phase was 1.0% and 1.6%, respectively. The proportion of nonqualified days to total hospital days that were attributable to "finishing intravenous antibiotics," "awaiting tests," "providing nutrition," "observation only," "tapering treatment," and "teaching" decreased significantly, whereas the "lack of an alternate level of care" increased significantly. An audit-and-feedback intervention directed at attending physicians was associated with a lower risk of inappropriate hospital days without an increase in the readmission rate. The utilization review tool also identified processes that impact on inappropriate hospital days.


Molecular cloning and sequencing of coho salmon growth hormone cDNA.
A cDNA library was constructed using mRNA isolated from coho salmon pituitaries. By employing rainbow trout growth hormone cDNA as a probe, the coho salmon cDNA was isolated and the complete nucleotide (nt) sequence determined. The coding region contains 630 nt while the 5'- and 3'-untranslated regions are 64 and 489 nt in length, respectively. Comparison of the noncoding regions of coho and chum salmon cDNAs reveal identity at the 5' end but significant variation in the 3' end. Chum salmon and rainbow trout have identical amino acid (aa) sequences, but coho salmon growth hormone has a sequence that differs by 6 of the 188 predicted aa. Since salmonids are tetraploid, this difference may be the result of either divergence of the same growth hormone locus or of variation between different loci. Comparisons of the cDNA restriction maps of these three fish species suggest the former possibility.


The effect of photopolymerization on stem cells embedded in hydrogels.
Photopolymerizable hydrogels, formed by UV-exposure of photosensitive polymers in the presence of photoinitiators, are widely used materials in tissue engineering research employed for cellular entrapment and patterning. During photopolymerization, the entrapped cells are directly exposed to polymer and photoinitiator molecules. To develop strategies that prevent potential photoexposure-damage to osteoprogenitor cells, it is important to further characterize the effects of photopolymerization on the exposed cells. In this study we analyzed the viability, proliferation and osteogenic differentiation of multipotent stromal cell (MSC) monolayers after exposure to UV-light in the presence of Irgacure 2959, a frequently used photoinitiator in tissue engineering research. Cell cycle progression, apoptosis and osteogenic differentiation of encapsulated goat MSCs were studied in photopolymerized methacrylate-derivatized hyaluronic acid hydrogel and methacrylated hyperbranched polyglycerol gel. We demonstrate adverse effects of photopolymerization on viability, proliferation and reentry into the cell cycle of the exposed cells in monolayers, whereas the MSCs retain the ability to differentiate towards the osteogenic lineage. We further show that upon encapsulation in photopolymerizable hydrogels the viability of the embedded cells is unaffected by the photopolymerization conditions, while osteogenic differentiation depends on the type of hydrogel used.


CHK1 monitors spindle assembly checkpoint and DNA damage repair during the first cleavage of mouse early embryos.
DNA damage and errors of accurate chromosome segregation lead to aneuploidy and foetal defects. DNA repair and the spindle assembly checkpoint (SAC) are the mechanisms developed to protect from these defects. Checkpoint kinase 1 (CHK1) is reported to be an important DNA damage response protein in multiple models, but its functions remain unclear in early mouse embryos. Immunofluorescence staining, immunoblotting and real-time reverse transcription polymerase chain reaction were used to perform the analyses. Reactive oxygen species levels and Annexin-V were also detected. Loss of CHK1 activity accelerated progress of the cell cycle at the first cleavage; however, it disturbed the development of early embryos to the morula/blastocyst stages. Further analysis indicated that CHK1 participated in spindle assembly and chromosome alignment, possibly due to its regulation of kinetochore-microtubule attachment and recruitment of BubR1 and p-Aurora B to the kinetochores, indicating its role in SAC activity. Loss of CHK1 activity led to embryonic DNA damage and oxidative stress, which further induced early apoptosis and autophagy, indicating that CHK1 is responsible for interphase DNA damage repair. Our results indicate that CHK1 is a key regulator of the SAC and DNA damage repair during early embryonic development in mice.


Expression of Glutamate and Glutamine Transporter Proteins in Neurovascular Unit Cells In Vitro.
Glutamine transporter protein SLC1A5 and glutamate transporter protein EAAT2 responsible for cell-cell communication and energetic coupling were studied using in vitro model of multicellular neurovascular unit consisting of astrocytes, neurons, and endotheliocytes under standard conditions and during chemical hypoxia in vitro. Hypoxic damage to the neurovascular unit cells increased the number of SLC1A5-expressing cells and reduced the number of EAAT2-expressing astrocytes. Metabolic uncoupling in the neurovascular unit cells under hypoxic conditions resulted from abnormal expression of glutamine and glutamate transporter proteins, which is indicative of impaired glutamine and glutamate transport.


Spatial distribution and pollution assessment of heavy metals in the surface sediments of the Bohai and Yellow Seas.
A total of 141 surface sediments were collected and analyzed for their geochemistry, total organic carbon, and grain size to assess the heavy metal pollution in the Bohai and Yellow Seas. The enrichment factor (EF) and geoaccumulation index (Igeo) of Cu, Pb, Zn, Cr, Cd, Ni, As, and Hg were calculated to assess anthropogenic contamination, and the results suggest that moderate Pb, Cd, and As contamination occurs in the study area. Sediment quality guidelines were applied to assess the adverse biological effects of these metals. The spatial distribution of the mean Effects Range-Median quotient for the vast majority of the study area is between 0.1 and 0.5, indicating low impact and potential negative biological effects. Multivariate analysis indicates that Cu, Pb, Zn, Cr, and Ni resulted primarily from lithogenic sources, whereas As, Cd, and Hg were mainly attributed to anthropogenic sources.


In vitro selection of ketoconazole-pentamidine-resistant Leishmania (Viannia) braziliensis strains.
The use of ketoconazole (KTZ) plus pentamidine (PMD) could be an interesting treatment option for New World cutaneous leishmaniasis. The aim of this work was to generate KTZ- and PMD-resistant strains and to determine some characteristics of the selection process and the resulting parasites. Resistance to one or two drugs was selected on promastigotes by progressively increasing drug concentrations for eleven months. The resistance levels (IC50) to one or two drugs (synergism assay) were determined using a colorimetric resazurin methodology. The stability of the resistance phenotype (without drug pressure or after mouse passage), cross resistance with paromomycin and miltefosine, and resistance transference to intracellular amastigotes were determined. In addition, some parasite attributes compared with WT, such as growth kinetics, amastigogenesis, THP-1 cells, and mouse infection, were determined. Promastigotes resistant to KTZ or PMD were obtained three times earlier than the combined KTZ + PMD-resistant strains. Resistant parasites (promastigotes and intracellular amastigotes) were three to twelve times less susceptible to KTZ and PMD than WT parasites. The resistance phenotype on parasites was unstable, and no cross resistance was observed. Similar parasite fitness related to our evaluated characteristics was observed except for in vivo infection, where a delay of the onset of cutaneous lesions was observed after KTZ + PMD-resistant parasite infection. CONCLUSION: Combined treatment with KTZ and PMD delayed the onset of parasite resistance and was more effective in vitro than each drug separately for WT and all resistant strains. Parasites resistant to KTZ and PMD acquired similar in vitro behaviour to WT parasites, were less virulent to mice and maintained their resistance phenotype on intracellular amastigotes but not without drug pressure or after mouse infection.


Politics of prevention: The emergence of prevention science.
This article critically examines the political dimension of prevention science by asking how it constructs the problems for which prevention is seen as the solution and how it enables the monitoring and control of these problems. It also seeks to examine how prevention science has established a sphere for legitimate political deliberation and which kinds of statements are accepted as legitimate within this sphere. The material consists of 14 publications describing and discussing the goals, concepts, promises and problems of prevention science. The analysis covers the period from 1993 to 2012. The analysis shows that prevention science has established a narrow definition of "prevention", including only interventions aimed at the reduction of risks for clinical disorders. In publications from the U.S. National Institute of Drug Abuse, the principles of prevention science have enabled a commitment to a zero-tolerance policy on drugs. The drug using subject has been constructed as a rational choice actor lacking in skills in exerting self-control in regard to drug use. Prevention science has also enabled the monitoring and control of expertise, risk groups and individuals through specific forms of data gathering. Through the juxtaposition of the concepts of "objectivity" and "morality", prevention science has constituted a principle of delineation, disqualifying statements not adhering to the principles of prevention science from the political field, rendering ethical and conflictual dimensions of problem representations invisible. The valorisation of scientific accounts of drugs has acted to naturalise specific political ideals. It simultaneously marginalises the public from the public policy process, giving precedence to experts who are able to provide information that policy-makers are demanding. Alternative accounts, such as those based on marginalisation, poverty or discrimination are silenced within prevention science.


Biomarkers research in neuromuscular disease Charcot-Marie-Tooth.
Charcot-Marie-Tooth disease (CMT) (ORPHA166) is the most frequent hereditary neuropathy. CMT is a heterogeneous group of disorders which, despite some variability in their clinical features, share the same general phenotype, usually characterized by wasting and weakness of distal limb muscles, decreased to absent deep tendon reflexes, distal sensory loss, and frequent skeletal deformities. Despite the clinical and molecular description of this disease in the last 20 years, there is no effective drug or advanced therapy available. Here we have pretend the identification of metabolic and oxidative stress biomarkers in plasmas from patients with duplication at PMP22 gene, the most frequent mutation causing CMT, and clinically characterized as CMT1A. The samples were collected in the neuropathy units from "La Fe" Hospital of Valencia, "Bellvitge" Hospital of Barcelona, "La Paz" Hospital of Madrid, and "Virgen del Rocío" Hospital of Sevilla. The metabolic biomarkers research was performed using 2D-DIGE analysis (Typhoon TRIO, GE) and DeCyder software (GE). Protein identification was made by mass spectrometry by MALDI-TOF-TOF (ABSciex) and liquid Chromatography analysis (ABSciex). The oxidative stress biomarkers research consisted in carbonylated proteins analysis by reaction with DNPH and Dot-blot. Total antioxidant capacity and GSSG/GSH ratio were analyzed with Antioxidant Assay kit (Cayman) and Glutathione Fluorescent detection Kit (Arbor Assays), respectively. Finally now we are performing the MDA levels by HPLC-UV. We found 8, 13 and 36 proteins with differential expression in mild, moderate and severely affected patients, respectively compared with their own matched controls. Also we found differences on oxidative stress parameters between de different groups analyzed. Our results suggest differences in the oxidative stress profile between the studied phenotypes in CMT1A patients.


Risk factors associated with preterm birth according to gestational age at birth.
To identify and quantify risk factors associated with preterm birth, stratified by gestational age at birth. Three case-control analyses were done. Controls were pregnancies of > or =37 weeks of gestational age at birth. Cases were defined as: <28, 28-32, 33- <37 weeks of gestational age at birth respectively in the three case-control analyses. Women were categorized according to whether they carried single or multiple infants. Obstetrical conditions (placenta previa, placental abruption), and maternal hypertension were significantly associated with preterm delivery in all case-control analyses (adjusted OR between 1.34-19.56, p < 0.05). Leading risk factors for preterm delivery in singleton pregnancies were placental abruption and placenta previa (adjusted ORs 4.85 and 4.13, p < 0.05). For multiple pregnancies they were polyhydramnios and maternal hypertension (adjusted ORs 4.39 and 2.45, p < 0.05). Obstetrical conditions during the pregnancy and maternal hypertension are important risk factors for preterm birth.


Retention and distribution of manganese in the mouse brain following acute exposure on postnatal day 0, 7, 14 or 42: an autoradiographic and gamma counting study.
The relationship between postnatal age at time of Mn exposure, and the retention and distribution of Mn in the brain of the mouse was studied using gamma counting and autoradiography. A single intraperitoneal dose of Mn2+ (11 micrograms/kg or 25 mg/kg) containing radioactive 54Mn was administered on postnatal day 0, 7, 14 or 42. Animals were then killed at various times post exposure (1-114 days) and retention and distribution determined. Maximum retention of Mn in the brain (calculated as a percentage of administered dose) occurred 43 days following exposure on day 0. For day 7, 14 or 42 the highest Mn retention was 24 h after exposure. Maximum retention was 2.9%, 3.5%, 2.5% or 0.3% respectively, Mn retention after 114 days was 0.4%, 0.3%, 0.3% or 0.04% respectively. For the carrier-added group maximum retention was lower with corresponding figures of 2.5%, 2.4%, 1.1% or 0.2% and retention after 114 days was also lower 0.1%, 0.06%, 0.05% or 0.01%. The autoradiography studies indicated that Mn was located in areas of the brain which had a high perikaryal density at the time of exposure and in the choroid plexus. High and low doses of Mn were similarly distributed and there was little change in distribution with time.


Heart valve replacement with the Björk-Shiley Monostrut valve: early results of a multicenter clinical investigation.
To evaluate the clinical performance of the Björk-Shiley Monostrut prosthesis, five centers combined their early experience. Between May, 1982, and June, 1985, 537 prostheses were implanted in 486 patients at these centers: 246 patients had aortic valve replacement (AVR), 163 underwent mitral valve replacement (MVR), and 47 had double-valve replacement (DVR). Thirty patients underwent other, more complex procedures. Concomitant cardiac procedures were performed in altogether 25%. Overall hospital (30 days) mortality was 5.1% (3.6% for AVR, 4.3% for MVR, 8.3% for DVR, and 16.6% for other procedures). The patients were followed up at 6- to 9-month intervals from 6 to 48 months (mean follow-up, 33 months). Follow-up was 99.6% complete. Late mortality was 7.2%. The three-year survival rate was 91.0% for AVR, 92.3% for MVR, and 76.2% for DVR. There was no structural failure of the prosthesis. No instances of valve thrombosis and fatal thromboembolism occurred in anticoagulated patients. The three-year incidence of freedom from thromboembolic events (including TIA) was 89.8% for AVR, 94.9% for MVR, and 90.2% for DVR. Preoperative and postoperative data for the assessment of mechanical hemolysis was available in 60% of the patients. The degree of mechanical hemolysis was low and did not change with time. Although the follow-up is still short, the Björk-Shiley Monostrut prosthesis appears to represent an improvement over previous Björk-Shiley models, particularly with regard to durability.


Multivariate time-series sensor vital sign forecasting of cardiovascular and chronic respiratory diseases.
Approximately 19 million people die each year from cardiovascular and chronic respiratory diseases. As a result of the recent Covid-19 epidemic, blood pressure, cholesterol, and blood sugar levels have risen. Not only do healthcare institutions benefit from studying physiological vital signs, but individuals also benefit from being alerted to health problems in a timely manner. This study uses machine learning to categorize and predict cardiovascular and chronic respiratory diseases. By predicting a patient's health status, caregivers and medical professionals can be alerted when needed. We predicted vital signs for 180 seconds using real-world vital sign data. A person's life can be saved if caregivers react quickly and anticipate emergencies. The tree-based pipeline optimization method (TPOT) is used instead of manually adjusting machine learning classifiers. This paper focuses on optimizing classification accuracy by combining feature pre-processors and machine learning models with TPOT genetic programming making use of linear and Prophet models to predict important indicators. The TPOT tuning parameter combines predicted values with classical classification models such as Naïve Bayes, Support Vector Machines, and Random Forests. As a result of this study, we show the importance of categorizing and increasing the accuracy of predictions. The proposed model achieves its adaptive behavior by conceptually incorporating different machine learning classifiers. We compare the proposed model with several state-of-the-art algorithms using a large amount of training data. Test results at the University of Queensland using 32 patient's data showed that the proposed model outperformed existing algorithms, improving the classification of cardiovascular disease from 0.58 to 0.71 and chronic respiratory disease from 0.49 to 0.70, respectively, while minimizing the mean percent error in vital signs. Our results suggest that the Facebook Prophet prediction model in conjunction with the TPOT classification model can correctly diagnose a patient's health status based on abnormal vital signs and enables patients to receive prompt medical attention.


Crossed facilitation and post-contraction depression of abductor pollicis brevis motor neurons.
Crossed facilitation of abductor pollicis brevis (APB) motor neurons by voluntary contraction of the contralateral APB was investigated using F response analysis. The integrated F response EMG showed a mean 4-fold increase during contraction. This enhancement was maintained until the onset of subjective fatigue and then declined. After isometric or isotonic contraction of the ipsilateral APB there was a significant depression of F responses with a progressive return to baseline values over a 6 minute period. The significance of the findings is discussed.


Calorimetric and spectroscopic investigations of the binding of metallated porphyrins to G-quadruplex DNA.
The human telomere contains tandem repeat of (TTAGG) capable of forming a higher order DNA structure known as G-quadruplex. Porphyrin molecules such as TMPyP4 bind and stabilize G-quadruplex structure. Isothermal titration calorimetry (ITC), circular dichroism (CD), and mass spectroscopy (ESI/MS), were used to investigate the interactions between TMPyP4 and the Co(III), Ni(II), Cu(II), and Zn(II) complexes of TMPyP4 (e.g. Co(III)-TMPyP4) and a model human telomere G-quadruplex (hTel22) at or near physiologic ionic strength ([Na(+)] or [K(+)]≈0.15M). The apo-TMPyP4, Ni(II)-TMPyP4, and Cu(II)-TMPyP4 all formed complexes having a saturation stoichiometry of 4:1, moles of ligand per mole of DNA. Binding of apo-TMPyP4, Ni(II)-TMPyP4, and Cu(II)-TMPyP4 is described by a "four-independent-sites model". The two highest-affinity sites exhibit a K in the range of 10(8) to 10(10)M(-1) with the two lower-affinity sites exhibiting a K in the range of 10(4) to 10(5)M(-1). Binding of Co(III)-TMPyP4, and Zn(II)-TMPyP4, is best described by a "two-independent-sites model" in which only the end-stacking binding mode is observed with a K in the range of 10(4) to 10(5)M(-1). In the case of apo-TMPyP4, Ni(II)-TMPyP4, and Cu(II)-TMPyP4, the thermodynamic signatures for the two binding modes are consistent with an "end stacking" mechanism for the higher affinity binding mode and an "intercalation" mechanism for the lower affinity binding mode. In the case of Co(III)-TMPyP4 and Zn(II)-TMPyP4, both the lower affinity for the "end-stacking" mode and the loss of the intercalative mode for forming the 2:1 complexes with hTel22 are attributed to the preferred metal coordination geometry and the presence of axial ligands. The preferred coordination geometry around the metal center strongly influences the energetics of the interactions between the metallated-TMPyP4 and the model human telomeric G-quadruplex.


Ultrasonographic evaluation of the thickness of the small intestinal wall in dogs with inflammatory bowel disease.
To establish whether the intestinal wall thickness, as measured ultrasonographically, is significantly increased in dogs with inflammatory bowel disease (IBD). The results would provide the information necessary to decide whether measurement of ultrasonographic wall thickness can predict IBD in dogs. The intestinal wall thickness of 75 dogs with idiopathic IBD, as measured by ultrasonography, was compared with recently published normal values. IBD was either confirmed histologically (n = 54) or suspected (n = 21). In all cases there was a positive response to immunosuppressive treatment. A positive association between intestinal wall thickness in dogs and either the histological diagnosis or the response to treatment was not found. Ultrasonographic intestinal wall measurements do not appear to be able to establish a diagnosis of intestinal inflammation and may result in a false negative diagnosis in cases of IBD. The same 'grey zone' of between 4 and 6 mm used in humans can be used in the canine duodenum to distinguish the normal range, reserving the term 'abnormal' for an intestinal measurement greater than 6 mm in the duodenum and greater than 4.7 mm in the jejunum.


Analysis of recombination in Campylobacter jejuni from MLST population data.
We analyze recombination in C. jejuni using MLST data from isolates taken from wild birds, cattle, wild rabbits, and water in a 100-km2 study region in Cheshire, UK. We use a recent approximate likelihood method for inference, based on combining likelihood information from all pairs of segregating (polymorphic) sites in the data. We find substantial evidence for recombination, but only for recombination with short tract lengths, of around 225-750 bp. We estimate that the rate of recombination is of a similar magnitude to the rate of mutation.


Immunocytochemical localization of vasotocin and mesotocin in the hypothalamus of lacertilian reptiles.
The hypothalamic magnocellular neurosecretory system of lizards was studied with the unlabeled antibody peroxidase-antiperoxidase complex (PAP) technique at the light microscopic level. It was shown that vasotocin and mesotocin are synthesized in separate neurons. The vasotocinergic as well as the mesotocinergic perikarya are of different sizes. Both cell types occur in close juxtaposition, but without a distinct pattern of distribution. The external zone of the lacertilian median eminence contains numerous immunoreactive vasotocinergic fibers and only few immunoreactive mesotocinergic fibers. The general organization of the hypothalamic magnocellular neurosecretory system of lizards, as revealed by immunocytochemistry, is essentially similar to that revealed with unspecific staining methods.


[Manifestations of domain organization of the Staphylococcus aureus protein A during heat denaturation of its structure].
Melting of protein A from Staphylococcus aureus has been studied in neutral medium by the methods of microcalorimetry and circular dichroism. The melting process of protein A is shown to consist of, at least, 5 independent transitions. The transition with the heat absorption maximum at 38 degrees is ascribed to the melting of the C-terminal domain of protein A. The analysis of amino acid sequences has shown the existence of structural basis for differences in heat stability of the Fc-binding domains of protein A.


Successful Incorporation of Exosome-Capturing Antibody-siRNA Complexes into Multiple Myeloma Cells and Suppression of Targeted mRNA Transcripts.
Nucleic acid medicines have been developed as new therapeutic agents against various diseases; however, targeted delivery of these reagents into cancer cells, particularly hematologic cancer cells, via systemic administration is limited by the lack of efficient and cell-specific delivery systems. We previously demonstrated that monoclonal antibody (mAb)-oligonucleotide complexes targeting exosomal microRNAs with linear oligo-D-arginine (Arg) linkers were transferred into solid cancer cells and inhibited exosomal miRNA functions. In this study, we developed exosome-capturing anti-CD63 mAb-conjugated small interfering RNAs (siRNAs) with branched Arg linkers and investigated their effects on multiple myeloma (MM) cells. Anti-CD63 mAb-conjugated siRNAs were successfully incorporated into MM cells. The incorporation of exosomes was inhibited by endocytosis inhibitors. We also conducted a functional analysis of anti-CD63 mAb-conjugated siRNAs. Ab-conjugated luciferase+ (luc+) siRNAs significantly decreased the luminescence intensity in OPM-2-luc+ cells. Moreover, treatment with anti-CD63 mAb-conjugated with MYC and CTNNB1 siRNAs decreased the mRNA transcript levels of MYC and CTNNB1 to 52.5% and 55.3%, respectively, in OPM-2 cells. In conclusion, exosome-capturing Ab-conjugated siRNAs with branched Arg linkers can be effectively delivered into MM cells via uptake of exosomes by parental cells. This technology has the potential to lead to a breakthrough in drug delivery systems for hematologic cancers.


'Ignorance' of antigen-specific murine CD4+ and CD8+ T cells is overruled by lipopolysaccharide and leads to specific induction of IFN-gamma.
Lipopolysaccharide (LPS) can activate human and murine T cells in vivo and in vitro. Here we analysed the effects of LPS on T cells with defined specificities in T-cell receptor (TCR)-transgenic systems. LPS rapidly induced high amounts of interferon (IFN)-gamma in a subpopulation of purified T cells from DO11.10 (OVA323-339/H2-Ad) and OT-1 (OVA257-264/H2-Kb) mice when coincubated with antigen-pulsed peritoneal exudate cells (PECs). LPS induced IFN-gamma in T cell cultures even when the number of antigenic major histocompatibility complex (MHC) class-I complexes was too small to stimulate the T cells. LPS, thus, overruled the unresponsiveness of the otherwise 'antigen-ignorant' T cells. The release of IFN-gamma strictly correlates with the PECs' ability to produce interleukin (IL)-12. In contrast to the induction of IFN-gamma, antigen-specific IL-2 secretion and proliferation of T cells were rather decreased in the presence of LPS. Only very few IFN-gamma-secreting natural killer (NK) cells and natural killer T (NKT) cells in the given experimental system could be detected using intracellular fluorescence-activated cell sorter (FACS) staining. Taken together, our results indicate that LPS has the potential to activate quiescent T cells and to specifically induce IFN-gamma in CD4 and CD8 T cells. This may have direct consequences for the activation of autoreactive T cells following bacterial infections.


Acute lower respiratory infections among children under five in Sub-Saharan Africa: a scoping review of prevalence and risk factors.
Acute lower respiratory tract infections (ALRTIs) among children under five are still the leading cause of mortality among this group of children in low and middle-income countries (LMICs), especially countries in sub-Saharan Africa (SSA). This scoping review aims to map evidence on prevalence and risk factors associated with ALRTIs among children under 5 years to inform interventions, policies and future studies. A thorough search was conducted via four main databases (PubMed, JSTOR, Web of Science and Central). In all, 3,329 records were identified, and 107 full-text studies were considered for evaluation after vigorous screening and removing duplicates, of which 43 were included in this scoping review. Findings indicate a high prevalence (between 1.9% to 60.2%) of ALRTIs among children under five in SSA. Poor education, poverty, malnutrition, exposure to second-hand smoke, poor ventilation, HIV, traditional cooking stoves, unclean fuel usage, poor sanitation facilities and unclean drinking water make children under five more vulnerable to ALRTIs in SSA. Also, health promotion strategies like health education have doubled the health-seeking behaviours of mothers of children under 5 years against ALRTIs. ALRTIs among children under five still present a significant disease burden in SSA. Therefore, there is a need for intersectoral collaboration to reduce the burden of ALRTIs among children under five by strengthening poverty alleviation strategies, improving living conditions, optimising child nutrition, and ensuring that all children have access to clean water. There is also the need for high-quality studies where confounding variables in ALRTIs are controlled.


Diabetes induced decreases in PKA signaling in cardiomyocytes: The role of insulin.
The cAMP-dependent protein kinase (PKA) signaling pathway is the primary means by which the heart regulates moment-to-moment changes in contractility and metabolism. We have previously found that PKA signaling is dysfunctional in the diabetic heart, yet the underlying mechanisms are not fully understood. The objective of this study was to determine if decreased insulin signaling contributes to a dysfunctional PKA response. To do so, we isolated adult cardiomyocytes (ACMs) from wild type and Akita type 1 diabetic mice. ACMs were cultured in the presence or absence of insulin and PKA signaling was visualized by immunofluorescence microscopy using an antibody that recognizes proteins specifically phosphorylated by PKA. We found significant decreases in proteins phosphorylated by PKA in wild type ACMs cultured in the absence of insulin. PKA substrate phosphorylation was decreased in Akita ACMs, as compared to wild type, and unresponsive to the effects of insulin. The decrease in PKA signaling was observed regardless of whether the kinase was stimulated with a beta-agonist, a cell-permeable cAMP analog, or with phosphodiesterase inhibitors. PKA content was unaffected, suggesting that the decrease in PKA signaling may be occurring by the loss of specific PKA substrates. Phospho-specific antibodies were used to discern which potential substrates may be sensitive to the loss of insulin. Contractile proteins were phosphorylated similarly in wild type and Akita ACMs regardless of insulin. However, phosphorylation of the glycolytic regulator, PFK-2, was significantly decreased in an insulin-dependent manner in wild type ACMs and in an insulin-independent manner in Akita ACMs. These results demonstrate a defect in PKA activation in the diabetic heart, mediated in part by deficient insulin signaling, that results in an abnormal activation of a primary metabolic regulator.


[A patient with white matter involvement and superficial hemosiderosis of the central nervous system].
We present a patient with a superficial siderosis and a white matter involvement on MRI and a demyelinating pattern on visual evoked potentials. White matter involvement is supposed to be secondary to vascular modifications induced by superficial siderosis.


Health in adulthood after severe anorexia nervosa in adolescence: a study of exposed and unexposed women.
To compare the global health status, frequency of somatic and psychological problems, and alcohol use in adulthood among women hospitalized in adolescence for severe anorexia nervosa (AN), with a matched control sample from the general population. Women (n = 86) who had been hospitalized for AN 9.31 ± 1.82 years previously were compared with 258 controls matched for gender, age, and socio-professional category. Data were retrieved from a French survey on health and social insurance coverage, and was mainly collected by self-report, except for the assessment of current eating disorders for those previously hospitalized for AN (assessed with the MINI). The women who had been hospitalized for AN reported significantly poorer current health status compared to controls (OR 2.9, 95% CI 1.5-5.79). According to the MINI, 13 women previously hospitalized with severe AN still presented an eating disorder (ED). Women with past AN reported more frequent acute throat infections (OR 4.9, 95% CI 1.81-13.51), gastralgia (OR 3.6, 95% CI 1.9-6.83), gastro-oesophageal reflux (OR 5.279, 95%CI 2.11-13.22), excess blood cholesterol or triglyceride levels (OR 2.55, 95% CI 1.03-6.33), anxiety (OR 8.7, 95% CI 3.48-21.8) and depression (OR 5.02 (2.8-9.01). These differences remained significant and of the same order of magnitude in sensitivity analyses among subjects with previous AN but without current ED, except for perceived health status and excess cholesterol and triglyceride levels. Women who had been hospitalized for severe AN reported more symptoms 10 years after treatment, implies psychological and somatic follow-up in the long term. Level III, case-control analytic study.


Expression of the protease gene of equine infectious anemia virus in Escherichia coli: formation of the mature processed enzyme and specific cleavage of the gag precursor.
A 620-bp Bg/II restriction fragment containing the putative protease coding sequence from equine infectious anemia virus (EIAV) proviral DNA was cloned and expressed in E. coli as a Pol precursor protein. In contrast to the 25-kDa fusion protein predicted from the expressed pol sequence, a protein of approximately 10 kDa was generated by apparent autocatalytic processing of the Pol precursor. This mature processed protein was detected in transformed cells using an antisera raised against synthetic peptide from the conserved carboxyl-terminal segment of the predicted EIAV protease coding sequence. Coexpression of this protein with a 35-kDa EIAV Gag-precursor fusion protein resulted in the specific proteolytic processing of the precursor as shown by formation of p26, the major capsid protein of EIAV.


The surgical management of locally advanced well-differentiated thyroid carcinoma: changes over the years according to the AJCC 8th edition Cancer Staging Manual.
Well-differentiated thyroid carcinoma is defined as locally advanced in the presence of an extra thyroid extension, e.g., when the surrounding structures such as the trachea, larynx, esophagus and main blood vessels are invaded by cancer. The 8th edition AJCC Cancer Staging Manual states that this is the main characteristic to evaluate for the staging and consequently for the prognosis in patients over 55 years old. Distinguishing different forms of locally advanced thyroid cancer is essential, and the various anatomical structures and the clinical and therapeutic consequences must be taken into account. An accurate diagnosis of the organs invaded by thyroid cancer is necessary for the planning of surgical treatment, and both aspects are crucial to improving the patients' survival. Patients affected by thyroid cancer with extra thyroid extension have a poor prognosis and the removal of the entire neoplasm represents a key factor for better disease-free survival. We discuss the changes introduced by the 8th edition AJCC Cancer Staging Manual, in terms of the diagnostic and surgical management of extra thyroid extension, in patients affected by papillary and follicular thyroid cancer.


Vascular heparan sulfates may limit the ability of leukocytes to penetrate the endothelial barrier--implications for use of glucosamine in inflammatory disorders.
Oral glucosamine has anti-inflammatory activity in rodents, and anecdotal evidence suggests that it may be clinically useful in inflammatory bowel disorders. A possible explanation is that supplemental glucosamine increases production of heparan sulfate (HS) proteoglycans by the vascular endothelium, thereby improving the endothelium's barrier function. Extravasation of leukocytes and metastatic cancer cells requires degradation of HS. Heparin can inhibit neutrophil activation, adhesion, and chemotaxis, and--like glucosamine--has been reported effective for managing inflammatory bowel syndromes. Cytokine-mediated loss of endothelial HS may be a key factor in the coordinated inflammatory response. These considerations suggest that glucosamine may have clinical utility in a range of inflammatory disorders, and should be assessed with regard to its impact on cancer metastasis and peripheral ischemic disease. In inflammatory bowel disease, fish oil, ginkgolides, and enteric-coated 5-aminosalicylic acid may safely complement the efficacy of glucosamine.


Cerebral oxygen balance is impaired during repair of aortic coarctation in infants and children.
During repair of aortic coarctation through a left thoracotomy without cardiopulmonary bypass, clamping the proximal transverse aortic arch occludes antegrade flow to the left carotid and vertebral arteries. It is assumed that flow through the right carotid and vertebral arteries is adequate for cerebral perfusion. The study objective is to determine whether aortic occlusion impairs left hemispheric cerebral oxygen balance measured by near-infrared spectroscopy. In 18 children having repair of aortic coarctation, we measured the maximum change and integral for hemoglobin D (difference of oxyhemoglobin and deoxyhemoglobin), total oxygenation index, and the redox state of cytochrome aa3. Thirteen subjects had recordings from the left hemisphere to test the hypothesis that aortic occlusion impairs left hemispheric oxygen balance. Five subjects had recordings from the right hemisphere for comparison. After aortic clamping, a significant decrease in hemoglobin D was observed in recordings from the left hemisphere compared with those from the right hemisphere (P = .03, maximum change in hemoglobin D). Total oxygenation index and cytochrome aa3 were generally preserved. There was an inverse linear relationship for the change in hemoglobin D during clamp application and after removal (Spearman rho = -0.74), with increased hemoglobin D after clamp removal in those subjects with the greatest decrease of hemoglobin D during arch occlusion. Linear regression analysis identified nitroprusside administration as significantly associated with a decrease in hemoglobin D (P < .001). Significant impairment in left hemispheric cerebral oxygen balance was identified during arch clamping. The neurodevelopmental significance of impaired cerebral oxygen balance detected by near-infrared spectroscopy during aortic coarctation repair remains to be elucidated.


Risk stratification after recurrence of human papillomavirus (HPV)-related and non-HPV-related oropharyngeal cancer: Secondary analysis of NRG Oncology RTOG 0129 and 0522.
No risk-stratification strategies exist for patients with recurrent oropharyngeal cancer (OPC). Retrospective analysis using data from prospective NRG Oncology clinical trials RTOG 0129 and 0522. Eligibility criteria included known p16 status and smoking history, and locoregional/distant recurrence. Overall survival (OS) was measured from date of recurrence. Recursive partitioning analysis was performed to produce mutually exclusive risk groups. Hundred and fifty-four patients were included with median follow-up after recurrence of 3.9 years (range 0.04-9.0). The most important factors influencing survival were p16 status and type of recurrence, followed by surgical salvage and smoking history (≤20 vs. >20 pack-years). Three significantly different risk groups were identified. Patients in the low-, intermediate-, and high-risk groups had 2-year OS after recurrence of 81.1% (95%CI 68.5-93.7), 50.2% (95%CI 36.0-64.5), and 20.8% (95%CI 10.5-31.1), respectively. Patient and tumor characteristics may be used to stratify patients into risk groups at the time of OPC recurrence.


The value of the intraoperative assessment of the SLN via frozen section in the post Z0011 era.
Sentinel node (SN) assessment via frozen section (FS) has declined since the publication of Z0011 which modified the management of a specific group of patients with positive SN. The risk of misleading the surgeons to a preventable ALND and the cost are among the main factors for that. The aim of our study is to assess the value of FS in the post Z0011. 244 patients out of 434 were eligible for an upfront SLNB. Based on the final histology and the clinical data we selected the eligible for breast conserving surgery patients (55.4%). 78 patients had positive SN and 26 of them fulfilled the criteria of Z0011. We assessed the false negative findings, the impact on the management and the indications and value of FS in the post Z0011 era. Overall, there were 12 FN cases out of which 7 were macrometastases (8.97%). Only in one case there were > 2 positive LN and 3 patients needed mastectomy. The remaining cases fulfilled the criteria of Z0011 and needed no further surgery hence in 96.1% of the cases the axillary status was correctly assessed via FS and the reoperation rate was 1.2%. On the contrary, if FS was not used, at least 21.3% of the patents would have needed reoperation based on the today's guidelines. We believe FS is still valuable and may spare a significant percentage of patients from a second operation (SNB) without leading to axillary overtreatment if used wisely.


One new species of the genus Savarna Huber, 2005 (Araneae, Pholcidae) from southern Thailand.
One new species Savarnakraburiensis sp. n. (♂♀) is reported from southern Thailand.


Exploring mHealth applications for self-management of chronic low back pain: A survey of features and benefits.
The adoption of Mobile Health (mHealth) for self-management is growing. mHealth solutions are commonly used in public healthcare and health services, where they are appreciated for their ease of use, broad reach, and wide acceptance. Chronic Low Back Pain (CLBP) is one of the most common health problems and a leading cause of disability. As such, it imposes a tremendous burden on patients and society. Studies have proposed that mHealth self-management solutions, such as mobile applications, can supplement traditional care methods and benefit patients, particularly in self-managing CLBP easier. To this end, the number of available mobile applications for CLBP has increased. This paper i) provides an overview of scientific studies on mobile applications for CLBP management from three different viewpoints: researchers, health professionals, and patients, ii) uncovers the application features that were seen as beneficial in the studies, and iii) contrasts the currently available applications for CLBP in Google Play Store and Apple App Store against the discovered features. The findings show that "Personalization and customization" is the most significant feature as it is beneficial from stakeholders' viewpoint and is represented by most applications. In contrast, "Gamification" and "Artificial intelligence" are the least significant features, indicating a lack of attention from application creators and researchers in this area.


Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal sarcomatosis-A systematic review and meta-analysis.
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) play an important role in the treatment of various peritoneal surface malignancies, but its efficacy in peritoneal sarcomatosis (PS) remains unknown. Hence, we performed a systematic review and meta-analysis to investigate outcomes of CRS-HIPEC in PS, in accordance with PRISMA guidelines. 16 studies with a total of 320 patients were included in the meta-analysis. Pooled mean length of hospital stay after CRS-HIPEC was 16.0 days (95% CI: 12.2-19.8) and rate of serious complications was 17.4% (95% CI: 9.8-26.3). The median DFS was 12.0 months (95% CI: 8.0-16.0) and the 5-year DFS was 21.8% (95% CI: 13.2-31.7). Overall pooled median OS was 29.3 months (95% CI: 23.8-34.8), with a 5-year OS of 35.3% (95% CI: 26.3-44.8). Subgroup analysis showed that patients with CC-0 cytoreduction had a higher median OS of 34.6 months (95% CI: 23.2-45.9). Median OS for patients with a primary tumour histology of leiomyosarcoma and liposarcoma was 33.5 months (95% CI: 15.9-51.1) and 39.1 months (95% CI: 20.8-57.5) respectively. The site of recurrence was locoregional in 57.3% (95% CI: 38.9-74.8), distant in 17.3% (95% CI: 3.9-35.6), and both in 17.4% (95% CI: 5.8-32.2). In conclusion, our results suggest that CRS-HIPEC may improve outcomes in a select group of PS patients.


Characterization of the complete mitochondrial genomes of five hard ticks and phylogenetic implications.
Ticks are blood-sucking ectoparasites with significant medical and veterinary importance, capable of transmitting bacteria, protozoa, fungi, and viruses that cause a variety of human and animal diseases worldwide. In the present study, we sequenced the complete mitochondrial (mt) genomes of five hard tick species and analyzed features of their gene contents and genome organizations. The complete mt genomes of Haemaphysalis verticalis, H. flava, H. longicornis, Rhipicephalus sanguineus and Hyalomma asiaticum were 14855 bp, 14689 bp, 14693 bp, 14715 bp and 14722 bp in size, respectively. Their gene contents and arrangements are the same as those of most species of metastriate Ixodida, but distinct from species of genus Ixodes. Phylogenetic analyses using concatenated amino acid sequences of 13 protein-coding genes with two different computational algorithms (Bayesian inference and maximum likelihood) revealed the monophylies of the genera Rhipicephalus, Ixodes and Amblyomma, however, rejected the monophyly of the genus Haemaphysalis. To our knowledge, this is the first report of the complete mt genome of H. verticalis. These datasets provide useful mtDNA markers for further studies of the identification and classification of hard ticks.


Joint Consensus Statement of the Indian National Association for Study of the Liver and Indian Radiological and Imaging Association for the Diagnosis and Imaging of Hepatocellular Carcinoma Incorporating Liver Imaging Reporting and Data System.
Hepatocellular carcinoma (HCC) is the 6th most common cancer and the second most common cause of cancer-related mortality worldwide. There are currently no universally accepted practice guidelines for the diagnosis of HCC on imaging owing to the regional differences in epidemiology, target population, diagnostic imaging modalities, and staging and transplant eligibility. Currently available regional and national guidelines include those from the American Association for the Study of Liver Disease (AASLD), the European Association for the Study of the Liver (EASL), the Asian Pacific Association for the Study of the Liver, the Japan Society of Hepatology, the Korean Liver Cancer Study Group, Hong Kong, and the National Comprehensive Cancer Network in the United States. India with its large population and a diverse health infrastructure faces challenges unique to its population in diagnosing HCC. Recently, American Association have introduced a Liver Imaging Reporting and Data System (LIRADS, version 2017, 2018) as an attempt to standardize the acquisition, interpretation, and reporting of liver lesions on imaging and hence improve the coherence between radiologists and clinicians and provide guidance for the management of HCC. The aim of the present consensus was to find a common ground in reporting and interpreting liver lesions pertaining to HCC on imaging keeping LIRADSv2018 in mind.


Effect of prolonged physical exercise on the fibrinolytic system.
The effect of a test marathon race on plasma fibrinolytic activity (FA) was studied in 16 endurance athletes before, immediately after, 3 h, and 31 h after the run. Tissue plasminogen activator (t-PA) activity increased about 31-fold immediately after the run. Similar increases were found in t-PA antigen concentration. Plasminogen activator inhibitor (PAI) was not detectable immediately after the race and was significantly decreased 3 h (P less than 0.05) and 31 h (P less than 0.01) later. B beta 15-42 peptide increased by 0.63 pmol.ml-1 (P less than 0.001), D-dimer by 68.3 ng.ml-1 (P less than 0.05). Euglobulin lysis time (ELT) was reduced from 109 to 18 min (P less than 0.001). The increased t-PA activity and t-PA antigen concentration disappeared in the course of the first 3 h after exertion. ELT also reached its pre-exercise levels at this time. Thirty-one hours after the race ELT and t-PA antigen levels were slightly but significantly reduced (P less than 0.05), whereas B beta 15-42 peptide remained increased (P less than 0.05). t-PA activity was unchanged compared with pre-exercise values. It seems that the exercise-induced FA is mainly caused by the marked increase of t-PA antigen and t-PA activity.


Large institutional experience with dose-intensive chemotherapy and stem cell support in the management of sarcoma patients.
The prognosis of patients with advanced sarcoma remains poor. Whether high-dose chemotherapy with stem cell support improves the long-term outcome for these patients or not is controversial. We present a large institutional experience of sarcoma patients treated with this therapy option. Thirty-eight patients with bone (n = 17) and soft tissue sarcomas (n = 21) were included. Apart from haematological complications, no WHO grade III-IV complications were observed. One patient died due to cardiac arrest after transplantation. Following chemotherapy and/or surgery, but prior to high-dose chemotherapy, diagnoses were made of: no evidence of disease (NED; n = 12), partial remission (n = 17), stable disease (n = 3) and progressive disease (PD; n = 6). Six patients died within 8 months due to PD, in 18 patients disease recurred and led to death and 13 patients are alive with/without disease. Median progression-free survival was 19.1 months (range: 0-121) for all patients, and 48.8 months (range: 3-121) for 12 patients with NED. A subgroup of patients with NED before high-dose chemotherapy gained survival benefit. Therefore, we emphasize the value of high-dose chemotherapy as a treatment option for younger patients with a good performance status in partial or complete remission.


[Autologous chondrocyte transplantation in the treatment of articular cartilage lesions of the talus].
In contrast to the knee joint, autologous chondrocyte transplantation (ACT) is rarely used for treating articular cartilage lesions in the ankle joint. Matrix-associated autologous chondrocyte transplantation (MACT) with the use of biomaterials as cell carriers has facilitated operative application and fixation within the lesion. We have gained experience in the use of two different MACT techniques. According to the Hannover scoring system for the ankle and visual analog scores, results improved significantly (p<or=0.001) after MACT with the Hyalograft C in nine ankles at a mean follow-up of 3.7 years (range 2.6-4.8 years). All patients had undergone prior operative treatment for the cartilage lesion. Two patients were rated as excellent and seven as good. According to the ICRS cartilage repair assessment score, the transplanted areas were rated nearly normal (grade II) in seven patients who underwent undergone repeat arthroscopy. Magnetic resonance imaging revealed that in the majority of cases, filling of the defect was accomplished with a nonhomogeneous surface and structure of the graft. The use of a purely arthroscopically applicable three-dimensional MACT (ARTROcell 3D) with chondrospheres further facilitates the process and reduces operative morbidity. We have included eight patients in a prospective study so far. Six patients had undergone prior operative treatment for the cartilage lesion. In two cases, culturing of the cells failed for unexplained reasons; therefore, only six patients finally received the MACT with chondrospheres, and only four patients were evaluated at a 6-month follow-up examination. Thus, valid results cannot be reported. In revision cases, MACT is suggested to be a reliable alternative for treating articular cartilage lesions of the talus, but longer-term results in more patients remain to be evaluated.


The uses of Kenyan aloes: an analysis of implications for names, distribution and conservation.
The genus Aloe is renowned for its medicinal and cosmetic properties and long history of use. Sixty-three Aloe species occur in Kenya, of which around 50 % are endemic. Several species of aloes are threatened with extinction and knowledge about their use is of major importance for sound conservation strategies. The main aims of this study were to assess the biocultural value of Aloe in Kenya by documenting local uses of aloes and evaluating how the vernacular names reflect the relative importance in different ethnic groups. Ethnobotanical and ethnotaxonomical data were collected using field observations and semi-structured interviews. Information was collected by interviewing 63 respondents from nine different ethnic groups, representing different ages, gender and occupations. Statistical analyses were performed using R version 3.1.2. A total of 19 species of Aloe were found in the study area, of which 16 were used. On the generic level Aloe was easily distinguished. At species level, the local and scientific delimitation were almost identical for frequently used taxa. Aloe secundiflora, with 57 unique use records was the most important species. The two most frequently mentioned Aloe treatments, were malaria and poultry diseases. In our study area neither age nor gender had a significant influence on the level of knowledge of Aloe use. Finally, no correlation was found between extent of use and people's perception of decrease in local aloe populations. The aloes are highly appreciated and are therefore propagated and transported over large areas when people relocate. Biocultural value is reflected in the ethnotaxonomy of Aloe in Kenya. Different ethnic groups recognise their most-valued Aloe at the genus level as "the aloe" and add explanatory names for the other species, such as the "spotted aloe" and the "one-legged aloe". Widespread species of Aloe have the highest number of uses. There is no obvious correlation with high use and decrease in abundance of aloes locally, and we found no compelling evidence for local uses causing devastating damage to populations of the 19 species in use, whereas habitat loss and commercial harvesting appear to be of urgent concern for these important plants.


Swallowing dysfunction in head and neck cancer patients treated by radiotherapy: review and recommendations of the supportive task group of the Italian Association of Radiation Oncology.
Dysphagia is a debilitating complication in head and neck cancer patients (HNCPs) that may cause a high mortality rate for aspiration pneumonia. The aims of this paper were to summarize the normal swallowing mechanism focusing on its anatomo-physiology, to review the relevant literature in order to identify the main causes of dysphagia in HNCPs and to develop recommendations to be adopted for radiation oncology patients. The chemotherapy and surgery considerations on this topic were reported in recommendations only when they were supposed to increase the adverse effects of radiotherapy on dysphagia. The review of literature was focused on studies reporting dysphagia as a pre-treatment evaluation and as cancer and cancer therapy related side-effects, respectively. Relevant literature through the primary literature search and by articles identified in references was considered. The members of the group discussed the results and elaborated recommendations according to the Oxford CRBM levels of evidence and recommendations. The recommendations were revised by external Radiation Oncology, Ear Nose and Throat (ENT), Medical Oncology and Speech Language Pathology (SLP) experts. Recommendations on pre-treatment assessment and on patients submitted to radiotherapy were given. The effects of concurrent therapies (i.e. surgery or chemotherapy) were taken into account. In HNCPs treatment, disease control has to be considered in tandem with functional impact on swallowing function. SLPs should be included in a multidisciplinary approach to head and neck cancer.


Comparison of finite-difference time-domain SAR calculations with measurements in a heterogeneous model of man.
A finite-difference time-domain technique was used to calculate the specific absorption rate (SAR) at various sites in a heterogeneous block model of man. The block model represented a close approximation to a full-scale heterogeneous phantom model. Both models were comprised of a skeleton, brain, lungs, and muscle. Measurements were conducted in the phantom model using an implantable electric-field probe and a computer-controlled data acquisition system. The calculation and measurement of SAR distributions were compared primarily in the head (including the neck) and chest. To obtain the necessary spatial resolution with the computer model, the head and neck were modeled with approximately 105,000 cells, while 86,000 cells were used to configure the chest. Planewave fields, polarized in the E orientation, were utilized to irradiate the models at an exposure frequency of 350 MHz. Reasonable correlation existed between the calculations and measurements.


The N-linked carbohydrate chain of the 85-kilodalton glycoprotein from Trypanosoma cruzi trypomastigotes contains sialyl, fucosyl and galactosyl (alpha 1-3)galactose units.
The structure of the N-linked oligosaccharide of the 85-kDa surface glycoprotein (Tc-85) from the infective trypomastigote form of Trypanosoma cruzi was investigated. Tc-85 metabolically labeled with [14C]glucose was purified by affinity chromatography on wheat germ agglutinin-Sepharose. Binding to the lectin was lost on treatment of Tc-85 with neuraminidase. The N-linked asialo-oligosaccharide was released by endo-beta-N-acetylglucosaminidase F digestion of asialo-Tc-85 and was further analyzed using specific exoglycosidases. [14C]fucose was detected after alpha-L-fucosidase treatment or mild acid hydrolysis. The afucosyl oligosaccharide was 3H-labeled by the galactose oxidase-NaB3H4 method. [3H]Galactose was released by alpha-galactosidase, and only then was beta-galactosidase effective in removing another galactose. The gal(alpha 1-3)gal unit was demonstrated by periodate oxidation studies on the [3H]galactose-labeled asialo-glycoprotein. The presence of gal(alpha 1-3)gal in Tc-85 could be related to the recent finding of elevated antibody levels against this epitope in patients with Chagas' disease.


Hepatic manifestations of tuberous sclerosis complex: a genotypic and phenotypic analysis.
Hepatic manifestations of tuberous sclerosis complex: a genotypic and phenotypic analysis. A retrospective review of the clinical records and radiological images of 205 patients with tuberous sclerosis complex (TSC) was performed to evaluate the prevalence and progression of hepatic lesions; examine the association of hepatic phenotype with genotype, age, and gender; and investigate the relationships between hepatic, renal, and pulmonary involvement. Hepatic angiomyolipomas (AML), cysts, and other benign lesions were identified in 30% of the cohort, and some lesions grew significantly over time. However, no patient had clinical symptoms or complications from hepatic lesions. TSC2 patients exhibited a higher frequency of AML compared to TSC1 patients (p = 0.037), and patients with no mutation identified exhibited a higher frequency of cysts compared to TSC2 patients (p = 0.023). Age was positively correlated with frequency of hepatic involvement (p < 0.001), whereas hepatic phenotype was independent of gender. Presence of hepatic AML was associated with presence of renal AML (p = 0.001). These findings confirm a high rate of asymptomatic hepatic lesions in TSC and further characterize the TSC phenotype.


Analysis of the predictive factors for a critical illness of COVID-19 during treatment - relationship between serum zinc level and critical illness of COVID-19.
Because most severely ill patients with COVID-19 in our hospital showed zinc deficiency, we aimed to examine the relationship between the patient's serum zinc level and severe cases of COVID-19. Serum zinc <70 μg/dL was defined as the criterion for hypozincemia, and patients continuously with serum zinc <70 μg/dL were classified in the hypozincemia cohort. To evaluate whether hypozincemia could be a predictive factor for a critical illness of COVID-19, we performed a multivariate analysis by employing logistic regression analysis. Prolonged hypozincemia was found to be a risk factor for a severe case of COVID-19. In evaluating the relationship between the serum zinc level and severity of patients with COVID-19 by multivariate logistic regression analysis, critical illness can be predicted through the sensitivity and false specificity of a ROC curve with an error rate of 10.3% and AUC of 94.2% by only two factors: serum zinc value (P = 0.020) and LDH value (P = 0.026). Proper management of the prediction results in this study can contribute to establishing and maintaining a safe medical system, taking the arrival of the second wave, and the spread of COVID-19 in the future into consideration.


Corrigendum: Heat Shock Protein HSP24 Is Involved in the BABA-Induced Resistance to Fungal Pathogen in Postharvest Grapes Underlying an NPR1-Dependent Manner.
[This corrects the article DOI: 10.3389/fpls.2021.646147.].


Developmental regulation of type 1 and type 3 interferon production and risk for infant infections and asthma development.
Virus-associated febrile lower respiratory tract infections (fLRIs) during infancy have been identified as risk factors for persistent wheeze development. We hypothesized that variations in innate immune defense capacity during this period, as exemplified by production of type 1 and 3 interferons (T1/3IFNs), might be an underlying determinant of risk. We sought to investigate relationships between postnatal development of innate interferon response capacity and susceptibility to early infections and persistent wheeze. We studied a subset of subjects from a birth cohort at high risk for asthma/allergy and determined the capacity of cord blood cells (n = 151) to produce any of a panel of 17 T1/3IFNs in response to the viral mimic polyinosinic-polycytidylic acid using a sensitive PCR assay. We investigated relationships between neonatal interferon responses and lower respiratory tract infection history during infancy, wheezing history to 5 age years, and ensuing maturation of innate immune capacity by age 4 years (n = 160) and 10 years (n = 125). Although cohort subjects produced an average of 2.6 ± 0.3 of the 17 innate interferons tested at birth, 24% showed no T1/3IFN production. This nonproducer subgroup showed increased risk for infant fLRIs (odds ratio, 2.62; 95% CI, 1.14-6.06; P = .024) and persistent wheeze (odds ratio, 4.24; 95% CI, 1.60-11.24; P = .004) at age 5 years relative to those producing 1 or more T1/3IFNs, whereas risk for infant wheezy lower respiratory tract infections or "transient early wheeze" was unaffected. Moreover, infants who experienced fLRIs subsequently demonstrated accelerated development of T1/3IFN response capacity between 1 and 4 years of age. T1/3IFN response capacity appears strongly developmentally constrained at birth. Infants in whom this negative regulation is strongest manifest increased risk for severe respiratory tract infections during infancy and subsequent persistent wheeze.


Isolation of the 3-phosphoglycerate kinase gene of the arbuscular mycorrhizal fungus Glomus mosseae (Nicol. & Gerd.) Gerdemann & Trappe.
The 3-phosphoglycerate kinase (PGK) gene of the arbuscular mycorrhizal fungus Glomus mosseae has been isolated by differential RNA display (DD). Experimentally, the technique of DD was utilized to simultaneously compare the mRNA transcript populations from Lycopersicon esculentum root systems colonized by the arbuscular mycorrhizal fungus G. mosseae and non-mycorrhizal plants. A differentially expressed band was isolated and cloned from mycorrhizal tissue. The isolated DD fragment was screened and sequenced. A reverse transcription-PCR (RT-PCR) technique detected transcripts in germinated spores and G. mosseae-colonized root systems but not in uncolonised root systems. The full-length cDNA was isolated by RACE and corresponded to the 3-phosphoglycerate kinase gene of G. mosseae. The cDNA encodes a polypeptide of 416 amino acids, with a predicted molecular weight of 44 764 Da. The PGK proteins shows high homology to those PGKs of other fungi and the phylogenetic relationship among 14 isolated fungal PGK sequences is illustrated.


The use of home care in terminal cancer.
In order to identify factors associated with the use of home care services and satisfaction with those services, interviews were conducted with 72 percent of the surviving relatives and 92 percent of the physicians of a random sample of 133 patients from the Rochester, New York, area who had died of cancer and who had been diagnosed at least two weeks before death. These interviews included a self-administered attitude questionnaire from which ten attitude-scale scores were derived. Forty-one percent of the sample had used organized home care services, almost all under a home-hospice program. In comparison with nonusers, home care users tended to be younger, married, to have a longer terminal care period, and to spend more of it at home. Relatives of patients who had used home care services, in comparison with relatives of nonusers, were less satisfied with the availability of care and reported that the patient had experienced more pain. This study also highlights problems in communication, particularly between the physician and the patients and their families, and the effects of home care on the families, especially the primary care-giver. In order for home care and home death to be viable options for a larger number of terminal cancer patients, family members need to be assured of around-the-clock availability of care, adequate pain control, and respite care to provide temporary relief from the burden of home care.


Peripheral extracorporeal membrane oxygenation: comprehensive therapy for high-risk massive pulmonary embolism.
Although commonly reserved as a last line of defense, experienced centers have reported excellent results with pulmonary embolectomy for massive and submassive pulmonary embolism (PE). We present a contemporary surgical series for PE that demonstrates the utility of peripheral extracorporeal membrane oxygenation (pECMO) for high-risk surgical candidates. Between June 2005 and April 2011, 29 patients were treated for massive or submassive pulmonary embolism, with surgical embolectomy performed in 26. Four high-risk patients were placed on pECMO, established by percutaneously cannulating the right atrium through a femoral vein and perfusing by a Dacron graft anastomosed to the axillary artery. A small, extracorporeal, rotary assist device was used, interposing a compact oxygenator in the circuit, and maintaining anticoagulation with heparin. Extracorporeal membrane oxygenation was weaned in 3 of 4 patients after 5.3 days (5, 5, and 6), with normalization of right ventricular dysfunction and pulmonary artery pressure (44.0 ± 2.0 to 24.5 ± 5.5 mm Hg) by ECHO. Follow-up computed tomographies showed several peripheral, nearly resorbed emboli in 1 case and complete resolution in 2 others. The fourth patient, not improving after 10 days, underwent surgery where an embolic liposarcoma was extracted. For all 29 cases, hospital and 30-day mortality was 0% and all patients were discharged, with average postoperative length of stay of 15 days for embolectomy and 17 days for pECMO. Heparin therapy with pECMO support is a rapid, effective option for patients who might benefit from pulmonary embolectomy but are at high risk for surgery.


Comprehensive treatment of chronic fire setting in a severely disordered boy.
A comprehensive, multidimensional treatment strategy was designed for a severely behaviorally disordered 10-year-old boy with a 7-year history of setting fires. The study replicates a previous study designed to suppress fire setting, teach appropriate substitute behavior and increase awareness of the consequences of fire setting. Three additional components were added to the original treatment program: relaxation training, a response cost for fire setting, and a visit to a hospital burn unit (overt sensitization). Follow-up data 1 year later indicate that treatment was successful in extinguishing all fire-setting behaviors. The additional treatment components presented in this paper may add to the efficacy and sustained durability of treatment gains in difficult, low frequency fire setting behavior.


Increased circulating fibrocytes are associated with higher reticulocyte percent in children with sickle cell anemia.
Interstitial lung disease is common in patients with sickle cell anemia (SCA). Fibrocytes are circulating cells implicated in the pathogenesis of pulmonary fibrosis and airway remodeling in asthma. In this study, we tested the hypotheses that fibrocyte levels are: (1) increased in children with SCA compared to healthy controls, and (2) associated with pulmonary disease. Cross-sectional cohort study of children with SCA who participated in the Sleep Asthma Cohort Study. Fibrocyte levels were obtained from 45 children with SCA and 24 controls. Mean age of SCA cases was 14 years and 53% were female. In children with SCA, levels of circulating fibrocytes were greater than controls (P < 0.01). The fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on the majority of cells and CCR2 and CCR7 expressed on a smaller subset. Almost half of fibrocytes demonstrated α-smooth muscle actin activation. Increased fibrocyte levels were associated with a higher reticulocyte count (P = 0.03) and older age (P = 0.048) in children with SCA. However, children with increased levels of fibrocytes were not more likely to have asthma or lower percent predicted forced expiratory volume in 1 sec/forced vital capacity (FEV1 /FVC) or FEV1 than those with lower fibrocyte levels. Higher levels of fibrocytes in children with SCA compared to controls may be due to hemolysis. Longitudinal studies may be able to better assess the relationship between fibrocyte level and pulmonary dysfunction.


Dermoscopy and ultrosound monitoring actinic keratosis with cutaneous squamous cell carcinoma: A case report and literature review.
Actinic keratosis(AK) is a common premalignant skin lesion that can progress to invasive squamous cell carcinoma(iSCC). Clinically, AK presents as reddish or brownish macules, papules, or hyperkeratotic plaques. AK cannot be reliably predicted whether it will transform into invasive carcinomas, so skin biopsy is currently a gold standard for identifying suspicious malignancy. Currently, there are non-invasive methods to help diagnose and determine the difference between AKs and iSCC. For example, dermoscopy and ultrasound can be very useful in diagnosing and monitoring skin diseases non-invasively. Therefore, we report a case of multiple facial AKs with poorly differentiated skin squamous cell carcinoma, which was diagnosed early through dermoscopy and ultrasound, and confirmed by histopathology.


The hidden breast lesions: A case report of bilateral breast cancer.
Bilateral breast cancer (BBC) is rare and is associated with an unfavorable prognosis. Consequently it is crucial to improve diagnostic performance of breast cancer in the clinical setting. We report a case of BBC in a 66-year-old woman and describe the imaging findings, including mammography, hand-held ultrasound, automated breast ultrasound, anatomical intelligence for breast ultrasound (AI-breast), and magnetic resonance imaging. Only AI-breast ultrasound successfully located the two tumors, while other imaging examinations failed to detect the tumor in the right breast.


Crohn's disease in a patient with systemic onset juvenile idiopathic arthritis. Association or associated side effect of treatment?
The progression of systemic-onset juvenile idiopathic arthritis (JIAs) to the different forms of presentation of inflammatory bowel disease is extremely rare. We present the first report of a patient with SJIA that progressed to Crohn's disease in which mutations have been detected in genes responsible for the adequate regulation of the innate immune system.


Musculoskeletal melioidosis: An under-diagnosed entity in developing countries.
Melioidosis is a saprophytic infectious disease caused by Gram-negative soil-dwelling bacillus Burkholderia pseudomallei. We report three cases of musculoskeletal melioidosis that are presented to our department from 2011 to 2013. One of the patients died due to post-septicemic ARDS. The other two patients have recovered fully and are followed up for minimum of 6 months. There were no recurrences. Though musculoskeletal infection due to melioidosis is not common in India, new cases are being reported from Karnataka, Goa and Southern Maharashtra. The need for diagnosing this entity is due to the fact that the septicemic form has a mortality rate that exceeds 90%, and though culture sensitivity report shows susceptibility to various antibiotics, the infection responds to only specific set of antibiotics i.e. intravenous ceftazidime and combination of trimethoprim and sulfamethoxazole.


Overexpression of MdMIPS1 enhances salt tolerance by improving osmosis, ion balance, and antioxidant activity in transgenic apple.
Myo-inositol and its derivatives play vital roles in plant stress tolerance. Myo-inositol-1-phosphate synthase (MIPS) is the rate-limiting enzyme of myo-inositol biosynthesis. However, the role of apple MIPS-mediated myo-inositol biosynthesis in stress tolerance remains elusive. In this study, we found that ectopic expression of MdMIPS1 from apple increased myo-inositol content and enhanced tolerance to salt and osmotic stresses in transgenic Arabidopsis lines. In transgenic apple lines over-expressing MdMIPS1, the increased myo-inositol levels could promote accumulation of other osmoprotectants such as glucose, sucrose, galactose, and fructose, to alleviate salinity-induced osmotic stress. Also, it was shown that overexpression of MdMIPS1 enhanced salinity tolerance by improving the antioxidant system to scavenge ROS, as well as Na+ and K+ homeostasis. Taken together, our results revealed a protective role of MdMIPS1-mediated myo-inositol biosynthesis in salt tolerance by improving osmotic balance, antioxidant defense system, and ion homeostasis in apple.


Inflammatory immune responses in a reproducible mouse brain death model.
Brain death impairs donor organ quality and accelerates immune responses after transplantation. Detailed aspects of immune activation following brain death remain unclear. We have established a mouse model and investigated the immediate consequences of brain death and anesthesia on immune responses. C57JBl/6 mice (n=6/group) were anesthetized with isoflurane (ISF) or ketamine/xylazine (KX); subsequently, animals underwent brain death induction and were followed for 3h under continuous ventilation. Blood pressure was monitored continuously and animals were resuscitated with normal saline to achieve normotension. Immune activation in brain dead animals was analyzed by IFNγ-ELispot, MLR, and flow-cytometry. Sham-operated and naïve animals served as controls. Blood pressure remained stable in both BD/KX and BD/ISF animals during the 3h observation time. Brain death was linked to systemic immune activation: IFNγ-expression of splenocytes and lymphocyte proliferation rates was significantly elevated subsequent to brain death (p<0.02, <0.01); T-cell activation markers CD28 and CD69 had increased in brain dead animals (p<0.03, <0.02). Isoflurane treatment in sham controls throughout the observation period (3.5h) revealed anesthesia associated IFNγ-expression and lymphocyte activation which were not observed when animals were treated with ketamine/xylazine (p<0.04, <0.009). This study reports on a reproducible and hemodynamically stable brain death mouse model. Hemodynamic stability was not impacted through either isoflurane or ketamine/xylazine induction. Of clinical relevance, prolonged anesthesia with isoflurane had been linked to pro-inflammatory cytokine activation. Brain death caused systemic immune activation in organ donors.


Society of Interventional Radiology Position Statement on the Management of Chronic Iliofemoral Venous Obstruction with Endovascular Placement of Metallic Stents.
To state the position of the Society of Interventional Radiology (SIR) on the endovascular management of chronic iliofemoral venous obstruction with metallic stents. A multidisciplinary writing group with expertise in treating venous disease was convened by SIR. A comprehensive literature search was conducted to identify studies on the topic of interest. Recommendations were drafted and graded according to the updated SIR evidence grading system. A modified Delphi technique was used to achieve consensus agreement on the recommendation statements. A total of 41 studies, including randomized trials, systematic reviews and meta-analyses, prospective single-arm studies, and retrospective studies were identified. The expert writing group developed 15 recommendations on the use of endovascular stent placement. SIR considers the use of endovascular stent placement for chronic iliofemoral venous obstruction to be likely to help selected patients, but the risks and benefits have not been fully quantified in well-designed randomized studies. SIR recommends urgent completion of such studies. In the meantime, careful patient selection and optimization of conservative therapy are recommended prior to stent placement, with attention to appropriate stent sizing and quality procedural technique. The use of multiplanar venography with intravascular ultrasound is suggested in diagnosing and characterizing obstructive iliac vein lesions and in guiding stent therapy. After stent placement, SIR recommends close patient follow-up to ensure optimal antithrombotic therapy, durable symptom response, and early identification of adverse events.


Quantitative assessment of the parotid gland using computed tomography texture analysis to detect parotid sialadenitis.
We aimed to quantitatively assess the parotid gland by using computed tomography (CT) texture analysis to detect parotid sialadenitis (PS). This retrospective case-control study included 43 patients with PS who underwent CT and magnetic resonance imaging (MRI). Parotid glands with an abnormal signal (STIR: High) on MRI were identified as showing PS. Patients with parotid gland tumors, bilateral PS, marked fatty degeneration, and severe artifacts on CT were excluded. The texture features of parotid glands with PS and the contralateral normal parotid glands were analyzed using the open-access software LIFEx. The regions of interest were manually placed by tracing contours of both parotid glands on CT images. The results were tested with the paired t-test (or Wilcoxon rank-sum test when appropriate). Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of texture features to predict PS. Six gray level run length matrix features, 2 neighborhood gray level difference matrix features, and 5 gray level zone length matrix features displayed significant differences between PS and normal glands (P ≤ .047). ROC curve analysis showed acceptable accuracy in 4 texture features. CT texture analysis allowed quantitative assessment of parotid glands and may have the potential to detect PS.


Author Correction: Signalling through the yeast MAPK Cell Wall Integrity pathway controls P-body assembly upon cell wall stress.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.