Effects of I2-imidazoline receptor (IR) alkylating BU99006 in the mouse brain: Upregulation of nischarin/I1-IR and μ-opioid receptor proteins and modulation of associated signalling pathways.
5-isothiocyanato-2-benzofuranyl-2-imidazoline (BU99006) was shown to selectively and irreversibly bind to I2-imidazoline receptors (IRs) in vitro and in vivo, but cell signalling consequences of I2-IR alkylation have not been reported previously. This study assessed by Western blot the effects of BU99006 on nischarin (candidate I1-IR), μ-OR (regulated by nischarin) and associated signalling mediators in the mouse brain. Acute treatment with BU99006 (20 mg/kg, i.p., 1-3 h) led to fast (peak at 1 h) and shortlasting (decline up to 3 h) upregulation of nischarin and μ-OR contents in the hippocampus (less or non-significant effects in cortex) and altered the expression of cytoskeletal β-actin (reduced contents at 3 h). In the same hippocampal samples of BU99006-treated mice, an inhibition of the MAPK species MEK, ERK and JNK was detected at 1 and/or 2 h after drug administration, which was paralleled by enhanced calpain activity (increased contents of p25 and spectrin breakdown products). Correlation analysis indicated the involvement of cdk5/p25 in MEK/ERK inhibition. These neurochemical effects of I2-alkylating BU99006 show a close relation between I1- and I2-IRs expressed in the mouse brain and between these receptors and the μ-OR, accompanied by cytoskeletal alterations and differential effects on multifunctional MAPK and cdk5 signalling pathways.


Recognition of DNA by single-chain derivatives of the phage 434 repressor: high affinity binding depends on both the contacted and non-contacted base pairs.
Single-chain derivatives of the phage 434 repressor, termed single-chain repressors, contain covalently dimerized DNA-binding domains (DBD) which are connected with a peptide linker in a head-to-tail arrangement. The prototype RR69 contains two wild-type DBDs, while RR*69 contains a wild-type and an engineered DBD. In this latter domain, the DNA- contacting amino acids of thealpha3 helix of the 434 repressor are replaced by the corresponding residues of the related P22 repressor. We have used binding site selection, targeted mutagenesis and binding affinity studies to define the optimum DNA recognition sequence for these single-chain proteins. It is shown that RR69 recognizes DNA sequences containing the consensus boxes of the 434 operators in a palindromic arrangement, and that RR*69 optimally binds to non-palindromic sequences containing a 434 operator box and a TTAA box of which the latter is present in most P22 operators. The spacing of these boxes, as in the 434 operators, is 6 bp. The DNA-binding of both single-chain repressors, similar to that of the 434 repressor, is influenced indirectly by the sequence of the non-contacted, spacer region. Thus, high affinity binding is dependent on both direct and indirect recognition. Nonetheless, the single-chain framework can accommodate certain substitutions to obtain altered DNA-binding specificity and RR*69 represents an example for the combination of altered direct and unchanged indirect readout mechanisms.


Drug use in very rural Alaska villages.
The Alaska Native Preschool Project was centered in the Head Start Programs of two typical Alaska native villages near the Bering Sea. Data were collected over 5 years, 1990 to 1995, from preschool parents (N = 342) with surveys, a panel of villagers (N = 25 to 30) using qualitative interviews; villagers using participant observation; and a limited review of public records. The villages typify the changing life of Alaskan villagers who live in the Bering Straits area. Qualitative data indicated that a number of problems were associated with drug and alcohol use in the villages. The level of smokeless tobacco use from surveys in the previous month among preschool parents (41%) was self-reported to be almost 10 times greater than the national level reported in the 1995 National Household Survey. The use of marijuana reported by preschool parents in the previous month was almost 3 times higher than the 1995 National Household Survey estimates (19 vs 6.7%). Tobacco use in the previous month was reported at over 56%, a level that was over 1 1/2 times the level of use at 34.7% estimated from the 1995 National Household Survey. For 26-34 year olds, previous month alcohol use was lower for the village parents than estimated from the 1995 National Household Survey (38 vs 63%). The self-reported levels of other drug use among preschool parents were very low compared with overall United States rates.


MXene-modified electrodes and electrolytes in dye-sensitized solar cells.
Dye-sensitized solar cells (DSSCs) have attracted much attention as promising tools in renewable energy conversion technology. This is mainly because of their beneficial qualities, such as their impressive efficiency levels and low-cost fabrication techniques. An overview of MXene-modified electrodes in DSSCs is given in this review article. MXenes are two-dimensional (2D) transition metal carbides or nitrides with remarkable properties such as high conductivity and large surface area. MXenes' properties make them an appealing material for various applications, including energy storage, catalysis, and electronic devices. MXene integration enhances ion transport, dye adsorption, and charge transport in DSSC electrodes. In-depth analysis of the use of 2D Mxene and integration with carbon nanotubes (CNTs), reduced graphene oxide (rGO), 2D MoS2, and hybrids like 2D-2D heterostructures for electrode modification in photovoltaics (PVs), including anodes, photoanodes, composite decorated electrodes, counter electrodes (CEs), and electrolytes, is provided in this review article. The effects on the performance metrics of various deposition techniques are discussed and assessed. The use of MXene-modified electrodes in DSSCs suggests potential for enhancing the performance and efficiency of these solar cells in general. The article examines this strategy's potential advantages and implications, illuminating the fascinating advancements in the area and emphasizing MXenes' potential as a valuable substance for renewable energy applications. We also discuss the difficulties and potential benefits of using MXene-modified electrodes in DSSCs and emphasize the need for additional study to enhance stability, optimize MXene integration techniques, and enhance long-term device performance. The scalability and potential of MXene-based electrode modifications for commercial applications are also covered, addressing issues and prospects for the future, focusing on the necessity of more study. Electrodes modified with MXenes can improve DSSC performance and advance sustainable energy conversion.


Closing the loop on inflammation and atherothrombosis: why perform the CIRT and CANTOS trials?
Inflammation contributes to all phases of the atherothrombotic process, patients with elevated inflammatory biomarkers such as high-sensitivity C-reactive protein (hsCRP) have increased cardiovascular risk, and recent work directly implicates the interleukin-1 (IL-1) and interleukin-6 (IL-6) pathways in atherogenesis. Yet, it remains unknown whether targeted inhibition of inflammation will reduce cardiovascular event rates. To address directly this fundamental hypothesis, our research group has initiated two large-scale, randomized, placebo-controlled trials using targeted anti-inflammatory agents for the secondary prevention of myocardial infarction. The first trial, the Cardiovascular Inflammation Reduction Trial (CIRT), has been funded by the NHLBI and will evaluate whether low-dose methotrexate (target dose, 20 mg/wk) as compared to placebo will reduce major vascular events among a group of post-myocardial infarction patients with either diabetes or metabolic syndrome, groups known to have high risk on the basis of a persistent pro-inflammatory response. CIRT is based, in part, on observational evidence of reduced vascular event rates among those treated with methotrexate in the setting of rheumatoid arthritis or psoriatic arthritis and on the ability of methotrexate to reduce TNF, IL-6, and CRP levels. The second trial, the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS), will evaluate whether interleukin-1β (IL-1β) inhibition as compared to placebo can reduce rates of recurrent myocardial infarction, stroke, and cardiovascular death among stable coronary artery disease patients who remain at high vascular risk due to persistent elevations of hsCRP (_2 mg/L) despite contemporary secondary prevention strategies. Canakinumab is a human monoclonal antibody that selectively neutralizes IL-1β, a pro-inflammatory cytokine that plays multiple roles in the atherothrombotic process and that undergoes activation by the NLRP3 inflammasome, a process promoted by cholesterol crystals that in turn leads directly to increased production of IL-1 and IL-6. Together, CIRT and CANTOS will enroll more than 25,000 patients worldwide and provide a fundamental test of the inflammatory hypothesis of atherothrombosis.


Auditory normalization of French vowels synthesized by an articulatory model simulating growth from birth to adulthood.
The present article aims at exploring the invariant parameters involved in the perceptual normalization of French vowels. A set of 490 stimuli, including the ten French vowels /i y u e ø o E oe (inverted c) a/ produced by an articulatory model, simulating seven growth stages and seven fundamental frequency values, has been submitted as a perceptual identification test to 43 subjects. The results confirm the important effect of the tonality distance between F1 and f0 in perceived height. It does not seem, however, that height perception involves a binary organization determined by the 3-3.5-Bark critical distance. Regarding place of articulation, the tonotopic distance between F1 and F2 appears to be the best predictor of the perceived front-back dimension. Nevertheless, the role of the difference between F2 and F3 remains important. Roundedness is also examined and correlated to the effective second formant, involving spectral integration of higher formants within the 3.5-Bark critical distance. The results shed light on the issue of perceptual invariance, and can be interpreted as perceptual constraints imposed on speech production.


Rat ovarian mast cells: distribution and cyclic changes.
Numerous tissue mast cells are present in the ovarian medulla and hilus and in the oviduct of rats. In the medulla, most of these mast cells are in the connective tissue of the stroma near blood and lymphatic vessels. During proestrus, many of the medullary mast cells totally degranulate and thus are not visible histochemically; they then regranulate during estrus. In contrast, the number of stainable mast cells in the ovarian hilus and oviduct does not change during the estrous cycle. Histofluorometric methods demonstrate that mast cells in the ovarian medulla and hilus, as well as the oviduct, contain histamine. In addition, the lining of small blood vessels in the ovarian medulla contains histamine. Thus, mast cell and blood vessel histamine secretion may play a role in ovarian function.


Executive Coaching for Leadership Development: Experience of Academic Physician Leaders.
To identify the perceived impact and benefit of executive coaching by a physician coach in the context of their leadership roles. A descriptive qualitative inquiry was conducted. Individual semi-structured interviews ex post facto were conducted with physician leaders who completed an executive coaching program during the period 2015-2016.Interviews were transcribed verbatim, and data were analyzed by applying an emergent thematic analysis approach. Five interviews were conducted. Participants were female specialist physicians age 25-50 years with leadership experience that was minimal (one), more than two years (one), five years (one) or greater than 10 years (two). The experiences of the interview participants captured seven themes: isolation, time management, self-doubt, support, productivity, moving forward and workplace culture change/shift. For all participants, executive coaching appeared to positively impact their personal and professional development. There was a high degree of congruence in the experience of the executive coaching program by participants. The physician leaders who underwent a series of executive coaching sessions had very similar experiences overall. The added professional development tool of executive coaching for specialist physicians may have a significant role in supporting productivity, increasing workplace engagement and transforming the culture of medical practice.


Hypertensive disorders of pregnancy and maternal and foetal outcome: a case controlled study.
A case controlled prospective study of 250 cases of hypertension complicating pregnancy (study group) and 400 normal pregnant women (control group) was carried out to determine the effect of hypertension on maternal and foetal outcome. Pregnancy induced hypertension was present in 96% cases and chronic hypertension in 4% cases. Preterm delivery (28.8% versus 3%), labour induction rate (52.8% versus 3.25%), caesarean section rate (14.8% versus 3.5%), stillbirth rate (4.8% versus 0.25%) and overall perinatal mortality rate (14.8% versus 1%) were higher in study group compared to controls. In study group (40%) babies required special nursery care compared to controls (6.75%). From these results it can be concluded that maternal hypertension is associated with adverse pregnancy outcome.


[Patient turnover in a multidisciplinary emergency department].
More than twenty emergency departments were opened across Hungary in the past years. Data deficiency on patient flow, trends and lack of knowledge of indicators could raise numerous logistical and organisational problems. Collection, analysis and provision of data to facilitate successful operations of emergency medical care services. During a three-year period investigated, at the multidisciplinary Emergency Department of "Moritz Kaposi" Teaching Hospital, data on patient flow (n = 106,203), epidemiology, triage and international classification of diseases were analysed. Analysis showed 73% of patients were suitable for medical discharge within 24 hours. Predominantly internal medicine, paediatric and neurological diseases indicated hospitalisation (21%). Patients in critical condition were found to be low (<2%). Distinct diurnal, weekly, monthly variations were found. Majority of cases were injuries and intoxications (40%). Low mortality rate (0.3%) validates the effectiveness of stabilisation. The patient safety value of the examined emergency medical care is great, and could exempt the hospital wards from unjustified hospitalisations of the patients. Orv Hetil. 2017; 158(21): 811-822.


Adenomatoid odontogenic tumor with extensive formation of tubular dentin.
Although the adenomatoid odontogenic tumor (AOT) is categorized as an odontogenic epithelial tumor with odontogenic ectomesenchyme, AOT with induction of true tubular dentin with or without concomitant formation of enamel is exceedingly rare. This paper reports a case of AOT showing evidence of extensive induction of tubular dentin, but without concomitant formation of enamel. The patient was a 20-year-old female with a rather well-circumscribed intraosseous lesion of the maxillary incisor-premolar area without an embedded tooth. Histologically, extensive induction of a dysplastic form of tubular dentin with globular calcification was evident, in addition to the characteristic histological features of AOT. The present case lends support to the categorization of AOT as an odontogenic tumor consisting of a disorderly mixture of odontogenic epithelium and odontogenic ectomesenchyme with or without dental hard tissue formation.


Recovery Curve for Patients With Pilon Fractures Using Patient-Reported Outcome Measurement Information System.
The time frame in which patients can expect functional improvement after open reduction internal fixation (ORIF) of pilon fractures is unclear. The purpose of this study was to determine the trajectory and rate at which patients' physical function improves up to 2 years postinjury. The patients studied sustained a unilateral, isolated pilon fractures (AO/OTA 43B/C) and followed at a level 1 trauma center over a 5-year period (2015-2020). Patient-Reported Outcomes Measurement Information Systems (PROMIS) Physical Function (PF) scores from these patients at defined follow-up times of immediately, 6 weeks, 3 months, 6 months, 1 year, and 2 years after surgery defined the cohorts and were retrospectively studied. There were 160 patients with PROMIS scores immediately postoperatively, 143 patients at 6 weeks, 146 patients at 12 weeks, 97 at 24 weeks, 84 at 1 year, and 45 at 2 years postoperatively. The average PROMIS PF score was 28 immediately postoperatively, 30 at 6 weeks, 36 at 3 months, 40 at 6 months, 41 at 1 year, and 39 at 2 years. There was a significant difference between PROMIS PF scores between 6 weeks and 3 months (P < .001), and between 3 and 6 months (P < .001). Otherwise, no significant differences were detected between consecutive time points. Patients with isolated pilon fractures demonstrate the majority of their improvement in terms of physical function between 6 weeks and 6 months postoperatively. No significant difference was detected in PF scores after 6 months postoperatively up to 2 years. Furthermore, the mean PROMIS PF score of patients 2 years after recovery was approximately 1 SD below the population average. This information is helpful in counseling patients and setting expectations for recovery after pilon fractures. Level III, prognostic.


1,25-Dihydroxy vitamin D3 inhibits adipocyte differentiation and gene expression in murine bone marrow stromal cell clones and primary cultures.
Bone marrow stromal stem cells differentiate into adipocytes and osteoblasts. These two lineages are thought to be reciprocally related, in part due to the observation that the osteoblast-inducing factor, 1,25 dihydroxy vitamin D3 [1,25(OH)2D3], inhibited adipogenesis of rat femoral-derived stromal cell cultures. However, the literature is divided concerning the adipogenic effects of this steroid hormone. This work examined the effect of 1,25(OH)2D3 (10(-12)-10(-8) M) on murine femoral-derived bone marrow stromal cell differentiation in response to adipogenic agonists employing two different classes of nuclear hormone receptors: the glucocorticoid receptor (hydrocortisone) or peroxisome proliferator-activated receptors (thiazolidinediones). Experiments used the multipotent murine bone marrow stromal cell line, BMS2, and its subclones, as well as primary-derived murine bone marrow stromal cell cultures. In all systems examined, 1,25(OH)2D3 blocked adipogenesis induced by hydrocortisone, methylisobutylxanthine, and indomethacin based on flow cytometric analysis of lipid accumulation. This correlated with reduced messenger RNA levels of the late adipocyte gene markers, aP2 and adipsin. In the BMS2 subclone no. 24, the 1,25(OH)2D3 actions were concentration dependent. Whereas 1,25(OH)2D3 partially inhibited thiazolidinedione-induced adipogenesis in the parental BMS2 cell line, it had minimal effect on the thiazolidinedione-induced differentiation of the BMS2 subclone and primary cultures. These findings indicate that 1,25(OH)2D3, at nanomolar concentrations, completely inhibits murine bone marrow stromal cell differentiation in response to glucocorticoid-based adipogenic agonists but is a less effective adipogenic antagonist following induction with thiazolidinediones. This work supports the conclusion that 1,25(OH)2D3 inhibits murine femoral-derived bone marrow stromal cell adipogenesis.


[Effects of antidepressants in models of brain self-stimulation and place preference after prolong social isolation and alcoholization].
In rats rearing in social isolation since 17th day of life and treated with 5-15% ethanol solution within 3 months, the effects of antidepressants on self-stimulation of lateral hypothalamus and place preference were studied. The comparative study of seven antidepressants with different mechanism of action (fluoxetine, maprotiline, tianaptine, pyrazidol, sertraline, citalopram, mianserin) was shown that pyrazidol and tianeptine and in a less degree sertraline and citalopram possessed the significant antidepressant activity in the model of social isolation and maprotiline and tianeptine did in model of alcoholization. It is concluded that antidepressants studied activate the reinforcing properties of the brain, that is associated with the involvement of both the catecholamine and serotonin system, working reciprocally.


Oxytocin Modulates Osteogenic Commitment in Human Adipose-Derived Stem Cells.
Human adipose-derived stem cells (hASCs) are commonly harvested in minimally invasive contexts with few ethical concerns, and exhibit self-renewal, multi-lineage differentiation, and trophic signaling that make them attractive candidates for cell therapy approaches. The identification of natural molecules that can modulate their biological properties is a challenge for many researchers. Oxytocin (OXT) is a neurohypophyseal hormone that plays a pivotal role in the regulation of mammalian behavior, and is involved in health and well-being processes. Here, we investigated the role of OXT on hASC proliferation, migratory ability, senescence, and autophagy after a treatment of 72 h; OXT did not affect hASC proliferation and migratory ability. Moreover, we observed an increase in SA-β-galactosidase activity, probably related to the promotion of the autophagic process. In addition, the effects of OXT were evaluated on the hASC differentiation ability; OXT promoted osteogenic differentiation in a dose-dependent manner, as demonstrated by Alizarin red staining and gene/protein expression analysis, while it did not affect or reduce adipogenic differentiation. We also observed an increase in the expression of autophagy marker genes at the beginning of the osteogenic process in OXT-treated hASCs, leading us to hypothesize that OXT could promote osteogenesis in hASCs by modulating the autophagic process.


Risk of Gonococcal Infection During Vaginal Exposure is Associated With High Vaginal pH and Active Menstruation.
An understanding of the biological reasons why 25% to 35% of women resist infection during vaginal intercourse with a man infected with Neisseria gonorrhoeae could lead to novel control measures. We sought modifiable biological bases for infection resistance by comparing women in the same core-mixing group who did or did not become infected after sexual exposure. We enrolled 61 female contacts of index men with gonorrhea seen at Baltimore City Health Department clinics from January 2008 through May 2012. Exposure and sexual practices and histories, co-infections, physical signs on exam, patient symptom report, and menstrual history were collected. Thirty-eight (62.3%) of the exposed women developed cervical infections. Multiple logistic regression found that a vaginal pH of 4.5 or higher at presentation to clinic was significantly associated with gonococcal infection (adjusted odds ratio, 5.5; P = 0.037) in women who presented within one menstrual cycle, 35 days. In this group of women, there was a significant association between acquiring an N. gonorrhoeae cervical infection and sexual exposure during menstruation (adjusted odds ratio 12.5; P = 0.05). Modification of vaginal pH could be explored as novel strategy for reducing the risk of N. gonorrhoeae infections in women.


A full-length enriched cDNA library and expressed sequence tag analysis of the parasitic weed, Striga hermonthica.
The obligate parasitic plant witchweed (Striga hermonthica) infects major cereal crops such as sorghum, maize, and millet, and is the most devastating weed pest in Africa. An understanding of the nature of its parasitism would contribute to the development of more sophisticated management methods. However, the molecular and genomic resources currently available for the study of S. hermonthica are limited. We constructed a full-length enriched cDNA library of S. hermonthica, sequenced 37,710 clones from the library, and obtained 67,814 expressed sequence tag (EST) sequences. The ESTs were assembled into 17,317 unigenes that included 10,319 contigs and 6,818 singletons. The S. hermonthica unigene dataset was subjected to a comparative analysis with other plant genomes or ESTs. Approximately 80% of the unigenes have homologs in other dicotyledonous plants including Arabidopsis, poplar, and grape. We found that 589 unigenes are conserved in the hemiparasitic Triphysaria species but not in other plant species. These are good candidates for genes specifically involved in plant parasitism. Furthermore, we found 1,445 putative simple sequence repeats (SSRs) in the S. hermonthica unigene dataset. We tested 64 pairs of PCR primers flanking the SSRs to develop genetic markers for the detection of polymorphisms. Most primer sets amplified polymorphicbands from individual plants collected at a single location, indicating high genetic diversity in S. hermonthica. We selected 10 primer pairs to analyze S. hermonthica harvested in the field from different host species and geographic locations. A clustering analysis suggests that genetic distances are not correlated with host specificity. Our data provide the first extensive set of molecular resources for studying S. hermonthica, and include EST sequences, a comparative analysis with other plant genomes, and useful genetic markers. All the data are stored in a web-based database and freely available. These resources will be useful for genome annotation, gene discovery, functional analysis, molecular breeding, epidemiological studies, and studies of plant evolution.


Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease.
The mild cognitive impairment (MCI) stage of dementia with Lewy bodies (MCI-DLB) has not yet been defined, but is likely to differ in the MCI stage of Alzheimer's disease (MCI-AD). To determine whether clinical features distinguish MCI-DLB and MCI-AD, 9 cases of neuropathologically confirmed MCI-DLB and 12 cases of MCI-AD were compared. No significant differences were found between MCI-DLB and MCI-AD cases in age at death, gender, ApoE status, education, time followed while clinically normal, or duration of MCI. MCI-DLB and MCI-AD cases differed clinically in the expression of Parkinsonism (P=0.012), provoked hallucinations or delirium (P=0.042), or the presence of any of these noncognitive symptoms of DLB (P<0.0001). Letter fluency (P=0.007) was significantly lower and Wechsler Logical Memory I (P=0.019) was significantly higher in MCI-DLB compared to MCI-AD cases. These data demonstrate the feasibility of differentiating underlying pathologic processes responsible for cognitive decline in the preclinical disease state and suggest that further refinement in diagnostic criteria may allow more accurate early detection of prodromal DLB and AD.


The study of binding of methyl tert-butyl ether to human telomeric G-quadruplex and calf thymus DNA by gas chromatography, a thermodynamic discussion.
Methyl-tert-butyl ether (MTBE) is widely used as an antiknock additive for increasing octane number of gasoline. Recently, the in vivo studies demonstrated that MTBE has genotoxic potential and able to form adducts with DNA. In the work, the interactions of MTBE with calf thymus DNA (ct-DNA) and the Na(+) form of G-quadruplex DNA (wtTel22) were studied by using of head space-solid phase microextraction technique coupled to gas chromatography. The binding equilibrium constants were measured through the equilibriums of a four phase system. In addition, the MTBE Henry's law constants for two different buffers in the temperature range of 283-303K were measured. Thermodynamic studies revealed that the complexation of MTBE to both DNAs is enthalpy favored and entropy disfavored. The thermodynamic results revealed that MTBE may have interaction with ct-DNA via the minor groove of DNA. Also, MTBE may be complexed into the basket of G-quadruplex structure. In addition, the low difference in the binding constants of MTBE for both different DNA targets may confirm that MTBE is poorly selective for different conformations of DNA.


Hertel Exophthalmometry Values in a Greek Adult Outpatient Clinic-Based Population: Association With Demographic Factors and Systemic Disease.
To investigate correlations of exophthalmometry values (EVs) with age, gender, and the presence of diabetes mellitus, arterial hypertension, and dyslipidemia. In a cross-sectional, clinic-based study, consecutive adult Greek patients presenting for evaluation at the outpatient general clinic on a scheduled appointment basis at a tertiary care referral center were submitted to Hertel exophthalmometry in both eyes by the same observer. Subjects with signs of history or orbital pathology, including thyroid-associated ophthalmopathy, were excluded. Demographics, as well as a detailed systemic history report, were recorded. Mixed effect linear regression analysis was performed to account for the correlation between the eyes of the same participant. A total of 800 eyes (400 subjects) were included, 194 males and 206 females, with a mean age of 67.82 ± 12 years (range: 18-92 years). The mean exophthalmometry value was 15.7 ± 2.6 mm (range: 11-21 mm). Every one year of increase in age is associated with a decrease in EVs by 0.03 mm (95% CI -0.04, -0.02/p-value<0.001). Female gender was associated with lower EVs by 0.33mm (95% CI-0.56, -0.1/p-value=0.005). Patients with diabetes mellitus had higher EVs by 0.47 mm (95% CI 0.25, 0.70/p-value<0.001) compared to patients without diabetes, and patients with arterial hypertension had lower EVs by 0.26 mm (95% CI -0.5, -0.02/p-value=0.034) compared to patients without hypertension. No association was found between dyslipidemia and systemic history of thyroid dysfunction. Conclusions: A negative correlation of EVs was noted with increasing age, female gender, as well as history of arterial hypertension and a positive correlation with diabetes mellitus.


Radium-223 in patients with metastatic castration-resistant prostate cancer: Efficacy and safety in clinical practice.
Radium-223 has improved overall survival (OS) and reduced symptomatic skeletal events (SSE) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases (ALSYMPCA trial). Our aim was to assess clinical and biochemical factors related to survival, safety and survival outcomes of Radium-223 in a clinical practice setting. We retrospectively analysed 32 mCRPC patients treated with Radium-223, assessing bone scan, pain reduction, alkaline phosphatase (ALP) and prostate-specific antigen (PSA) response (≥30% reduction). At scintigraphic assessment, 41% had partial response with a disease control rate of 91%; 56% had ALP response and 25% had PSA response; 41% had pain reduction with pain control of 72%. Scintigraphic response and stability were correlated with longer median progression-free survival (mPFS) (13 and 12 vs. 6 months; P=0.002) and mOS (16 and 12 vs. 6 months; P=0.003). ALP response was associated with longer mPFS (13 vs. 12 months; P=0.2) and mOS (16 vs. 12 months; P=0.2). PSA response was associated with longer mPFS (13 vs. 12 months; P=0.02), whereas mOS could not be computed. Pain response and stability were associated with survival benefit according to mPFS (13 and 12 vs. 9 months) and mOS (both 16 vs. 12 months) without statistical significance. Baseline ALP <220 UI/l, Eastern Cooperative Oncology Group (ECOG) performance status 0 and absence of previous chemotherapy correlated with statistically significantly longer survival outcomes. Skeletal-related events (SRE) occurred in three patients and median time to first SRE was 9.5 months, mPFS was 12 months and mOS 14 months. G3-G4 toxicities developed in 16% of patients. Our results are in line with those reported in the pivotal trial and in other retrospective studies. In conclusion, Radium-223 was associated with high scintigraphic, biochemical and pain response rates and was tolerated well by most patients. Response to Radium-223 and better baseline factors correlated to longer survival in clinical practice experience as in the clinical trial setting.


Quantifying impacts of short-term plasticity on neuronal information transfer.
Short-term changes in efficacy have been postulated to enhance the ability of synapses to transmit information between neurons, and within neuronal networks. Even at the level of connections between single neurons, direct confirmation of this simple conjecture has proven elusive. By combining paired-cell recordings, realistic synaptic modeling, and information theory, we provide evidence that short-term plasticity can not only improve, but also reduce information transfer between neurons. We focus on a concrete example in rat neocortex, but our results may generalize to other systems. When information is contained in the timings of individual spikes, we find that facilitation, depression, and recovery affect information transmission in proportion to their impacts upon the probability of neurotransmitter release. When information is instead conveyed by mean spike rate only, the influences of short-term plasticity critically depend on the range of spike frequencies that the target network can distinguish (its effective dynamic range). Our results suggest that to efficiently transmit information, the brain must match synaptic type, coding strategy, and network connectivity during development and behavior.


Production of VO2 M1 and M2 nanoparticles and composites and the influence of the substrate on the structural phase transition.
A two-step, high-purity, high-yield synthesis of nanoparticulate vanadium dioxide, which has a greater than 10-fold potential cost reduction is reported. This consists of a short reflux of V2O5 with aspartic acid, followed by calcination at 600 degrees C or above. The particles produced have a mean diameter of approximately 90 nm with phase change characteristics of transition temperature and enthalpy that compare favorably with a commercial standard. In cases where the reduction reaction has progressed too far and a mixture of vanadium(III) and -(IV) is formed, redispersion and aging of the particulate product in water preferentially oxidizes the vanadium(III) component to vanadium(IV), thus allowing a versatile route to achieving a high-purity material. The synthesis was also used to deposit high-purity phases of VO2 onto the surfaces of other particles, and significant differences in the structural phase transition behavior and even the crystal structure were found for deposited samples. The data suggest that substrate properties may affect the characteristics of the structural phase transition, and this has significant implications for measurements on, and applications of, deposited VO2 layers and films.


Therapeutic Potential of Natural Plants Against Non-Alcoholic Fatty Liver Disease: Targeting the Interplay Between Gut Microbiota and Bile Acids.
Non-alcoholic fatty liver disease (NAFLD) remains a common disease with a significant health and economic burden worldwide. The gut microbiota (GM) and bile acids (BAs), which play important roles in the gut-liver axis, have been confirmed to jointly participate in the development of NAFLD. GM not only regulate bile acids' synthesis, transport, and reabsorption by regulating other metabolites (such as trimetlyl amine oxide, butyrate), but also regulate dehydrogenation, dehydroxylation and desulfurization of bile acids. Meanwhile, disordered bile acids influence the gut microbiota mainly through promoting the bacterial death and lowering the microbial diversity. Although weight loss and lifestyle changes are effective in the treatment of NAFLD, the acceptability and compliance of patients are poor. Recently, increasing natural plants and their active ingredients have been proved to alleviate NAFLD by modulating the joint action of gut microbiota and bile acids, and considered to be promising potential candidates. In this review, we discuss the efficacy of natural plants in treating NAFLD in the context of their regulation of the complex interplay between the gut microbiota and bile acids, the crosstalk of which has been shown to significantly promote the progression of NAFLD. Herein, we summarize the prior work on this topic and further suggest future research directions in the field.


Basal ganglia volumes following CO poisoning: A prospective longitudinal study.
Carbon monoxide (CO) poisoning may result in focal and diffuse neuropathological changes, including basal ganglia lesions. The effect of CO poisoning on basal ganglia volumes over time is unclear. We assessed basal ganglia volumes longitudinally following CO poisoning. We prospectively enrolled 73 CO poisoned patients who underwent brain MR imaging on day 1 (baseline), 2 weeks, and 6 months post-CO poisoning. Basal ganglia volumes were obtained. One patient had bilateral globus pallidus lesions at two weeks and 6 months. Of the CO-poisoned patients 28% had volume reduction in at least one basal ganglia structure by 6 months, of which 21% had putamen, 15% had caudate, 15% had globus pallidus, and 16% had total basal ganglia volume reduction. Putamen volumes were significantly smaller from baseline to six months (p = 0.02). Verbal memory and mental processing speed correlated with smaller putamen and globus pallidus volumes. Carbon monoxide poisoning results in basal ganglia volume reduction 6 months post CO poisoning. Slow mental processing speed and impaired memory correlated with smaller putamen and globus pallidus volumes. Clinicians need to be aware of basal ganglia neuropathologic changes in the absence of observable lesions following CO poisoning.


Adenosine A3 receptor agonist reduces early brain injury in subarachnoid haemorrhage.
Inflammation plays an important role in the pathogenesis of early brain injury after subarachnoid haemorrhage. Adenosine A3 receptor (A3R) activation produces anti-inflammatory effects. In this study, the effects of a selective A3R agonist, 2-chloro-N⁶-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (CL-IB-MECA), on early brain injury and inflammatory response after subarachnoid haemorrhage were studied. Our results showed that mortality, neurological impairment and brain oedema were significantly attenuated after the administration of CL-IB-MECA. Moreover, treatment with CL-IB-MECA inhibited microglial activation and reduced the expression of proinflammatory cytokines including tumour necrosis factor-α and interleukin-1β. These data suggest that activation of A3R provides a neuroprotective effect against brain injury after subarachnoid haemorrhage, and that these effects may be associated with the anti-inflammatory properties of A3R.


[Severe hypothermia associated with cesarean section under spinal anesthesia].
Temperature monitoring and prevention of hypothermia are rarely used during spinal anaesthesia for caesarean section because hypothermia risk is considered very low. However, in same conditions, we observed two cases of severe hypothermia. We report these two cases and discuss the effects of spinal anaesthesia on thermoregulatory system. Hypothermia seems explained by the effects of perimedullar anaesthesia that decrease the shivering and the vasoconstriction thresholds. These effects are potentiated by morphinomimetic adjunction. At last, we recall prophylactics measures.


Nitrogen Starvation-induced Phosphorylation of Ras1 Protein and Its Potential Role in Nutrient Signaling and Stress Response.
Ras1 is a small GTPase in the budding yeast Saccharomyces cerevisiae that regulates nutrient signaling. It has been shown that Ras1 undergoes phosphorylation, but the functional consequences and regulation of Ras1 phosphorylation remain unknown. Here we identify Ser-226 as an important residue for Ras1 phosphorylation, as mutating this residue to an alanine drastically diminishes the level of Ras1 phosphorylation. Notably, phosphorylated Ras1 accumulates as the cells approach the stationary phase of growth. Likewise, subjecting cells to nitrogen starvation also elevates the level of Ras1 phosphorylation. Interestingly, blocking Ras1 phosphorylation diminishes the level of autophagy and also renders the cells more sensitive to heat shock. Together, these data suggest a role of Ras1 phosphorylation in modulating nutrient signaling and stress response.


Uremic pruritus in the chronic renal failure patients.
Chronic renal failure is connected with various cutaneous symptoms, of which the persistent pruritus is regarded as the most distressing and severily affecting the quality of life. The pathophysiology of uremic pruritus is poorly understood but believed to result from metabolic disequilibrium, increased release of pruritogenic mediators and altered balance between the opioid receptors. Several methods of controlling pruritus are considered, including pharmacologic and nonpharmacologic options, but their efficacy is still unsatisfactory.


Effects of transforming growth factor β2 and connective tissue growth factor on induction of epithelial mesenchymal transition and extracellular matrix synthesis in human lens epithelial cells.
To investigate the effects of transforming growth factor β2 (TGF-β2) and connective tissue growth factor (CTGF) on transdifferentiation of human lens epithelial cells (HLECs) cultured in vitro and synthesis of extracellular matrix (ECM). HLECs were treated with TGF-β2 (0, 0.5, 1.0, 5, 10µg/L) and CTGF (0, 15, 30, 60, 100µg/L) for different times (0, 24, 48, 72h) in vitro and the expression of α-smooth muscle actin (α-SMA), the main component of the extracellular matrix type I collagen (Col-1) and fibronectin (Fn) were measured by using real-time polymerase chain reaction (PCR) and western-blot. TGF-β2 and CTGF significantly increased expression of α-SMA mRNA and protein (P<0.05, P<0.001), Fn mRNA and protein (P<0.001), Col-1 mRNA and protein (P<0.001). TGF-β2 could induce HLECs expression of CTGF mRNA and protein in dose-dependent manner (P<0.05, P<0.001). TGF-β2 and CTGF could induce HLECs to express α-SMA, Fn and Col-1 in time-dependent manner. Each time of TGF-β2 and CTGF induced HELCs expression of α-SMA, Fn, Col-1 mRNA and protein was significant increase compared with control (P<0.05, P<0.001). TGF-β2 and CTGF could induce HLECs epithelial mesenchymal transition and ECM synthesis.


Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo.
To study the effect of E2 and P on the epithelial cell cycle of normal human breast in vivo. Double-blind, randomized study. Topical application to the breast of a gel containing either a placebo, E2, P, or a combination of E2 and P, daily, during the 10 to 13 days preceding breast surgery. Forty premenopausal women undergoing breast surgery for the removal of a lump. MAIN OUTCOME MEASURES. Plasma and breast tissue concentrations of E2 and P. Epithelial cell cycle evaluated in normal breast tissue areas by counting mitoses and proliferating cell nuclear antigen immunostaining quantitative analyses. Increased E2 concentration increases the number of cycling epithelial cells. Increased P concentration significantly decreases the number of cycling epithelial cells. Exposure to P for 10 to 13 days reduces E2-induced proliferation of normal breast epithelial cells in vivo.


Induction of heavy-metal-transporting CPX-type ATPases during acid adaptation in Lactobacillus bulgaricus.
Lactobacillus bulgaricus is a lactic acid bacteria (LAB) that, through the production of lactic acid, gradually acidifies its environment during growth. In the course of this process, L. bulgaricus acquires an improved tolerance to acidity. A survey of the recently established genome sequence shows that this bacterium possesses few of the pH control functions that have been described in other LAB and raises the question of what other mechanisms could be involved in its adaptation to the decreasing environmental pH. In some bacteria other than LAB, ion transport systems have been implicated in acid adaptation. We therefore studied the expression of this type of transport system during acid adaptation in L. bulgaricus by reverse transcription and real-time quantitative PCR and mapped transcription start sites. Intriguingly, the most significantly induced were three ATPases carrying the CPX signature of heavy-metal transporters. Protein homology and the presence of a conserved sequence motif in the promoter regions of the genes encoding these proteins strongly suggest that they are involved in copper homeostasis. Induction of this system is thought to assist in avoiding indirect damage that could result from medium acidification.


Oxidative injury associated with stenting of asymptomatic carotid artery stenosis.
After carotid artery stenting (CAS), neurological complications that cannot be explained with imaging methods may develop. In our study we aimed to show, using oxidative stress markers, isolated oxidative damage and resulting neurological findings following CAS in patients with asymptomatic carotid artery stenosis. We included 131 neurologically asymptomatic patients requiring CAS. The neurological findings were evaluated using the modified Rankin Scale (mRS) prior to the procedure, one hour post-procedure, and two days after. Patients with elevated mRS scores but with or without typical hyperintense lesions observed on an MRI and with changes of oxidative stress marker levels at the time (Δtotal-thiol, Δtotal antioxidative status [TAS], and Δtotal oxidant status [TOS]) were evaluated. In the neurological examination carried out one hour prior to the procedure, there were 92 patients with mRS = 0, 20 with mRS = 1, and 12 with mRS = 2. When Δtotal-thiol, ΔTAS, and ΔTOS values and the mRS were compared, it was observed that as the difference in oxidative parameters increased, clinical deterioration also increased proportionally (p = 0.001). We demonstrate a possible correlation between oxidative damage and neurological findings after CAS which could not be explained by routine imaging methods.


[The tasks and role of pathology among other medical sciences].
The results of discussion on the current state of pathology in medical science and practical hospital work are presented in this paper which is the author's report on the 2nd symposium of the societies of pathologists in socialist countries. Special attention is drawn to the significance of necropsies in comparing clinical and post-mortem diagnoses, the related numerical materials are provided. The decrease of necropsies of patients dying in hospitals in most countries of the world is noted, and the methods of getting rid of this are indicated both for scientific goals and health service. The increasing necessity of contacts between pathologists and clinicians is pointed out and the ways of realization of this important tool for further development of medicine are traced. The comparative data on the methods of training in pathology in many European countries and USA are presented. The paper is concluded by a review on the state of pathology in the GDR, measures taken by the GDR Ministry of Health and by the Society of GDR pathologists. The confidence is expressed in success of these measures in the process of realization by the GDR government of the X Party Congress and the 5th Plenum of the SUPG Decisions on the development of science and its effectiveness.


Shaking-induced motility in suspensions of soft active particles.
We investigate theoretically the collective dynamics of soft active particles living in a viscous fluid. We focus on a minimal model for active but nonmotile particles consisting of N>1 elastic dimers deformed by active stresses and interacting hydrodynamically. We first derive a set of effective equations of motion for the positions of the particles. We then exploit these equations in two experimentally relevant cases: uncorrelated random internal stresses, and uniform monochromatic external shaking. In both cases, we show that small groups of intrinsically nonmotile particles can display nontrivial modes of locomotion resulting from the hydrodynamic correlations between the particle-conformation fluctuations. In addition, we demonstrate that a coherent shaking yields spatial ordering in suspension of soft particles interacting solely through the fluid.


[Characteristics of glucose absorption by the adipose tissue in renal and spontaneous hypertension in rats].
In vitro glucose-14C uptake by the epididymal adipose tissue was studied in young rats with spontaneous hypertension (SHR), in rats with two-kidney Goldblatt hypertension, and in control rats with normal pressure. Some of the animals were subjected to bilateral adrenalectomy one week before the study. Rats with either type of hypertension and intact adrenals did not differ from the controls in the intensity of glucose-14C uptake by the adipose tissue both with and without stimulation of its transmembranous tranport with insulin. Adrenalectomy revealed that the response of the adipose tissue to insulin in rats with hypertension differed from that in the controls. In the control animals adrenalectomy causes marked decrease in insulin "sensitivity" of the fat cells, whereas in adrenalectomized rats with hypertension the level of glucose-14C in stimulation of its transport with insulin does not change. The results of the study testify to qualitative changes in the membranes of the fat cells in rats with chronic arterial hypertension and may be proof of extensive alteration of the cell membranes in this disease.


Rapid, automated assay for progesterone on the Abbott AxSYM analyzer.
We describe an automated assay for progesterone (P4) in human serum and plasma with the Abbott AxSYM random-access immunoassay analyzer. In this one-step competitive assay, P4 immobilized onto latex microparticles competes with sample P4 for binding to a conjugate of alkaline phosphatase (AP) and anti-P4 antibody. Total CVs ranged from 3.4% to 8.2% in multiple precision studies conducted according to the 20-day NCCLS EP5-T protocol. The detection limit (zero calibrator + 2 SD) was 0.10 microg/L across 36 experiments. Values for diluted samples were 83-116% of expected. Recovery of P4 added to serum specimens was 92-115%. Cross-reactivities with 43 natural and synthetic steroids were 0-6.3%. No significant interference was detected from bilirubin, protein, erythrocytes, hemoglobin, triglycerides, or cholesterol. In a multisite correlation study, AxSYM P4 results compared well with results from a commercial RIA method (n = 1156; r = 0.976; slope = 1.03; y-intercept = 0.04). Assay throughput is >80 tests per hour in batch mode, 60 tests per hour with mixed load list configurations.


Anaemia in persons with HIV infection: prognostic marker and contributor to morbidity.
Human immunodeficiency virus (HIV)-infected patients experience a range of haematological complications including anaemia, neutropenia, lymphopenia and thrombocytopenia. Anaemia is a prognostic marker of future disease progression or death, independent of CD4 and viral load. Recovery from anaemia reduces the risk of disease progression to approximately the same level as seen among patients who have never had anaemia. Additionally, anaemia impacts a range of dimensions of quality of life, most commonly through fatigue. Anaemia can be caused by a range of mechanisms including infections, neoplasms, dietary deficiencies, blood loss and medication. Histologically, bone marrow hypoproliferation and dysplasia are the most commonly seen. Both AZT and d4T induce macrocytosis, however, AZT, but not d4T, has broader myelosuppressive effects both in vitro and in vivo. The management of anaemia typically includes correction of the underlying cause(s) and blood transfusion or erythropoietin. However, blood transfusions and iron supplementation may activate HIV expression and possibly worsen immunosuppression. Recombinant human erythropoietin (rHuEPO) is an effective means of improving haemoglobin and reducing transfusion requirements in patients who have low (< 500 IU/L) endogenous erythropoietin levels.


Association of mean RDW values and changes in RDW with in-hospital mortality in ventilator-associated pneumonia (VAP): Evidence from MIMIC-IV database.
Ventilator-associated pneumonia (VAP) is a hospital-acquired infection with high mortality, and remains a challenge for clinical treatment. Red blood cell distribution width (RDW) was associated with worse outcomes in several diseases. The purpose of this study was to investigate the relationship between mean RDW values, changes in RDW (delta RDW), and in-hospital mortality among patients with VAP. In the present study, we enrolled 1266 VAP patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. All patients were categorized into low group, medium group, and high group according to tertiles of mean RDW values. The primary outcome was all-cause in-hospital mortality. Univariate logistic regression analysis, multivariate logistic regression analysis, and restricted cubic spline (RCS) curve were performed to determine the association between mean RDW values and in-hospital mortality in VAP. Moreover, RCS curve was plotted to explore the dose-response relationship between delta RDW and in-hospital mortality in VAP. Among the VAP patients included in the study, the in-hospital mortality was 20.85% with 264 non-survivors and 1002 survivors. The non-survivors exhibited significantly higher mean RDW values and delta RDW values compared to survivors. Multivariate logistic regression analysis indicated that mean RDW values were positively associated with in-hospital mortality in VAP after adjusting for relevant covariates. The RCS curve demonstrated a dose-response relationship between mean RDW and the mortality in VAP. Moreover, a linear relationship was observed between delta RDW and in-hospital mortality in VAP. Higher mean RDW values were significantly associated with an increased risk of in-hospital mortality in VAP. Additionally, a linear relationship was found between delta RDW values and in-hospital mortality. These findings suggest that RDW can be used to identify high-risk patients with poorer outcomes in VAP.


Effectiveness of neuromuscular electrical stimulation for management of shoulder subluxation post-stroke: a systematic review with meta-analysis.
To examine the effectiveness of neuromuscular electrical stimulation (NMES) for the management of shoulder subluxation after stroke including assessment of short (1 hour or less) and long (more than one hour) daily treatment duration. MEDLINE, CENTRAL, CINAHL, WOS, KoreaMed, RISS and reference lists from inception to January 2017 Review methods: We considered randomized controlled trials that reported neuromuscular electrical stimulation for the treatment of shoulder subluxation post-stroke. Two reviewers independently selected trials for inclusion, assessed trial quality, and extracted data. Eleven studies were included (432 participants); seven studies were good quality, four were fair. There was a significant treatment effect of neuromuscular electrical stimulation for reduction of subluxation for persons with acute and subacute stroke (SMD:-1.11; 95% CI:-1.53, -0.68) with either short (SMD:-0.91; 95% CI:-1.43, -0.40) or long (SMD:-1.49; 95% CI:-2.31, -0.67) daily treatment duration. The effect for patients with chronic stroke was not significant (SMD:-1.25; 95% CI:-2.60, 0.11). There was no significant effect of neuromuscular electrical stimulation on arm function or shoulder pain. This meta-analysis suggests a beneficial effect of neuromuscular electrical stimulation, with either short or long daily treatment duration, for reducing shoulder subluxation in persons with acute and subacute stroke. No significant benefits were observed for persons with chronic stroke or for improving arm function or reducing shoulder pain.


WGS based analysis of acquired antimicrobial resistance in human and non-human Acinetobacter baumannii isolates from a German perspective.
Acinetobacter baumannii ability to develop and acquire resistance makes it one of the most critical nosocomial pathogens globally. Whole-genome sequencing (WGS) was applied to identify the acquired or mutational variants of antimicrobial resistance (AMR) genes in 85 German A. baumannii strains utilizing Illumina technology. Additionally, the whole genome of 104 German isolates deposited in the NCBI database was investigated. In-silico analysis of WGS data revealed wide varieties of acquired AMR genes mediating resistance mostly to aminoglycosides, cephalosporins, carbapenems, sulfonamides, tetracyclines and macrolides. In the 189 analyzed genomes, the ant (3″)-IIa conferring resistance to aminoglycosides was the most frequent (55%), followed by blaADC.25 (38.6%) conferring resistance to cephalosporin, blaOXA-23 (29%) and the blaOXA-66 variant of the intrinsic blaOXA-51-likes (26.5%) conferring resistance to carbapenems, the sul2 (26%) conferring resistance to sulfonamides, the tet. B (19.5%) conferring resistance to tetracycline, and mph. E and msr. E (19%) conferring resistance to macrolides. blaTEM variants conferring resistance to cephalosporins were found in 12% of genomes. Thirteen variants of the intrinsic blaOXA-51 carbapenemase gene, blaOXA-510 and blaADC-25 genes were found in isolates obtained from dried milk samples. The presence of strains harboring acquired AMR genes in dried milk raises safety concerns and highlights the need for changes in producing dried milk. Acquired resistance genes and chromosomal gene mutation are successful routes for disseminating AMR determinants among A. baumannii. Identification of chromosomal and plasmid-encoded AMR in the genome of A. baumannii may help understand the mechanism behind the genetic mobilization and spread of AMR genes.


Intravitreal Bevacizumab for Choroidal Neovascular Membrane in Macular Telangiectasia Type 2.
We report a case of macular telangiectasia type 2 with an associated choroidal neovascular membrane and its treatment. A 54-year-old female presented with a history of gradual vision loss in both eyes. A physical exam showed visual acuity of 20/40 in both eyes and significant metamorphopsia in the right eye. A fundus examination of the right eye was remarkable for right-angled vessels in the juxtafoveal region and subretinal fibrosis temporal to the fovea. A fundus examination of the left eye revealed intraretinal crystals in the juxtafoveal region and right-angled vessels. Optical coherence tomography and angiography confirmed the diagnosis of macular telangiectasia type 2 as well as the presence of a choroidal neovascular membrane in the right eye. The patient was treated with 18 intravitreal injections of anti-vascular endothelial growth factor agent in the right eye for two years, with five to six weeks between each treatment, which resulted in the membrane's stability. Our report suggests that anti-vascular endothelial growth factor therapy via intravitreal injection may be beneficial in treating choroidal neovascular membranes in patients with macular telangiectasia type 2.


Reactions of artemisinin and arteether with acid: implications for stability and mode of antimalarial action.
The currently accepted mechanism of trioxane antimalarial action involves generation of free radicals within or near susceptible sites probably arising from the production of distonic radical anions. An alternative mechanistic proposal involving the ionic scission of the peroxide group and consequent generation of a carbocation at C-4 has been suggested to account for antimalarial activity. We have investigated this latter mechanism using DFT (B3LYP/6-31+G* level) and established the preferred Lewis acid protonation sites (artemisinin O5a>>O4a approximately O3a>O2a>O1a; arteether O4a>or=O3a>O5b>>O2a>O1a; Figure 3) and the consequent decomposition pathways and hydrolysis sites. In neither molecule is protonation likely to occur on the peroxide bond O1-O2 and therefore lead to scission. Therefore, the alternative radical pathway remains the likeliest explanation for antimalarial action.


Disseminated cutaneous histoplasmosis in acquired immunodeficiency syndrome: report of 23 cases.
Disseminated cutaneous histoplasmosis is an opportunistic infection in patients with acquired immunodeficiency syndrome. We report a series of 23 cases (21 men, two women; median age 29 years) with disseminated cutaneous histoplasmosis seen at two hospital centres. Most of the patients (21/23) were classified as stage C3. The most common dermatological findings were papules, crusting plaques, nodules and ulcers, mainly located on the face and chest. Of the 23 cases, 15 (65%) had pulmonary involvement. Amphotericin B and itraconazole were the main drugs used for treatment. Treatment response was variable: four of the patients were cured, six improved and remain stable, nine patients died, and four patients were lost to follow-up.


Helicity and Polarization Gradient Optical Trapping in Evanescent Fields.
Optical traps using nonconservative forces instead of conservative intensity-gradient forces expand the trap parameter space. Existing traps with nonconservative helicity-dependent forces are limited to chiral particles and fields with helicity gradients. We relax these constraints by proposing helicity and polarization gradient optical trapping of achiral particles in evanescent fields. We further propose an optical switching system in which a microsphere is trapped and optically manipulated around a microfiber using polarization gradients. Our Letter deepens the understanding of light-matter interactions in polarization gradient fields and expands the range of compatible particles and stable trapping fields.


Utility of PET/CT imaging performed early after surgical resection in the adjuvant treatment planning for head and neck cancer.
To evaluate the utility of positron emission tomography (PET)/computed tomography (CT) early after surgical resection and before postoperative adjuvant radiation therapy. We studied a prospective cohort of 91 consecutive patients referred for postoperative adjuvant radiation therapy after complete surgical resection. Tumor histologies included 62 squamous cell and 29 non-squamous cell cancers. Median time between surgery and postoperative PET/CT was 28 days (range, 13-75 days). Findings suspicious for persistent/recurrent cancer or distant metastasis were biopsied. Correlation was made with changes in patient care. Based on PET/CT findings, 24 patients (26.4%) underwent biopsy of suspicious sites. Three patients with suspicious findings did not undergo biopsy because the abnormalities were not easily accessible. Eleven (45.8%) biopsies were positive for cancer. Treatment was changed for 14 (15.4%) patients (11 positive biopsy and 3 nonbiopsied patients) as a result. Treatment changes included abandonment of radiation therapy and switching to palliative chemotherapy or hospice care (4), increasing the radiation therapy dose (6), extending the radiation therapy treatment volume and increasing the dose (1), additional surgery (2), and adding palliative chemotherapy to palliative radiation therapy (1). Treatment for recurrent cancer and primary skin cancer were significant predictors of having a biopsy-proven, treatment-changing positive PET/CT (p < 0.03). Even with an expectedly high rate of false positive PET/CT scans in this early postoperative period, PET/CT changed patient management in a relatively large proportion of patients. PET/CT can be recommended in the postoperative, preradiation therapy setting with the understanding that treatment-altering PET/CT findings should be biopsied for confirmation.


Brown tumour of the jaw.
Brown tumours are classic bony lesions that arise as a result of the effect of parathyroid hormone on bone tissue in some patients with hyperparathyroidism. They are erosive bony lesions caused by rapid osteolysis and peritrabecular fibrosis, resulting in a local destructive phenomenon. Facial skeleton is involved in about 2% of all cases of which the mandible is frequently affected. A 35-year-old female who was diagnosed with osteomalacia and brown tumour in posterior mandible as the sign of secondary hyperparathyroidism secondary to vitamin D deficiency is presented.


Towards accurate ab initio calculations on the vibrational modes of the alkaline earth metal hydrides.
The fundamental modes of the alkaline earth metal hydrides (BeH2, MgH2, CaH2) and their dimers, HX(H)2XH, have been studied by vibrational configuration-interaction calculations based on very accurate potential energy surfaces. Comparison with experimental data obtained from matrix isolation and gas phase measurements is provided and the agreement was found to be excellent for the monomers but poor for the dimers. In addition, many fundamental bands are predicted which have not yet been detected experimentally.


BIOBRAD Study: The Search for Biomarkers of Bradykinin-Mediated Angio-Oedema Attacks.
The aetiology of angio-oedema (AE) is difficult to determine; however, it is essential in emergency situations when two major contexts may be present: mast cell-mediated AE and bradykinin-mediated AE. Different forms of AE are currently distinguished based on clinical criteria (spontaneous duration of the attack, presence of concomitant or late-appearing superficial urticaria, history of atopy, and others), but specific biomarkers could improve patient management. In this prospective study, potential biomarkers have been identified, and their statistical characteristics were examined. Samples were taken on day 0 (D0) and D7 for 3 patient groups (n = 11 each): bradykinin-mediated AE [peripheral site of attack, ear, nose, throat (ENT), and abdominal involvement], mast cell-mediated AE, and non-bradykinin-mediated abdominal pain. Assay of the potential biomarkers revealed no significant differences in C1 inhibitor and C4 levels. In contrast, D-dimer levels peaked during bradykinin-mediated AE attacks (median 2.2 mg/l at D0 vs. 0.52 mg/l at D7; p < 10-3) as well as during mast cell-mediated AE attacks (1.97 vs. 0.65 mg/l; p = 0.04) and were high in bradykinin-mediated AE compared to the control group (0.69 mg/l; p = 0.01). A threshold value of 0.62 mg/l was found to have a negative predictive value of 100% for bradykinin-mediated AE compared to other causes of abdominal pain (group 3). Circulating VE-cadherin levels were also increased during an attack (1,990 at D0 vs. 1,566 ng/ml at D7; p = 0.01), but could not distinguish between bradykinin-mediated and mast cell-mediated AE, like D-dimers. Exploration of changes in fibrinolysis-related markers (particularly D-dimers) is thus promising for the diagnosis of AE attacks in difficult-to-diagnose abdominal forms, although it was not able to differentiate between bradykinin and mast cell-mediated AE.


Role of Cardiac Magnetic Resonance in Diagnosis and Treatment of Ball Thrombus in Left Atrium - Trust But Verify! - Case Report.
Male patient with left atrial cardiac mass was in need of a quick diagnosis for individualized and effective treatment. Transthoracic echocardiography showed presence of а giant left atrial cardiac mass with atypical location for thrombus. Cardiac Magnetic Resonance (CMR) Imaging was performed for histological discrimination, and showed a large cardiac mass wall attached in the left atrium, homogeneous, with diameter of 3.4cm x 3.2cm. Late Gadolinium Enhancement sequences revealed black avascular tissue without signal, confirming the characterization of a thrombus. The patient refused hospital initiation of low molecular weight heparin treatment and started treatment with Rivaroxaban. Six weeks later he presented with NYHA class II, almost complete dissolving of the thrombus on CMR scan. Seven months from the initial CMR scan, echocardiography screen was done showing complete absence of the left atrial mass. With this case report we have demonstrated the significance of the CMR as one step further in the precise diagnostics of cardiac masses, solving critical clinical dilemma.


The effect of surface adsorption on tertiary structure formation in helical polymers.
The formation of tertiary structures made up of helical polymer segments is influenced by the introduction of an attractive substrate onto which the polymer can adsorb. We perform replica-exchange Monte Carlo simulations to study the formation of helical structures in the vicinity of an attractive generic substrate by means of a coarse-grained hybrid model and compare the structural phase space for both adsorbed and free helical polymers. We introduce suitable structural order parameters to understand the features of distinct structural phases. Hyperphase diagrams, parameterized by the torsional energy scale and temperature, enable the investigation of structural properties of entire classes of helical polymers.


18F-FDG PET/CT Finding of Drop Metastases from Germ Cell Tumor of Pineal Gland.
Tumors of the pineal region are rare, accounting for fewer than 1% of all intracranial neoplasms. Fifty percent of pineal region tumors are germ cell tumors (GCTs). However, spinal seeding and extracranial metastases from intracranial GCTs are uncommon. We present a case of pineal gland GCT in which 18F-FDG PET/CT imaging demonstrated drop metastases to the spinal cord in addition to tracer uptake in the primary lesion.


Current DVT imaging.
Accurate diagnosis of deep venous thrombosis (DVT) is very difficult, and imaging plays a crucial role in the diagnosis or exclusion of DVT. The initial test of choice for diagnosis of acute thigh as well as upper extremity DVT is ultrasound, because of its high accuracy, relatively low cost, portability, and lack of ionizing radiation. In patients who are undergoing CT pulmonary angiography for suspected pulmonary embolism, CT venography can be performed as part of the examination, for comprehensive evaluation of the venous system in the legs, abdomen, and pelvis. MR has a problem-solving role, and conventional venography is now limited to specific scenarios including evaluation of central DVT in the upper extremities, as a prelude to intervention for thrombolysis/thrombectomy, and prior to placement of an inferior vena cava filter. This article discusses the imaging findings of DVT, and the role of these imaging examinations in the evaluation of patients with suspected DVT.


Consistency of Trans-Abdominal and Water-Immersion Ultrasound Images of Diseased Intestinal Segments in Crohn's Disease.
The aim of this study is to clarify whether trans-abdominal ultrasound (TAUS) can reflect actual intestinal conditions in Crohn's disease (CD) as effectively as water-immersion ultrasound (WIUS) does. This retrospective study enrolled 29 CD patients with 113 intestinal lesions. Five ultrasound (US) parameters (distinct presence/indistinct presence/disappearance of wall stratification in the submucosal and mucosal layers; thickened submucosal layer; irregular mucosal surface; increased fat wrapping around the bowel wall; and fistula signs) that may indicate different states in CD were determined by TAUS and WIUS for the same lesion. Using WIUS as a reference standard, the sensitivity, specificity, and accuracy of TAUS were calculated. The degree of agreement between TAUS and WIUS was evaluated by the kappa coefficient. All US parameters of TAUS had an accuracy >70% (72.6-92.7%). The highest efficacy of TAUS was obtained for fistula signs (sensitivity, specificity, and accuracy values were 63.6%, 96.0%, and 92.7%, respectively). All US parameters between TAUS and WIUS had a definitive (p ≤ 0.001) and moderate-to-substantial consistency (kappa value = 0.446-0.615). The images of TAUS showed substantial similarity to those of WIUS, suggesting that TAUS may function as a substitute to evaluate the actual intestinal conditions of CD.


Accuracy and consistency of KC60 diagnoses and coding in a department of genitourinary medicine.
The accuracy and completeness of KC60 coding is important to ensure that accurate local, regional and national data on sexually transmitted infections (STIs) are produced. Following alterations to the codes in 1995 a review of the process and accuracy in one department of genitourinary medicine was undertaken. Over a 6-month period 239 episodes and 407 diagnoses were reviewed in the notes of 172 patients. An error was found in 17.9% of diagnoses, and 32.6% of episodes had at least one error. Only one episode had been diagnosed but not coded. Subsequently the procedure for diagnosing episodes was altered and a subsequent review of 122 episodes and 239 diagnoses in the notes of 94 patients identified only 4 errors.


Posterior chamber lens implantation for primary repair of corneal lacerations and traumatic cataracts in children.
Children older than 3 years of age rarely tolerate contact lenses for unilateral surgical aphakia. This problem is even more pronounced following repair of corneal lacerations or perforations that are associated with traumatic cataracts. Even if surgery is successful, such eyes are functionally doomed because of deep anisometropic amblyopia. We evaluated prospectively in 15 children (3 to 8 years) the results of combined operation of corneal repair, aspiration of traumatic cataract, and primary posterior chamber lens implantation. Postoperative occlusion treatment was carefully monitored. Follow up ranged from 6 to 60 months, with an average of 39.2 months. The final best corrected visual acuity at the patient's last visit was 20/40 or better in 11 of 15 children (73.3%). The most frequent complication was a nonfunctional pupil due to traumatic iris damage or posterior synechiae in 13 cases. The most visually significant complication was posterior membrane formation and/or posterior capsule opacification, which required additional surgeries in six children.


Different school placements following language unit attendance: which factors affect language outcome?
The study compared the outcomes of two groups of children who were attending language unit provision at 7 years of age. Of 242 children in the original study, 62 (28%) transferred to mainstream school placements at age 8 years. These children were then closely matched to children still attending language unit provision at this age using measures of non-verbal IQ, expression and comprehension. These two groups of children were compared on outcome at 11 years in the areas of language skill, non-verbal IQ and social behaviour. Teacher/speech-language therapist opinions of placement were also examined as factors affecting outcome. Results show that children who moved to mainstream provision at 8 years were more likely to be attending mainstream at 11 years, although the majority received extra support. No further differences were evident in outcome according to placement type. However, there was a main effect of teacher/therapist opinion on outcome--children whose teachers were not entirely happy with the 8-year placement performed more poorly at 11 years on language measures. There were no differences on any other measures. The findings suggest that follow-on placements for children attending language units need to be more closely in line with teacher's opinions and that more flexibility needs to be evident in school placement policy in order that appropriate educational settings can be arranged.


Detection of fraudulent addition of bovine whey in water buffalo ricotta cheese by isoelectric focusing.
Prevention of food fraud in the dairy field is a difficult issue for researchers, industries and policy makers, both for commercial and health reasons. Currently, no analytical method allows detection of the addition of bovine whey to water buffalo ricotta, so this fraudulent practice cannot be prevented. The authors' aim was to develop such a method. The conditions for extraction and purification of denatured ricotta whey proteins, which are unfolded and coagulated by heating during the production process, were optimized. The optimal composition of the polyacrylamide gel (pH range, type and concentration of chemical separator) was first evaluated and then the best conditions to perform the separation by isoelectric focusing were established. The performance of the method (precision, selectivity, robustness, sensibility) was determined. The method was shown to be reliable and robust for detection of the presence of bovine whey added to water buffalo Ricotta at percentages above 5% (v/v). The results suggest that the differences observed between bovine and water buffalo electrophoretic profiles are due to bovine β-lactoglobulin isoform A, which is never detected in water buffalo samples.


IDL composition and angiographically determined progression of atherosclerotic lesions during simvastatin therapy.
Some patients with coronary artery disease experience continued progression of one or more coronary lesions despite treatment with drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and markedly lower plasma cholesterol levels. We examined relationships between the progression of coronary artery lesions and plasma lipoproteins, in particular intermediate density lipoprotein (IDL) and its composition, in 38 patients with coronary artery disease who had been treated with simvastatin for 2 years. Patients were given lipid-lowering dietary advice; 3 months later they were started on simvastatin therapy (10 mg/d) for 1 month, and after review of their plasma cholesterol levels, the dose was increased to 20 mg/d and later to 40 mg/d if the target level of plasma cholesterol had not been attained. Progression of lesions was determined by serial quantitative coronary angiography (variability of 5.5%) and was defined as an increase in percent diameter stenosis (%S)> or =10%; regression was defined as a decrease in %S > or =10%. The proportions of cholesteryl esters (CEs) and free cholesterol decreased significantly (P<.001), and proportions of protein and triglycerides increased significantly (P<.001) in IDL during simvastatin therapy. The CE content of IDL decreased significantly (-7.2 weight [wt]%, n=20, P<.001) in nonprogressors (patients who did not show progression of any lesions) and did not change significantly (-1.8 wt%, n=14, P=.36) in progressors (patients who showed progression of one or more lesions without regression of any lesion). This decrease in IDL CE content in nonprogressors was significantly (P=.01) different compared with the corresponding change in patients classified as progressors. Mean plasma cholesterol concentration tended to increase in progressors (0.47 mmol/L) and tended to decrease in nonprogressors (-0.39 mmol/L) during the initial 3-month diet period, and these changes were significantly different (P=.02). Furthermore, this change in plasma cholesterol level during the initial diet period was correlated significantly with the change in IDL CE content during the entire study (r=.348, n=38, P=.03). These data suggest that IDL CE content may be a determinant of progression of coronary lesions and may be influenced by compliance with or metabolic response to lipid-lowering dietary advice in patients with coronary artery disease during simvastatin treatment.


Evolutionary relatedness between glycolytic enzymes most frequently occurring in genomes.
More than 100 sequenced genomes were searched for genes coding for the enzymes involved in glycolysis in an effort to find the most frequently occurring ones. Triosephosphate isomerase (TIM), glyceraldehyde-3-phosphate dehydrogenase (GAPD), phosphoglycerate kinase (PGK) and enolase (ENOL) were found to be present in 90 investigated genomes all together. The final set consisted of 80 prokaryotic and 10 eukaryotic genomes. Of the 80 prokaryotic genomes, 73 were from Bacteria, 7 from Archaea. Two microbial genomes were also from Eucarya (yeasts). Eight genomes of nonmicrobial origin were included for comparison. The amino acid sequences of TIMs, GAPDs, PGKs and ENOLs were collected and aligned, and their individual as well as concatenated evolutionary trees were constructed and discussed. The trees clearly demonstrate a closer relatedness between Eucarya and Archaea (especially the concatenated tree) but they do not support the hypothesis that eukaryotic glycolytic enzymes should be closely related to their alpha-proteobacterial counterparts. Phylogenetic analyses further reveal that although the taxonomic groups (e.g., alpha-proteobacteria, gamma-proteobacteria, firmicutes, actinobacteria, etc.) form their more or less compact clusters in the trees, the inter-clade relationships between the trees are not conserved at all. On the other hand, several examples of conservative relatedness separating some clades of the same taxonomic groups were observed, e.g., Buchnera along with Wigglesworthia and the rest of gamma-proteobacteria, or mycoplasmas and the rest of firmicutes. The results support the view that these glycolytic enzymes may have their own evolutionary history.


REM syndrome: an immediate therapeutic response to hydroxychloroquine sulphate.
A 22-year-old woman had been suffering for 11 years with a REM syndrome. Her symptoms were provoked and aggravated by exposure to sunlight. The administration of hydroxychloroquine sulphate had a quick effect. The drug was given for 6 months, and the patient remained symptom-free even in summer, when sunbathing.


Treatment of depression in cancer.
Depression occurs in about 15% of the general population and is at least two to three times more common in patients with cancer. Depression is often difficult to diagnose in these patients because of the complexity and constraints of cancer care, patient and family reluctance to acknowledge distress, and the presence of multiple other symptoms. Both antidepressants and psychotherapy are effective in treating depression in patients with cancer, much like in patients with other significant medical problems. Precise assessments of the benefits of treating depression in these patients are important in weighing them against the costs and potential adverse effects. Such estimates are limited by a paucity of randomized, placebo-controlled trials and methodological problems in the existing studies that reflect some of the clinical difficulties in case-finding, treatment, and follow-up of patients with cancer. The existing body of research about depression in cancer patients is extremely limited in terms of the number of studies published and the number of total patients reported over the last 30 years. Moreover, these limited data may not generalize well because of high rates of patient dropout and the very limited enrollment of children, adolescents, older adults, and minority groups. There is an emerging trend toward simplifying the assessment of depression in outpatient cancer care settings and studying depression therapies in cohorts of patients with cancer other than those with fully characterized depressive disorders.


A new methionine antagonist that has antifungal activity: mode of action.
A new antifungal, azoxybacilin (an unusual amino acid with an azoxy moiety) was identified from Bacillus cereus, and its in vitro antifungal activity and mode of action were investigated. Azoxybacilin was active against a broad spectrum of fungi. It was especially active against mycelial fungi, such as Aspergillus, and did not show antibacterial activity. No cross-resistance with antifungals currently on the market was observed. The IC50 values of azoxybacilin antifungal activity against Saccharomyces cerevisiae were significantly greater when amino acids containing sulfur were added to the growth medium, whereas other amino acids were not effective at all. We, therefore, tested the effect of the intermediates involved in the synthetic pathway of these amino acids. The activity markedly diminished when one of the following four intermediates was present in the medium:homocysteine, cysteine, cystathionine or methionine. These four intermediates were the same as those required for the growth of the O-acetylhomoserine sulfhydrylase mutant, S. cerevisiae ONO726, indicating that azoxybacilin would inhibit a step or steps in the sulfur-fixation pathway.


Comprehensive clinical and statistical analysis of hemophilia in Korea.
A Total of 498 cases of hemophilia which were reported by sixteen medical centers in Korea were reviewed and analyzed. Hemophilia A comprised 425 cases (85.3%) and the remaining 73 cases (14.7%) were hemophilia B. One case was female and all other cases were male. There were known hemophilia patients in the family in 43.0% of cases and the involved members were brothers, maternal cousins, maternal uncles, and maternal grandfathers in descending order of frequency. The major symptoms of the patients were hemorrhagic, such as easy bruising and hemarthrosis followed by prolonged bleeding after trauma and soft tissue hematoma. The incidence of hemarthrosis increased significantly with age. The pediatric age group below the age of 15 consisted of 67.1% of the cases. According to the age at diagnosis, half (54.2%) of the severe cases were diagnosed before the age of 1 year. APTT was prolonged over 40 seconds in all cases and 291 cases showed severe prolongation over 80 seconds. Of 498 cases 273 cases (54.8%) belonged to the severe form (factor VII or IX level, less then 1%), whereas 182 cases (36.5%) and 43 cases (8.7%) belonged to the moderate (factor VIII or IX, 2-5%) and mild form (factor VIII or IX, 6-25%), respectively, Chronic arthropathy was present in 236 cases (49.6%), and the incidence increased significantly with age. The management of chronic arthropathy most commonly employed was rehabilitation in 25.4% of cases, but in 50.8% no management was given at all. The involved joints in descending order of frequency were knees, elbows and ankles. The complications were intracranial hemorrhage, Gl bleeding and nerve palsy in 48, 24, and 13 cases, respectively.


[Unexpected demonstration of copper deficiency in the rat].
During many years, Wistar's rats were fed after weaning a semipurified diet containing 0.4 ppm copper and did not present clinical disorders of copper deficiency. Rats of same strain fed on the same diet, but housed in a new physical environment presented, a year later, specific signs of deficiency. A new salt-mixture raising the copper content of the diet to, 5.2 ppm made the deficiency signs diseapear and the rats growth come back to the initial rate. These results showed once again the important relations existing between the organism and its physical environment, the diet being just one of these elements. Rigorous breeding conditions, animal selection and modernisation of animal houses involve a specific feeding related to this new conditions particularly when semipurified diets are used for weaning rats.


Cardiovascular burden and unemployment: A retrospective study in a large population-based French cohort.
The specific effect of unemployment on cardiovascular health relatively to the effects of social position and work environment is still unclear. To clarify this effect, the associations between current or past unemployment and the prevalence of common cardiovascular risk factor and events were tested using multiple logistic regression models with adjustment for both social position and prior work environment. The analyses were performed in a population-based French cohort (CONSTANCES) that included 131,186 adults enrolled between 2012 and 2021. Participants who were unemployed at inclusion (n = 8278) were overexposed to non-moderate alcohol consumption, smoking, leisure-time physical inactivity and depression (odds ratios (ORs) from 1.19 to 1.58) whereas those who have been unemployed at least once in the past (n = 19,015) were additionally overexposed not only to the previous risk factors but also to obesity, diabetes and sleep disorders (ORs from 1.10 to 1.35). These latter were also more exposed to non-fatal myocardial infarction and peripheral arterial disease (ORs of 1.44 and 1.47 respectively), overexposures that persisted after further adjustment for cardiovascular risk factors (ORs of 1.36 and 1.33). The overexposures to risk factors and cardiovascular events were both dependent on the duration of past unemployment. They were equally observed in participants with low social position or bad work environment. These results suggest that unemployment increases cardiovascular risk independently from social position and work environment with a cumulative effect over time. The effect of unemployment could add up to those of low social position and bad work environment during lifetime to further increase cardiovascular risk. They also suggest that long-term unemployment increases the prevalence of cardiovascular events through pathways including but not limited to overexposure to common risk factors.


Synthesis of a new solid-phase extractor and its application to preconcentration and determination of lead in water samples.
A procedure for preconcentration and determination of lead in water is described. The method is based on the sorption of Pb(II) in a minicolumn packed with a functionalized sorbent and subsequent elution with acidic solution. The determination of lead content in the eluate was carried out using flame atomic absorption spectrometry. The sorbent was prepared by immobilization of the ligand 4-(5'-bromo-2'-thiazolylazo)orcinol on polystyrene-divinylbenzene through an azo spacer. Diazotization and coupling reactions were used for synthesis of the sorbent. Some variables affecting the preconcentration were optimized using a full factorial design. Under optimized conditions, the method presented a detection limit of 0.5 microg/L and enrichment factor of 36 for a sample volume of 25 mL. The accuracy of the method was tested by the determination of lead in a standard reference material (National Institute of Standards and Technology 1643d Fresh Water). The proposed procedure was applied to the determination of lead in samples of natural and drinking waters.


The adipokine tartrate-resistant acid phosphatase 5a in serum correlates to adipose tissue expansion in obesity.
Tartrate-resistant acid phosphatase (TRAP) exists as two isoforms, 5a and 5b. TRAP 5a is elevated in adipose tissue of obese women, interacts with pre-adipocytes and is linked to insulin-sensitive hyperplastic obesity when overexpressed in mice. The aim of this study was to investigate the relation between serum TRAP 5a, adiposity indices and metabolic syndrome risk markers in lean and obese women, using a newly developed TRAP 5a-specific ELISA. A TRAP 5a sandwich ELISA was optimized using TRAP 5a-specific monoclonal antibodies and tested in sera of healthy males. TRAP 5a levels were quantitated in sera from healthy males and lean and obese women. Serum TRAP 5a protein levels were lower in obese women in comparison with lean. In obese, but not in lean women, serum TRAP 5a correlated positively to % fat mass, BMI, waist- and hip circumference, waist-to-hip ratio and PAI, while no correlations to serum leptin, HOMA, glucose, insulin, FFA, HDL, TG, APO-A1 and APO-B were observed. TRAP 5a serum levels correlated positively to anthropometric obesity parameters but not to metabolic syndrome risk factors, indicating that serum TRAP 5a is associated with pathological adipose tissue expansion.


Efficacy of tolterodine in women with detrusor overactivity and anterior vaginal wall prolapse: is it the same?
The aim of this study was to assess the efficacy of tolterodine in women with overactive bladder (OAB) and concomitant anterior vaginal prolapse. In this prospective study, 235 consecutive women with OAB symptoms and urodynamic diagnosis of detrusor overactivity who either had no prolapse or had pure anterior vaginal prolapse were included: 184 women (group 1) had no prolapse and 51 women (group 2) had anterior prolapse greater than and equal to stage IIa. Tolterodine 4 mg slow release once a day was prescribed. After 12 weeks, women were reassessed using a 3-point scale (no change, improvement and cured). A total of 158 (85.9%) women in group 1 and 31 (60.8%) women in group 2 reported improvement or cure (P = 0.0002). Women with OAB and significant anterior vaginal prolapse should be informed of a reduced efficacy of antimuscarinics in treating their urinary symptoms.


Development of microsatellite markers for the annual andromonoecious herb Commelina communis f. ciliata (Commelinaceae).
Commelina communis f. ciliata (Commelinaceae), a newly distinguished taxon, is an annual andromonoecious herb exhibiting a mixed mating system, the details of which remain unclear. We developed microsatellite markers for use in exploring the evolution of andromonoecy and mixed mating in the species. Fifteen microsatellite loci were developed using next-generation sequencing. The primer sets were used to evaluate 65 C. communis f. ciliata individuals from three populations in Japan; we found 1-13 alleles per locus and the expected heterozygosity ranged from 0.00 to 0.76. The markers are potentially useful to examine intra- and interspecies genetic structure and the mixed mating strategy of Commelina species via paternity analysis.


Engaging in Awkward Social Interactions in a Virtual Environment Designed for Exposure-Based Psychotherapy for People with Generalized Social Anxiety Disorder: An International Multisite Study.
The effectiveness of in virtuo exposure-based treatment of performance-only social anxiety disorder (SAD) has been demonstrated in several studies. However, few studies have validated virtual environments with participants suffering from generalized SAD. The goal of this study is to confirm the potential of a virtual environment in inducing anxiety in adults suffering from generalized SAD, compared to adults without SAD, when engaged in awkward social interactions. Differences between participants from two different countries were also explored. The sample consisted of 15 participants with SAD from Canada, 17 participants without SAD from Canada, 16 participants with SAD from Spain, and 21 participants without SAD from Spain. All participants were immersed in a control virtual environment and in an experimental virtual environment considered potentially anxiety-inducing for individuals with generalized SAD. As hypothesized, results showed that the experimental virtual environment induced a higher level of anxiety than the control environment among participants with SAD compared to those without SAD. The impact on anxiety of each socially threatening task performed during the experimental immersion was statistically significant. In terms of anxiety responses, no significant differences were found between participants from Canada and Spain. However, spatial presence and ecological validity were higher in Canadians than in Spaniards. Unwanted negative side effects induced by immersions in virtual reality were higher in the SAD group. This study highlights the importance for therapists to engage people with SAD in clinically relevant tasks while immersed in VR psychotherapeutic applications.


Regulation of Müller glial dependent neuronal regeneration in the damaged adult zebrafish retina.
This article examines our current knowledge underlying the mechanisms involved in neuronal regeneration in the adult zebrafish retina. Zebrafish, which has the capacity to regenerate a wide variety of tissues and organs (including the fins, kidney, heart, brain, and spinal cord), has become the premier model system to study retinal regeneration due to the robustness and speed of the response and the variety of genetic tools that can be applied to study this question. It is now well documented that retinal damage induces the resident Müller glia to dedifferentiate and reenter the cell cycle to produce neuronal progenitor cells that continue to proliferate, migrate to the damaged retinal layer and differentiate into the missing neuronal cell types. Increasing our understanding of how these cellular events are regulated and occur in response to neuronal damage may provide critical information that can be applied to stimulating a regeneration response in the mammalian retina. In this review, we will focus on the genes/proteins that regulate zebrafish retinal regeneration and will attempt to critically evaluate how these factors may interact to correctly orchestrate the definitive cellular events that occur during regeneration.


Managing and monitoring a pandemic: showcasing a practical approach for the genomic surveillance of SARS-CoV-2.
With the rapidly growing amount of biological data, powerful but also flexible data management and visualization systems are of increasingly crucial importance. The COVID-19 pandemic has more than highlighted this need and the challenges scientists are facing. Here, we provide an example and a step-by-step template for non-IT personnel to easily implement an intuitive, interactive data management solution to manage and visualize the high influx of biological samples and associated metadata in a laboratory setting. Our approach is illustrated with the genomic surveillance for SARS-CoV-2 in Germany, covering over 11 600 internal and 130 000 external samples from multiple datasets. We compare three data management options used in laboratories: (i) simple, yet error-prone and inefficient spreadsheets, (ii) complex and long-to-implement laboratory information management systems and (iii) high-performance database management systems. We highlight the advantages and pitfalls of each option and outline why a document-oriented NoSQL option via MongoDB Atlas can be a suitable solution for many labs. Our example can be treated as a template and easily adapted to allow scientists to focus on their core work and not on complex data administration.


Spindle Cell Lipoma With Florid Primary Follicular Lymphocytic Hyperplasia: A Novel Association With Potential Diagnostic Pitfalls.
Spindle cell lipoma (SCL) is a benign subcutaneous lipomatous neoplasm with a heterogeneous histologic appearance that varies greatly depending on the amount of fat, collagen, and myxoid stroma, which define the multiple subtypes of SCL, such as fat poor SCL, pseudoangiomatous SCL, and dendritic fibromyxolipoma. Cutaneous lymphoid hyperplasia is a spectrum of benign conditions characterized by reactive B-cell and T-cell cutaneous lymphocytic infiltrates. Cutaneous B-cell lymphoid hyperplasia is a heterogeneous group of non-neoplastic conditions that can be observed as reactive phenomena to infections, medications, allergens, or neoplasms and must be distinguished from cutaneous B-cell lymphomas. Here, we report a novel case of spindle cell lipoma, associated with B-cell primary lymphoid follicular hyperplasia, mixed within the tumor in a peculiar pattern, while discussing potential diagnostic pitfalls with low-grade B-cell lymphomas. This is the first report of such association in the literature.