A randomized trial and novel SPR technique identifies altered lipoprotein-LDL receptor binding as a mechanism underlying elevated LDL-cholesterol in APOE4s.
At a population level APOE4 carriers (~25% Caucasians) are at higher risk of cardiovascular diseases. The penetrance of genotype is however variable and influenced by dietary fat composition, with the APOE4 allele associated with greater LDL-cholesterol elevation in response to saturated fatty acids (SFA). The etiology of this greater responsiveness is unknown. Here a novel surface plasmon resonance technique (SPR) is developed and used, along with hepatocyte (with the liver being the main organ modulating lipoprotein metabolism and plasma lipid levels) uptake studies to establish the impact of dietary fatty acid composition on, lipoprotein-LDL receptor (LDLR) binding, and hepatocyte uptake, according to APOE genotype status. In men prospectively recruited according to APOE genotype (APOE3/3 common genotype, or APOE3/E4), triglyceride-rich lipoproteins (TRLs) were isolated at fasting and 4-6 h following test meals rich in SFA, unsaturated fat and SFA with fish oil. In APOE4s a greater LDLR binding affinity of postprandial TRL after SFA, and lower LDL binding and hepatocyte internalization, provide mechanisms for the greater LDL-cholesterol raising effect. The SPR technique developed may be used for the future study of the impact of genotype, and physiological and behavioral variables on lipoprotein metabolism. Trial registration number NCT01522482.


Comment on "Elastic constants from microscopic strain fluctuations".
Sengupta [Phys. Rev. E 61, 1072 (2000)] presented an elegant and simple finite-size scaling method for the calculation of elastic constants and their corresponding correlation lengths, which is suitable for many finite discrete systems considered through simulations or experiments. We take into account a mathematical finite-size effect that was neglected by the authors in order to propose a more accurate method. Consequences on the authors' results are also discussed.


[Comparative study between laparoscopic "TEP" and "tension-free" repair of groin hernia].
The "Tension free" and TEP (total preperitoneal repair) of groin hernia gained more popularity in surgical practice in the last five years. The aim of the study was to reveal our experience with these two surgical techniques. The TEP procedure was done in 29 cases, till "Tension free" herniorraphy was performed at 32 cases. Postoperative complications in the group with TEP hernia repair were found in 1 case. Two complications were observed in the "Tension free" group. The follow up of the patients revealed I recurrence in the group of TEP herniorraphy and no recurrence in "Tension free" group. These two techniques for repair of groin hernias had several advantages and in spite of increased operating theater costs should be adopted on a routine basis in some cases than conventional techniques for repair of groin hernia.


Oral antipsychotic update: a brief review of new and investigational agents for the treatment of schizophrenia.
Antipsychotics are the mainstay of treatment for patients with schizophrenia. However, these medications only work if they are taken and perhaps work best if they are taken for longer periods of time than seen in typical research trials. Here we explore the idea of "time as drug" by reviewing the data showing the potential benefits of long-term antipsychotic use. We also discuss the utility of depot antipsychotic formulations for improving the chances of attaining long-term therapeutic results.


Effects of a 2-year school-based intervention of enhanced physical education in the primary school.
This study aimed to assess whether a school-based physical education intervention was effective in improving physical abilities and influencing daily physical activity habits in primary school children. The possible effect on body mass index (BMI) was also considered. Twenty-six 3rd-grade classes were randomly selected stratifying by geographic location (city, plain, hills) and were assigned either to an intervention (127 boys; 120 girls) or to a traditional (129 boys; 121 girls) physical education program. At baseline (age: 8-9 years) and after a 2-year follow-up (age: 10-11 years), information was collected about sport participation and daily activity habits using a self-administered questionnaire. Height, weight, and BMI were measured and physical performance was assessed by means of standardized tests. The enhanced program of physical education was effective in improving physical abilities of children and determining a decrease (boys: 10%; girls: 12%) in daily sedentary activities (preintervention versus postintervention, p < .05; intervention versus control group, p < .01). The percentages of overweight and obese children did not vary significantly, but the experimental group showed a significantly lower rise in BMI compared to the control group (p < .001). The school proved to be an ideal setting for promoting physical activity and achieving the required daily activity levels.


Model-Based Approach for Optimizing Ceftobiprole Dosage in Pediatric Patients.
Ceftobiprole is an advanced-generation cephalosporin for intravenous administration with activity against Gram-positive and Gram-negative organisms. A population pharmacokinetic (PK) model characterizing the disposition of ceftobiprole in plasma using data from patients in three pediatric studies was developed. Model-based simulations were subsequently performed to assist in dose optimization for the treatment of pediatric patients with hospital-acquired or community-acquired pneumonia. The population PK data set comprised 518 ceftobiprole plasma concentrations from 107 patients from 0 (birth) to 17 years of age. Ceftobiprole PK was well described by a three-compartment model with linear elimination. Ceftobiprole clearance was modeled as a function of glomerular filtration rate; other PK parameters were scaled to body weight. The final population PK model provided a robust and reliable description of the PK of ceftobiprole in the pediatric study population. Model-based simulations using the final model suggested that a ceftobiprole dose of 15 mg/kg of body weight infused over 2 h and administered every 12 h in neonates and infants <3 months of age or every 8 h in older pediatric patients would result in a ceftobiprole exposure consistent with that in adults and good pharmacokinetic-pharmacodynamic target attainment. The dose should be reduced to 10 mg/kg every 12 h in neonates and infants <3 months of age who weigh <4 kg to avoid high exposures. Extended intervals and reduced doses may be required for pediatric patients older than 3 months of age with renal impairment.


Application of Structure-Based Design and Parallel Chemistry to Identify a Potent, Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor.
Phosphodiesterase 2A (PDE2A) inhibitors have been reported to demonstrate in vivo activity in preclinical models of cognition. To more fully explore the biology of PDE2A inhibition, we sought to identify potent PDE2A inhibitors with improved brain penetration as compared to current literature compounds. Applying estimated human dose calculations while simultaneously leveraging synthetically enabled chemistry and structure-based drug design has resulted in a highly potent, selective, brain penetrant compound 71 (PF-05085727) that effects in vivo biochemical changes commensurate with PDE2A inhibition along with behavioral and electrophysiological reversal of the effects of NMDA antagonists in rodents. This data supports the ability of PDE2A inhibitors to potentiate NMDA signaling and their further development for clinical cognition indications.


A case of type B lactic acidosis in acute leukemia.
Type B lactic acidosis is a rare condition in patients with solid tumors or hematological malignancies. Although there have been several theories to explain its mechanism, the exact cause of lactic acidosis remains to be discovered. Lactic acidosis is usually related to increased tumor burden in patients with malignancy. We experienced a case of lactic acidosis in a 39-year-old man who visited an emergency room because of dyspnea, and the cause of lactic acidosis turned out to be recurrent acute leukemia. Chemotherapy relieved the degree of lactic acidosis initially, but as the disease progressed, lactic acidosis became aggravated. Type B lactic acidosis can be a clinical presentation of acute exacerbation of acute leukemia.


Prognostic value of preoperative squamous cell carcinoma antigen level in patients surgically treated for cervical carcinoma.
Preoperative evaluation of squamous cell carcinoma antigen (SCCa) was performed in 220 patients with surgically treated early-stage carcinoma of the cervix. The median duration of follow-up was 1.9 years. SCCa was significantly higher in tumors with a squamous element (P < 0.001). There was a squamous element in 171 tumors. SCCa was elevated (>2 ng/ml) in 21.6%. Significantly higher levels were associated with stage II disease (P < 0.001), tumors >4-cm size (P < 0.001), and lymph node metastases (P < 0.001). The positive predictive value for lymph node metastases at >2, >4, and >8.6 ng/ml SCCa is 51.4, 70.0, and 100% and the sensitivity is 58.1, 45.2, and 22.6%, respectively. Low SCCa is a poor predictor of absence of lymph node metastasis. The median SCCa for patients who developed tumor recurrence was greater than those who remained disease free (1.7 and 1.0 ng/ml, respectively, P = 0.009); however, in a multivariate analysis only lymph node metastasis and tumor size were of independent prognostic significance (P = 0.002 and P = 0.004, respectively). SCCa level >8.6 ng/ml is highly predictive of lymph nodal disease. There is no independent prognostic significance in patients with early-stage surgically treated cervical carcinoma.


Multiplexed gene control reveals rapid mRNA turnover.
The rates of mRNA synthesis and decay determine the mRNA expression level. The two processes are under coordinated control, which makes the measurements of these rates challenging, as evidenced by the low correlation among the methods of measurement of RNA half-lives. We developed a minimally invasive method, multiplexed gene control, to shut off expression of genes with controllable synthetic promoters. The method was validated by measuring the ratios of the nascent to mature mRNA molecules and by measuring the half-life with endogenous promoters that can be controlled naturally or through inserting short sequences that impart repressibility. The measured mRNA half-lives correlated highly with those obtained with the metabolic pulse-labeling method in yeast. However, mRNA degradation was considerably faster in comparison to previous estimates, with a median half-life of around 2 min. The half-life permits the estimation of promoter-dependent and promoter-independent transcription rates. The dynamical range of the promoter-independent transcription rates was larger than that of the mRNA half-lives. The rapid mRNA turnover and the broad adjustability of promoter-independent transcription rates are expected to have a major impact on stochastic gene expression and gene network behavior.


[Breast examination in women from the Pałuk region].
Breast examination for early cancer detection in high risk patients are being performed even more frequently in our country and in other ones. Wide availability of mammosonography facilitates such management. X-ray mammography in view of irradiation is less frequently used. An attempt has been undertaken at carrying out breast examinations of a selected Pałuski area. The analysis included 180 women who after carrying out comprehensive breast examination and obtaining of history data were qualified for the group of high risk for breast cancer.


The added value of respect: reaching across inequality.
The experiment (N=80) tested whether the effectiveness of intragroup respect is moderated by structural (in)equality between the self and the rest of one's group. Equality (restricted vs. full rights) and respect (disrespect vs. respect) were manipulated as independent variables, while collective identification and willingness to engage in group-serving behaviour were the main dependent variables. Moderation was confirmed such that the positive effects of respect were more pronounced among group members with restricted rights than among group members with full rights. Moreover, respect fully compensated for the initial deficit in self-perception as a fully fledged group member. However, there was also some indication that, when money is at stake, formal guarantees of equality may be necessary for respect to have a facilitative effect on individual sacrifices for the sake of the group. The practical and political implications of the results are discussed.


The effect of ageing on the plasma renin-angiotensin-aldosterone system in elderly hypertensive patients.
Plasma renin activity, renin concentration and aldosterone concentration were measured in 78 untreated hypertensive patients aged 60-83 years. In a cross-sectional analysis, plasma renin activity, renin concentration and aldosterone concentration showed no relationship with age. Half of these patients were subsequently followed on placebo over a 3-year period during which the plasma constituents of the renin-angiotensin-aldosterone system remained stable. From these cross-sectional and longitudinal observations we conclude that beyond the age of 60 ageing has no detectable effect on plasma renin and aldosterone levels in these elderly hypertensive patients.


Repeatability of Oral Sugar Test Results, Glucagon-Like Peptide-1 Measurements, and Serum High-Molecular-Weight Adiponectin Concentrations in Horses.
Repeatability of the oral sugar test (OST) has not been evaluated. We hypothesized that OST glucose, insulin, active (aGLP-1) and total (tGLP-1) glucagon-like peptide 1, and high-molecular-weight (HMW) adiponectin results would be repeatable. Fifty-three horses from a Tennessee research facility (n = 23) and private practice in Missouri (n = 30), including animals with medical histories of equine metabolic syndrome. Two OSTs were performed 7-14 days apart and plasma glucose and insulin concentrations were measured at 0, 60, and 75 minutes; a positive result was defined as detection of an insulin concentration >45 μU/mL at 60 or 75 minutes. Plasma aGLP-1 and serum tGLP-1 concentrations at 75 minutes and serum HMW adiponectin concentrations at 0 minute were measured in the Missouri group. Bland-Altman analyses were performed. No adverse events were reported. Bland-Altman analysis indicated mean ± SD bias of 1.5 ± 14.8 μU/mL (95% confidence interval [CI], -27.6 to 30.5 μU/mL) and 1.2 ± 16.1 μU/mL (95% CI, -30.4 to 32.8 μU/mL) for insulin concentrations at 60 and 75 minutes, respectively. There was 91 and 83% agreement in test interpretation between test days for OST insulin results for all horses in the Tennessee and Missouri groups, respectively. Repeatability of the OST was acceptable when values obtained from Bland-Altman analyses were evaluated, and there was good agreement in binary (negative/positive) test interpretation for insulin concentrations. However, wide 95% CIs were detected for insulin concentrations.


[Experimental evaluation of materials for electrodes in transcutaneous recording of bioelectric signals].
The authors examined electrodes made of stainless steel, graphitic and metalized polymeric materials for transcutaneous recording of biopotentials from the human services by the following parameters: electrode potential difference, noise voltage, phase difference-signal frequency relationships. If the phase is adequately corrected, the electrode made of graphitic cloth is effective in recording biopotentials at an amplitude of more than 20 microV over a wide frequency range.


In Vitro Antibiofilm Activity of Eucarobustol E against Candida albicans.
Formyl-phloroglucinol meroterpenoids (FPMs) are important types of natural products with various bioactivities. Our antifungal susceptibility assay showed that one of the Eucalyptus robusta-derived FPMs, eucarobustol E (EE), exerted a strong inhibitory effect against Candida albicans biofilms at a concentration of 16 μg/ml. EE was found to block the yeast-to-hypha transition and reduce the cellular surface hydrophobicity of the biofilm cells. RNA sequencing and real-time reverse transcription-PCR analysis showed that exposure to 16 μg/ml of EE resulted in marked reductions in the levels of expressions of genes involved in hyphal growth (EFG1, CPH1, TEC1, EED1, UME6, and HGC1) and cell surface protein genes (ALS3, HWP1, and SAP5). Interestingly, in response to EE, genes involved in ergosterol biosynthesis were downregulated, while the farnesol-encoding gene (DPP3) was upregulated, and these findings were in agreement with those from the quantification of ergosterol and farnesol. Combined with the obvious elevation of negative regulator genes (TUP1, NRG1), we speculated that EE's inhibition of carbon flow to ergosterol triggered the mechanisms of the negative regulation of hyphal growth and eventually led to biofilm inhibition.


Lateral approach to the sciatic nerve block in the popliteal fossa: correlation between evoked motor response and sensory block.
The purpose of this study was to identify which of two motor responses of the foot (plantar flexion versus dorsiflexion) best predicts complete sensory blockade of the sciatic nerve when is used for lateral popliteal sciatic nerve block. Thirty American Society of Anesthesiologist physical status I or II patients scheduled for foot and ankle surgery under lateral popliteal sciatic nerve block were enrolled in the study. During each block, the needle was placed to evoke one of the following motor responses of the foot: plantar flexion or dorsiflexion. Thirty milliliters of 0.75% ropivacaine was injected after the motor response was elicited at <0.5 mA. The sequence of elicited motor response was randomized. Sensory blockade of the areas of the foot innervated by the deep peroneal, superficial peroneal, posterior tibial, and sural nerves was checked in a blinded manner. Time required for onset of sensory and motor block of the foot was recorded. The 2 groups were similar with regard to demographic variables and type of surgery. The total of nerves blocked (deep and superficial peroneal, posterior tibial, and sural nerves) after elicited plantar flexion was greater (complete sensory block in 58 of 60 nerve distributions) than after elicited dorsiflexion (34 of 60 nerve distributions) (P <.05). Onset of complete sensory and motor blockade of the foot was faster after elicited plantar flexion (16.6 +/- 5.1 minutes, 20.1 +/- 5.1 minutes, respectively) than after elicited dorsiflexion (24.3 +/- 5.1 minutes, 28.1 +/- 5.0 min, P <.05). After stimulation of the sciatic nerve, plantar flexion better predicts complete sensory blockade of the foot than dorsiflexion when using the lateral approach to the popliteal fossa. The findings of the present study apply to a single injection of 30 mL of ropivacaine 0.75%.


Tonatiuh II: assisting manipulator for laparoscopic surgery.
In this article we show the design of the Tonatiuh II robotic manipulator. This robotic assistant has an original electromechanical configuration and respects the laparoscope center of insertion as an invariant point for navigation in the work space. The manipulator went through several stages before reaching its final version. Surgical trials have shown the robot to be useful in the operating room and as a training assistant in specialty microsurgery.


Access to Imidazolidine-Fused Sulfamidates and Sulfamides Bearing a Quaternary Center via 1,3-Dipolar Cycloaddition of Nonstabilized Azomethine Ylides.
A 1,3-dipolar cycloaddition reaction of nonstabilized azomethine ylides and cyclic N-sulfonyl imines has been developed providing a workable access to imidazolidine-fused sulfamidates, sulfamides, and benzosultams bearing a quaternary center. Distinct from the available literature, this current work enables to make entry, for the first time, into the novel imidazolidine-fused sulfamidates and sulfamides. Furthermore, the selective imidazolidine ring opening accompanied by CH2 extrusion yielded tetra-substituted sulfamidates with an aminomethyl group. In addition, imidazolidine ring opening coupled with SO2 extrusion provided synthetically useful 1,2-diamines.


The Synergistic Effect of Proanthocyanidin and HDAC Inhibitor Inhibit Breast Cancer Cell Growth and Promote Apoptosis.
Histone deacetylase inhibitor (HDACi) is a drug mainly used to treat hematological tumors and breast cancer, but its inhibitory effect on breast cancer falls short of expectations. Grape seed proanthocyanidin extract (GSPE) with abundant proanthocyanidins (PAs) has been explored for its inhibition of HDAC activity in vitro and in vivo. To enhance HDACi's effectiveness, we investigated the potential of PA to synergistically enhance HDACi chidamide (Chi), and determined the underlying mechanism. We evaluated the half-inhibitory concentration (IC50) of PA and Chi using the cell counting kit 8 (CCK8), and analyzed drugs' synergistic effect with fixed-ratio combination using the software Compusyn. Breast cancer cell's phenotypes, including short-term and long-term proliferation, migration, invasion, apoptosis, and reactive oxygen species (ROS) levels, were assessed via CCK8, clone-formation assay, wound-healing test, Transwell Matrigel invasion assay, and flow-cytometry. Protein-protein interaction analysis (PPI) and KEGG pathway analysis were used to determine the underlying mechanism of synergy. PA + Chi synergistically inhibited cell growth in T47D and MDA-MB-231 breast cancer cell lines. Short-term and long-term proliferation were significantly inhibited, while cell apoptosis was promoted. Ten signaling pathways were identified to account for the synergistic effect after RNA sequencing. Their synergism may be closely related to the steroid biosynthesis and extracellular matrix (ECM) receptor interaction pathways. PA + Chi can synergistically inhibit breast cancer cell growth and proliferation, and promote apoptosis. These effects may be related to steroid biosynthesis or the ECM receptor pathway.


Shelf-life, bioburden, water and oxygen permeability studies of laser welded SEBS/PP blended polymer.
The most common material used for blood bags is PVC, which requires the addition of DEHP to increase its flexibility. DEHP is known to cross the polymer barrier and move into the stored blood and, ultimately, the patient's bloodstream. In this work, an alternative prototype composed of SEBS/PP was fabricated through blow-moulding and compared with the commercially available PVC-based blood bag which was designated as the control. The blow-moulded sample layers were welded together using CO2 lasers and optimized to obtain complete sealing of the sides. The samples' performance characteristics were analyzed using water permeability, oxygen permeability, shelf-life, and bioburden tests. The SEBS/PP sample exhibited the highest oxygen permeability rate of 1486.6 cc/m2/24 h after 40 days of ageing, indicating that the sample is conducive for red blood cell (RBC) respiration. On the other hand, the SEBS/PP sample showcased a lower water permeability rate of 0.098 g/h m2 after 40 days of aging, indicating a high-water barrier property and thus preventing water loss during storage. In comparison, the oxygen and water permeability rates of PVC-DEHP were found to be distinctly lower in performance (662.7 cc/m2/24 h and 0.221 g/h m2, respectively). In addition, shelf-life analyses revealed that after 40 days of ageing, polymer samples exhibited no visual damage or degradation. The optimal parameters to obtain adequate welding of the SEBS/PP were determined to be power of 60% (18 W), speed of 70 in/sec and 500 Pulse Per Inch (PPI). Furthermore, the bioburden estimates of SEBS/PP of 115 CFU are markedly lower compared to the bioburden estimate of PVC-DEHP of 213 CFU. The SEBS/PP prototype can potentially be an effective alternative to PVC-based blood bags, particularly for high-risk patients in order to reduce the likelihood of medical issues.


Association of tenofovir diphosphate and lamivudine triphosphate concentrations with HIV and HBV viral suppression.
Concentrations of tenofovir diphosphate (TFV-DP) and lamivudine triphosphate (3TC-TP) in cells are correlates of medication adherence and antiviral activity. However, studies have yet to characterize the simultaneous relationship between TFV-DP and 3TC-TP concentrations with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) suppression. Individuals with HIV/HBV coinfection on tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART) were enrolled. Peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) samples were collected and steady-state TFV-DP and 3TC-TP concentrations quantified using validated methods. The relationship between patient factors, TFV-DP and 3TC-TP concentrations in PBMCs and DBS with HBV and HIV viral suppression were examined. Of 138 participants on TDF-containing ART for a median duration (range) of 6 (0.75-15) years, the median age was 43 years and 64% were female. Overall, 128 (92.8%) and 129 (93.5%) had suppressed HIV and HBV viral loads, respectively. Of the 128 participants with suppressed HIV, 122 (95.3%) had suppressed HBV. Self-reported ART adherence, recent change to dolutegravir-based ART, TFV-DP and 3TC-TP concentrations in PBMCs and DBS were associated with HIV RNA suppression, while HBe antigen positivity, HIV suppression and TFV-DP concentrations in DBS were associated with HBV DNA suppression (including six persons with HBV non-suppression and HIV suppression). Long-term TDF/3TC-conatining ART was highly efficacious in individuals with HIV/HBV coinfection. Higher TFV-DP concentrations were predictive of suppression for both viruses. Persistent HBV viremia on TDF/3TC-containg ART requires additional research, but may represent poor adherence and the need for adherence interventions or novel antivirals.


Pharmacokinetics of new anticonvulsants in psychiatry.
The newer AEDs have potential in the treatment of psychiatric disorders. In light of this expanding spectrum of activity, it is necessary to refine and focus the safety and efficacy of the use of these agents among a wider population. The classic AEDs had numerous problems, ranging from inconvenient dosing schedules to frequent side effects due to active metabolites and common drug interactions; newer agents have been developed to avoid some of these pitfalls. Indeed, a generation of drugs that appears to have relatively simple pharmacokinetics and limited drug interactions--making them safer and easier to administer--is now available. The use of these agents in psychiatry will necessitate additional investigation into their dosing and administration guidelines, as well as their interactions with other common psychiatric or concomitant drugs. Certainly, over time, they will be evaluated for these parameters in the newer indications. In the meantime, a review of the established pharmacokinetic and pharmacodynamic activities of these agents is the first step in defining their optimal uses and limitations in the psychiatric setting.


The impact of race/ethnicity on preoperative time to hip stabilization procedure after hip fracture.
We sought to examine the preoperative time for hip stabilization procedure among Hispanics, non-Hispanic blacks (blacks) and non-Hispanic whites (whites). This was a secondary data analysis using Medicare claims data. Our analysis included 40,321 patients admitted for hip fracture hospitalization from 2001-2005. Our primary analysis was generalized linear modeling, and our dependent variable was preoperative time. Our independent variable was race/ethnicity (Hispanics, blacks versus whites), and covariates were age, gender, income, type of hip fracture and comorbidities. Bivariate analyses showed that both Hispanics and blacks experienced a longer preoperative time (P < 0.01). The average (mean) of days to surgery was 1.2 for whites, 1.6 for blacks and 1.7 for Hispanics. The delayed preoperative time among Hispanics and blacks persisted after adjusting for covariates. The delayed preoperative time among minorities suggests the need to closely monitor care among minorities with hip fracture to determine how to best address their developing needs.


Genetic Patterns of Myrceugenia correifolia, a Rare Species of Fog-Dependent Forests of Mediterranean Chile: Is It a Climatic Relict?
Rare species frequently occur in areas with microclimatic conditions that are atypical for their regions, but that were more common in the past, and that probably have operated as climatic refugia for a long time. Myrceugenia correifolia is a rare arboreal species that grows in deep canyons and hilltops of the Coast Range of north-central Chile between 30° and 35°S. In the northern edge of its distribution M. correifolia grows in small patches of fog-dependent forest surrounding by xeric vegetation. These forest formations are thought to be remnants of an ancient and continuous rainforest that according to some authors became fragmented during aridization of the Neogene (Neogene relict) and to others during warm-dry cycles of the Pleistocene (glacial relicts). Here we asked whether the northernmost populations of M. correifolia are Neogene relicts, glacial relicts, or the result of a recent northward colonization. To answer this question we examined genetic diversity and population divergence of M. correifolia using microsatellite markers, tested various competing population history scenarios with an approximate Bayesian computation (ABC) method, and complemented these data with ecological niche modeling (ENM). We detected three genetic clusters with a distinctive latitudinal pattern (north, center, and south) and high levels of differentiation (FST = 0.36). Demographic inference supported an admixture event 31 kya between two populations that diverged from an ancient population 139 kya. The admixture time coincides with the beginning of a period of wet conditions in north-central Chile that extended from 33 to 19 kya and was preceded by dry and cold conditions. These results suggest that increased precipitation during glacial periods triggered northward expansion of the range of M. correifolia, with subsequent admixture between populations that remained separated during interglacial periods. Accordingly, ENM models showed that suitable habitats for M. correifolia in north-central Chile were larger and less fragmented during the Last Glacial Maximum than at present, suggesting that northernmost populations of this species are glacial relicts.


Development of MRI phantom equivalent to human tissues for 3.0-T MRI.
A 3.0-T MRI phantom (called the CAGN-3.0T phantom) having human-equivalent relaxation times and human-equivalent conductivity was developed. The ingredients of the phantom are carrageenan (as a gelatinizer), agarose (as a T2-relaxation modifier), GdCl3 (as a T1-relaxation modifier), NaCl (as a conductivity modifier), and NaN3 (as an antiseptic). Numerous samples with varying concentrations of agarose, GdCl3, and NaCl were prepared, and T1 and T2 values were measured using 3.0-T MRI. The T1 values of the CAGN-3.0T phantom were unaffected by NaCl, while the T2 values were only slightly affected. Based on the measured data, empirical formulae were devised to express the relationships between the concentrations of agarose, GdCl3, and NaCl and the relaxation times. The formula for expressing the conductivity of the CAGN-3.0T phantom was obtained. By adjustments to the concentrations of agarose, GdCl3, and NaCl, the relaxation times and conductivity of almost all types of human tissues can be simulated by CAGN-3.0T phantoms. The phantoms have T1 values of 395-2601 ms, T2 values of 29-334 ms, and conductivity of 0.27-1.26 S/m when concentrations of agarose, GdCl3, and NaCl are varied from 0 to 2.0 w/w%, 0 to 180 μmol/kg, and 0 to 0.7 w/w%, respectively. The CAGN-3.0T phantom has sufficient strength to replicate the torso without using reinforcing agents, and can be cut with a knife into any shape.


The tender tooth. Dentoalveolar, pericoronal, and periodontal infections.
Dental caries and periodontal disease are the most common afflictions of the tooth. These infectious diseases cause considerable pain and discomfort and ultimately loss of the tooth. Apart from local effects, these infections may extend beyond natural barriers and result in complications that can vary in severity from the excruciating pain of acute pulpitis to life-threatening infections of the deep fascial spaces of the head and neck. In this article, the clinical and pathologic features of dental caries, pulpitis, periapical abscess, pericoronitis, and periodontal infections are discussed as well as prevention and treatment of infections involving the tooth, with emphasis on endocarditis prophylaxis.


Differential absorption sensor applied for liquid oxygen measurements.
Differential laser absorption was investigated for its merit in liquid oxygen (LOX) sensing. Whereas previous researchers have used differential absorption to detect trace concentrations of a substance, we use differential absorption to monitor small changes in large amounts of a substance. Two lasers of different wavelengths were intensity modulated 180 deg out of phase from each other and multiplexed into a single beam. After probing the LOX, the total transmitted signal was demodulated by a lock-in amplifier. Our experiment simulated rapid changes in LOX number density by varying the length of an approximately 73 mm path through pure LOX. In this experiment, we demonstrated the ability to monitor LOX number density with an uncertainty of approximately 1% with a time constant of 3 micros. The uncertainty could be halved by doubling the path length, and this improvement could be repeated as long as the relative intensity noise of the lasers is the dominating factor. We discuss the benefits of differential absorption for problems requiring an extended dynamic range.


A canonical discriminant analysis of post-embryonic development in Notonecta Maculata fabricius (Insecta:Heteroptera).
A multivariate method, canonical discriminant analysis, was used to discern a pattern of growth in Notonecta maculata. A stepwise procedure reduced the 11 metrical characters measured on individuals of both sexes, from the 1st larval stage to the adult, to 4 significant variates which were used in the canonical analysis. The four canonical variates accounted for the meaningful part of the variablity. Relying on bivariate allometry and on an experimentation with a juvenile hormone analogue, each independent direction of variation was related to combined effects of such biological factors as a general growth trend, sex and juvenile hormone.


Association Between Telepsychiatry Capability and Treatment of Patients With Mental Illness in the Emergency Department.
Because of limited access to psychiatrists, patients with acute mental illness in some emergency departments (EDs) may wait days for a consultation in the ED or as a medical-surgical admission. The study assessed whether telepsychiatry improves access to care and decreases ED wait times and hospital admissions. ED visits with a primary diagnosis of mental illness were identified from 2010-2018 Medicare claims. A total of 134 EDs across 22 states that implemented telepsychiatry between 2013 and 2016 were matched 1:1 with control EDs without telepsychiatry on several characteristics, including availability of in-person psychiatrist consultations. Outcomes included patients' likelihood of admission to a medical-surgical or psychiatric bed, mental illness spending, prolonged ED length of stay (LOS) (two or more midnights in the ED), 90-day mortality, and outpatient follow-up care. Using a difference-in-difference design, changes in outcomes between the 3 years before telepsychiatry adoption and the 2 years after were examined. There were 172,708 ED mental illness visits across the 134 matched ED pairs in the study period. Telepsychiatry adoption was associated with increased admissions to a psychiatric bed (differential increase, 4.3 percentage points; p<0.001), decreased admissions to a medical-surgical bed (differential decrease, 2.0 percentage points; p<0.001), increased likelihood of a prolonged ED LOS (differential increase, 3.0 percentage points; p<0.001), and increased mental illness spending (differential increase, $292; p<0.01). Telepsychiatry adoption was associated with a lower likelihood of admission to a medical-surgical bed but an increased likelihood of admission to a psychiatric bed and a prolonged ED LOS.


Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles.
Macrophages are becoming increasingly significant in the progression of atherosclerosis (AS). Molecular imaging of macrophages may improve the detection and characterization of AS. In this study, dendrimer-entrapped gold nanoparticles (Au DENPs) with polyethylene glycol (PEG) and fluorescein isothiocyanate (FI) coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT) imaging of macrophages in atherosclerotic lesions. Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0 μM) and can be efficiently taken up by murine macrophages in vitro. These nanoparticles were administered to apolipoprotein E knockout mice as AS models, which demonstrated that the macrophage burden in atherosclerotic areas can be tracked noninvasively and dynamically three-dimensionally in live animals using micro-CT. Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases.


Stem Cell Transplantation for Light Chain Amyloidosis: Decreased Early Mortality Over Time.
Purpose Autologous stem-cell transplantation (ASCT) has been used in patients with immunoglobulin light chain (AL) amyloidosis for more than two decades. Early experience raised concerns regarding safety with high early-mortality rates. Patients and Methods We report 20 years of experience with ASCT for AL amyloidosis at the Mayo Clinic Rochester. In all, 672 consecutive patients receiving ASCT for AL amyloidosis were divided into three cohorts on the basis of date of transplantation (cohort 1, 1996-2002 [n = 124]; cohort 2, 2003-2009 [n = 302]; and cohort 3, 2010-2016 [n = 246]). Results The median age for the entire cohort was 59 years, with patients in cohort 3 being slightly older than those in the other two cohorts (60 v 58 v 54 years for cohorts 3, 2, and 1, respectively; P < .001). Fewer patients in cohort 3 had more than two organs involved (9% v 18% v 19% for cohorts 3, 2, and 1, respectively; P < .001). More patients received pretransplantation therapy in cohort 3 compared with earlier time periods (49% v 38% v 42% for cohorts 3, 2, and 1, respectively; P = .02). Hematologic response was higher in cohort 3 (84% v 79% v 69% for cohorts 3, 2, and 1, respectively; P = .002). Median overall survival for the entire cohort was 122 months and improved over time (not reached v 120 months v 75 months for cohorts 3, 2, and 1, respectively; P < .001). Treatment-related mortality declined over time (2.4% v 8.6% v 14.5% for cohorts 3, 2, and 1, respectively; P < .001). On multivariable analysis, conditioning dose, Mayo stage 2012, and hematologic response were independent predictors of survival. Conclusion ASCT is a highly effective therapy for AL amyloidosis. The improved survival and markedly reduced treatment-related mortality in eligible patients indicate that this will remain an important first-line option even in the era of treatment approaches that use novel agents.


Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta 1 (TGF-beta 1) inhibit the expression and activity of Na+/K(+)-ATPase in FRTL-5 rat thyroid cells.
We recently reported that tumor necrosis factor-alpha (TNF-alpha) induction of the synthesis and secretion of transforming growth factor (TGF)-beta 1 by FRTL-5 cells is a thyroid-stimulating hormone (TSH)-dependent and age-dependent process. TNF-alpha is only cytotoxic to aged (> 40 passages) FRTL-5 cells grown in TSH-containing medium, whereas TGF-beta induces programmed cell death (apoptosis) in epithelial cells but not in FRTL-5 cells, which otherwise retain many properties of normal thyroid follicular cells. This cell line is, therefore, a convenient model for studies on the TSH-dependent and age-dependent inhibitory effects of these cytokines on epithelial cell growth, viability, and function. One prominent effect of TNF-alpha (and TGF-beta 1) on FRTL-5 cell function is suppression of iodide uptake, which is markedly stimulated by TSH. In aged FRTL-5 cells, iodide uptake is only about 10% that of young control cells. Na+/K(+)-ATPase activity, which drives iodide uptake by thyroid cells, is inhibited by TNF-alpha and TGF-beta. The following experiments quantitate the effects of TSH, aging, TNF-alpha, and TGF-beta 1 on the expression and activity of Na+/K(+)-ATPase activity in FRTL-5 cells. Young (< 20 passages) and aged (> 40 passages) FRTL-5 cells were treated with various doses (0-100 ng/ml) of recombinant human TNF-alpha or TGF-beta 1 for various times (0-3 days) with and without 2 U/liter TSH. These treatments reduced the rate-limiting Na+/K(+)-ATPase beta 1 mRNA level and Na+/K(+)-ATPase activity in parallel in a dose-dependent and time-dependent fashion. Aged FRTL-5 cells were more sensitive to the inhibitory effects of TNF-alpha, whereas young cells were more sensitive to the suppressive effects of TGF-beta 1 on the expression and activity of Na+/K(+)-ATPase. We conclude that inhibition of Na+/K(+)-ATPase activity by TNF-alpha and TGF-beta in FRTL-5 cells is differentially affected by aging and that this inhibitory effect can be dissociated from effects on cell viability.


Scrapie-infected spleens: analysis of infectivity, scrapie-associated fibrils, and protease-resistant proteins.
Scrapie-associated fibrils (SAF) and protease-resistant proteins (PrP) were isolated from spleens and brains of clinical animals (mice and hamsters) from three scrapie agent-host strain combinations, and their concentrations were compared with infectivity levels. The spleens of infected animals contained lower levels of infectivity, PrP, and SAF than did brains. Regardless of the route of infection, both SAF and infectivity were detected in spleen before brain. Infectivity increased in brains and spleens of 139A-infected mice before the detection and increase in SAF, suggesting that the synthesis of SAF and PrP may not be the limiting factor in agent replication. In contrast to those in ME7- and 263K-infected animals, the Western blot profiles for PrP from brain and spleen of 139A-infected mice exhibited distinct differences. Results indicate that SAF and PrP found in the spleens are both organ- and scrapie strain-specific.


Graphical model for joint segmentation and tracking of multiple dividing cells.
To gain fundamental insight into the development of embryos, biologists seek to understand the fate of each and every embryonic cell. For the generation of cell tracks in embryogenesis, so-called tracking-by-assignment methods are flexible approaches. However, as every two-stage approach, they suffer from irrevocable errors propagated from the first stage to the second stage, here from segmentation to tracking. It is therefore desirable to model segmentation and tracking in a joint holistic assignment framework allowing the two stages to maximally benefit from each other. We propose a probabilistic graphical model, which both automatically selects the best segments from a time series of oversegmented images/volumes and links them across time. This is realized by introducing intra-frame and inter-frame constraints between conflicting segmentation and tracking hypotheses while at the same time allowing for cell division. We show the efficiency of our algorithm on a challenging 3D+t cell tracking dataset from Drosophila embryogenesis and on a 2D+t dataset of proliferating cells in a dense population with frequent overlaps. On the latter, we achieve results significantly better than state-of-the-art tracking methods. Source code and the 3D+t Drosophila dataset along with our manual annotations will be freely available on http://hci.iwr.uni-heidelberg.de/MIP/Research/tracking/


The Role of Local Educational Institutions in Educating of EMDR Practitioners in Bosnia-Herzegovina.
Providing good mental health services to the vulnerable and needy should be of utmost importance to all mental health professionals. To be able to do so, professionals require to be, not only educated but actually properly trained and supervised in specially, among various skills, psychotherapy orientation. Unlike developed countries, psychotherapy services and professional career in psychotherapy in Bosnia and Herzegovina (B&H) is relatively new primarily due to the recent historical developments and events in B&H. Besides, there is scarcity of professional institutions in B&H which could, not only establish structure for, promote but also educate mental health professionals, according to the European psychotherapy standards as well as accredit and certify psychotherapists, locally or internationally. The purpose of the present study is to show the role of International University of Sarajevo (IUS) as a local private educational institution in educating and training EMDR therapist in B&H. The collaboration between EMDR HAP UK & Ireland, Association of EMDR Therapists in Bosnia and Herzegovina (AEMDRTBH), Department of Psychiatry University Clinical Center (UCC) Tuzla and Psychiatry Clinic, Clinical Center of University (CCU) Sarajevo described with focus on the collaboration with International University in Sarajevo. Local institutions in B&H can in a variety of ways make a significant contribution to the education and training of therapists in BiH in the following ways: providing rooms for realizing of education and training and/or conferences (pro bono), promoting EMDR as a successful therapeutic method for treating of stress and trauma within relevant subjects and programs, providing scholarships for excellent students for EMDR education, and in collaboration with local and European EMDR therapists to offer EMDR specializations for professionals. Since 2010, one group of therapists has been educated and trained by EMDR HAP UK at Department of Psychiatry UCC Tuzla, two groups at the Psychiatric Clinic CCU in Sarajevo and one group at IUS. Thanks to EMDR HAP UK&Ireland, EMDR therapists in B&H are among the youngest yet very efficient and successful therapists who greatly contribute to improving mental health of fellow citizens. Collaboration between Association of EMDR Therapists in Bosnia-Herzegovina, HAP UK & Ireland AP B&H and local educational institutions such as IUS can significantly contribute to training efficient preparation of EMDR professionals in B&H and help improve overall mental health and wellbeing of B&H citizens.


Accessibility of long-term family planning methods: a comparison study between Output Based Approach (OBA) clients verses non-OBA clients in the voucher supported facilities in Kenya.
The study seeks to evaluate the difference in access of long-term family planning (LTFP) methods among the output based approach (OBA) and non-OBA clients within the OBA facility. The study utilises a quasi experimental design. A two tailed unpaired t-test with unequal variance is used to test for the significance variation in the mean access. The difference in difference (DiD) estimates of program effect on long term family planning methods is done to estimate the causal effect by exploiting the group level difference on two or more dimensions. The study also uses a linear regression model to evaluate the predictors of choice of long-term family planning methods. Data was analysed using SPSS version 17. All the methods (Bilateral tubal ligation-BTL, Vasectomy, intrauterine contraceptive device -IUCD, Implants, and Total or combined long-term family planning methods -LTFP) showed a statistical significant difference in the mean utilization between OBA versus non-OBA clients. The difference in difference estimates reveal that the difference in access between OBA and non OBA clients can significantly be attributed to the implementation of the OBA program for intrauterine contraceptive device (p = 0.002), Implants (p = 0.004), and total or combined long-term family planning methods (p = 0.001). The county of residence is a significant determinant of access to all long-term family planning methods except vasectomy and the year of registration is a significant determinant of access especially for implants and total or combined long-term family planning methods. The management level and facility type does not play a role in determining the type of long-term family planning method preferred; however, non-governmental organisations (NGOs) as management level influences the choice of all methods (Bilateral tubal ligation, intrauterine contraceptive device, Implants, and combined methods) except vasectomy. The adjusted R2 value, representing the percentage of the variance explained by various models, is larger than 18% for implants and total or combined long-term family planning. The study showed that the voucher services in Kenya has been effective in providing long-term family planning services and improving access of care provided to women of reproductive age. Therefore, voucher scheme can be used as a tool for bridging the gap of unmet needs of family planning in Kenya and could potentially be more effective if rolled out to other counties.


Prognostic Significance of Aneurysm Sac Shrinkage After Endovascular Aneurysm Repair.
Purpose: To investigate whether patients who develop aneurysm sac shrinkage following endovascular aneurysm repair (EVAR) have better outcomes than patients with a stable or increased aneurysm sac. Materials and Methods: The Healthcare Databases Advanced Search interface developed by the National Institute for Health and Care Excellence was used to interrogate MEDLINE and EMBASE. Thesaurus headings were adapted accordingly. Case-control studies were identified comparing outcomes in patients demonstrating aneurysm sac shrinkage after EVAR with those of patients with a stable or expanded aneurysm sac. Pooled estimates of dichotomous outcome data were calculated using the odds ratio (OR) and 95% confidence interval (CI). Meta-analysis of time-to-event data was conducted using the inverse-variance method; the results are reported as a summary hazard ratio (HR) and 95% CI. Summary outcome estimates were calculated using random-effects models. Results: Eight studies were included in quantitative synthesis reporting a total of 17,096 patients (8518 patients with sac shrinkage and 8578 patients without sac shrinkage). The pooled incidence of sac shrinkage at 12 months was 48% (95% CI 40% to 56%). Patients with aneurysm sac shrinkage had a significantly lower hazard of death (HR 0.73, 95% CI 0.60 to 0.87), secondary interventions (HR 0.42, 95% CI 0.29 to 0.62), and late complications (HR 0.37, 95% CI 0.24 to 0.56) than patients with a stable or increased aneurysm sac. Furthermore, their odds of rupture were significantly lower than those in patients without shrinkage (OR 0.09, 95% CI 0.02 to 0.36). Conclusion: Sac regression is correlated to improved survival and a reduced rate of secondary interventions and EVAR-related complications. The prognostic significance of sac regression should be considered in surveillance strategies. Intensified surveillance should be applied in patients who fail to achieve sac regression following EVAR.


Double blind study of intrathecal beta-interferon in multiple sclerosis: clinical and laboratory results.
Sixteen patients with clinically definite MS admitted to a double blind randomised controlled trial of intrathecal natural beta-IFN were followed for a mean of 22 months including the six month treatment period. Clinical response, evaluated in terms of relapse frequency and of progression rate, showed an increase in relapse rate in treated patients during the six month treatment period and, overall, no benefit in treated versus placebo patients. Serial evaluations were made of cerebrospinal fluid (CSF) cells, IgG, myelin basic protein and CSF and blood T-cell subsets. A rise in CSF IgG Index, MBP and DR+ cells in IFN-treated patients suggested an activation of intrathecal immune response in treated patients.


Surveillance for nosocomial infections: can the sources of data be reduced?
With the goal of achieving economy in infection control surveillance we tested the relative efficiency of the various surveillance sources for detecting nosocomial infections (NIs). We reviewed the initial and final surveillance sources of 415 NIs at Hackensack Hospital during an 11-month period; cultures were taken on most of the patients with NIs. Positive microbiology cultures were the initial sources in 64.8% of NIs and secondary sources in 23.6%. Chart review of patients with positive cultures added another 2.9%. Therefore, 91.3% of NIs could have been detected by positive culture reports. The remainder were discoverable by notification from nurses, or by studying admission cards or temperature rounds. Although the NIs missed by lack of a positive culture report often were significant infections, these alternate methods of surveillance did not help to detect any clusters of infections that could be traced to a particular source among the staff or the environment.


[Application of an air-powder abrasive system in periodontal therapy and its effect on root surfaces].
An air-powder abrasive device used to remove stain and debris adherent to tooth surface is now available for use by dentist. Air Flow was evaluated for its effectiveness in removing stains and debris from teeth. Split design in anterior was used, and half was treated with the device and the contralateral side with a brush cone and tooth polishing paste. Time required by each method to remove stain and debris completely was recorded and compared. A gingival trauma index was assessed according to the method of Weaks L.M. et al. (1984). Air-powder abrasive system removed stain and debris in less time than brush cone technique (P less than 0.001). The system was also most effective in removing stains in pit, fissure and contact areas. The device caused a significant increase (P less than 0.01) in gingival irritation immediately posttreatment, but there was no statistically and clinically significance in the effect on the gingiva at 7 days posttreatment between two techniques. In vitro study, the effect of the device on root surfaces was also assessed. 5, 10, 20, 40 and 60 seconds exposure of a fixed point on root surfaces to the device produced defects 137, 245, 308, 945 and 1,394 microns in depth, respectively. The resulting surface was smooth and all cementum was removed. And the average loss of root structure as a function of the exposure time was also assessed. The average losses were 0.2, 0.6, 1.7, 1.8, 2.0, 2.1, 2.3 and 2.4 mg by 5, 10, 15, 20, 30, 40, 50 and 60 seconds exposures, respectively. Root surface roughness, resulting from hand curette, ultrasonic curette and air-powder abrasive system was examined histologically. The hand curette produced smooth root surface. The ultrasonic instrument produced a surface characterized by irregular ridges. The air powder abrasive system was found to produce a root surface favorably comparable to manual root planing and remove cementum from areas of difficult treatment, such as furcations.


The greatest health problem of the Middle Ages? Estimating the burden of disease in medieval England.
To identify the major health problems of the Middle Ages. Bubonic plague is often considered the greatest health disaster in medieval history, but this has never been systematically investigated. We triangulate upon the problem using (i) modern WHO data on disease in the modern developing world, (ii) historical evidence for England such as post-medieval Bills of Mortality, and (iii) prevalences derived from original and published palaeopathological studies. Systematic analysis of the consequences of these health conditions using Disability Adjusted Life Years (DALYs) according to the Global Burden of Disease methodology. Infant and child death due to varied causes had the greatest impact upon population and health, followed by a range of chronic/infectious diseases, with tuberculosis probably being the next most significant one. Among medieval health problems, we estimate that plague was probably 7th-10th in overall importance. Although lethal and disruptive, it struck only periodically and had less cumulative long-term human consequences than chronically endemic conditions (e.g. bacterial and viral infections causing infant and child death, tuberculosis, and other pathogens). In contrast to modern health regimes, medieval health was above all an ecological struggle against a diverse host of infectious pathogens; social inequality was probably also an important contributing factor. Methodological assumptions and use of proxy data mean that only approximate modelling of prevalences is possible. Progress in understanding medieval health really depends upon understanding ancient infectious disease through further development of biomolecular methods.


[Epidemiology of diabetes mellitus: prevalence, incidence, pathogenesis, and prognosis].
According to the WHO definition the term diabetes mellitus covers a group of metabolic diseases characterized by elevated blood glucose levels. The two main representatives of this group are type 1 and type 2 diabetes. All forms of diabetes have in common that, due to hyperglycemia, complications (vascular damage in particular) can occur, which are responsible for the high rate of morbidity as well as the excess mortality of the group of persons affected. In all populations--Germany included--the overwhelming majority of diabetics are subjects with type 2 diabetes. Type 2 diabetes is almost 20 times more common than type 1 diabetes, i.e. almost 90% of all diabetic persons can be assigned to the type 2 diabetes category. The rest can be split up into 5-7% type 1 diabetics and 2%-5% of persons suffering from secondary forms of diabetes (pancreatic and hepatic diseases). Positive antibody tests in older diabetic persons suggest that type 2 diabetes may not be a uniform disease and that in almost 10% of cases an autoimmune disease might be the cause of diabetes in old age (LA-DA diabetes). The data of the diabetes register of the former German Democratic Republic (East Germany) together with representative samples obtained from the federal states that comprised West Germany indicate a diabetes prevalence of about 5% in the adult population of Germany. Once the new WHO diagnostic criteria for diabetes mellitus are used and an early-diagnosis procedure (the oral glucose tolerance test) is widely applied the prevalence is expected to be shown to be higher. What is more, the global trend toward higher figures for type 1 and type 2 diabetes can also be observed in Germany. Whereas the pathogenesis of type 1 diabetes results from the autoimmune destruction of beta cells, leading to insulin deficiency, in type 2 diabetes insulin resistance as well as impaired insulin secretion are present; mechanisms that interact closely in the development of glucose intolerance. Strong genetic and environmental factors operate with regard to both types. The reduction of the life expectancies for type 1 and type 2 diabetes is contingent upon the appearance of micro- and/or macrovascular complications. At the top of the mortality statistics are patients suffering from cardiovascular and/or kidney diseases. However, by applying metabolic control and by means of other intervention strategies the prognoses for diabetic patients can be improved significantly.


Complex central nervous system malformations in a Dutch Warmblood foal.
A neonatal Dutch Warmblood colt was evaluated for inability to stand, incoordination and intention tremor. Despite partial improvement in clinical signs during the first 4 days of hospitalization, neurological deficits remained. Magnetic resonance imaging identified a unilateral infratentorial arachnoid cyst-like lesion with ipsilateral compression and displacement of the cerebellar hemisphere, absent corpus collosum, polymicrogyria, suspect leukoencephalopathy, and noncompressive occipitoatlantal malformation. Improvement in clinical signs during the first 6 months of life suggests that horses can survive with complex congenital neurological malformations, but prognosis for athletic performance is poor. The accessibility of magnetic resonance imaging should improve the diagnostic accuracy of central nervous system disorders in neonatal foals in which congenital malformations are suspected. Euthanasia often is elected in foals with suspected congenital central nervous system disorders because of poor prognosis for athletic performance, limiting understanding of clinical progression in these cases.


Protocol biopsy: today's fine-needle aspiration biopsy?
This counter view of protocol biopsy suggests that the widespread clinical use of this technique may be questionable. It may remain primarily a valuable research tool. Cost and risk remain as major issues. Be it screening by routine computed tomography scan for apparently normal people or routine biopsy of normal functioning kidneys there is always the risk that more harm than good might be done. The proof of benefit should be strong (scientifically strong), which requires confirmation and reproducibility of controlled trials. Patients need to know how protocol biopsy is to be used (research, management or both) and the strength of the scientific evidence concerning benefit in long-term management.


Internal Physiological Load Measured Using Training Impulse in Varsity Men's and Women's Ice Hockey Players Between Game Periods.
Bigg, JL, Gamble, ASD, and Spriet, LL. Internal physiological load measured using training impulse in varsity men's and women's ice hockey players between game periods. J Strength Cond Res 35(10): 2824-2832, 2021-This study quantified internal load in male and female ice hockey players throughout a season, with comparisons between game periods and match outcome. Twenty-seven male and 24 female varsity ice hockey players participated in this longitudinal prospective cohort study monitoring internal load, using Banister's training impulse (TRIMP). Data were assessed according to game periods, match outcome (win or loss), and games played in noncongested (1 game/wk) or congested (2 + games/wk) weeks. Statistical significance was considered at p < 0.05. The TRIMP for period 1 for both male (25 ± 16 arbitrary units [AU]) and female (23 ± 19 AU) players was significantly lower than period 3 (males: 30 ± 21 AU; p = 0.001; females: 29 ± 21 AU; p = 0.003) but not period 2 (males: 27 ± 17 AU; p = 0.183; females: 27 ± 19 AU; p = 0.681). There were no differences in TRIMP within any period between games resulting in a win compared with a loss. Overall, there were no differences in TRIMP between male and female players. However, when stratified by position, male forwards experienced greater TRIMP than female forwards (p < 0.001 for all periods), whereas female defense had greater TRIMP than male defense (p ≤ 0.032 for all periods). There were no differences between noncongested and congested week games and no differences in TRIMP between nonback-to-back and back-to-back games, or the first and second games played of a back-to-back series. This study measured physiological demand throughout the periods of ice hockey games in men and women and concluded that internal load was highest in the third period. Understanding the demands throughout a game can provide information to coaches and players that would be useful in managing fatigue and optimizing physical performance.


Underlying dimensions and individual differences in auditory, visual, and auditory-visual vowel perception by hearing-impaired children.
Vowel perception studies were conducted on a group of four adolescent children with congenital profound sensorineural hearing impairments in the three conditions of audition alone, vision alone, and audition plus vision. Data were analyzed using the ALSCAL multidimensional scaling procedure to identify the underlying dimensions and individual differences in dimension emphasis. The three dimensions obtained from the analysis of data for the audition alone condition were interpreted as the parameters of first and second formant frequencies, and vowel length. The one dimension for the vision alone condition was interpreted as the parameter of the width of the internal lip opening. The three dimensions for the audition plus vision condition were interpreted as the parameters of first formant frequency, vowel length, and the width of the internal lip opening. Subject variations in parameter preferences were observed for the audition alone and audition plus vision conditions but not for the vision alone condition.


Mutagen sensitivity in patients with head and neck cancers: a biologic marker for risk of multiple primary malignancies.
Eighty-four patients with head and neck cancers were evaluated for in vitro sensitivity to mutagens and then followed longitudinally for development of multiple primary malignancies. We assessed mutagen sensitivity by exposing lymphocytes to bleomycin in vitro and quantitating the bleomycin-induced chromosomal breaks per cell. The mutagen-hypersensitive patients, ie, those who expressed greater than 1.0 break per cell, were significantly more likely to develop multiple primary cancers than were patients who were less sensitive (less than or equal to 1.0 break per cell) (relative risk = 4.4; 95% confidence limits = 1.2, 15.8). This relationship was independent of age, sex, site, and treatment of first primary cancer and tobacco or alcohol exposures. Sensitivity to bleomycin-induced chromosomal damage serves as an indicator of genetic susceptibility to multiple primary malignancies in patients with head and neck cancers.


Utilizing dental hygienists to undertake dental examination and referral in residential aged care facilities.
The Australian population is ageing, and a growing proportion of elderly Australians are now living in residential aged care facilities (RACFs). These residents are commonly dependent on others for their daily oral hygiene care and often display high levels of plaque and calculus. With declining edentulism rates, periodontal disease is becoming more prevalent in this population. The aim of this study was to investigate the ability of a dental hygienist to undertake a dental examination for residents of aged care facilities, devise a periodontal and preventive treatment plan and refer patients appropriately to a dentist. A total of 510 residents from 31 Victorian RACFs were examined, with 275 dentate residents included in this study. Between May 2005 and June 2006, residents were examined by a single experienced dental epidemiologist and one of four dental hygienists using a plane mouth mirror and periodontal probe. A total of 510 residents from 31 RACFs had a dental examination from a dentist and one of four dental hygienists. The treatment needs of residents examined were high, with nearly all of the 275 dentate residents requiring preventive and periodontal treatment, and three-quarters requiring referral to a dentist for treatment. There was excellent agreement between the dentist and hygienists regarding the decision to refer residents to a dentist for treatment, with high sensitivity (99.6%) and specificity (82.9%). Only 8.0% of residents were referred by a hygienist to a dentist when the dentist considered that no referral was required. Dental hygienists have the skills and knowledge necessary for undertaking a dental examination for residents, correctly identifying the majority of residents who require a referral to a dentist. They are capable of formulating appropriate dental hygiene treatment plans for residents of aged care facilities. It is recommended that there should be greater utilization of hygienists in the provision of dental care to residents of aged care facilities, as a safe, efficient and effective use of health resources.


[The hemodynamic effect on the spatial organization of atherosclerotic lesions in the human aorta. Plaques at the sites of arterial branching].
By means of light microscopy of whole-mounted membranous preparations and scanning electron microscopy differences of the three-dimensional organization in the macroscopically intact and atherosclerotic human aortic intima in the sites of intercostal artery ostium were investigated. It was shown that the process of atherogenesis begins in the lateral areas and later involves the site of the entry. The flow divider does not contain lipids and resembles fibrous cap of the plaque. Such differences in the three-dimensional organization are accounted for by the local hemodynamic properties.


Highly cited publication performance in the ophthalmology category in the Web of Science database: a bibliometric analysis.
To determine and evaluate the features of highly cited articles (HCAs) in the ophthalmology category in the Science Citation Index Expanded (SCI-EXPANDED) from 1991 to 2020. The Web of Science Core Collection documents with at least 100 citations from their publication year until December 31, 2020, were evaluated as highly cited. The examined features were the distribution of yearly output and its average number of per publication, HCAs, authors, institutions, journals, and nations. The publication performance of nations and organizations was assessed using six publication indicators. The Y-index was employed to compare the research outputs of various authors. Publications that had cited the most references were highly published in high-impact factor journals. The United States of America came out on top across all six publication indicators, and it was home to eight of the top 10 most productive institutions. The articles written by Breivik et al (2006) and Farrar et al (2001) were highly cited and had a significant impact in 2020. The authors had a higher number of highly cited articles published as corresponding authors than as first authors. The findings of the present study highlight the current scope of global research in ophthalmology. The findings can help policy-makers and advisory groups of research centers to develop future policies. In addition, the findings can guide researchers in this field.


Hyaluronic-Acid-Presenting Self-Assembled Nanoparticles Transform a Hyaluronidase HYAL1 Substrate into an Efficient and Selective Inhibitor.
In this study, an original method of macromolecular design was used to develop a hyaluronidase-1 (HYAL1) inhibitor from its principal substrate, hyaluronic acid (HA). HA-based nanoparticles (HA-NP) were obtained by copolymer self-assembly and their effects on HYAL1 activity were investigated by combining different analytical tools. Compared to HA, HA-NP exhibited an enhanced stability against HYAL1 degradation while maintaining its interaction with the HA receptors CD44 and aggrecan. HA-NP displayed a strong and selective inhibition of HYAL1 activity and retarded the hydrolysis of higher-molar-mass HA in solution. A co-nanoprecipitation process was used to formulate a range of hybrid nanoparticle samples, which demonstrated the specificity and efficiency of HA-NP in HYAL1 inhibition.


Delayed Expression of PD-1 and TIGIT on HIV-Specific CD8 T Cells in Untreated HLA-B*57:01 Individuals Followed from Early Infection.
While the relationship of protective human leukocyte antigen (HLA) class I alleles and HIV progression is well defined, the interaction of HLA-mediated protection and CD8 T-cell exhaustion is less well characterized. To gain insight into the influence of HLA-B*57:01 on the deterioration of CD8 T-cell responses during HIV infection in the absence of antiretroviral treatment, we compared HLA-B*57:01-restricted HIV-specific CD8 T-cell responses to responses restricted by other HLA class I alleles longitudinally after control of peak viremia. Detailed characterization of polyfunctionality, differentiation phenotypes, transcription factor, and inhibitory receptor expression revealed progression of CD8 T-cell exhaustion over the course of the infection in both patient groups. However, early effects on the phenotype of the total CD8 T-cell population were apparent only in HLA-B*57-negative patients. The HLA-B*57:01-restricted, HIV epitope-specific CD8 T-cell responses showed beneficial functional patterns and significantly lower frequencies of inhibitory receptor expression, i.e., PD-1 and coexpression of PD-1 and TIGIT, within the first year of infection. Coexpression of PD-1 and TIGIT was correlated with clinical markers of disease progression and declining percentages of the T-bethi Eomesdim CD8 T-cell population. In accordance with clinical and immunological deterioration in the HLA-B*57:01 group, the difference in PD-1 and TIGIT receptor expression did not persist to later stages of the disease.IMPORTANCE Given the synergistic nature of TIGIT and PD-1, the coexpression of those inhibitory receptors should be considered when evaluating T-cell pathogenesis, developing immunomodulatory therapies or vaccines for HIV, and when using immunotherapy or vaccination for other causes in HIV-infected patients. HIV-mediated T-cell exhaustion influences the patient´s disease progression, immune system and subsequently non-AIDS complications, and efficacy of vaccinations against other pathogens. Consequently, the possibilities of interfering with exhaustion are numerous. Expanding the use of immunomodulatory therapies to include HIV treatment depends on information about possible targets and their role in the deterioration of the immune system. Furthermore, the rise of immunotherapies against cancer and elevated cancer incidence in HIV-infected patients together increase the need for detailed knowledge of T-cell exhaustion and possible interactions. A broader approach to counteract immune exhaustion to alleviate complications and improve efficacy of other vaccines also promises to increase patients' health and quality of life.


Combination of specific allergen and probiotics induces specific regulatory B cells and enhances specific immunotherapy effect on allergic rhinitis.
The therapeutic efficacy of allergen specific immunotherapy (SIT) on allergic diseases is to be improved. Probiotics can regulate immune response. This study aims to promote the effect of SIT on allergic rhinitis (AR) by co-administration with Clostridium butyricum (Cb). In this study, patients with AR sensitized to mite allergens were enrolled to this study, and treated with SIT or/and Cb. The therapeutic efficacy was evaluated by the total nasal symptom scores (NSS), medication scores, serum specific IgE levels and T helper (Th)2 cytokine levels. The improvement of immune regulation in the AR patients was assessed by immunologic approaches. The results showed that treating AR patients with SIT alone markedly reduced NSS and medication scores; but did not alter the serum specific IgE, Th2 cytokines and skin prick test (SPT) index. The clinical symptoms on AR in SIT group relapsed one month after stopping SIT. Co-administration of Cb significantly enhanced the efficacy of SIT on AR as shown by suppression of NSS, medication scores, serum specific IgE, Th2 cytokines and SPT index; the regulatory B cell frequency was also markedly increased. Such an effect on AR was maintained throughout the observation period even after stopping the treatment. Butyrate blocked the activation of histone deacetylase-1, the downstream activities of epsilon chain promoter activation, and the IgE production in the antigen specific B cells. On the other hand, butyrate induced the IL-10 expression in B cells with a premise of the B cell receptor activation by specific antigens. In conclusion, administration with Cb can markedly enhance the efficacy of SIT on AR.


Effect of a neutrophil elastase inhibitor on acute lung injury after cardiopulmonary bypass.
Cardiopulmonary bypass (CPB) has been implicated as a cause of acute lung injury (ALI) in cardiac surgical patients. We used a bronchoscopic microsampling (BMS) probe to examine alveolar biochemical constituents and evaluated the effect of sivelestat sodium hydrate, a novel synthesized polymorphonuclear (PMN) neutrophil elastase inhibitor, on ALI induced by CPB. Twelve patients undergoing aortic valve replacement were treated with either sivelestat 0.2 mg/kg/h (sivelestat group, n=6) or 0.9% saline (control group, n=6) from the start of surgery. Samples were collected by the BMS probe at three time points: after tracheal intubation, 1 h after CPB introduction, and 3 h after CPB termination. Pulmonary function was assessed perioperatively. There were no differences in baseline characteristics. The concentration of PMN elastase was significantly suppressed in the sivelestat group, compared with the control group (P=0.001). The sivelestat group also had lower levels of interleukin-6 and interleukin-8. Alveolar-arterial oxygen difference markedly increased, and a worsening of the PaO(2)/FiO(2) ratio indicated severe impairment after CPB. However, sivelestat attenuated the pattern of physiological deterioration of gas exchange. Sivelestat may attenuate neutrophil elastase or proinflammatory cytokines, and improve pulmonary dysfunction in patients undergoing CPB.


Amylase secretion in response to activation of different autonomic receptors in the rabbit parotid gland.
The contribution by different autonomic receptors to the amylase secretion from the parotid gland of the anaesthetized rabbit was studied as the response to various parasympathomimetic and sympathomimetic drugs. Amylase secretion by infusions of pilocarpine and parasympathetic nerve stimulation was low, but regularly higher in response to pilocarpine than to parasympathetic nerve stimulation. These effects were reduced to the same level by beta-adrenoceptor block indicating the presence and for pilocarpine also the release of catecholamines, probably from the adrenals. Isoprenaline injections produced a high amylase secretion, that was blocked by atenolol, indicating that predominantly beta 1-adrenoceptors were activated. Phenylephrine was without amylase secretory effects. By accepting isoprenaline maximum as maximum for sympathetically produced amylase secretion, a theoretical frequency-response relationship for amylase secretion by sympathetic nerve stimulation could be calculated: ED50 was 0.9 Hz. The results indicate that under experimental conditions in vivo there are certain differences between the rat and the rabbit parotid glands in the autonomic control not only of fluid, but particularly of amylase secretion.


Chloroplast Lipids Metabolism and Function. A Redox Perspective.
Plant productivity is determined by the conversion of solar energy into biomass through oxygenic photosynthesis, a process performed by protein-cofactor complexes including photosystems (PS) II and I, and ATP synthase. These complexes are embedded in chloroplast thylakoid membrane lipids, which thus function as structural support of the photosynthetic machinery and provide the lipid matrix to avoid free ion diffusion. The lipid and fatty acid composition of thylakoid membranes are unique in chloroplasts and cyanobacteria, which implies that these molecules are specifically required in oxygenic photosynthesis. Indeed, there is extensive evidence supporting a relevant function of glycerolipids in chloroplast biogenesis and photosynthetic efficiency in response to environmental stimuli, such as light and temperature. The rapid acclimation of higher plants to environmental changes is largely based on thiol-based redox regulation and the disulphide reductase activity thioredoxins (Trxs), which are reduced by ferredoxin (Fdx) via an Fdx-dependent Trx reductase. In addition, chloroplasts harbour an NADPH-dependent Trx reductase C, which allows the use of NADPH to maintain the redox homeostasis of the organelle. Here, we summarise the current knowledge of chloroplast lipid metabolism and the function of these molecules as structural basis of the complex membrane network of the organelle. Furthermore, we discuss evidence supporting the relevant role of lipids in chloroplast biogenesis and photosynthetic performance in response to environmental cues in which the redox state of the organelle plays a relevant role.


Prevention of Biomaterial Infection by Pre-Operative Incubation with Human Cells.
Cells of tissues and biofilm forming bacteria compete for the living space on the surface of an implant. We hypothesized the incubation of the implant (titanium, polydimethylsiloxane, and polystyrene surface) with human cells before implantation as a strategy to prevent bacterial adhesion and biofilm formation. After 24 hours of incubation with human osteogenic sarcoma SaOS-2 cells (1 × 105 cells/mL), the materials were incubated for 4.5 hours or two days with Staphylococcus aureus in serial 1:10 dilutions of 108 colony-forming units/mL. The bacterial adherence and biofilm biomass on materials pre-incubated with SaOS-2 cells were compared with our previous results on materials incubated only with bacteria or in simultaneous co-culture of SaOS-2 cells and S. aureus. Fluorescent microscopy and crystal violet stain were used. The number of viable SaOS-2 and bacterial cells present was tested using colorimetric methods (MTT, LDH) and drop plate method, respectively. The pre-treatment with human cells was associated with a reduction of bacterial colonization of the biomaterial at 4.5 hours and 48 hours compared with the non-pre-treated materials. The presence of bacteria decreased the number of viable human cells on all materials. ( Supplementary Fig. 1 ; see online supplementary materials at www.liebertpub.com/sur ). These results suggest that the pre-operative incubation of prostheses with host cells could prevent infection of biomaterials.


Preinvasive disease of the airway.
Squamous cell carcinoma of the lung arises from preinvasive progenitors in the central airways. The archetypal model appears to be a stepwise morphological progression until there is invasion of the basement membrane. However, not every lesion appears to follow this course and many individuals can have stable disease, or indeed regress to normal epithelium. From our increased understanding of the molecular pathology it is becoming apparent that the respiratory epithelium accumulates progressive genetic and epigenetic insults in response to carcinogens. Still, little is known about how to predict those 'at risk' of progression, and it is likely that in the future molecular signatures will underpin prediction models of developing invasive lung cancer. Currently, autofluorescence bronchoscopy gives us the ability to follow the natural history of these lesions, with the prospect that detecting and treating lesions early may improve survival. However, treatment remains controversial, and radical therapies are offered to individuals with carcinoma in situ who may never develop invasive cancer. This has paved the way for the use of minimally invasive bronchoscopic treatments, which, while apparently effective, have not been tested in randomised controlled trials. In this paper we describe the known biology and natural history of preinvasive lesions and review the current treatment strategies.


Stabilization of body balance with Light Touch following a mechanical perturbation: Adaption of sway and disruption of right posterior parietal cortex by cTBS.
Light touch with an earth-fixed reference point improves balance during quite standing. In our current study, we implemented a paradigm to assess the effects of disrupting the right posterior parietal cortex on dynamic stabilization of body sway with and without Light Touch after a graded, unpredictable mechanical perturbation. We hypothesized that the benefit of Light Touch would be amplified in the more dynamic context of an external perturbation, reducing body sway and muscle activations before, at and after a perturbation. Furthermore, we expected sway stabilization would be impaired following disruption of the right Posterior Parietal Cortex as a result of increased postural stiffness. Thirteen young adults stood blindfolded in Tandem-Romberg stance on a force plate and were required either to keep light fingertip contact to an earth-fixed reference point or to stand without fingertip contact. During every trial, a robotic arm pushed a participant's right shoulder in medio-lateral direction. The testing consisted of 4 blocks before TMS stimulation and 8 blocks after, which alternated between Light Touch and No Touch conditions. In summary, we found a strong effect of Light Touch, which resulted in improved stability following a perturbation. Light Touch decreased the immediate sway response, steady state sway following re-stabilization, as well as muscle activity of the Tibialis Anterior. Furthermore, we saw gradual decrease of muscle activity over time, which indicates an adaptive process following exposure to repetitive trials of perturbations. We were not able to confirm our hypothesis that disruption of the rPPC leads to increased postural stiffness. However, after disruption of the rPPC, muscle activity of the Tibialis Anterior is decreased more compared to sham. We conclude that rPPC disruption enhanced the intra-session adaptation to the disturbing effects of the perturbation.


In vitro fertilization is associated with placental accelerated villous maturation.
Accelerated placental maturation is regarded as a sign of vascular malperfusion and is often interpreted as a compensatory response by the placenta. In vitro embryo culture affects placental development. This study assessed placental maturation in spontaneous conceived and in vitro conceived pregnancies. Retrospective cohort study on a single center between 2014 and 2017. For this study, preterm placentas of singleton pregnancies between 24 and 36 weeks were considered. Routine placental examinations were retrospectively reviewed. During the considered period, 423 placentas of singleton pregnancies were assessed. Three hundred ninety-six placentas were from spontaneous conception and 20 from in vitro fertilization and embryo transfer (IVF/ET). IVF/ET was significantly associated with accelerated villous maturation (AVM) and distal villous hypoplasia (DVH) (P<0.05). Placental AVM and DVH were significantly associated with in vitro fertilization in singleton pregnancies. This result supports the hypothesis that AVM is a compensatory response by the placenta to improve its transport capacity in specific settings such as in vitro fertilization.


Common and separate origins of the left and right inferior phrenic artery with a review of the literature.
In a 94-year-old male cadaver, upon which routine dissection was being conducted, a rare variation was found in the gastrophrenic trunk (GPT), the common trunk of the left gastric artery (LGA), right inferior phrenic artery (RIPA), and left inferior phrenic artery (LIPA); the GPT arises from the abdominal aorta. A hepatosplenic trunk accompanied the variation. In this variation, the RIPA first branched from the GPT and then to the LIPA and LGA. Variations in the common trunk of the LIPA and RIPA in the GPT are common, but to our knowledge, a variation (separate inferior phrenic artery in the GPT) similar to our findings has not been previously reported. We discuss the incidence and developmental and clinical significance of this variation with a detailed review of the literature. Knowledge of such a case has important clinical significance for invasive and non-invasive arterial procedures. Therefore, different variations concerning the LGA and inferior phrenic artery should be considered during surgical and non-surgical evaluations.


The protective role of thiola and soybean seeds against the genotoxicity induced by potassium dichromate in mice.
The genotoxic potential of potassium dichromate (K(2)Cr(2)O(7)) was evaluated in vivo in mice using different mutagenic end points. Chromosomal aberrations in bone-marrow and spermatocytes as well as sperm abnormalities in the tested mice were determined. The doses used were 3, 6, 12 mg K(2)Cr(2)O(7)kg(-1) body weight which correspond to 1/16, 1/8, 1/4 the experimental LD(50), respectively. The protective roles of i.p. injection with thiola (a synthetic sulfhydryl compound) at 20 mg kg(-1) body weight and feeding treatment with soybean seeds (30% of the diet) were also studied. For chromosomal aberration analysis, subacute treatment for a period of 3 weeks were performed. All the tested doses of K(2)Cr(2)O(7) induced a statistically significant increase in the percentage of chromosomal aberrations in both somatic and germ cells with dose and time relationships. The percentage of the induced chromosomal aberrations was significantly minimized in all groups of mice i.p. treated with thiola or fed soybean seeds during the period of treatment. Potassium dichromate also induced a significant increase (P<0.01) in the percentage of abnormal sperms at the doses 6 and 12 mg kg(-1) body weight. Such percentage reached 7.52+/-0.45, 5.50+/-0.53 and 4.28+/-0.45 in mice treated with the highest tested dose of K(2)Cr(2)O(7), K(2)Cr(2)O(7) and thiola; K(2)Cr(2)O(7) and soybean, respectively compared with 2.14+/-0.33 for the control. In conclusion, the results demonstrate the genotoxic effect of potassium dichromate in mice. The results also confirm the protective role of thiola and soybean seeds against the genotoxicity of potassium dichromate.


Plasmodial modifications of erythrocyte surfaces.
The maturation of malarial parasites in red blood cells produces major alterations in the composition and properties of the host cell surfaces. Existing surface-exposed proteins are modified and new antigenic glycoproteins are synthesized by the parasite and inserted into the membrane. Some of the neoproteins are associated with surface excrescences on the host cells and in some cases these foster adhesion of those cells to capillary endothelium. The erythrocyte endoskeleton is degraded and in association the infected cells become deformed and lose pliability. An increase in intracellular Ca2+ may contribute to the changes in host cells surfaces.


[Pigmented dermatofibrosarcoma protuberans (Bednar's tumor)].
Pigmented dermatofibrosarcoma protuberans, first described by Bednar under the term storiform neurofibroma, is an infrequent neoplasm accounting for 1 to 5% of cases of dermatofibrosarcoma protuberans. Bednar's tumor is composed of spindle shaped cells arranged in a distinctive storiform or carthwheel pattern, and melanin-containing dendritic cells scattered within the tumor. The differential diagnosis with (non-pigmented) dermatofibrosarcoma protuberans is based on the presence of this population of pigmented cells. Two cases of pigmented dermatofibrosarcoma protuberans (Bednar's tumor) are reported here in, and a discussion follows on the clinicopathological features of this neoplasm and the different hypotheses on its histogenesis.


Clinical outcomes in cats with renal carcinoma undergoing nephrectomy: A retrospective study.
Renal carcinomas (RC) are uncommonly encountered in feline medicine. Limited information regarding clinical presentation and postoperative outcomes is available. The purpose of this multi-institutional, retrospective study was to describe the presenting features and clinical outcomes of cats with RC undergoing nephrectomy. Thirty-six client-owned cats were included. Medical records from participating institutions were searched to identify cats that had a histopathologic diagnosis of RC and underwent nephrectomy from January 2001 to October 2021. The most common presenting complaints were weight loss (36.1%) and hyporexia (30.6%). Based on preoperative imaging and intraoperative findings, eight cats had suspected metastasis at the time of surgery (22.2%). Twenty-eight cats survived to discharge (77.8%). Median progression free interval (PFI) could not be determined, as only six cats developed suspected recurrence (16.7%) and seven cats developed suspected metastasis (19.4%). The all-cause median survival time (MST) was 203 days (95% confidence interval [CI]: 84, 1379 days). When cases that died prior to discharge were excluded, MST increased to 1217 days (95% CI: 127, 1641 days). One-year, two-year, and three-year survival rates were all 40.4%. Neither renal tumour histologic subtype nor the presence of preoperative azotemia, anaemia, erythrocytosis, haematuria, or suspected metastasis at diagnosis were found to influence survival. For cats surviving to discharge, prolonged survival times were possible. Further studies are necessary to elucidate other potential prognostic factors, the utility of postoperative adjuvant treatment, and to identify cats at-risk of mortality in the perioperative period.


Recent advances in the construction of fluorescent metallocycles and metallocages via coordination-driven self-assembly.
During the last few years, the construction of fluorescent metallocycles and metallocages has attracted considerable attention because of their wide applications in fluorescence detection of metal ions, anions, or small molecules, mimicking complicated natural photo-processes, and preparing photoelectric devices, etc. This perspective focuses on the recent advances in the construction of a variety of fluorescent metallocycles and metallocages via coordination-driven self-assembly. In addition, the fluorescence properties and the applications of these organometallic architectures have also been discussed.


Xerostomia: its prevalence and associations in the adult Australian population.
Little is known of the occurrence of dry mouth among Australians. To describe the prevalence and associations of xerostomia in a nationally representative sample of Australian adults. Dentate persons aged 15+ years were asked 'How often does your mouth feel dry?' (response options 'never', 'occasionally', 'frequently' or 'always'). Those responding 'frequently' or 'always' were classified as xerostomic. The prevalence of xerostomia was 13.2% (95% CI 12.4, 14.0). It ranged from 9.3% (95% CI 7.9, 10.8) among 15-to-34-year-old to 26.5% (95% CI 23.3, 30.0) among those aged 75+ years. Prevalence was higher in the lowest income tertiles (24.5%, 95% CI 22.6, 26.5), lowest SEIFA tertiles (15.7%, 95% CI 14.2, 17.3), those who were dentally uninsured (16.6%, 95% CI 15.4, 17.8) and those with unfavourable dental visiting patterns (18.1%, 95% CI 16.2, 20.1). More than one in ten Australians experience dry mouth. Among older Australians, this estimate is one in four. With an ageing, medicated population that is increasing in size, xerostomia is a condition that needs to be better understood, recognized and managed by both dental and general health practitioners.


Epidemiological trends among the population with chronic HCV infection in the Netherlands.
As the field of antiviral therapy for chronic HCV infection is rapidly evolving, this study aimed to assess the epidemiological changes in patient and disease characteristics among individuals with chronic HCV infection. This study included all consecutive patients with chronic HCV monoinfection who were referred between 1990 and 2013 to the Erasmus MC University Medical Center Rotterdam, a large tertiary centre in the Netherlands. To identify trends over time, the study population was divided into six equal eras based on date of first visit to the outpatient clinic. A total of 1,779 patients were diagnosed with chronic HCV infection. Mean age increased over time from 43.6 (sd 13.8) years to 51.7 (sd 11.2) years (P<0.001). The number of patients who were referred with cirrhosis increased over time, from 31 (25%) patients in Era 1 to 118 (42%) patients in Era 6 (P<0.001), respectively. More patients were referred with HCV genotype 1a and 3 in the last era, with 27 (48.2%) and 15 (14.0%) patients in Era 1 and 58 (54.2%) and 60 (21.8%) patients in Era 6 (P<0.001 both), respectively. The vast majority of patients (69.5%) were born between 1950 to 1975, with 62.5% of the patients being born between 1945 and 1965. The HCV-infected population is ageing and is more often referred with severe liver disease. This study stresses the importance of urgently implementing national HCV screening programmes in order to be able to decrease the future burden of chronic HCV infection in the Netherlands.