Lipid concomitant γ-oryzanol decreased oil absorbency of French fries by changing the microstructure of French fries and physical properties of frying oil.
The aim of this research was to evaluate the possibility of lipid concomitant γ-oryzanol reducing oil absorbency of fried foods and the underlying mechanism. Therefore, the influence of γ-oryzanol on moisture and oil content, and distribution and micromorphology of French fries and the viscosity, fatty acid composition and total polar compounds content of rice bran oil (RBO) after frying were studied. Our results showed that the incorporation of low concentration of γ-oryzanol (LAG) (5.754 g/kg) decreased the oil absorbency and porous structure of French fries during frying. Additionally, LAG incorporation inhibited the degradation of linoleic acid, decreased the growth rate of saturated fatty acids, total polar compounds and viscosity of frying oil. Consequently, it was recommended to incorporate small amount of γ-oryzanol in frying oil because it could inhibit oil absorption behavior of French fries. This article is protected by copyright. All rights reserved.


First In-Human Experience With Complete Integration of Neuromodulation Device Within a Customized Cranial Implant.
Neuromodulation devices have the potential to transform modern day treatments for patients with medicine-resistant neurological disease. For instance, the NeuroPace System (NeuroPace Inc, Mountain View, California) is a Food and Drug Administration (FDA)-approved device developed for closed-loop direct brain neurostimulation in the setting of drug-resistant focal epilepsy. However, current methods require placement either above or below the skull in nonanatomic locations. This type of positioning has several drawbacks including visible deformities and scalp pressure from underneath leading to eventual wound healing difficulties, micromotion of hardware with infection, and extrusion leading to premature explantation. To introduce complete integration of a neuromodulation device within a customized cranial implant for biocompatibility optimization and prevention of visible deformity. We report a patient with drug-resistant focal epilepsy despite previous seizure surgery and maximized medical therapy. Preoperative imaging demonstrated severe resorption of previous bone flap causing deformity and risk for injury. She underwent successful responsive neurostimulation device implantation via complete integration within a clear customized cranial implant. The patient has recovered well without complication and has been followed closely for 180 d. Device interrogation with electrocorticographic data transmission has been successfully performed through the clear implant material for the first time with no evidence of any wireless transmission interference. Cranial contour irregularities, implant site infection, and bone flap resorption/osteomyelitis are adverse events associated with implantable neurotechnology. This method represents a novel strategy to incorporate all future neuromodulation devices within the confines of a low-profile, computer-designed cranial implant and the newfound potential to eliminate contour irregularities, improve outcomes, and optimize patient satisfaction.


Why Lyme disease is common in the northern US, but rare in the south: The roles of host choice, host-seeking behavior, and tick density.
Lyme disease is common in the northeastern United States, but rare in the southeast, even though the tick vector is found in both regions. Infection prevalence of Lyme spirochetes in host-seeking ticks, an important component to the risk of Lyme disease, is also high in the northeast and northern midwest, but declines sharply in the south. As ticks must acquire Lyme spirochetes from infected vertebrate hosts, the role of wildlife species composition on Lyme disease risk has been a topic of lively academic discussion. We compared tick-vertebrate host interactions using standardized sampling methods among 8 sites scattered throughout the eastern US. Geographical trends in diversity of tick hosts are gradual and do not match the sharp decline in prevalence at southern sites, but tick-host associations show a clear shift from mammals in the north to reptiles in the south. Tick infection prevalence declines north to south largely because of high tick infestation of efficient spirochete reservoir hosts (rodents and shrews) in the north but not in the south. Minimal infestation of small mammals in the south results from strong selective attachment to lizards such as skinks (which are inefficient reservoirs for Lyme spirochetes) in the southern states. Selective host choice, along with latitudinal differences in tick host-seeking behavior and variations in tick densities, explains the geographic pattern of Lyme disease in the eastern US.


Molecular dynamics simulations of binary sphere mixtures.
Explicit simulations of fluid mixtures of highly size-dispersed particles are constrained by numerical challenges associated with identifying pair-interaction neighbors. Recent algorithmic developments have ameliorated these difficulties to an extent, permitting more efficient simulations of systems with many large and small particles of disperse sizes. We leverage these capabilities to perform molecular dynamics simulations of binary sphere mixtures with elastically stiff particles approaching the hard sphere limit and particle size ratios of up to 50, approaching the colloidal limit. The systems considered consist of 500 large particles and up to nearly 3.6×10^{6} small particles with total particle volume fractions up to 0.51. Our simulations confirm qualitative predictions for correlations between large particles previously obtained analytically and for simulations employing effective depletion interactions, but also reveal additional insights into the near-contact structure that result from the explicit treatment of the small particle solvent. No spontaneous crystal nucleation was observed during the simulations, suggesting that nucleation rates in the fluid-solid coexistence region are too small to observe crystal nucleation for feasible simulation system sizes and timescales.


Left ventricular electrical activation during right ventricular pacing in heart failure patients with LBBB: visualization by electrocardiographic imaging and implications for cardiac resynchronization therapy.
Assess effect of right ventricular pacing (RVP) on left ventricular (LV) activation in heart failure patients with left bundle branch block (LBBB). LV activation during RVP is regarded as similar to LBBB; hence novel CRT algorithms may avoid RVP by adopting "fusion" pacing with intrinsic RBB-mediated conduction. However, other CRT techniques demand RV paced wavefronts for optimal resynchronization. Appropriate selection may require attention to interaction between RVP-generated wavefronts with preexisting conduction abnormalities posed by LBBB i.e. transseptal delay and LV activation. We hypothesized that LV activation during RVP would differ to LBBB. Eleven patients (59±19years, 8 male, LV ejection fraction 25±10%; ischemic etiology 45%) were studied 5.4±5months after CRT implant. All had intact AV conduction with LBBB (PR interval 204±55; QRS 167±27ms) prior to CRT. None had mid-septal/outflow tract lead positions. Using non-invasive electrocardiographic imaging (ECGI), LV activation was contrasted in each patient between intrinsic conduction and RVP with minimized AV interval (i.e. committing ventricular excitation to the paced wavefront). RVP affected LV activation variably. Transseptal time decreased in 64% of patients. More LV conduction barriers were created than resolved, slowing LV free wall activation from 67±29ms during intrinsic conduction to 104±24ms with RVP (p=0.025). The load of late-activated LV myocardium increased in 73% but decreased in 27% patients. Changes were not reflected by QRS duration. Ultimate action of RVP in any patient depended on summary effects of transseptal breakthrough and following LV activation. If both were enhanced then LV preexcitation occurred. If one was delayed but other accelerated, then the outcome of their balance determined the ultimate effect on LV depolarization. RVP may aggravate or resolve LBBB-induced conduction problems at one or more levels. Its avoidance vs integration (or timing relative to LV pacing) during CRT depends on its electrical action in any particular individual.


Obesity bias in primary care providers.
At the forefront of the obesity epidemic, obesity bias is an under-recognized and widely prevalent barrier to optimal care of the obese patient, even among primary care professionals. Recommendations for the reduction of obesity bias include increasing provider awareness about the complex etiology of obesity and the difficulties obtaining sustainable weight loss. Obesity bias was measured in primary care professionals (n=233) participating in a continuing education program, using the Anti-Fat Attitudes Questionnaire (AFAQ). Three sub-factors, "Fear of Fat," "Willpower," and "Dislike," were evaluated. Participants were divided into three primary care experience groups: least experienced (0--9 years, n=67), moderately experienced (10--19 years, n=49), and most experienced (20+ years, n=98). "Fear of Fat" and "Willpower" components were found to be more prevalent than "Dislike"; however, scores on the "Dislike" subscale were highest and significantly more prevalent in the group with the most experience. Results indicated that more experienced primary care professionals reported greater bias toward obese people than less experienced colleagues. Ongoing continuing education that recognizes the wide prevalence of obesity, encourages respect for people of size, and mitigates obesity stigma should be promoted for all providers, particularly those who have been in practice for many years.


Stimulation of the side population fraction of ATDC5 chondroprogenitors by hypoxia.
The influence of oxygen tension on the side population (SP) fraction sorted from ATDC5 chondroprogenitor cells was investigated. ATDC5 cells cultured in normoxia (20%) or hypoxia (1% oxygen) were compared. The SP fraction was significantly higher in the cells cultured in hypoxia. The gene expression of 3 ABC transporters, abcb1a/b (mdr1a/b) and abcg2 (bcrp1) was quantified by RT-PCR. SP cells were characterized by the higher expression of abcb1a. The expression levels of abcb1b and abcg2 were higher than abcb1a. However, there was no significant difference between SP and non-SP fractions in the expression of abcb1b and abcg2. The telomeric repeat amplification protocol assay showed that SP cells tended to show lower telomerase activity than non-SP cells. Chondrogenic properties of ATDC5 cells derived from SP or non-SP were assessed by micromass culture. There were not significant differences between SP and non-SP derived cells in Alcian blue staining and sox9, Aggrecan, Col2a1 and SZP mRNA expression. The results demonstrate that the SP fraction was stimulated by hypoxia and chondrogenic properties of SP and non-SP fraction of ATDC5 cells were similar.


N-acetyl cysteine prevents polymethyl methacrylate bone cement extract-induced cell death and functional suppression of rat primary osteoblasts.
This study examines the cytotoxicity of bone cement extract to osteoblasts and the potential detoxification and restoration of osteoblastic function by an antioxidant amino acid, N-acetyl cysteine (NAC). The osteoblastic cells derived from rat femurs were cultured with extract from polymethyl methacrylate (PMMA)-based bone cement. The calcein and ethidium homodimer staining of the cells after 24-h incubation showed that 23.0% of the cells were dead in the culture with bone cement extract, while the addition of 5 mM NAC into the culture reduced the percentage to 4.3%. Annexin V and propidium iodide-based flow cytometric analysis also revealed that the apoptotic cells present at 15.8% in the culture with bone cement extract was reduced to 2.4% in the culture cotreated with bone cement extract and NAC. Severely suppressed alkaline phosphatase activity and matrix mineralization in the culture with bone cement extract (reduced to 10% and 5%, respectively, compared with the control culture) were restored to a normal level when treated with 5 mM NAC. The bone cement extract-induced, downregulated expression of osteoblastic genes, such as alkaline phosphatase, collagen I, and osteocalcin, was also restored to the baseline level by cotreatment with NAC. The data indicated that the addition of NAC into acrylic bone cement extract remarkably ameliorated the cytotoxicity to osteoblasts and restored their phenotype and function to a biologically significant degree, suggesting the potential usefulness of NAC in developing more biocompatible acrylic bone cement.


Reduced graphene oxide-silsesquioxane hybrid as a novel supercapacitor electrode.
Supercapacitor energy storage devices recently garnered considerable attention due to their cost-effectiveness, eco-friendly nature, high power density, moderate energy density, and long-term cycling stability. Such figures of merit render supercapacitors unique energy sources to power portable electronic devices. Among various energy storage materials, graphene-related materials have established themselves as ideal electrodes for the development of elite supercapacitors because of their excellent electrical conductivity, high surface area, outstanding mechanical properties combined with the possibility to tailor various physical and chemical properties via chemical functionalization. Increasing the surface area is a powerful strategy to improve the performance of supercapacitors. Here, modified polyhedral oligosilsesquioxane (POSS) is used to improve the electrochemical performance of reduced graphene oxide (rGO) through the enhancement of porosity and the extension of interlayer space between the sheets allowing efficient electrolyte transport. rGO-POSS hybrids exhibited a high specific capacitance of 174 F g-1, power density reaching 2.25 W cm-3, and high energy density of 41.4 mW h cm-3 endowed by the introduction of POSS spacers. Moreover, these electrode materials display excellent durability reaching >98% retention after 5000 cycles.


Hearing acuity of children with otitis media with effusion.
Hearing levels are reported for a cohort of 222 infants (aged 7 to 24 months) and 540 older children (aged 2 to 12 years) with otitis media with effusion (OME). The infants had an average speech awareness threshold of 24.6 dB hearing level (HL). The older group had mean bone conduction thresholds less than 10 dB HL, and air conduction thresholds averaged 27 dB HL; however, acuity was 7 dB less impaired at 2,000 Hz. The mean three-frequency pure tone average and speech reception threshold were 24.5 and 22.7 dB, respectively. Hearing acuity was not significantly related to age or previous duration of OME. The otoscopic observation of an air-fluid level or bubbles was associated with less hearing impairment; however, a predictive relationship between hearing levels and tympanogram characteristics could not be demonstrated.


Real-time PCR of single bacterial cells on an array of adhering droplets.
Real-time PCR at the single bacterial cell level is an indispensable tool to quantitatively reveal the heterogeneity of isogenetic cells. Conventional PCR platforms that utilize microtiter plates or PCR tubes have been widely used, but their large reaction volumes are not suited for sensitive single-cell analysis. Microfluidic devices provide high density, low volume PCR chambers, but they are usually expensive and require dedicated equipment to manipulate liquid and perform detection. To address these limitations, we developed an inexpensive chip-level device that is compatible with a commercial real-time PCR thermal cycler to perform quantitative PCR for single bacterial cells. The chip contains twelve surface-adhering droplets, defined by hydrophilic patterning, that serve as real-time PCR reaction chambers when they are immersed in oil. A one-step process that premixed reagents with cell medium before loading was applied, so no on-chip liquid manipulation and DNA purification were needed. To validate its application for genetic analysis, Synechocystis PCC 6803 cells were loaded on the chip from 1000 cells to one cell per droplet, and their 16S rRNA gene (two copies per cell) was analyzed on a commercially available ABI StepOne real-time PCR thermal cycler. The result showed that the device is capable of genetic analysis at single bacterial cell level with C(q) standard deviation less than 1.05 cycles. The successful rate of this chip-based operation is more than 85% at the single bacterial cell level.


[Morphogenesis of cancer of the corpus uteri].
Histological assays of the endometrium in females aged over 48 (curettement performed for metrorrhagia, preparations of the corpus uteri cancer and of the uterus, taken from cadavers of persons having no genital lesions) have demonstrated atrophy and transitional mucosa on which background there occurred microadenomatosis foci in some cases. Enhancement of epithelial atypism, its proliferation and larger microadenomatosis foci, microcarcinoma foci allow microadenomatosis to be referred to as precancer proper.


Effects of benserazide on L-DOPA-derived extracellular dopamine levels and aromatic L-amino acid decarboxylase activity in the striatum of 6-hydroxydopamine-lesioned rats.
Benserazide is commonly used for Parkinson's disease in combination with L-DOPA as a peripheral aromatic L-amino acid decarboxylase (AADC) inhibitor. However, recent studies using intact animals indicate that benserazide acts also in the central nervous system. We determined the influence of benserazide on the central AADC activity in rats with dopaminergic denervation and observed changes in extracellular dopamine (DA) levels after benserazide and L-DOPA administration. First, using in vivo microdialysis technique, we measured extracellular DA levels in the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rats treated with benserazide and L-DOPA. Second, we measured AADC activity in the striatal tissues after benserazide administration. Although administration of 5, 10 and 50 mg/kg benserazide to 6-OHDA-lesioned rats showed an identical increase in exogenous L-DOPA-derived extracellular DA levels, the time to reach the peak DA levels were significantly prolonged by benserazide dose-dependently. The AADC activity in the denervated striatal tissues showed a significant decrease by 10 mg/kg and 50 mg/kg benserazide. These results suggest that benserazide reduces the central AADC activity in the striatum of rats with nigrostriatal denervation, which leads to changes in the metabolism of exogenous L-DOPA. Central activity of AADC inhibitors should be taken into consideration when they are used both in experimental and clinical studies on Parkinson's disease.


NK cell inhibitory receptors prevent tyrosine phosphorylation of the activation receptor 2B4 (CD244).
2B4 is an NK cell activation receptor that can provide a co-stimulatory signal to other activation receptors and whose mode of signal transduction is still unknown. We show that cross-linking of 2B4 on NK cells results in its rapid tyrosine phosphorylation, implying that this initial step in 2B4 signaling does not require coligation of other receptors. Ligation of 2B4 in the context of an NK cell-target cell interaction leads to 2B4 tyrosine phosphorylation, target cell lysis, and IFN-gamma release. Coligation of 2B4 with the inhibitory receptors killer cell Ig-like receptor (KIR)2DL1 or CD94/NKG2 completely blocks NK cell activation. The rapid tyrosine phosphorylation of 2B4 observed upon contact of NK cells with sensitive target cells is abrogated when KIR2DL1 or CD94/NKG2 are engaged by their cognate MHC class I ligand on resistant target cells. These results demonstrate that NK inhibitory receptors can interfere with a step as proximal as phosphorylation of an activation receptor.


Partial deafness treatment with the nucleus straight research array cochlear implant.
The Nucleus Straight Research Array (SRA) cochlear implant has a new 25-mm electrode carrier designed to minimize insertion trauma, in particular allowing easy insertion via the round window. The aims of this study were to measure preoperative to postoperative benefit in terms of speech recognition in quiet and in noise in three groups of patients (electrical complement, EC; electrical stimulation, ES; electro-acoustic stimulation, EAS) with varying levels of low-frequency hearing, and to evaluate the preservation of residual hearing after implantation with the SRA cochlear implant. The study design was prospective with sequential enrolment and within-subject comparisons: 23 adult cochlear implant candidates were divided into three groups according to their level of preoperative residual hearing at 500 Hz (EC ≤50 dB; 50 dB < EAS < 80 dB; ES ≥80 dB). Monosyllabic word recognition using the SRA cochlear implant in combination with residual low-frequency hearing was assessed at 4 and 13 months after implantation. Hearing threshold levels were also monitored over time. Subjects across all three groups had significant improvements in speech recognition scores (i.e. >20 percentage points) both for listening in quiet (71% of subjects) and in noise (100% of subjects). The average score at 4 months after operation for words presented in quiet was 61.7%, and in 10 dB SNR noise 46.5%, compared to 34.4 and 10.6% preoperatively (p < 0.001). All subjects retained measurable hearing at 500 Hz in the implanted ear at 4 months after the operation; mean increases were 19, 29 and 1 dB for the EC, EAS and ES groups (n = 21). Across frequencies of 125-1000 Hz, the median increase in thresholds was 15 dB up to 13 months postoperatively (n = 15). Speech recognition performance of subjects with various levels of residual low-frequency hearing was significantly improved with the SRA cochlear implant. A high level and rate of hearing preservation was achieved with the SRA implanted using a round window surgical technique. Subjects with preoperative low-frequency hearing levels between 50 and 80 dB HL (EAS group) tended to lose more hearing than those with either better or worse hearing.


Genomic characterization reconfirms the taxonomic status of Lactobacillus parakefiri.
Whole-genome sequencing was performed for Lactobacillus parakefiri JCM 8573T to confirm its hitherto controversial taxonomic position. Here, we report its first reliable reference genome. Genome-wide metrics, such as average nucleotide identity and digital DNA-DNA hybridization, and phylogenomic analysis based on multiple genes supported its taxonomic status as a distinct species in the genus Lactobacillus. The availability of a reliable genome sequence will aid future investigations on the industrial applications of L. parakefiri in functional foods such as kefir grains.


[Pressure therapy using a mercury bath].
The principle of compression of the limbs by means of a mercury pressure gradient has repercussions at various levels of the vascular physiology. This study demonstrates its effects on the lymphatic system, where post-radiotherapeutic, post-surgical and post-traumatic lymphedema (LE) can easily be reduced. The same is true for inflammatory, infectious and congenital LE as well as for venolymphatic edema. Brief periods of compression, with bandaging between sessions, stimulate the resumption of lymph drainage. This study demonstrates that recalcitrant hypodermititis also benefits considerably from compression of this type. The other sectors of peripheral vascular disease are under investigation, and preliminary findings are encouraging.


[Influence of previous hepatitis B virus infection on liver fibrosis in patients with chronic hepatitis C: a retrospective case series evaluation].
Hepatitis C is a major cause of liver disease worldwide. Its evolutionary course is dynamics and may be influenced by several cofactors. Among them, previous hepatitis B virus infection (anti-HBcAg [+] and HBsAg [-]) has been associated with worse histological and therapeutic prognosis. This study had the objective of independently assessing the relationship between previous hepatitis B infection and liver fibrosis in patients with chronic hepatitis C. The medical records of patients chronically infected with the hepatitis C virus who had been seen consecutively during a one-year period at the infectious and parasitic diseases outpatient clinic of HC FMUSP were retrospectively reviewed in relation to epidemiological, clinical and histological data. Analysis on the independence of the previous hepatitis B infection was performed using the statistical model of multivariate logistic regression. Detection of anti-HBcAg was taken to be the independent variable. The outcome was taken to be grade 3 and 4 histopathological abnormality (septa with nodule formation and cirrhosis). 145 subjects were evaluated in this study. 47.2% of them were anti-HBcAg (+). The main risk factor for infection was blood and blood derivative transfusion (35.9%). Findings of anti-HBcAg (+) were not related to advanced liver fibrosis, although piecemeal necrosis has been found frequently in patients with this serological marker. Previous hepatitis B infection does not seem to increase the structural liver damage triggered by chronic hepatitis C virus infection, after statistical control for other co-factors capable to impact the natural history of this infection.


The ron receptor tyrosine kinase: a key regulator of inflammation and cancer progression.
Numerous studies have documented abnormal expression and activation of the Ron receptor tyrosine kinase in a variety of human malignancies. Here we review the literature regarding the molecular mechanisms governing Ron regulation, the biological functions of Ron, the effect of Ron on cancer development, and potential therapeutic implications. In epithelial cells, activation of Ron by its ligand, macrophage stimulating protein, mediates a number of biological events including cell growth, motility, and epithelial to mesenchymal transition. Overexpression and/or activation of Ron has been implicated in the progression and metastasis of diverse epithelial cancers, where it plays a causal role in tumor development by promoting growth, survival, and motility of tumor cells. As a crucial regulator of inflammation, Ron inhibits classic macrophage activation and promotes alternative activation of macrophages, resulting in the resolution of inflammation and tissue repair. In addition, Ron alleviates antitumor immunity by promoting the alternative activation of tumor-associated macrophages, and Ron expression in the tumor microenvironment promotes the outgrowth of metastatic colonies. Hence, Ron is a promising therapeutic target for the treatment of epithelial cancers.


Spectral selectivity in optical fiber capillary dye lasers.
We explore the spectral properties of a capillary dye laser in the highly multimode regime. Our experiments indicate that the spectral behavior of the laser does not conform to a simple Fabry-Perot (FP) analysis; rather, it is strongly dictated by a Vernier resonant mechanism involving multiple modes, which propagate with different group velocities. The laser operates over a very broad spectral range and the Vernier effect gives rise to a free spectral range, which is orders of magnitude larger than that expected from a simple FP mechanism. The theoretical calculations presented confirm the experimental results. Propagating modes of the capillary fiber are calculated using the finite-element method and it is shown that the optical path lengths resulting from simultaneous beatings of these modes are in close agreement with the optical path lengths directly extracted from the Fourier transform of the experimentally measured laser emission spectra.


Experimental measurement and prediction of ionic liquid ionisation energies.
Ionic liquid (IL) valence electronic structure provides key descriptors for understanding and predicting IL properties. The ionisation energies of 60 ILs are measured and the most readily ionised valence state of each IL (the highest occupied molecular orbital, HOMO) is identified using a combination of X-ray photoelectron spectroscopy (XPS) and synchrotron resonant XPS. A structurally diverse range of cations and anions were studied. The cation gave rise to the HOMO for nine of the 60 ILs presented here, meaning it is energetically more favourable to remove an electron from the cation than the anion. The influence of the cation on the anion electronic structure (and vice versa) were established; the electrostatic effects are well understood and demonstrated to be consistently predictable. We used this knowledge to make predictions of both ionisation energy and HOMO identity for a further 516 ILs, providing a very valuable dataset for benchmarking electronic structure calculations and enabling the development of models linking experimental valence electronic structure descriptors to other IL properties, e.g. electrochemical stability. Furthermore, we provide design rules for the prediction of the electronic structure of ILs.


Anterior movement of ventral diencephalic precursors separates the primordial eye field in the neural plate and requires cyclops.
A currently favored hypothesis postulates that a single field of cells in the neural plate forms bilateral retinas. To learn how retinal precursors segregate, we followed individual labeled neural plate cells in zebrafish. In the late gastrula, a single field of odd-paired-like-expressing cells contributed to both retinas, bordered posteriorly by diencephalic precursors expressing mariposa. Median mariposa-expressing cells moved anteriorly, separating the eyes, and formed ventral anterior diencephalon, the presumptive hypothalamus. In cyclops mutants, corresponding cells failed to move anteriorly, a ventral diencephalon never formed, and the eyes remained fused. Ablation of the region containing these cells induced cyclopia in wild types. Our results indicate that movement of a median subpopulation of diencephalic precursors separates retinal precursors into left and right eyes. Wild-type cyclops gene function is required for these morphogenetic movements.


Regional differences in opinions on adjuvant radioactive iodine treatment of thyroid carcinoma within Canada and the United States.
To identify regional differences in recommendations for radioactive iodine remnant ablation (RRA) in early stage well-differentiated thyroid carcinoma (WDTC) within Canada and the United States. A cross-sectional written survey of a sample of physicians in specialties potentially involved in thyroid cancer care was performed in 2006. Participants were asked if they recommended RRA for a hypothetical 38-year-old woman with a solitary, 1.6-cm papillary carcinoma resected by total thyroidectomy. Exploratory regional comparisons were performed using Student t tests or analysis of variance. The regions studied were western Canada, eastern Canada (Ontario, the Maritimes), Quebec, the northeastern United States, the western and midwestern United States, and the southern United States. In a secondary multivariable logistic regression analysis, we explored potential relationships between individual respondent characteristics RRA recommendations. Agreement with case-based RRA recommendations was measured on a Likert scale of 1 to 7 (7 = strongest agreement). The effective response rate was 56.3% (486/864). There were significant differences in RRA recommendations among the regions studied (F = 11.99, 5 df, p < 0.001); national boundaries did not explain regional variations. For the sample case, the strongest support for RRA was in Quebec and the southern United States, intermediate support in eastern Canada and the northeastern United States, and the least support in western Canada and the western and midwestern United States. Academic affiliation and surgical specialty were independently inversely associated with strong RRA recommendations. There are significant regional differences in physician-based RRA recommendations in early stage WDTC within Canada and the United States. Physician specialty and practice characteristics may influence RRA recommendations.


Association of high estimated glomerular filtration rate with risk of atrial fibrillation: a nationwide cohort study.
While the relationship between impaired kidney function and atrial fibrillation (AF) is well established, there is limited research exploring the association between elevated estimated glomerular filtration rate (eGFR) and AF development. This study aimed to examine the association between higher-than-normal eGFR and AF risk using a nationwide longitudinal study of the general population in Korea. This study utilized the National Health Insurance Service cohort database of Korea, analyzing data from 2,645,042 participants aged 20-79 years who underwent health examinations between 2010 and 2011. Participants with a history of end-stage renal disease, renal transplantation, and AF prior to the index date were excluded. Renal function was assessed using eGFR levels, calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Baseline characteristics were gathered through questionnaires, while comorbidities and AF occurrence outcomes were identified and validated using diagnostic codes and medication histories. The study employed Kaplan-Meier survival curves and Cox proportional hazard models to evaluate the association between eGFR and AF occurrence. The mean age of subjects was 48.82 ± 10.08 years. Over a median follow-up of 9.58 years, 27,469 (1.04%) AF cases were identified. The risk for AF increased in the higher-than-normal decile, as demonstrated by Kaplan-Meier survival curves (p < 0.001). The eGFR <30 mL/min/1.73 m2 group was associated with an increased risk of AF [hazard ratio (HR): 1.22, 95% confidence interval (CI) (1.01, 1.46), p = 0.039], while the eGFR >120 mL/min/1.73 m2 group was associated with a decreased risk of AF [HR: 0.88, 95% CI (0.78, 0.98), p = 0.045]. Compared to the 5th decile, the 1st [HR: 1.08, 95% CI (1.03, 1.13), p = 0.010] eGFR decile was significantly associated with an increased risk of AF, while the 10th [HR: 0.77, 95% CI (0.70, 0.85), p < 0.001] eGFR decile was significantly associated with a reduced risk of AF. The study revealed that individuals with eGFR>120 mL/min/1.73 m2 or those falling within eGFR 10th decile (>113.41 mL/min/1.73 m2) demonstrated an inverse association linked to a reduced risk of AF. Our study suggests that general population with higher-than-normal eGFR levels may have a lower risk of developing AF.


A defective seed coat pattern (Net) is correlated with the post-transcriptional abundance of soluble proline-rich cell wall proteins.
The pigmented seed coats of several soybean (Glycine max (L.) Merr.) plant introductions and isolines have unusual defects that result in cracking of the mature seed coat exposing the endosperm and cotyledons. It has previously been shown that the T (tawny) locus that controls the color of trichomes on stems and leaves also has an effect on both the structure and pigmentation of the seed coat. Distribution of pigmentation on the seed coat is controlled by alleles of the I (inhibitor) locus. It was also found that total seed coat proteins were difficult to extract from pigmented seed coats with i T genotypes because they have procyanidins that exhibit tannin properties. We report that the inclusion of poly-L-proline in the extraction buffer out-competes proteins for binding to procyanidins. Once this problem was solved, we examined expression of the proline-rich cell wall proteins PRP1 and PRP2 in pigmented genotypes with the dominant T allele. We found that both homozygous i T and i t genotypes have reduced soluble PRP1 levels. The epistatic interaction of the double recessive genotype at both loci is necessary to produce the pigmented, defective seed coat phenotype characteristic of seed coats with the double recessive i and t alleles. This implies a novel effect of an enzyme in the flavonoid pathway on seed coat structure in addition to its effect on flavonoids, anthocyanidins, and proanthocyanidins. No soluble PRP1 polypeptides were detectable in pigmented seed coats (i T genotypes) of isolines that also display a net-like pattern of seed coat cracking, known as the Net defect. PRP2 was also absent in one of the these lines. However, both PRP1 and PRP2 cytoplasmic mRNAs were found in the Net-defective seed coats. Together with in vitro translation studies, these results suggest that the absence of soluble PRP polypeptides in the defective Net lines is post-translational and could be due to a more rapid or premature insolubilization of PRP polypeptides within the cell wall matrix.


Center of rotation locations during lumbar spine movements: a scoping review protocol.
The objective of this review is to identify and map current literature describing the center of rotation locations and migration paths during lumbar spine movements. Altered lumber spine kinematics has been associated with pain and injury. Intervertebral segments' center of rotations, the point around which spinal segments rotate, are important for determining the features of lumbar spine kinematics and the potential for increased injury risk during movements. Although many studies have investigated the center of rotations of humans' lumbar spine, no review has summarized and organized the state of the science related to center of rotation locations and migration paths of the lumbar spine during lumbar spine movements. This review will consider studies that include human lumbar spines of any age and condition (e.g. heathy, pathological) during lumbar spine movements. Quantitative study designs, including clinical, observational, laboratory biomechanical experimental studies, mathematical and computer modeling studies will be considered. Only studies published in English will be included, and there will be no limit on dates of publication. PubMed, MEDLINE, Embase, the Cochrane Library Controlled Register of Trials, CINAHL, ACM Digital Library, Compendex, Inspec, Web of Science, Scopus, Google Scholar, and dissertation and theses repositories will be searched. After title and abstract screening of identified references, two independent reviewers will screen the full-text of identified studies and extract data. Data will be summarized and categorized, and a comprehensive narrative summary will be presented with the respective results.


Role of phospholipase C-gamma in NGF-stimulated differentiation and gene induction.
The PC12 phaeochromocytoma cell line provides a useful model to study nerve growth factor-induced neuronal differentiation. The central signaling route of this process is mediated by the Ras-dependent extracellular signal-regulated kinase cascade. However, Ras-independent pathways are also stimulated by nerve growth factor and may contribute to differentiation signaling. One mediator for Ras-independent signal transduction in PC12 cells is phospholipase C-gamma that generates the second messengers diacylglycerol and inositol-trisphosphate. To probe the possible involvement of this enzyme in nerve growth factor-promoted differentiation, we used the phospholipase C inhibitor U73122 and the inositol-trisphosphate-receptor inhibitor Xestospongin C. Our results show that both chemicals block nerve growth factor-promoted neurite outgrowth, but the blockage of phospholipase C does not inhibit nerve growth factor-induced expression of c-fos, zif268 and transin genes. In addition, induction of these genes by nerve growth factor plus dibutyryl-cAMP is comparable in wild-type PC12 cells as well as in cells in which both Ras- and phospholipase C-gamma-mediated pathways are inhibited. The phospholipase C-gamma pathway thus belongs to those nerve growth factor receptor-originated signaling routes that contribute to the biological response of PC12 cells to nerve growth factor, but its gene activating potential does not have a major role in its neuritogenic effect.


The athlete biological passport.
In elite sports, the growing availability of doping substances identical to those naturally produced by the human body seriously limits the ability of drug-testing regimes to ensure fairness and protection of health. The Athlete Biological Passport (ABP), the new paradigm in testing based on the personalized monitoring of biomarkers of doping, offers the enormous advantage of being independent of this endless pharmaceutical race. Doping triggers physiological changes that provide physiological enhancements. In the same way that disease-related biomarkers are invaluable tools that assist physicians in the diagnosis of pathology, specifically selected biomarkers can be used to detect doping. The ABP is a new testing paradigm with immense potential value in the current climate of rapid advancement in biomarker discovery. In addition to its original aim of providing proof of a doping offense, the ABP can also serve as a platform for a Rule of Sport, with the presentation before competition of the ABP to objectively demonstrate that the athlete will participate in a healthy physiological condition that is unaltered by performance-enhancing drugs. Finally, the decision-support system used today for the biological monitoring of world top-level athletes can also be advantageously transferred to other areas of clinical practice to reach the goal of personalized medicine.


"Where is the Heart?" When Cardiac Magnetic Resonance Imaging Helps if Echocardiography is Inconclusive.
Cardiovascular magnetic resonance (CMR) is the gold standard technique to comprehensively assess cardiac structure and function. A 64-year-old male, planned for surgical coronary revascularization, underwent transthoracic and transesophageal echocardiography for a mitral regurgitation, with an eccentric jet of unclear mechanism; these examinations were inconclusive because of the lack of adequate visualization of the cardiac structures. A CMR was then performed to quantify mitral regurgitation and, additionally, it documented a giant hiatus hernia with gastric sliding into the thorax. In this case, CMR helped to better define the severity of a valvular disease and provided ancillary information from the extracardiac findings.


Autophagy promotes the replication of encephalomyocarditis virus in host cells.
A growing number of studies have demonstrated that autophagy has a diverse role in the infection process of different pathogens. However, to date, it is unknown whether autophagy is activated in encephalomyocarditis virus (EMCV)-infected host cells, and if so, what its role is in this process. In the present study, we first demonstrated that EMCV infection significantly increases the number of double- and single-membrane vesicles in the cytoplasm of host cells. It was then confirmed that these observed vesicles are indeed related to autophagy, and that EMCV replication is required for the induction of autophagy by examining LC3-I/-II conversion and p62/SQSTM1 degradation using immunoblotting. Next, we performed confocal immunofluorescence analysis and discovered that, during EMCV replication, both the nonstructural protein 3A and capsid protein VP1 colocalized with LC3. The colocalizations of both 3A and VP1 protein with autophagosome-like vesicles were further confirmed using immunoelectron microscopy, indicating that EMCV undergoes RNA replication on the membranes of these vesicles. Finally, we used pharmacological regulators and siRNAs to examine the role of autophagy in EMCV replication. Our results suggest that autophagy not only promotes the replication of EMCV in host cells, but it also provides a topological mechanism for releasing cytoplasmic viruses in a nonlytic manner. Noticeably, the autophagic pharmaceuticals we used had no significant effect on virus entry or cell viability, both of which may affect viral replication. To our knowledge, ours is the first strong evidence indicating that autophagy is involved in EMCV infection in host cells.


Acute kidney injury: definitions and new paradigms.
Changes in terminology and new consensus definitions of acute kidney injury (AKI) and stages of severity have simplified some of the problems in the clinical approach to this complex syndrome. Nevertheless, new proactive approaches to the diagnosis of kidney injury instead of kidney failure are required to allow clinical translation of successful therapies developed for experimental AKI. The recent development of novel urinary and plasma biomarkers, which predict kidney failure, has allowed the development of new paradigms for detection, prevention, and stage-specific treatment.


Combination of patch clamp and Raman spectroscopy for single-cell analysis.
In this contribution we present the combination of patch clamp with Raman spectroscopy for a label-free quantitative detection of intracellular components. Patch clamp is used to gain controlled access to the cytosol and internalize water-soluble compounds into the cell. The presence and concentration of these substances inside the living mammalian cell are probed by means of Raman spectroscopy in a label-free manner. A proof of principle was given using the carotinoid crocin as a sample compound that does not show specific interaction with the cell. When the intracellular crocin concentration as determined from the Raman spectra was monitored, the kinetics of internalization/diffusion into the cell could be characterized by a single-exponential function. Furthermore, the technique was successfully applied to observe differences in the internalization of free and protein-bound heme into the living cell. Although the peptide-capped microperoxidase MP-11 did not show specific interactions, free heme accumulated in the cell by binding to cellular components.


Comparative epidemiology of Clostridium difficile infection: England and the USA.
To examine whether there is an epidemiological difference between Clostridium difficile infection (CDI) inpatient populations in England and the United States. A cross-sectional study. National administrative inpatient discharge data from England (Hospital Episode Statistics) and the USA (National Inpatient Sample) in 2012. De-identifiable non-obstetric inpatient discharges from the national datasets were used to estimate national CDI incidence in the United States and England using ICD9-CM(008.45) and ICD10(A04.7) respectively. The rate of CDI was calculated per 100 000 population using national population estimates. Rate per 100 000 inpatient discharges was also calculated separated by primary and secondary diagnosis of CDI. Age, sex and Elixhauser comorbidities profiles were examined. The USA had a higher rate of CDI compared to England: 115.1/100 000 vs. 19.3/100 000 population (P < 0.001). CDI age profiles differed between the countries (P < 0.001): in England, patients ≥75 years constitute a larger proportion of CDI cases, whilst those aged 25-70 constitute more cases in the US (P < 0.001). Overall adjusted odds of CDI in females compared to males was elevated in both England (odds ratios (OR) 1.26 95% CI [1.21,1.31] P < 0.001) and the USA (OR 1.20 95% CI [1.18,1.22] P < 0.001). The proportion of CDI patients with comorbidities was greater in the USA compared to England apart from dementia, which was greater in England (9.63% vs. 1.25%, P < 0.0001). The 2012 inpatient CDI rate within the USA was much higher than in England. Age and comorbidity profiles also differed between CDI patients in both countries. The reasons for this are likely multi-factorial but may reflect national infection control policy.


Pharmacokinetics of Benzylpenicillin (Penicillin G) during Prolonged Intermittent Renal Replacement Therapy.
Prolonged intermittent renal replacement therapy (PIRRT) is an increasingly adopted method of renal replacement in critically ill patients. Like continuous renal replacement therapy, PIRRT can alter the pharmacokinetics (PK) of many drugs. In this setting, dosing data for antibiotics like benzylpenicillin are lacking. In order to enable clinicians to prescribe benzylpenicillin safely and effectively, knowledge of the effects of PIRRT on the plasma PK of benzylpenicillin is required. Herein, we describe the PK of benzylpenicillin in 2 critically ill patients on PIRRT for the treatment of penicillin-susceptible Staphylococcus aureus bacteremia complicated by infective endocarditis. Blood samples were taken for each patient taken over dosing periods during PIRRT and off PIRRT. Two-compartment PK models described significant differences in the mean clearance of benzylpenicillin with and without PIRRT (6.61 vs. 3.04 L/h respectively). We would suggest a benzylpenicillin dose of 1,800 mg (3 million units) every 6-h during PIRRT therapy as sufficient to attain PK/pharmacodynamic target.


Loss of alveolar membrane diffusing capacity and pulmonary capillary blood volume in pulmonary arterial hypertension.
Reduced gas transfer in patients with pulmonary arterial hypertension (PAH) is traditionally attributed to remodeling and progressive loss of pulmonary arterial vasculature that results in decreased capillary blood volume available for gas exchange. We tested this hypothesis by determination of lung diffusing capacity (DL) and its components, the alveolar capillary membrane diffusing capacity (D(m)) and lung capillary blood volume (V(c)) in 28 individuals with PAH in comparison to 41 healthy individuals, and in 19 PAH patients over time. Using single breath simultaneous measure of diffusion of carbon monoxide (DL(CO)) and nitric oxide (DL(NO)), DL and D(m) were respectively determined, and V(c) calculated. D(m) and V(c) were evaluated over time in relation to standard clinical indicators of disease severity, including brain natriuretic peptide (BNP), 6-minute walk distance (6MWD) and right ventricular systolic pressure (RVSP) by echocardiography. Both DL(CO) and DL(NO) were reduced in PAH as compared to controls and the lower DL in PAH was due to loss of both D(m) and V(c) (all p < 0.01). While DL(CO) of PAH patients did not change over time, DL(NO) decreased by 24 ml/min/mmHg/year (p = 0.01). Consequently, D(m) decreased and V(c) tended to increase over time, which led to deterioration of the D(m)/V(c) ratio, a measure of alveolar-capillary membrane functional efficiency without changes in clinical markers. The findings indicate that lower than normal gas transfer in PAH is due to loss of both D(m) and V(c), but that deterioration of D(m)/V(c) over time is related to worsening membrane diffusion.


[An instrument for measuring the protein concentration in urine].
The measuring of the protein concentration in urine provides for an early diagnosis of a number of diseases at the early stage of their onset. Determination of the protein concentration in urine in patients after renal transplantation made during the early postoperative period is of special diagnostic importance. The protein content in urine varies significantly during 24 hours. With urgent information on losses of the protein in urine being available, the doctor can correct, purpose-orientedly, such losses, assess the activity of the pathological process in the kidneys and evaluate the efficiency of a conducted treatment. The known methods of determining the protein concentration in biological liquids are discussed; their advantages and disadvantages are pointed out. We suggested a new method for determining the protein content in urine, which is based on changes in the electric resistance of fluid (urine) according to its protein content; the method was patented in Russia. The technique of measuring the protein concentration in urine consists in measuring the electric resistance of the examined urine before and after its filtration through a micro-pore filter, with a pore size of 2-3 nm (2-3 x 10(-9) m), intercepting the protein. There is a description of the elaborated-by-authors instrument, which is based on the mentioned technology and which cuts the time of determining the protein concentration in urine; it also makes any chemical reagents unnecessary and provides for automating the measurement process.


[Testicular morphology in rats in the early and late periods after platidiam administration].
The experiments performed on Wistar rats showed morphological damages of the rat testis over a one-month period after platidiam administration (4 mg/kg, one-time intravenous injection), namely a decrease in the index of spermatogenesis, in the number of normal spermatogonia, Leydig cells, and testis tubes at the 12th stage of meiosis and an increase in the number of testis tubes squamous epithelium. In the remote period (3 and 6 month after platidiam administration) the recovery of morphological and functional state of the rat testis was observed.


Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model.
Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ischemia/reperfusion (I/R) injury with myriad negative consequences. Potential I/R injury in marginal organs destined for liver transplantation contributes to the current donor shortage secondary to a decreased organ utilization rate. A significant need exists to explore hepatic I/R injury in order to mediate its impact on graft function in transplantation. Rat liver hilar clamp models are used to investigate the impact of different molecules on hepatic I/R injury. Depending on the model, these molecules have been delivered using inhalation, epidural infusion, intraperitoneal injection, intravenous administration or injection into the peripheral superior mesenteric vein. A rat liver hilar clamp model has been developed for use in studying the impact of pharmacologic molecules in ameliorating I/R injury. The described model for rat liver hilar clamp includes direct cannulation of the portal supply to the ischemic hepatic segment via a side branch of the portal vein, allowing for direct segmental hepatic delivery. Our approach is to induce ischemia in the left lateral and median lobes for 60 min, during which time the substance under study is infused. In this case, pegylated-superoxide dismutase (PEG-SOD), a free radical scavenger, is infused directly into the ischemic segment. This series of experiments demonstrates that infusion of PEG-SOD is protective against hepatic I/R injury. Advantages of this approach include direct injection of the molecule into the ischemic segment with consequent decrease in volume of distribution and reduction in systemic side effects.


Percutaneous delivery of a heparin-impregnated collagen stent-graft in a porcine model of atherosclerotic disease.
To develop collagen stent-grafts impregnated with heparin to improve the biocompatibility of endovascular stents and to design a percutaneous delivery system for graft deployment in a swine model. Heparin-impregnated collagen stent-grafts were deployed, and follow-up angiograms were obtained every 15 minutes for 90 minutes to assess acute thromboses and again at 2 and 4 weeks afterward to assess patency. If stenosis or occlusion was detected at the 2-week evaluation, guidewire passage across the lesion was attempted and angioplasty was performed. If stenosis or occlusion was present at the 4-week evaluation, only guidewire passage was attempted; thereafter, the animals were killed and the stent-grafts were harvested and reviewed by a vascular pathologist. Group A represents a feasibility study to optimize the deployment method applied in groups B and C. Fifteen of 17 stent-grafts were successfully deployed using this method. In group B, 89% of grafts were successfully deployed; 12% were patent at 2 weeks and none at 4 weeks. In group C, a 10-minute inflation time was added to the deployment procedure; 88% of grafts were successfully deployed and 28% were patent at 2 weeks and 14% at 4 weeks. Extensive luminal thrombosis and myointimal hyperplasia were present in every case. A method was developed for percutaneous implantation of collagen stent-grafts into peripheral vessels. The heparin-impregnated grafts did not prevent vessel restenosis. Modification of the graft-processing technique may improve patency.


The influence of sevoflurane anesthesia on the rat red blood cell deformability.
Alterations in blood rheology under the influence of anesthesia have been observed and discussed among the responsible factors for the deterioration of tissue and organ perfusion related to anesthetic procedures. Sevoflurane is one of the volatil anesthetics which is being used very common in surgery. In this study, the effects of sevoflurane anesthesia were investigated in different age groups of rats. 22 male rats were used in the study and the rats were divided into two groups according to their age (young and old) comprising of two subgroups in each. First group was the young control (n = 5), the second was the young group treated with sevoflurane (n = 5), the third group was the old control (n = 7) and the last group was the old group treated with sevoflurane (n = 5). %2 of sevoflurane was applied to the rats with inhalation in a adjustable cage for one hour. The deformability indexes of the erythrocytes were measured by a laser diffractometer (Myrenne Rheodyne SSD). Deformability indexes of red blood cells were significantly decreased with sevoflurane in old rats (p = 0.028) whereas it had not any significant effect in young group compared with their controls. When we compared the young and old control groups, the deformability indexes were significantly higher in old ones (p < 0.001). However, there were not any significant difference between the old and the young sevoflurane applied groups. A volatil anesthetic agent sevoflurane has impaired the deformability of erythrocytes in old rats compared to their controls, whereas it had not any significant effect in young ones which may be due to the flexibility of the young erythrocytes leading them to tolerate to the environmental changes. These results reveal that the inhalation anesthetics like sevoflurane may cause more serious problems in the elder people and their hemodynamic parameters should be checked more seriously during the surgery.


Vogt-Koyanagi-Harada disease: review of a rare autoimmune disease targeting antigens of melanocytes.
Vogt-Koyanagi-Harada disease (VKHD) is a rare granulomatous inflammatory disease that affects pigmented structures, such as eye, inner ear, meninges, skin and hair. This disease is mainly a Th1 lymphocyte mediated aggression to melanocytes after a viral trigger in the presence of HLA-DRB1*0405 allele. The absence of ocular trauma or previous intraocular surgery sets VKHD appart from sympathetic ophthalmia, its main differential diagnosis. The disease has an acute onset of bilateral blurred vision with hyperemia preceded by flu-like symptoms. The acute uveitic stage is characterized by a diffuse choroiditis with serous retinal detachment and optic disc hyperemia and edema. Fluorescein angiography in this phase demonstrates multiple early hyperfluorescent points. After the acute uveitic stage, ocular and integumentary system pigmentary changes may appear. Ocular findings may be accompanied by lymphocytic meningitis, hearing impairment and/or tinnitus in a variable proportion of patients. Prompt diagnosis followed by early, aggressive and long-term treatment with high-dose corticosteroids is most often ensued by good visual outcomes. However, some patients may experience chronic uveal inflammation with functional eye deterioration. The current review discusses the general features of VKHD, including epidemiology, classification into categories, differential diagnosis and current therapeutic approaches.


Reference values for biochemical parameters in blood serum of young and adult alpacas (Vicugna pacos).
The aim of this study was to establish reference interval for biochemical parameters in blood of alpacas on the basis of large population of clinically healthy animals, and to determine the influence of sex, age and season on nitrogen and lipid metabolites, enzymes, electrolytes, vitamins and minerals in blood of alpacas. Blood samples were collected from 311 alpacas (61 males and 201 females >6 months of age and 49 crias (21 males and 28 females) ⩽6 months of age). Selected farms were located in Central Europe (Czech Republic and Germany). We determined 24 biochemical parameters from blood serum. We performed the comparison of results by the sex of animals and for the older group also the comparison of the results with regard to the season, respectively, to the feeding period. We found no highly significant difference (P<0.01) between males and females with the exception of γ-glutamyl transferase (GGT), alkaline phosphatase (ALP) and cholesterol. We found 15 significantly different parameters between the group of crias 6 months of age and the older alpacas. Based on our findings we suggest for most parameters to use different reference intervals (especially ALP, cholesterol, total protein, globulin, non-esterified fatty acids (NEFA), GGT and phosphorus) for the two above-mentioned age groups. Another important finding is the differences between some parameters in older group of alpacas in summer/winter feeding period. Animals in the summer feeding period have higher values of parameters related to fat mobilization (β-hydroxybutyrate, NEFA) and liver metabolism (bilirubin, alanine aminotransferase). The winter period with increased feeding of supplements with higher amount of fat, vitamins and minerals is characteristic by increased values of cholesterol, triglycerides, vitamins A and E, and some minerals (K, Ca, Mg and Cl) in blood serum. Clinical laboratory diagnosis of metabolic disturbances may be improved with use of age-based reference values and with consideration of seasonal differences.


Antifungal Immunological Defenses in Newborns.
Newborns are prone to fungal infections, largely due to Candida species. The immunological basis for this vulnerability is not yet fully understood. However, useful insights can be gained from the knowledge of the maturation of immune pathways during ontogeny, particularly when placed in context with how rare genetic mutations in humans predispose to fungal diseases. In this article, we review these most current data on immune functions in human newborns, highlighting pathways most relevant to the response to Candida. While discussing these data, we propose a framework of why deficiencies in these pathways make newborns particularly vulnerable to this opportunistic pathogen.


Elucidating measures of systemic racism to mitigate racial disparities in kidney transplantation.
Given recent national attention to the role of racism in perpetuating racial inequities in society and health, this review provides a timely and relevant summary of key measures of systemic racism in kidney transplantation. More specifically, the review identifies current and promising interventions, whereas highlighting the need for more sustainable and impactful interventions. Racial disparities persist in kidney transplantation. Black and Hispanic individuals are less likely to receive a kidney transplant than non-Hispanic Whites despite disproportionately higher rates of kidney failure. Studies demonstrate that socioeconomic factors do not fully explain existing racial disparities in transplantation. Systemic racism at all levels, individual, interpersonal, institutional, and structural, is at the core of racial disparities, and current interventions are insufficient in mitigating their effects. Thus, targeted and sustainable interventions must be implemented to mitigate systemic racism in kidney transplantation. Systemic racism in all its forms continues to influence disparities at all stages of kidney transplantation. This paper highlights recent findings that shed light on how racism contributes to racial disparities in kidney transplantation. Using these findings to identify targets and strategies for mitigation, relevant interventions and policies that show promise are detailed.


Suicidality among Hong Kong nurses: prevalence and correlates.
The study estimates the prevalence and examines the socio-economic and psychological correlates of suicidality among professional nurses in Hong Kong. Suicide rates among middle-aged employed groups have been increasing over the past few decades. There is a concern that medical occupational groups worldwide are at elevated risk of suicide. Nonetheless there are few population-based studies of suicide dealing with working-age Asian nurses. The study uses a cross-sectional survey design. Data were collected in Hong Kong over 4 weeks from October-November 2013. Statistical methods including descriptive analysis and univariate and multivariate cumulative logit modelling were used to examine the weighted prevalence rates of past-year suicidality and its associated factors in nurses. A total of 850 nurses participated in the study; 14·9% of participants had contemplated suicide while 2·9% had attempted suicide once or more in the past year. Women report suicidal thoughts or attempts more often than men. Religion, poor health, deliberate self-harm, depressive symptoms and poor self-perceived physical and mental health were significantly associated with nurses' suicidality. Nurse professionals are not immune from mental health issues. Hong Kong's local health authority should put in place a raft of suicide prevention initiatives to promote mental wellness in the profession.


Tandem Electrocatalytic CO2 Reduction with Efficient Intermediate Conversion over Pyramid-Textured Cu-Ag Catalysts.
If combined with renewably generated electricity, electrochemical CO2 reduction (E-CO2R) could be used as a sustainable source of chemicals and fuels. Tandem catalysis approaches are attractive for providing the product selectivity, which would be required for commercial applications. Here, we demonstrate a two-step tandem electrocatalytic E-CO2R with efficient conversion of the intermediate species. The catalyst scaffold is Si(100), which is etched to form a textured surface consisting of micron-sized pyramid structures with the {111} facets. Two metals are used in the electrocatalytic cascade: Ag is employed to perform a two-electron reduction of CO2 to the intermediate CO, and Cu performs conversion to more reduced products. Using high-angle physical vapor deposition, we form separated, micron-scale areas of the two electrocatalysts on opposite sides of the pyramids, with their relative surface coverages being tunable with the deposition angle. Compared to the textured scaffolds with blanket Ag and Cu used as controls, bimetallic pyramid tandem catalysts have higher current densities and much lower faradic efficiencies (FE) for CO. These effects are due to efficient conversion of the CO formed on Ag to more reduced products on Cu. Methane is the main product to be enhanced by the cascade pathway: a bimetallic catalyst with approximately equal coverages of Ag and Cu produces methane with a FE of 62% at -1.1 VRHE, corresponding to a partial current density of 12.7 mA cm-2. We estimate an intermediate conversion yield for the CO intermediate of 80-90%, which is close to the mass-transport limited value predicted by reaction-diffusion simulations.


Bypass surgery in limb salvage: inflow procedures.
Proper management of lower-extremity inflow vessel disease is critical to the success of distal interventions. Aortobifemoral bypass is the most effective means of treating aortoiliac disease, but this invasive procedure is not always ideal for a patient population that often has diffuse vascular disease and multiple comorbidities. Technologic advances and increasing experience have fundamentally altered the management algorithm for lower-extremity vascular lesions, and endovascular options have become the first-line therapy for Trans-Atlantic Inter-Society Guidelines (TASC) class A and B lesions. In fact, an endovascular first approach is being endorsed even for highly complex TASC C and even TASC D lesions. Other alternatives include minimally invasive (laparoscopic or robotic) options or extra-anatomic bypass procedures. Inadequate outflow can compromise any inflow procedure, but inflow treatment failures are the crux of all limb salvage in patients with lower-extremity vascular disease.


Protection of primary glial cells by grape seed proanthocyanidin extract against nitrosative/oxidative stress.
Previous studies showed that proanthocyanidins provide potent protection against oxidative stress. Here we investigate the effects of grape seed proanthocyanidin extract (GSPE) as a novel natural antioxidant on the generation and fate of nitric oxide (NO) in rat primary glial cell cultures. GSPE treatment (50 mg/L) increased NO production (measured by NO(2-) assay) by stimulation of the inducible isoform of NOS. However, GSPE failed to affect the LPS/IFN-gamma-induced NO production or iNOS expression. Similar responses were found in the murine macrophage cell line RAW264.7. GSPE did not show any effect on dihydrodichlorofluorescein fluorescence (ROS marker with high sensitivity toward peroxynitrite) either in control or in LPS/IFN-gamma-induced glial cultures even in the presence of a superoxide generator (PMA). GSPE treatment alone had no effect on the basal glutathione (GSH) status in glial cultures. Whereas the microglial GSH level declined sharply after LPS/IFN-gamma treatment, the endogenous GSH pool was protected when such cultures were treated additionally with GSPE, although NO levels did not change. Glial cultures pretreated with GSPE showed higher tolerance toward application of hydrogen peroxide (H(2)O(2)) and tert-butylhydroperoxide. Furthermore, GSPE-pretreated glial cultures showed improved viability after H(2)O(2)-induced oxidative stress demonstrated by reduction in lactate dehydrogenase release or propidium iodide staining. We showed that, in addition to its antioxidative property, GSPE enhances low-level production of intracellular NO in primary rat astroglial cultures. Furthermore, GSPE pretreatment protects the microglial GSH pool during high output NO production and results in an elevation of the H(2)O(2) tolerance in astroglial cells.


The undue influence of genetic information on senior medical students' treatment decisions.
Knowledge of the genetic basis of health conditions can influence how the public perceives their own and others' health. When there are known genetic associations for such conditions, genetic essentialist biases facilitate deterministic thinking and an over-emphasis of genetic causality. This study investigates the role that genetic essentialist biases play in medical decision-making. Senior postgraduate medical students (N = 102) read a scenario in which a patient presents with gastroenterological symptoms. Half of the students were told that the patient tested positive for HLADQ2 - a gene implicated in, but not deterministic of, coeliac disease. The other half received no genetic information. Students were assessed on their recommendations for investigation and management using a multiple-choice questionnaire. Twenty-two of these students participated in a qualitative follow-up which used focus groups and semi-structured interviews to explore the reasoning behind students' responses. Management recommendations differed between the two groups, with those receiving genetic information more likely to recommend a gluten free diet. Recommendations for further investigation did not differ significantly between groups. Interviews suggested that these findings arose despite the students' good understanding of the common non-deterministic nature of genes, such as HLADQ2. Differences in management recommendations suggest that the inclusion of genetic information unduly biased students towards a premature diagnosis of a serious health condition, coeliac disease. Follow-up interviews introduced the possibility that observed manipulation-based differences may have been based on anticipated expectations of examiners, rather than perceived future clinical practice. Based on the present results it is unclear whether intentional exam-taking strategies fully account for medical students' decisions, or if they contribute in addition to the activation of genetic essentialist biases. Further research in clinical settings may ascertain whether genetic essentialist biases would truly influence medical student and doctors within their clinical practice environment.


Gender differences in tryptophan hydroxylase-2 mRNA, serotonin, and 5-hydroxytryptophan levels in the brain of catfish, Clarias gariepinus, during sex differentiation.
Tryptophan hydroxylase (tph) is the key regulator in serotonin (5-HT) biosynthesis that stimulates the release of GnRH and gonadotropins by acting at the level of hypothalamo-hypophyseal axis. In brain, 5-HT is expressed predominantly in preoptic area-hypothalamus (POA-HYP) region in teleosts. Therefore, in the present study we isolated tph2 from catfish brain to evaluate its expression pattern in male and female brains during early development. Tph2 cloned from catfish brain is 2.768 Kb in length which encodes predicted protein of 488 amino acid residues. The characterization of recombinant tph2 was done by transient transfection in CHO cells. Tissue distribution of tph2 revealed ubiquitous expression except ovary. Real time PCR analysis in discrete regions of adult male brain revealed that tph2 mRNA was abundant in the POA-HYP and optic tectum+cerebellum+thalamus (OCT) regions. Differential expression of tph2 was observed at mRNA and protein levels in the POA-HYP and OCT regions of male and female brains during development that further correlate with the 5-hydroxytryptophan (5-HTP) and 5-HT levels measured using HPLC method in these regions of male and female brains. Tph2 immunoreactive neurons were observed in different regions of brain at 50 days post hatch using catfish specific tph2 antibody. Changes in tph2 mRNA expression, 5-HTP, and 5-HT levels in the POA-HYP+OCT region of brains of methyltestosterone and para-chlorophenylalanine treated fishes during development further endorse our results. Based on our results, we propose that the serotonergic system is involved in brain sex differentiation in teleosts.


Elevated glutamate levels in the vitreous body of humans and monkeys with glaucoma.
To explore the possibility that the excitatory amino acid glutamate might be associated with the disease process of glaucoma, which is characterized by the death of retinal ganglion cell neurons and subsequent visual dysfunction. Amino acid analyses were performed on vitreous specimens that were obtained from patients who were undergoing cataract extraction. Samples were collected prospectively from those patients who sustained inadvertent rupture of the posterior capsule between 1988 and 1993. An additional set of specimens, obtained from both eyes of monkeys, was analyzed; in these monkeys, glaucoma had been experimentally induced in one eye only. A twofold elevation in the level of glutamate was detected in the vitreous body of the group of patients with glaucoma when compared with that in a control population of patients with cataracts only. An even greater elevation of the glutamate level was found in the vitreous body of glaucomatous eyes of monkeys when compared with that in control eyes. No statistical differences were detected among other amino acid levels from the vitreous body of glaucomatous and nonglaucomatous eyes in humans or monkeys. The excitatory amino acid glutamate is found in the vitreous body of glaucomatous eyes at concentrations that are potentially toxic to retinal ganglion cells. The increased level of this known neurotoxin is consistent with an "excitotoxic" mechanism for the retinal ganglion cell and optic nerve damage in glaucoma. Therapies to protect neurons against glutamate toxic effects may prove to be useful in the management of this blinding disease.


Effect of tumor necrosis factor alpha on mitogen-activated human B cells.
In this study we demonstrate that the monocyte/macrophage product, tumor necrosis factor alpha (TNF-alpha), has significant in vitro effects of B cell function. It costimulated with anti-mu in the induction of B cell DNA synthesis, and it prolonged the DNA synthesis initiated in B cell cultures stimulated with the human B cell mitogen, Staphylococcus aureus Cowan strain I (SAC). The addition of either IL-1 or IFN-gamma to TNF-alpha resulted in a substantial further increase in DNA synthesis. The addition of TNF-alpha to IL-2, a known inducer of SAC-activated B cell Ig secretion, resulted in a twofold enhancement in the amount of IL-2 stimulated B cell Ig secretion. Receptor binding studies with 125I-TNF-alpha demonstrate a marked increase in TNF-alpha binding sites after B cell activation (approximately 6,000 sites per cell, with an apparent Kd of 2.0 X 10(-10) M). Thus, TNF-alpha may be an important factor in human B cell function and is likely to interact with other T cell and monocyte derived cytokines in the regulation of human B cell proliferation and Ig production.


Nitrofurantoin: friend or foe?
Nitrofurantoin remains the gold standard treatment of uncomplicated cystitis as well as prophylactic treatment of recurrent urinary tract infections. Drug-induced hepatotoxicity presents in acute (3 in 1 000 000) and chronic (1 in 1500) forms. We present a patient with acute liver failure after 5 days of treatment. A 69-year-old man admitted for chronic obstructive pulmonary disease exacerbation 5 days into treatment for cystitis with nitrofurantoin. On admission he was noted to be jaundiced with elevated liver enzymes and normal international normalised ratio. Investigation for infectious, autoimmune and cholestatic causes of hepatotoxicity was negative. The patient improved after discontinuation of the drug and 10 days of methylprednisolone. There are scant data on acute liver failure in the setting of short-term nitrofurantoin administration. The mechanism of toxicity remains unclear, but is hypothesised to be an autoimmune process in which steroids may play a role in treatment. Diagnosis is one of exclusion as the only definitive method of diagnosis is rechallenge.


Gastrointestinal Complications After Bariatric Surgery.
Bariatric surgery is increasingly being performed in the medically complicated obese population as convincing data continue to mount, documenting the success of surgery not only in achieving meaningful weight loss but also in correcting obesity-related illnesses. Several surgical procedures with varying degrees of success and complications are currently being performed. This article discusses the short- and long-term gastrointestinal complications for the 4 most common bariatric surgical procedures: laparoscopic adjustable gastric banding, vertical sleeve gastrectomy, Roux-en-Y gastric bypass, and biliopancreatic diversion with duodenal switch.


Expression dynamics indicate the involvement of SPG7 in the reproduction and spermiogenesis of Phascolosoma esculenta.
Spastic paraplegia 7 (SPG7) is an m-AAA protease subunit involved in mitochondrial morphology and physiology. However, its function in animal reproduction is yet to be evaluated. In this study, its molecular features, subcellular localization, and expression dynamics were investigated to analyze its potential function in the reproduction of male Phascolosoma esculenta, an economically important marine species in China. The full-length cDNA of P. esculenta spg7 (Pe-spg7) measures 3053 bp and encodes an 853-amino acid protein (Pe-SPG7). Pe-SPG7 includes two transmembrane domains, an AAA domain and a proteolytic domain. Amino acid sequence alignment revealed that SPG7 was conserved during evolution. The mRNA and protein expression of spg7 indicated its involvement in reproduction. Its expression was the highest in coelomic fluid, where spermatids develop, and it was significantly higher in the breeding stage than in the nonbreeding stage. SPG7 was mainly found in the mitochondria of spermatids in the coelomic fluid, indicating that it functions in this organelle in spermatids. Immunofluorescence experiments showed that SPG7 was expressed and colocalized in the mitochondria during spermiogenesis, suggesting its involvement in P. esculenta spermiogenesis. Therefore, SPG7 may participate in spermiogenesis by functioning in the mitochondria and regulate the reproduction of male P. esculenta. This study provided insights into the function of SPG7 in animal reproduction and P. esculenta gametogenesis.


Plasmon field effects on the nonradiative relaxation of hot electrons in an electronically quantized system: CdTe-Au core-shell nanowires.
The intense electromagnetic fields of plasmonic nanoparticles, resulting from the excitation of their localized surface plasmon oscillations, are known to enhance radiative processes. Their effect on the nonradiative electronic processes, however, is not as well-documented. Here, we report on the enhancement of the nonradiative electronic relaxation rates in CdTe nanowires upon the addition of a thin gold nanoshell, especially at excitation energies overlapping with those of the surface plasmon oscillations. Some possible mechanisms by which localized surface plasmon fields can enhance nonradiative relaxation processes of any quantized electronic excitations are proposed.


MicroRNAs in melanoma development and resistance to target therapy.
microRNAs constitute a complex class of pleiotropic post-transcriptional regulators of gene expression involved in the control of several physiologic and pathologic processes. Their mechanism of action is primarily based on the imperfect matching of a seed region located at the 5' end of a 21-23 nt sequence with a partially complementary sequence located in the 3' untranslated region of target mRNAs. This leads to inhibition of mRNA translation and eventually to its degradation. Individual miRNAs are capable of binding to several mRNAs and several miRNAs are capable of influencing the function of the same mRNAs. In recent years networks of miRNAs are emerging as capable of controlling key signaling pathways responsible for the growth and propagation of cancer cells. Furthermore several examples have been provided which highlight the involvement of miRNAs in the development of resistance to targeted drug therapies. In this review we provide an updated overview of the role of miRNAs in the development of melanoma and the identification of the main downstream pathways controlled by these miRNAs. Furthermore we discuss a group of miRNAs capable to influence through their respective up- or down-modulation the development of resistance to BRAF and MEK inhibitors.


QSARs for the aquatic toxicity of aromatic aldehydes from Tetrahymena data.
The aim of the study was to develop quantitative structure-activity relationships (QSARs) for a large group of 77 aromatic aldehydes tested for acute toxicity to the ciliate Tetrahymena pyriformis using mechanistically interpretable descriptors. The resulting QSARs revealed that the 1-octanol/water partition coefficient (log K(ow)), is the most important descriptor of aldehyde aquatic toxic potency. The model with log K(ow) was improved by adding electronic descriptor (the maximum acceptor superdelocalizability in a molecule--A(max)) based on calculations with the semi-empirical AM1 model. The two descriptors reflect the two main processes responsible for demonstration of acute aquatic toxicity, namely penetration through cell membranes (log K(ow)) and interaction with the biomacromolecules (A(max)) into the cells. Results showed that generally the studied group of aldehydes could be modeled by this simple two-descriptor approach. However, the group of 2- and/or 4-hydroxylated aldehydes demonstrates enhanced toxicity compared to the other aldehydes. Transformation to quinone-like structures is proposed as the explanation for this enhanced potency. The 2- and/or 4-hydroxylated aldehydes are modeled successfully by [log(1/IGC50) = 0.540(0.038) log K(ow) + 8.30(2.88)A(max) - 3.11(0.92), n = 25, R2 = 0.916, R(CV)2 = 0.896, s = 0.141, F = 120], while the other aldehydes are modeled by the relationship [log(1/IGC50) = 0.583 (0.034)log K(ow) + 9.80(2.62)A(max) - 4.04 (0.85), n = 52, R2 = 0.864, R(CV)2 = 0.844, s = 0.203, F = 156], which is similar to the general benzene model.


Tetrahydrobiopterin inhibits monomerization and is consumed during catalysis in neuronal NO synthase.
The biosynthesis of nitric oxide (NO) is catalyzed by homodimeric NO synthases (NOS). For unknown reasons, all NOS co-purify with substoichiometric amounts of (6R)-5,6,7,8-tetrahydrobiopterin (H(4)Bip) and require additional H(4)Bip for maximal activity. We examined the effects of H(4)Bip and pterin-derived inhibitors (anti-pterins) on purified neuronal NOS-I quaternary structure and H(4)Bip content. During L-arginine turnover, NOS-I dimers time dependently dissociated into inactive monomers, paralleled by a loss of enzyme-associated pterin. Dimer dissociation was inhibited when saturating levels of H(4)Bip were added during catalysis. Similar results were obtained with pterin-free NOS-I expressed in Escherichia coli. This stabilizing effect of H(4)Bip was mimicked by the anti-pterin 2-amino-4,6-dioxo-3,4,5,6,8,8a,9, 10-octahydro-oxazolo[1,2f]-pteridine (PHS-32), which also displaced NOS-associated H(4)Bip in a competitive manner. Surprisingly, H(4)Bip not only dissociated from NOS during catalysis, but was only partially recovered in the solute (50.0 +/- 16.5% of control at 20 min). NOS-associated H(4)Bip appeared to react with a NOS catalysis product to a derivative distinct from dihydrobiopterin or biopterin. Under identical conditions, reagent H(4)Bip was chemically stable and fully recovered (95.5 +/- 3.4% of control). A similar loss of both reagent and enzyme-bound H(4)Bip and dimer content was observed by NO generated from spermine NONOate. In conclusion, we propose a role for H(4)Bip as a dimer-stabilizing factor of neuronal NOS during catalysis, possibly by interfering with enzyme destabilizing products.


An oxidative burst of superoxide in embryonic axes of recalcitrant sweet chestnut seeds as induced by excision and desiccation.
Recalcitrant seeds are intolerant of desiccation and cannot be stored in conventional seed banks. Cryopreservation allows storage of the germplasm of some recalcitrant seeded species, but application to a wide range of plant diversity is still limited. The present work aimed at understanding the stresses that accompany the first steps in cryopreservation protocols, wounding and desiccation, both of which are likely to lead to the formation of reactive oxygen species (ROS). Extracellular ROS production was studied in isolated embryonic axes of sweet chestnut (Castanea sativa). Axis excision was accompanied by a burst of superoxide (O(2)(*-)), demonstrated by a colorimetric assay using epinephrine, electron spin resonance and staining with nitroblue tetrazolium. Superoxide was immediately produced on the cut surface after isolation of the axis from the seed, with an initial 'burst' in the first 5 min. Isolated axes subjected to variable levels of desiccation stress showed a decrease in viability and vigour and increased electrolyte leakage, indicative of impaired membrane integrity. The pattern of O(2)(*-) production showed a typical Gaussian pattern in response to increasing desiccation stress. The results indicate a complex interaction between excision and subsequent drying and are discussed with a view of manipulating ROS production for optimisation of cryopreservation protocols.


Landmark analysis at the 25-year landmark point.
This statistical primer presents the landmark analysis method, exploring its appropriate use and interpretation while recognizing its limitations. This observational method is used for comparing time-to-event outcome between groups determined during study follow-up. The goal of the landmark method is to estimate in an unbiased way the time-to-event probabilities in each group conditional on the group membership of patients at a specific time point, the landmark time. The need that led to its development, the impact of the method, and its pros and cons, along with available alternative approaches, are presented. Simulations explore its performance, using realistic parameters from a recent cardiovascular study. As long as the limitations of the method are recognized and the interpretation of its results clearly reflect their "conditional" nature, landmark analysis, 25 years from its introduction, can still be of value.


A temporal dissociation of energy liberation and high energy phosphate splitting during shortening in frog skeletal muscles.
Measurements of the time course of high energy phosphate splitting and energy liberation were performed on rapidly shortening Rana pipiens skeletal muscles. In muscles contracting 30 times against small loads (less the 0.02P), the ratio of explained heat + work (H + W) (calculated from the measured high energy phosphate splitting) to observed H + W (from myothermal and mechanical measurements) was 0.68 +/- 0.08 and is in agreement with results obtained in isometric tetani of R. pipiens skeletal muscle. In lightly afterloaded muscles which were tetanized for 0.6a and whose metabolism was arrested at 3.0 s after the beginning of stimulation, a similar ratio of explained H + W to observed H + W was obtained. However, in identical contractions in which metabolism was arrested at 0.5-0.75 s after the beginning of stimulation, the ratio of explained H + W to observed H + W declined significantly to values ranging from 0.15 to 0.40. These results suggest that rapid shortening at the beginning of contraction induces a delay between energy production and measurable high energy phosphate splitting. This interpretation was tested and confirmed in experiments in which one muscle of a pair contracted isometrically while the other contracted against a small afterload. The afterload and stimulus pattern were arranged so that at the time metabolism was arrested, 0.5 s after the beginning of stimulation, the total energy production by both muscles was the same. Chemical analysis revealed that the isotonically contracting muscle spilt only 25% as much high energy phosphate as did the isometrically contracting muscle.


The Effect of Sows' and Piglets' Behaviour on Piglet Crushing Patterns in Two Different Farrowing Pen Systems.
Pens with farrowing crate (FC) and two differently designed free-farrowing pens (LH-pens: 7.3 m², plastic flooring; GH-pens: 5 m², cast-iron and concrete flooring) were compared regarding piglet losses and postpartum sow behaviour (all treatments) and reasons for piglet crushing and postpartum litter behaviour (LH and GH). One-hundred-and-three crushing events were analysed in eight batches concerning sows' posture changes that crushed piglets and age of crushed piglets. Posture change frequency, amounts of single posture changes and total time spent in different body postures were evaluated for 41 sows (14 FC-sows, 13 LH-sows and 14 GH-sows) in six batches. Litter behaviour (location, active/inactive scoring, resting behaviour next to the sow) was analysed during sows' posture changes and piglet crushing. Piglet mortality was higher in LH (25.6%) and GH (19.9%) compared to FC (12.3%) due to higher levels of piglet crushing. Most crushing occurred during the three days postpartum in LH (92.7%) and GH (83.9%). However, crushing patterns differed between LH (rolling: 68.2%; sit-to-lie: 18.2%; stand-to-lie: 11.4%) and GH (rolling: 38.2%; sit-to-lie: 30.9%; stand-to-lie: 16.4%) and varying piglet behaviour may be the cause for this. The postpartum period was characterized by inactivity of the sow and behavioural differences were rarely seen between systems.


Three ways of reminiscence in theory and practice.
Experimental studies disagree on the frequency and effects of reminiscence among the elderly. However, efficacy in working with recollection can be increased by an understanding of three types of reminiscence: informative, evaluative and obsessive. Informative reminiscence involves recollection for the pleasure of reliving and retelling. Reviewing memories can be used to revive interest, self-esteem, and personal relationships. Evaluative reminiscence is based on Butler's life review. A more favorable resolution is likely when it ranges over the lifetime and is shared. Groups and oral history projects can be tailored to support informative and evaluative reminiscences. Obsessive reminiscence may result from guilt, stress or grief. Relieving stress and finding new outlets can be combined with techniques like psychodrama and Progoff's journal workshop, to work through obstructing experiences.


Role of SpoIVA ATPase Motifs during Clostridioides difficile Sporulation.
The nosocomial pathogen Clostridioides difficile is a spore-forming obligate anaerobe that depends on its aerotolerant spore form to transmit infections. Functional spore formation depends on the assembly of a proteinaceous layer known as the coat around the developing spore. In C. difficile, coat assembly depends on the conserved spore protein SpoIVA and the clostridial-organism-specific spore protein SipL, which directly interact. Mutations that disrupt their interaction cause the coat to mislocalize and impair spore formation. In Bacillus subtilis, SpoIVA is an ATPase that uses ATP hydrolysis to drive its polymerization around the forespore. Loss of SpoIVA ATPase activity impairs B. subtilis SpoIVA encasement of the forespore and activates a quality control mechanism that eliminates these defective cells. Since this mechanism is lacking in C. difficile, we tested whether mutations in the C. difficile SpoIVA ATPase motifs impact functional spore formation. Disrupting C. difficile SpoIVA ATPase motifs resulted in phenotypes that were typically >104-fold less severe than the equivalent mutations in B. subtilis Interestingly, mutation of ATPase motif residues predicted to abrogate SpoIVA binding to ATP decreased the SpoIVA-SipL interaction, whereas mutation of ATPase motif residues predicted to disrupt ATP hydrolysis but maintain ATP binding enhanced the SpoIVA-SipL interaction. When a sipL mutation known to reduce binding to SpoIVA was combined with a spoIVA mutation predicted to prevent SpoIVA binding to ATP, spore formation was severely exacerbated. Since this phenotype is allele specific, our data imply that SipL recognizes the ATP-bound form of SpoIVA and highlight the importance of this interaction for functional C. difficile spore formation.IMPORTANCE The major pathogen Clostridioides difficile depends on its spore form to transmit disease. However, the mechanism by which C. difficile assembles spores remains poorly characterized. We previously showed that binding between the spore morphogenetic proteins SpoIVA and SipL regulates assembly of the protective coat layer around the forespore. In this study, we determined that mutations in the C. difficile SpoIVA ATPase motifs result in relatively minor defects in spore formation, in contrast with Bacillus subtilis Nevertheless, our data suggest that SipL preferentially recognizes the ATP-bound form of SpoIVA and identify a specific residue in the SipL C-terminal LysM domain that is critical for recognizing the ATP-bound form of SpoIVA. These findings advance our understanding of how SpoIVA-SipL interactions regulate C. difficile spore assembly.


Markers of the HIV-1 reservoir: facts and controversies.
The HIV-1 reservoir is composed of infected cells poised to replicate and spread the virus upon treatment interruption. It constitutes the main obstacle toward an HIV-1 cure. Whether marker(s) may allow the detection of cells that form the reservoir is an outstanding question. Here, we present and discuss recent advances and controversies in the identification and characterization of markers of the HIV-1 reservoir. Latently infected T cells that persist under successful therapy do not express viral antigens, making their identification challenging. HIV is not equally distributed across T cells subsets. For instance, central memory, Th17, and T follicular helper cells largely contribute to viral persistence. Recently, novel markers of the reservoir have been identified. Using various strategies, different teams have reported that surface molecules such as immune checkpoints inhibitors, CD30, or CD32a may be enriched in latently infected cells or in cells harboring viral RNA. Understanding the mechanisms underlying the presence of markers of HIV-1 infected cells will provide new insights into the formation and maintenance of the viral reservoir. These markers should also facilitate the detection of persistently infected cells in patients' samples and in animal models, and represent potential targets for elimination of these cells.