Effect of fibre level, particle size and adaptation period on digestibility and rate of passage as measured at the ileum and in the faeces in the adult rabbit.
The use of specific methods other than gravimetric ones to analyse fibre permitted a more precise study of the degradation of cell wall (CW) in the digestive tract. Digesta flow and rate of passage measurements have not been assessed previously in rabbits to investigate fibre digestion and fibre effects simultaneously in the proximal and in the distal segments of the tract. The effect of the level of dietary fibre on ileal and overall digestibility and rate of passage were studied by comparing semi-purified diets containing only one source of CW (dehydrated lucerne (Medicago sativa) meal) given to adult female rabbits. The effect of fibre particle size and adaptation period were also investigated. Measurements of fibre composition using both colorimetric and gas-liquid chromatographic techniques, showed that large amounts of (CW) were degraded in the caecocolic segments. Increasing dietary fibre level reduced the rate of passage but fibre degradation was increased, at the same time a lower digestive efficiency for energy in the small intestine was found. A small quantity of CW was apparently degraded before the caecum, assuming that the water-soluble fraction of CW was essentially implicated. Grinding lucerne meal through a 1 mm instead of a 3 mm screen did not improve CW digestibility in spite of a longer rate of passage in the caeco-colic segments. Adaptation to a high-fibre diet resulted in an higher digestive volume for colon and caecum, related to an improved degradation of CW. Furthermore, digestive efficiency in the small intestine appeared higher for rabbits adapted to a high-fibre diet than that for rabbits initially fed on a low-fibre diet.


Influence of parasitic infection on food intake.
The results of controlled experiments have demonstrated unequivocally that host food intake is often altered during the course of infections with eukaryotic parasites. Generally, host food intake is reduced depending on either the infective dose given to the host or the number of established parasites present. The onset in the reduction of host food intake varies according to the species of parasite involved and may be related to a particular developmental stage or event during the course of the host-parasite relationship. Some of the many sensory, neural, and hormonal factors that are now considered to modulate food intake in healthy animals are known to be affected during certain host-parasite relationships, and it is tentatively suggested that these physiological perturbations may initiate the observed changes in host food intake. Not unexpectedly, human appetite for food and food intake have been reported to become depressed during parasitic infections.


Topological lines in 3D tensor fields and discriminant Hessian factorization.
This paper addresses several issues related to topological analysis of 3D second order symmetric tensor fields. First, we show that the degenerate features in such data sets form stable topological lines rather than points, as previously thought. Second, the paper presents two different methods for extracting these features by identifying the individual points on these lines and connecting them. Third, this paper proposes an analytical form of obtaining tangents at the degenerate points along these topological lines. The tangents are derived from a Hessian factorization technique on the tensor discriminant and leads to a fast and stable solution. Together, these three advances allow us to extract the backbone topological lines that form the basis for topological analysis of tensor fields.


Genes showing altered expression in the medial preoptic area in the highly social maternal phenotype are related to autism and other disorders with social deficits.
The mother-child relationship is the most fundamental social bond in mammals, and previous studies indicate that the medial preoptic area (MPOA) contributes to this increase in sociability. It is possible that the same genes that lead to elevated sociability in one condition (the maternal state) might also be dysregulated in some disorders with social deficits (e.g. autism). In this study, we examined whether there was enrichment (greater than chance overlap) for social deficit disorder related genes in MPOA microarray results between virgin and postpartum female mice. We utilized microarrays to assess large scale gene expression changes in the MPOA of virgin and postpartum mice. The Modular Single Set Enrichment Test (MSET) was used to determine if mental health disorder related genes were enriched in significant microarray results. Additional resources, such as ToppCluster, NIH DAVID, and weighted co-expression network analysis (WGCNA) were used to analyze enrichment for specific gene clusters or indirect relationships between significant genes of interest. Finally, a subset of microarray results was validated using quantitative PCR. Significant postpartum MPOA microarray results were enriched for multiple disorders that include social deficits, including autism, bipolar disorder, depression, and schizophrenia. Together, 98 autism-related genes were identified from the significant microarray results. Further, ToppCluser and NIH DAVID identified a large number of postpartum genes related to ion channel activity and CNS development, and also suggested a role for microRNAs in regulating maternal gene expression. WGCNA identified a module of genes associated with the postpartum phenotype, and identified indirect links between transcription factors and other genes of interest. The transition to the maternal state involves great CNS plasticity and increased sociability. We identified multiple novel genes that overlap between the postpartum MPOA (high sociability) and mental health disorders with low sociability. Thus, the activity or interactions of the same genes may be altering social behaviors in different directions in different conditions. Maternity also involves elevated risks for disorders, including depression, psychosis, and BPD, so identification of maternal genes common to these disorders may provide insights into the elevated vulnerability of the maternal brain.


Porcine dermal matrix sandwich graft for lower eyelid reconstruction.
Purpose: To report the clinical outcomes of porcine acellular dermal matrix implants sandwiched between skin and conjunctival flaps for lower eyelid reconstruction following Mohs surgery. Methods: A retrospective review was performed on patients with lower eyelid defects following Mohs surgery treated using a porcine acellular dermal matrix sandwich graft from 2013 to 2018. Patient demographics, defect size and characteristics, and collagen matrix implant dimensions were evaluated. Postoperative course and complications were also reviewed. Results: The dermal matrix sandwich graft was performed in 13 cases (12 patients). Average horizontal marginal defect width was 11.7 mm (range: 6-16 mm). Mean width of the implanted dermal matrix was 7.7 mm (range: 5-9 mm). There were no instances of infection or graft failure. The reconstructed lid had an excellent marginal contour in 11 cases (84.6%), while 2 had minimal irregularities. All patients had an excellent thickness of the reconstructed margin. One patient (7.7%) required cauterization of overgrown marginal conjunctiva after surgery. Two patients (15.4%) experienced symptomatic trichiasis, requiring electrolysis (n = 1) and epilation (n = 1). Conclusions: The dermal matrix sandwich graft is an effective method for marginal defect repair when the remaining conjunctiva and skin are sufficient to develop the necessary flaps. While the resolution of edema and erythema may take several months, an excellent final result is achieved in the majority of cases. Complications are mild, relatively uncommon, and similar to those encountered in other reconstructive procedures. This single-stage, tissue-sparing technique preserves the capability of performing future tarsoconjunctival flaps or lateral canthal procedures, should the need arise.


High repetition rate UV ultrafast laser inscription of buried channel waveguides in Sapphire: fabrication and fluorescence imaging via ruby R lines.
We report on the fabrication of buried cannel waveguides in Sapphire crystals by 250-kHz high repetition rate ultrafast laser inscription with 385 nm pulses. The propagation properties of the waveguides were studied as a function of the writing conditions. The micro-fluorescence analysis of the R lines generated by trace Cr(3+) dopant in Sapphire is used to elucidate the micro-structural modifications induced in the crystal network. It is revealed that waveguide has been formed due to local dilatation of the Sapphire network generated in the surroundings of the focal volume. The refractive index increment due to the dilatation induced electronic polarizability enhancement has been estimated to be of the order of Deltan approximately 10(-4).


Identification of Mycobacterium tuberculosis Infection in Infants and Children With Partial Discrimination Between Active Disease and Asymptomatic Infection.
Background: Improved diagnostic tests are needed for the early identification of Mycobacterium tuberculosis-infected young children exposed to an active TB (aTB) index case. We aimed to compare the diagnostic accuracy of new blood-based tests to that of the tuberculin skin test (TST) for the identification of all infected children and for a potential differentiation between aTB and latent TB infection (LTBI). Methods: 144 children exposed to a patient with aTB were included, and those who met all inclusion criteria (130/144) were classified in three groups based on results from classical investigations: non-infected (NI: n = 69, 53%, median age 10 months), LTBI (n = 28, 22%, median age 96 months), aTB disease (n = 33, 25%, median age 24 months). The first whole blood assay consisted of a 7-days in vitro stimulation of blood with four different mycobacterial antigens (40 μl/condition), followed by flow cytometric measurement of the proportions of blast cells appearing among lymphocytes as a result of their specific activation. Thresholds of positivity were determined by Receiver Operating Characteristic (ROC) curve analysis (results of NI children vs. children with LTBI/aTB) in order to identify infected children in a first stage. Other cut-offs were determined to discriminate subgroups of infected children in a second step (results from children with aTB/LTBI). Analysis of blood monocytes and dendritic cell subsets was performed on 100 μl of blood for 25 of these children as a second test in a pilot study. Results: Combining the results of the blast-induced CD3+ T lymphocytes by Heparin-Binding Haemagglutinin and by Culture Filtrate Protein-10 identified all but one infected children (sensitivity 98.2% and specificity 86.9%, compared to 93.4 and 100% for the TST). Further identification among infected children of those with aTB was best achieved by the results of blast-induced CD8+ T lymphocytes by purified protein derivative (sensitivity for localized aTB: 61.9%, specificity 96.3%), whereas high proportions of blood type 2 myeloid dendritic cells (mDC) were a hallmark of LTBI. Conclusions: New blood-based tests requiring a very small volume allow the accurate identification of M. tuberculosis-infected young children among exposed children and are promising to guide the clinical classification of children with aTB or LTBI.


Ultra-rapid and automatic interplay between L1 and L2 semantics in late bilinguals: EEG evidence.
Converging behavioral and neuroimaging evidence suggests parallel activation of native (L1) and second (L2) language codes in bilinguals, with the modulation of the N400 as the most likely neural correlate of such L1-L2 interplay at lexico-semantic level. However, this relatively late effect may reflect secondary controlled processes, in contrast to earlier modulations found in monolinguals (<200 msec) indicative of fast and automatic lexico-semantic L1 access, which has so far not been documented for bilingualism. To address this, we investigated early neurophysiological crosslinguistic activation during bilingual word access. EEG signals were recorded from a group of late bilinguals during a masked-priming crosslinguistic task in which L1 (Russian) words were presented as subliminal primes for 50 msec before L2 (English) target words. Prime-target pairs matched either phonologically only, semantically only, both phonologically and semantically, or did not match. Cluster-based random permutation analyses revealed a main effect of semantic similarity at 40-60 msec over centro-posterior scalp sites, reflecting a negative-going shift of ERP amplitudes for semantically similar prime-target pairs. Importantly, neural source reconstruction showed activations within a left-hemispheric network comprising the middle and superior temporal cortex and the angular gyrus as the most likely neural substrate of this early semantic effect. Furthermore, analyses also revealed significant differences over frontocentral sites for the main effect of semantic and phonological similarity, ranging from 312 to 356 and 380-444 msec respectively, thus confirming previously described N400 crosslinguistic effects. Our findings confirm the existence of an integrated brain network for the bilingual lexicon and reveal the earliest (∼50 msec) crosslinguistic effect reported so far, suggesting fast and automatic L1-L2 interplay, followed by later (possibly top-down controlled) processing stages.


Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid.
Type I interferons (IFNs), including alpha IFN (IFN-α) and IFN-β, potently suppress HIV-1 replication by upregulating IFN-stimulated genes (ISGs). The viral capsid protein (CA) partly determines the sensitivity of HIV-1 to IFNs. However, it remains to be determined whether CA-related functions, including utilization of known host factors, reverse transcription, and uncoating, affect the sensitivity of HIV-1 to IFN-mediated restriction. Recently, we identified an HIV-1 CA variant that is unusually sensitive to IFNs. This variant, called the RGDA/Q112D virus, contains multiple mutations in CA: H87R, A88G, P90D, P93A, and Q112D. To investigate how an IFN-hypersensitive virus can evolve to overcome IFN-β-mediated blocks targeting the viral capsid, we adapted the RGDA/Q112D virus in IFN-β-treated cells. We successfully isolated IFN-β-resistant viruses which contained either a single Q4R substitution or the double amino acid change G94D/G116R. These two IFN-β resistance mutations variably changed the sensitivity of CA binding to human myxovirus resistance B (MxB), cleavage and polyadenylation specificity factor 6 (CPSF6), and cyclophilin A (CypA), indicating that the observed loss of sensitivity was not due to interactions with these known host CA-interacting factors. In contrast, the two mutations apparently functioned through distinct mechanisms. The Q4R mutation dramatically accelerated the kinetics of reverse transcription and initiation of uncoating of the RGDA/Q112D virus in the presence or absence of IFN-β, whereas the G94D/G116R mutations affected reverse transcription only in the presence of IFN-β, most consistent with a mechanism of the disruption of binding to an unknown IFN-β-regulated host factor. These results suggest that HIV-1 can exploit multiple, known host factor-independent pathways to avoid IFN-β-mediated restriction by altering capsid sequences and subsequent biological properties.IMPORTANCE HIV-1 infection causes robust innate immune activation in virus-infected patients. This immune activation is characterized by elevated levels of type I interferons (IFNs), which can block HIV-1 replication. Recent studies suggest that the viral capsid protein (CA) is a determinant for the sensitivity of HIV-1 to IFN-mediated restriction. Specifically, it was reported that the loss of CA interactions with CPSF6 or CypA leads to higher IFN sensitivity. However, the molecular mechanism of CA adaptation to IFN sensitivity is largely unknown. Here, we experimentally evolved an IFN-β-hypersensitive CA mutant which showed decreased binding to CPSF6 and CypA in IFN-β-treated cells. The CA mutations that emerged from this adaptation indeed conferred IFN-β resistance. Our genetic assays suggest a limited contribution of known host factors to IFN-β resistance. Strikingly, one of these mutations accelerated the kinetics of reverse transcription and uncoating. Our findings suggest that HIV-1 selected multiple, known host factor-independent pathways to avoid IFN-β-mediated restriction.


Viability of Hand and Wrist Photogoniometry.
No goniometric technique is both maximally convenient and completely accurate, although photogoniometry (ie, picture taking to facilitate digital angle measurement) shows promise in this regard. Our purpose was to test the feasibility and reliability of a photogoniometric protocol designed to measure wrist and digit range of motion in general. Two independent observers examined a sample of joints in both normal and abnormal hands according to a photogoniometric protocol. Interrater and intrarater correlation were calculated, and these measurements were compared with measurements made by a third independent examiner with a manual goniometer. The photo-based measurements were reliable within and between observers; however, only a minority of these measurements were in agreement with manually collected values. At present, photogoniometry is not an acceptable alternative to manual goniometry for determining wrist and digit range of motion in general. Joint-specific photogoniometry should be the subject of future study, as should relevant imaging and software technology.


Analysis of therapeutic proteins and peptides using multiangle light scattering coupled to ultra high performance liquid chromatography.
Analysis of the physical properties of biotherapeutic proteins is crucial throughout all the stages of their lifecycle. Herein, we used size-exclusion ultra high performance liquid chromatography coupled to multiangle light scattering and refractive index detection systems to determine the molar mass, mass-average molar mass, molar-mass dispersity and hydrodynamic radius of two monoclonal antibodies (rituximab and trastuzumab), a fusion protein (etanercept), and a synthetic copolymer (glatiramer acetate) employed as models. A customized instrument configuration was set to diminish band-broadening effects and enhance sensitivity throughout detectors. The customized configuration showed a performance improvement with respect to the high-performance liquid chromatography standard configuration, as observed by a 3 h column conditioning and a higher resolution analysis in 20 min. Analysis of the two monoclonal antibodies showed averaged values of 148.0 kDa for mass-average molar mass and 5.4 nm for hydrodynamic radius, whereas for etanercept these values were 124.2 kDa and 6.9 nm, respectively. Molar-mass dispersity was 1.000 on average for these proteins. Regarding glatiramer acetate, a molar mass range from 3 to 45 kDa and a molar-mass dispersity of 1.304 were consistent with its intrinsic peptide diversity, and its mass-average molar mass was 10.4 kDa. Overall, this method demonstrated an accurate determination of molar mass, overcoming the difficulties of size-exclusion chromatography.


Sequential effects in naming: a time-criterion account.
S. J. Lupker, P. Brown, and L. Colombo (1997) reported that target naming latencies are strongly affected by the difficulty of the other stimuli in a trial block, an effect they attributed to readers' strategic use of a time criterion to guide responding. In the present research, the authors asked whether there are also trial-by-trial ("sequential") effects by examining naming latency as a function of the difficulty of the preceding stimulus. In Experiment 1, both nonwords and high-frequency regular words were named more rapidly following a word than a nonword. Experiments 2, 3, and 4 were parallel experiments involving a variety of stimulus types (e.g., high- and low-frequency inconsistent words, easy and hard nonwords). In all cases, similar sequential effects were observed (i.e., all stimulus types had shorter latencies following an easier-to-name than a harder-to-name stimulus). In terms of the time-criterion account, criterion placement appears to be affected by the relative difficulty of the preceding stimulus in a way that is independent of stimulus type.


Evaluation of Long-Term Outcomes of Transverse Facial Cleft Repair.
To evaluate the long-term outcomes of linear commissuroplasty and linear skin closure with a focus on commissural migration. Retrospective study. Individuals who underwent transverse facial cleft repair at a single institution between 2004 and 2021. The disrupted orbicularis oris muscle was reoriented and sutured. A simple linear commissuroplasty technique was used, and the cheek skin was closed linearly without Z-plasty. The distances from Cupid's bow peak to the oral commissure were measured bilaterally, and the difference between the normal and cleft sides was obtained. Finally, its proportional value as a percentage of the total lip length was calculated from short- and long-term follow-up photographs. Cheek scarring and its effects on melolabial fold breakage were evaluated. Of the 18 patients who underwent transverse facial cleft repair, 12 were included in this study. The mean follow-up period based on medical photographs was 1773.5 days. The average proportional difference was 4.6%, demonstrating no observable commissural migration. There were no consistent trends in the direction of migration, either on the cleft or normal side. In patients with a transverse cleft crossing the melolabial fold, the folds appeared broken before and after the cleft repair surgery. No significant long-term commissural migration was observed after transverse facial cleft repair with simple linear commissuroplasty and linear skin closure. Deliberate positioning of the new oral commissure, proper myoplasty, and meticulous skin closure with minimal scar burden can be considered key procedures for successful transverse cleft repair.


Patients with primary cervical dystonia have evidence of discrete deficits in praxis.
Functional imaging and electrophysiological data from patients with primary dystonia reveal widespread abnormalities in brain areas associated with higher motor functions but to date there has been little investigation of the functional consequences of these abnormalities. The aim of this study was to use a battery of tests of praxis, based on those tests used in routine clinical examination, to uncover evidence of higher motor dysfunction in patients with primary cervical dystonia. Praxis was assessed in 13 patients with primary cervical dystonia without hand involvement and in 29 age and sex matched controls. A semiquantitative praxis assessment was used which combined timed tests of meaningful and meaningless movements with copying of transitive and intratransitive hand movements and pantomime of tool use. Control tasks consisted of evaluation of motor speed, strength and a number of additional cognitive tasks. Patients made significantly more errors in copying meaningless gestures and were slow in the performance of meaningless sequences of hand movements. Copying meaningful gestures and performance of meaningful sequences of hand movements were normal. This study has identified a discrete deficit in praxis in dystonia patients and suggests additional functional consequences from the widespread pathophysiological abnormalities seen in primary dystonia.


Habitat zonation on coral reefs: Structural complexity, nutritional resources and herbivorous fish distributions.
Distinct zonation of community assemblages among habitats is a ubiquitous feature of coral reefs. The distribution of roving herbivorous fishes (parrotfishes, surgeonfishes and rabbitfishes) is a particularly clear example, with the abundance of these fishes generally peaking in shallow-water, high-energy habitats, regardless of the biogeographic realm. Yet, our understanding of the factors which structure this habitat partitioning, especially with regards to different facets of structural complexity and nutritional resource availability, is limited. To address this issue, we used three-dimensional photogrammetry and structure-from-motion technologies to describe five components of structural complexity (rugosity, coral cover, verticality, refuge density and field-of-view) and nutritional resource availability (grazing surface area) among habitats and considered how these factors are related to herbivorous fish distributions. All complexity metrics (including coral cover) were highest on the slope and crest. Nutritional resource availability differed from this general pattern and peaked on the outer-flat. Unexpectedly, when compared to the distribution of herbivorous fishes, none of the complexity metrics had a marked influence in the models. However, grazing surface area was a strong predictor of both the abundance and biomass of herbivorous fishes. The strong relationship between grazing surface area and herbivorous fish distributions indicates that nutritional resource availability may be one of the primary factors driving the distribution of roving herbivorous fishes. The lack of a relationship between complexity and herbivorous fishes, and a strong affinity of herbivorous fishes for low-complexity, algal turf-dominated outer-flat habitats, offers some cautious optimism that herbivory may be sustained on future, low-complexity, algal turf-dominated reef configurations.


Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis.
Mobilization of bone marrow-derived stem cells (BMCs) was shown to have protective effects after myocardial infarction (MI). However, the classical mobilizing agent, granulocyte-colony stimulating factor (G-CSF) relapsed after revealing an impaired homing capacity. In the search for superior cytokines, erythropoietin (EPO) appears to be a promising agent. Therefore, we analyzed in a murine model of surgically induced MI the influence of EPO treatment on survival and functional parameters as well as BMC mobilization, homing, and effect on resident cardiac stem cells (CSCs). Human EPO was injected intraperitoneally after ligation of the left anterior descendens (LAD) for 3 days with a total dose of 5000 IU/kg 6 and 30 days after MI, and pressure volume relationships were investigated in vivo. Cardiac tissues were analyzed by histology. To show the effect on BMCs and CSCs, FACS analyses were performed. Homing factors were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and ELISA. EPO-treated animals showed a significant improvement of survival post-MI (62 vs. 36%). At days 6 and 30, all hemodynamic parameters associated with attenuated remodeling, enhanced neovascularization, and diminished apoptotic cells in the peri-infarct area were improved. BMC subpopulations (CD31(+), c-kit(+), and Sca-1(+) cells) were mobilized, and homing of Sca-1(+) and CXCR4(+) BMCs toward an SDF-1 gradient into the ischemic myocardium was enhanced. However, there was no beneficial effect on CSCs. We have shown that EPO application after MI shows cardioprotective effects. This may be explained by mobilization of BMCs, which are homing via the CXCR-4/SDF-1 axis. However, EPO has no beneficial effects on resident CSCs. Therefore, new treatment regimes using EPO together with other agents may combine complementary beneficial effects preventing ischemic cardiomyopathy.


Shortening and Angulation Strategies to Address Composite Bone and Soft Tissue Defects.
Gustilo-Anderson IIIB tibial fractures and infected tibial nonunions represent particular challenges for the orthopaedic trauma surgeon. Debridement of dysvascular bone and soft tissues can create composite bone and soft tissue defects. Restoring the soft tissue envelope is a critical step in preventing or treating ongoing infection and in restoring local blood supply. Shortening and angulation techniques, including the gradual expansion muscle flap, rely on distraction histogenesis to address composite bone and soft tissue loss. These strategies can be used to treat large soft tissue defects when flap coverage or free tissue transfer is not available.


Use of Measures of Inflammation and Kidney Function for Prediction of Atherosclerotic Vascular Disease Events and Death in Patients With CKD: Findings From the CRIC Study.
Traditional risk estimates for atherosclerotic vascular disease (ASVD) and death may not perform optimally in the setting of chronic kidney disease (CKD). We sought to determine whether the addition of measures of inflammation and kidney function to traditional estimation tools improves prediction of these events in a diverse cohort of patients with CKD. Observational cohort study. 2,399 Chronic Renal Insufficiency Cohort (CRIC) Study participants without a history of cardiovascular disease at study entry. Baseline plasma levels of biomarkers of inflammation (interleukin 1β [IL-1β], IL-1 receptor antagonist, IL-6, tumor necrosis factor α [TNF-α], transforming growth factor β, high-sensitivity C-reactive protein, fibrinogen, and serum albumin), measures of kidney function (estimated glomerular filtration rate [eGFR] and albuminuria), and the Pooled Cohort Equation probability (PCEP) estimate. Composite of ASVD events (incident myocardial infarction, peripheral arterial disease, and stroke) and death. Cox proportional hazard models adjusted for PCEP estimates, albuminuria, and eGFR. During a median follow-up of 7.3 years, 86, 61, 48, and 323 participants experienced myocardial infarction, peripheral arterial disease, stroke, or death, respectively. The 1-decile greater levels of IL-6 (adjusted HR [aHR], 1.12; 95% CI, 1.08-1.16; P<0.001), TNF-α (aHR, 1.09; 95% CI, 1.05-1.13; P<0.001), fibrinogen (aHR, 1.07; 95% CI, 1.03-1.11; P<0.001), and serum albumin (aHR, 0.96; 95% CI, 0.93-0.99; P<0.002) were independently associated with the composite ASVD-death outcome. A composite inflammation score (CIS) incorporating these 4 biomarkers was associated with a graded increase in risk for the composite outcome. The incidence of ASVD-death increased across the quintiles of risk derived from PCEP, kidney function, and CIS. The addition of eGFR, albuminuria, and CIS to PCEP improved (P=0.003) the area under the receiver operating characteristic curve for the composite outcome from 0.68 (95% CI, 0.66-0.71) to 0.73 (95% CI, 0.71-0.76). Data for cardiovascular death were not available. Biomarkers of inflammation and measures of kidney function are independently associated with incident ASVD events and death in patients with CKD. Traditional cardiovascular risk estimates could be improved by adding markers of inflammation and measures of kidney function.


Is driving experience all that matters? Drivers' takeover performance in conditionally automated driving.
In conditionally automated driving, drivers are allowed to engage in non-driving related tasks (NDRTs) and are occasionally requested to take over vehicle control in situations that the automation system cannot handle. Drivers may not be able to adequately perform such requests if they have limited driving experience. This study investigates the influence of driving experience on takeover performance in conditionally automated driving. Nineteen subjects participated in this driving simulator study. The NDRTs consisted of three tasks: writing business emails (working condition), watching videos (entertaining condition), and taking a break with eyes closed (resting condition). These three NDRTs require drivers to invest high, moderate, and low levels of mental workload, respectively. The duration of engagement in each NDRT before a takeover request (TOR) was either 5 minutes (short interval) or 30 minutes (long interval). Drivers' driving experience and performance during the control period are highly correlated with their TOR performance. Furthermore, the type and duration of NDRT influence TOR performance, and inexperienced drivers exhibit poorer TOR performance than experienced drivers. These findings have relevance for the types of NDRTs that ought to be permitted during automated driving, the design of automated driving systems, and the formulation of regulations regarding the responsible use of automated vehicles.


The use of nomegestrol acetate in rapid preparation of endometrium before operative hysteroscopy in pre-menopausal women.
The presence of a thin endometrium has an important role in allowing the best conditions for hysteroscopic surgery. Here, we explored the efficacy of a 14-day administration of nomegestrol acetate, a progestogen with high progestogen potency effects, in rapid endometrial preparation to operative hysteroscopy. A total of 86 fertile women selected for operative hysteroscopy received for 14 days either 5mgday(-1) of nomegestrol acetate (n=43; group A) or 4mgday(-1) of folic acid (n=43; group B), starting on day 1 of the subsequent menstrual cycle. Before treatments on days 12-14 of the menstrual cycle, all patients underwent endometrial thickness measurement; ultrasonography of the ovaries to measure the appearance of a dominant follicle; diagnostic hysteroscopy with endometrial biopsy; plasma estradiol (E2), progesterone (P), luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels measurements. On the day of surgery, patients repeated endometrial and ovarian ultrasonography and, E2, P, LH and FSH measurement. At enrolment, endometrial thickness, mean follicular diameter and E2, P, LH and FSH concentrations did not differ between groups. At the time of operative hysteroscopy (i.e., after 14 days' treatment) group A, but not group B, showed significant (all P<0.001) reduction of endometrial thickness, mean diameter of dominant follicle, E2, P and LH concentrations. Endometrial preparation was judged more effective in group A than B, since the endometrial mucosa in all of the women of group A appeared to be very thin, hypotrophic, regular and pale. In conclusion, administration of nomegestrol acetate was effective in reducing endometrial thickness, also acting on the hypothalamus-pituitary-ovarian axis, thus allowing highly favourable operative hysteroscopic conditions.


[Post-traumatic syringomyelia (author's transl)].
We have examined a clinical case concerning a patient who, five years after a spinal cord injury, showed a series of symptoms due to the presence of a intramedullary cyst according to neurologists' general opinion. They think this cavitation is a development of acute myelomalacic cores or of a central haemorrhage. The extension of the cavities is regarded as a result of trasmission of venous pressure, brought about by coughing, straining and sneezing, to the spinal cord and of tethering of the cord at the side of trauma by dense arachnoidal adhesions, hence its adaptability to the extremes of movements is hampered.


Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status.
Breast cancer is a highly heterogeneous disease, with several different subtypes being characterized by distinct histology, gene expression patterns, and genetic alterations. The tumor suppressor gene retinoblastoma 1 (RB1) is frequently lost in both luminal-B and triple-negative tumor (TNT; i.e., estrogen receptor-, progesterone receptor-, and human epidermal growth factor receptor 2-negative) breast cancer subtypes. However, a causal role for RB1 loss in different subtypes remains undefined. Here we report that deletion of Rb alone or together with its relative p107 in mouse mammary stem/bipotent progenitor cells induced focal acinar hyperplasia with squamous metaplasia. These lesions progressed into histologically diverse, transplantable mammary tumors with features of either luminal-B or TNT subtypes. The TNTs included basal-like tumors as well as tumors that exhibited epithelial-to-mesenchymal transition (EMT). The EMT-type tumors and a subset of the basal-like tumors, but not luminal-B-like tumors, expressed mutant forms of the tumor suppressor p53. Accordingly, targeted deletion of both Rb and p53 in stem/bipotent progenitors led to histologically uniform, aggressive, EMT-type tumors. Reintroduction of Rb into these tumor cells suppressed growth in vitro and tumor formation in vivo. These results establish a causal role for Rb loss in breast cancer in mice and demonstrate that cooperating oncogenic events, such as mutations in p53, dictate tumor subtype after Rb inactivation.


The analysis of metabolite channelling in multienzyme complexes and multifunctional proteins.
Multienzyme complexes and multifunctional proteins may confer a kinetic advantage by channelling reaction intermediates between consecutive enzymes and reducing the transient time for the establishment of steady states. A general means for quantitatively assessing the contribution of channelling to the reduction of pool size and transient time is presented. Restrictions to the kinetic advantage are identified, and it is shown that no channelling advantage is obtained at high enzyme concentration or for enzymes which exhibit rapid-equilibrium kinetic behaviour.


Nanoparticle catalysts with high energy surfaces and enhanced activity synthesized by electrochemical method.
Electrochemical shape-controlled synthesis of metal nanocrystal (NC) catalysts bounded by high-index facets with high surface energy was achieved by developing a square-wave potential route. Tetrahexahedral Pt NCs with 24 {hk0} facets, concave hexoctahedral Pt NCs with 48 {hkl} facets, and multiple twinned Pt nanorods with {hk0} facets were produced. The method was employed also to synthesize successfully trapezohedral Pd NCs with 24 {hkk} facets, and concave hexoctahedral Pd NCs with 48 {hkl} facets. It has been tested that, thanks to the high-index facets with high density of atomic steps and dangling bonds, the tetrahexahedral Pt NCs exhibit much enhanced catalytic activity for equivalent Pt surface areas for electrooxidation of small organic fuels such as ethanol. These results demonstrate that the developed square-wave potential method has surmounted the limit of conventional chemical methods that could synthesize merely metal nanocrystals with low surface energy, and opened a new prospect avenue in shape-controlled synthesis of nanoparticle catalysts with high surface energy and enhanced activity.


GWAS with longitudinal phenotypes: performance of approximate procedures.
Analysis of genome-wide association studies with longitudinal data using standard procedures, such as linear mixed model (LMM) fitting, leads to discouragingly long computation times. There is a need to speed up the computations significantly. In our previous work (Sikorska et al: Fast linear mixed model computations for genome-wide association studies with longitudinal data. Stat Med 2012; 32.1: 165-180), we proposed the conditional two-step (CTS) approach as a fast method providing an approximation to the P-value for the longitudinal single-nucleotide polymorphism (SNP) effect. In the first step a reduced conditional LMM is fit, omitting all the SNP terms. In the second step, the estimated random slopes are regressed on SNPs. The CTS has been applied to the bone mineral density data from the Rotterdam Study and proved to work very well even in unbalanced situations. In another article (Sikorska et al: GWAS on your notebook: fast semi-parallel linear and logistic regression for genome-wide association studies. BMC Bioinformatics 2013; 14: 166), we suggested semi-parallel computations, greatly speeding up fitting many linear regressions. Combining CTS with fast linear regression reduces the computation time from several weeks to a few minutes on a single computer. Here, we explore further the properties of the CTS both analytically and by simulations. We investigate the performance of our proposal in comparison with a related but different approach, the two-step procedure. It is analytically shown that for the balanced case, under mild assumptions, the P-value provided by the CTS is the same as from the LMM. For unbalanced data and in realistic situations, simulations show that the CTS method does not inflate the type I error rate and implies only a minimal loss of power.


Thermal versus impedance-based ablation of renal cell carcinoma: a meta-analysis.
Percutaneous radiofrequency ablation (RFA) of renal carcinoma has become an established treatment modality. However, thermal (TB) versus impedance-based (IB)-RF generators have not been previously compared. A literature search on the application of RFA for renal masses using TB or IB-RF generators was performed. The safety, efficacy, and long-term outcomes of TB versus IB-based RFA were assessed using the outcome measures of technical success, local recurrence rate, complications, and preservation of renal function. Across the 27 included studies, pooled results suggested comparable results for technical success (TB-RFA 98.53 % vs. IB-RFA 98.78 %, P = 0.9813). Clinical efficacy results were also similar across both generators (91.0 % TB-RFA vs. 91.5 % IB-RFA; P = 0.73). At follow-up, no differences in renal function (relative risk [RR] 0.5, 95 % confidence interval [CI] 0.45-5.48), and local recurrence (RR 0.717, 95 % CI 0.49-1.50) were observed. The pooled proportion of overall complication rates was 13.1 % for TB-RFA and 11.5 % for IB-RFA. No differences in the observed parameters were found either during surgery or at follow-up.


A Gnotobiotic Pig Model for Determining Human Norovirus Inactivation by High-Pressure Processing.
Human norovirus (NoV) is responsible for over 90% of outbreaks of acute nonbacterial gastroenteritis worldwide and accounts for 60% of cases of foodborne illness in the United States. Currently, the infectivity of human NoVs is poorly understood due to the lack of a cell culture system. In this study, we determined the survival of a human NoV genogroup II, genotype 4 (GII.4) strain in seeded oyster homogenates after high-pressure processing (HPP) using a novel receptor binding assay and a gnotobiotic pig model. Pressure conditions of 350 MPa at 0°C for 2 min led to a 3.7-log10 reduction in the number of viral RNA copies in oysters, as measured by the porcine gastric mucin-conjugated magnetic bead (PGM-MB) binding assay and real-time RT-PCR, whereas pressure conditions of 350 MPa at 35°C for 2 min achieved only a 1-log10 reduction in the number of RNA copies. Newborn gnotobiotic piglets orally fed oyster homogenate treated at 350 MPa and 0°C for 2 min did not have viral RNA shedding in feces, histologic lesions, or viral replication in the small intestine. In contrast, gnotobiotic piglets fed oysters treated at 350 MPa and 35°C for 2 min had high levels of viral shedding in feces and exhibited significant histologic lesions and viral replication in the small intestine. Collectively, these data demonstrate that (i) human NoV survival estimated by an in vitro PGM-MB virus binding assay is consistent with the infectivity determined by an in vivo gnotobiotic piglet model and (ii) HPP is capable of inactivating a human NoV GII.4 strain at commercially acceptable pressure levels.


A Longitudinal Examination of Support, Self-esteem, and Mexican-origin Adolescent Mothers' Parenting Efficacy.
Guided by a risk and resilience framework, this study used a prospective longitudinal, multiple-reporter design to examine how social support from a mother figure during pregnancy interacted with Mexican-origin adolescent mothers' self-esteem to inform their parenting efficacy when their children were 10 months old. Using reports of perceived social support by adolescent mothers (Mage = 16.24, SD =099) and their mother figures (Mage = 40.84, SD = 7.04) in 205 dyads, and controlling for demographic factors (i.e., adolescent age, adolescent nativity, family income, mothers' educational attainment, adolescent-mother coresidence) and adolescents' social support from a significant other, findings indicated that social support during pregnancy was positively associated with adolescent mothers' future parenting efficacy when adolescent mothers had relatively lower self-esteem. Findings were consistent for adolescents' and mothers' reports, and emphasize the value of social support from a mother figure among adolescent mothers with lower self-esteem. Implications for interventions are presented.


What functional strategies drive drought survival and recovery of perennial species from upland grassland?
Extreme climatic events such as severe droughts are expected to increase with climate change and to limit grassland perennity. The present study aimed to characterize the adaptive responses by which temperate herbaceous grassland species resist, survive and recover from a severe drought and to explore the relationships between plant resource use and drought resistance strategies. Monocultures of six native perennial species from upland grasslands and one Mediterranean drought-resistant cultivar were compared under semi-controlled and non-limiting rooting depth conditions. Above- and below-ground traits were measured under irrigation in spring and during drought in summer (50 d of withholding water) in order to characterize resource use and drought resistance strategies. Plants were then rehydrated and assessed for survival (after 15 d) and recovery (after 1 year). Dehydration avoidance through water uptake was associated with species that had deep roots (>1·2 m) and high root mass (>4 kg m(-3)). Cell membrane stability ensuring dehydration tolerance of roots and meristems was positively correlated with fructan content and negatively correlated with sucrose content. Species that survived and recovered best combined high resource acquisition in spring (leaf elongation rate >9 mm d(-1) and rooting depth >1·2 m) with both high dehydration avoidance and tolerance strategies. Most of the native forage species, dominant in upland grassland, were able to survive and recover from extreme drought, but with various time lags. Overall the results suggest that the wide range of interspecific functional strategies for coping with drought may enhance the resilience of upland grassland plant communities under extreme drought events.


Prognostic significance of immunophenotypic and karyotypic features of Philadelphia positive B-lymphoblastic leukemia in the era of tyrosine kinase inhibitors.
Philadelphia chromosome (Ph)-positive B-lymphoblastic leukemia exhibits immunophenotypic, karyotypic, and molecular genetic heterogeneity. The prognostic significance of these parameters was assessed in the context of intensive tyrosine kinase inhibitor (TKI)-based chemotherapy. The authors studied 65 adult patients with Ph-positive acute lymphoblastic leukemia (ALL) who received treatment with TKI-based therapy, correlated their clinicopathologic heterogeneity with patient outcome, and compared the findings with those from 60 adult patients with diploid B-cell ALL who received similar chemotherapy without a TKI. Ph-positive ALL was associated with older age (P = .01), the common-B immunophenotype characterized by a greater frequency of CD13 (alanine aminopeptidase) coexpression (P = .004), CD66c (carcinoembryonic antigen-related cell adhesion molecule 3) expression (P = .007), and CD25 (interleukin-2 receptor alpha chain) expression (P < .001) and with a lower frequency of CD15 (3-fucosyl-N-acetyl-lactosamine) expression (P < .001). Conventional karyotypic analyses indicated that the Ph chromosome was the sole abnormality in 19 patients (30%), was present with other aberrancies in 43 patients (65%), and was absent (detectable only by fluorescence in situ hybridization [FISH] or quantitative reverse transcriptase-polymerase chain reaction [RT-PCR] analysis) in 3 patients (5%). The presence of the breakpoint cluster region-v-Abelson murine leukemia viral oncogene homolog fusion gene (BCR-ABL) was confirmed in all patients by FISH or RT-PCR (the 190-kDa protein [p190] construct was present in 49 patients [77%], and the p210 fusion transcript construct was present in 15 patients [23%]). The presence of a supernumerary Ph chromosome was correlated with a higher incidence of CD20 (B-lymphocyte antigen, nonglycosylated phosphoprotein) expression (P < .001), whereas the p210 construct was correlated with aberrant CD25 expression (P = .05). Outcomes were not influenced by the degree of karyotypic complexity (including the presence or absence of a supernumerary Ph chromosome), CD20 expression, or myeloid antigen expression (CD13, CD33 [myeloid lineage transmembrane receptor], CD66c). CD25 expression was associated with inferior survival in univariate analysis (P = .051) but not in multivariate analysis (P = .092). In the context of intensive, TKI-based chemotherapy, the immunophenotypic, karyotypic, and molecular heterogeneity of Ph-positive ALL no longer influences outcome.


Papaverine hydrochloride for the treatment of renal colic: an old drug revisited. A prospective, randomized study.
We assessed the efficacy of papaverine hydrochloride, a commonly used smooth muscle relaxant, for the treatment of renal colic as a single agent and in combination with sodium diclofenac. A prospective, single-blind clinical study was performed at 2 centers. A total of 86 patients with acute renal colic were randomized to 3 treatment groups of 120 mg intravenous papaverine hydrochloride (29), 75 mg intramuscular sodium diclofenac (30), and papaverine hydrochloride plus sodium diclofenac (27). Pain intensity was assessed with the Visual Analog Scale at 0, 20 and 40 minutes after treatment. Further analgesia given at patient request consisted of 1 mg/kg intramuscular meperidine. Urinalysis, complete blood evaluation and imaging were performed in all patients. All adverse effects were recorded. Baseline characteristics were similar in the 3 groups. Pain intensity decreased significantly (p <0.01) after 20 and 40 minutes in all groups. Papaverine hydrochloride was as effective as sodium diclofenac in alleviating pain and the combined treatment group showed a slight trend of more rapid relief. Significantly more patients in the papaverine group required further analgesia and 4 patients (14.8%) reported minor adverse effects (dizziness in 3, sleepiness in 1). Papaverine hydrochloride is as effective as sodium diclofenac for the short-term relief of acute renal colic pain and may be advantageous in patients with contraindications for nonsteroidal anti-inflammatory drugs. However, sodium diclofenac appears to provide a longer effective analgesia.


[Fungal biota in manned space environment and impact on human health].
It is important to promote microbiological research essential for long-term manned space activities under microgravity and in a completely closed environment in space craft in relation to long-duration space expeditions on the International Space Station (ISS) or to the moon and Mars in the future. Environmental monitoring data from the space shuttle, the Mir, and the ISS have already shown that microorganisms isolated from air and on inner surfaces of space craft were generally carried by crew members. The Japanese Experiment Module (JEM) "KIBO" was attached to the ISS and started its operation from 2008. It is an invaluable opportunity to begin the survey of the transition of microbiota, particularly fungal biota, in JEM from "brand-new" to "well-used" condition at various periods. Therefore, we are preparing the on-board analyzing systems for microbiota in air and on inner surfaces of ISS/JEM and normal microbiota of the astronauts themselves. In this paper, we introduce the current status and future plans on fungal research on ISS/JEM to protect flight crew members and flight hardware from potentially hazardous microorganisms from the environmental and biomedical aspects of Japan Aerospace Exploration Agency (JAXA).


Pencil back-projection method for SAR imaging.
We present a high-resolution method for spotlight mode SAR imaging that utilizes parametric modeling of projected target reflectivity density function and tomographic reconstruction. The method requires no polar-to-cartesian interpolation in spectral domain. Utilization of forward-backward total least squares bandpass matrix pencil method allows super resolution to be achieved in range for a single imaging angle. Hence, the quality of the image reconstructed by convolution back-projection is also improved. It is shown that the method is very resistant to noise and can generate images down to very low SNR values. Direct formulation in terms of physical quantities such as electric field and current density is another contribution of this paper.


Factors Associated With Healthcare-Acquired Catheter-Associated Urinary Tract Infections: Analysis Using Multiple Data Sources and Data Mining Techniques.
The purpose of this study was to identify factors associated with healthcare-acquired catheter-associated urinary tract infections (HA-CAUTIs) using multiple data sources and data mining techniques. Three data sets were integrated for analysis: electronic health record data from a university hospital in the Midwestern United States was combined with staffing and environmental data from the hospital's National Database of Nursing Quality Indicators and a list of patients with HA-CAUTIs. Three data mining techniques were used for identification of factors associated with HA-CAUTI: decision trees, logistic regression, and support vector machines. Fewer total nursing hours per patient-day, lower percentage of direct care RNs with specialty nursing certification, higher percentage of direct care RNs with associate's degree in nursing, and higher percentage of direct care RNs with BSN, MSN, or doctoral degree are associated with HA-CAUTI occurrence. The results also support the association of the following factors with HA-CAUTI identified by previous studies: female gender; older age (>50 years); longer length of stay; severe underlying disease; glucose lab results (>200 mg/dL); longer use of the catheter; and RN staffing. Additional findings from this study demonstrated that the presence of more nurses with specialty nursing certifications can reduce HA-CAUTI occurrence. While there may be valid reasons for leaving in a urinary catheter, findings show that having a catheter in for more than 48 hours contributes to HA-CAUTI occurrence. Finally, the findings suggest that more nursing hours per patient-day are related to better patient outcomes.


Molecular Modeling and Physicochemical Properties of Supramolecular Complexes of Limonene with α- and β-Cyclodextrins.
This study evaluated three different methods for the formation of an inclusion complex between alpha- and beta-cyclodextrin (α- and β-CD) and limonene (LIM) with the goal of improving the physicochemical properties of limonene. The study samples were prepared through physical mixing (PM), paste complexation (PC), and slurry complexation (SC) methods in the molar ratio of 1:1 (cyclodextrin:limonene). The complexes prepared were evaluated with thermogravimetry/derivate thermogravimetry, infrared spectroscopy, X-ray diffraction, complexation efficiency through gas chromatography/mass spectrometry analyses, molecular modeling, and nuclear magnetic resonance. The results showed that the physical mixing procedure did not produce complexation, but the paste and slurry methods produced inclusion complexes, which demonstrated interactions outside of the cavity of the CDs. However, the paste obtained with β-cyclodextrin did not demonstrate complexation in the gas chromatographic technique because, after extraction, most of the limonene was either surface-adsorbed by β-cyclodextrin or volatilized during the procedure. We conclude that paste complexation and slurry complexation are effective and economic methods to improve the physicochemical character of limonene and could have important applications in pharmacological activities in terms of an increase in solubility.


Phentolamine for vasodilator therapy in left ventricular failure complicating acute myocardial infarction. Haemodynamic study.
In 15 patients with acute myocardial infarction associated with signs of left ventricular dysfunction, phentolamine was infused intravenously in a dose of 10 mg per hour. This therapy induced a substantial reduction in mean right atrial pressure from 10 to 7 mmHg (1.3 to 0.9 kPa) (P) less than 0.001), and in pulmonary capillary wedge pressure from 20 to 13 mmHg (2.7 to 1.7 kPa) (P less than 0.001). The cardiac index increased from 2.5 to 3.0 1/min per m-minus 2 (P less than 0.001) accompanied by a fall in both the systemic and pulmonary vascular resistances (P less than 0.001). On the other hand, the mean stroke work index did not change significantly after phentolamine, because of tar resistance. With the dose used the mean arterial pressure decreased from 112 to 99 mmHg (14.9 to 13.2 kPa) (P less than 0.001). No adverse effects attributable to the drug treatment were noted. Benefits of this treatment are probably related to reduction in the impedance of left ventricular ejection and possibly to its relaxant effect on the venous tone. The drug may also improve subendocardial perfusion by decreasing left diastolic ventricular pressure. This could possibly limit extension of necrosis. Thus vasodilator therapy appears to be of particular interest in left ventricular failure complicating acute myocardial infarction, where inotropic agents may be contraindicated.


Quaternary structures of Vac8 differentially regulate the Cvt and PMN pathways.
Armadillo (ARM) repeat proteins constitute a large protein family with diverse and fundamental functions in all organisms, and armadillo repeat domains share high structural similarity. However, exactly how these structurally similar proteins can mediate diverse functions remains a long-standing question. Vac8 (vacuole related 8) is a multifunctional protein that plays pivotal roles in various autophagic pathways, including piecemeal microautophagy of the nucleus (PMN) and cytoplasm-to-vacuole targeting (Cvt) pathways in the budding yeast Saccharomyces cerevisiae. Vac8 comprises an H1 helix at the N terminus, followed by 12 armadillo repeats. Herein, we report the crystal structure of Vac8 bound to Atg13, a key component of autophagic machinery. The 70-Å extended loop of Atg13 binds to the ARM domain of Vac8 in an antiparallel manner. Structural, biochemical, and in vivo experiments demonstrated that the H1 helix of Vac8 intramolecularly associates with the first ARM and regulates its self-association, which is crucial for Cvt and PMN pathways. The structure of H1 helix-deleted Vac8 complexed with Atg13 reveals that Vac8[Δ19-33]-Atg13 forms a heterotetramer and adopts an extended superhelical structure exclusively employed in the Cvt pathway. Most importantly, comparison of Vac8-Nvj1 and Vac8-Atg13 provides a molecular understanding of how a single ARM domain protein adopts different quaternary structures depending on its associated proteins to differentially regulate 2 closely related but distinct cellular pathways. Ape1: aminopeptidase I; ARM: armadillo repeat; Atg: autophagy-related; AUC: analytical ultracentrifugation; Cvt: cytoplasm-to-vacuole targeting; DIC: differential interference contrast; GFP: green fluorescent protein; GST: glutathione-S-transferase; ITC: isothermal titration calorimetry; NVJ: nucleus-vacuole junction; PDB: protein data bank; PMN: piecemeal microautophagy of the nucleus; prApe1: precursor Ape1; RMSD: root-mean-square deviation; SAXS: small-angle X-ray scattering; SD-N: nitrogen starvation medium; SEC: size-exclusion chromatography; tAtg13: Atg13 construct comprising residues 567-695; tNvj1: Nvj1 construct comprising residues 229-321; tVac8: Vac8 construct comprising residues 10-515; Vac8: vacuole related 8.


[Elastomeric impression materials].
Elastomeric impression materials are in common use. The impression taken should be highly precise, thus, requiring specific care when manipulatingthese materials. There are 4 groups of elastomers; polysulfide, condensation silicone, addition silicone and polyether; each differ in their setting mechanism and their physical and chemical properties. This review elaborates the major properties of elastomers and its implications on their use. The impression material is inserted into the patient's mouth in a viscous state and transforms into viscoelastic state, upon withdrawal, influencing the residual deformation. The requirements are minimal residual deformation or maximal elastic recovery. As the mouth is a wet environment a major consideration is hydrophilicity. The wettability which is estimated by measuring either the contact angle of a droplet of water and the substrate post setting or the contact angle of a droplet of impression material and the wet tooth pre setting, determines the interaction of the material with both mouth fluids and gypsum. As the primary end target is to obtain a model depicting accurately the oral details, an attention to the impressions' compatibility with gypsum should also be given. Many studies were conducted to get a thorough understanding of the hydrophilic properties of each material, and the mechanism utilized, such as surfactants in hydrophilic PVS. Polyether is the only material that is truly hydrophilic; it exhibits the lowest contact angle, during and after setting. Recent studies show that during setting the Polyether hydrophilicity is increased compared to the condition after setting. Dimensional stability, a crucial property of the impression, is affected by the physical and chemical attributes of the material, such as its tear strength. Polysulfide has the highest tear strength. Tear Strength is affected by two major parameters, viscosity, a built-in property, and how fast the impression is pulled out of the mouth, the faster the impression is loaded and pulled out, the higher the tear strength is. The clinical use is dictated from the properties of each impression material, and the understanding of those enables the practitioner to minimize failures.


Pattern recognition of spectral entropy features for detection of alcoholic and control visual ERP's in multichannel EEGs.
This paper presents a novel ranking method to select spectral entropy (SE) features that discriminate alcoholic and control visual event-related potentials (ERP'S) in gamma sub-band (30-55 Hz) derived from a 64-channel electroencephalogram (EEG) recording. The ranking is based on a t test statistic that rejects the null hypothesis that the group means of SE values in alcoholics and controls are identical. The SE features with high ranks are indicative of maximal separation between their group means. Various sizes of top ranked feature subsets are evaluated by applying principal component analysis (PCA) and k-nearest neighbor (k-NN) classification. Even though ranking does not influence the performance of classifier significantly with the selection of all 61 active channels, the classification efficiency is directly proportional to the number of principal components (pc). The effect of ranking and PCA on classification is predominantly observed with reduced feature subsets of (N = 25, 15) top ranked features. Results indicate that for N = 25, proposed ranking method improves the k-NN classification accuracy from 91 to 93.87% as the number of pcs increases from 5 to 25. With same number of pcs, the k-NN classifier responds with accuracies of 84.42-91.54% with non-ranked features. Similarly for N = 15 and number of pcs varying from 5 to 15, ranking enhances k-NN detection accuracies from 88.9 to 93.08% as compared to 86.75-91.96% without ranking. This shows that the detection accuracy is increased by 6.5 and 2.8%, respectively, for N = 25, whereas it enhances by 2.2 and 1%, respectively, for N = 15 in comparison with non-ranked features. In the proposed t test ranking method for feature selection, the pcs of only top ranked feature candidates take part in classification process and hence provide better generalization.


Differential temperature sensitivity of synaptic and firing processes in a neural mass model of epileptic discharges explains heterogeneous response of experimental epilepsy to focal brain cooling.
Experiments with drug-induced epilepsy in rat brains and epileptic human brain region reveal that focal cooling can suppress epileptic discharges without affecting the brain's normal neurological function. Findings suggest a viable treatment for intractable epilepsy cases via an implantable cooling device. However, precise mechanisms by which cooling suppresses epileptic discharges are still not clearly understood. Cooling experiments in vitro presented evidence of reduction in neurotransmitter release from presynaptic terminals and loss of dendritic spines at post-synaptic terminals offering a possible synaptic mechanism. We show that termination of epileptic discharges is possible by introducing a homogeneous temperature factor in a neural mass model which attenuates the post-synaptic impulse responses of the neuronal populations. This result however may be expected since such attenuation leads to reduced post-synaptic potential and when the effect on inhibitory interneurons is less than on excitatory interneurons, frequency of firing of pyramidal cells is consequently reduced. While this is observed in cooling experiments in vitro, experiments in vivo exhibit persistent discharges during cooling but suppressed in magnitude. This leads us to conjecture that reduction in the frequency of discharges may be compensated through intrinsic excitability mechanisms. Such compensatory mechanism is modelled using a reciprocal temperature factor in the firing response function in the neural mass model. We demonstrate that the complete model can reproduce attenuation of both magnitude and frequency of epileptic discharges during cooling. The compensatory mechanism suggests that cooling lowers the average and the variance of the distribution of threshold potential of firing across the population. Bifurcation study with respect to the temperature parameters of the model reveals how heterogeneous response of epileptic discharges to cooling (termination or suppression only) is exhibited. Possibility of differential temperature effects on post-synaptic potential generation of different populations is also explored.


Axis I psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar disorder.
Bipolar disorder often co-occurs with other axis I disorders, but little is known about the relationships between the clinical features of bipolar illness and these comorbid conditions. Therefore, the authors assessed comorbid lifetime and current axis I disorders in 288 patients with bipolar disorder and the relationships of these comorbid disorders to selected demographic and historical illness variables. They evaluated 288 outpatients with bipolar I or II disorder, using structured diagnostic interviews and clinician-administered and self-rated questionnaires to determine the diagnosis of bipolar disorder, comorbid axis I disorder diagnoses, and demographic and historical illness characteristics. One hundred eighty-seven (65%) of the patients with bipolar disorder also met DSM-IV criteria for at least one comorbid lifetime axis I disorder. More patients had comorbid anxiety disorders (N=78, 42%) and substance use disorders (N=78, 42%) than had eating disorders (N=9, 5%). There were no differences in comorbidity between patients with bipolar I and bipolar II disorder. Both lifetime axis I comorbidity and current axis I comorbidity were associated with earlier age at onset of affective symptoms and syndromal bipolar disorder. Current axis I comorbidity was associated with a history of development of both cycle acceleration and more severe episodes over time. Patients with bipolar disorder often have comorbid anxiety, substance use, and, to a lesser extent, eating disorders. Moreover, axis I comorbidity, especially current comorbidity, may be associated with an earlier age at onset and worsening course of bipolar illness. Further research into the prognostic and treatment response implications of axis I comorbidity in bipolar disorder is important and is in progress.


New evidence on intravenous cocaine use and the risk of infection with human immunodeficiency virus type 1.
To examine whether recent intravenous use of cocaine might be associated with increased risk of human immunodeficiency virus type 1 (HIV) infection, the authors studied 2,597 active intravenous drug users: 2,399 with recent cocaine injection and 198 with recent injection of heroin or other drugs but not cocaine. These subjects were adult residents of Baltimore City and the surrounding Maryland counties, recruited via outreach into the community between February 1988 and March 1989. In contrast to the first report on the cocaine-HIV association, the present study sample was not recruited solely from drug treatment programs. In the present study, estimated HIV seroprevalence was 26.4% for recent cocaine injectors as compared with 10.6% among all other recent intravenous drug users; the relative odds estimate was 3.03. In the untreated segment of the sample, HIV seroprevalence was 26.0% for recent cocaine injectors as compared with 8.9% among others (relative odds (RO) = 3.61). The estimated degree of association did not change appreciably when multiple logistic regression was used to hold constant potentially confounding and/or mediating variables such as receptive anal intercourse, number of sex partners, and use of injection equipment obtained at shooting galleries (RO = 2.64). Augmenting these cross-sectional data, preliminary prospective data showed excess risk of HIV seroconversion among recent cocaine injectors (estimated relative risk = 2.11). While other research has examined the cocaine-HIV association, the present study differs in that it has allowed a test for whether the association was a spurious artifact of studying drug users recruited solely from drug treatment programs, a broad array of alternative determinants of HIV infection have been held constant, and the association has been examined with seroconversion data. The results lend support to the abiding concern about the risk of HIV infection among cocaine users.


A reexamination of connectivity trends via exponential random graph modeling in two IDU risk networks.
Patterns of risk in injecting drug user (IDU) networks have been a key focus of network approaches to HIV transmission histories. New network modeling techniques allow for a reexamination of these patterns with greater statistical accuracy and the comparative weighting of model elements. This paper describes the results of a reexamination of network data from the SFHR and P90 data sets using Exponential Random Graph Modeling. The results show that "transitive closure" is an important feature of IDU network topologies, and provides relative importance measures for race/ethnicity, age, gender, and number of risk partners in predicting risk relationships.


Towards a geography of fitness: an ethnographic case study of the gym in British bodybuilding culture.
During recent years, research in health geography has engaged with peoples' health as well as diseases, an interest reflected by therapeutic geographies and geographies of public health. At the same time, studies have focused on micro-contexts such as the body, reflected in geographies of diseased and disadvantaged bodies. However, little research has combined elements of the two approaches and engaged in research on active healthy bodies and fitness. Equally the sub-discipline of sports geography provides little insight into fitness activities because this research has tended to focus on elite sports, their fans and facilities. Given these contexts, a detailed case study is presented to demonstrate the potential for geographical research on fitness. Through an observational study of a specialist gym facility, the study investigates how bodybuilding culture and place are co-produced. Indeed, the gym provides a narrative resource and a crucial setting for individual body projects and collective body culture which involve social conflicts, cohesions and hierarchies, illegal and potentially health harming activities, as well as personal comfort and therapeutic attachments. It is argued that beyond this case study, many activities crosscut health maintenance, or conversely risks to health, and the enjoyment of sports and fitness. A greater emphasis therefore at the sub-disciplinary interface of sports and health geography on hybrid 'fitness geographies' may help researchers towards a more comprehensive understanding, and coverage, of health issues in society.


The surgical management of scoliosis: a scoping review of the literature.
Scoping reviews are innovative studies that can map a range of evidence to convey the breadth and depth of a large field. An evidence-based approach to the wide spectrum of surgical interventions for scoliosis is paramount to enhance clinical outcomes. The objectives of this scoping review were to identify critical knowledge gaps and direct future research. This study was completed according to the methodology of Arksey and O'Malley. Two reviewers performed duplicate systematic screening of eligibility. Studies were classified according to patient age, scoliosis etiology, outcomes reported, study design, and overall research theme. There were 1763 eligible studies published between 1966 and 2013. The literature focused on adolescents (83% of studies) with idiopathic scoliosis (72%). There was a dominance of observational designs (88%), and a paucity of randomized trials (4%) or systematic reviews (1%). Fifty six percent of studies were conducted in North America, followed by 23% in Europe and 18% in Asia. Few high-level studies investigated surgical indications, surgical approaches, surgical techniques, or implant selection. Patient important outcomes including function, health-related quality of life, pain, and rates or re-operation were infrequently reported. Current research priorities are to (1) undertake high-quality knowledge synthesis and knowledge translation activities; (2) conduct a series of planning meetings to engage clinicians, patients, and methodologists; and (3) clarify outcome reporting and strategies for methodological improvement. Higher-quality studies are specifically needed to inform surgical indications, surgical approaches, surgical techniques, and implant selection. Engaging global partners may increase generalizability.


Factors Associated With Hospital Mortality in Acute Myocardial Infarction.
Aim To determine clinical and laboratory parameters associated with in-hospital mortality in patients with acute myocardial infarction and to develop a multifactorial prognostic model of in-hospital mortality.Material and methods This was a study based on the 2019-2020 Registry of acute coronary syndrome of the Tyumen Cardiology Research Center, a branch of the Tomsk National Research Medical Center. The study included 477 patients with ST-segment elevation acute myocardial infarction (AMI), 617 patients with non-ST segment elevation AMI, and 26 patients with unspecified AMI. In-hospital mortality was 6.0 % (n=67). Clinical and laboratory parameters were assessed on the day of admission. The separation power of indicators associated with in-hospital mortality was determined using a ROC analysis. The data array of each quantitative parameter was converted into a binary variable according to the obtained cut-off thresholds, followed by creation of a multifactorial model for predicting in-hospital mortality using a stepwise analysis with backward inclusion (Wald). The null hypothesis was rejected at p<0.05.Results The multivariate model for prediction of in-hospital mortality included age (cut-off, 72 years), OR 3.0 (95 % CI: 1.5-5.6); modified shock index (cut-off threshold, 0.87), OR 1.5 (95 % CI: 1.1-2.0); creatine phosphokinase-MB (cut-off threshold, 32.8 U / L), OR 4.1 (95 % CI: 2.2-7.7); hemoglobin (121.5 g / l), OR 1.7 (95 % CI: 1.2-2.3); leukocytes (11.5×109 / l), OR 1.9 (95 % CI: 1.3-2.6); glomerular filtration rate (60.9 ml / min), OR 1.7 (95 % CI: 1.2-2.2); left ventricular ejection fraction (42.5 %), OR 4.1 (95 % CI: 2.0-8.3); and size of myocardial asynergy (32.5 %), OR 2.6 (95 % CI: 1.4-5.0).Conclusions Independent predictors of in-hospital mortality in AMI are age, modified shock index, creatine phosphokinase-MB, peripheral blood leukocyte count, hemoglobin concentration, left ventricular ejection fraction, size of myocardial asynergy, and glomerular filtration rate. The in-hospital mortality model had a high predictive potential: AUC 0.930 (95 % CI: 0.905-0.954; p <0.001) with a cutoff threshold of 0.15; sensitivity 0.851, and specificity 0.850.


Novel amoxicillin nanoparticles formulated as sustained release delivery system for poultry use.
Amoxicillin is used in the treatment and prevention of a wide range of diseases in poultry breeding. However, its short half-life and low bioavailability restrict its clinical application in these species. Entrapment of drugs into polymeric nanoparticles (nps) presents a means to improve gastrointestinal absorption and oral bioavailability of drugs. This study was aimed to overcome limitation of amoxicillin use in poultry breeding. Amoxicillin was loaded into sodium alginate-polyvinyl alcohol (NaAlg-PVA) blend nps, and characterization of the prepared nps was performed. For pharmacokinetic study, commercial male broilers were used and comparative pharmacokinetics of free and nanoparticle form of amoxicillin were investigated. Twenty-one broilers were divided into three groups. All groups received 10 mg/kg drug. Blood samples were collected, and drug plasma concentrations were determined by HPLC. The results demonstrated that the particle size, zeta potential, encapsulation efficiency, and loading capacity of the nps were 513.96 ± 19.46 nm, -45.36 ± 1.35 mV, 43.66 ± 3.30, and 12.06 ± 0.83%, respectively. In vitro drug release exhibited a biphasic pattern with an initial burst release of 18% within 2 hr followed by a sustained release over 22 hr. The pharmacokinetic results showed that amoxicillin nps have higher bioavailability and longer plasma half-life (p < .01) than free amoxicillin. These results indicate that amoxicillin nano formulation is suitable for oral administration in broilers.


Amphibian Speciation Rates Support a General Role of Mountains as Biodiversity Pumps.
AbstractContinental mountain areas cover <15% of global land surface, yet these regions concentrate >80% of global terrestrial diversity. One prominent hypothesis to explain this pattern proposes that high mountain diversities could be explained by higher diversification rates in regions of high topographic complexity (HTC). While high speciation in mountains has been detected for particular clades and regions, the global extent to which lineages experience faster speciation in mountains remains unknown. Here we addressed this issue using amphibians as a model system (>7,000 species), and we found that families showing high speciation rates contain a high proportion of species distributed in mountains. Moreover, we found that lineages inhabiting areas of HTC speciate faster than lineages occupying areas that are topographically less complex. When comparing across regions, we identified the same pattern in five biogeographical realms where higher speciation rates are associated with higher levels of complex topography. Low-magnitude differences in speciation rates between some low and high complex topographies suggest that high mountain diversity is also affected by low extinction and/or high colonization rates. Nevertheless, our results bolster the importance of mountains as engines of speciation at different geographical scales and highlight their importance for the conservation of global biodiversity.


Postlumbar puncture headache and its relation to chronic tension-type headache.
One hundred consecutive patients, the majority suffering from bilateral chronic tension-type headache, investigated with lumbar puncture, were studied as to age, sex, body mass index, diagnosis, lumbar cerebrospinal fluid pressure, and signs of inflammation in the serum in relation to postlumbar puncture headache. Patients younger than 40 years of age were significantly more prone to develop postlumbar puncture headache than patients older than 40 years of age (P = 0.01). Sex, body mass index, cerebrospinal fluid pressure, and signs of inflammation in the serum were not related to the frequency of postlumbar puncture headache in the present study. Postlumbar puncture headache occurred significantly more often in patients with bilateral chronic tension-type headache than in patients with unilateral headache (P = 0.02) and in patients without headache (P < 0.01). In a regression analysis with age, sex, and chronic tension-type headaches, only bilateral headache contributed significantly to the prediction of postlumbar puncture headache (P < 0.01). Age did not contribute apart from the common variance with chronic tension-type headache/no chronic tension-type headache. The results may indicate that postlumbar puncture headache and chronic tension-type headache have etiologic mechanisms in common, mechanisms presumably localized intracranially rather than extracranially.


Laboratory testing for ADAMTS13: Utility for TTP diagnosis/exclusion and beyond.
The metalloproteinase ADAMTS13 (a disintegrin with a thrombospondin type 1 motif, member 13), also known as VWF (von Willebrand factor) protease, may be assessed in a vast array of clinical conditions. Notably, a severe deficiency of ADAMTS13 characterizes TTP (thrombotic thrombocytopenic purpura), a rare but potentially fatal disorder associated with thrombosis due to accumulation of prothrombotic ultra-large VWF multimers. Although prompt identification/exclusion of TTP can be facilitated by rapid ADAMTS13 testing, the most commonly utilized assays are based on ELISA (enzyme linked immunosorbent assay) and require long turnaround time and have relatively limited throughput. Nevertheless, several rapid ADAMTS13 assays are now available, at least in select geographies. The current mini-review discusses these issues, as well as the potential utility of ADAMTS13 testing in a range of other conditions, including coronavirus disease 2019 (COVID-19).


[Ocular hemodynamic in patients with diabetic retinopathy according to ultrasound dopplerography data].
Hemodynamic indices were estimated in ophthalmic artery, central retinal artery and short posterior ciliary artery using ultrasound dopplerography in patients with diabetic retinopathy receiving "Piyavit'". "Piyavit" improves hemodynamic indices in this patient group resulting in increasing of visual functions and reduction of macula edema height.


Ghrelin increases growth hormone production and functional expression of NaV1.1 and Na V1.2 channels in pituitary somatotropes.
A variety of ion channels are expressed in the plasma membrane of somatotropes within the anterior pituitary gland. Modification of these channels is linked to intracellular Ca2+ levels and therefore to hormone secretion. Previous investigations have shown that the gut-derived orexigenic peptide hormone ghrelin and synthetic GH-releasing peptides (GHRPs) stimulate release of growth hormone (GH) and increase the number of functional voltage-gated Ca2+ and Na+ channels in the membrane of clonal GC somatotropes. Here, we reveal that chronic treatment with ghrelin and its synthetic analog GHRP-6 also increases GH release from bovine pituitary somatotropes in culture, and that this action is associated with a significant increase in Na+ macroscopic current. Consistent with this, Na+ current blockade with tetrodotoxin (TTX) abolished the ghrelin- and GHRP-6-induced increase in GH release. Furthermore, semi-quantitative and real-time RT-PCR analysis revealed an upregulation in the transcript levels of GH, as well as of NaV1.1 and NaV1.2, two isoforms of TTX-sensitive Na+ channels expressed in somatotropes, after treatment with ghrelin or GHRP-6. These findings improve our knowledge on (i) the cellular mechanisms involved in the control of GH secretion, (ii) the molecular diversity of Na+ channels in pituitary somatotropes, and (iii) the regulation of GH and Na+ channel gene expression by ghrelin and GHRPs.


Multistage Continuous Targeting with Quantitatively Controlled Peptides on Chitosan-Lipid Nanoparticles with Multicore-Shell Nanoarchitecture for Enhanced Orally Administrated Anticancer In Vitro and In Vivo.
A DOX-loaded polysaccharide-lecithin reverse micelles triglyceride-based oral delivery nanocarrier (D-PL/TG NPs) conjugated with (i) RGD peptide for targeting to β1 integrin of M cells and (ii) Lyp-1 peptide for targeting to the p32 receptor of MDA-MB-231 cells is used to investigate the multistage continuous targeting capabilities of these peptide-conjugated nanocarriers (GLD-PL/TG NPs) for tumor therapy. Variations in the targeting efficacy and pharmacokinetic properties are investigated by quantitatively controlling the surface density of different peptides on the nanoparticles. In vitro permeability in a human follicle-associated epithelium model and cytotoxicity against MDA-MB-231 cells indicate that the nanocarriers conjugated with high RGD peptide concentrations display a higher permeability due to the existence of M cells with higher transcytosis activity, but a higher concentration of conjugated Lyp-1 peptide exhibits the lowest cell viability. Being benefited from specific targeting of peptide conjugation, improved bioavailability and enhanced tumor accumulation are achieved by the GLD-PL/TG NPs, leading to better antitumor efficacy. The results of in vivo biodistribution and antitumor studies reveal that the effect of LyP-1 peptide is more predominant than that of RGD peptide. This proof of multistage continuous targeting may open the door to a new generation of oral drug delivery systems in targeted cancer therapy.


Shuttle peptide delivers base editor RNPs to rhesus monkey airway epithelial cells in vivo.
Gene editing strategies for cystic fibrosis are challenged by the complex barrier properties of airway epithelia. We previously reported that the amphiphilic S10 shuttle peptide non-covalently combined with CRISPR-associated (Cas) ribonucleoprotein (RNP) enabled editing of human and mouse airway epithelial cells. Here, we derive the S315 peptide as an improvement over S10 in delivering base editor RNP. Following intratracheal aerosol delivery of Cy5-labeled peptide in rhesus macaques, we confirm delivery throughout the respiratory tract. Subsequently, we target CCR5 with co-administration of ABE8e-Cas9 RNP and S315. We achieve editing efficiencies of up-to 5.3% in rhesus airway epithelia. Moreover, we document persistence of edited epithelia for up to 12 months in mice. Finally, delivery of ABE8e-Cas9 targeting the CFTR R553X mutation restores anion channel function in cultured human airway epithelia. These results demonstrate the therapeutic potential of base editor delivery with S315 to functionally correct the CFTR R553X mutation in respiratory epithelia.


Relationship of chronic histologic prostatic inflammation in biopsy specimens with serum isoform [-2]proPSA (p2PSA), %p2PSA, and prostate health index in men with a total prostate-specific antigen of 4-10 ng/ml and normal digital rectal examination.
To investigate the relationship between serum [-2]proPSA (p2PSA) and derivatives with chronic histologic prostatic inflammation (CHPI) in men undergoing prostate biopsy for suspected prostate cancer (PCa). This nested case-control study resulted from an observational prospective trial for the definition of sensibility, specificity, and accuracy of p2PSA, %p2PSA, and Beckman Coulter Prostate Health Index (PHI), in men undergoing prostate biopsy, with a total prostate-specific antigen (PSA) of 4-10 ng/mL and normal digital rectal examination. CHPI was the outcome of interest and defined as the presence of moderate to large infiltration of lymphomononuclear cells with interstitial and/or glandular disruption in absence of PCa. p2PSA, %p2PSA, and PHI were considered the index tests and compared with the established biomarker reference standard tests: tPSA, fPSA, %fPSA. Of 267 patients subjected to prostate biopsy, 73 (27.3%) patients were diagnosed with CHPI. Comparing CHPI with PCa patients, %p2PSA and PHI were found to be significantly lower, whereas fPSA and %fPSA were significantly higher. %p2PSA and PHI were the most accurate predictors of CHPI at biopsy, significantly outperforming tPSA, fPSA, and %fPSA. On the contrary, no significant differences were found in PSA, p2PSA, and derivatives between CHPI and benign prostatic hyperplasia (BPH) patients. Our findings showed that p2PSA, %p2PSA, and PHI values might discriminate PCa from CHPI or BPH, but not CHPI from BPH, in men with a total PSA 4-10 ng/mL and normal digital rectal examination. p2PSA isoform and its derivatives could be useful in clinical decision making to avoid unnecessary biopsies in patients with CHPI and elevated tPSA value.


Brown Macroalgae (Phaeophyceae): A Valuable Reservoir of Antimicrobial Compounds on Northern Coast of Spain.
The search for new sources of antimicrobial compounds has become an urgent need, due to the threat that the spread of bacterial resistance represents for global health and food safety. Brown macroalgae have been proposed as a great reservoir in the search for novel antimicrobial compounds. In this study, mid-polarity extracts were performed with a selection of 20 brown macroalgae species from northern Spain. The total polyphenol, carbohydrate and protein contents were quantified by spectrophotometry. The volatile organic compounds (VOCs) of whole macroalgae were also studied as a biomarker of their metabolic state in the representative species of the tested families by gas chromatography-mass spectrometry (GC-MS). The antimicrobial potential of the extracts was assessed by a disk diffusion assay against 20 target bacteria and further determinations of the minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) were performed by a microdilution assay for the active extracts. Ericaria selaginoides, Bifurcaria bifurcata and Dictyota dichotoma showed an antimicrobial effect against six Gram-positive strains: Bacillus cereus, Bacillus subtilis, Geobacillus stearothermophilus, Listeria monocytogenes, Staphylococcus aureus and Staphylococcus haemolyticus. The phenolic content was generally higher in the extracts that showed antimicrobial activity, followed by carbohydrates and low contents of proteins. The results obtained in this study reveal the potential of brown macroalgae as a promising alternative source of antimicrobial compounds as functional ingredients for the application in industrial fields.


Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic-scattering spectroscopy.
We review the application of fluorescence spectroscopy and elastic-scattering spectroscopy, over the ultraviolet-to-visible wavelength range, to minimally invasive medical diagnostics. The promises and hopes, as well as the difficulties, of these developing techniques are discussed.


Intravenous sedation with low-dose dexmedetomidine: its potential for use in dentistry.
This study investigated the physiologic and sedative parameters associated with a low-dose infusion of dexmedetomidine (Dex). Thirteen healthy volunteers were sedated with Dex at a loading dose of 6 mcg/kg/h for 5 minutes and a continuous infusion dose of 0.2 mcg/kg/h for 25 minutes. The recovery process was observed for 60 minutes post infusion. The tidal volume decreased significantly despite nonsignificant changes in respiratory rate, minute ventilation, oxygen saturation, and end-tidal carbon dioxide. The mean arterial pressure and heart rate also decreased significantly but within clinically acceptable levels. Amnesia to pin prick was present in 69% of subjects. A Trieger dot test plot error ratio did not show a significant change at 30 minutes post infusion despite a continued significant decrease in bispectral index. We conclude that sedation with a low dose of Dex appears to be safe and potentially efficacious for young healthy patients undergoing dental procedures.


The immunobiology of Guillain-Barré syndromes.
This presentation highlights aspects of the immunobiology of the Guillain-Barré syndromes (GBS), the world's leading cause of acute autoimmune neuromuscular paralysis. Understanding the key pathophysiological pathways of GBS and developing rational, specific immunotherapies are essential steps towards improving the clinical outcome of this devastating disorder. Much of the research into GBS over the last decade has focused on the forms mediated by anti-ganglioside antibodies, and we have made substantial progress in our understanding in several related areas. Particular highlights include (a) the emerging correlations between anti-ganglioside antibodies and specific clinical phenotypes, notably between anti-GM1/anti-GD1a antibodies and the acute motor axonal variant and anti-GQ1b/anti-GT1a antibodies and the Miller Fisher syndrome; (b) the identification of molecular mimicry between GBS-associated Campylobacter jejuni oligosaccharides and GM1, GD1a, and GT1a gangliosides as a mechanism for anti-ganglioside antibody induction; (c) the development of rodent models of GBS with sensory ataxic or motor phenotypes induced by immunisation with GD1b or GM1 gangliosides, respectively. Our work has particularly studied the motor nerve terminal as a model site of injury, and through combined active and passive immunisation paradigms, we have developed murine neuropathy phenotypes mediated by anti-ganglioside antibodies. This has been achieved through use of glycosyltransferase and complement regulator knock-out mice, both for cloning anti-ganglioside antibodies and inducing disease. Through such studies, we have proven a neuropathogenic role for murine anti-ganglioside antibodies and human GBS-associated antisera and identified several determinants that influence disease expression including (a) the level of immunological tolerance to microbial glycans that mimic self-gangliosides; (b) the ganglioside density in target tissue; (c) the level of complement activation and the neuroprotective effects of endogenous complement regulators; and (d) the role of calcium influx through complement pores in mediating axonal injury. Such studies provide us with clear information on an antibody-mediated pathogenesis model for GBS and should lead to rational therapeutic testing of agents that are potentially suitable for use in humans.


Fever in the Returning Traveler.
It is predicted that approximately two billion tourist trips to foreign countries will be taken worldwide each year by 2030. Germany has long been among the most active countries in tourism. The frequency of illness among persons returning from developing and newly industrialized countries is 43-79%. The appropriate diagnosis of fever in returning travelers is a clinically important matter, as it can be a sign of a life-threatening illness. This review is based on publications (2001-2022) retrieved by a selective search in PubMed for studies on the epidemiology, diagnosis, and treatment of febrile illnesses in returning travelers, or on specific tropical diseases. Diarrhea, fever, and skin changes are the most common manifestations of disease after travel to tropical and sub - tropical areas. The diagnostic evaluation should be performed in a series of steps, beginning with a precise travel history and the identification of specific risk factors. Among travelers returning from sub-Saharan Africa, Plasmodium falciparum malaria is the most common cause of fever on presentation to centers for infectious diseases and tropical medicine, affecting approximately 50 per 1000 travelers. Among persons returning from travel to Southeast Asia, dengue fever is the most common infectious disease, affecting 50-160 per 1000 travelers. Further potentially dangerous diseases include chikungunya and zika fever, typhoid and paratyphoid fever, amoebic liver abscess, visceral leishmaniasis (kala-azar), leptospirosis, and, very rarely, imported cases of viral hemorrhagic fever. COVID-19 and influenza are important differential diagnoses. The differential diagnosis can be narrowed by thorough history-taking with particular attention to the patient's travel route, combined with a good knowledge of the geographic spread and incubation times of the main tropical diseases. Algorithms help clinicians to focus the diagnostic work-up and select the appropriate further laboratory tests and diagnostic procedures.


Therapy of endocrine disease: steroidogenesis enzyme inhibitors in Cushing's syndrome.
Steroidogenesis enzyme inhibitors are the mainstay of medical therapy in Cushing's syndrome (CS). Ketoconazole (KTZ) and metyrapone are the most commonly used agents. Although there is considerable experience of their use in individual specialist centres, these drugs have not been rigorously tested in prospective clinical trials. Clinicians face uncertainties and concerns with respect to the safety profile of these agents, and best means to monitor effect. We review steroidogenesis inhibitors in the management of CS, including older agents (KTZ, metyrapone, etomidate and mitotane) and those currently under development (LCI699, non-racemic KTZ), and offer a practical approach for their use in clinical practice.