A 220 GHz-1.1 THz continuous frequency and polarization tunable quasi-optical electron paramagnetic resonance spectroscopic system.
Here, we describe a custom-designed quasi-optical system continuously operating in the frequency range 220 GHz to 1.1 THz with a temperature range of 5-300 K and magnetic fields up to 9 T capable of polarization rotation in both transmitter and receiver arms at any given frequency within the range through a unique double Martin-Puplett interferometry approach. The system employs focusing lenses to amplify the microwave power at the sample position and recollimate the beam to the transmission branch. The cryostat and split coil magnets are furnished with five optical access ports from all three major directions to the sample sitting on a two-axes rotatable sample holder capable of performing arbitrary rotations with respect to the field direction, enabling broad accessibility to experimental geometries. Initial results from test measurements on antiferromagnetic MnF2 single crystals are included to verify the operation of the system.


Inflection point of ascending aortic waveform is a predictive factor for major adverse cardiac events after successful coronary stent placement in acute myocardial infarction.
The reflection waveform in the ascending aortic pressure has been reported to reflect systemic arterial stiffness, and increase the risk of coronary heart disease. The purpose of this study is to evaluate prospectively whether the reflection waveform in the ascending aortic pressure is associated with the risk of major adverse cardiac events (MACE) after successful coronary stenting in acute myocardial infarction (AMI). One hundred and twenty-five patients with AMI and undergoing successful coronary stenting were enrolled in this study. We measured the inflection time to determine the reflection waveform in the ascending aortic pressure at angioplasty. Inflection time was defined as the time interval from initiation of a systolic pressure waveform to the inflection point. During a period of 2945 person-months, we confirmed 42 cases of MACE. Shorter inflection time increased incident MACE. Kaplan-Meier analysis demonstrated a significantly reduced event-free rate in patients with inflection time < or = 86 ms (MACE; p < 0.01, cardiovascular death; p < 0.001 by log-rank test). The multiple-adjusted hazard ratio for a I standard deviation (SD) magnitude decrease in inflection time was 1.46 (95% confidence interval, 1.03 to 2.05) for MACE, and 5.76 (95% confidence interval, 1.78 to 18.67) for cardiovascular death. Shorter inflection time increased the risk of MACE after successful coronary stenting in patients with AMI.


Interactions of nitrilotriacetic acid (NTA) with Cr(VI) compounds in the induction of gene mutations in cultured mammalian cells.
We used the V79 Chinese hamster cell line to detect the induction by NTA of 6-thioguanine resistance, due to mutation at the HGPRT locus, with direct and indirect mutagens as positive controls. NTA was tested within the 10(-4)-1.5 X 10(-2) M concentration range: although it was cytotoxic above the 10(-2) M dose, it did not increase the frequency of mutations at any of the tested concentrations, independently of metabolic activation (rat-liver S9 fraction). NTA is known to dissolve heavy metals and therefore to increase their genotoxicity. We found that an insoluble Cr(VI) compound, lead chromate (PbCrO4), was not cytotoxic nor mutagenic on V79 cells, probably because it is taken up by the cells very slowly, whereas the presence of NTA (2.5 X 10(-3) M in water) elicited a direct cytotoxicity and mutagenicity, which was dose-dependent from 5 X 10(-5) M to 10(-4) M PbCrO4. This effect was due to solubilization of the chromate anion by NTA, as determined by comparing spectrophotometric determinations of Cr(VI) in PbCrO4 treatment solutions with a mutagenicity titration curve obtained with a completely soluble Cr(VI) salt (potassium dichromate, K2Cr2O7).


The influence of motor unit composition and stature on fractionated patellar reflex times in untrained men.
The purpose of the present study was to investigate the influence of muscle fibre composition and stature on fractionated patellar reflex times in ten healthy untrained men (mean age: 23.3 years, SD 3.1; mass: 65.9 kg, SD 8.5; height: 172.3 cm, SD 5.3). Biopsies were taken from the right vastus lateralis muscle. Using staining for myofibrillar adenosine triphosphatase after pre-incubation at pH 4.3 and 4.6, muscle fibres were classified into slow twitch (ST), fast twitch, oxidative-glycolytic (FTa) and fast twitch, glycolytic (FTb) fibres. Total patellar reflex time (TRT) and its fractionated components--reflex latency (LAT) and reflex motor time (MT)--were obtained from the mean of ten trials in each subject whilst performing Jendrassik's maneuvre. The TRT, LAT and MT were 77.7 ms, SD 16.5, 23.4 ms, SD 1.3 and 54.2 ms, SD 16.3, respectively. The LAT was significantly correlated to the percentage number of ST (r = 0.758, P less than 0.05) and FTa fibres (r = -0.657, P less than 0.05), fast twitch:slow twitch ratio (r = -0.799, P less than 0.01) and to the height of the subjects (r = 0.901, P less than 0.001), whereas TRT and MT were not significantly correlated with either fibre types or the height of the subjects. From these results it can be concluded that the LAT during the patellar reflex is influenced by muscle fibre composition and the length of the sensory and/or motor nerve.


Genome-wide effects of postglacial colonization in Arabidopsis lyrata.
The perennial outcrossing Arabidopsis lyrata is becoming a plant model species for molecular ecology and evolution. However, its evolutionary history, and especially the impact of the climatic oscillations of the Pleistocene on its genetic diversity and population structure, is not well known. We analyzed the broad-scale population structure of the species based on microsatellite variation at 22 loci. A wide sample in Europe revealed that glaciations and postglacial colonization have caused high divergence and high variation in variability between populations. Colonization from Central Europe to Iceland and Scandinavia was associated with a strong decrease of genetic diversity from South to North. On the other hand, the Russian population included in our data set may originate from a different refugium probably located more to the East. These genome-wide patterns must be taken into account in studies aiming at elucidating the genetic basis of local adaptation. As shown by sequence data, most of the loci used in this study do not evolve like typical microsatellite loci and show variable levels of homoplasy: this mode of evolution makes these markers less suitable to investigate the between-continent divergence and more generally the worldwide evolution of the species. Finally, a strong negative correlation was detected between levels of within-population diversity and indices of differentiation such as F(ST). We discuss the causes of this correlation as well as the potential bias it induces on the quantification and interpretation of population structure.


Automatic multicommuted flow-batch setup for photometric determination of mercury in drinking water at ppb level.
Herein, a multicommuted flow-batch setup and a photometric procedure for the determination of mercury at the ppb level in aqueous samples are described. The setup was designed to implement a versatile solvent extraction and pre-concentration strategy by combining flow-batch and multicommuted flow analysis approaches. The photometric method was based on Hg(II) reaction with dithizone in a chloroform medium, which was also used as the extracting organic solvent. The flow analysis system was composed of a homemade syringe pump module, a set of solenoid valves, two Aquarius mini-pumps, and a flow-batch chamber. The homemade photometer was comprised of a light emitting diode (LED), photodiode, and homemade flow cell (50 mm length). The flow system and photometer were controlled using an Arduino Due board, running custom-written software. After optimizing the operational conditions, the effectiveness of the developed system was evaluated for the determination of the mercury concentration in drinking water. For accuracy assessment, samples were analyzed using a spiking methodology and an independent method, yielding a recovery ranging from 92% to 108%. Other important characteristics of the proposed method were found as follows: linear response range, 0.5-10.0 μg L-1 (r = 0.9984); limit of detection 0.38 μg L-1 Hg(II); consumption of dithizone and chloroform, 1.85 μg L-1 and 0.8 mL per analysis, respectively; coefficient of variation, 2% (n = 10); sampling throughput, 20 determinations per h.


Identification of two novel epitopes targeting glycoprotein E of pseudorabies virus using monoclonal antibodies.
Pseudorabies virus (PRV), the agent of pseudorabies, has raised considerable attention since 2011 due to the outbreak of emerging PRV variants in China. In the present study, we obtained two monoclonal antibodies (mAbs) known as 2E5 and 5C3 against the glycoprotein E (gE) of a PRV variant (JS-2012 strain). The two mAbs reacted with wild PRV but not the vaccine strain (gE-deleted virus). The 2E5 was located in 161RLRRE165, which was conserved in almost of all PRV strains, while 5C3 in 148EMGIGDY154 was different from almost of all genotype I PRV, in which the 149th amino acid is methionine (M) instead of arginine (R). The two epitopes peptides located in the hydrophilic region and reacted with positive sera against genotype II PRV (JS-2012), which suggests they were likely dominant B-cell epitopes. Furthermore, the mutant peptide 148ERGIGDY154 (genotype I) did not react with the mAb 5C3 or positive sera against genotype II PRV (JS-2012). In conclusion, both mAb 2E5 and 5C3 could be used to identify wild PRV strains from vaccine strains, and mAb 5C3 and the epitope peptide of 5C3 might be used for epidemiological investigation to distinguish genotype II from genotype I PRV.


Comparison of patient satisfaction with acrylic and flexible partial dentures.
Restoration of partial edentulous mouth may be done using a variety of treatment options. Removable partial denture (RPD) is commonly used because of its availability. RPDs from flexible resins unlike those from acrylic engage hard and soft tissue undercuts and feel more comfortable in the mouth. The aim of the study was to compare satisfaction with dentures made from these two types of materials. It was a quasi-experimental study among thirty patients at the Prosthetics Clinic, University College Hospital, Ibadan. Patients aged 16 years or more, requiring RPDs with one to three missing teeth in the anterior region of either the upper or lower arch participated. A modified semi-structured interviewer-administered questionnaire was used to collect data on sociodemographics and oral health variables. The level of satisfaction was assessed using a visual analogue scale. Data were analysed using descriptive and multivariate statistics at a significance level of P < 0.05. The participants' ages ranged between 16 and 51 years, mean age was 33.8 ± 10.01 years. Male: female ratio was 1:1 and mean duration of edentulousness was 11.37 ± 10.52 years (median - 9.50). Most 28 (93.3%) subjects delayed replacement of their missing teeth; reasons were indifference 13 (43.4%), financial constraint 10 (33.3%), ignorance 4 (13.3%) and fear of aspiration 1 (3.3%). Overall, 21 (70.0%) participants were more satisfied with the flexible dentures, 6 (20.0%) with acrylic dentures while 3 (10.0%) were equally satisfied with both types of dentures (P = 0.04). Subjects were more satisfied with the flexible RPD than the acrylic resin RPD.


Vitamin D receptors and anti-proliferative effects of vitamin D derivatives in human pancreatic carcinoma cells in vivo and in vitro.
The GER human pancreatic carcinoma cell line possesses receptors for 1,25-dihydroxyvitamin D3. We report that the vitamin D analogue EB 1089 inhibits the growth of these cells in vitro and when grown as tumour xenografts in immunodeficient mice. Tumour-bearing mice were given EB 1089 at a dose of 5 microg kg(-1) body weight i.p. thrice weekly for 4-6 weeks. Tumour growth was significantly inhibited in treated animals compared with controls in the absence of hypercalcaemia. These findings may have therapeutic implications in pancreatic cancer.


Torsional stability of cross-link configurations: a biomechanical analysis.
Cross-link systems have been used to augment segmental spinal instrumentation since the earliest introduction of these fixation systems. Although transverse cross-links have little impact on sagittal motion of spinal constructs, cross-linkage does affect torsional rigidity. Despite the wide variety of cross-link designs, almost all have been configured as transverse devices. The relative mechanical benefit of different cross-link configurations is not known. The purpose of this study was to compare the torsional stability of three different cross-link configurations. Biomechanical analysis of segmental instrumentation constructs using porcine spines. Thoracic porcine spines (T4 to T10) were instrumented with 6.5-mm conical pedicle screws and 7.0-mm connecting rods from T5 to T9. Terminal vertebrae were embedded in polymethylmethacrylate (PMMA) after a T7 corpectomy. Four cross-link configurations were tested in a randomized manner: Un-cross-linked Control (CONT); Transverse Rod-Rod (RR); Transverse Screw-Screw (SS); and Diagonal Screw-Screw (DX) Cross-links. The specimens were rotated to 3 Nm at a rate of 0.2 degrees/s and cycled six times with data acquisition over the final two cycles. Stiffness, rotation, and energy data were normalized to each control. A Newman-Keuls repeated measures analysis of variance was used to infer significant differences. Diagonal cross-link configurations provided the most rigid construct. Transverse cross-links did not significantly change torsional behavior compared with the unlinked control. Rotation and energy expended were not significantly greater torsional stiffness compared with other constructs tested (p<.01). The diagonal cross-link configuration provided increased torsional stiffness as compared with unlinked or transverse configurations. This observation should be considered in future cross-link designs.


Progressive lateralization and constant hip geometry in children with DDH, NDH, and LCPD following hip reconstructive surgery: a cohort study of 73 patients with a mean follow-up of 4.9 years.
Pelvic and femoral osteotomies have been effective methods to treat developmental dysplasia of the hip (DDH), neurogenic dislocation of the hip (NDH), and Legg-Calvé-Perthes disease (LCPD). The aim of this study was to evaluate the mid-term results after hip reconstruction in children with DDH, NDH, and LCPD. In a retrospective study, X-rays of 73 children (2-19 years) with DDH, NDH, and LCPD were measured before, 3 months, and at final follow-up (FU) after hip reconstructive surgery (open reduction, and femoral and/or pelvic osteotomy ± soft-tissue procedures between 2008 and 2018). Measurement of hip geometry included acetabular index (AI), center-edge angle (CE), and Reimers migration index (RMI). Mean follow-up time at final FU was 4.9 years. P value was set P < 0.05. After surgery (femoral osteotomy: 84 hips, Salter innominate osteotomy: 21 hips, Pemberton osteotomy: 30 hips, open reduction: 28 hips, Chiari osteotomy: 4 hips, and soft-tissue release: 24 hips), hip geometry parameters improved significantly. Nevertheless, at final FU, there was deterioration in hip geometry with femoral head lateralization (RMI) compared to the data at 3 months after surgery (RMI: preop/3 months/final FU: 40.6 ± 16.1%/6.1 ± 9.0/15.4 ± 16.0%; CE: 11.3° ± 20.0°/30.2° ± 9.5°/27.9 ± 15.4°; AI: 28.8° ± 9.6°/19.1° ± 7.6°/18.3 ± 7.6°). Sub-group analysis did not show differences concerning the progression of RMI in DDH, NDH, and LCPD at final FU. Regardless of basic disease, the lateralization was observed in all three groups (DDH, NDH, and LCPD) and statistically significant comparing X-rays 3 months postoperatively to maximum follow-up (DDH; NDH; LCPD: 2.7 ± 6.8%/7.6 ± 10.1%; 13.7 ± 15.3%/22.8 ± 19.8%; 1.7 ± 4.1%/14.9 ± 11.3%). Additional soft-tissue release techniques in patients with DDH or NDH did not show postoperative differences with statistical significance. Concerning surgical techniques, a connection between the lower RMI and the procedure of osteotomy of the ilium was found. In 25 patients, (34%) complications were observed: superficial skin lesions in 8, deep skin lesions in 3, contraction of adductors in 3, subluxation in 2, dislocations of the cast in 2, osteonecrosis of the femoral head in 2 cases, reluxation in 1, infection of the implanted plate in 1, compliance problem in 1, delayed bone healing in 1, and contraction of knee flexors in 1 case. The basic results of this study show a significant improvement of hip geometry at a follow-up of 4.9 years and prove findings of previously published literature. Moreover, the study was able to show a progression of RMI in all patient groups, which have undergone reconstructive surgery, despite basic hip geometry data (AI, CE angle) did not change. Those findings were independent from underlying pathology. Complications were counted in 34% of the patients and involved all known adverse events after hip reconstructive surgery. This makes clear why annual follow-up checks are needed not to miss the right indication for revision surgery. Evidence level: Level IV, case series. This manuscript is part of a prospective randomized clinical trial, registered in the German Clinical Trials Register DRKS-ID: DRKS00016861.


LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease.
Genetic variation in the leucine-rich repeat and Ig domain containing 1 gene (LINGO1) was recently associated with an increased risk of developing essential tremor (ET) and Parkinson disease (PD). Herein, we performed a comprehensive study of LINGO1 and its paralog LINGO2 in ET and PD by sequencing both genes in patients (ET, n=95; PD, n=96) and by examining haplotype-tagging single-nucleotide polymorphisms (tSNPs) in a multicenter North American series of patients (ET, n=1,247; PD, n= 633) and controls (n=642). The sequencing study identified six novel coding variants in LINGO1 (p.S4C, p.V107M, p.A277T, p.R423R, p.G537A, p.D610D) and three in LINGO2 (p.D135D, p.P217P, p.V565V), however segregation analysis did not support pathogenicity. The association study employed 16 tSNPs at the LINGO1 locus and 21 at the LINGO2 locus. One variant in LINGO1 (rs9652490) displayed evidence of an association with ET (odds ratio (OR) =0.63; P=0.026) and PD (OR=0.54; P=0.016). Additionally, four other tSNPs in LINGO1 and one in LINGO2 were associated with ET and one tSNP in LINGO2 associated with PD (P<0.05). Further analysis identified one tSNP in LINGO1 and two in LINGO2 which influenced age at onset of ET and two tSNPs in LINGO1 which altered age at onset of PD (P<0.05). Our results support a role for LINGO1 and LINGO2 in determining risk for and perhaps age at onset of ET and PD. Further studies are warranted to confirm these findings and to determine the pathogenic mechanisms involved.


Gastrointestinal Side Effects of Triple Immunosuppressive Therapy Evaluated by AC Biosusceptometry and Electrogastrography in Rats.
Triple immunosuppressive therapy is associated with several gastrointestinal disorders. The aim of this study was to investigate the effects induced by the triple immunosuppressive therapy on the gastrointestinal tract of rats. Male Wistar rats were randomly assigned into three experimental groups: Control: filtered water; TAC + MPS + PRED: treated with Tacrolimus plus Mycophenolate Sodium plus Prednisone; and CSA + AZA + PRED: treated with Cyclosporine plus Azathioprine plus Prednisone. The treatment was done for 14 days by gavage. Gastric emptying and contractility were evaluated by the Alternating Current Biosusceptometry (ACB) and Electrogastrography (EGG). Histological, biochemical and hematological analyses were also performed. Gastric emptying time was slower in the CSA + AZA + PRED group in comparison with control (p<0.01) and TAC + MPS + PRED groups (p<0.001). Animals treated with TAC + MPS + PRED showed accelerated gastric emptying (p<0.05) compared to control. The amplitude of gastric contractions in both immunosuppressed groups was higher than observed in the control. The frequency of gastric contractions for the CSA + AZA + PRED group was also increased (p<0.01). Results obtained by EGG were similar to those recorded with the ACB. The thickness of the circular layer from stomach muscle decreased in both immunosuppressed groups, while the longitudinal layer was reduced only in the CSA + AZA + PRED group. Triple immunosuppressive therapy alters gastric motility, compromises the muscular layers and the association between CSA, AZA, and PRED provokes the major alterations in the structure and gastric function. Specific gastrointestinal side effects resulting from different immunosuppressive therapies still need to be elucidated in order to provide more effective and personalized therapy for patients.


Turbo prediction: a new approach for bioactivity prediction.
Nowadays, activity prediction is key to understanding the mechanism-of-action of active structures discovered from phenotypic screening or found in natural products. Machine learning is currently one of the most important and rapidly evolving topics in computer-aided drug discovery to identify and design new drugs with superior biological activities. The performance of a predictive machine learning model can be enhanced through the optimal selection of learning data, algorithm, algorithm parameters, and ensemble methods. In this article, we focus on how to enhance the prediction model using the learning data. However, get an option to add more and accurate data is not easy and available in many cases. This motivated us to propose the turbo prediction model, in which nearest neighbour structures are used to increase prediction accuracy. Five datasets, well known in the literature, were used in this article and experimental results show that turbo prediction can improve the quality prediction of the conventional prediction models, particularly for heterogeneous datasets, without any additional effort on the part of the user carrying out the prediction process, and at a minimal computational cost.


Impact of Parkinson's Disease on Caregiver Quality of Life in Japan.
Parkinson's disease (PD) adversely affects the quality of life (QoL) of not only patients but also their caregivers. To determine the factors that most impact the QoL of family caregivers of patients with PD in a large Japanese population using data from the Japanese Quality-of-Life Survey of Parkinson's Disease (JAQPAD) study. Questionnaires, including the Parkinson's Disease Questionnaire-Carer (PDQ-Carer), were distributed to patients and their caregivers. Univariate and multivariate regression analyses were performed with the PDQ-Carer Summary Index (SI) score as the dependent variable to determine the factors that impact caregiver QoL. Overall, 1,346 caregivers were included in the analysis. Female sex, unemployment, caring for a patient with a high-level need for nursing care, and a high Nonmotor Symptoms Questionnaire score were factors with a significant negative impact on caregiver QoL. Results from this study identified several factors that affect caregiver QoL in Japan.


Synthetic neural-like computing in microbial consortia for pattern recognition.
Complex biological systems in nature comprise cells that act collectively to solve sophisticated tasks. Synthetic biological systems, in contrast, are designed for specific tasks, following computational principles including logic gates and analog design. Yet such approaches cannot be easily adapted for multiple tasks in biological contexts. Alternatively, artificial neural networks, comprised of flexible interactions for computation, support adaptive designs and are adopted for diverse applications. Here, motivated by the structural similarity between artificial neural networks and cellular networks, we implement neural-like computing in bacteria consortia for recognizing patterns. Specifically, receiver bacteria collectively interact with sender bacteria for decision-making through quorum sensing. Input patterns formed by chemical inducers activate senders to produce signaling molecules at varying levels. These levels, which act as weights, are programmed by tuning the sender promoter strength Furthermore, a gradient descent based algorithm that enables weights optimization was developed. Weights were experimentally examined for recognizing 3 × 3-bit pattern.


Protection of Batf3-deficient mice from experimental cerebral malaria correlates with impaired cytotoxic T-cell responses and immune regulation.
Excessive inflammatory immune responses during infections with Plasmodium parasites are responsible for severe complications such as cerebral malaria (CM) that can be studied experimentally in mice. Dendritic cells (DCs) activate cytotoxic CD8+ T-cells and initiate immune responses against the parasites. Batf3-/- mice lack a DC subset, which efficiently induces strong CD8 T-cell responses by cross-presentation of exogenous antigens. Here we show that Batf3-/- mice infected with Plasmodium berghei ANKA (PbA) were protected from experimental CM (ECM), characterized by a stable blood-brain barrier (BBB) and significantly less infiltrated peripheral immune cells in the brain. Importantly, the absence of ECM in Batf3-/- mice correlated with attenuated responses of cytotoxic T-cells, as their parasite-specific lytic activity as well as the production of interferon gamma and granzyme B were significantly decreased. Remarkably, spleens of ECM-protected Batf3-/- mice had elevated levels of regulatory immune cells and interleukin 10. Thus, protection from ECM in PbA-infected Batf3-/- mice was associated with the absence of strong CD8+ T-cell activity and induction of immunoregulatory mediators and cells.


Quantitative Behavioral Analysis and Qualitative Classification of Attachment Styles in Domestic Dogs: Are Dogs with a Secure and an Insecure-Avoidant Attachment Different?
Since several modified Strange Situation Procedures (SSP) have been used to investigate dog-to-owner attachment, in this study two different samples of dog-owner dyads underwent two modified versions of the SSP. Dogs' attachment style to the owner was assessed based on a novel adaptation of the attachment pattern classification used for infant-caregivers. Dogs' behavioral data were collected using continuous sampling and, in the second protocol, also with a scoring system for greeting and social play. In both studies, secure and avoidant dogs' behavior was compared using the Mann Whitney test, while differences within each group across episodes were analyzed using the Wilcoxon paired sample test. The classification seemed to be effective at identifying both avoidant and secure attachment patterns in dogs. As expected, differences in key attachment behaviors, such as proximity/contact seeking toward the caregiver, between secure and avoidant dogs were more evident in the final episodes of the test. Differently from secure dogs, avoidant dogs did not show an increase in proximity/contact seeking behavior with the caregiver in any of the procedures. Further studies with larger samples are needed to support the effectiveness of this classification and investigate on the remaining attachment styles.


Preventing hairline elevation in endoscopic browlifts.
An endoscopic-assisted method of brow elevation using galea aponeurosis plication with direct suture fixation is presented. This technique does not elevate the hairline, nor is any skin or scalp resected. Dissection is easy because it is limited to the subgaleal plane of the forehead.


[Peroneal tendon pathologies : From the diagnosis to treatment].
Peroneal tendon pathologies are rare but often underdiagnosed. There may be an association with chronic lateral ankle instability as well as with varus hindfoot alignment. Pathologies of the tendons fall into three categories: tendinitis and tenosynovitis, tendon ruptures and tears, and tendon subluxation and dislocation. Magnetic resonance imaging is the standard method for radiological assessment; however, the diagnosis and treatment are based primarily on patient history and clinical examination. A primary conservative treatment can be attempted, except for peroneal tendon dislocations in professional athletes. Surgical treatment should be targeted to the underlying pathology and can accordingly vary from tendoscopic synovectomy to anatomic repair of the superior peroneal retinaculum with deepening of the retromalleolar groove. Postoperative results show high patient satisfaction and low reluxation rates.


Clinical psychology Ph.D. program rankings: evaluating eminence on faculty publications and citations.
Program rankings and their visibility have taken on greater and greater significance. Rarely is the accuracy of these rankings, which are typically based on a small subset of university faculty impressions, questioned. This paper presents a more comprehensive survey method based on quantifiable measures of faculty publications and citations. The most frequently published core clinical faculty across 157 APA-approved clinical programs are listed. The implications of these data are discussed.


Lower limb salvage to allow planned trans-tibial amputation.
Early, primary amputations are still necessary for certain patients sustaining high impact lower limb trauma. For cases with extensive proximal tibial bone loss a turn-up bone flap technique has been described to achieve a below-knee stump suitable for a prosthesis. However, in certain circumstances, for example if posterior soft tissues are injured, this type of reconstruction is not possible. This case report demonstrates that converting a severe open proximal tibial fracture to a successful below-knee amputation is also possible with acute limb shortening, flap cover and planned subsequent trans-tibial amputation.


[Pregnancy beyond age 40 in 382 women: a retrospective study in Reunion Island].
To examine obstetrical and neonatal outcomes among women age 40 years and older. There was a retrospective study including 382 pregnant women at least 40 years of age and 7786 controls aged 20-34, stratified according to parity. Associations between maternal age and pregnancy outcomes were assessed using Pearson's chi(2) test, Fischer exact test, Student test or Mann and Whitney test, as appropriate. Maternal age 40 and over was associated with an increased risk for gestational diabetes (multiparas: OR 3.2, 95%CI 2.2-4.8; grandmultiparas: 2.8, 1.6-5.0), chronic diabetes (multiparas: 3.5, 1.04-10.6), chronic hypertension (multiparas: 3.1, 1.5-6.1; grandmultiparas: 12.1, 3.3-53.2), pregnancy-induced hypertension (nulliparas: 4.6, 1.01-17.3; multiparas: 2.6, 1.3-5.4) and preclampsia (multiparas: 2.9, 1.1-7.2). The risk for cesarean section was 2-fold higher in older multiparas and grandmultiparas. The same was true for the rate of operative vaginal delivery. The rate of fetal chromosomal abnormalities was 7-fold higher in older gravidas. Rates of fetal death were significantly increased in the cohort of older pregnant women (nulliparas: 11.2, 2.9-44.0; multiparas: 3.9, 1.4-10.9). Pregnancy at age 40 and over is associated with high rates of obstetrical complications, cesarean sections and operative vaginal deliveries, emphasizing the importance of rigorous antenatal care.


A conceptual model for judging the truthfulness of a young child's allegation of sexual abuse.
Because of the increased number of allegations of sexual abuse made by young children and the often severe legal penalties given to adult perpetrators, there is reason for concern about false or mistaken accusations. This paper develops a conceptual model for judging the truthfulness of such allegations by a young child.


Memantine Usage for Management of Korsakoff Syndrome in the Setting of Chronic Alcohol Use and Unspecified Eating Disorder.
Korsakoff syndrome is a neuropsychiatric condition frequently seen as a progression of Wernicke's encephalopathy and is often associated with long-term alcohol abuse. It is characterized by further cognitive impairments, such as indiscriminate anterograde and retrograde amnesia, in addition to executive function deficits. As the syndrome is a result of severe thiamine deficiency, its management primarily focuses on nutritional replenishment and electrolyte maintenance. In recent years, a few published reports have detailed the off-label use of Food and Drug Administration (FDA) approved drugs for Alzheimer's in an attempt to treat neurocognitive deficits associated with Korsakoff patients. In this particular case, we note subjective improvement in cognition after initiating memantine, an N-Methyl-d-aspartate (NMDA) receptor antagonist.


Purification and biological activities of pokeweek (Phytolacca americana) mitogens.
Five mitogens, designated Pa-1 through Pa-5, were purified from the roots of pokeweed (Phytolacca americana) by means of ethanol fractionation, DEAE-cellulose column chromatography, affinity chromatography on a column of desialized human erythrocyte glycopeptide-Sepharose 4B, and gel filtration. Among these mitogens, only Pa-1 was mitogenic for both murine B-cells and T-cells, and the other mitogens were T-cell mitogens. Binding experiments with 125I-labeled Pa-1, a potent mitogen for B-cells, and with 125I-labeled Pa-2, the strongest T-cell mitogen, revealed that murine B-cells have more receptor sites for Pa-1 than for Pa-2 and murine T-cells have more receptor sites for Pa-2 than for Pa-1. The change of membrane fluidity within 30 min after binding of the mitogens to murine B- and T-cells was measured by fluorescence polarization of fluorescent hydrocarbon, 1,6-diphenyl-1,3,5-hexatriene, embedded in the membrane. Pa-1 induced increase of membrane fluidity of B-cells more markedly than Pa-2, whereas Pa-2 had a larger effect on the membrane fluidity of T-cells than Pa-1. Although both Pa-1 and Pa-2 stimulated the incorporation of 32 Pi into phosphatidylinositol of murine T-cells, neither Pa-1 nor bacterial lypopolysaccharide induced the activation of phospholipid metabolism of murine B-cells.


Reduction of brain infarction induced by a transient brain ischemia in mdr1a knockout mice.
In order to evaluate the functional role of P-glycoprotein (P-gp) in cerebral ischemia, both multidrug resistance 1a knockout (KO) mice and wild-type mice were subjected to transient focal ischemia under a constant body and brain temperature about 37 degrees C. The results showed that the volume of brain infarction induced by middle cerebral artery occlusion in KO mice was significantly smaller than that seen in wild-type mice, although there were no significant differences in cerebral blood flow, physiological data and on anatomical analysis of cerebrovasculature between both groups. We suggest that multidrug resistance 1a P-gp plays a role for adjusting the expressions of endogenous neuronal cell modulating substances, such as cytokines, neuronal peptides, and others, in the brain, which is consistent with a previous paper (Bobrov et al. Neurosci Lett 24: 6-11, 2008).


The effects of CRF and the urocortins on [3H]GABA release from the rat amygdala--an in vitro superfusion study.
Corticotropin-releasing factor (CRF) is the major neuromodulator of the hypothalamic-pituitary-adrenal axis, regulating the behavioural, endocrine, autonomic and immune responses to stress. Together with the recently discovered members of the CRF peptide family, urocortin 1, urocortin 2 and urocortin 3, it also has neurotransmitter actions. Previous publication has demonstrated that stress induces CRF release in the paraventricular nucleus of the hypothalamus and the release of both CRF and GABA in the amygdala. Accordingly, the aim of the present study was to determine the effects of the members of the CRF peptide family on GABA release from the amygdala by using an in vitro superfusion system. In order to study the participation of different CRF receptors (CRF1 and CRF2) in this process, rat amygdalar slices were pretreated with selective CRF1 and CRF2 antagonists. CRF and urocortin 1 significantly increased the release of [(3)H]GABA from the slices following electrical stimulation, whereas urocortin 2 and urocortin 3 were ineffective. The actions of CRF and urocortin 1 were blocked by the selective CRF1 receptor antagonist antalarmin, but were not inhibited by the selective CRF2 receptor antagonist astressin 2B, both administered in equimolar doses. Our results demonstrate that the release of GABA from the amygdala is mediated by CRF and urocortin 1 through the activation of CRF1 receptors.


A comparative 2-year study of the effects of sequential regimens of 1 mg 17beta-estradiol and trimegestone with a regimen containing estradiol valerate and norethisterone on the bleeding profile and endometrial safety in postmenopausal women.
To compare the bleeding profiles and endometrial protection of two sequential regimens of 17beta-estradiol (17beta-E2) and trimegestone (TMG) with a sequential estradiol valerate (E2V)/norethisterone (NET) regimen. This was a randomized, double-blind, multicenter study conducted in eight countries in healthy, postmenopausal women with an intact uterus. A total of 1218 women were enrolled into the initial 1-year study (13 cycles), and subsequently 531 of these received treatment for a further year (26 cycles). Treatment regimens were 1 mg 17beta-E2 on days 1-14 and 1 mg 17beta-E2/0.125 mg TMG or 1 mg 17beta-E2/0.25 mg TMG on days 15-28, and 1 mg E2V on days 1-16 and 1 mg E2V/1 mg NET on days 17-28. Mean percentage of women reporting onset of withdrawal bleeding episodes during the week following discontinuation of progestogen was higher in the 1 mg 17beta-E2/0.25 mg TMG group than in the other two treatments, showing a more efficient progestogen effect on the endometrium and good predictability of bleeding onset with this treatment. The mean numbers and average lengths of bleeding episodes were similar in the three treatment groups. Overall, the bleeding profile was more favorable with 1 mg 17beta-E2/0.25 mg TMG than with the lower-dose TMG preparation. Both of the TMG regimens demonstrated a good protective effect on endometrial proliferation, with the 0.25 mg TMG dose showing a lower incidence of proliferative endometrium. The 1 mg 17beta-E2/0.25 mg TMG regimen showed an adequate protection of the endometrium, with an overall favorable bleeding profile.


The association between early in marriage fertility pressure from in-laws' and family planning behaviors, among married adolescent girls in Bihar and Uttar Pradesh, India.
Married adolescent girls are vulnerable to risky sexual and reproductive health outcomes. We examined the association of fertility pressure from in-laws' early in marriage with contraceptive use ever, parity, time until first birth, and couple communication about family size, among married adolescent girls. Data were taken from a cross-sectional survey with married girls aged 15-19 years (N = 4893) collected from September 2015 to July 2016 in Bihar and Uttar Pradesh, India. Multivariable regression assessed associations between in-laws' fertility pressure and each outcome, adjusting for sociodemographic covariates. We found that 1 in 5 girls experienced pressure from in-laws' to have a child immediately after marriage. In-laws' fertility pressure was associated with lower parity (Adj. β Coef. - 0.10, 95% CI - 0.17, - 0.37) and couple communication about family size (AOR = 1.77, 95% CI 1.39, 2.26), but not contraceptive use or time until birth. Our study adds to the literature identifying that in-laws' pressure on fertility is common, affects couple communication about family size, and may be more likely for those yet to have a child, but may have little effect impeding contraceptive use in a context where such use is not normative.


Epoxide hydrase in Trypanosoma cruzi epimastigotes.
1. Microsomal fractions from Trypanosoma cruzi epimastigotes catalyze the hydration of styrene oxide to styrene glycol. The activity is linear up to 45 min of incubation, is proportional to microsomal protein concentration within certain range, and has an optimum pH of 8.5. 2. Double-reciprocal plots indicate a Km value of 5.3 . 10(-4) M for styrene oxide and a V of 29.6 pmol of styrene glycol formed/min per mg protein at 37 degrees C. 4-Chlorophenyl-2,3-epoxypropyl either (Ki = 2.08 . 10(-4) M) and juvenile hormone I (Ki = 2.7 . 10(-4) M) are competitive inhibitors; whereas, 1-chloro-2,3-epoxypropane is a non-competitive inhibitor. The enzyme is induced about three-fold by 5 mM phenobarbital in the growth medium. 3. The epoxide hydrase is not activated by detergents but rather inhibited by concentrations of Tween-80 and Lubrol as low as 0.025%. 4. Experiments with intact cells indicate that about 3% of [8-14C]styrene oxide penetrates after 90 min of incubation; whereas, over 30% of juvenile hormone I is found intracellularly after the same incubation period. Intracellular styrene oxide is hydrated to styrene glycol to a significant extent and the in vivo hydration is increased by pretreatment with phenobarbital and inhibited upon the addition of 4-chlorophenyl-2,3-epoxypropyl ether. Only a small amount of the intracellular juvenile hormone I is recovered as the corresponding diol ester.


Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children.
Altered brain volumes and associations between volumes and developmental outcomes have been reported in prematurely born children. To assess which regional brain volumes are different in very low birth weight (VLBW) children without neurodevelopmental impairments ([NDI] cerebral palsy, hearing loss, blindness and significantly delayed cognitive performance) compared with VLBW children with NDI, and to evaluate the association between regional brain volumes at term-equivalent age and cognitive development and neurological performance at a corrected age of 2 years. The study group consisted of a regional cohort of 164 VLBW children, divided into one group of children without NDI (n = 148) and one group of children with NDI (n = 16). Brain (MRI) was performed at term-equivalent age, from which brain volumes were manually analysed. Cognitive development was assessed with the Bayley Scales of Infant Development II (BSID-II), and neurological performance with the Hammersmith Infant Neurological Examination at the corrected age of 2 years. The volumes of total brain tissue, cerebrum, frontal lobes, basal ganglia and thalami, and cerebellum were significantly smaller, and the volume of the ventricles significantly larger, in the children with NDI than in those without NDI. Even in children without NDI, a smaller cerebellar volume was significantly correlated with poor neurological performance at 2 years of corrected age. Volumetric analysis at brain MRI can provide an additional parameter for early prediction of outcome in VLBW children.


Prospective associations between HIV-related stigma, transmission risk behaviors, and adverse mental health outcomes in men who have sex with men.
The vast majority of research on HIV-related stigma has been cross sectional, and few studies have examined whether experiencing stigma is associated with sexual risk behaviors. The purpose of this study is to examine the prospective relationships between experiencing HIV-related stigma and symptoms of anxiety and depression, as well as sexual transmission risk behavior. The sample included HIV-infected men who have sex with men (n = 314) who participated in a secondary HIV-prevention study at their primary care site. Participants were assessed at baseline, and then completed follow-up assessments at 3, 6, 9, and 12 months. Experiencing HIV-related stigma was prospectively associated with symptoms of depression (β = 0.16, p < .001), panic (β = 0.11, p = .01), and generalized anxiety (β = 0.05, p = .05). In addition, perceiving HIV-related stigma was prospectively associated with transmission risk behaviors, including unprotected receptive or insertive anal intercourse with HIV-seronegative or status unknown partners (β = 0.06, p = .047). Experiencing HIV-related stigma may increase risk for sexual transmission risk behavior and mental health problems.


Additively manufactured titanium scaffolds and osteointegration - meta-analyses and moderator-analyses of in vivo biomechanical testing.
Maximizing osteointegration potential of three-dimensionally-printed porous titanium (3DPPT) is an ongoing focus in biomaterial research. Many strategies are proposed and tested but there is no weighted comparison of results. We systematically searched Pubmed and Embase to obtain two pools of 3DPPT studies that performed mechanical implant-removal testing in animal models and whose characteristics were sufficiently similar to compare the outcomes in meta-analyses (MAs). We expanded these MAs to multivariable meta-regressions (moderator analysis) to verify whether statistical models including reported scaffold features (e.g., "pore-size", "porosity", "type of unit cell") or post-printing treatments (e.g., surface treatments, adding agents) could explain the observed differences in treatment effects (expressed as shear strength of bone-titanium interface). "Animal type" (species of animal in which the 3DPPT was implanted) and "type of post-treatment" (treatment performed after 3D printing) were moderators providing statistically significant models for differences in mechanical removal strength. An interaction model with covariables "pore-size" and "porosity" in a rabbit subgroup analysis (the most reported animal model) was also significant. Impact of other moderators (including "time" and "location of implant") was not statistically significant. Our findings suggest a stronger effect from porosity in a rat than in a sheep model. Additionally, adding a calcium-containing layer does not improve removal strength but the other post-treatments do. Our results provide overview and new insights, but little narrowing of existing value ranges. Consequent reporting of 3DPPT characteristics, standardized comparison, and expression of porosity in terms of surface roughness could help tackle these existing dilemmas.


Establishment of a highly efficient transformation system for pepper (Capsicum annuum L.).
Application of modern genetic manipulation has been limited in pepper ( Capsicum annuum L.) due to the lack of an efficient transformation system. Following the development of an efficient protocol for in vitro regeneration of pepper cotyledons, we investigated the key factors affecting transformation and established a highly efficient genetic transformation system using the pepper cotyledon as starting material. In this system, cotyledon explants are preconditioned for 2 days on kanamycin (km)-free DM1 medium [Murashige and Skoog (MS) salts/Gamborg B5 vitamins basal medium supplemented with 20 g/l sucrose, 5,000 mg/l DJ nutrients and a hormone combination of 1.0 mg/l indoleacetic acid (IAA) and 5.0 mg/l 6-benzyladenine (BA) solidified with 0.7% agar, pH 5.8], followed by co-cultivation with Agrobacterium tumefaciens on DM1 for 2 days and delay selection on DM1 with 500 mg/l carbenicillin (carb) for 2 days. The explants are then placed on DM1 containing 10 mg/l AgNO(3), 50 mg/l km-sulfate and 500 mg/l carb. After 4-5 weeks, the explants with buds are transferred to EM1 medium (MS salts/Gamborg B5 vitamins basal medium supplemented with 20 g/l sucrose, 5,000 mg/l DJ nutrients, 10 mg/l AgNO(3) and a hormone combination of 1.0 mg/l IAA, 3.0 mg/l BA and 2.0 mg/l gibberellic acid, solidified with 0.7% agar, pH 5.8) with 50 mg/l kanamycin and 500 mg/l carbenicillin for the elongation of buds. After 3-6 weeks, 1- to 2-cm-long elongated shoots are excised and planted on RM1 medium (MS basal medium supplemented with a hormone combination of 0.2 mg/l NAA and 0.1 mg/l IAA, solidified with 0.8% agar, pH 5.8) with 25 mg/l km and 200 mg/l carb for rooting. We tested four genotypes of pepper, and all presented a high differentiation efficiency (81.3% on average), elongation rate (61.5%) and rooting efficiency (89.5%). Polymerase chain reaction analysis results showed that 40.8% of the regenerated plantlets were transgenic plants.


Zoning laminectomy for the treatment of ossification of the thoracic ligamentum flavum.
Spinal cord injury is a common occurrence during spinal surgery. In this study, we proposed a zoning laminectomy, which could reduce the incidence of nerve injury. We also discussed the safety and clinical efficacy of the zoning laminectomy for thoracic ossification of the ligamentum flavum (TOLF). Forty-five patients with TOLF who underwent zoning laminectomy from October 2016 to February 2020 were included in the retrospective analysis. The Japan Orthopedic Association (JOA) score was used to evaluate clinical outcomes. Meanwhile, the occurrence of complications was recorded. All 45 patients underwent the operation successfully, and the mean follow-up period was 25.3 months, the mean operation time was 160.2 min, the average blood loss was 474.2 ml, and the average hospital time was 8.0 days. At the final evaluation, the JOA score was significantly higher than the preoperative JOA score (P < 0.001) and the overall recovery rate of the JOA score averaged 69.6%. Seventeen patients were graded as excellent, twenty-six as good, and two as fair. The complications included dural tears in nine patients (20.0%), cerebrospinal fluid leakage in seven patients (15.6%), deep infection in one patient (2.2%), and epidural hematoma in one patient (2.2%). All patients recovered well after treatment. Besides, there was no neurological deterioration and thoracic kyphosis occurred. Zoning laminectomy adopts a phased resection from "safe zone" to "danger zone" and defines the safe removal range of the lamina, which reduces the risks of spinal cord injury caused by instrument manipulation. Therefore, it is a safe and effective surgical option.


[Smoking behaviours among staff of two university hospitals in Paris, 2021].
A survey on smoking prevalence was conducted among staff at the Georges Pompidou and Corentin Celton hospitals in the framework of the "smoke-free hospital" project. It aimed to determine the smoking status of different categories of personnel, their desire to be helped to quit and, as regards healthcare staff, whether or not they were encouraging patients who smoked to try to quit. From February to May 2021, an anonymous survey was distributed, first on paper in the occupational health unit, and then online in all wards. All in all, 775 people, three quarters of whom were women, participated in the survey (15% of the workforce). Among the respondents, 27% said they smoked: 29.6% of the men and 26.1% of the women. Unsurprisingly, the age group with the highest prevalence was 18-24years. High prevalence was likewise found among technical and administrative staff. More than half of the smokers, who consumed an average of 8 cigarettes a day, were interested in receiving smoking cessation support. As regards smoking cessation support for patients, 49% of medical and nursing staff (70% of the doctors) frequently or systematically advised them to quit. Our results illustrate a need to reach high-prevalence categories of smokers in a hospital setting, the objective being to help them to consider quitting, and also a need to train health professionals in smoking cessation counseling.


Automatic brain extraction from 3D fetal MR image with deep learning-based multi-step framework.
Brain extraction is a fundamental prerequisite step in neuroimage analysis for fetus. Due to surrounding maternal tissues and unpredictable movement, brain extraction from fetal Magnetic Resonance (MR) images is a challenging task. In this paper, we propose a novel deep learning-based multi-step framework for brain extraction from 3D fetal MR images. In the first step, a global localization network is applied to estimate probability maps for brain candidates. Connected-component labeling algorithm is applied to eliminate small erroneous components and accurately locate the candidate brain area. In the second step, a local refinement network is implemented in the brain candidate area to obtain fine-grained probability maps. Final extraction results are derived by a fusion network with the two cascaded probability maps obtained from previous two steps. Experimental results demonstrate that our proposed method has superior performance compared with existing deep learning-based methods.


Editorial for the Special Issue: "Antimicrobial Resistance and Molecular Tracing of Foodborne Pathogens".
Foodborne pathogens are a major cause of diarrheal disease worldwide, but also constitute a severe threat for the spread of antimicrobial-resistant bacteria from livestock via food products to humans [...].


Long-term hospitalization of failure-to-thrive infants: developmental outcome at three years.
The present study documented later developmental outcome in a group of 29 failure-to-thrive (FTT) infants who received extended hospitalization in infancy as an intervention for their growth failure. All infants were seen at approximately 3 years of age and were given standardized assessments of intellectual and physical development. A standard interview documented demographic variables, health problems, placements subsequent to hospitalization and additional psychological and medical treatment. Infants were divided into three groups dependent on medical and treatment factors. Means and percentages of occurrence of outcome variables were compared through either one-way ANOVAS or single sample chi-square tests with post hoc analyses. Correlational analyses were used to understand the relationships between outcome and relevant demographic, medical, and treatment variables. In general, the infants manifest persistent intellectual delays at follow-up despite maintenance of weight gains achieved during early hospitalization. More than half the group suffered from chronic health problems. A large percentage of infants had been removed from parental custody at the time of follow-up. Several demographic, medical, and treatment factors bore moderate relationships to developmental outcome. Infants who achieved more optimal growth tended to be full-term at birth, later born and without a question of physical abuse in their social histories. Intellectual functioning was related only to parental and caretaker socioeconomic status. Infants placed in foster care were unlikely to return to their families of origin. The findings suggest the need for further investigation into the determinants and outcome of extended hospitalization as a treatment for FTT.


Acetaminophen glucuronide and plasma glucose report identical estimates of gluconeogenesis and glycogenolysis for healthy and prediabetic subjects using the deuterated water method.
Plasma glucose (2) H-enrichment in positions 5 ((2) H5) and 2 ((2) H2) from deuterated water ((2) H2 O) provides a measure of the gluconeogenic contribution to endogenous glucose production. Urinary glucuronide analysis can circumvent blood sampling but it is not known if glucuronide and glucose enrichments are equal. Thirteen subjects with impaired fasting glucose/impaired glucose tolerance and 11 subjects with normal fasting glucose and normal glucose tolerance ingested (2) H2 O to ∼0.5% body water and acetaminophen. Glucose and glucuronide (2) H5 and (2) H2 were measured by (2) H NMR spectroscopy of monoacetone glucose. For normal fasting glucose/normal glucose tolerance, (2) H5 was 0.23 ± 0.02% and 0.25 ± 0.02% for glucose and glucuronide, respectively, whereas (2) H2 was 0.47 ± 0.01% and 0.49 ± 0.02%, respectively. For impaired fasting glucose/impaired glucose tolerance, (2) H5 was 0.22 ± 0.01% and 0.26 ± 0.02% for glucose and glucuronide, respectively, whereas (2) H2 was 0.46 ± 0.01% and 0.49 ± 0.02%, respectively. The gluconeogenic contribution to endogenous glucose production measured from glucose and glucuronide were identical for both normal fasting glucose/normal glucose tolerance (48 ± 4 vs. 51 ± 3%) and impaired fasting glucose/impaired glucose tolerance (48 ± 2 vs. 53 ± 3%).


Predictors of response to second-line endocrine therapy for breast cancer.
This study reports on factors predicting response to second-line endocrine therapy in 250 patients with breast cancer for which they were assessable for response by the International Union Against Cancer (UICC) criteria. Clinical details relating to first-line endocrine therapy were available for all patients. We have not included in this study patients who received first-line endocrine therapy but did not or have not yet proceeded to second-line hormone therapy--e.g. died from rapidly progressive disease, started chemotherapy for rapidly progressive disease, or remained in long-term remission on first-line endocrine therapy. One hundred and fifty nine patients (72%) achieved remission (objective response and static disease [OR + SD]) on first-line endocrine therapy with a median duration of 19 months. For second-line endocrine therapy the remission rate was 53% (132/225) with a median duration of 15 months. Tumour grade and oestrogen receptor status of the primary tumour were shown to be independent predictors of response to second-line endocrine therapy while response to first-line endocrine therapy was a predictor of the duration of response to second-line endocrine therapy. In the sub-group of patients who showed OR or SD to both first and second-line therapies, there was no correlation between the time to progression (TTP) on first and second-line therapies.


Is screening for psychosocial risk factors associated with mental health care in older adults with cancer undergoing surgery?
Surgery is a notable stressor for older adults with cancer, who often are medically and psychosocially complex. The current study examined rates of preoperative psychosocial risk factors in older adults with cancer who were undergoing elective surgery and the relationship between these risk factors and the provision of mental health services during the postoperative hospitalization. A total of 1211 patients aged ≥75 years who were referred to the geriatrics service at a comprehensive cancer center were enrolled. Patients underwent elective surgery with a length of stay of ≥3 days and were followed for at least 30 days after surgery. A comprehensive geriatric assessment was administered as part of routine preoperative care. Bivariate relationships between demographic and surgical characteristics and the preoperative comprehensive geriatric assessment and the receipt of mental health services during the postoperative hospitalization period were examined. Characteristics with bivariate relationships that were significant at the level of P < .10 were entered into a multivariable regression predicting postoperative mental health service use. Approximately one-fifth of the total sample (20.6%) received postoperative mental health services. In multivariable analyses, high distress (P = .007) and poor social support (P = .02) were found to be associated with a greater likelihood of the receipt of mental health services. Of those patients with high distress and poor social support, only approximately one-quarter (24.6%-25.5%) received mental health care. Distressed older adults and those with low levels of support preoperatively were found to be more likely to receive mental health services after surgery. Nevertheless, less than one-third of these patients received inpatient postoperative mental health care, indicating that barriers to translating screening into the provision of psychosocial services remain.


Activation of Stat-3 as one of the early events in tobacco chewing-mediated oral carcinogenesis.
The Jak/Stat signaling pathway transmits signals from many cytokines and growth factor receptors to target genes in the nucleus. Constitutive activation of Stat-3 recently has been observed in many tumor cells, and dysregulation of the Stat signaling pathway has been proposed to be implicated in malignant transformation. In the current study for the first time to the authors's knowledge, the expression of STAT-3 was analyzed in various stages and sites of squamous cell carcinoma of the head and neck (HNSCC). Tissue samples from 90 patients of tobacco chewing-mediated HNSCC representing various stages, sites, and differentiation states were selected for studying STAT-3 protein and RNA expression. In vivo localization of STAT-3 was studied by immunohistochemistry of paraffin embedded sections. The presence of STAT-3 and its phophorylated and activated form pSTAT-3 was checked by Western blotting. mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Apoptosis analysis was conducted by in situ ENA nick end labeling assay and hematoxylin and eosin staining. Overall, 58.9% of HNSCC tumors showed very high Stat-3 protein accumulation, and 23.3% showed intermediate accumulation whereas 17.8% of HNSCC tumors were negative for Stat-3. No Stat-3 was detected in normal samples, and only one of eight premalignant lesions showed intermediate Stat-3 accumulation. On immunoblotting, very high protein accumulation was detected in T1 and T2 classification, moderate in T3 and T4 (P = 0.033, chi-square test), whereas no Stat-3 was detected in normal samples. Similar trend also was found in Stat-3 mRNA expression by RT-PCR analysis which was high in T1 and T2 (early stages), moderate in T3 and T4 (late stages), and no expression in normal samples. The mean apoptotic indices were 1.75, 1.88, and 1.66 for normal, premalignant lesions, and HNSCC cases, respectively. Stat-3 activation is an early event in head and neck carcinogenesis though its role in blocking the apoptosis in vivo in solid tumors was not observed.


Interferon regulatory factor 8/interferon consensus sequence binding protein is a critical transcription factor for the physiological phenotype of microglia.
Recent fate-mapping studies establish that microglia, the resident mononuclear phagocytes of the CNS, are distinct in origin from the bone marrow-derived myeloid lineage. Interferon regulatory factor 8 (IRF8, also known as interferon consensus sequence binding protein) plays essential roles in development and function of the bone marrow-derived myeloid lineage. However, little is known about its roles in microglia. The CNS tissues of IRF8-deficient mice were immunohistochemically analyzed. Pure microglia isolated from wild-type and IRF8-deficient mice were studied in vitro by proliferation, immunocytochemical and phagocytosis assays. Microglial response in vivo was compared between wild-type and IRF8-deficient mice in the cuprizon-induced demyelination model. Our analysis of IRF8-deficient mice revealed that, in contrast to compromised development of IRF8-deficient bone marrow myeloid lineage cells, development and colonization of microglia are not obviously affected by loss of IRF8. However, IRF8-deficient microglia demonstrate several defective phenotypes. In vivo, IRF8-deficient microglia have fewer elaborated processes with reduced expression of IBA1/AIF1 compared with wild-type microglia, suggesting a defective phenotype. IRF8-deficient microglia are significantly less proliferative in mixed glial cultures than wild-type microglia. Unlike IRF8-deficient bone marrow myeloid progenitors, exogenous macrophage colony stimulating factor (colony stimulating factor 1) (M-CSF (CSF1)) restores their proliferation in mixed glial cultures. In addition, IRF8-deficient microglia exhibit an exaggerated growth response to exogenous granulocyte-macrophage colony stimulating factor (colony stimulating factor 2) (GM-CSF (CSF2)) in the presence of other glial cells. IRF8-deficient microglia also demonstrate altered cytokine expressions in response to interferon-gamma and lipopolysaccharide in vitro. Moreover, the maximum phagocytic capacity of IRF8-deficient microglia is reduced, although their engulfment of zymosan particles is not overtly impaired. Defective scavenging activity of IRF8-deficient microglia was further confirmed in vivo in the cuprizone-induced demyelination model in mice. This study is the first to demonstrate the essential contribution of IRF8-mediated transcription to a broad range of microglial phenotype. Microglia are distinct from the bone marrow myeloid lineage with respect to their dependence on IRF8-mediated transcription.


The correlation between white-matter microstructure and the complexity of spontaneous brain activity: a difussion tensor imaging-MEG study.
The advent of new signal processing methods, such as non-linear analysis techniques, represents a new perspective which adds further value to brain signals' analysis. Particularly, Lempel-Ziv's Complexity (LZC) has proven to be useful in exploring the complexity of the brain electromagnetic activity. However, an important problem is the lack of knowledge about the physiological determinants of these measures. Although a correlation between complexity and connectivity has been proposed, this hypothesis was never tested in vivo. Thus, the correlation between the microstructure of the anatomic connectivity and the functional complexity of the brain needs to be inspected. In this study we analyzed the correlation between LZC and fractional anisotropy (FA), a scalar quantity derived from diffusion tensors that is particularly useful as an estimate of the functional integrity of myelinated axonal fibers, in a group of sixteen healthy adults (all female, mean age 65.56±6.06 years, intervals 58-82). Our results showed a positive correlation between FA and LZC scores in regions including clusters in the splenium of the corpus callosum, cingulum, parahipocampal regions and the sagittal stratum. This study supports the notion of a positive correlation between the functional complexity of the brain and the microstructure of its anatomical connectivity. Our investigation proved that a combination of neuroanatomical and neurophysiological techniques may shed some light on the underlying physiological determinants of brain's oscillations.


Microsatellite genotypes of the South African Cape vulture, Gyps coprotheres.
Across the globe, vulture species are experiencing major population declines. A key factor for the long-term persistence of these endangered species is the maintenance of genetic diversity patterns within wild populations. The datasets presented in this descriptor includes microsatellite genotypes of 605 Cape vultures (Gyps coprotheres) drawn from across the southern African distribution of the species. Microsatellites are useful in quantifying genetic diversity at the population level. Populations of the endangered Cape vulture are currently monitored by conservation agencies and the data presented here can be used as an important baseline for future population genetic monitoring.


Development of a novel DNA delivery system based on rice bran polysaccharide-Fe(III) complexes.
Metal complexes, as a type of potential non-virus gene carriers, have gained much attention due to their properties of high charge density and unique three-dimensional structure. This study investigated the potential of polyethyleneimine (PEI)-modified rice bran polysaccharide-Fe(III) complex (PEI-PI) as a safe gene delivery system and explored the effect of Fe(III) on the efficiency of gene transfection mediated by PEI modified rice bran polysaccharide (PEI-P) and PEI-PI. Gel retardation assay was used to study the DNA binding and protection capability, MTT assay was performed to evaluate the biocompatibility, and PEI-PI complex-mediated EGFP gene transfection was studied in vitro. Results showed the PEI-PI could induce DNA condensation and protect DNA from degradation by DNase I at a low weight ratio (vector/DNA) of 2. At the same weight ratio, PEI exhibited the strongest DNA binding capability but PEI-PI exhibited the highest gene transfection efficiency among all carrier systems. Compared with the PEI-P + Fe(III) system, PEI-PI not only had a more significant capability to condense DNA but also presented higher gene transfection efficiency. Moreover, PEI-PI exhibited no obvious cytotoxicity to cells. This work provides a strategy for the design and development of gene vectors based on PI complexes.


Thrombophlebitis of the inferior vena cava involving the retroperitoneum with Crohn's disease: MR demonstration.
We present a case of thrombophlebitis of the inferior vena cava (IVC) with Crohn's disease after intestinal perforation and prolonged indwelling of a catheter in the IVC. Magnetic resonance imaging demonstrated abnormal thickening and enhancement of the IVC wall. In addition, IVC thrombus formation was shown. The abnormal enhancement extended from the wall in the pericaval tissue and into the retroperitoneum, and regressed as the Crohn's disease subsided.


Featured counter trafficking program: The law enforcement first responder protocol.
This invited article is one of several comprising part of a special issue of Child Abuse and Neglect focused on child trafficking and health. The purpose of each invited article is to describe a specific program serving trafficking children. Featuring these programs is intended to raise awareness of innovative counter-trafficking strategies emerging worldwide and facilitate collaboration on program development and outcomes research. This article describes the Law Enforcement First Responder Protocol, which trained law enforcement to recognize youth engaged in sex work as survivors of commercial sexual exploitation, rather than as "prostitutes", and to connect these survivors immediately with social services, advocates, timely medical care and ongoing follow-up.


Signal-transducing GTP-binding proteins of mammalian heart and lungs.
Signal-transducing GTP-binding Proteins of Mammalian Heart and Lungs. Journal of Molecular and Cellular Cardiology (1989) 21 (Suppl I) 91-95. Three distinct G-proteins have been found in mammalian heart sarcolemma: Gi (alpha i = 40 kDa, beta = 36 kDa, and lambda less than 14 kDa), Gp (alpha p = 23 kDa, beta = 36 kDa, and lambda less than 14 kDa), and Gs (alpha s = 42 kDa). ADP-ribosylation of sarcolemmal alpha i by pertussis toxin (PT) or preincubation of sarcolemma with protein kinase C and PMA resulted in increased adenylate cyclase activity and blockade of GTP-dependent inhibition by carbachol whereas the GTP-dependent activating effect of isoproterenol on the adenylate cyclase was preserved. ADP-ribosylation of alpha i in sarcolemma by endogenous NADP-sensitive ADP-ribosyltransferase abolished the PT-induced ADP-ribosylation of alpha i. Gpp (NH)p attenuated the PT-induced ADP-ribosylation of alpha i and promoted the cholera toxin (CT)-induced ADP-ribosylation of alpha s. The CT-induced alpha s ADP-ribosylation was enhanced in the presence of heart cytosol. Soluble Gi- and Gs-proteins were identified in lung cytosol. The 40 kDa alpha i in membrane and soluble fractions was ADP-ribosylated by PT, while the soluble 42 kDa alpha s was ADP-ribosylated by CT in lung tissue. The ADP-ribosylation of soluble alpha i by PT-suppressed guanyl nucleotide binding to Gi. The apparent molecular mass of partially purified soluble Gi was 75 kDa.


Management of stroke patients submitted to botulinum toxin type A therapy: a Delphi survey of an Italian expert panel of specialist injectors.
Spasticity is a common disabling symptom of several neurological conditions including stroke. Botulinum toxin type A (BTX-A) injection represents the gold standard therapy for focal spasticity. Post-stroke management of patients receiving BTX-A therapy has been variously investigated, but general agreement on how and when to implement rehabilitation is lacking. To perform a national survey of experts on the most appropriate rehabilitation procedures after BTX-A therapy for the focal treatment of spasticity. The study employed the Delphi technique through the COSMO project (Consensus on Post-Injection Management in Post-stroke Spasticity). Italian neurologists and physiatrists with experience in BTX-A therapy were selected to participate in the survey. Their anonymous opinions on key issues in treatment strategies in post-stroke spasticity were collected in three sequential rounds facilitated by a web platform. Consensus on a given issue was defined as agreed opinion by at least 66% of the survey participants. In all, 44 Italian experts were involved. Positive consensus was reached on the need to start rehabilitation during the first week after BTX-A injection therapy, with a rehabilitation program comprising both stretching combined with electrical stimulation and exercise therapy. Functional surgery may be considered only after 12-24 months in cases of BTX-A therapy failure. The use of commercial or custom-made orthoses in selected cases was recommended. The appropriate time interval between two BTX-A injections is 3-6 months, and clinical assessment should be performed 1 month after injection. The results of this national survey confirm that clinical experts on the use of BTX-A therapy for spasticity after stroke agree on the need to initiate rehabilitation treatment immediately after BTX-A injection: muscle stretching exercises, eventually combined with neuromuscular electrical stimulation, may enhance the effect of BTX-A therapy. Outcome after BTX-A therapy should be assessed at repeated follow-up visits. This expert panel survey can provide guidance for clinicians in the assessment of patients treated with BTX-A therapy.


Effect of angiotensin II on energetics, glucose metabolism and cytosolic NADH/NAD and NADPH/NADP redox in vascular smooth muscle.
Angiotensin II (AII) is a neurohormone and contractile agonist of vascular smooth muscle that has been shown to be involved in the pathogenesis of vascular disease, which may be partially caused by its effect on oxidant stress. Energy metabolism was examined in pig carotid arteries treated with AII, because the activity of pathways of intermediary metabolism of glucose determines the status of cytosolic NADH/NAD and NADPH/NADP redox, factors which are involved in oxidant stress. Contractile responses to AII were characterized by an increase in isometric force followed by a gradual decline to near-basal levels. Despite contractile activation, no change in glycolysis, lactate production, glucose oxidation, fatty acid oxidation, O2 consumption, glycogen content or high-energy phosphates was detected when compared to resting unstimulated arteries. Paradoxically, total uptake of glucose was inhibited by AII. Treatment with diphenylene iodinium, an inhibitor of NAD(P)H oxidase and superoxide production, reversed the inhibition of glucose uptake and revealed the expected increase in glucose uptake and oxidation upon contractile activation of smooth muscle by AII. The intracellular [lactate]/[pyruvate] ratio was increased, reflecting an increase in cytosolic NADH/NAD redox, whereas NADPH/NADP redox was decreased by AII. No change in NADPH/NADP redox was observed when membrane depolarization with K+ was used as the contractile agent. It is concluded that the pattern of force generation, metabolism and energetics of AII-stimulated contraction are significantly different from that of other contractile agonists. Most notably AII inhibited glucose uptake. NAD(P)H oxidase and/or attendant superoxide may play a role in modulating glucose metabolism. AII induces opposite changes in NADH/NAD redox and NADPH/NADP redox, which may have important consequences for oxidant stress.


Transcriptional analysis of the xylose ABC transport operons in the thermophilic anaerobe Thermoanaerobacter ethanolicus.
Thermoanaerobacter ethanolicus is a Gram-positive thermophile that converts xylose to ethanol. A portion of the T. ethanolicus xylose transport permease gene ( xylH) was cloned, and the deduced protein exhibited greater than 60% similarity to homologs in enterobacteria. Xylose-binding protein ( xylF) and ( xylH) transcripts were quantitated and compared from cells grown in batch or continuous cultures grown on xylose, glucose, or a mixture of both sugars. In contrast to the strong repression of xyl operons by glucose in other bacteria, both xylF and xylH expression were detected in the presence of this hexose sugar. Expression of xylF and xylH generally increased with dilution rate (3- and 1.5-fold, respectively) and seemed to be growth rate rather than substrate dependent. Overall, these unusual sugar utilization patterns in batch and continuous culture seem to result from a basal expression level of xyl genes in the absence of xylose. T. ethanolicus is unique in possessing a triumvirate of xylose transport and catabolism operons and, given its extensive hemicellulolytic capabilities, may have evolved to constitutively express xyl genes.


Functional magnetic resonance imaging of human hypothalamic responses to sweet taste and calories.
Evidence exists that beverages do not trigger appropriate anticipatory physiologic responses, such as cephalic phase insulin release. Therefore, it is of interest to elucidate the food properties necessary for triggering adaptive responses. Previously, we found a prolonged dose-dependent decrease in the hypothalamic functional magnetic resonance imaging signal after ingestion of a glucose solution. The aims of the present study were to measure the effects of sweet taste and energy content on the hypothalamic response to glucose ingestion and to measure the concomitant changes in blood glucose and insulin concentrations. Five healthy, normal-weight men participated in a randomized crossover design trial. The subjects were scanned 4 times for 37 min on separate days with functional magnetic resonance imaging. After 7 min, they ingested 1 of the following 4 stimuli (300 mL of each): water (control), a glucose solution, an aspartame (sweet taste) solution, or a maltodextrin (nonsweet carbohydrate) solution. Glucose ingestion resulted in a prolonged and significant signal decrease in the upper hypothalamus (P < 0.05). Water, aspartame, and maltodextrin had no such effect. Glucose and maltodextrin ingestions resulted in similar increases in blood glucose and insulin concentrations. However, only glucose triggered an early rise in insulin concentrations. Aspartame did not trigger any insulin response. Our findings suggest that both sweet taste and energy content are required for a hypothalamic response. The combination of sweet taste and energy content could be crucial in triggering adaptive responses to sweetened beverages.


Assembly and interactions of cotJ-encoded proteins, constituents of the inner layers of the Bacillus subtilis spore coat.
During Bacillus subtilis endospore formation, a complex protein coat is assembled around the maturing spore. The coat is made up of more than two dozen proteins that form an outer layer, which provides chemical resistance, and an inner layer, which may play a role in the activation of germination. A third, amorphous layer of the coat occupies the space between the inner coat and the cortex, and is referred to as the undercoat. Although several coat proteins have been characterized, little is known about their interactions during assembly of the coat. We show here that at least two open reading frames of the cotJ operon (cotJA and cotJC) encode spore coat proteins. We suggest that CotJC is a component of the undercoat, since we found that its assembly onto the forespore is not prevented by mutations that block both inner and outer coat assembly, and because CotJC is more accessible to antibody staining in spores lacking both of these coat layers. Assembly of CotJC into the coat is dependent upon expression of cotJA. Conversely, CotJA is not detected in the coats of a cotJC insertional mutant. Co-immunoprecipitation was used to demonstrate the formation of complexes containing CotJA and CotJC 6 h after the onset of sporulation. Experiments with the yeast two-hybrid system indicate that CotJC may interact with itself and with CotJA. We suggest that interaction of CotJA with CotJC is required for the assembly of both CotJA and CotJC into the spore coat.


Restrictive endocardial fibroelastosis in a neonate without other cardiac pathology.
A case is presented of constrictive endocardial fibroelastosis without other cardiac abnormality in a newborn infant who was treated successfully by orthotopic heart transplantation.


Excision of postesophageal parathyroid adenoma in posterior mediastinum with intraoperative 99mTechnetium sestamibi scanning.
Although approximately 25% of parathyroid tumors in patients with primary hyperparathyroidism are located in the mediastinum, nearly all these tumors can be removed through cervical exploration. However, 1% to 2% of the mediastinal tumors require a transthoracic approach for removal. The mediastinal tumors are usually located in the inferior parathyroid gland, and the ectopic mediastinal tumors derived from the superior glands are extremely rare. We present a case of retroesophageal mediastinal parathyroid adenoma that developed in the left superior parathyroid gland. A thoracotomy was required to remove this tumor. Radioisotope-guided surgery was effective at identifying the tumor.


Engineering of Saccharomyces cerevisiae for the production of (+)-ambrein.
The triterpenoid (+)-ambrein is the major component of ambergris, a coprolite of the sperm whale that can only be rarely found on shores. Upon oxidative degradation of (+)-ambrein, several fragrance molecules are formed, amongst them (-)-ambrox, one of the highest valued compounds in the perfume industry. In order to generate a Saccharomyces cerevisiae whole-cell biocatalyst for the production of (+)-ambrein, intracellular supply of the squalene was enhanced by overexpression of two central enzymes in the mevalonate and sterol biosynthesis pathway, namely the N-terminally truncated 3-hydroxy-3-methylglutaryl-CoA reductase 1 (tHMG) and the squalene synthase (ERG9). In addition, another key enzyme in sterol biosynthesis, squalene epoxidase (ERG1) was inhibited by an experimentally defined amount of the inhibitor terbinafine in order to reduce flux of squalene towards ergosterol biosynthesis while retaining sufficient activity to maintain cell viability and growth. Heterologous expression of a promiscuous variant of Bacillus megaterium tetraprenyl-β-curcumene cyclase (BmeTC-D373C), which has been shown to be able to catalyse the conversion of squalene to 3-deoxyachillol and then further to (+)-ambrein resulted in production of these triterpenoids in S. cerevisiae for the first time. Triterpenoid yields are comparable with the best microbial production chassis described in literature so far, the methylotrophic yeast Pichia pastoris. Consequently, we discuss similarities and differences of these two yeast species when applied for whole-cell (+)-ambrein production.


Reperfusion normalizes motor activation patterns in large-vessel disease.
Hemodynamic impairment in one hemisphere has been shown to trigger ipsilateral motor activation in the opposite hemisphere on functional imaging. We hypothesized that reversing the hypoperfusion would normalize the motor activation pattern. We studied four patients with high-grade stenosis and impaired vasomotor reactivity (VMR) but no stroke. Functional magnetic resonance imaging motor activation pattern before and after VMR normalization was compared with seven healthy control subjects scanned at an interval of 3 months using voxel-wise statistical parametric maps and region of interest analysis. Subjects performed a repetitive hand closure task in synchrony with 1Hz metronome tone. We used repeated-measures analysis of variance to compute the interaction between group (patients/control subjects) and time by obtaining the average blood oxygen level dependent signal of three motor regions of interest in each hemisphere. Two patients normalized their VMR after spontaneous resolution of dissection, and two after revascularization procedures. Both voxel-wise statistical maps and region of interest analysis showed that VMR normalization was associated in each case with a reduction in the atypical activation in the hemisphere opposite to the previously hypoperfused hemisphere (p < 0.001). In the presence of a physiological stressor such as hypoperfusion, the brain is capable of dynamic functional reorganization to the opposite hemisphere that is reversible when normal blood flow is restored. These findings are important to our understanding of the clinical consequences of hemodynamic failure and the role of the ipsilateral hemisphere in maintaining normal neurological function.


Medicinal plants used for the management of respiratory diseases in Zimbabwe: Review and perspectives potential management of COVID-19.
Respiratory diseases have in the recent past become a health concern globally. More than 523 million cases of coronavirus disease (COVID19), a recent respiratory diseases have been reported, leaving more than 6 million deaths worldwide since the start of the pandemic. In Zimbabwe, respiratory infections have largely been managed using traditional (herbal) medicines, due to their low cost and ease of accessibility. This review highlights the plants' toxicological and pharmacological evaluation studies explored. It seeks to document plants that have been traditionally used in Zimbabwe to treat respiratory ailments within and beyond the past four decades. Extensive literature review based on published papers and abstracts retrieved from the online bibliographic databases, books, book chapters, scientific reports and theses available at Universities in Zimbabwe, were used in this study. From the study, there were at least 58 plant families comprising 160 medicinal plants widely distributed throughout the country. The Fabaceae family had the highest number of medicinal plant species, with a total of 21 species. A total of 12 respiratory ailments were reportedly treatable using the identified plants. From a total of 160 plants, colds were reportedly treatable with 56, pneumonia 53, coughs 34, chest pain and related conditions 29, asthma 25, tuberculosis and spots in lungs 22, unspecified respiratory conditions 20, influenza 13, bronchial problems 12, dyspnoea 7, sore throat and infections 5 and sinus clearing 1 plant. The study identified potential medicinal plants that can be utilised in future to manage respiratory infections.


High-tone external muscle stimulation in patients with acute kidney injury (AKI): beneficial effects on NO metabolism, asymmetric dimethylarginine, and endothelin-1.
The aim of this study was to assess potential effects of high-tone external muscle stimulation (HTEMS) on parameters of endothelial dysfunction (ED) in patients with acute kidney injury (AKI). The bad outcome of AKI patients is markedly influenced by ED, microinflammation, oxidative stress and protein hypercatabolism. Recently, we have shown that intradialytic application of HTMS was associated with a faster resolution of AKI. Here, we investigated in the same cohort of patients whether parameters of ED such as nitric oxide (NO), asymmetric-dimethylarginine (ADMA), and endothelin 1 (ET-1) are modulated by HTEMS as compared to non-HTEMS-treated AKI patients. In a post-hoc study we analyzed plasma samples of the 34 AKI patients stage 5, of whom 17 underwent intradialytic HTEMS treatment while the other 17 served as AKI dialysis controls. Measurements included plasma nitrate and nitrite (NOx), ADMA, ET-1 and were performed before and on days 3, 7, 14, 21, and 28 after start of daily dialysis. Additional 16 healthy volunteers served as controls. Initially, in both AKI groups NOx levels were markedly lower and ADMA and ET-1 levels were higher compared to the healthy controls. After initiation of daily hemodialysis the HTEMS group showed a faster improvement of NOx and ET-1 (after 1 week) and ADMA levels (after 2 weeks) compared to the No- HTEMS group. After 2 weeks, all parameters of the HTEMS group were not different from healthy controls, while the No-HTEMSAKI group needed 3 - 4 weeks. Our findings suggest for the first time that in AKI patients, application of HTEMS is associated with a faster normalization of lowered NOx and elevated ADMA and ET-1 plasma levels. We hypothesize that the more rapid amelioration of these parameters in the HTEMS group contributed to the accelerated recovery of AKI. With regard to the small study groups with different causes of AKI, investigations in a greater number of AKI patients is required.


Biochemical study of dermatan sulfate glycosaminoglycan in adult male patients with Nyhus type II inguinal hernia.
To compare the amount of the dermatan sulfate glycosaminoglycan between male patients with Nyhus type II inguinal hernias and subjects without inguinal hernia, aged between 20 and 40 years. Two groups were formed: One with 15 male patients with Nyhus type II inguinal hernia and aged between 20 and 40 years with ASA risk I and II, and a control group of ten individuals, also males between 20 and 40, who had died up to 24 h before. We excluded female patients, diabetic patients with connective tissue disease, smokers and surgical risk ASA III and IV. We resected a sample of 1 cm² of the transversalis fascia in the middle of the inguinal trigone, and 1 cm² of the anterior sheath of the rectus abdominis muscle in the groin for the quantification of dermatan sulfate glycosaminoglycans by densitometry after agarose gel electrophoresis. The amount of dermatan sulfate showed no statistically significant difference between patients with inguinal hernia and individuals without inguinal hernia in both the transverse fascia (p = 0.108) and anterior sheath of the rectus abdominis muscle (p = 0.292). There was no difference in the amount of the dermatan sulfate glycosaminoglycan among patients with Nyhus type II inguinal hernias and subjects without inguinal hernia in adult males.


Evaluation of long-term weight changes after a multidisciplinary weight control program.
The American Medical Association Council on Scientific Affairs recently emphasized the importance of nutritionally sound weight reduction diets and changes in life-style to promote long-term weight control. The purpose of this study was to evaluate long-term effectiveness and to identify predictors of success of an intensive multidisciplinary program utilizing the time-calorie displacement diet, a low-fat, high-complex-carbohydrate diet, to promote and maintain reduced body weight. In 213 obese adults consecutively entering the program, including dropouts, weight loss averaged 6.3 kg (0.4 kg/week) and 16% of excess weight over 7 months of treatment. The 78 (37%) completing the recommended 15 visits lost a mean of 10.8 kg and 28% of their excess weight while under treatment. Weight loss was largely predicted by number of visits, which was more important than treatment duration. An increased number of visits was predicted by being married, being female, and reporting a usual diet low in snack foods. Of 147 patients contacted at posttreatment follow-up, 53% maintained their weight loss or continued to lose weight an average of 25 months later and 24% experienced weight rebound but were still below their pretreatment weight; only 23% regained their lost weight. Mean net weight loss from pretreatment to follow-up was 8.0 +/- 1.0 kg (mean +/- standard error of the mean). No factor significantly predicted posttreatment weight rebound. Results suggest that a nutritionally sound diet, prescribed in a multidisciplinary program and emphasizing life-style changes, can result in long-term weight control in a majority of patients treated.


Into the Labyrinth of the Lipocalin α1-Acid Glycoprotein.
α1-acid glycoprotein (AGP), also known as Orosomucoid (ORM), belongs to the Lipocalin protein family and it is well-known for being a positive acute-phase protein. AGP is mostly found in plasma, with the liver as main contributor, but it is also expressed in other tissues such as the brain or the adipose tissue. Despite the vast literature on AGP, the physiological functions of the protein remain to be elucidated. A large number of activities mostly related to protection and immune system modulation have been described. Recently created AGP-knockout models have suggested novel physiological roles of AGP, including regulation of metabolism. AGP has an outstanding ability to efficiently bind endogenous and exogenous small molecules that together with the complex and variable glycosylation patterns, determine AGP functions. This review summarizes and discusses the recent findings on AGP structure (including glycans), ligand-binding ability, regulation, and physiological functions of AGP. Moreover, this review explores possible molecular and functional connections between AGP and other members of the Lipocalin protein family.


Field-inversion gel electrophoresis.
Among the techniques to separate large DNA fragments, field-inversion gel electrophoresis (FIGE, 1)is probably the easiest to perform with a minimum of special equipment. Indeed, the only requirement besides a regular gel electrophoresis box and a power supply is a device enabling the periodic inversion of the electric field direction over the course of the experiment. This method was derived from experiments done on a modified orthogonal-field-alternation gel electrophoresis (OFAGE) apparatus (2) based on the observation that obtuse angles lead to a better separation. The widest angle being 180°, the four electrode pulsed-field gel electrophoresis (PFGE) system was reduced to a standard submarine gel electrophoresis box with only two electrodes. This simple configuration generates a highly uniform electric field across the gel, making the lane to lane comparison very easy (Fig. 1). Two basic electrophoretic modes can be used in order to achieve a net migration in this configuration:


One-handed phacoemulsification with low settings.
We describe a technique in which one-handed phacoemulsification with low aspiration flow and vacuum is performed with a peristaltic pump machine. With this technique, ultrasonic energy can be used for nucleus segmentation without the need for a second instrument. Measurements in cadaver eyes and clinical experience showed the technique to be simple, effective, and safe.


Cotton GhSSI2 isoforms from the stearoyl acyl carrier protein fatty acid desaturase family regulate Verticillium wilt resistance.
Lipids are major and essential constituents of plant cells and provide energy for various metabolic processes. However, the function of the lipid signal in defence against Verticillium dahliae, a hemibiotrophic pathogen, remains unknown. Here, we characterized 19 conserved stearoyl-ACP desaturase family proteins from upland cotton (Gossypium hirsutum). We further confirmed that GhSSI2 isoforms, including GhSSI2-A, GhSSI2-B, and GhSSI2-C located on chromosomes A10, D10, and A12, respectively, played a dominant role to the cotton 18:1 (oleic acid) pool. Suppressing the expression of GhSSI2s reduced the 18:1 level, which autoactivated the hypersensitive response (HR) and enhanced cotton Verticillium wilt and Fusarium wilt resistance. We found that low 18:1 levels induced phenylalanine ammonia-lyase-mediated salicylic acid (SA) accumulation and activated a SA-independent defence response in GhSSI2s-silenced cotton, whereas suppressing expression of GhSSI2s affected PDF1.2-dependent jasmonic acid (JA) perception but not the biosynthesis and signalling cascade of JA. Further investigation showed that structurally divergent resistance-related genes and nitric oxide (NO) signal were activated in GhSSI2s-silenced cotton. Taken together, these results indicate that SA-independent defence response, multiple resistance-related proteins, and elevated NO level play an important role in GhSSI2s-regulated Verticillium wilt resistance. These findings broaden our knowledge regarding the lipid signal in disease resistance and provide novel insights into the molecular mechanism of cotton fungal disease resistance.


Special Issue "In Vivo Nuclear Molecular Imaging in Drug Development and Pharmacological Research".
Nuclear molecular imaging is increasingly important in aiding diagnosis, monitoring disease progression, and assessing response to treatment [...].


Detrimental effect of intraoperative hypothermia on pancreatic fistula after pancreaticoduodenectomy: A single-centre retrospective study.
Although perioperative hypothermia was found to be associated with gastrointestinal anastomotic leakage in preclinical studies, its association with postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy was never evaluated. We investigated the association between intraoperative hypothermia and clinically relevant (CR)-POPF following pancreaticoduodenectomy. We retrospectively reviewed 2163 consecutive patients who underwent pancreaticoduodenectomy during 2007-2019. Based on intraoperative time-weighted average core temperature, patients were grouped into normothermia (36.0-37.5°C), mild hypothermia (35.0-<36.0°C), and severe hypothermia (<35°C). We conducted multivariable logistic regression analysis for CR-POPF, a propensity score analysis using inverse probability of treatment weighting (IPTW) to adjust the baseline differences between the three groups, followed by multivariable logistic regression with IPTW for CR-POPF. Among the 2008 patients analysed, 1118 (55.7%) and 120 (6.0%) had mild and severe hypothermia, respectively, and 14.2% overall incidence of CR-POPF. Severe intraoperative hypothermia was significantly associated with CR-POPF before and after IPTW (before: odds ratio [OR] 1.79, 95% confidence interval [CI]: 1.03-3.09, P = .038; after: OR 2.48, 95% CI: 1.28-4.81, P = .007); however, mild hypothermia had no significant associations. Severe intraoperative hypothermia is significantly associated with the occurrence of CR-POPF following pancreaticoduodenectomy, suggesting that hypothermia is deleterious on pancreaticojejunal anastomotic healing.