Taurine protects cerebellar neurons of the external granular layer against ethanol-induced apoptosis in 7-day-old mice.
Acute alcohol administration is harmful especially for the developing nervous system, where it induces massive apoptotic neurodegeneration leading to alcohol-related disorders of newborn infants. Neuroprotection against ethanol-induced apoptosis may save neurons and reduce the consequences of maternal alcohol consumption. Previously we have shown that taurine protects immature cerebellar neurons in the internal granular layer of cerebellum from ethanol-induced apoptosis. Now we describe a similar protective action for taurine in the external layer of cerebellum of 7-day-old mice. The mice were divided into three groups: ethanol-treated, ethanol + taurine-treated and controls. Ethanol (20% solution) was administered subcutaneously at a total dose of 5 g/kg (2.5 g/kg at time 0 h and 2.5 g/kg at 2 h) to the ethanol and ethanol + taurine groups. The ethanol + taurine group also received subcutaneously two injections of taurine (1 g/kg each, 1 h before the first dose of ethanol and 1 h after the second dose of ethanol). To verify apoptosis, immunostaining for activated caspase-3 and TUNEL staining were made in the mid-sagittal sections containing lobules I-X of the cerebellar vermis at 8 h after the first ethanol injection. Ethanol induced apoptosis in the cerebellar external granular layer. Taurine treatment significantly reduced the number of activated caspase-3-immunoreactive and TUNEL-positive cells. Taurine has thus a neuroprotective antiapoptotic action in the external granular layer of the cerebellum, preserving a number of neurons from ethanol-induced apoptosis.


Report of two Chinese patients suffering from CLCN7-related osteopetrosis and root dysplasia.
Osteopetrosis is a group of genetic bone disorders. There are three types of osteopetrosis: autosomal recessive osteopetrosis (ARO), autosomal dominant osteopetrosis type II (ADO II), and intermediate autosomal recessive osteopetrosis (IARO). The prevalence of ADO II is about 1:100,000, while no more than 20 cases of IARO have been reported worldwide. We present the first Chinese IARO patient with a novel homozygous variant in CLCN7 gene (p. Pro470Leu) and an ADO II patient with a heterozygous variant in CLCN7 gene (p. Arg286Trp). In addition to general osteosclerosis, the striking features of these two patients are unerupted teeth with root dysplasia. We speculate that ClC-7 in different tooth cells may contribute directly to the root development, the defect of ClC-7 may have a dose dependent effect on the phenotype of root dysplasia, and the tooth position may also affect the root phenotype with dysfunctional ClC-7.


Dizocilpine and reduced body temperature do not prevent methamphetamine-induced neurotoxicity in the vervet monkey: [11C]WIN 35,428 - positron emission tomography studies.
[11C]WIN 35,428 (WIN), a cocaine analog that binds to the dopamine transporter (DAT), and positron emission tomography (PET) were used to evaluate the potential neuroprotective effects of dizocilpine (MK-801) on methamphetamine (MeAmp) induced neurotoxicity in the striatal dopamine system of the vervet monkey. MK-801 (1 mg/kg, i.m.) was administered 30 min prior to a neurotoxic MeAmp dosage for this species (2 x 2 mg/kg, 4 h apart); control subjects received MeAmp. MK-801 treated subjects were anesthetized by the drug for 6-8 h; throughout that period, a 2-3 degrees C decrease in body temperature was measured. At 1-2 weeks post-MeAmp, decreases of approximately 75% in striatal WIN binding were observed for both MK-801/MeAmp and MeAmp subjects. Thus, in this non-human primate species, the combination of MK-801 pretreatment and reduced body temperature did not provide protection from the MeAmp-induced loss of DAT. Further, the absence of an elevated body temperature during the acute MeAmp exposure period indicated that hyperthermia, per se, was not a necessary concomitant of the MeAmp neurotoxicity profile as has been previously demonstrated in rodents. These results provide evidence that different regulatory factors maintain the integrity of the rodent and primate striatal dopamine systems.


In silico identification of the rare-coding pathogenic mutations and structural modeling of human NNAT gene associated with anorexia nervosa.
Increased susceptibility towards anorexia nervosa (AN) was reported with reduced levels of neuronatin (NNAT) gene. We sought to investigate the most pathogenic rare-coding missense mutations, non-synonymous single-nucleotide polymorphisms (nsSNPs) of NNAT and their potential damaging impact on protein function through transcript level sequence and structure based in silico approaches. Gene sequence, single nucleotide polymorphisms (SNPs) of NNAT was retrieved from public databases and the putative post-translational modification (PTM) sites were analyzed. Distinctive in silico algorithms were recruited for transcript level SNPs analyses and to characterized high-risk rare-coding nsSNPs along with their impact on protein stability function. Ab initio 3D-modeling of wild-type, alternate model prediction for most deleterious nsSNP, validation and recognition of druggable binding pockets were also performed. AN 3D therapeutic compounds that followed rule of drug-likeness were docked with most pathogenic variant of NNAT to estimate the drugs' binding free energies. Conclusively, 10 transcript (201-205)-based nsSNPs from 3 rare-coding missense variants, i.e., rs539681368, rs542858994, rs560845323 out of 840 exonic SNPs were identified. Transcript-based functional impact analyses predicted rs539681368 (C30Y) from NNAT-204 as the high-risk rare-coding pathogenic nsSNP, deviating protein functions. The 3D-modeling analysis of AN drugs' binding energies indicated lowest binding free energy (ΔG) and significant inhibition constant (Ki) with mutant models C30Y. Mutant model (C30Y) exhibiting significant drug binding affinity and the commonest interaction observed at the acetylation site K59. Thus, based on these findings, we concluded that the identified nsSNP may serve as potential targets for various studies, diagnosis and therapeutic interventions. No level of evidence-open access bioinformatics research.


Sarcomatoid tumours of the breast in Denmark from 1977 to 1987. A clinicopathological and immunohistochemical study of 100 cases.
One hundred sarcomatoid breast tumours, which had been diagnosed and registered in Denmark from January 1977 to January 1987, were subclassified using a combination of conventional morphological evaluation and immunohistochemistry, and the diagnosis was in each case related to clinical follow-up of 5-14 years or until death of the patient. Conventional histological examination resulted in 36 benign, 19 borderline and 18 malignant phyllodes tumours, 1 angiosarcoma and 26 non-specified sarcomatous tumours, 6 with small carcinoma-like foci. Immunohistochemical staining revealed that 23 of the non-phylloid sarcomatous tumours showed a tumour cell reaction for epithelial markers, predominantly cytokeratin and, therefore, the tumours were interpreted as metaplastic carcinomas. Clinical follow-up showed for phyllodes tumours and for the three cytokeratin-negative sarcomatous tumours local recurrence rates of 21 and 33%, respectively, whereas metastases only occurred from the angiosarcoma and from one borderline phyllodes tumour with five recurrences (5%). In contrast, metaplastic carcinomas gave rise to distant metastases in 50% of cases but no local recurrences. Axillary lymph nodes had been examined in 28 cases, 13 from metaplastic carcinomas. Only two of these showed metastatic spread, both with a pattern similar to the primary tumour. The differences in survival between patients with metaplastic carcinoma and patients with a borderline/malignant phyllodes tumour or a cytokeratin-negative sarcomatous tumour has in this study proven to be highly significant (P < 0.0001), and we find it of importance to use immunohistochemistry in the subclassification of sarcomatous breast tumours for appropriate surgery, reliable prognostic outlook and optimal postoperative therapy.


Evaluating the effects of spatial frequency on migraines by using pattern-reversal visual evoked potentials.
To clarify the effects of contrast and spatial frequency in patients with migraine by means of pattern-reversal visual evoked potentials (PVEPs). PVEPs were obtained from 14 patients who had migraine without aura (MO), 11 patients who had migraine with aura (MA), and 25 age-matched, healthy controls (CO). PVEPs were binocularly recorded with a reversal rate of 1Hz (2 reversal/s) at 3 spatial frequencies (0.5, 1.0 and 4.0 cpd) at high (98%), medium (83%) and low (29%) contrast. N75, P100 and N135 latency and the amplitudes of P50-N75, N75-P100 and P100-N135 were analyzed. Increased amplitude of PVEPs in patients with migraines were revealed at 3 different spatial frequencies in all components. The MO and the MA showed increased amplitudes mostly in high contrasts (98%). These findings were detected more at a high spatial frequency (4.0 cpd) than at a low spatial frequency (0.5 cpd). Increased amplitude with prolonged latency of N135 were found both in MO and MA at 4.0 cpd. We conclude that pattern stimuli of high contrasts may be particularly effective in uncovering abnormal cortical reactivity which may be modified in the primary and secondary visual cortex in the interictal state of migraine. These findings indicate that there is abnormal visual cortex processing in patients with migraine.


Effects of Cryptosporidium parvum infection on intestinal fungal microbiota in yaks (Bos grunniens).
During the last decade, researchers had started to focus on the relationship between intestinal parasitic infection and variation of intestinal microflora. Cryptosporidium is a widely known opportunistic and zoonotic pathogen. Several studies have shown that Cryptosporidium infection has impact to alter the gut microflora. However, there are only few studies referring to the fungal microflora changes in response to Cryptosporidium infection in highland ruminants. Therefore, the present study was performed for exploring the alternations of intestinal fungal microbiota in yaks after exposure to Cryptosporidium infection. In present study, Amplicon sequencing of ITS regions was used to study the variations of fungal microflora in yaks. After filtering the raw data, over 45 000 and 62 000 clean data were obtained in uninfected and infected yaks, respectively. By using alpha diversity analysis, it was found that there is no significant difference in the richness and evenness when positive samples were compared with negative ones, whereas intestinal fungal communities in different taxa in yaks were changed. The results of present study depicted that 2-phyla and 21-genera in the infected animals had significantly (P < 0.05) changed. These genera were Septoria, Coniothyrium, Cleistothelebolus, Bensingtonia, Cystobasidium, Filobasidium, Coprotus, Carex, Blumeria, Coprinellus, Leucosporidium, Phialophora, Isolepis, Ascobolus, Thecaphora, Mortierella, Urocystis, Symmetrospora and Lasiobolus. In addition, we found variations in 28 enzymes suggesting that the function of microbiota was also affected. It is concluded that there are drastic changes in the fungal microflora and microbiota functions after exposure to Cryptosporidium infection in yak. Our results help to focus on the prompt way for the development of new therapies to control Cryptosporidiosis.


A preliminary evaluation of a web-based intervention for college marijuana use.
Young adults in college have high rates of marijuana use, abuse, and dependence. Web-based interventions are increasingly popular, but their dissemination exceeds empirical support. One popular but understudied program is The Marijuana eCHECKUP TO GO (e-TOKE) for Universities & Colleges (San Diego State University Research Foundation, 2009). The aim of the present study was to evaluate its short-term effectiveness in changing marijuana involvement and perceived norms in undergraduates. Participants were 317 undergraduates (52% female, 78% White) who reported marijuana use within the month preceding baseline; each was randomly assigned to 1 of 4 conditions formed by crossing e-TOKE versus assessment only, with brief versus extensive baseline assessment (to assess assessment reactivity). Thus, 161 (51%) received eTOKE (77 with extended baseline, 84 with brief baseline), and 156 (49%) received assessment-only control (85 with extended baseline, 71 with brief baseline). 1 month later, all participants reported on marijuana use, problems, abuse and dependence symptoms, and norms. Assessment reactivity analyses yielded no significant differences by assessment condition. Individuals completing the e-TOKE program reported less extreme descriptive norms (ps < 0.01) but no decrease in marijuana use frequency, problems, abuse or dependence symptoms, or changes in injunctive norms (ps > 0.10). Thus, e-TOKE reduces perceptions of others' use, but this study did not provide evidence for its utility in changing personal use and problem indicators in the short-term. More research with longer follow-ups is indicated, given the possibility that descriptive norms could mediate behavior change.


Intracellular calcium homeostasis and signaling.
Ca(2+) is a universal carrier of biological information: it controls cell life from its origin at fertilization to its end in the process of programmed cell death. Ca(2+) is a conventional diffusible second messenger released inside cells by the interaction of first messengers with plasma membrane receptors. However, it can also penetrate directly into cells to deliver information without the intermediation of first or second messengers. Even more distinctively, Ca(2+) can act as a first messenger, by interacting with a plasma membrane receptor to set in motion intracellular signaling pathways that involve Ca(2+) itself. Perhaps the most distinctive property of the Ca(2+) signal is its ambivalence: while essential to the correct functioning of cells, Ca(2+) becomes an agent that mediates cell distress, or even (toxic) cell death, if its concentration and movements inside cells are not carefully tuned. Ca(2+) is controlled by reversible complexation to specific proteins, which could be pure Ca(2+) buffers, or which, in addition to buffering Ca(2+), also decode its signal to pass it on to targets. The most important actors in the buffering of cell Ca(2+) are proteins that transport it across the plasma membrane and the membrane of the organelles: some have high Ca(2+) affinity and low transport capacity (e.g., Ca(2+) pumps), others have opposite properties (e.g., the Ca(2+) uptake system of mitochondria). Between the initial event of fertilization, and the terminal event of programmed cell death, the Ca(2+) signal regulates the most important activities of the cell, from the expression of genes, to heart and muscle contraction and other motility processes, to diverse metabolic pathways involved in the generation of cell fuels.


Gain Modulation by Corticostriatal and Thalamostriatal Input Signals during Reward-Conditioned Behavior.
The cortex and thalamus send excitatory projections to the striatum, but little is known about how these inputs, either individually or collectively, regulate striatal dynamics during behavior. The lateral striatum receives overlapping input from the secondary motor cortex (M2), an area involved in licking, and the parafascicular thalamic nucleus (PF). Using neural recordings, together with optogenetic terminal inhibition, we examine the contribution of M2 and PF projections on medium spiny projection neuron (MSN) activity as mice performed an anticipatory licking task. Each input has a similar contribution to striatal activity. By comparing how suppressing single or multiple projections altered striatal activity, we find that cortical and thalamic input signals modulate MSN gain and that this effect is more pronounced in a temporally specific period of the task following the cue presentation. These results demonstrate that cortical and thalamic inputs synergistically regulate striatal output during reward-conditioned behavior.


Feasibility study of a clinically-integrated randomized trial of modifications to radical prostatectomy.
Numerous technical modifications to radical prostatectomy have been proposed. Such modifications are likely to lead to only slight improvements in outcomes. Although small differences would be worthwhile, an appropriately powered randomized trial would need to be very large, and thus of doubtful feasibility given the expense, complexity and regulatory burden of contemporary clinical trials. We have proposed a novel methodology, the clinically-integrated randomized trial, which dramatically streamlines trial procedures in order to reduce the marginal cost of an additional patient towards zero. We aimed to determine the feasibility of implementing such a trial for radical prostatectomy. Patients undergoing radical prostatectomy as initial treatment for prostate cancer were randomized in a factorial design to involvement of the fascia during placement of the anastomotic sutures, urethral irrigation, both or neither. Endpoint data were obtained from routine clinical documentation. Accrual and compliance rates were monitored to determine the feasibility of the trial. From a total of 260 eligible patients, 154 (59%) consented; 56 patients declined to participate, 20 were not approached on recommendation of the treating surgeon, and 30 were not approached for logistical reasons. Although recording by surgeons of the procedure used was incomplete (~80%), compliance with randomization was excellent when it was recorded, with only 6% of procedures inconsistent with allocation. Outcomes data was received from 71% of patients at one year. This improved to 83% as the trial progressed. A clinically-integrated randomized trial was conducted at low cost, with excellent accrual, and acceptable compliance with treatment allocation and outcomes reporting. This demonstrates the feasibility of the methodology. Improved methods to ensure documentation of surgical procedures would be required before wider implementation. ClinicalTrials.gov NCT00928850.


Minimally invasive posterior transforaminal lumbar interbody fusion: One-year postoperative morbidity, clinical and radiological results of a prospective multicenter study of 182 cases.
Interbody fusion is the gold standard treatment for the management of numerous diseases of the spine. Minimally invasive techniques may be more beneficial than conventional techniques. The main goal of this study was to report the one-year postoperative results of a series of posterior lumbar interbody fusions by a minimally invasive technique in relation to improvement in functional outcome, interbody fusion and morbidity. Between January 2012 and May 2013, 182 patients treated by minimally invasive posterior transforaminal lumbar interbody fusion (TLIF) were included in this prospective multicenter study. Clinical assessment was based on a comparison of the preoperative and one-year postoperative Oswestry (ODI), SF-12 and Quebec Scores and the Visual Analog Scale (VAS). Surgical and postoperative follow-up data were evaluated. Radiological assessment was based preoperative and one-year postoperative full spine teleradiographs. Interbody fusion at one-year was systematically evaluated by CT scan. One hundred and eighty-two patients were included, mean age 58.9 years old. Surgery lasted a mean 101 minutes, mean preoperative bleeding was 143 mL, and mean radiation exposure was 247.4 cGy/cm(2). The rate of postoperative complications was 7.7%. The ODI, the Quebec Score, the SF-12 and the VAS were all significantly improved at one-year (P<0.0001). The rate of fusion was 72.6% at the final follow-up. There was no significant difference in functional outcome between patients with and without fusion. The one-year postoperative radiological results and functional outcome of minimally invasive posterior lumbar fusion are satisfactory. The benefits of this minimally invasive approach are mainly found in the first 6 postoperative months. Successful radiological interbody fusion was not correlated to functional outcome at the final follow-up.


Intra- and extravascular volume changes in the human forearm after static hand grip exercise.
Studies have been conducted to evaluate intra- and extravascular volume changes and blood flow in the exercising human forearm by means of (1) combining plethysmographic and scintigraphic methods, (2) an indirect procedure using the relationship of blood flow and volume change from reactive hyperemia. A static hand grip exercise of 60% maximal voluntary contraction and 30 s duration increased the forearm volume by 3.03 +/- 0.65 ml/100 ml soft tissue, involving both the intra- and extravascular volume components. There is a quantitative and qualitative difference in the time course of change in these components, showing an extravascular part of about 50% for the 2-min post-exercise value and a substantially slower rate of recovery. Experiments involving muscle work at intervals (50% maximal voluntary contraction, 30 s duration, 2-min intervals) caused a further increase in extravascular volume. Furthermore, the study suggests that the flow-volume relationship from reactive hyperemia may be considered to be available for the determination of local blood volume changes in exercise hyperemia. The results are discussed in connection with the influence of anaerobic muscle metabolism and conclusions referring to this are drawn about the use of plethysmographic methods.


POLθ processes ssDNA gaps and promotes replication fork progression in BRCA1-deficient cells.
Polymerase theta (POLθ) is an error-prone DNA polymerase whose loss is synthetically lethal in cancer cells bearing breast cancer susceptibility proteins 1 and 2 (BRCA1/2) mutations. To investigate the basis of this genetic interaction, we utilized a small-molecule inhibitor targeting the POLθ polymerase domain. We found that POLθ processes single-stranded DNA (ssDNA) gaps that emerge in the absence of BRCA1, thus promoting unperturbed replication fork progression and survival of BRCA1 mutant cells. A genome-scale CRISPR-Cas9 knockout screen uncovered suppressors of the functional interaction between POLθ and BRCA1, including NBN, a component of the MRN complex, and cell-cycle regulators such as CDK6. While the MRN complex nucleolytically processes ssDNA gaps, CDK6 promotes cell-cycle progression, thereby exacerbating replication stress, a feature of BRCA1-deficient cells that lack POLθ activity. Thus, ssDNA gap formation, modulated by cell-cycle regulators and MRN complex activity, underlies the synthetic lethality between POLθ and BRCA1, an important insight for clinical trials with POLθ inhibitors.


Analysis of peripheral blood for prostate cells after autologous transfusion given during radical prostatectomy.
To determine if cells expressing prostate-specific antigen (PSA) can be detected in blood collected by a cell-saver during radical prostatectomy (RP) or in the peripheral blood after intraoperative autotransfusion (IAT). In all, 112 men with clinical T1c-T2 prostate cancer undergoing RP were prospectively assessed. A cell-saver system was used in each to collect blood from the surgical field after prostate manipulation. IAT was given based on clinical indications. Standardized peripheral blood samples were collected from patients before RP, in the recovery room afterward, and at 3-5 weeks after surgery. A reverse-transcriptase-polymerase chain reaction assay for PSA mRNA was used to detect prostate cells in cell-saver and peripheral blood samples. Patients were followed after surgery with PSA measurements to assess biochemical failure. PSA-expressing cells were detected in 88% of cell-saver reservoir and 13% of preoperative blood samples. No PSA-expressing prostate cells were detected in any peripheral blood samples collected 3-5 weeks after surgery. Analysis of data with 40 months of follow-up showed IAT was not an independent predictor of biochemical failure in multivariate analysis. Although IAT blood contains PSA-expressing cells, none could be detected 3-5 weeks after surgery. IAT during RP was not associated with a greater risk of biochemical failure.


Increased use of oral chemotherapy drugs spurs increased attention to patient compliance.
Ensuring that patients with breast cancer are taking the oral aromatase inhibitors prescribed as follow-up treatment to surgery is an ongoing concern for oncologists.


Adaptive closed-loop paradigm of electrophysiology for neuron models.
The traditional electrophysiological experiments based on an open-loop paradigm are relatively complicated and limited when facing an individual neuron with uncertain nonlinear factors. Emerging neural technologies enable tremendous growth in experimental data leading to the curse of high-dimensional data, which obstructs the mechanism exploration of spiking activities in the neurons. In this work, we propose an adaptive closed-loop electrophysiology simulation experimental paradigm based on a Radial Basis Function neural network and a highly nonlinear unscented Kalman filter. On account of the complex nonlinear dynamic characteristics of the real neurons, the proposed simulation experimental paradigm could fit the unknown neuron models with different channel parameters and different structures (i.e. single or multiple compartments), and further compute the injected stimulus in time according to the arbitrary desired spiking activities of the neurons. However, the hidden electrophysiological states of the neurons are difficult to be measured directly. Thus, an extra Unscented Kalman filter modular is incorporated in the closed-loop electrophysiology experimental paradigm. The numerical results and theoretical analyses demonstrate that the proposed adaptive closed-loop electrophysiology simulation experimental paradigm achieves desired spiking activities arbitrarily and the hidden dynamics of the neurons are visualized by the unscented Kalman filter modular. The proposed adaptive closed-loop simulation experimental paradigm can avoid the inefficiency of data at increasingly greater scales and enhance the scalability of electrophysiological experiments, thus speeding up the discovery cycle on neuroscience.


Exogenous methyl jasmonate and cytokinin antagonistically regulate lignin biosynthesis by mediating CsHCT expression in Camellia sinensis.
Tea plant, an important beverage crop, is cultivated worldwide. Lignification can improve the hardness of tea plant, which is of great significance for tea quality. Jasmonates (JAs) and cytokinin are plant hormones that control processes of plant development and secondary metabolite accumulation. Hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (HCT) is primarily involved in lignin biosynthesis. The effects of exogenous application of JAs and cytokinin on lignin biosynthesis and related HCT gene expression profiles in tea plants are still unclear. In order to investigate the effects of exogenous JAs and cytokinin on lignin accumulation, anatomical structures, and CsHCT gene profiles in tea plants, we treated tea plants with methyl jasmonate (MeJA) and cytokinin (6-BA). MeJA and 6-BA treatments triggered the lignification at 6 and 12 d in tea leaves. The combined treatment resulted in an increase in lignin content at 6 d, which was 1.32 times of that at 0 d for 'Mengshan 9.' The CsHCTs in clade 2 (CsHCT5, CsHCT6, CsHCT7, and CsHCT8) were mainly expressed in leaves. We found that exogenous MeJA and cytokinin might be able to antagonistically regulate tea plant lignin accumulation through the mediation of CsHCT expression. This study revealed that HCTs play potential important roles involved in lignin biosynthesis of tea plant development and hormonal stimuli.


Differential neural predictors of treatment response for fear and dysphoric features of posttraumatic stress disorder.
Although trauma-focused cognitive behavioral therapy (TF-CBT) is the frontline treatment for posttraumatic stress disorder (PTSD), at least one-third of patients are treatment nonresponders. This study aimed to identify neural markers of treatment response, specifically the prediction of remission of specific PTSD symptoms. This study assessed PTSD treatment-seeking patients (n = 40) before TF-CBT during functional magnetic brain resonance imaging (fMRI) when they processed fearful, sad, happy, and neutral faces. Patients underwent nine sessions of TF-CBT and were independently assessed on the Clinician-Administered PTSD Scale (CAPS) following treatment. Treatment responders and nonresponders were compared with healthy controls (n = 40). The severity of PTSD was assessed with the CAPS. fMRI responses were calculated for each emotion face compared to neutral contrast, which were correlated with reduction in PTSD severity from pretreatment to posttreatment. Treatment response was categorized by at least 50% reduction in the severity of PTSD. The activation of left insula during the processing of both sad and fearful faces was associated with a greater reduction of fear but not with dysphoric symptoms after treatment. Connectivity of the left insula to the pregenual anterior cingulate cortex was associated with poorer response to treatment. Responders and controllers had similar levels of activation and connectivity and were different from nonresponders. Positive response to TF-CBT is predicted during emotion processing by normal levels of recruitment of neural networks implicated in emotional information. These findings suggest that distinct neural networks are predictive of PTSD fear and dysphoric symptom reduction following TF-CBT.


Influence of stimulus intensity on waveform of sympathetic skin response evoked by magnetic stimulation.
The aim of this study was to investigate the influence of stimulus intensity on the waveform of sympathetic skin response (SSR). The origin of the SSR waveform was discussed. A total of 12 SSRs from palm skin were analyzed in 40 normal subjects. SSR was evoked by magnetic stimulation to the neck at 3 different intensities (10, 35, and 70% of the maximum output). The 3 stimuli were repeatedly applied in 4 separate sets. Waveforms were classified as either the P type, in which the positive component was larger than the negative one, or the N type, in which the negative component was larger than the positive one. Amplitude values of peak-to-peak, the first negative (N1), and subsequent positive (P1) components were compared among the 12 responses. When the stimulation was increased, the SSR size became larger. The P type SSR was most frequently found in the maximum stimulation. Strong stimulation generally produced a large P1. Only the N type SSR exhibited a large N1 response to the maximum stimulation. There was a significant, negative correlation between N1 peak duration (difference between the SSR onset and N1 peak latencies) and P1 amplitude. These results suggested that strong responses probably produced a P type SSR with a large P1 component. In this condition, a rapid change of potential from negative to positive prevented any correlation between N1 amplitude and the magnitude of the response. In the N type SSR, however, a large N1 was associated with a strong response. These findings can be explained by a newly presented theory on the neurophysiological origin of the negative and positive components, based on a model of equivalent current dipole dependent on the Na+ concentration gradient. The present study provided some suggestions on the neurophysiological mechanism of SSR waveform.


[Structure of inclusion bodies and electron microscopic virus detection in naturally occurring inclusion body hepatitis in chickens].
Electron microscopy was used to examine the liver of chickens with spontaneous inclusion body hepatitis. Eosinophilic inclusion bodies only were established from two flocks, mainly amphophilic from one flock, and primarily basophilic from another two flocks. Eosinophilic inclusion bodies were predominant in broiler chickens with dystrophic fatty degeneration of the liver, while basophile inclusion bodies were recorded primarily from parental or laying-hen chickens with reduced metabolic stress of the liver and more focal necrosis. The eosinophilic inclusion bodies consitsed of a filamentous matrix, with virus particles not safely detectable. The amphophilic inclusion bodies contained parvovirus particles, most likely adenoassociated virus, while the basophilic inclusion bodies inclused parvoviruses or adenoviruses (in flock NO. IV) or adenoviruses only (in flock No. V) in an amorphous chromatin matrix. The presence of parvoviruses in field material was taken to suggest a possible role of those pathogens in inclusion body hepatitis.


Detection of non-HLA-DR determinants by alloreactive lymphocyte clones.
Using the soft-agar colony assay, we have generated three MT3-associated clones: HJ1, HJ13, and HJ39, from an MLR combination of two unrelated individuals. Another clone, HJ37, appeared to recognize a novel HLA-D determinant. PLT inhibition studies with monoclonal anti-Ia-like antibodies (Mab) were conducted on clones HJ1, HJ39, and HJ37. Five different anti-DR Mab had no significant inhibitory effect on these clones. On the other hand, two Mab SG171 and Q5/13 which appear to react with DR and MT3 (I-A like) molecules strongly inhibited the two MT3-specific PLT clones. While SG171 and Q5/13 had little effect on HJ37, it was observed that a polymorphic Mab 17.15 had a strong inhibitory effect. These results, in concordance with biochemical data on Ia molecules precipitated by these Mab, suggest that these alloreactive clones may recognize non-DR PLT determinants. They also provide further indirect support that MT3 molecules represent the human homologue of murine I-A molecules.


The functions of antennal mechanoreceptors and antennal joints in tactile discrimination of the honeybee (Apis mellifera L.).
Honeybees learn and discriminate excellently between different surface structures and different forms of objects, which they scan with their antennae. The sensory plate on the antennal tip plays a key role in the perception of mechanosensory and gustatory information. It is densely covered with small tactile hairs and carries a few large taste hairs. Both types of sensilla contain a mechanoreceptor, which is involved in the antennal scanning of an object. Our experiments test the roles of the mechanoreceptors on the antennal tip in tactile antennal learning and discrimination. Joints between head capsule and scapus and between scapus and pedicellus enable the bee to perform three-dimensional movements when they scan an object. The role of these joints in tactile antennal learning and discrimination is studied in separate experiments. The mechanoreceptors on the antennal tip were decisive for surface discrimination, but not for tactile acquisition or discrimination of shapes. When the scapus-pedicellus joint or the headcapsule-scapus joint was fixed on both antennae, tactile learning was still apparent but surface discrimination was abolished. Fixing both scapi to the head capsule reduced tactile acquisition.


Modulation of intracellular Ca2+ in the parathyroid cell. Release of Ca2+ from non-mitochondrial pools by inositol trisphosphate.
Stimuli which enhance secretion from parathyroid cells such as low extracellular Ca2+ or Mg2+ are associated with a decrease in the cytosolic Ca2+ concentration as measured by quin2. Current evidence suggests that increased production of inositol 1,4,5-triphosphate (IP3) releases Ca2+ from cellular stores thus increasing cytosolic Ca2+. We used saponin-permeabilized dispersed bovine parathyroid cells to study the effect of IP3 on intracellular Ca2+. IP3 released Ca2+ from these cells in a dose-dependent manner; half-maximal response occurred with 0.3 microM IP3 and maximal response with 1.2 microM IP3. Permeabilized cells incubated in the presence of the mitochondrial inhibitor antimycin A released a similar amount of Ca2+ suggesting that IP3 releases Ca2+ from a non-mitochondrial pool. These results suggest that IP3 regulates cytosolic Ca2+ in this system and may function as a second messenger controlling hormone secretion.


The common ultrasonographic features of pilomatricoma.
The purpose of this series was to describe typical ultrasonographic features of 20 cases of pilomatricoma and to improve its diagnostic rate with the use of an ultrasonographic approach. For 20 pilomatricomas in 19 patients with preoperative ultrasonography from 1995 to 2004, we reviewed age, sex, symptoms, duration, referring clinician, and tumor sites. The ultrasonographic findings were retrospectively analyzed for tumor location, shape, size, margin, echo texture, echogenicity, presence, amount, and shape of calcification, presence of a hypoechoic rim, and Doppler flow pattern. The mean age of the 19 patients was 6.9 years (range, 1-21 years), and the female-male ratio was 1.1:1. Patients had a painful palpable mass in 10 cases (50%). Nine lesions occurred in the neck, 5 in the cheek, 2 in the preauricular region, and 4 in the extremity. All tumors were located in the subcutaneous layer. The mean size of the tumors was 13.4 mm. Fourteen pilomatricomas (70%) appeared as well-defined oval masses. Tumors were heterogeneously hyperechoic in 80% of cases. All tumors had internal echogenic foci. A hypoechoic rim was seen in 17 cases (85%). Doppler flow signals were observed in the peripheral region in 14 cases (70%). A correct preoperative diagnosis was made in 33% on the basis of clinical findings and in 76% by ultrasonography. Diagnosis of pilomatricoma should be considered when a well-defined mass with inner echogenic foci and a peripheral hypoechoic rim or a completely echogenic mass with strong posterior acoustic shadowing in the subcutaneous layer of the head, neck, or extremity is found on ultrasonography.


[Isolation of antigens from Echinococcus granulousus cysts by gradual membrane filtration].
High molecular fractions were obtained by gradual membrane diafiltration and their antigenic and enzymatic (carboxylesterase) activity were analyzed. Degree of the fractions' homogeneity was determined by high performance liquid chromatography. Active antigenic complexes were discovered in fractions with m. m. over 300.000 and 100.000 = 300.000.


A Golgi fragmentation pathway in neurodegeneration.
The Golgi apparatus processes intracellular proteins, but undergoes disassembly and fragmentation during apoptosis in several neurodegenerative disorders such as amyotrophic lateral sclerosis and Alzheimer's disease. It is well known that other cytoplasmic organelles play important roles in cell death pathways. Thus, we hypothesized that Golgi fragmentation might participate in transduction of cell death signals. Here, we found that Golgi fragmentation and dispersal precede neuronal cell death triggered by excitotoxins, oxidative/nitrosative insults, or ER stress. Pharmacological intervention or overexpression of the C-terminal fragment of Grasp65, a Golgi-associated protein, inhibits fragmentation and decreases or delays neuronal cell death. Inhibition of mitochondrial or ER cell death pathways also decreases Golgi fragmentation, indicating crosstalk between organelles and suggesting that the Golgi may be a common downstream-effector of cell death. Taken together, these findings implicate the Golgi as a sensor of stress signals in cell death pathways.


Distinct clinical phenotypes of congestion in acute heart failure: characteristics, treatment response, and outcomes.
Patients with acute heart failure (AHF) are included into clinical trials regardless of differences in baseline clinical characteristics. The aim of this study was to assess patients with AHF according to the presence of central and/or peripheral congestion at hospital admission and evaluate treatment response and outcomes in studied phenotypes. We investigated retrospectively 352 patients (mean age: 68 ± 13 years, 77% men) hospitalized due to AHF with the signs of congestion on admission. Patients were divided according to the type of signs of congestion into three groups: A, isolated pulmonary congestion (n = 52, 15%); B, isolated peripheral congestion (n = 31, 9%); and C, signs of mixed (peripheral and central) congestion (n = 269, 76%). Patients from Group A had lower concentration of urea, bilirubin, and gamma-glutamyl transferase whereas higher level of haematocrit, albumin, and leukocytes on admission. The highest baseline N-terminal pro-B-type natriuretic peptide level (median: 4113 vs. 3634 vs. 6093 pg/mL) and percentage of patients with chronic heart failure (56 vs. 58 vs. 74%; A vs. B. vs. C, respectively, all P < 0.01) were observed in Group C. There were no differences in terms of demographics, co-morbidities, left ventricular ejection fraction, and applied treatment between studied groups. Patients from Group A had the highest systolic blood pressure on admission (145 ± 37 vs. 122 ± 20 vs. 130 ± 29 mmHg) and the biggest decrease in systolic blood pressure [-22 (-45 to -4) vs. -2 (-13 to 2) vs. -10 (-25 to 0) mmHg] and heart rate [-16 (-35 to -1.5) vs. -1 (-10 to 5) vs. -7 (-20 to 0) b.p.m.] with the lowest weight change [-1.0 (-1.0 to 0) vs. -2.9 (-3.8 to -0.9) vs. -2.0 (-3.0 to -1.0) kg; all P < 0.01] after 48 h of hospitalization. There were differences in short-term and long-term outcomes with favourable results in Group A. Group A experienced less frequent in-hospital heart failure worsening during the first 48 h (4 vs. 23 vs. 7%), had shorter length of hospital stay [6 (5-8) vs. 7 (5-11) vs. 7 (6-11) days], and had lower 1 year all-cause mortality (12 vs. 28 vs. 29%; all P < 0.05). Presence of peripheral congestion on admission was independent predictor for all-cause mortality within 1 year [hazard ratio (95% confidence interval): 2.68 (1.06-6.79); P = 0.04]. Patterns of congestion in AHF are associated with differences in clinical characteristics, treatment response, and outcomes. It needs to be considered once planning clinical trials in AHF.


Articular morphology of the proximal ulna in extant and fossil hominoids and hominins.
Extant hominoids share similar elbow joint morphology, which is believed to be an adaptation for elbow stability through a wide range of pronation-supination and flexion-extension postures. Mild variations in elbow joint morphology reported among extant hominoids are often qualitative, where orangutans are described as having keeled joints, and humans and gorillas as having flatter joints. Although these differences in keeling are often linked to variation in upper limb use or loading, they have not been specifically quantified. Many of the muscles important in arboreal locomotion in hominoids (i.e., wrist and finger flexors and extensors) take their origins from the humeral epicondyles. Contractions of these muscles generate transverse forces across the elbow, which are resisted mainly by the keel of the humeroulnar joint. Therefore, species with well-developed forearm musculature, like arboreal hominoids, should have more elbow joint keeling than nonarboreal species. This paper explores the three- and two-dimensional morphology of the trochlear notch of the elbow of extant hominoids and fossil hominins and hominoids for which the locomotor habitus is still debated. As expected, the elbow articulation of habitually arboreal extant apes is more keeled than that of humans. In addition, extant knuckle-walkers are characterized by joints that are distally expanded in order to provide greater articular surface area perpendicular to the large loads incurred during terrestrial locomotion with an extended forearm. Oreopithecus is characterized by a pronounced keel of the trochlear notch and resembles Pongo and Pan. OH 36 has a morphology that is unlike that of extant species or other fossil hominins. All other hominin fossils included in this study have trochlear notches intermediate in form between Homo and Gorilla or Pan, suggesting a muscularity that is less than in African apes but greater than in humans.


Gastro-gastric Fistula: Late Complication After Roux-en-Y Gastric Bypass.
Gastro-gastric fistula is a rare complication after divided Roux-en-Y gastric by-pass. 52-year-old male with a BMI over 49 who underwent divided Roux-en-Y gastric by-pass presented with weight regain 2 years later and a type 2 gastro-gastric fistula. Laparoscopic revision, excision of the fistula with re-do of gastrojejunal anastomosis and remnant gastrectomy, was performed CONCLUSION: Laparoscopic resolution is a technical challenge in this case due to the local inflammatory environment.


Characterization of binding of [3H]PD 128907, a selective dopamine D3 receptor agonist ligand, to CHO-K1 cells.
PD 128907 [4a R, 10 b R-(+)-trans-3, 4, 4a, 10 b - tetrahydro - 4- n -propyl2 H,5H-[1]benzop-yrano[4,3-b]1,4-oxazin-9-ol.], a selective dopamine (DA) D3 receptor agonist ligand exhibits about a 1000-fold selectivity for human D3 receptors (Ki, 1 nM) versus human D2 receptors (Ki, 1183 nM) and a 10000-fold selectivity versus human D4 receptors (Ki, 7000 nM) using [3H]spiperone as the radioligand in CHO-K1-cells. Studies with [3H]PD 128907, showed saturable, high affinity binding to human D3 receptors expressed in CHO-K1 cells (CHO-K1-D3) with an equilibrium dissociation constant (Kd) of 0.99 nM and a binding density (Bmax) of 475 fmol/mg protein. Under the same conditions, there was no significant specific binding in CHO-K1-cells expressing human D2 receptors (CHO-K1-D2). The rank order of potency for inhibition of [3H]PD 128907 binding with reference DA agents was consistent with reported values for D3 receptors. These results indicate that [3H]PD 128907 is a new, highly selective D3 receptor ligand with high specific activity, high specific binding and low non-specific binding and therefore should be useful for further characterizing the DA D3 receptors.


Visualization of skin appendages by scanning electron microscopy.
A method for SEM visualization of skin appendages and elastic fibres around them is described. Skin sections were autoclaved for 4 h and followed by fixation, dehydration and xylol-air drying. Using this method, the three-dimensional architectural details of each type of skin appendage and related elastic fibre network were demonstrated.


Perioperative nursing and education: what the IOM future of nursing report tells us.
Changes in the current health care system have rendered the system unprepared to support new demands. Similarly, nursing education both before and after licensure is no longer adequate. Four of the eight recommendations in the Institute of Medicine's Future of Nursing report involve changes to nursing education and pose significant goals to achieve. This makes creating innovative ways to meet the demand for educating RNs a necessity. This article discusses the Institute of Medicine's recommendations, how they relate to perioperative nursing, and ways in which nurses and educators can help promote expectations.


Response of microglial cells after a cryolesion in the peripheral proliferative retina of tench.
We studied the glial response after inducing a lesion in the zone of the peripheral retina of tench, where there is proliferative neuroepithelium. In the retina and optic nerve, the microglial response was analysed with tomato lectin and the macroglial response with antibodies against GFAP and S-100. In lesioned retinas, there was a temporal-spatial distribution pattern of microglia. One day after lesion, primitive ramified cells appeared in the nerve fibre layer. These cells appeared progressively from the vitreal to the scleral layers until day 7 when cells appeared in all layers, with the exception of the outer plexiform layer. From this point, labelling decreased. In the optic nerve, 3 days after lesion, an increase in the number of microglial cells was observed, first in the nerve folds and from day 15 in specific areas of the optic nerve. In the central retina, in the optic nerve head and within the optic nerve itself, the appearance of microglial cells, after the lesion, near the blood vessels, could indicate a vascular origin of microglia, as has been proposed by many authors. However, we cannot discount the idea that some of the reactive microglial cells arise by proliferation of the microglia existing in the normal state. Using GFAP and S-100 antibodies, no important changes in the retina were observed, however in the optic nerve there was response to the lesion. Thus, the macroglial cells appeared to be involved in reorganisation of the optic nerve axons after lesion.


Intrathoracic solitary fibrous tumor - an international multicenter study on clinical outcome and novel circulating biomarkers.
Intrathoracic solitary fibrous tumor (SFT) is a rare disease. Radical resection is the standard of care. However, estimating prognosis and planning follow-up and treatment strategies remains challenging. Data were retrospectively collected by five international centers to explore outcome and biomarkers for predicting event-free-survival (EFS). 125 histological proven SFT patients (74 female; 59.2%; 104 benign; 83.2%) were analyzed. The one-, three-, five- and ten-year EFS after curative-intent surgery was 98%, 90%, 77% and 67%, respectively. Patients age (≥59 vs. <59 years hazard ratio (HR) 4.23, 95 confidence interval (CI) 1.56-11.47, p = 0.005), tumor-dignity (malignant vs. benign HR 6.98, CI 3.01-16.20, p <0.001), tumor-size (>10 cm vs. ≤10 cm HR 2.53, CI 1.10-5.83, p = 0.030), de Perrot staging (late vs. early HR 3.85, CI 1.65-8.98, p = 0.002) and resection margins (positive vs. negative HR 4.17, CI 1.15-15.17, p = 0,030) were associated with EFS. Furthermore, fibrinogen (elevated vs. normal HR 4.00, CI 1.49-10.72, p = 0.006) and the neutrophil-to-lymphocyte-ratio (NLR > 5 vs. < 5 HR 3.91, CI 1.40-10.89, p = 0.009) were prognostic after univariate analyses. After multivariate analyses tumor-dignity and fibrinogen remained as independent prognosticators. Besides validating the role of age, tumor-dignity, tumor-size, stage and resection margins, we identified for the first time inflammatory markers as prognosticators in SFT.


Effectiveness of routine follow-up of patients treated for T1-2N0 oral squamous cell carcinomas of the floor of mouth and tongue.
The duration of follow-up after treatment for head and neck cancer, the depth of the routine visits, and the diagnostic tools used are determined on the basis of common acceptance rather than evidence-based practice. Patients with early-stage tumors are more likely to benefit from follow-up programs, because they have the best chance for a second curative treatment after recurrence. The purpose of this study was to determine the benefit of our 10-year follow-up program in patients with stage I and II squamous cell carcinoma (SCC) of the floor of mouth and tongue. In a longitudinal cohort study involving 102 patients who were treated with curative intent for a pT1-2N0M0 SCC of the floor of mouth and tongue from 1989-1998 with a minimum follow-up of 5 years, we evaluated the effect of routine follow-up. During the follow-up (mean, 61 months; SD, 4 months), 10 patients had a recurrence, and 20 patients had a second primary tumor. No regional lymph node recurrences in the neck were detected. Location, T classification of the primary tumor, choice of therapy, or measure of tumor-free margins in the resection did not significantly affect the occurrence of a secondary event (p >or= .1). The secondary event was discovered during a patient-initiated visit for complaints in 14 patients and was found during routine follow-up visits in 16 patients. Only seven second primary tumors were detected after 60 months, four on routine follow-up and three on a self-initiated visit. The mean disease-free survival time after treatment of the secondary event was 72 months (SD, 17 months) in the "own initiative" group and 65 months (SD, 13 months) in the routine follow-up group; this difference was not statistically significant (p=.3). The effectiveness of a 10-year routine follow-up, even in patients with early-stage oral SCC, is very limited. These visits on routine basis can be stopped after 5 years.


Pain in the athlete's knee.
When the athlete develops knee pain, conventional radiographs are often helpful to establish the correct diagnosis. Knee arthrography may provide additional information when conventional radiography shows no specific abnormality. A number of causes of knee pain in the athlete are illustrated.


A systematic review of self-help for disfigurement: effectiveness, usability, and acceptability.
Self-help has been found to be efficacious in treating mood disorders, however, little is known about its use, effectiveness, or user satisfaction, in reducing distress associated with disfigurement. This review describes the content and focus of self-help interventions available in this area. A systematic search and appraisal protocol facilitated identification of studies, extraction of data, and appraisal of quality. Clinical trials were included if the primary method of intervention delivery was via self-help. Other types of study were included if they investigated user perspectives of a self-help intervention. Eleven studies covering a range of populations met the inclusion criteria. There is tentative support for the use of self-help to manage anxiety associated with disfigurement but little is known about the management of other psychosocial difficulties. Further research and intervention development is required to examine the effectiveness, acceptability, and utility of self-help in managing the appearance related distress associated with disfigurement.


A quantitative analysis of CT and cognitive measures in normal aging and Alzheimer's disease.
Patients with presumptive Alzheimer's disease (AD) and healthy community volunteers received computed tomographic (CT) brain scans and cognitive tests. The CT scans were quantitatively analyzed with a semiautomated thresholding technique to derive volumetric measures of cerebrospinal fluid (CSF)-to-tissue ratios in six regions of interest (ROIs): lateral ventricles; vertex sulci, frontal sulci, Sylvian fissures, parieto-occipital sulci, and third ventricle. Regression analysis was performed on CT data from 85 older volunteers (ages 51-82) to generate age norms for each ROI. Within this group, tissue loss, as measured by the % CSF in each ROI, was highly correlated with age, although each ROI showed different rates of change over age. For all ROIs, the AD group had significantly more tissue loss than expected in normal aging. In addition, AD patients with a presenescent onset (before age 65) tended to have greater vertex sulcal and frontal sulcal tissue reduction than AD patients with a senescent onset (age 65 or after). When regional tissue reduction, corrected for age, was correlated with cognitive test scores, two sets of double dissociations emerged within the AD group: large CT z scores (i.e., decreased tissue and increased CSF) of frontal sulci, but not of the third ventricle, correlated with low Comprehension and Boston Naming Test scores, whereas large CT z scores of the third ventricle, but not of the frontal sulci, correlated with low scores on Digit Symbol and Picture Arrangement. These results suggest that heterogeneity of structural and functional integrity exists among patients with AD.


The effect of race and co-morbidities on Alzheimer's disease based on Medicare data.
Alzheimer's disease (AD) incidence is thought to be higher among Black than White individuals. We studied the US Medicare population from 2000 to 2018. Cox regression was used to determine the roles of race and co-morbidities for AD incidence. We studied 11,880,906 Medicare beneficiaries, with 774,548 AD cases. Hazard ratios (HRs) by increasing numbers of co-morbidities (1-7) were 1.51, 2.00, 2.55, 3.16, 2.89, 4.77, and 5.65. Among those with no co-morbidities, Black individuals had a lower rate than those who are White (HR = 0.69), while among those with one more co-morbidities, Black individuals had a higher rate (HR = 1.19). The presence of hypertension increased AD rates by 14% for White individuals, but 69% for those who are Black. More co-morbidities was strongly associated with higher AD rates. The higher rates for Black versus White individuals was apparent only for those with co-morbidities and appears driven both by more co-morbidities, and the greater effect of hypertension. Black individuals have been shown to have higher Alzheimer's disease (AD) rates than those who are White. Some co-morbidities are known to increase AD risk. Among those In Medicare data with no co-morbidities, Black individuals have less risk than those who are White. Among those with co-morbidities, Black individuals have higher rates than those who are White. Hypertension results in a much stronger increase in AD risk for Black versus White individuals.


Application of marine microbial enzymes in the food and pharmaceutical industries.
Over billions of years, the ocean is regarded as the origin of life on Earth, and the ocean includes the largest habitats hosting the most life forms. Competition among microorganisms for space and nutrients in the marine environment is a powerful selective force, which has led to the evolution. The evolution prompts the marine microorganisms to generate multifarious enzyme systems to adapt to the complicated marine environments. Therefore, marine microbial enzymes can offer novel biocatalysts with extraordinary properties. This review deals with the research and development work done on the occurrence and bioprocessing of marine microbial enzymes.


A case of isolated bilateral pulmonary arterial calcification diagnosed in utero.
We report a very rare case of isolated multiple pulmonary arterial calcification with severe bilateral peripheral pulmonary arterial stenosis diagnosed in utero. Despite treatment with bisphosphonate for 6 months, systolic right ventricular pressure increased persistently and surpassed left ventricular pressure. After successful bilateral pulmonary arterioplasty at 13 months of age, the patient showed decreased systolic right ventricular pressure with normal interventricular septal configuration. This is the first case report for an isolated pulmonary artery calcification without other arterial calcification proven by non-contrast computed tomography of a living patient.


A practical guide on how osmolytes modulate macromolecular properties.
Osmolytes are a class of compounds ubiquitously used by living organisms to respond to cellular stress or to fine-tune molecular properties in the cell. These compounds are also highly useful in vitro. In this chapter, we give an overview of the possible uses of osmolytes in the laboratory, and how we can investigate and understand their modes of action. Experimental procedures are discussed with a specific emphasis on osmolyte-related aspects and on the theoretical aspects that are important to both introductory and more advanced interpretations of such experiments.


Reference Standards for Cardiorespiratory Fitness Measured With Cardiopulmonary Exercise Testing: Data From the Fitness Registry and the Importance of Exercise National Database.
To develop standards for cardiorespiratory fitness by establishing reference values derived from cardiopulmonary exercise testing (CPX) in the United States. Eight laboratories in the US experienced in CPX administration with established quality control procedures contributed data from January 1, 2014, through February 1, 2015, from 7783 maximal (respiratory exchange ratio, ≥ 1.0) treadmill tests from men and women (aged 20-79 years) without cardiovascular disease (CVD) to the Fitness Registry and the Importance of Exercise: A National Data Base (FRIEND). Percentiles of maximal oxygen consumption (VO 2max) for men and women were determined for each decade from 20 years of age through 79 years of age. Comparisons of VO 2max were made to reference data established with CPX data from Norway and to US reference data established without CPX measurements. There were significant differences between sex and age groups for VO 2max. In FRIEND, the 50th percentile VO 2max of men and women aged 20 to 29 years decreased from 48.0 and 37.6 mLO2 · kg(-1) · min(-1) to 24.4 and 18.3 mLO2 · kg(-1) · min(-1) for ages 70 to 79 years, respectively. The rate of decline in this cohort during a 5-decade period was approximately 10% per decade. These are the first cardiorespiratory fitness reference data using measures obtained from CPX in the United States. FRIEND can be used to provide a more accurate interpretation of measured VO 2max from maximal exercise tests for the US population compared with previous standards on the basis of workload-derived estimations.


Segmental cervical esophagectomy with free jejunal flap reconstruction for cervical esophageal cancer in patients with previous history of gastric surgery: a report of two cases.
Although free-flap jejunal reconstruction is frequently performed after cervical esophagectomy for cervical esophageal cancer, the procedure after gastric surgery has not been reported. We encountered two patients with esophageal cancer and previous gastric surgeries who eventually underwent segmental esophagectomy with free-flap jejunal reconstruction. Case one involved a 75-year-old man who underwent abdominal abscess and duodenal ulcer perforation surgeries (abdominal drainage and subsequent gastrojejunal bypass). A type 0-IIa tumor was located posterior to the cervical esophagus's right wall, 21 cm from the incisor, without lymph node swelling or distant metastasis. The left lobe of the thyroid gland was mobilized to ensure an oral resection margin. Severe abdominal adhesions required careful adhesiolysis to harvest the jejunum (20 cm long) 40 cm from the jejunojejunostomy. An end-to-side and side-to-end esophagojejunostomy were performed for the proximal and distal ends, respectively. Case two involved a 75-year-old male with a history of distal gastrectomy with Billroth I reconstruction for early gastric cancer. A submucosal tumor-like lesion was located on the cervical esophageal wall on the left side, 21 cm from the incisor. The distal esophagus required additional segmental resection because the anal resection line was close to the tumor. Jejunum (10 cm long) 30 cm from Ligament of Treitz was harvested. An end-to-side and end-to-end esophagojejunostomy for the proximal and distal ends, respectively, was performed. This surgery requires a thorough preoperative examination to ensure an adequate surgical margin and a careful free-flap harvest based on post-gastric surgery anatomy.


Quantifying Fibrinogen-Dependent Aggregation of Red Blood Cells in Type 2 Diabetes Mellitus.
Fibrinogen is regarded as the main glycoprotein in the aggregation of red blood cells (RBCs), a normally occurring phenomenon that has a major impact on blood rheology and hemodynamics, especially under pathological conditions, including type 2 diabetes mellitus (T2DM). In this study, we investigate the fibrinogen-dependent aggregation dynamics of T2DM RBCs through patient-specific predictive computational simulations that invoke key parameters derived from microfluidic experiments. We first calibrate our model parameters at the doublet (a rouleau consisting of two aggregated RBCs) level for healthy blood samples by matching the detaching force required to fully separate RBC doublets with measurements using atomic force microscopy and optical tweezers. Using results from companion microfluidic experiments that also provide in vitro quantitative information on cell-cell adhesive dynamics, we then quantify the rouleau dissociation dynamics at the doublet and multiplet (a rouleau consisting of three or more aggregated RBCs) levels for obese patients with or without T2DM. Specifically, we examine the rouleau breakup rate when it passes through microgates at doublet level and investigate the effect of rouleau alignment in altering its breakup pattern at multiplet level. This study seamlessly integrates in vitro experiments and simulations and consequently enhances our understanding of the complex cell-cell interaction, highlighting the importance of the aggregation and disaggregation dynamics of RBCs in patients at increased risk of microvascular complications.


Extreme concentrations of high density lipoprotein cholesterol affect the calculation of low density lipoprotein cholesterol in the Friedewald formula and other proposed formulas.
To investigate the effect of extreme levels of high density lipoprotein cholesterol (HDL-C) in the calculation of low density lipoprotein cholesterol (LDL-C) using Friedewald's formula (FF) and other formulas proposed recently. Lipoprotein profile was performed in 2603 samples with HDL-C ≤ 20 mg/dL and 1953 samples with HDL-C ≥ 100 mg/dL. Wilcoxon's and Student's t-tests showed significant differences (p<0.001) between calculated LDL-C by different formulas and direct determination in the two groups of HDL-C values. Passing-Bablok regression and Bland-Altman plot showed disagreement for the four formulas studied, except for Vujovic formula in the HLD-C ≥ 100 mg/dL group. Our results suggested that none of the formulas under analysis should be used for estimating LDL-C in samples with extreme HDL-C concentrations due to absence of statistical correlation with LDL-C direct measurement.


Simulating biologically plausible complex survival data.
Simulation studies are conducted to assess the performance of current and novel statistical models in pre-defined scenarios. It is often desirable that chosen simulation scenarios accurately reflect a biologically plausible underlying distribution. This is particularly important in the framework of survival analysis, where simulated distributions are chosen for both the event time and the censoring time. This paper develops methods for using complex distributions when generating survival times to assess methods in practice. We describe a general algorithm involving numerical integration and root-finding techniques to generate survival times from a variety of complex parametric distributions, incorporating any combination of time-dependent effects, time-varying covariates, delayed entry, random effects and covariates measured with error. User-friendly Stata software is provided.


Cerebral Aneurysm Size before and after Rupture: Case Series and Literature Review.
The conclusions of the International Study of Unruptured Intracranial Aneurysms (ISUIA) demonstrating that anterior circulation aneurysms less than 7 mm in maximal diameter have a 0% risk of rupture continue to be widely cited despite discordance with the anecdotal observation that the majority of ruptured cerebral aneurysms are less than 7 mm. The leading hypothesis to reconcile this discrepancy is that cerebral aneurysms shrink after rupture. Our case series of 6 subjects adds to the scarce published literature that addresses our limited understanding of aneurysm size before and after rupture. Our institutional database was evaluated for patients with brain vascular imaging before and after cerebral aneurysm rupture. We evaluated clinical and anatomic features as well as aneurysm dimensions using a submillimeter measurement tool with adjudication between 2 physicians. Among our 6 subjects who met the inclusion criteria, and even when combined with the 17 subjects published in the literature with similar information before rupture, no aneurysms decreased in size more than 2 mm. In total, 17 out of 23 aneurysms studied increased in size after rupture. Our data add additional evidence that unruptured aneurysms do not shrink in size after rupture. The discrepancy between the ISUIA conclusion on aneurysm size and rupture risk and what is observed anecdotally remains an area in need of additional study.


Identifying monoclonal gammopathy of undetermined significance in electronic health data.
Monoclonal gammopathy of undetermined significance (MGUS) is a prevalent yet largely asymptomatic precursor to multiple myeloma. Patients with MGUS must undergo regular surveillance and testing, with few known predictors of progression. We developed an algorithm to identify MGUS patients in electronic health data to facilitate large-scale, population-based studies of this premalignant condition. We developed a four-step algorithm using electronic health record and health claims data from men and women aged 50 years or older receiving care from a large, multispecialty medical group between 2007 and 2015. The case definition required patients to have at least two MGUS ICD-9 diagnosis codes within 12 months, at least one serum and/or urine protein electrophoresis and one immunofixation test, and at least one in-office hematology/oncology visit. Medical charts for selected cases were abstracted then adjudicated independently by two physicians. We assessed algorithm validity by positive predictive value (PPV). We identified 833 people with at least two MGUS diagnosis codes; 429 (52%) met all four algorithm criteria. We randomly selected 252 charts for review, including 206 from patients meeting all four algorithm criteria. The PPV for the 206 algorithm-identified charts was 76% (95% CI, 70%-82%). Among the 49 cases deemed to be false positives (24%), 33 were judged to have multiple myeloma or another lymphoproliferative condition, such as lymphoma. We developed a simple algorithm that identified MGUS cases in electronic health data with reasonable accuracy. Inclusion of additional steps to eliminate cases with malignant disease may improve algorithm performance.


Human serum albumin-coated lipid nanoparticles for delivery of siRNA to breast cancer.
Human serum albumin (HSA)-coated lipid nanoparticles (HSA-LNPs) loaded with phrGFP-targeted siRNA (HSA-LNPs-siRNA) were prepared and evaluated for gene downregulation effect in phrGFP-transfected breast cancer cells and the corresponding xenograft tumor model. HSA-LNPs-siRNA were successfully prepared with a particle size of 79.5±5.5 nm. In phrGFP-transfected MCF-7 cells, HSA-LNPs-siRNA significantly decreased cell fluorescence even in the presence of fetal bovine serum (FBS). Moreover, cell fluorescence and phrGFP mRNA expression were significantly downregulated by HSA-LNPs-siRNA in phrGFP-transfected MCF-7, MDA-MB-231, and SK-BR-3 cells in comparison with control or HSA-LNPs-siRNA (scrambled). In phrGFP-transfected MCF-7 xenograft tumor model, tumor fluorescence was significantly decreased after three IV administrations of HSA-LNPs-siRNA at a dose of 3 mg/kg in comparison with siRNA alone. HSA-LNPs-siRNA demonstrated a superior pharmacokinetic profile in comparison with siRNA at a dose of 1mg/kg. These results show that the novel nonviral carrier, HSA-LNPs, may be used for the delivery of siRNA to breast cancer cells. Targeted delivery of siRNA to cancer cells may be a viable anti-cancer strategy with low toxicity. In this study the novel nonviral carrier, human serum albumin-coated lipid nanoparticles (HSA-LNP) were demonstrated as an efficient delivery agent of siRNA to breast cancer cells.


Examining psychometric properties of the Turkish version of the Women's Perceptions of Unplanned Pregnancy Questionnaire.
This study was designed to determine the validity and reliability of the Turkish version of the "Women's Perceptions of Unplanned Pregnancy Questionnaire". The study was methodological and was conducted with 310 pregnant women. A descriptive information form and "Women's Perceptions of Unplanned Pregnancy Questionnaire" were used to collect the data. The Content Validity Index rate of the "Women's Perceptions of Unplanned Pregnancy Questionnaire" was found to be 0.885 on the basis of the scale. Construct validity was found to be Kaiser-Meyer-Olkin = 0.898 and Bartlett's Test of Sphericity test result was X2 = 7373.95 (p < 0.001). In the reliability analysis, it was determined that Cronbach's alpha coefficient for the whole scale was 0.935, and its sub-dimensions ranged between 0.801 and 0.934. The total variance explained by the scale was 75.42%. It was understood that the Turkish version of the scale consisted of 27 items and 6 sub-dimensions for women who had unplanned pregnancy. The Turkish version of the "Women's Perceptions of Unplanned Pregnancy Questionnaire" was evaluated and it was found to be a valid and reliable measurement tool for Turkish pregnancy. The scale can be used in other studies to assess the severity of anxieties and fears of women who have had an unplanned pregnancy.


Effects of gastric electrical stimulation with short pulses and long pulses on gastric dysrhythmia and signs induced by vasopressin in dogs.
This study was to investigate the effect of gastric electrical stimulation (GES) with short pulses, long pulses, short-pulse trains or long-pulse trains on gastric dysrhythmia and motion-sickness signs induced by vasopressin. Seven male beagle dogs implanted with four pairs of electrodes on gastric serosa were studied. The study was performed in six sessions in a randomized order. In session 1 or 2, either saline or vasopressin was infused without GES. In session 3, 4, 5 and 6, GES with short pulses, long pulses, trains of short pulses or trains of long pulses was performed before and during vasopressin infusion. Gastric slow waves and motion-sickness signs were recorded in each session. (1) Vasopressin induced gastric dysrhythmia and motion sickness-like signs (ANOVA, P < 0.001). (2) GES with short pulses or trains of short pulses was capable of preventing vasopressin-induced emetic response (P < 0.001), but did not normalize gastric dysrhythmia. (3) GES with long pulses or trains of long pulses was able to normalize gastric dysrhythmia induced by vasopressin (P < 0.001), but showed no effects on vasopressin-induced motion-sickness signs. GES with short pulses or trains of short pulses prevents vasopressin-induced emetic response with no improvement in gastric dysrhythmia. GES with long pulses or trains of long pulses normalizes gastric dysrhythmia induced by vasopressin with no effects on signs.


Social correlates of distress following hematopoietic stem cell transplantation: exploring the role of loneliness and cognitive processing.
This study investigated whether loneliness and cognitive processing explain the influence of negative (social constraints) and positive (emotional support) relationship qualities on cancer survivors' distress. Participants were 195 cancer survivors who had undergone hematopoietic stem cell transplantation. Path analysis supported the hypothesis that loneliness and cognitive processing would mediate the association between social constraints and distress. Only loneliness mediated the association between emotional support and distress - an indirect effect significant only when support came from family and friends rather than a partner. Findings suggest that addressing social constraints may enhance cancer survivors' adjustment.


Note on the effects of protein concentration on responses to dietary lysine by chicks.
1. This paper gives further analyses of data from previously reported trials in which chicks were fed diets with protein concentrations ranging from 140 to 280 g/kg diet, with the lysine content varied at each protein concentration. 2. Alternative methods of estimating the lysine requirement, at each concentration of protein, are investigated. 3. Although these methods produce rather different estimates of requirement, they do not change the conclusion that the lysine needed for maximum growth or maximum efficiency of food utilisation is a linear function of dietary protein concentration throughout the range from 140 to 280 g crude protein/kg. 4. It is concluded that lysine requirements for growing chicks should be specified as a proportion of the protein and not as a proportion of the diet.


HLA-A*11:235Q, a novel HLA-A*11 variant, detected in a Taiwanese individual.
Nucleotide deletions from residue 120 to 125 of HLA-A*11:01:01:01 result in a novel allele, HLA-A*11:235Q.


Effect of hypothermia on plasma metabolites in preterm newborn infants with particular references to plasma free amino acids.
Blood glucose, blood lactate, plasma free fatty acids, plasma alpha-amino nitrogen, plasma free amino acids and blood urea nitrogen were measured in 15 hypothermic preterm infants (mean rectal temperature: 34.5 +/- 0.28 degrees C) during a 2-hour 'warming-up' period following admission to our neonatal intensive care unit. Hypothermia was associated with lactacidemia and hyperalaninemia. The increase in body temperature of the infants resulted in the decrease of lactacidemia and hyperalaninemia. Normal levels of other metabolites remained unchanged.


Face-to-face, online, or blended: which method is more effective in teaching electrocardiogram to medical students.
Electrocardiogram (ECG) remains an important medical diagnostic and screening tool. This study aimed to compare the effectiveness of online classes instead of traditional face-to-face or blended methods in medical students' ECG learning. Two hundred and fifteen medical students (including 105 (48.8%) males and 110 (51.2%) females) were studied from February 2021 to February 2022. Regardless of their grade, participants were divided into three groups: online, face-to-face, and blended. Then all participants sat for an ECG interpretation exam, and their results were compared. Twenty-six (12.1%) participants were residents, and 189 (87.9%) were interns. Thirty-five (16.3%), 85 (39.5%), and 95 (44.2%) participants were taught ECG through face-to-face, online, and blended methods, respectively. Regarding participants' preferences on teaching methods, 118 (54.9%) preferred face-to-face learning, and the remaining 97 (45.1%) chose online learning (p < 0.001). The blended method seemed more promising in almost half of the exam questions regarding teaching method effectiveness. The mean total exam score was also significantly higher in participants who were taught blended than in the others (7.20 ± 1.89, p = 0.017). Face-to-face (5.97 ± 2.33) and online teaching methods (6.07 ± 2.07) had similar efficacy according to the mean total score (p = 0.819). While most students preferred face-to-face learning to online learning, a blended method seemed more promising regarding students' skill enhancement to interpret ECG.


The Hidden Pathogenesis of CML: Is BCR-ABL1 the First Event?
Identification of the BCR-ABL1 fusion oncogene in patients diagnosed with chronic myeloid leukemia (CML) led to the development of targeted therapy responsible for the dramatic survival benefits observed in the past two decades. However, despite these revolutionary findings, there remains marked disparity in patient outcomes. Why do some patients present de novo while others evolve to the more aggressive stages of CML? Why can select patients successfully discontinue therapy as part of a treatment-free remission attempt whereas others fail to meet specific molecular milestones? BCR-ABL1 kinase mutations are only identified in approximately 50% of patients with poor responses and disease progression, suggesting the presence of alternative resistance mechanisms. Numerous institutions have identified the presence of additional genomic events in addition to BCR-ABL1 with the increasing availability of next-generation sequencing. We explore the potential pathways and events that may cooperate with BCR-ABL1 to answer these questions but also challenge the fundamental tenet that BCR-ABL1 is always the sole event initiating CML.


Inter-rami intraoral fixation of severely comminuted mandibular war injuries.
A new technique is presented for the reduction, stabilization and immobilization of an avulsed maxilla and severe comminuted body and symphysis injuries of the mandible sustained by Iraqi soldiers in combat. The technique consists of the use of intraoral inter-rami horseshoeshaped Kirschner wire as a scaffolding for multiple circumferential wires tied around bone fragments. The technique is simple, short, effective and allows function of the lower jaw.


Why we should attempt to eliminate (silent and symptomatic) ischemia in patients with chronic stable angina.
There is no doubt that angina patients with symptomatic ischemia face a poor prognosis and that treatment of these patients is necessary. However, there is no consensus regarding the prognostic value or treatment of silent ischemia in patients with stable angina. It is in this context that the advantages of treating silent ischemia are presented.


Signal-off photoelectrochemical determination of miRNA-21 using aptamer-modified In2O3@Cu2MoS4 nanocomposite.
In2O3@Cu2MoS4 nanocomposite with superior photoelectrochemical (PEC) performance is used for the first time as a photoactivity material, and a signal-off PEC biosensing platform for miRNA detection has been successfully constructed. Firstly, the Cu2MoS4 nanosheets are synthesized by a hydrothermal method, and then, the homogeneous In2O3 nanoparticles (In2O3 NPs) are synthesized by calcination in the air. The In2O3@Cu2MoS4 nanocomposite is constructed with the Cu2MoS4 nanosheets as matrix and In2O3 NPs as sensitizer through a layer-by-layer assembly strategy. The nanocomposite with a tight interface and the matched band structure restrains the electron-hole pair recombination. Under visible light (400-700 nm), the nanocomposite exhibits a strong initial signal. With the catalyzed hairpin assembly, dozens of PbS quantum dots (QDs) are introduced on the surface of an electrode, significantly reducing the photocurrent of n-type In2O3@Cu2MoS4. Since PbS QDs can compete with the nanocomposite for light energy and electron donors, the signal decreased. Under optimal conditions, the biosensor manifests a broad linear range (1 fM-1 nM) and a low detection limit of about 0.57 fM, at a working potential of 0 V (vs. Ag/AgCl). The recovery of spiked human serum is between 94.0 and 102%, and the relative standard deviation (RSD) is between 1.3 and 2.7%. Therefore, the as-fabricated biosensor exhibits a potential for the determination of miRNA-21 in practical applications.Graphical abstract The In2O3@Cu2MoS4 nanocomposite owns a strong anode photocurrent signal, which can be used as a photoactive material to construct a "signal-off" biosensor for the detection of miRNA in non-enzymatically catalyzed hairpin assembly (CHA) reaction.


Excitability of corticospinal neurons during tonic muscle contractions in man.
A magnetic stimulus applied to the human scalp over the motor cortex causes a short latency contraction of contralateral limb muscles. This is presumed to result from the indirect excitation of corticospinal neurons with monosynaptic connections to motoneurons. The excitability of these cortical neurons can be estimated from the magnitude of the postsynaptic potentials produced in spinal motoneurons by a given magnetic stimulus. In man the characteristics of these postsynaptic potentials can be derived from changes in the firing probability of single motor units. When a subject increases the level of a sustained voluntary contraction the excitability of the corticospinal neurons estimated in this way becomes less. We conclude that the additional synaptic input to motoneurons required to maintain a stronger muscle contraction comes from fiber systems other than the population of fast corticospinal neurons activated by magnetic stimulation.


Polyoxometalate-based inorganic-organic hybrid film structure with reversible electroswitchable fluorescence property.
A novel inorganic-organic hybrid film structure based on polyoxometalate and conventional organic dye has been fabricated, whose fluorescence can be reversibly switched using the electrochromic component to activate or suppress the related fluorescence quenching mechanism upon applying reduction or oxidation potentials of polyoxometalates.


Assessment of CXCL12 (SDF-1α) polymorphisms and its serum level in posttransfusion occult HBV-infected patients in Southeastern Iran.
Occult hepatitis B infection (OBI) is defined as a form of hepatitis in which, despite absence of detectable HBsAg, HBV-DNA is present in peripheral blood of patients. The main aim of this study was to determine an association between polymorphisms in +801 of CXCL12 (SDF-1α) and its serum level in OBI patients. In this experimental study, plasma samples of 3700 blood donors were tested for HBsAg and anti-HBc by ELISA. The HBsAg(-)/anti-HBc(+) samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples assigned as OBI cases and PCR-RFLP techniques were performed to examine the CXCL12 (SDF-1α) polymorphisms. The serum level of CXCL12 (SDF-1α) was also analyzed by ELISA. Of 3700 blood samples, 352 (9.5%) were HBsAg/anti-HBc(+) and HBV-DNA was detected in 57/352 (16.1%) of HBsAg(-)/anti-HBc(+) samples. Our results showed a significant difference in genotypes and alleles of +801 region of CXCL12 (SDF-1α). However, the serum level of CXCL12 (SDF-1α) was decreased in OBI patients but was not significant. Our results also showed that the alleles of +801 region of CXCL12 (SDF-1α) were also not associated with serum level of the chemokine. The polymorphisms in +801 region of CXCL12 (SDF-1α) are possibly related to OBI.


Binding of polynucleotides to fibroblasts. Effects of complex formation with vinyl analogs of nucleic acids.
The binding of polynucleotides or of their vinyl analogs to human fibroblasts is changed when complexes are formed between these compounds. The following polymers have been studied: poly(1-vinylcytosine), poly(1-vinyluracil, poly(9-vinyladenine), polyuridylate, polyadenylate and polyinosinate. Only that complex formation (between poly(1-vinylcytosine) and polyinosinate) which is accompanied by aggregation leads to a considerable increase (30 fold) in binding to cells; all the other complex formations have only moderate effects (0.2-3 fold). Furthermore, a comparison of unordered complexes containing polyinosinate whows that enhanced binding to cells is paralleled by an increased cellular resistance to viral infection.


Kinetic/thermodynamic study of immobilized β-fructofuranosidase from Aspergillus tamarii URM4634 in chitosan beads and application on invert sugar production in packed bed reactor.
β-fructofuranosidase (FFase) from Aspergillus tamarii URM4634 was immobilized covalently in chitosan beads. It was characterized biochemically, studied in terms of kinetic and thermodynamic parameters, and applied on conversion of sucrose for invert sugar production in a packed bed reactor (PBR). The optimum reactional conditions were determined and obtained at pH 5.0 and 60 °C. FFase was thermostable at 50-55°C. At 50°C, the enzyme shows longer half-life (t1/2) (594.13 min) and a higher D-value (1,973.64 min). This indicates that immobilized FFase was stable at temperature commonly used in invert sugar production. The following thermodynamic parameters were obtained: activation energy (E*d = 301.57 kJ mol-1), enthalpy (298.76 ≤ ΔH*d ≤ 298.89 kJ mol-1), entropy (579.88 ≤ ΔS*d ≤ 589.27 J K-1 mol-1) and Gibbs free energy (100.29 ≤ ΔG*d ≤ 108.47 kJ mol-1). The high E*d, ΔH*d and ΔG*d values confirmed FFase thermostability. The high and positive values for ΔS*d indicate an increase in disorder due opening of the enzyme structure. The sucrose hydrolysis in PBR showed a maximum invert sugar yield (96.0%) at 15 min of operation. The hydrolysis process remained efficient up to 100 min (70.22%). The results obtained in the present study provide a good indication that immobilized FFase on chitosan beads in PBR is efficient to invert sugar production for food industry.


Artificial pneumothorax suppresses postoperative inflammatory reaction in mediastinal tumor surgery.
The induction of artificial pneumothorax has many intraoperative advantages. However, few reports on the postoperative effects of artificial pneumothorax induction are available. In this study, we investigated the effect of artificial pneumothorax on postoperative clinical course in patients with mediastinal tumors. We retrospectively investigated the clinical courses of 89 patients who had undergone mediastinal tumor resection between January 2010 and December 2020. Sixty-five patients had undergone resection with artificial pneumothorax. The tumor location significantly varied across patients. The proportion of patients in whom artificial pneumothorax was induced was higher among those having anterior mediastinal tumors. The number of ports and the total skin incision length were significantly higher in patients without artificial pneumothorax. The C-reactive protein level elevation on postoperative day 2 and pleural effusion at 24 h after surgery were significantly higher in patients without artificial pneumothorax. Furthermore, the albumin level reduction and hospital stay after surgery were significantly lower in patients with artificial pneumothorax. Multiple regression analysis showed that the use of artificial pneumothorax was an independent predictive factor of the C-reactive protein level elevation on postoperative day 2 and pleural effusion at 24 h after surgery. In patients without artificial pneumothorax, the operation time positively correlated with the C-reactive protein level (r = 0.646, P < 0.001). Artificial pneumothorax suppressed the postoperative inflammatory response, pleural effusion, and albumin reduction, and shortened the hospital stay in patients undergoing mediastinal tumor surgery.


Histochemical studies of intercellular components of salivary gland tumors with special reference to glycosaminoglycan, laminin and vascular elements.
In 41 salivary gland tumors, the characteristics of the intercellular components and vascular endothelial cells were surveyed by immunohistochemical staining for laminin and factor VIII-related antigen (VIII R:Ag), and by mucopolysaccharidase-digestion for glycosaminoglycan (GAG). In myxomatous areas of pleomorphic adenomas, small vessels (diameter 6.5 +/- 0.11 micron) were frequent and found to be negative or weakly positive by VIIIR:Ag staining although endothelial cells were clearly positive for VIIIR:Ag in capsule surrounding the tumor tissues. Alcian blue stainability was diminished by treatment with both Streptomyces hyaluronidase and chondroitinase. By laminin staining, a vascular pattern was clearly detected, but the majority of tumor cells were not stained. In adenomatous areas, the basement membrane-like linear laminin-staining reaction was observed to be weak and inconsistent around some tumor cell nests. However, in adenoid cystic carcinomas, laminin-positivity was much more intense than in other tumors such as pleomorphic adenoma, mucoepidermoid tumor and adenocarcinoma. In cylindromatous areas, the inner luminal surface in the pseudocysts was markedly positive for laminin, and there was weak positivity around tumor cell nests having a trabecular pattern. By immunoelectron microscopy, a juxtacellular network of replicated basal lamina of tumor cells which lined the inner surface of pseudocysts was positive for laminin. Alcian blue-positivity in the pseudocyst was abolished with heparitinase and chondroitinase, but not with hyaluronidase.


[Bacterial motion in porous media].
The motion of chemotactically different Escherichia coli C600, cheB287, and AW405 cells was studied using a column packed with silica gel. The model chemotaxis of bacteria in porous media seems to be adequate to natural bacterial chemotaxis in soils. The porous structure of silica gel prevents interfering convective flows. Silica gel columns make it possible to separate bacterial cells differing in motility and chemotaxis. Relevant physical phenomena are discussed. The concept of fast and slow chemotaxis is considered.


Avoiding the diagnostic pitfalls of a pancreatic cystic lesion.
Cystic pancreatic lesions present a diagnostic challenge. Accurate characterisation of an isolated cystic pancreatic lesion is therefore vital as this dictates the management strategy which may vary from radical resection to simple observation. This report describes how a detailed preoperative assessment led to the correct diagnosis of an isolated pancreatic lesion and appropriate safe and curative surgical management.


[Microbiological diagnosis of mycoplasma infections].
The microbiological diagnosis of mycoplasma and ureaplasma infections has always been limited due to the fastidious growth of these microorganisms, as well as the lack of commercially prepared growth media, absence of rapid diagnostic procedures, and the clinical perception that these organisms are less significant in the infectious diseases setting. During the last few years, this situation has substantially improved due to the commercial availability of culture media, the development of rapid serological techniques, and, in particular, to the introduction of nucleic acid amplification assays, commercially available or "in-house" preparations. Despite the lack of proper standardisation and validation of the molecular and serological techniques, methodological advances have led to an increased detection of these microorganisms and, consequently, a greater appreciation of their clinical relevance.


Long-term activation of c-Fos and c-Jun in optic nerve head astrocytes in experimental ocular hypertension in monkeys and after exposure to elevated pressure in vitro.
This study investigates whether the immediate early gene (IEG) products c-Fos and c-Jun are activated in vivo in monkeys with experimental glaucoma, and in vitro in cultured human ONH astrocytes exposed to hydrostatic pressure (HP). Three Rhesus monkeys with mild glaucomatous damage (mean intraocular pressure (IOP) 27 +/- 1.3 mm Hg approximately 42 weeks) and three with moderate glaucomatous damage (mean IOP 44 +/- 6.7% mm Hg approximately 11 weeks) were used for this study; the contralateral eye served as normal control (mean IOP 18.6 +/- 1.7 mm Hg). ONH tissues were stained with GFAP, DAPI, and c-Jun or c-Fos, and transcription factor positive and negative nuclei were counted to determine nuclear localization. Cultured human normal and glaucomatous ONH astrocytes exposed to elevated HP served as the in vitro model of elevated pressure. Activation and nuclear localization of c-Fos and c-Jun increased significantly in the monkeys with elevated IOP. These data correlated with axonal loss, reactive astrocytes, and remodeling of the optic disc. Cultured human ONH astrocytes showed increased nuclear localization of c-Fos and c-Jun under exposure to HP. Immunohistochemistry demonstrated that the upstream regulators of c-Fos and c-Jun, ERK-MAPK and MAPKp38 localized to the nuclei of ONH astrocytes in monkeys with experimental glaucoma. Taken together, these results demonstrate c-Fos and c-Jun activation in ONH astrocytes in vivo and in vitro, and that activation of both transcription factors is associated with ERK and MAPKp38 activation in experimental glaucoma, suggesting that activation of transcription factors may participate in the induction and maintenance of the reactive astrocyte phenotype in glaucomatous optic neuropathy.


[Particular aspects of cardiomyopathy in Landouzy-Déjérine's progressive muscular dystrophy. Study of a family (author's transl)].
In the study of a family affected by progressive muscular dystrophy (DMP) of facio-scapulo-humeral type (f.s.o.) the myocardial involvement has been found to be constant and of moderate degree. The myocardial component has been found to appear in the adult age with initial and prevalent atrial involvement. In one case the myocardiopathy was not associated with appreciable clinical signs of skeletric myopathy. Possible causes of the pecuationship between the DPM type f.s.o. associated myocardiopathies and familial idiopathic cardiomyopathies are outlined.


Correlations between estimated and true dietary intakes: using two instrumental variables.
We describe a new application of the method of triads that allows an estimate of the correlation between a dietary questionnaire measure (Q) and true intake (T). Three surrogate variables Q, M, and P are observed where M and P are both instrumental (often biological) variables. A reference dietary method (R) is not required. The variables M and P may be concentration rather than recovery biomarkers. Estimating equations produce Corr(Q,T), Corr(M,T), Corr(P,T), conditional on assumptions about error correlations. Correlations between errors in both Q and a reference dietary measure can also be estimated if R is available. A small validation study of California Seventh-day Adventists provided food frequency, repeated 24-hour dietary recalls (R), and biological data (blood, overnight urines, and subcutaneous fat). Values of Corr(Q,T) ranged between 0.40 and 0.66. Values of Corr(R,T) were higher, between 0.48 and 0.83. Estimated correlations between errors in R and Q were all positive. When carefully chosen, M and P, rather than M and R, should better satisfy assumptions about error correlations. Food frequency data and repeated 24-hour recalls both provide estimates of T, but the latter has greater validity. Standard errors suggest that for good precision Corr(Q,T) requires large validation studies (2000-3000 subjects).


Clinicopathological and Prognostic Value of Gastric Carcinoma Highly Expressed Transcript 1 in Cancer: A Meta-Analysis.
Long noncoding RNA gastric cancer highly expressed transcript 1 (lncRNA GHET1) is often reported to be abnormally expressed in multiple cancers, but the situation is different in different cancers. Therefore, a meta-analysis is necessary to clarify the value of lncRNA GHET1 as a prognostic indicator in cancer. Relevant research studies on lncRNA GHET1 and cancer were retrieved from three electronic literature databases of Web of Science, PubMed, and OVID. Meanwhile, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between lncRNA GHET1 expression and survival of cancer patients. The odds ratios (ORs) and 95% CIs were calculated to assess the association of lncRNA GHET1 expression with pathological parameters of cancer patients. The meta-analysis included a total of 11 studies involving 714 cancer patients. The pooled HR suggests that high lncRNA GHET1 expression is associated with poor overall survival. In addition, high expression of lncRNA GHET1 was found to be associated with larger tumor size, poor histological grade, high tumor stage, lymph node metastasis, and distant metastasis. High lncRNA GHET1 expression can predict poor survival and pathological parameters. And lncRNA GHET1 could serve as a new indicator in multiple cancers.