Drug-eluting versus bare-metal stents in ST-segment elevation myocardial infarction: a mortality analysis from the EUROTRANSFER Registry.
To assess the patterns of drug-eluting stent (DES) and bare-metal stent (BMS) implantation and associated real-life outcomes in patients with ST-segment elevation myocardial infarction (STEMI) transferred for primary percutaneous coronary intervention (PCI). Data were gathered for 1,650 consecutive STEMI patients transferred for primary PCI from hospital networks in seven countries of Europe from November 2005 to January 2007. We identified 1,428 patients with ≥1 stent implanted (86.5%). DES were implanted in 382 patients (26.8%) and BMS in 1,046 patients (73.2%) of 1,428 who received stent. High variability in DES use among countries participating in the registry (range from 6.8 to 72.1%) was observed. The use of DES in STEMI declined during the fourth quarter of 2006 through the first quarter of 2007. In the assessed population, age, previous PCI, systolic and diastolic pressures on admission, clopidogrel before admission, left anterior descending artery as the infarct-related artery, and thrombus aspiration device use were identified as the independent predictors of DES implantation. Use of DES was associated with significantly lower rates of ischemic events during follow-up (1-year mortality: BMS vs. DES: 6.7% vs. 3.1%; p = 0.014), but observed difference was no longer significant after adjustment for propensity score (adjusted OR (95% CI): 0.55 (0.28-1.06); p = 0.07). In this large, prospective European registry, the presence of large geographical and temporal variation of DES utilization in STEMI in Europe was confirmed. DES in STEMI appear to be as safe as BMS, with similar mortality after adjustment for potential confounders and trend toward lower 1-year mortality in patients treated with DES.


A landmark-free framework for the detection and description of shape differences in embryos.
This paper introduces a new method to quantify and characterize shape changes during early facial development without the use of landmarks. Landmarks are traditionally used in morphometric analysis, but very few can be identified reliably across all stages of embryonic development. This method uses deformable registration to produce a dense vector field describing the point correspondences between two images. Low and mid-level features are extracted from the deformable vector field to find regions of organized differences that are biologically relevant. These methods are shown to detect regions of difference when evaluated on chick embryo images warped with small magnitude deformations in regions critical to midfacial development.


An institutional experience with cervical vagus nerve trunk stimulation for medically refractory epilepsy: rationale, technique, and outcome.
Intermittent stimulation of the left cervical vagus nerve trunk is emerging as a novel adjunct in the treatment of medically refractory seizures. We sought to evaluate theoretical and practical issues attendant to this concept. We review the anatomic and physiological background arguing for clinical application of vagus nerve stimulation, discuss salient aspects of patient selection and the nuances of surgical technique, and present our observations of and results from application of the method. Each of 18 patients with medically refractory epilepsy and at least six complex partial or secondarily generalized seizures per month underwent placement of a NeuroCybernetic Prosthesis pulse generator (Cyberonics, Webster, TX) in the chest, connected to helical platinum leads applied to the left cervical vagus nerve trunk. The patients were then randomized in a double-blinded fashion to receive either high (presumably therapeutic) or low (presumably less therapeutic) levels of vagus nerve stimulation. Reduction in seizure frequency, global assessments of quality of life, physiological measurements, and adverse events were recorded during a 3-month period. Patients in the low group were then crossed over to high-stimulation paradigms during a 15-month extension trial. All operations were successful, uneventful, and without adverse postoperative sequelae. One patient was excluded from analysis because of inadequate seizure calendars. Of the seven patients initially assigned to high stimulation, the mean reduction in seizure frequency was 71% at 3 months and 81% at 18 months. Five (72%) of these patients had a greater than 75% reduction in seizure frequency, and one (14%) remained seizure-free after more than 1.5 years of follow-up. The mean reduction in seizure frequency among the low-stimulation group was only 6% at 3 months. No serious complications, device failures, or physiological perturbations occurred. In our experience, vagus nerve stimulation has proven to be a safe, feasible, and potentially effective method of reducing seizures in select patient populations. However, the elements of strict definition for the application of the method require further study.


Long-term outcome of cervical lymph node metastasis in superficial pharyngeal squamous cell carcinoma after endoscopic submucosal dissection.
Superficial pharyngeal squamous cell carcinoma (PSCC) has received increasing attention as a therapeutic target in the GI field with recent innovations in endoscopic submucosal dissection (ESD). However, there are currently no defined criteria for the application of ESD to superficial PSCC. One of the problems encountered during follow-up after ESD is cervical lymph node metastasis (LNM). Identifying the clinicopathologic predictors of cervical LNM can help to provide a basis for the refinement of therapeutic strategies for superficial PSCC. The risk of cervical LNM was evaluated in 331 patients with superficial PSCC who underwent initial ESD between 2008 and 2021. Since tumor size, rather than depth, is the dominant factor in the current TNM classification for PSCC, the correlation between tumor size and thickness was investigated. The median follow-up period was 4.8 years. The cumulative 5-year cervical LNM rate was 6.1%. Multivariate Cox proportional hazards regression analysis identified tumor thickness ≥1000 μm and lymphatic invasion as significant independent predictors. Among 204 cases with subepithelial invasion, both factors were also revealed to be significant independent predictors, suggesting that tumor thickness was superior to tumor size in predicting cervical LNM. Despite the positive correlation between tumor thickness and size, there was noticeable variability in the values (R = .20), and the current staging was inadequate to identify groups at high risk for cervical LNM. Tumor thickness and lymphatic invasion are validated as significant independent predictors for cervical LNM and can be useful indicators to optimize the therapeutic strategies for superficial PSCC.


Effect of dipeptidyl peptidase-4 inhibitors on glycated hemoglobin levels relies on dietary sodium intake.
Sodium load increases endogenous glucagon-like peptide-1 (GLP-1) levels in humans. Therefore, patients with an increased amount of dietary sodium intake are supposed to have higher endogenous GLP-1 levels compared to those with less dietary sodium intake. Therefore, it can be hypothesized that patients with type 2 diabetes mellitus (T2DM) with more dietary sodium intake show better dipeptidyl peptidase-4 inhibitor (DPP-4i) effect on glycemic control because of the expected higher GLP-1 level. Thus, we performed a single-center cohort study to explore this idea. Medical records of patients with T2DM prescribed DPP-4i in the last 11 years were investigated. Dietary sodium intake was measured before the DPP-4i prescription with Tanaka's formula using casual spot urine samples. The effect of DPP-4i on glycemic control was estimated by the subtraction of glycated hemoglobin (HbA1c) before DPP-4i initiation from HbA1c 1 year after DPP-4i administration. We analyzed 50 patients. DPP-4i improved HbA1c by -0.41% ± 0.66%. The effect of DPP-4i on glycemic control was significantly negatively correlated with the dietary sodium intake (r = -0.400). Thus, the more dietary sodium intake, the better the glycemic control by DPP-4i. Thus, patients can expect better plasma glucose control by DPP-4is if patients are taking increased dietary sodium intake.


Improving Bed Utilization in a Cohort of Bariatric Surgical Patients Using a Perioperative Obstructive Sleep Apnea Treatment and Bed Triage Protocol.
Postoperative bariatric management often includes high-intensity monitoring for respiratory complications since > 70% of patients have obstructive sleep apnea. Given the increasing number of bariatric surgeries, there is a need to determine safe and cost-effective processes for postoperative care.The objective of this study was to determine if a novel triage and perioperative management guideline reduces postoperative monitoring and costs following bariatric surgery. Using a pre-post design, this is a retrospective analysis of 501 patients who had bariatric surgery. Half the patients were managed with usual care, and the other half received obstructive sleep apnea screening and treatment of moderate/severe obstructive sleep apnea with perioperative continuous positive airway pressure. The intervention group was triaged preoperatively to a postoperative nursing location based on risk factors. There were no significant differences in demographics, comorbidities, frequency, or severity of OSA between groups. In the intervention group, there were fewer admissions to the intensive care unit (2.0% vs 9.1%; p < 0.01) and high acuity unit (9.6% vs 18.3%; p < 0.01). The length of stay was shorter in the intervention group (1.3 vs 2.3 days; p < 0.01) with a 50% reduction in costs. There were no statistically significant differences in the incidence of postoperative respiratory and non-respiratory complications between the two groups. Most postoperative bariatric surgery patients can be safely managed on the surgical ward with monitoring of routine vitals alone if patients with moderate/severe obstructive sleep apnea receive perioperative continuous positive airway pressure.


Kinetic studies of mobilization of copper(II) from human serum albumin with chelating agents.
The kinetics of the mobilizing reactions of five chelating agents for human serum albumin (HSA)-bound copper(II) [Cu(II)] have been studied spectrophotometrically. The decreasing sequence of reaction rate has been determined to be EDTA greater than DTPA greater than EGTA greater than NTA greater than IDA. A group of mathematical models were established to define the mechanisms of the competitive reactions between low-molecular-weight ligand and macromolecular ligand. All reactions of the five chelating agents follow a process involving the intermediate ternary complexes: (formula; see text) The reactions of DTPA and EDTA were found to be different from those of EGTA, NTA, and IDA. In the former cases, the reactions are likely following an overlapping mechanism in which the rate constant k1 was closed to k2. The reactions involving the other three chelators are different in k1 much greater than k2.


Probiotic-fermented Pueraria lobata (Willd.) Ohwi alleviates alcoholic liver injury by enhancing antioxidant defense and modulating gut microbiota.
Pueraria lobata (Willd.) Ohwi (PL) has been used in China to detoxify alcohol and protect the liver for millennia, though its mechanism of liver protection has not been elucidated. However, fermentation is considered to be one of the effective ways to enhance the efficacy of traditional Chinese medicine. The aim of this study was to investigate the hepatoprotective mechanism of probiotic-fermented PL (FPL). Sprague Dawley rats were administered with FPL followed by gavage of alcohol for seven consecutive days; following that, liver injury levels were evaluated in rats. FPL ameliorated lipid accumulation and inflammation levels in rats. Meanwhile, the levels of ethanol dehydrogenase, acetaldehyde dehydrogenase, and cytochrome P4502E1 were elevated by FPL treatment. It was observed that the levels of catalase, superoxide dismutase, and glutathione peroxidase were elevated, and the expression of nuclear transcriptional factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 genes and proteins were increased by FPL treatment, demonstrating that the Nrf2-mediated signal pathway was activated. Furthermore, FPL restored the composition of the gut microbiota with an increase in the abundances of Firmicutes and Lactobacillus and a decrease in the abundances of Bacteroidota and Akkermansia. Additionally, a strong correlation was found between the gut microbiota and the antioxidant parameters. The results indicate that FPL possesses an excellent protective effect in alcoholic liver injury. Our findings are beneficial to the development of hepatoprotective nutraceuticals for alcoholics. © 2022 Society of Chemical Industry.


Out-patient lumbar radiculography with iohexol.
A prospective study of 200 patients undergoing lumbar radiculography using 10 ml iohexol (240 mgI/ml) was undertaken to determine whether the procedure could be safely performed on an out-patient basis. No statistically significant differences in the incidence and severity of side-effects were found between the 99 out-patients and 101 in-patient controls. Three out-patients had to be kept in hospital at the end of the observation period and a further three out-patients were re-admitted to hospital because of severe side-effects. Out-patient lumbar radiculography is a safe procedure provided there is careful patient selection, adequate advice and easy access to medical help should problems arise following the examination. Adopting this practice considerably reduces the cost of lumbar radiculography and indirectly increases the availability of orthopaedic beds.


Pan-ebolavirus protective therapy by two multifunctional human antibodies.
Ebolaviruses cause a severe and often fatal illness with the potential for global spread. Monoclonal antibody-based treatments that have become available recently have a narrow therapeutic spectrum and are ineffective against ebolaviruses other than Ebola virus (EBOV), including medically important Bundibugyo (BDBV) and Sudan (SUDV) viruses. Here, we report the development of a therapeutic cocktail comprising two broadly neutralizing human antibodies, rEBOV-515 and rEBOV-442, that recognize non-overlapping sites on the ebolavirus glycoprotein (GP). Antibodies in the cocktail exhibited synergistic neutralizing activity, resisted viral escape, and possessed differing requirements for their Fc-regions for optimal in vivo activities. The cocktail protected non-human primates from ebolavirus disease caused by EBOV, BDBV, or SUDV with high therapeutic effectiveness. High-resolution structures of the cocktail antibodies in complex with GP revealed the molecular determinants for neutralization breadth and potency. This study provides advanced preclinical data to support clinical development of this cocktail for pan-ebolavirus therapy.


USP13 modulates the stability of the APC/C adaptor CDH1.
The cell division cycle is a process that is exquisitely controlled by a complex interplay between E3 ubiquitin ligases and deubiquitinating enzymes (DUBs). We have previously reported that the DUB USP13 regulates Aurora B levels along the cell cycle. That observation prompted us to explore any possible connection between USP13 and the APC/CCDH1, the major E3 controlling Aurora B levels in cells. We performed immunoprecipitation assays followed by western-blotting to assess the interaction between USP13 and CDH1. The cellular effects of USP13 gain or loss of function were analyzed by transfection of FLAG-tagged USP13 plasmid or small interfering RNAs and short hairpin RNAs directed against USP13. The levels of CDH1 and other proteins were quantified in cell extracts by western-blotting. We found that USP13 binds to the APC/C adaptor CDH1. In addition, we report for the first time that USP13 controls CDH1 protein levels in cells: overexpression of USP13 increased CDH1 levels, whereas depletion of USP13 decreased CDH1 levels. We unveil the existing interplay between USP13 and CDH1: USP13 is capable of stabilizing CDH1 levels. We previously reported that USP13 stabilizes Aurora B in cells, a known substrate of the APC/CCDH1 E3 ubiquitin ligase, before their entry into mitosis. Altogether, our data identify and establish the USP13-CDH1-Aurora B axis as a new regulatory module required for flawless cell cycle progression in mammalian cells, whose misfunction may be involved in the rewiring of cell cycle pathways linked to cancer development.


Non-photochemical quenching kinetics during the dark to light transition in relation to the formation of antheraxanthin and zeaxanthin.
Nonlinear regression analysis (NLR) is applied to quantify the dynamic response of non-photochemical fluorescence quenching (NPQ) of Trifolium repens cv. Regal upon dark to light transition. Commonly, only steady-state levels of NPQ are evaluated, ignoring transient kinetics. Experimental NPQ kinetics are fitted best with a sum of two functions: a sigmoidal Hill function plus a transient logarithmic normal function. It is shown that not only steady-state level of NPQ, but also the speed at which steady state is reached, increased with light intensity. The question is raised which biological processes cause the induction of the components of NPQ kinetics. The NPQ kinetics are found to resemble the kinetics of antheraxanthin and zeaxanthin formation during a dark to light transition. Furthermore, both molecules are known to induce NPQ. The hypothesis is put forward that a transient phase of NPQ (0-2 min after transition) is dependent upon concentrations of antheraxanthin, whereas the saturating phase corresponds with the production of zeaxanthin. A mathematical model, based on the presented hypothesis, predicts the effect of increasing light intensity on concentrations of antheraxanthin and zeaxanthin which correspond with experimental results. Implications of the hypothesis are discussed as well as the role of NLR in evaluating chlorophyll a fluorescence kinetics.


Bioconcentrations, depuration, shift in metabolome and a behavioural response in the nymphs of the dragonfly Aeshna cyanea (Müller, 1764) to environmentally relevant concentrations of methamphetamine.
Methamphetamine (MEA) is commonly detected in municipal wastewater. It causes imbalances in the system of neurotransmitters as well as several other adverse effects on human health. The aim of this study was to investigate bioconcentration and depuration rates at an environmentally relevant concentration of 1 µg·L-1 in Aeshna cyanea nymphs exposed to MEA for six days followed by three days of depuration. The metabolomes of nymphs sampled during exposure and depuration were compared using non-targeted screening. Concurrently, a behavioural experiment was run to evaluate the effect of MEA on movement. Since most samples were below the limits of quantification (LOQs) - MEA was quantified in only four out of the 87 samples and only during the first 24 h of exposure at concentrations at LOQ level - we estimated maximal possible bioconcentration factor (BCF) on 0.63 using the LOQ. An MEA metabolite - amphetamine - was not detected in any sample at levels above their LOQs. From 247 up to 1458 significant down- and up-regulated metabolite signals (p ≤ 0.05) were detected by non-targeted screening during initial times of exposure and depuration. Numbers of significant down- and/or up-regulated signals in metabolomes (p ≤ 0.05) calculated for particular sampling times possibly correlated with the size of the effect on movement recorded at the same times. In the MEA treatment, movement was not significantly greater during exposure (p > 0.05) but was significantly lower during depuration (p < 0.05). This study shows how MEA acts on dragonfly nymphs, an ecologically important group of aquatic insects with a high trophic level.


Molecular characterization of marker-free transgenic lines of indica rice that accumulate carotenoids in seed endosperm.
A single Agrobacterium strain harbouring two binary plasmids was successfully used for the first time to develop a marker-free transgenic rice of improved nutritional value. Sixty-eight T0 co-transformants were obtained in three indica rice cultivars--two popular high-yielding Bangladeshi varieties (BR28 and BR29), and one high-iron rice cultivar (IR68144). Marker-free lines were obtained from 14 out of 24 selected co-transformants screened in the T1 generation. The accumulation of total carotenoids in polished T2 rice seeds of the primary transgenic VPBR29-17-37 reached levels of up to 3.0 microg/g, with the level of beta-carotene reaching 1.8 microg/g. In the cultivars BR28 and IR68144, total carotenoid levels in the transformants reached 2.0 microg/g of polished rice seeds. The levels of lutein and other carotenoids in the seeds were also significantly enhanced. T1 plants obtained from primary transgenics with simple gene-integration patterns tended to have a lower carotenoid content than the original parental lines. This study describes the development of marker-free transgenic rice lines containing high levels of carotenoids, and addresses the relationship between the rearrangement of transgenes and the presence of metabolic end products in transgenic rice.


Acinetobacter peritonitis during chronic peritoneal dialysis.
Among gram-negative bacilli isolated during peritonitis in chronic peritoneal dialysis (CPD), Pseudomonas species are most common but Acinetobacter species are nearly as frequent. A survey of more than 450 patient-years' experience with CPD revealed 23 episodes of Acinetobacter peritonitis (AP), making this the second most common form of gram-negative peritonitis. Concomitant break in sterile technique and exit-site/tunnel infection were infrequent. AP appeared as the first peritonitis episode in five cases and as the second in six cases, and the duration of CPD at the time of AP ranged from less than 1 to greater than 56 months. However, AP was noted to appear shortly after treatment of another peritonitis episode or shortly after CPD access placement, within 2 months in 11 cases (47%) and within 3 months in 14 cases (61%). Treatment with intraperitoneal antibiotics succeeded in 21 cases (91%) without CPD interruption or catheter removal, with tobramycin or gentamicin alone in 16 cases, and with combined aminoglycoside and penicillin or cephalosporin in six cases. In two cases intraperitoneal antibiotics alone were insufficient therapy: one case with concomitant tunnel infection and dialysate leak and one case with bacteremia while receiving corticosteroids. The time-dependent incidence of AP suggests opportunistic infection during a vulnerable period in the first 2 to 3 months following another peritonitis episode, but AP also appears amenable to intraperitoneal antibiotic therapy alone without interruption of the CPD routine in the majority of cases.


Theoretical approach to intraocular lens calculation using Gaussian optics.
A computer-assisted method of calculating intraocular lens (IOL) power using formulas according to Gaussian optics is described. The method is more exact than current theoretical formulas, especially in calculating corneal power and in dealing with principal planes, and tends to give somewhat higher values for IOL power. One advantage of the theoretical approach is that the eye can be analyzed optically in a conventional manner, not only for the IOL power of emmetropia but also for the power of the biological lens, the total refractive power of the eye, and the magnification of the entire system. The relation to other theoretical formulas is discussed.


Evaluation of silicone-based wristbands as passive sampling systems using PAHs as an exposure proxy for carcinogen monitoring in firefighters: Evidence from the firefighter cancer initiative.
Compared to the general population, firefighters are known to sustain greater levels of exposure to hazardous compounds, despite their personal protective equipment, also known as turnout gear. Among the most significant toxins that firefighters are chronically exposed to are polycyclic aromatic hydrocarbons (PAHs). Additionally, firefighters have also been noted to exhibit an increased incidence of certain types of cancer. Considering a probable link between exposure to PAHs and increased rates of cancer in the fire service, we aim to document ambient chemical concentrations in the firefighter work environment. Our strategy involves the use of silicone-based wristbands that have the capacity to passively sorb PAHs. To determine if wristbands can serve as an effective chemical monitoring device for the fire service, silicone wristbands were pilot-tested as personal sampling devices for work environment risk monitoring in active-duty firefighters. Recovered wristbands underwent multiple extraction steps, followed by GC-MS analysis to demonstrate their efficacy in monitoring PAHs in the firefighter environment. Initial findings from all wristband samples taken from firefighters showed multiple exposures to various PAHs of concern for the health of the firefighters when in a fire environment. In addition to PAH monitoring, we examined known and potential sources of PAH contamination in their work environment. To that end, profiles of elevated PAH concentrations were documented at various fire stations throughout South Florida, for individual firefighters both during station duties and active fire response.


Myocardial involvement in coronavirus disease 19.
In late 2019, a cohort of patients presenting with pneumonia of unclear etiology in Wuhan, China, heralded the outbreak of coronavirus disease 19 (COVID-19). Previous severe acute respiratory syndrome (SARS) beta-coronavirus infections have been associated with tachyarrhythmias and signs and symptoms of heart failure. The emergence of SARS coronavirus 2 (SARS-CoV-2), which causes COVID-19, has rapidly developed into a pandemic, and a large number of infected patients have been reported to have underlying cardiovascular disease. Since there are only scant published data regarding cardiovascular burden in the wake of viral epidemics, this study aimed to evaluate cardiac involvement in COVID-19. This prospective cohort study included 40 adult inpatients at two centers in Germany. Adult patients diagnosed with COVID-19 in accordance with World Health Organization (WHO) interim guidance were included in the study, which focused on the potential cardiac involvement of SARS-CoV‑2. It was based on laboratory parameters as well as electro- and echocardiographic values to determine the impact of SARS-CoV‑2 virus on heart tissues. The conducted investigations confirmed the relationship between the presence of acute cardiac injury and COVID-19. Myocardial injury and impaired myocardial function due to COVID-19 are common; however, no correlation was established between cardiac laboratory or echocardiographic values and mortality. Cardiovascular monitoring upon COVID-19 infection is crucial to determine the burden of cardiac involvement.


Complex character of senS, a novel gene regulating expression of extracellular-protein genes of Bacillus subtilis.
The senS gene of Bacillus subtilis, which in high copy number stimulates the expression of several extracellular-protein genes, has been cloned, genetically mapped, and sequenced. The gene codes for a highly charged basic protein containing 65 amino acid residues. The gene is characterized by the presence of a transcription terminator (attenuator) located between the promoter and open reading frame, a strong ribosome-binding site, and a strong transcription terminator at the 3' end of this monocistronic gene. The amino acid sequence of SenS showed partial homology with the N-terminal core binding domain region of bacterial RNA polymerase sigma factors and a helix-turn-helix motif found in DNA-binding proteins. The gene can be deleted without any effect on growth or sporulation.


A comparison of X-irradiation and ferrous ion-ascorbate on oxidation of phosphatidylglycerols in multilamellar liposomes.
The effect of ferrous ion-ascorbate and X-radiation on multilamellar liposomes, composed of either completely saturated, unsaturated or a mixture of saturated and unsaturated fatty acids, is reported. Lipid composition is shown to be of critical importance in determining the extent to which peroxidation occurs. Liposomes composed of the mixture of saturated and unsaturated fatty acids are peroxidized to a lesser extent by ferrous ion-ascorbate. The reduced peroxidation is apparently the result of an inhibition mechanism shown by the saturated lipid component. In contrast, liposomes composed of mixed lipids do not reduce the level of peroxidation induced by ionizing radiation. These results show that the composition of liposomes plays a role in determining the extent to which peroxidation occurs when a chemical oxidant is employed, but composition is a negligible factor when ionizing radiation is the oxidant.


Per-operative haemodynamic assessment of lower limb arterial surgery. Part 1: Hydraulic impedance measurement.
Hydraulic impedance measurements have been made during surgery on 32 patients undergoing reconstructive arterial surgery. The reconstructive procedures included aorto-iliac, femoro-popliteal and axillo-femoral bypass, and extended deep femoral angioplasty. It was found that in aorto-iliac reconstruction the phase curves provide the means of assessing success, but that in other cases the impedance measurements though showing a similar trend are unable unequivocally to differentiate between success or failure.


Long non-coding RNA UCA1 promotes breast cancer by upregulating PTP1B expression via inhibiting miR-206.
The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) is involved in various cancers and often functions through microRNAs. The pro-survival protein PTP1B is known to play important roles in cancer development. However, the connection between UCA1 and PTP1B in breast cancer is not well studied. In this study, we first evaluated the correlation between UCA1 level and PTP1B expression in breast tissues, which showed the expression of PTP1B were much higher in the breast tumor tissues than in the peritumor normal tissues. The UCA1 level was positively associated with PTP1B expression in breast tumor tissues. We observed that UCA1 could up-regulate PTP1B expression in breast cancer cells. We also found that miR-206 could inhibit the expression of PTP1B by directly binding to the 3'-UTR of its mRNA. Interestingly, UCA1 could increase the expression of PTP1B through sequestering miR-206 at post-transcriptional level. The results also suggested that UCA1-induced PTP1B expression facilitated the proliferation of breast cancer cells. We conclude that UCA1 can up-regulates PTP1B to enhance cell proliferation through sequestering miR-206 in breast cancer. Our finding provides new insights into the mechanism of breast cancer regulation by UCA1, which could be a potential target for breast cancer treatment.Trial registration 2012N5hSYSU48573. Registered at Oct 12, 2012.


Microsurgical treatment and outcomes of spinal arteriovenous lesions: Learned from consecutive series of 105 lesions.
Spinal arteriovenous lesions (SAVLs), arteriovenous fistulas (AVFs) and arteriovenous malformations (AVMs), are rare and can devastatingly impair spinal cord function. This study aimed to evaluate clinical outcomes after microsurgical treatment with the aid of intraoperative indocyanine green video-angiography (ICG-VA) in a large series of patients with SAVLs. We retrospectively reviewed the cases of 95 consecutive patients with 105 SAVLs (77 spinal AVFs, 28 spinal AVMs) who had been treated surgically during 2010-2016 in two hospitals by the same experienced surgeon. All patients had undergone magnetic resonance imaging and digital subtraction angiography preoperatively and were assessed using the modified Aminoff and Logue Scale (mALS). All lesions were resected or occluded using ICG-VA. No ICG-VA-related complications occurred. Compared with AVF, patients with AVM tended to be younger (p<0.001) and were at higher risk of an associated aneurysm (p=0.021), hemorrhage (p<0.001), pain (p<0.001) and abrupt onset (p<0.001). SAVLs were most common in the lower thoracic region (45.71%), and their most common clinical presentation was paresthesia (89.52%). At a mean follow-up of 33.3months, mALS indicated significant improvement in patients with spinal AVFs (p<0.001) and AVMs (p=0.002) compared with their status preoperatively. An improved, stable clinical status was noted at the last follow-up in 93.51% of those with AVFs and 89.28% of those with AVMs. Thus, microsurgical treatment of SAVLs produced a lasting positive clinical outcome in a large cohort of consecutive patients. ICG-VA proved to be an efficient intraoperative tool during resection of these lesions, especially in patients with an AVF.


Expression and regulation of neuronal acetylcholine receptor mRNA in chick ciliary ganglia.
A chicken genomic clone encoding a portion of the neuronal acetylcholine receptor (AChR) alpha 3 subunit was used to identify homologous mRNA in embryonic chick ciliary ganglia. In situ hybridization indicated that the mRNA was neuronal. Northern blot analysis revealed a major hybridizing species of 3.5 kb. Protection experiments confirmed that ganglionic RNA contained material indistinguishable by RNAase digestion from the 300 nucleotide probe used. No transcripts were detected by in situ hybridization or Northern blot analysis for chick neuronal AChR alpha 2 or alpha 4 genes. alpha 3 transcripts were present at all times examined (E6 to 1 year posthatch). Both postganglionic axotomy and preganglionic denervation of ciliary ganglia in newly hatched chicks produced declines in alpha 3 mRNA levels, implying regulation of neuronal AChR mRNA by cell-cell interactions.


Diagnostic accuracy of vaccine and vaccine excipient testing in the setting of allergic reactions to COVID-19 vaccines: A systematic review and meta-analysis.
For persons with immediate allergic reactions to mRNA COVID-19 vaccines, skin testing (ST) to the vaccine/excipients (polyethylene glycol[PEG] and polysorbate 80 [PS]) has been recommended, but has unknown accuracy. To assess vaccine/excipient ST accuracy in predicting all-severity immediate allergic reactions upon re-vaccination, systematic review was performed searching Medline, EMBASE, Web of Science, and the WHO global coronavirus database (inception-Oct 4, 2021) for studies addressing immediate (≤4 h post-vaccination) all-severity allergic reactions to 2nd mRNA COVID-19 vaccination in persons with 1st dose immediate allergic reactions. Cases evaluating delayed reactions, change of vaccine platform, or revaccination without vaccine/excipient ST were excluded. Meta-analysis of diagnostic testing accuracy was performed using Bayesian methods. The GRADE approach evaluated certainty of the evidence, and QUADAS-2 assessed risk of bias. Among 20 studies of mRNA COVID-19 first dose vaccine reactions, 317 individuals underwent 578 ST to any one or combination of vaccine, PEG, or PS, and were re-vaccinated with the same vaccine. Test sensitivity for either mRNA vaccine was 0.2 (95%CrI 0.01-0.52) and specificity 0.97 (95%CrI 0.9-1). PEG test sensitivity was 0.02 (95%CrI 0.00-0.07) and specificity 0.99 (95%CrI 0.96-1). PS test sensitivity was 0.03 (95%CrI 0.00-0.0.11) and specificity 0.97 (95%CrI 0.91-1). Combined for use of any of the 3 testing agents, sensitivity was 0.03 (95%CrI 0.00-0.08) and specificity was 0.98 (95%CrI 0.95-1.00). Certainty of evidence was moderate. ST has low sensitivity but high specificity in predicting all-severity repeat immediate allergic reactions to the same agent, among persons with 1st dose immediate allergic reactions to mRNA COVID-19 vaccines. mRNA COVID-19 vaccine or excipient ST has limited risk assessment utility.


Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype.
HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemotherapy (NACT). The tumoral pathological complete response (pCR) rate was 40.9%. High tumoral pCR show a scarce mortality rate vs subjects with a lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with a high percentage of infiltrating immune cells and right-sided tumors, that reduce distant metastasis and improve survival, but no incidence difference. HER2 IHC score and laterality emerge as strong predictors of tumoral pCR after NACT from machine learning analysis. HER2 IHC3+ and G3 are poor prognostic factors for HER2+ BC patients, and could be considered in the application of neoadjuvant therapy. Increasing TILs concentrations, lower lymph node ratio and lower residual tumor cellularity are associated with a better outcome. The immune microenvironment and scarce lymph node involvement have crucial role in clinical outcomes. The combination of all predictors might offer new options for NACT effectiveness prediction and stratification of HER2+ BC during clinical decision-making.


Cryotop vitrification of large batches of pig embryos simultaneously provides excellent postwarming survival rates and minimal interference with gene expression.
The most commonly used technique to vitrify pig embryos is the super open pulled straw (SOPS), where a maximum of 6 embryos can be vitrified simultaneously per device without compromising the minimum volume necessary for optimal preservation. Since optimal embryo transfer (ET) demands a transfer of 20-40 embryos per recipient, the customary use of SOPS complicates embryo warming and ET in field conditions. Such complications could be avoided when using the Cryotop® (OC) system, which has been proven to be an effective option for vitrifying at least 20 porcine embryos simultaneously. This study aimed to investigate the changes in the transcriptome of blastocysts caused by vitrification using both systems. In vivo-derived blastocysts were OC- (n = 60; 20 embryos/device) and SOPS- (n = 60; 4-6 embryos/device) vitrified and cultured for 24 h after warming. Nonvitrified blastocysts (n = 60) cultured for 24 h postcollection acted as controls. At the end of culture, 48 viable embryos from each group (6 pools of 8 embryos) were selected for microarray (GeneChip® Porcine Genome Array, P/N 900624, Affymetrix) analysis of differentially expressed genes (DEGs). The survival rate of embryos vitrified with the OC and SOPS systems (>97%) was similar to that of the control embryos (100%). Microarray analysis of each vitrification system compared to the control group showed 245 DEGs (89 downregulated and 156 upregulated) for the OC system and 210 (44 downregulated and 166 upregulated) for the SOPS system. Two pathways were enriched for the DEGs specifically altered in each vitrification system compared to the control (glycolysis/gluconeogenesis and carbon metabolism pathways for the OC system and amino sugar and nucleotide sugar metabolism and lysosome pathways in the SOPS group). The OC group showed 31 downregulated and 24 upregulated genes and two enriched pathways (mineral absorption and amino sugar and nucleotide sugar metabolism pathways) when compared to the SOPS group. In summary, vitrification with the OC system altered fewer genes related to apoptosis and activated genes related to cell proliferation. We conclude that vitrification with either the OC or SOPS system has a moderate to low effect on the transcriptome of in vivo-derived porcine blastocysts. Further investigation is needed to elucidate how the differences in the transcriptome of embryos vitrified with these systems affect their subsequent developmental ability after ET.


Elevated parathyroid hormone-related protein and hypercalcemia in a patient with cutaneous squamous cell carcinoma complicating hidradenitis suppurativa.
We have described the case of a patient with long-standing hidradenitis suppurativa in whom associated cutaneous squamous cell carcinoma developed; this was complicated by hypercalcemia. Serum PTH-RP levels were elevated to 14.8 pmol/L. This is the third case report of hypercalcemia associated with squamous cell carcinoma complicating hidradenitis suppurativa and the first in which an elevated serum PTH-RP level has been documented in cutaneous squamous cell carcinoma.


Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry.
Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied. The extent and implications of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated, to the authors' knowledge. The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry, the Archives of General Psychiatry, the Journal of Clinical Psychopharmacology, and the Journal of Clinical Psychiatry between 2001 and 2003. Among 397 clinical trials identified, 239 (60%) reported receiving funding from a pharmaceutical company or other interested party, and 187 studies (47%) included at least one author with a reported financial conflict of interest. Among the 162 randomized, double-blind, placebo-controlled studies examined, those that reported conflict of interest were 4.9 times more likely to report positive results; this association was significant only among the subset of pharmaceutical industry-funded studies. Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo.


Endogenous theta stimulation during meditation predicts reduced opioid dosing following treatment with Mindfulness-Oriented Recovery Enhancement.
Veterans experience chronic pain at greater rates than the rest of society and are more likely to receive long-term opioid therapy (LTOT), which, at high doses, is theorized to induce maladaptive neuroplastic changes that attenuate self-regulatory capacity and exacerbate opioid dose escalation. Mindfulness meditation has been shown to modulate frontal midline theta (FMT) and alpha oscillations that are linked with marked alterations in self-referential processing. These adaptive neural oscillatory changes may promote reduced opioid use and remediate the neural dysfunction occasioned by LTOT. In this study, we used electroencephalography (EEG) to assess the effects of a mindfulness-based, cognitive training intervention for opioid misuse, Mindfulness-Oriented Recovery Enhancement (MORE), on alpha and theta power and FMT coherence during meditation. We then examined whether these neural effects were associated with reduced opioid dosing and changes in self-referential processing. Before and after 8 weeks of MORE or a supportive psychotherapy control, veterans receiving LTOT (N = 62) practiced mindfulness meditation while EEG was recorded. Participants treated with MORE demonstrated significantly increased alpha and theta power (with larger theta power effect sizes) as well as increased FMT coherence relative to those in the control condition-neural changes that were associated with altered self-referential processing. Crucially, MORE significantly reduced opioid dose over time, and this dose reduction was partially statistically mediated by changes in frontal theta power. Study results suggest that mindfulness meditation practice may produce endogenous theta stimulation in the prefrontal cortex, thereby enhancing inhibitory control over opioid dose escalation behaviors.


Ultrastructural effects induced by global ischaemia on the AV node compared with the working myocardium. A qualitative and morphometric investigation on the canine heart.
The cardiac conduction system is considered to be particularly resistant to ischaemia. Nevertheless, following open heart surgery with short periods of ischaemia disturbances in AV conduction or ventricular arrhythmia have been reported. We compared the ultrastructure of AV node and working myocardium following 30 min global ischaemia at 25 degrees C, during pure ischaemia and with HTK cardioplegia qualitatively and morphometrically. After 30 min of pure ischaemia, interstitial and intracellular oedema together with considerable changes in organelles in AV nodes predominate over mainly cellular oedema in working myocardium. Sometimes irregular overcontractions of sarcomeres occur in the AV node, though very seldom in working myocardium. In pure ischaemia, mitochondrial swelling is comparable in both types of tissue. Following HTK cardioplegia and 30 min ischaemia, cellular oedema and mitochondrial swelling are significantly reduced in AV nodal cells and working myocardium, but remain more extensive in the AV nodes. Irregularities in the contractile state of sarcomeres are not observed. The extent of the ultrastructural alterations corresponds to the degree of metabolic change in the working myocardium. Thus, despite considerable differences during pure ischaemia and HTK cardioplegia, ultrastructurally the AV nodal cells do not display a greater resistance to ischaemia than working myocardium.


Randomized Controlled Trial of Automated Directly Observed Therapy for Measurement and Support of PrEP Adherence Among Young Men Who have Sex with Men.
Measurement of adherence to oral pre-exposure prophylaxis (PrEP) in real-time has been challenging. We developed DOT Diary, a smartphone application that combines automated directly observed therapy with a PrEP adherence visualization toolkit, and tested its ability to measure PrEP adherence and to increase adherence among a diverse cohort of young men who have sex with men (MSM). We enrolled 100 MSM in San Francisco and Atlanta and randomly assigned them 2:1 to DOT Diary versus standard of care. Concordance between DOT Diary measurement and drug levels in dried blood spots was substantial, with 91.0% and 85.3% concordance between DOT Diary and emtricitabine-triphosphate and tenofovir-diphosphate, respectively. There was no significant difference in the proportion of participants with detectable PrEP drug levels at 24 weeks between study arms. These results suggest DOT Diary is substantially better than self-reported measures of adherence, but additional interventions are needed to improve PrEP adherence over time.


Risk of venous thromboembolism in thromboprophylaxis between aspirin and low molecular weight heparins after total hip arthroplasty or total knee arthroplasty: Systematic review and meta-analysis.
The aim of this study was to evaluate the efficacy of aspirin versus low molecular weight heparins (LMWH) for the prophylaxis of venous thromboembolism (VTE), deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing total knee arthroplasty (TKA) and/or total hip arthroplasty (THA). Systematic review and meta-analysis. Sixteen studies were selected. The risk of VTE, DVT and PE were analyzed. Mortality, risk of bleeding and surgical wound complications was also analyzed. 248,461 patients were included. 176,406 patients with thromboprophylaxis with LMWH and 72,055 patients with aspirin thromboprophylaxis. There were no significant differences in the risk of VTE (OR = 0.93; 95% CI: 0.69-1.26; P = .64), DVT (OR = 0.72; 95% CI: 0.43-1.20; P = .21) or PE (OR = 1.13; 95% CI: 0.86-1.49; P = .38) between both groups. No significant differences were found in mortality (P = .30), bleeding (P = .22), or complications in the surgical wound (P = .85) between both groups. These same findings were found in the sub-analysis of only randomized clinical trials (P>.05). No increased risk of PE, DVT, or VTE was found among patients with aspirin thromboprophylaxis versus patients with LMWH thromboprophylaxis. There was also no greater mortality, greater bleeding, or greater complications in the surgical wound found among patients with aspirin thromboprophylaxis versus patients with LMWH thromboprophylaxis.


Discovery of (S)-6-methoxy-chroman-3-carboxylic acid (4-pyridin-4-yl-phenyl)-amide as potent and isoform selective ROCK2 inhibitors.
ROCK1 and ROCK2 are highly homologous isoforms. Accumulated studies indicate that they have distinct different functions, and the development of isoform selective ROCK inhibitors will pave new roads for the treatment of various diseases. In this work, a series of amide-chroman derivatives were synthesized and biologically evaluated in order to develop potent and isoform selective ROCK2 inhibitors. Remarkably, (S)-6-methoxy-chroman-3-carboxylic acid (4-pyridin-4-yl-phenyl)-amide ((S)-7c) possessed ROCK2 inhibitory activity with an IC50 value of 3 nM and 22.7-fold isoform selectivity (vs. ROCK1). Molecular docking indicated that hydrophobic interactions were the key element for the high potency and isoform selectivity of (S)-7c. The binding free energies predicted by MM/GBSA were in good agreement with the experimental bioactivities, and the analysis of individual energy terms suggested that residue Lys105 in ROCK1 or Lys121 in ROCK2 was the key residue for the isoform selectivity of (S)-7c.


Reprint of: Safe Route for Cervical Approach: Partial Pediculotomy, Partial Vertebrotomy Approach for Posterior Endoscopic Cervical Foraminotomy and Discectomy.
Cervical radiculopathy is a common cervical spine condition. However, a paucity of data is available on the effect of partial pediculotomy and partial vertebrotomy (PPPV) for posterior endoscopic cervical foraminotomy (PECF) to treat cervical radiculopathy. We investigated the radiological and clinical outcomes of this approach. We performed a retrospective evaluation of 30 patients with cervical radiculopathy who had undergone PPPV PECF. Pre- and postoperative radiographs were performed to evaluate for stability, and computed tomography (CT) was used to evaluate the foraminal dimensions and area in the sagittal view. Three-dimensional reconstruction of the area of decompression was also performed. The clinical outcomes were evaluated using the visual analog scale, Oswestry disability index, and the MacNab criteria. No complications or recurrence developed in our PPPV PECF cohort during the study period. At the preoperative, 1-week postoperative, 3-month postoperative, and final follow-up examinations, the mean visual analog scale scores and mean Oswestry disability index showed significant improvement (score, 7.6, 3.0, 2.1, and 1.7, respectively; P < 0.05; and score, 73.9, 28.1, 23.3, and 21.5, respectively; P < 0.05). All the patients scored good to excellent using the MacNab criteria. The radiological findings showed that PPPV PECF resulted in a significant increase in decompression in the foramen area for all CT-measured parameters compared with the mean preoperative values: 1) the sagittal area increased 60.1 ± 23.1 mm2; 2) the craniocaudal length increased 4.0 ± 1.54 mm; and 3) the ventrodorsal length increased 4.0 ± 1.97 mm; Also, the 3-dimensional CT scan reconstruction decompression area had increased 996 ± 266 mm2 (P < 0.05). PPPV PECF is a safe route for decompression of the cervical spine with good clinical and radiological outcomes.


Risk factors for brucellosis seropositivity of goat herds in the Mexicali Valley of Baja California, Mexico.
A case-control study was conducted in the Mexicali Valley to identify risk factors for goat-herd seropositivity for Brucella melitensis. Nineteen case herds (> or = 2 positive results with the 8% rose bengal plate test (RBT)) and 55 control herds (zero positive results in RBT), matched for herdsize and geographic location, were enrolled. Conditional logistic regression was used to construct a multivariable model of the odds of seropositivity using variables assessed in a questionnaire administered to goat ranchers. The final model for herd seropositivity included increased risk from importation of goats from other Mexican states, the presence of La Mancha breed does, and the presence of does born outside the herd. Increasing herdsize was also highly significant (p < 0.01). In addition, a significant (p < 0.05) positive association was found between the presence of seropositive dogs (as assessed by RBT) and seropositive goats on the same ranch.


Effect of sucrose availability on wheel-running as an operant and as a reinforcing consequence on a multiple schedule: Additive effects of extrinsic and automatic reinforcement.
As a follow up to Belke and Pierce's (2014) study, we assessed the effects of repeated presentation and removal of sucrose solution on the behavior of rats responding on a two-component multiple schedule. Rats completed 15 wheel turns (FR 15) for either 15% or 0% sucrose solution in the manipulated component and lever pressed 10 times on average (VR 10) for an opportunity to complete 15 wheel turns (FR 15) in the other component. In contrast to our earlier study, the components advanced based on time (every 8min) rather than completed responses. Results showed that in the manipulated component wheel-running rates were higher and the latency to initiate running longer when sucrose was present (15%) compared to absent (0% or water); the number of obtained outcomes (sucrose/water), however, did not differ with the presentation and withdrawal of sucrose. For the wheel-running as reinforcement component, rates of wheel turns, overall lever-pressing rates, and obtained wheel-running reinforcements were higher, and postreinforcement pauses shorter, when sucrose was present (15%) than absent (0%) in manipulated component. Overall, our findings suggest that wheel-running rate regardless of its function (operant or reinforcement) is maintained by automatically generated consequences (automatic reinforcement) and is increased as an operant by adding experimentally arranged sucrose reinforcement (extrinsic reinforcement). This additive effect on operant wheel-running generalizes through induction or arousal to the wheel-running as reinforcement component, increasing the rate of responding for opportunities to run and the rate of wheel-running per opportunity.


Tension viscerothorax after blunt abdominal trauma: a case report and review of the literature.
Tension viscerothorax is herniation of abdominal viscera into the thorax. Tension viscerothorax can simulate tension pneumothorax. Immediate decompression with a nasogastric tube is required for hemodynamic stabilization. A case of tension viscerothorax is reported along with a review of the literature to highlight this rare complication of blunt abdominal trauma, and to emphasize the importance of nasogastric tube decompression in tension viscerothorax. A 10-year-old boy with a remote history of trauma related to a motor vehicle crash was brought into the Emergency Department with a 3-day history of vomiting, epigastric pain, and dyspnea. By physical examination and chest X-ray study, tension gastrothorax was diagnosed. Nasogastric tube placement was difficult and delayed, and the patient deteriorated into cardiac arrest, but after successful cardiopulmonary resuscitation and nasogastric tube insertion, the patient was stabilized. Laparotomy was performed and primary repair of a ruptured diaphragm was done. The patient made an uneventful recovery. Acute tension viscerothorax should be considered in the differential diagnosis of tension pneumothorax, and its initial resuscitation should include nasogastric tube insertion for immediate decompression.


Risk of adverse pregnancy and infant outcomes associated with prenatal Zika virus infection: a post-epidemic cohort in Central-West Brazil.
This study aimed to estimate the risks of adverse infant outcomes in the first year of life related to prenatal Zika virus (ZIKV) exposure. A prospective cohort of pregnant women with rash was recruited in Central-West Brazil in a post-epidemic period (January 2017 to April 2019). We evaluated participants' medical histories and performed ZIKV diagnostic testing using molecular (reverse transcription polymerase chain reaction [RT-PCR]) and serologic (immunoglobulin [Ig]M and plaque reduction neutralization tests [PRNT90]) assays. The ZIKV-positive group included both RT-PCR-confirmed cases as well as IgM and/or PRNT90-positive probable cases. Children were evaluated at birth and in the first 12 months of life. Transfontanellar ultrasound, central nervous system computed tomography, eye fundoscopy and retinography were performed. We estimated the absolute risk and 95% confidence interval (95% CI) of adverse infant outcomes among confirmed prenatally ZIKV-exposed children. Among 81 pregnant women with rash, 43 (53.1%) were ZIKV infected. The absolute risk of microcephaly among offspring of ZIKV-infected pregnant women was 7.0% (95% CI: 1.5-19.1), including the two cases of microcephaly detected prenatally and one detected postnatally. In total, 54.5% (95% CI: 39.8-68.7) of children in the ZIKV-exposed group had at least one ophthalmic abnormality, with the most frequent abnormalities being focal pigmentary mottling and chorioretinal atrophy or scarring. Our findings reinforce the importance of long-term monitoring of prenatally ZIKV-exposed children born apparently asymptomatic for Congenital Zika Syndrome.


An autoantibody against a 48-Kd fragment of human DNA-topoiomerase I in breast cancer: Implication for diagnosis and prognosis, and antibody-dependent cellular cytotoxicity in vitro.
Previously, we reported a novel tumor-associated antigen (TAA) derived from human DNA-topoiomerase I (TOP 1). In the present study, we demonstrated that the autoantibody against the TAA could be a potential biomarker in the early diagnosis and favorable prognosis of patients with breast cancer (BC). To understand the survival benefits in BC patients, we investigated whether the autoantibody could induce antibody-dependent cellular cytotoxicity activities (ADCC) against breast cancer cells in vitro. We found that the autoantibody exhibited significant ADCC activities that destroyed breast cancer MCF-7 and MDA-MB-231cells with peripheral blood mononuclear cells (PBMCs). The ADCC activities of the autoantibody were significantly correlated with the number of natural killer (NK) cells, NKT cells, and CD4+/CD8+ T cells. Accordingly, our findings showed that the autoantibody not only represented an early index of immune response to the TAA, but also was involved in host immune defense mechanisms that initiated the destruction of cancer cells.


Helicobacter pylori resistance rates for levofloxacin, tetracycline and rifabutin among Irish isolates at a reference centre.
Helicobacter pylori eradication rates using conventional triple therapies are falling, making viable second-line and rescue regimens necessary. Levofloxacin, tetracycline and rifabutin are three efficacious antibiotics for rescue therapy. We aimed to assess the resistance rates for H. pylori against these antibiotics in an Irish cohort. Gastric biopsies were collected from 85 patients infected with H. pylori (mean age 46 years) in the Adelaide and Meath Hospital, Dublin in 2008 and 2009. Susceptibility to antibiotics was tested using the Etest. Clinical information was obtained from endoscopy reports and chart review. 50.6 % of patients were females. Mean age was 47 years. Ten had prior attempts at eradication therapy with amoxicillin-clarithromycin-PPI, two had levofloxacin-based second-line therapy. 11.7 % [95 % CI (6.5-20.3 %)] (N = 10) had strains resistant to levofloxacin. There were no strains resistant to rifabutin or tetracycline. Levofloxacin resistance in the under 45 age group was 2.6 % (1/38) compared to 19.1 % (9/47) of above 45 age group (p = 0.02). The levofloxacin rates illustrated in this study are relatively low by European standards and in line with other studies from the United Kingdom and Germany, with younger patients having very low levels of resistance. Levofloxacin, tetracycline and rifabutin are all valid options for H. pylori eradication in Irish patients but the importance of compliance cannot be underestimated.


Differential regulation of phospholipase A2 (PLA2)-dependent Ca2+ signaling in smooth muscle by cAMP- and cGMP-dependent protein kinases. Inhibitory phosphorylation of PLA2 by cyclic nucleotide-dependent protein kinases.
Both cAMP- and cGMP-dependent protein kinases inhibit agonist-stimulated phospholipase C-beta (PLC-beta) activity and inositol 1,4,5-trisphosphate-dependent Ca2+ release in vascular and visceral smooth muscle. In smooth muscle of the intestinal longitudinal layer, however, the initial steps in Ca2+ mobilization involve activation of cytosolic PLA2 (cPLA2) and arachidonic acid (AA)-dependent stimulation of Ca2+ influx. The present study examined whether cAMP- and cGMP-dependent protein kinases are capable of regulating these processes also. Agents that activated cAMP-dependent protein kinase (5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole 3',5'-cyclic monophosphothioate (Sp-isomer) and isoproterenol), cGMP-dependent protein kinase (8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphate and Na nitroprusside), or both kinases (vasoactive intestinal peptide and isoproterenol >1 microM) induced phosphorylation of cPLA2 and inhibition of agonist-stimulated cPLA2 activity. Phosphorylation and inhibition of cPLA2 activity by cAMP- and cGMP-dependent protein kinases were blocked by the corresponding selective inhibitors (cAMP-dependent protein kinase, N-[2(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide hydrochloride (H-89) and myristoylated protein kinase inhibitor () amide; cGMP-dependent protein kinase, (8R,9S, 11S)-(-)-9-methoxy-carbamyl-8-methyl-2,3,9,10-tetrahydro-8, 11-epoxy-1H,8H,11H,-2,7b,11a-trizadizobenzo(a,g)cycloocta(c, d, e)-trinden-1-one (KT-5823)). In contrast, AA-stimulated Ca2+ influx was inhibited by agents that activated cGMP-dependent protein kinase only; the inhibition was selectively blocked by KT-5823. The study provides the first evidence of inhibitory phosphorylation of cPLA2 in vivo by cAMP- and cGMP-dependent protein kinases. Inhibition of cPLA2 activity and AA-induced Ca2+ influx partly account for the ability of cAMP-dependent protein kinase and/or cGMP-dependent protein kinase to cause relaxation. Their importance resides in their location at the inception of the Ca2+ signaling cascade.


A type III effectiveness-implementation hybrid evaluation of a multicomponent patient navigation strategy for advanced-stage Kaposi's sarcoma: protocol.
For people with advanced-stage Kaposi's sarcoma (KS), a common HIV-associated malignancy in sub-Saharan Africa, mortality is estimated to be 45% within 2 years after KS diagnosis, despite increasingly wide-spread availability of antiretroviral therapy and chemotherapy. For advanced-stage KS, chemotherapy in addition to antiretroviral therapy improves outcomes and saves lives, but currently, only ~50% of people with KS in western Kenya who have an indication for chemotherapy actually receive it. This protocol describes the evaluation of a multicomponent patient navigation strategy that addresses common barriers to service penetration of and fidelity to evidence-based chemotherapy among people with advanced-stage KS in Kenya. This is a hybrid type III effectiveness-implementation study using a non-randomized, pre- post-design nested within a longitudinal cohort. We will compare the delivery of evidence-based chemotherapy for advanced-stage KS during the period before (2016-2020) to the period after (2021-2024), the rollout of a multicomponent patient navigation strategy. The multicomponent patient navigation strategy was developed in a systematic process to address key determinants of service penetration of and fidelity to chemotherapy in western Kenya and includes (1) physical navigation and care coordination, (2) video-based education, (3) travel stipend, (4) health insurance enrollment assistance, (5) health insurance stipend, and (6) peer mentorship. We will compare the pre-navigation period to the post-navigation period to assess the impact of this multicomponent patient navigation strategy on (1) implementation outcomes: service penetration (chemotherapy initiation) and fidelity (chemotherapy completion) and (2) service and client outcomes: timeliness of cancer care, mortality, quality of life, stigma, and social support. We will also describe the implementation process and the determinants of implementation success for the multicomponent patient navigation strategy. This study addresses an urgent need for effective implementation strategies to improve the initiation and completion of evidence-based chemotherapy in advanced-stage KS. By using a clearly specified, theory-based implementation strategy and validated frameworks, this study will contribute to a more comprehensive understanding of how to improve cancer treatment in advanced-stage KS.


Machine-learning-assisted SERS nanosensor platform toward chemical fingerprinting of Baijiu flavors.
A novel fingerprinting platform for multiplex detection of flavor molecules in Baijiu was developed by using a surface-enhanced Raman scattering (SERS) nanosensor array in combination with machine learning. The SERS sensors were constructed by core-shell Fe3O4@Ag nanoparticles modified with molecules carrying end-groups of hydroxyl, pyridyl, methyl, and amino, respectively, which interacted with flavors and led to changes in the sensors' spectra. All the Raman spectra acquired from the nanosensor array contacting with the sample were concatenated into a single SERS super-spectrum, representing the flavor fingerprint which was recognized through machine learning. Principal component analysis, support vector machine, and partial least squares were utilized to build classification and quantitation models for predictive analyses. The SERS nanosensor array was successfully used for fingerprinting ten typical flavors in Baijiu including four esters, three alcohols, and three acids, with an accuracy of 100%, linear detection ranges over two orders of magnitude, and limits of detection ranging from 3.45 × 10-3 mg/L of phenylethyl acetate to 1.21 × 10-2 mg/L of ethyl hexanoate. It was also demonstrated that satisfactory accuracies (recoveries) ranging from 96.2 to 104% and relative standard deviations ranging from 0.65 to 2.78% were obtained for the simultaneous quantification of 3-methylbutyl acetate and phenylethyl acetate in eighteen Baijiu samples of three flavor types including sauce flavor, strong flavor, and light flavor. Compared with the existing detection techniques, this chemical fingerprinting platform is easy to use, highly sensitive, and can perform multiplex detection, which has great potential for practical applications.


Carcinoembryonic antigen in colonic lavage.
Colonoscopic lavage was performed for assay of carcinoembryonic antigen (CEA) concentration in patients with small and large colonic adenomas, in patients with adenocarcinoma of the colon, and in normal controls. CEA concentration was considerably higher in colonoscopic lavage as compared to plasma. CEA concentration in normal controls and in patients with colonic adenomas less than 1 cm in size were not significantly different. CEA concentrations in patients with colonic adenomas greater than 1 cm in size and in patients with adenocarcinoma of the colon were significantly higher than those observed in patients with small adenomas and in the normal controls. In all except 2 patients, plasma CEA concentrations were normal. Assay of CEA concentrations in colonic lavage may have potential application in the further assessment of the mucosa at risk for colon adenomas and for colon cancer. It does not appear to be accurate enough for diagnosis of colon cancer in individual patients.


Trends in utilisation and inequality in the use of reproductive health services in Sub-Saharan Africa.
The paper argues that unlike the income literature, the public health literature has not paid much attention to the distribution of substantial improvements in health outcomes over the last decade or more, especially, in the Sub-Saharan African (SSA) context. Thus, the paper examines current levels of utilisation, changes in utilisation as well as inequality in utilisation of reproductive health services over the last 10 years in SSA. The paper uses two rounds of Demographic and Health Survey (DHS) data from 30 SSA countries (latest round) and 21 countries (earlier round) to compute simple frequencies, cross-tabulated frequencies and concentration indices for health facility deliveries, skilled delivery assistance, 4+ antenatal visits and use of modern contraceptives. The results confirm the fact that utilisation of the selected reproductive health services have improved substantially over the last 10 year in several SSA countries. However, current levels of inequality in the use of reproductive health services are high in many countries. Interestingly, Guinea's pro-poor inequality in health facility delivery and skilled attendance at birth changed to pro-rich inequality, with the reverse being true in the case of use of modern contraceptives for Ghana, Malawi and Rawanda. The good news however is that in a lot of countries, the use of reproductive health services has increased while inequality has decreased within the period under study. The paper argue that whiles income levels may play a key role in explaining the differences in utilisation and the levels of inequality, indepth studies may be needed to explain the reason for differential improvements and stagnation or deterioration in different countries. In this way, best practices from better performing countries can be documented and adapted by poor performing countries to improve their situation.


Modulation of vitronectin receptor-mediated osteoclast adhesion by Arg-Gly-Asp peptide analogs: a structure-function analysis.
This study details the investigation of induction of retractile shape change in the osteoclast through inhibition of adhesion between osteoclasts and matrix with (1) peptide analogs bearing an Arg-Gly-Asp (RGD) sequence, (2) antibodies to the integrin alpha V beta 3 vitronectin receptor, and (3) the RGD-containing snake venom peptide echistatin. Osteoclast retraction on dentin has been demonstrated for GRGDSP peptide, in contrast to the inactivity of the analog containing the conservative RGE sequence modification. An osteoclast adhesion assay employing rat or chick bone cells and serum-coated glass coverslips as substrate was developed for routine evaluation of inhibition of adhesion. Antibodies F4 and F11 to the beta 3 chain of rat vitronectin receptor were effective at submicromolar concentrations in rat osteoclasts (IC50 0.29 and 0.05 microM, respectively), whereas MAb 23C6 to human/chick vitronectin receptor was somewhat less effective against chick osteoclasts (IC50 1.6 microM). A rank order of RGD analog activity (mean IC50, microM) in the serum-coated glass adhesion assay was derived for the linear peptides GRGDSP (201 microM), GRGDTP (180 microM), Ac-RGDS-NH2 (84 microM), Ac-RGDV-NH2 (68 microM), RGDV (43 microM), GRGDS (38 microM), and RGDS (26 microM). The two most potent short peptides were the cyclic analog SK&F 106760 Ac-S,S-cyclo-(Cys-(N alpha Me)Arg-Gly-Asp-Pen)-NH2 (IC50 7.0 microM), and the Telios peptide H-Gly-S,S-cyclo-(Pen-Gly-Arg-Gly-Asp-Ser-Pro-Cys)-Ala-OH (IC50 6.6 microM). The snake venom peptide echistatin was the most potent substance evaluated in the serum-coated glass assay (IC50 0.78 nM) employing either rat or chick osteoclasts.(ABSTRACT TRUNCATED AT 250 WORDS)


Purification from bovine liver membranes of a guanine nucleotide-dependent activator of phosphoinositide-specific phospholipase C. Immunologic identification as a novel G-protein alpha subunit.
Cholate-solubilized extracts from bovine liver plasma membranes preincubated with the nonhydrolyzable GTP analog guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) displayed enhanced phosphoinositide-specific phospholipase C activity compared with extracts from membranes incubated without nucleotide or with ATP or GDP analog. Resolution of the GTP gamma S-elicited activator of phospholipase C was achieved using heparin-Sepharose which bound the phospholipase C activity. Recombination of non-adsorbed extract with salt-eluted phospholipase C activity resulted in a stimulation of enzyme activity. The GTP gamma S-dependent activator was purified, on the basis of its ability to activate partially purified phospholipase C, by sequential chromatography on Q-Sepharose, Sephacryl S-300, octyl-Sepharose, and Mono Q. The presence of G-protein beta subunits and the alpha subunits of Gi1, Gi2, and Gi3 was detected, by immunoblot analysis, in Mono Q-purified phospholipase C activator preparations. Resolution of the activator from these alpha subunits was achieved by incubation with pertussis toxin in the presence of millimolar NAD+ followed by rechromatography on Mono Q. The phospholipase C activator, thus resolved from ADP-ribosylated alpha i subunits, possessed an approximate Mr of 42 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and copurified with a substoichiometric amount of beta subunit. Immunoblot analysis of fractions from the final Mono Q column revealed cross-reactivity of the 42-kDa phospholipase C activator with antipeptide antibodies raised against residues 160-169 of alpha i1 and a region of sequence common to all known G-protein alpha subunits. The 42-kDa activator was not recognized by other alpha subunit-specific or common antibodies. These findings identify the purified phospholipase C activator as a novel G-protein alpha subunit. This may represent the active subunit of the pertussis toxin-insensitive G-protein mediating receptor-stimulated phosphoinositide breakdown in mammalian liver.


Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism.
The identification of the candidate genes for autism through linkage and association studies has proven to be a difficult enterprise. An alternative approach is the analysis of cytogenetic abnormalities associated with autism. We present a review of all studies to date that relate patients with cytogenetic abnormalities to the autism phenotype. A literature survey of the Medline and Pubmed databases was performed, using multiple keyword searches. Additional searches through cited references and abstracts from the major genetic conferences from 2000 onwards completed the search. The quality of the phenotype (i.e. of the autism spectrum diagnosis) was rated for each included case. Available specific probe and marker information was used to define optimally the boundaries of the cytogenetic abnormalities. In case of recurrent deletions or duplications on chromosome 15 and 22, the positions of the low copy repeats that are thought to mediate these rearrangements were used to define the most likely boundaries of the implicated 'Cytogenetic Regions Of Interest' (CROIs). If no molecular data were available, the sequence position of the relevant chromosome bands was used to obtain the approximate molecular boundaries of the CROI. The findings of the current review indicate: (1) several regions of overlap between CROIs and known loci of significant linkage and/or association findings, and (2) additional regions of overlap among multiple CROIs at the same locus. Whereas the first finding confirms previous linkage/association findings, the latter may represent novel, not previously identified regions containing genes that contribute to autism. This analysis not only has confirmed the presence of several known autism risk regions but has also revealed additional previously unidentified loci, including 2q37, 5p15, 11q25, 16q22.3, 17p11.2, 18q21.1, 18q23, 22q11.2, 22q13.3 and Xp22.2-p22.3.


Quantitative selenium metabolism in normal New Zealand women.
1. Quantitative selenium metabolism has been studied in normal young New Zealand women by measuring total Se intake and urinary and faecal Se output, and by using values for absorption, excretion and turnover of 75Se determined after administration of[75Se]selenomethionine or [75Se]selenite. 2. In a period of 14 d when a normal ad lib. diet was being consumed, mean dietary Se for four women was 24.2 microgram/d, mean urinary Se was 13.1 microgram/d and mean faecal Se was 10.8 microgram/d; mean Se balance during this time was + 0.3 microgram/d. 3. Intestinal absorption of food Se was 0.76--0.83 of intake (mean 0.79). 4. Whole-body Se was calculated in three different ways; (a) using the specific activity of urinary Se and retained whole-body 75Se; (b) using plasma Se and the occupancy of 75Se in whole-body and plasma; (c) using absorbed food Se and the occupancy of absorbed 75Se in whole-body. 5. Whole-body Se calculated from measurements obtained following the administration of [75Se]selenomethionine was 4.7--10.0 mg (mean 6.9) using method (a), 4.1--7.2 mg (mean 5.2) using method (b) and 4.3--8.9 mg (mean 6.2) using method (c). 6. Whole-body Se calculated from results obtained after giving [75Se]selenite was 2.7--3.4 mg (mean 2.9) using method (a), 2.3--5.0 mg (mean 3.5) using method (b) and 2.1--3.0 mg (mean 2.6) using method (c). 7. The results of this study indicate that the minimum dietary requirement of Se for the maintenance of normal human health is probably not more than 20 microgram/d.


Induction of apoptosis in Eμ-myc lymphoma cells in vitro and in vivo through calpain inhibition.
Calpains are cysteine proteases that have been implicated as both effectors and suppressors of apoptosis. Previously, we showed that c-myc transformation regulated calpain activity and sensitized cells to apoptosis induced by calpain inhibition. The objective of this study was to investigate the role of calpain in the Eμ-myc transgenic model of B-cell lymphoma. Calpain activity assays, apoptosis, cell cycle assays, and expression measurements were used to determine the activity and role of calpain in vitro and in vivo. We found that Eμ-myc transgenic cells have highly elevated calpain activity. Calpastatin, the negative calpain regulator, was expressed at much lower levels in Eμ-myc lymphoma cells compared to normal splenic B cells. The primary isoform in Eμ-myc lymphoma is calpain 1. Treatment of Eμ-myc lymphoma cells with the calpain inhibitors PD150606 or calpain inhibitor III induced caspase-3-dependent apoptosis in vitro. General caspase inhibitors or caspase-3/7 inhibitor protected cells from death induced by calpain inhibitor, whereas caspase-9 inhibitors failed to rescue cells. Human Burkitt's lymphoma (BL2) cells display a pattern of sensitivity and caspase-3 dependence similar to calpain inhibition. Treatment of Eμ-myc lymphoma-bearing mice with PD150606 inhibited calpain activity in vivo and induced cell death in these cells as determined by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining. Multiple daily treatments resulted in reduced tumor load, particularly in combination with etoposide. In conclusion, calpain is highly elevated in the Eμ-myc lymphoma and calpain inhibition has therapeutic potential.


Effect of high-frequency stimulation of the subthalamic nucleus on the neuronal activities of the substantia nigra pars reticulata and ventrolateral nucleus of the thalamus in the rat.
Electrophysiological recordings were made in anaesthetized rats to investigate the mode of function of high-frequency stimulation of the subthalamic nucleus used as a therapeutic approach for Parkinson's disease. High-frequency electrical stimulation of the subthalamic nucleus (130 Hz) induced a net decrease in activity of all cells recorded around the site of stimulation in the subthalamic nucleus. It also caused an inhibition of the majority of neurons recorded in the substantia nigra pars reticulata in normal rats (94%) and in rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (90%) or with ibotenic acid lesions of the globus pallidus (79.5%). The majority of cells recorded in the ventrolateral nucleus of the thalamus responded with an increase in their activity (84%). These results show that high-frequency stimulation of the subthalamic nucleus induces a reduction of the excitatory glutamatergic output from the subthalamic nucleus which results in deactivation of substantia nigra pars reticulata neurons. The reduction in tonic inhibitory drive of nigral neurons induces a disinhibition of activity in the ventrolateral motor thalamic nucleus, which should result in activation of the motor cortical system.


Properties of the exchange rate of guanine nucleotides to the novel rap-2B protein.
Rap-2B is a novel ras-related protein that is 89% identical to rap-2 at the amino acid level. Based on its amino acid sequence, it is anticipated that rap-2B binds guanine nucleotides. Here we show that purified, bacterially expressed rap-2B does bind both GTP and GDP in a Mg2(+)-dependent fashion. The relative affinity of rap-2B for GTP is higher than that for GDP, both at low and high concentrations of Mg2+. This contrasts with N-ras p21 and could be of functional significance. Moreover, a polyclonal antiserum was raised against the recombinant rap-2B protein purified from E. coli lysates. This antiserum recognized a major protein of Mr approximately 21000 on Western blots of platelet membrane proteins, and immunoprecipitates rap-2B complexed with GTP or GDP.


Procedure-specific costs and savings in a mandatory program for second opinion on surgery.
Initial examination of the surgery experience of participants in a large employer-sponsored second opinion program revealed minimal savings in medical resource costs. But closer examination of relative savings for specific procedure categories showed that the greatest savings are for high-cost procedures: hysterectomy, prostatectomy, back surgery, and hip replacement. Furthermore, a nonconfirming second opinion does not dissuade patients from some procedures. Decisions about which procedures to include in a mandatory program should consider volume, costs, and effects of nonconfirmation, as well as the advantages of a mandatory second opinion for skeptical patients, or for patients for whom a controversial procedure has been recommended.


Retrograde intubation in patients undergoing open heart surgery.
Cardiovascular changes during difficult intubation were studied in 25 patients undergoing open heart surgery. The study was divided into two phases. Phase A from the first laryngoscopy to the fourth unsuccessful one; Phase B from a stabilization period until after retrograde intubation was performed. During phase A, heart rate (HR) increased significantly from 75 +/- 6.5 beats/min before laryngoscopy to 95 +/- 8.5 (p less than 0.05) after the last laryngoscopy. Mean arterial pressure (MAP) also increased from 82.5 +/- 4.75 mmHg to 105 +/- 5.15 (p less than 0.005) after the last laryngoscopy. Cardiac index (CI) decreased from 2.9 +/- 0.3 L . min-1 . m-2 before to 2.55 +/-0.2 after the last laryngoscopy. Pulmonary capillary wedge pressure (PCWP) increased from 10.5 +/- 1 mmHg before to 19.25 +/- 1.5 (p less than 0.01) after the last laryngoscopy. No statistically significant changes in HR, MAP, CI, and PCWP occurred before and after intubation during Phase B. Three patients had elevated ST segments during Phase A which responded to IV nitroglycerin and propranolol. None was detected during Phase B. There were more lacerated lips and teeth damaged during Phase A. One patient developed a small peritracheal haematoma after the retrograde intubation, for which no treatment was required. This technique is safe and produces minimal cardiovascular changes for difficult intubation in patients undergoing open heart surgery.


A modified experimental model of malignant pleural disease induced by lung Lewis carcinoma (LLC) cells.
Malignant pleural effusion resulting mainly from pleural metastases of lung adenocarcinoma has clinical relevance, being a sign of poor prognosis and low life expectancy. Experimental models can mimic the human condition, contributing to advances in current understanding of the mechanisms patients' pleural fluid accumulation and possible therapeutic strategies. The objective of this study is to evaluate the role of different concentrations of Lewis lung carcinoma cells (LLC cells) at the time of induction of experimental MPE and the main effects on survival of animals. C57BL/6 mice received intrapleural injection of 0.1, 0.5 or 1.5 × 10(5) LLC cells and survival curve, biochemical and pathological analyses of pleural fluid and tissue were analyzed. Evaluation of weight loss, mobility and survival showed that animals that received 0.5 × 10(5) cells maintained more stable condition up to day 14 and a gain of 6 days survival over mice that received the highest concentration. This study may allow a better understanding the mechanisms involved in the development of malignant pleural effusion and it may be promising in evaluating therapy to avoid recurrence, as the best time to indicate pleurodesis or target therapies.


Sexual dysfunctions in the patients hospitalized in psychiatric wards compared to other specialized wards in Isfahan, Iran, in 2012.
Having pleasurable sexual intercourses plays a major role in marital life satisfaction. Many of the medical and psychiatric disorders may affect the sexual function of the patients. The present study aims to investigate the relative frequency of sexual dysfunctions in the patients hospitalized in psychiatric wards and that of the patients in other specialized wards. This study is a descriptive-analytical, cross-sectional one, carried out on 900 patients hospitalized in psychiatric, cardiac, orthopedic, ophthalmology, and dermatology and plastic surgery wards of 5 hospitals in Isfahan. Data collection tools included demographic questionnaire and Arizona Sexual Experiences Scale (ASEX). Sexual dysfunction in the patients hospitalized in psychiatric wards (38%) was significantly higher than in the patients in other wards (27%), (P = 0.00). Among the patients hospitalized in psychiatric wards, those with bipolar disorder (37.3%) had the highest prevalence rate of sexual dysfunction. The patients with schizophrenia, major depression, substance abuse, and anxiety disorders had the following rates respectively. Among the patients in non-psychiatric wards, those in cardiac wards (37.1%) had the highest prevalence rate of sexual dysfunction. There was a significant relationship between the drug uses, mostly psychiatric drugs especially anti-psychotics, and the occurrence of sexual dysfunction. Considering the significant relative frequency of sexual dysfunction in psychiatric patients and undesired effects of simultaneous occurrence of both of these disorders in the patients, more emphasis is recommended to be placed on the prevention and proper treatment of these disorders in the patients.


Characterization of an epoxide hydrolase from the Florida red tide dinoflagellate, Karenia brevis.
Epoxide hydrolases (EH, EC 188.8.131.52) have been proposed to be key enzymes in the biosynthesis of polyether (PE) ladder compounds such as the brevetoxins which are produced by the dinoflagellate Karenia brevis. These enzymes have the potential to catalyze kinetically disfavored endo-tet cyclization reactions. Data mining of K. brevis transcriptome libraries revealed two classes of epoxide hydrolases: microsomal and leukotriene A4 (LTA4) hydrolases. A microsomal EH was cloned and expressed for characterization. The enzyme is a monomeric protein with molecular weight 44kDa. Kinetic parameters were evaluated using a variety of epoxide substrates to assess substrate selectivity and enantioselectivity, as well as its potential to catalyze the critical endo-tet cyclization of epoxy alcohols. Monitoring of EH activity in high and low toxin producing cultures of K. brevis over a three week period showed consistently higher activity in the high toxin producing culture implicating the involvement of one or more EH in brevetoxin biosynthesis.


Enhanced photocatalytic activity of hydrozincite-TiO2 nanocomposite by copper for removal of pharmaceutical pollutant mefenamic acid in aqueous solution.
Nanocomposites based on hydrozincite-TiO2 and copper-doped HZ-xCu-TiO2 (x = 0.1; 0.25; 0.35) were synthesized in a single step using the urea method. The samples were characterized by XRD, FTIR, SEM/TEM, and DRS. The study of adsorption capacity and photocatalytic efficiency of these nanocomposites have been tested on a pharmaceutical pollutant, mefenamic acid (MFA). Kinetic study of removal of MFA indicates that this pollutant was adsorbed on the surface of the synthesized phases, according to Langmuir's model. Such adsorption proved to be well adapted in a kinetic pseudo-second-order model with capacity of 13.08 mg/g for HZ-0.25Cu-TiO2. Subsequently, the kinetics of photocatalytic degradation under UV-visible irradiation was studied according to several parameters, which allowed us to optimize our experimental conditions. The nanocomposite HZ-0.25Cu-TiO2 showed significant removal efficiency of MFA. Elimination rate reached 100% after 20 min under UV-vis irradiation, and 77% after 7 h under visible light irradiation. Repeatability tests have shown that this nanocomposite is extremely stable after six photocatalytic cycles. By-products of MFA were detected by LC/MS. These photoproducts was produced by three types of reactions of hydroxylation: cyclization and cleavage of the aromatic ring. MFA underwent complete mineralization after 22 h of irradiation in the presence of the HZ-0.25Cu-TiO2.


Properties of ultrasonic waves in bovine bone marrow.
We investigated the properties of ultrasonic waves in bovine bone marrow. Six bone marrow samples were obtained from different parts (proximal, middle and distal) of the shafts of two bovine femora without destruction. The measured frequency range was 3 to 10 MHz, and the temperature range was 15 to 40°C. Both wave velocity and attenuation coefficient in bone marrow always decreased as temperature increased. The velocity ranged from 1400 to 1610 m/s and attenuation coefficient ranged from 4 to 16 dB/cm. Wave velocities in bone marrow were similar to those in water, whereas the temperature dependences were different, and the wave attenuation coefficients were much higher than those in water. The dependence of velocity on temperature changed slightly around 23-24°C, where a transition from soft gel to oily liquid occurred. The transition temperature was confirmed by differential scanning calorimetry (DSC). Below this transition temperature, positive velocity dispersion was observed.


Laser-photophoretic migration and fractionation of human blood cells.
Laser photophoretic migration behavior of human blood cells in saline solution was investigated under the irradiation of Nd:YAG laser beam (532 nm) in the absence and the presence of the flow in a fused silica capillary. Red blood cells (RBC) were migrated faster than white blood cells (WBC) and blood pellets to the direction of propagation of laser light. The observed photophoretic velocity of RBC was about 11 times faster than those of others. This was understood from the larger photophoretic efficiency of RBC than that of WBC, which was simulated based on the Mie scattering theory. Furthermore, it was found that, during the photophoretic migration, RBCs spontaneously orientated parallel to the migration direction so as to reduce the drag force. Finally, it was demonstrated that RBC and WBC were separated in a micro-channel flow system by the laser photophoresis.


X-linked hypophosphatemic rickets: Case report of late diagnosis and bone pain improvement with targeted treatment.
X-linked hypophosphatemia (XLH) is a rare disexase in which patients present with severe bowing of the legs, joint pain, and mobility problems. XLH has major adverse repercussions on the quality of life.


Flow cytometric evaluation of the effects of 2.3 MeV neutrons and 240 kV X rays on mouse spermatogenic S-phase cells using bromodeoxyuridine incorporation.
A sensitive flow cytometric assay has been developed to assess the effect of X rays or neutrons on the DNA-synthesizing ability of mouse testis cells. The dose to reduce the labelling index (LI) to 50% (ED50) was 25 cGy for X rays and 5 cGy for neutrons, giving a relative biological effectiveness (RBE) of 5.0. A significant reduction of the LI was seen at X-ray doses as low as 10 cGy. Neutron treatment resulted in an exponential decrease in functional S-phase cells while the X-ray response was biphasic. The sensitivity and rapidity of the assay would be suitable for use in biological dosimetry.


[Update on the management of desmoids tumors].
Desmoids tumors are rare fibrous tumors of soft tissue. These tumors are located in the abdominal wall, abdomen or extra abdominal. Parietal location is very common among pregnant women and in postpartum period. Hormonal factors are implicated as well. Starting from the observation of 30-year-old patient, in whom a soft tissue mass in the abdominal wall was discovered in the post-partum period, we then emphasize the potential role of cross sectional imaging (ultrasound, CT and especially MRI) in the diagnostic approach, which was confirmed by postoperative pathological examination.


Strong correlation between levels of tropospheric hydroxyl radicals and solar ultraviolet radiation.
The most important chemical cleaning agent of the atmosphere is the hydroxyl radical, OH. It determines the oxidizing power of the atmosphere, and thereby controls the removal of nearly all gaseous atmospheric pollutants. The atmospheric supply of OH is limited, however, and could be overcome by consumption due to increasing pollution and climate change, with detrimental feedback effects. To date, the high variability of OH concentrations has prevented the use of local observations to monitor possible trends in the concentration of this species. Here we present and analyse long-term measurements of atmospheric OH concentrations, which were taken between 1999 and 2003 at the Meteorological Observatory Hohenpeissenberg in southern Germany. We find that the concentration of OH can be described by a surprisingly linear dependence on solar ultraviolet radiation throughout the measurement period, despite the fact that OH concentrations are influenced by thousands of reactants. A detailed numerical model of atmospheric reactions and measured trace gas concentrations indicates that the observed correlation results from compensations between individual processes affecting OH, but that a full understanding of these interactions may not be possible on the basis of our current knowledge of atmospheric chemistry. As a consequence of the stable relationship between OH concentrations and ultraviolet radiation that we observe, we infer that there is no long-term trend in the level of OH in the Hohenpeissenberg data set.


Skin/mucosa avoidance radiotherapy (SMART) versus conventional volumetric arc-based radiotherapy (VMAT) for the treatment of head and neck cancer: Dosimetric feasibility study.
Intensity modulated radiotherapy (IMRT) for head and neck cancer has led to a reduction in radiotherapy doses to normal tissues, like the salivary glands, while maintaining high rates of local control. Oral mucosal and skin toxicity is still a major source of treatment-related morbidity, occurring in most patients. We conducted a dosimetric feasibility study with the goal of creating a methodology that could theoretically reduce the dose of radiation to skin and oral mucosa, while maintaining comparable avoidance of other organs at risk, and planning target volume (PTV) coverage. The clinical plans of patients treated previously were replanned using coplanar VMAT arcs on a TrueBeam STx using the photon optimizer (PO) version 15.6 and the Acuros XB dose calculation algorithm. Comparisons were made between three methodologies: "Conventional," "Skin Sparing" and a skin/mucosa avoiding ("SMART") technique, with dose metrics being compared using analysis of variance, with a Bonferroni correction to account for multiple pairwise comparisons. The maximum grade of mucositis and radiation dermatitis during treatment was correlated to different dose-volume metrics to predict what could be clinically meaningful. Sixteen patients met the study criteria and were replanned using the skin sparing and SMART techniques. Maximum doses to the skin sparing structure were reduced from 64.2 Gy to 56.6 and 55.9 Gy, in the skin sparing and SMART plans (p < 0.0001), and mean doses reduced from 26.7 Gy to 20.0 and 20.2 Gy, respectively (p < 0.0001). Maximum doses to the oral cavity structure were not reduced by either technique, however mean dose to the oral cavity structure was reduced from 39.03 Gy to 33.5 Gy by the SMART technique (p < 0.0001). There was a slight reduction in PTV_High coverage by the V95% in the SMART plans (99.52% vs. 98.79%, p = 0.0073), and a similar slight reduction in PTV_Low coverage by the V95% by both the skin sparing and SMART plans (99.74% vs. 97.89% vs. 97.42%, p < 0.0001). Maximum doses to organs at risk were not statistically different between techniques. Dose to oral cavity and maximum grade experienced during radiotherapy correlated. The Spearman correlation coefficient for dose to 20%, 50%, and 80% of the volume of oral cavity was 0.5 (p = 0.048), 0.64 (p = 0.007), and 0.62 (p = 0.010), respectively. Skin toxicity grade was only found to be correlated with the D20% of the skin sparing structure (Spearman correlation coefficient of 0.58, p = 0.0177). The SMART technique appears to be able to reduce maximum and mean skin dose, as well as mean oral cavity doses, while only slightly reducing PTV coverage, with acceptable OAR doses. We feel the improvements warrant investigation in a clinical trial.