Evaluation of the contribution of mast cell mediators to the hypotensive activity of various peptides in rats.
We have tested the effects of intravenous injections of substance P (SP), bradykinin (BK), somatostatin (SS) and vasoactive intestinal peptide (VIP) on the blood pressure, histaminemia and hematocrit in pentobarbital-anesthetized rats. The four peptides elicited a decrease of the mean arterial blood pressure which varied both in amplitude and in duration depending both on the peptide and on the doses utilized. The hypotensive effects of SP and VIP were more persistent than those caused by BK or SS. Only SP evoked an increase of histaminemia. Both SP and BK caused an increase of hematocrit. The change of hematocrit was more prominent and of longer duration after Sp than after BK. Pretreatment of rats with the antiinflammatory drug dexamethasone inhibited markedly the changes of blood pressure, histaminemia and hematocrit caused by SP. The hypotensive effects of BK, SS and VIP as well as the transient change of hematocrit evoked by BK were not affected by dexamethasone. The results suggest that part of the hypotensive activity and changes of hematocrit evoked by SP in rats is due to the release and action of histamine and possibly of other vasoactive substances, of mast cell origin. The results also indicate that mast cell mediators, particularly histamine, are unlikely to be instrumental in the hypotensive activity of BK, SS or VIP in rats.


Effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes.
Currently there is no effective treatment for nonalcoholic fatty liver disease (NAFLD), especially hepatic fibrosis induced by type 2 diabetes. Valsartan maybe has beneficial effect on the liver disease. The aim of the present study was to investigate the effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes. An animal model of hepatic fibrosis with type 2 diabetes was developed using a high-sucrose, high-fat diet and low-dose streptozotocin. Valsartan (15 mg/kg/day, i.g.) was orally administered for four months. The livers were removed to make hematoxylin-eosin (HE) staining and Picric acid-Sirius red staining, and immunohistochemistry staining of α-smooth-muscle-actin (α-SMA), transforming growth factor β1 (TGF-β1), tumor necrosis factor (TNF-α) and monocyte chemotactic protein-1 (MCP-1). Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to detect hepatocyte apoptosis. The liver mitochondria were isolated to measure the mitochondrial respiratory function. The results showed that valsartan significantly alleviated the lesion of hepatic steatosis and hepatic fibrosis by HE staining and Picric acid-Sirius red staining. Immunohistochemical staining suggested that the expression of α-SMA, TGF-β1, TNF-α and MCP-1 in liver tissue of diabetic rats was markedly reduced by valsartan. TUNEL staining showed that there were fewer TUNEL-positive apoptotic hepatocytes in valsartan group. In addition, valsartan restored the injured hepatic mitochondrial respiratory function. The findings demonstrated that valsartan prevented the pathological progression of hepatic fibrosis in type 2 diabetic rats, correlated with reducing α-SMA, TGF-β1, TNF-α and MCP-1 expression, also anti-apoptosis and mitochondria-protective potential.


Absolute blood flow and oxygen consumption in stunned myocardium in patients with coronary artery disease.
In patients with coronary artery disease (CAD), we sought to demonstrate normal myocardial blood flow (MBF) and myocardial oxygen consumption (MMRO(2)) to post-ischemic myocardium that exhibited reversible dysfunction and the relation between the severity of the dysfunction and the preceding ischemia. In animal models of stunning, MBF and MMRO(2) are normal or near normal, and the severity of stunning is related to the degree of the preceding ischemia. Myocardial blood flow and MMRO(2) were measured using positron emission tomography and oxygen 15-labelled water (H(2)(15)O) and oxygen 15-labelled oxygen ((15)O(2)), respectively, in 14 patients with CAD and normal left ventricular (LV) function. Global ejection fraction and regional LV systolic function (SF) were measured using quantitative echocardiography during and after dobutamine-induced ischemia. Ejection fraction and SF were reduced 30 min after dobutamine (both: p < 0.01) but recovered by 120 min. Myocardial blood flow (ml/min per g) to regions with reversible LV dysfunction was normal at baseline and during dysfunction (0.88 [0.82 to 0.99] and 1.09 [0.75 to 1.37], respectively, p = NS) as was MMRO(2) (ml/min per 100 g) (16.64 [10.16 to 16.18] and 11.68 [8.43 to 15.30] respectively, p = NS). Left ventricular dysfunction was related to stenosis severity and peak MBF. Regions were divided into those subtended by a stenosis of <50%, 50% to 80% and >80% luminal diameter. Systolic function 30 min after dobutamine was 93.9% (83.4% to 104.4%) (p = NS), 85.4% (80.0% to 90.9%) and 67.4% (56.2% to 78.7%) (both: p < 0.001), respectively. Peak MBF was 2.0 (1.71 to 2.31), 1.75 (1.65 to 1.85) (p = 0.01 compared with <50%) and 1.47 (1.33 to 1.60) (p = 0.03 compared with 50% to 80% and p = 0.002 compared with <50%), respectively. In patients with CAD, dobutamine produces prolonged, but reversible, LV dysfunction when MBF is normal, confirming stunning. This stunning is related to the severity of the coronary stenosis and the reduction in peak MBF. Myocardial oxygen consumption to stunned myocardium is normal.


The future of general surgery in Ireland: factors influencing career decisions of medical students.
The decline in popularity of general surgery as a career has been well described. A number of factors have been put forward to explain this, for example, trainee burnout and perceived difficulty with work/life balance. The aim of this study was to elucidate the reasons for this among medical students in Ireland. A questionnaire was distributed to clinical year medical students in Ireland using an online survey via SurveyMonkey™. Domains assessed included demographics, career plan and associated rationale. Anonymised responses were collated and evaluated. There were 307 responses (response 23%). Females accounted for 66% (202). Mean age was 24 years (SD = 2.89). One hundred twelve responses (36%) were contemplating becoming surgeons. One hundred nine-five responses were not considering surgery: however 87 had previously considered. Of the 87, 41 (47%) attributed the decision to work/life balance, 30 (35%) to impact on personal relationships and 10 (11%) blamed unclear career projection. Students interested in surgery were asked to quantify their knowledge of the application process-17 (15%) good, 39 (35%) fair and 56 (50%) poor. A small proportion of respondents plan to pursue a career in general surgery. This is concerning in view of attrition rates through junior years. Although lifestyle factors are significant, clarity regarding training pathways was also reported. Undergraduate education regarding career trajectory, quality of life and practicalities of a career in general surgery may increase applications.


Low-dose electron beam radiation and romidepsin therapy for symptomatic cutaneous T-cell lymphoma lesions.
Romidepsin is a structurally unique histone deacetylase inhibitor approved by the U.S. Food and Drug Administration for therapy of relapsed or refractory cutaneous T-cell lymphoma (CTCL). Localized electron beam radiation therapy (LEBT) is standard practice in the care of patients with chronically traumatized and painful lesions. Combination therapy of those two modalities may be beneficial for the therapy of CTCL. To report observations on supportive LEBT utilized for isolated refractory lesions in patients on romidepsin. Observations were made during a phase II clinical trial sponsored by the National Cancer Institute (NCI-1312) examining the efficacy of romidepsin for patients with relapsed, refractory or advanced CTCL, stage IB-IVA mycosis fungoides (MF) or Sézary syndrome. Skin responses were assessed by evaluation of five target lesions only. Patients with objective clinical responses in target lesions who had symptomatic nontarget lesions were allowed limited LEBT to isolated lesions for symptomatic relief. Patients who received localized radiation were not considered complete responders at any point. Five patients with advanced MF (three stage IIB and two stage IVA2) received LEBT to symptomatic nontarget lesions while on a protocol with romidepsin. None of these patients experienced additional or unexpected toxicity. Four of the five patients demonstrated fast and durable responses. We noted that significantly lower than standard doses of LEBT effectively treated symptomatic lesions in these patients. LEBT demonstrated significant responses at very low doses without additional toxicity in patients on protocol treatment with the histone deacetylase inhibitor romidepsin. This merits formal investigation in a clinical trial for potential synergy in patients with CTCL.


Enteral nutrition: a first option for nutritional support of children following allo-SCT?
Parenteral nutrition (PN) is the treatment of choice for nutritional support of patients undergoing allo-SCT following myeloablative conditioning (MAC). Here we prospectively assessed the outcomes of early enteral nutrition (EN) in a paediatric cohort. From 2003 to 2010, all 65 consecutive children undergoing MAC allo-SCT at our referral centre began EN the day after transplantation. Post-transplant and nutritional outcomes of patients receiving only EN (EN group, n=50) were compared with those of patients requiring additional PN (EN-PN group, n=15). In the EN group time to platelet recovery (P=0.01) and length of hospitalisation (P<0.001) were shorter, while in the EN-PN group the proportion of unrelated donors (P=0.02) and the frequency of severe acute GVHD (aGVHD; P=0.004) were higher. All patients were alive at day 100. PN was started 14 days after transplant because of poor digestive tolerance to EN or severe gut aGVHD. The body mass index Z-score in the EN-PN group decreased from transplant to discharge (P=0.02). In only 23% of cases was PN required for severely ill patients. Our results suggest that EN might be considered to be an option for nutritional support in children undergoing MAC allo-SCT, while PN should be used only as a rescue option, possibly in combination with EN.


Oncologic outcomes after splenectomy during initial cytoreductive surgery in advanced epithelial ovarian cancer: a nationwide population-based cohort study.
Epithelial ovarian cancer (EOC) patients undergoing splenectomy during cytoreductive surgery represent a small subgroup of patients. Splenic metastases or technical reasons due to extensive upper abdominal disease may require a splenectomy. It has been hypothesized that as the spleen's antitumor immunologic functions may inhibit cancer growth, splenectomy may promote the growth of residual disease as observed in other cancer types of murine studies. The few studies assessing the impact of splenectomy on the oncologic outcomes of advanced stage EOC patients have reported inconsistent results. It remains unclear whether splenectomy during cytoreductive surgery is justified to achieve complete cytoreduction. The aim of this study was to assess the impact of a splenectomy on perioperative outcomes and survival of advanced stage EOC patients. In this nationwide population-based study, all consecutive patients diagnosed with FIGO stage IIIC and IV EOC between 1 January 2008 and 31 December 2015 were identified from the Netherlands Cancer Registry. Patients who underwent cytoreductive surgery combined with platinum-based chemotherapy as primary treatment were selected. Differences in clinicopathologic characteristics between splenectomy and non-splenectomy patients were assessed. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier survival curves and log-rank tests. Cox proportional hazards models were used to adjust for covariates that influence survival. A total of 3911 patients were identified: 99 splenectomy and 3812 non-splenectomy patients. Splenectomy patients were more likely to undergo extensive surgery or surgical reintervention, to receive intraperitoneal chemotherapy, intraoperative and postoperative blood transfusion, to experience postoperative infections, and to be admitted to an intensive care unit (all p < 0.002). No significant differences in PFS or OS were observed between splenectomy vs non-splenectomy patients after adjusting for covariates. Although advanced stage EOC patients who undergo splenectomy during cytoreductive surgery have less favorable perioperative outcomes, no adverse impact of splenectomy on the survival of advanced stage EOC patients was observed. Splenectomy during cytoreductive surgery seems to be justified to achieve complete cytoreduction in advanced stage EOC patients.


[Serological detection of Brucella suis, influenza virus and Aujeszky's disease virus in backyard and small swine holders in Argentina].
Farmers raising less than 100 sows represent more than 99% of swine producers in Argentina, although little is known about their sanitary status and productive characteristics in the country. Sanitary and productive information was obtained. Furthermore, samples for serological studies were taken to detect antibodies against Brucella suis (Bs), Aujeszky's disease virus (AV) and influenza virus (IV) in 68 backyard and small producers with less than 100 sows located in the north, central and south regions of Argentina. Antibodies against H1 pandemic were detected in 80% of the farms while 11%, 11.7% and 6.0% of the producers were positive to influenza H3 cluster 2, AV and Bs, respectively. None of the producers was aware of the risk factors concerning the transmission of diseases from pigs to humans. A percentage of 47% of them buy pigs for breeding from other farmers and markets. With regard to biosecurity measures, only 16% of the farms had perimeter fences. The results of this study demonstrate that productive characterization and disease surveys are important to improve productivity and to reduce the risk of disease transmission among animals and humans. The study of sanitary status and risk factors is necessary for better control and eradication of diseases in backyard or small producers. More representative studies at country level should be carried out to detect the pathogensthat circulate and, with this knowledge, to implement prevention and control measures.


Virtual human technology: capturing sex, race, and age influences in individual pain decision policies.
Pain assessment is subject to bias due to characteristics of the individual in pain and of the observing person. Few research studies have examined pain assessment biases in an experimental setting. This study employs innovative virtual human technology to achieve greater experimental control. A lens model design was used to capture decision-making policies at the idiographic and nomothetic level. Seventy-five undergraduates viewed virtual humans (VH) that varied in sex, race, age, and pain expression. Participants provided computerized ratings with Visual Analogue Scales on the VH's pain intensity, pain unpleasantness, negative mood, coping, and need for medical treatment. Idiographic analyses revealed that individuals used pain expression most frequently as a significant cue. Nomothetic analyses showed that higher pain expression VH and female VH were viewed as having higher pain intensity, higher pain unpleasantness, greater negative mood, worse coping, and a greater need to seek medical treatment than lower pain expression VH and male VH, respectively. Older VH were viewed as having worse coping and a greater need to seek medical treatment than younger VH. This innovative paradigm involving VH technology and a lens model design was shown to be highly effective and could serve as a model for future studies investigating pain-related decision making in healthcare providers.


Aspirin-induced urticaria in a recently diagnosed ischemic stroke patient: A case report and literature review.
NSAIDs may be rare but an important cause of urticarial which should not be missed. The aspirin and urticaria correlation has not been fully understood. The pharmacological inference is suspected to be the diversion of arachidonic acid metabolism. Aspirin sensitivity can aggravate preexisting chronic urticaria and in some instances causes acute urticaria. We report a case of a 53-year-old male, recently diagnosed with a stroke, who presented with complaints of multiple rashes over the trunk and upper extremities with aspirin. NSAIDs induced urticarial are usually neglected by physicians during diagnosis.


Neurotrophic factor changes in the rat thick skin following chronic constriction injury of the sciatic nerve.
Cutaneous peripheral neuropathies have been associated with changes of the sensory fiber innervation in the dermis and epidermis. These changes are mediated in part by the increase in local expression of trophic factors. Increase in target tissue nerve growth factor has been implicated in the promotion of peptidergic afferent and sympathetic efferent sprouting following nerve injury. The primary source of nerve growth factor is cells found in the target tissue, namely the skin. Recent evidence regarding the release and extracellular maturation of nerve growth factor indicate that it is produced in its precursor form and matured in the extracellular space. It is our hypothesis that the precursor form of nerve growth factor should be detectable in those cell types producing it. To date, limitations in available immunohistochemical tools have restricted efforts in obtaining an accurate distribution of nerve growth factor in the skin of naïve animals and those with neuropathic pain lesions. It is the objective of this study to delineate the distribution of the precursor form of nerve growth factor to those cell types expressing it, as well as to describe its distribution with respect to those nerve fibers responsive to it. We observed a decrease in peptidergic fiber innervation at 1 week after the application of a chronic constriction injury (CCI) to the sciatic nerve, followed by a recovery, correlating with TrkA protein levels. ProNGF expression in CCI animals was significantly higher than in sham-operated controls from 1-4 weeks post-CCI. ProNGF immunoreactivity was increased in mast cells at 1 week post-CCI and, at later time points, in keratinocytes. P75 expression within the dermis and epidermis was significantly higher in CCI-operated animals than in controls and these changes were localized to neuronal and non-neuronal cell populations using specific markers for each. We describe proNGF expression by non-neuronal cells over time after nerve injury as well as the association of NGF-responsive fibers to proNGF-expressing target tissues. ProNGF expression increases following nerve injury in those cell types previously suggested to express it.


Botulinum toxin A versus bupivacaine trigger point injections for the treatment of myofascial pain syndrome: a randomised double blind crossover study.
The treatment of myofascial pain syndrome (MPS) is diverse and includes trigger point injections of various substances including local anesthetics, steroids and Botulinum toxin A (BTX A). The purpose of this study was to compare the effectiveness of trigger point injections using BTX A versus bupivacaine, both in combination with a home-based rehabilitation program. To be enrolled, subjects first had to demonstrate responsiveness to bupivacaine trigger point injection. In this single center, double blind, randomized, cross-over trial, 18 patients with MPS received trigger point injections of either 25 units Botulinum toxin A or 0.5 ml of 0.5% bupivacaine per trigger point. A maximum of eight trigger points were injected per subject. Subjects were followed until their pain returned to 75% or more of their pre-injection pain for two consecutive weeks, after which there was a 2 week wash-out period. The subjects then crossed over and had the same trigger points injected with the other agent. All subjects participated in a home exercise program involving static stretches of the affected muscles. Both treatments were effective in reducing pain when compared to baseline (P=0.0067). There was, however, no significant difference between the BTX A and 0.5% bupivacaine groups in duration or magnitude of pain relief, function, satisfaction or cost of care (cost of injectate excluded). Considering the high cost of BTX A, bupivacaine is deemed a more cost-effective injectate for MPS.


[Detection of pregnancy-specific beta 1-glycoproteins (SP1) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum. Diagnostic significance in intrauterine fetal retardation].
The problem was to prove the value of SP1 (pregnancy specific beta 1-glycoprotein) and PAPP-A (pregnancy-associated plasmaprotein A) estimations in maternal serum samples for diagnosis of intrauterine growth retardation (IUGR). After delivery the pediatrician confirmed the diagnose of IUGR by means of clinical assessment. SP1 was estimated in 25 serum samples from 8 patients with IUGR and in 36 samples from healthy women by means of single radial immunodiffusion (24h-RID). Low SP1-values were found in serum samples from 4 patients with IUGR. There was a significant correlation (p less than 0,01) between SP1 concentrations and pregnancy weeks only in the control group. The regression line of the IUGR group was not different from 0 significantly. The estimations of PAPP-A were performed in 17 serum samples from 6 patients with IUGR. 24 serum samples from 12 healthy pregnant women were applied to control group. There was no difference between the 2 groups. PAPP-A is not suitable for diagnosis of IUGR.


Differences between zofenopril and ramipril, two ACE inhibitors, on cough induced by citric acid in guinea pigs: role of bradykinin and PGE2.
Dry and persistent cough is one of the commonest side effects experienced by patients treated with angiotensin-converting enzyme (ACE) inhibitors for the therapy of hypertension and congestive heart failure. The present study investigated the effect of zofenopril and ramipril on cough induced by citric acid in guinea pig and the involvement of bradykinin (BK) and prostaglandin E2 (PGE2) in mediating the responses of these drugs. Zofenopril (10 mg/kg) or ramipril (3-10 mg/kg), which is threefold more potent than zofenopril, on a mg basis, in lowering blood pressure, was orally administered daily in drinking water for 2 weeks. At the end of this period, aerosol of citric acid solution (0.1 M) was performed and the number of cough counted for 10 min. The role of the kinin B(2) receptor was also investigated. BK and PGE2 levels in the bronchoalveolar lavage (BAL) fluid were measured after repeated oral treatment with zofenopril or ramipril (10 mg/kg). Ramipril (3-10 mg/kg) increased citric acid-induced cough by 40% and 60%, respectively, as compared to the vehicle control group (15.0 ± 1.8), while zofenopril (10 mg/kg) was without effect. The enhancement of citric acid-induced cough caused by ramipril (10 mg/kg) was reduced by the kinin B(2) receptor antagonist MEN16132 (0.25 mg/kg ip). BK and PGE2 levels in the BAL fluid were increased, in comparison to the control group, after ramipril treatment, while they were unchanged after zofenopril administration. Zofenopril, contrary to ramipril, did not affect either citric acid-induced cough in the guinea pigs or BK and PGE2 production in the airways.


Pretreatment methods prior to gaschromatographic analysis of volatile fatty acids from faecal samples.
Vacuum distillation and steam distillation have been compared as pretreatment methods prior to the GC analysis of volatile fatty acids (VFA) in faecal material. Vacuum distillation resulted in a recovery range of 90-110% for all VFA in standard solutions. This was superior to the recovery ranges found after pretreatment by steam distillation. Coefficients of variance for steam distilled samples were higher than for vacuum distilled samples. Using a faecal homogenate, the vacuum distillation method was found to be highly reproducible. Spiking experiments substantiated the quantitative recovery of VFA from vacuum distilled samples. Modifications of the standard vacuum distillation procedure showed that care must be taken to ensure adequate cooling of the receiver tube.


Sparse pixel image sensor.
As conventional frame-based cameras suffer from high energy consumption and latency, several new types of image sensors have been devised, with some of them exploiting the sparsity of natural images in some transform domain. Instead of sampling the full image, those devices capture only the coefficients of the most relevant spatial frequencies. The number of samples can be even sparser if a signal only needs to be classified rather than being fully reconstructed. Based on the corresponding mathematical framework, we developed an image sensor that can be trained to classify optically projected images by reading out the few most relevant pixels. The device is based on a two-dimensional array of metal-semiconductor-metal photodetectors with individually tunable photoresponsivity values. We demonstrate its use for the classification of handwritten digits with an accuracy comparable to that achieved by readout of the full image, but with lower delay and energy consumption.


Zinc levels in seminal plasma and their correlation with male infertility: A systematic review and meta-analysis.
Zinc is an essential trace mineral for the normal functioning of the male reproductive system. Current studies have investigated the relationship between seminal plasma zinc and male infertility but have shown inconsistent results. Hence, we systematically searched PubMed, EMBASE, Science Direct/Elsevier, CNKI and the Cochrane Library for studies that examined the relationship between seminal plasma zinc and male infertility, as well as the effects of zinc supplementation on sperm parameters. Twenty studies were identified, including 2,600 cases and 867 controls. Our meta-analysis results indicated that the seminal plasma zinc concentrations from infertile males were significantly lower than those from normal controls (SMD (standard mean differences) [95% CI] -0.64 [-1.01, -0.28]). Zinc supplementation was found to significantly increase the semen volume, sperm motility and the percentage of normal sperm morphology (SMD [95% CI]: -0.99 [-1.60, -0.38], -1.82 [-2.63, -1.01], and -0.75 [-1.37, -0.14], respectively). The present study showed that the zinc level in the seminal plasma of infertile males was significantly lower than that of normal males. Zinc supplementation could significantly increase the sperm quality of infertile males. However, further studies are needed to better elucidate the correlation between seminal plasma zinc and male infertility.


Suicide risk in the elderly: data from Brazilian public health care program.
Examine prevalence and level of suicide risk, and its associations with sociodemographic factors and mood disorders. A cross-sectional study with a random sample of 530 individuals aged 60 years or more from Family Health Strategy of Porto Alegre, Brazil. Diagnosis was made by psychiatrists using the Mini International Neuropsychiatric Interview plus (MINIplus). Suicide risk was found in 15.7% of the sample. Female gender, elderly with no income or with no paid activity and those who have lost one or more of his sons presented association with suicide risk. Bipolar disorder shows association with suicide risk for those with or without current episode. For unipolar depression only elderly with a current episode shows association with suicide risk. The cross-sectional design limits the examination of causative relationships. The MINIplus questions are not broad enough to assess other important self-destructive behaviors. A high rate of suicide risk was found. As expected an increased rate of mood disorders were related to the risk of suicide. The loss of sons may partly explain a subtype of late-life risk of suicide or mood disorders especially in the oldest-old. These findings can be a useful to generate other research hypothesis and for health professionals who care older persons. Detecting characteristics linked to suicide, therefore opening up the possibility of preventing tragic outcomes providing a proper treatment.


Analysis of human prostate cancers and cell lines for mutations in the TP53 and KLF6 tumour suppressor genes.
A recent report suggests that the KLF6 gene encoding the Krüppel-like factor 6 protein is a frequently mutated, putative tumour suppressor gene in prostate cancer. The aims of the present study were to confirm these initial findings by determining the frequency of exon2 KLF6 mutations in a cohort of European prostate cancer patients, and to investigate whether there was evidence for mutational inactivation of both the KLF6 and TP53 tumour suppressor loci in some tumours. We examined 32 primary prostate tumours and three prostate tumour cell lines for mutations by PCR amplification and direct dideoxy sequencing (KLF6), and by oligonucleotide microarray (p53GeneChip) analysis and dideoxy sequencing (TP53). Whereas TP53 mutations typical of prostate cancer were found at a frequency consistent with the literature, no KLF6 mutations were found in any of the tumour samples nor in the three prostate cancer cell lines.


Endometrial cancer following radiation therapy for cervical cancer.
The clinical and histologic features of eight cases of carcinoma of the endometrium which developed following radiation therapy for squamous cell carcinoma of the cervix are described. No patient had a well-differentiated tumor and significant myometrial invasion was present in all cases. Three of the eight tumors were papillary serous adenocarcinoma. Five of the eight patients developed recurrent tumor and died of their disease. The risk of endometrial cancer in patients previously radiated for cervical cancer is evaluated.


Cloning, sequencing and developmental expression of the genes encoding S4 and S10 ribosomal proteins in the cellular slime mould Dictyostelium discoideum.
The sequences of the rps4 and rps10 genes encoding the Dictyostelium discoideum homologues of the basic ribosomal proteins S4 and S10 were determined from cDNA and genomic DNA clones. They are expressed respectively as 266 and 153 amino-acid-long proteins. In both cases, the N-terminal methionine is cleaved in the mature proteins. S4 contains two putative nuclear targeting signals and displays a strong overall identity (around 60%) to eukaryotic S4 homologues. The rps10 gene harbours a 314-bp intron located close to its 5'-coding end. The overall identity between D. discoideum S10 and eukaryotic homologues is around 38% and rises to 53% in the N-terminal domain. Southern blots suggest that both S4 and S10 are encoded by single genes that are regulated during development. The corresponding mRNAs decrease sharply after 8 h of differentiation.


Cortical thickness and surface area correlates with cognitive dysfunction among first-episode psychosis patients.
In studies using magnetic resonance imaging (MRI), some have reported specific brain structure-function relationships among first-episode psychosis (FEP) patients, but findings are inconsistent. We aimed to localize the brain regions where cortical thickness (CTh) and surface area (cortical area; CA) relate to neurocognition, by performing an MRI on participants and measuring their neurocognitive performance using the Cambridge Neuropsychological Test Automated Battery (CANTAB), in order to investigate any significant differences between FEP patients and control subjects (CS). Exploration of potential correlations between specific cognitive functions and brain structure was performed using CANTAB computer-based neurocognitive testing and a vertex-by-vertex whole-brain MRI analysis of 63 FEP patients and 30 CS. Significant correlations were found between cortical parameters in the frontal, temporal, cingular and occipital brain regions and performance in set-shifting, working memory manipulation, strategy usage and sustained attention tests. These correlations were significantly dissimilar between FEP patients and CS. Significant correlations between CTh and CA with neurocognitive performance were localized in brain areas known to be involved in cognition. The results also suggested a disrupted structure-function relationship in FEP patients compared with CS.


Health care provider and patient preparedness for alternative colorectal cancer follow-up; a review.
Follow-up after curative treatment for colorectal cancer (CRC) puts pressure on outpatient services due to the growing number of CRC survivors. The aim of this state-of-the-art review was to evaluate setting, manner and provider of follow-up. Moreover, perceptions of CRC survivors and health care providers regarding standard and alternative follow-up were examined. After a comprehensive literature search of the PubMed database, 69 articles were included reporting on CRC follow-up in the hospital, primary care and home setting. Hospital-based follow-up is most common and has been provided by surgeons, medical oncologists, and gastroenterologists, as well as nurses. Primary care-based follow-up has been provided by general practitioners or nurses. Even though most hospital- or primary care-based follow-up care requires patients to visit the clinic, telephone-based care has proven to be a feasible alternative. Most patients perceived follow-up as positive; valuing screening and detection for disease recurrence and appreciating support for physical and psychosocial symptoms. Hospital-based follow-up performed by the medical specialist or nurse is highly preferred by patients and health care providers. However, willingness of both patients and health care providers for alternative, primary care or remote follow-up exists. Nurse-led and GP-led follow-up have proven to be cost-effective alternatives compared to specialist-led follow-up. If proven safe and acceptable, remote follow-up can become a cost-effective alternative. To decrease the personal and financial burden of follow-up for a growing number of colorectal cancer survivors, a more acceptable, flexible and dynamic care follow-up mode consisting of enhanced communication and role definitions among clinicians is warranted.


Adjudication history and African American adolescents' risk for acquiring sexually transmitted diseases: an exploratory analysis.
Little is known about sexually transmitted disease (STD) risk behavior among adjudicated African American adolescents. The goal of the study was to compare STD-associated risk profiles of African American adolescents reporting a history of adjudication and those not reporting adjudication. A cross-sectional survey of 304 African American adolescent males and females (aged 15-21 years) was conducted. Adolescents were recruited from primary care clinics and through outreach activities. Twenty-six percent of the adolescents reported adjudication. After adjusting for gender, adjudicated adolescents were about 3.6 and 4.5 times, respectively, more likely than nonadjudicated adolescents to report ever having one of three STDs (gonorrhea, chlamydia, and trichomoniasis) or to report having one of these in the past 90 days. Reporting recent sex with someone known or suspected of having an STD was about nine times more likely among adjudicated adolescents, and they were about 2.6 times more likely than their nonadjudicated counterparts to report using drugs or alcohol during their last sexual experience and 2.2 times more likely to report frequent sex in the past 90 days. African American adolescents with a history of adjudication may have greater risk for acquisition of STDs than their peers not reporting adjudication.


[Rehabilitation of an edentulous patient with implant supported all-porcelain bridges after orthognathic surgery].
This case report presents a 43-year-old woman who was not happy with her complete dentures both from the functional and the esthetic point of view. The combined therapy of orthognathic surgery, insertion of endosteal oral implants and the loading with all-porcelain cantilevered bridges made out of In-Ceram is reported.


A method for expansion and retroviral transduction of mouse regulatory T cells.
Adoptive cell therapy with genetically modified regulatory T cells (Tregs) is under clinical investigation for the treatment of transplant rejection and various autoimmune conditions. A limitation of modelling this approach in mice is the lack of optimized protocols for expanding and transducing mouse Tregs. Here we describe a protocol for purifying, expanding and retrovirally transducing mouse Tregs with a vector encoding a chimeric antigen receptor as a model transgene. We found that isolation of Tregs from C57Bl/6J Foxp3EGFP mice solely based on eGFP expression resulted in sufficiently pure cells; co-sorting of CD25hi cells was not essential. Although expansion with rapamycin reduced Treg expansion, it promoted maximal in vitro suppressive activity. Retroviral transduction of Tregs following 2 days of stimulation with anti-CD3/CD28 beads achieved a transduction efficiency of ~40% and did not impair their suppressive capacity. When injected into a conventional T cell (Tconv)-transfer-induced colitis model, transduced Tregs inhibited colitis progression at ratios as low as 1 Treg to 100 Tconvs, and maintained Foxp3 and transgene expression throughout an 8-week period. This method facilitates the study of transduced Tregs in animal models and will enable the study of genetically engineered Treg therapy for a variety of inflammatory diseases.


A 37-year-old spinal cord-injured female patient, transplanted of multipotent stem cells from human UC blood, with improved sensory perception and mobility, both functionally and morphologically: a case study.
HLA-matched UC blood-derived multipotent stem cells were directly transplanted into the injured spinal cord site of a 37-year-old female patient suffering from spinal cord injury (SPI). In this case, human cord blood (UCB)-derived multipotent stem cells improved sensory perception and movement in the SPI patient's hips and thighs within 41 days of cell transplantation. CT and MRI results also showed regeneration of the spinal cord at the injured site and some of the cauda equina below it. Therefore, it is suggested that UCB multipotent stem cell transplantation could be a good treatment method for SPI patients.


Pathologic sequelae of vascular cognitive impairment and dementia sheds light on potential targets for intervention.
Vascular contributions to cognitive impairment and dementia (VCID) is one of the leading causes of dementia along with Alzheimer's disease (AD) and, importantly, VCID often manifests as a comorbidity of AD(Vemuri and Knopman 2016; Schneider and Bennett 2010)(Vemuri and Knopman 2016; Schneider and Bennett 2010). Despite its common clinical manifestation, the mechanisms underlying VCID disease progression remains elusive. In this review, existing knowledge is used to propose a novel hypothesis linking well-established risk factors of VCID with the distinct neurodegenerative cascades of neuroinflammation and chronic hypoperfusion. It is hypothesized that these two synergistic signaling cascades coalesce to initiate aberrant angiogenesis and induce blood brain barrier breakdown trough a mechanism mediated by vascular growth factors and matrix metalloproteinases respectively. Finally, this review concludes by highlighting several potential therapeutic interventions along this neurodegenerative sequalae providing diverse opportunities for future translational study.


Biochemical and white blood cell profiles of baboon neonates consuming formulas with moderate and high dietary long-chain polyunsaturated fatty acids.
Clinical chemistry and complete blood count (CBC) values were determined in 14 term baboons (Papio species) consuming formula with moderate or high levels of dietary long-chain polyunsaturated fatty acids (LCPUFA) from 2-12 weeks of age. Neonates were randomized to three groups: C: Control, no LCPUFA; L: 0.33% docosahexaenoic acid (DHA)/0.67% arachidonic acid (ARA) (w/w); L3:1.00% DHA/0.67% ARA (w/w). Blood chemistries were assessed at 6 and 12 weeks and CBC parameters were measured at 2, 4, 8, 10, 12 weeks of age. Dietary LCPUFA had significant effects on serum triglyceride (C > L,L3) and calcium (L > C,L3). No other significant effects of diet were detected; pooled values are presented for all other parameters. These data provide longitudinal biochemical and white cell/platelet/immunological data on LCPUFA-fed baboons over the first 12 weeks of life. Data ranges are similar to reference data in cases for which values exist and hematological changes reflect trends observed during human neonatal development.


Differences in albumin distribution and dynamics between toxaemic and non-toxaemic pregnant women.
By using least squares curve fitting techniques, double exponential curves were fitted to points representing the decay of plasma 131I-albumin after blood volume estimation of 48 pregnant women. Data from the fitted curves provided estimates of the distribution of albumin between plasma and extravascular compartments, exchange between the two and rate of albumin catabolism. The lower total extracellular albumin mass of a group of 23 severely toxaemic patients was shown to arise solely from the difference in plasma albumin mass between this group and the remaining 25 patients. Comparison of these results with those in the literature suggests that pregnant women have a higher proportion of their exchangeable albumin mass in the plasma compartment and a higher rate of albumin catabolism than non-pregnant women.


A proposed mechanism for detergent-assisted foam fractionation of lysozyme and cellulase restored with beta-cyclodextrin.
Foam fractionation by itself cannot effectively concentrate hydrophilic proteins such as lysozyme and cellulase. However, the addition of a detergent to a protein solution can increase the foam volume, and thus, the performance of the foam fractionation process. In this article, we propose a possible protein concentration mechanism of this detergent-assisted foam fractionation: A detergent binds to an oppositely charged protein, followed by the detergent-protein complex being adsorbed onto a bubble during aeration. The formation of this complex is inferred by a decrease in surface tension of the detergent-protein solution. The surface tension of a solution with the complex is lower than the surface tension of a protein or a detergent solution alone. The detergent can then be stripped from the adsorbed protein, such as cellulase, by an artificial chaperone such as beta-cyclodextrin. Stripping the detergent from the protein allows the protein to return to its original conformation and to potentially retain all of its original activity following the foam fractionation process. Low-cost alternatives to beta-cyclodextrin such as corn dextrin were tested experimentally to restore the protein activity through detergent stripping, but without success.


Effect of enzymatic degradation on the mechanical properties of biological scaffold materials.
Biological scaffolds must support a complex balance of resisting enzymatic degradation while promoting tissue remodeling. Thus, the purpose of this study was to evaluate the effects of in vitro enzymatic exposure on the mechanical properties of biological scaffolds. It was hypothesized that exposure to an enzyme solution would result in decreased tensile strength and that crosslinked scaffolds would resist enzymatic degradation more effectively than noncrosslinked scaffolds. Nine scaffolds were evaluated (four porcine dermis: Permacol™, CollaMend™, Strattice™, XenMatrix™; two human dermis: AlloMax™, FlexHD(®); two bovine pericardium: Veritas(®), PeriGuard(®); and one porcine small intestine submucosa: Surgisis™). Ten specimens (n = 10) were hydrated in saline at 37 °C and subjected to uniaxial testing to establish baseline properties. 50 specimens (n = 50) were incubated in collagenase solution at 37 °C for 2, 6, 12, 24, or 30 h (n = 10 each group) followed by uniaxial tensile testing. Tensile strength was significantly reduced after 30 h for CollaMend™, AlloMax™, Veritas(®), Strattice™, XenMatrix™, Permacol™, and FlexHD(®) (p < 0.01), while PeriGuard(®) demonstrated a slight increase in tensile strength (p = 0.0188). Crosslinked bovine pericardium (PeriGuard(®)) maintained greater tensile strength than noncrosslinked bovine pericardium (Veritas(®)) throughout all exposure periods (p < 0.0001). Similarly, crosslinked porcine dermis (Permacol™) maintained greater tensile strength than noncrosslinked porcine dermis (Strattice™ and XenMatrix™) throughout all exposure periods (p < 0.0001). Materials that deteriorate rapidly after in vitro enzymatic exposure may also deteriorate rapidly in vivo, particularly when exposed to a wound environment with elevated levels of matrix metalloproteinases. Permacol™, CollaMend™, Strattice™, FlexHD(®), and PeriGuard(®) survived the longest incubation period (30 h) and withstood mechanical testing. XenMatrix™, AlloMax™, Veritas(®), and Surgisis™ degraded more quickly and did not survive the longer exposure periods. Scaffolds that maintain strength characteristics after in vitro collagenase exposure may be advantageous for long-term hernia repair scenarios where elevated enzyme levels are expected.


Multicenter, randomized, double-blinded, placebo-controlled study of rabacfosadine in dogs with lymphoma.
Rabacfosadine (RAB, Tanovea-CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs. To determine the efficacy and safety of RAB in dogs with lymphoma. One hundred and fifty-eight client-owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019. Dogs were randomized to receive RAB or placebo at a 3 : 1 ratio. Treatment was given every 21 days for up to 5 treatments. Study endpoints included progression-free survival (PFS), overall response rate (ORR) at a given visit, best overall response rate (BORR), and percent progression free 1 month after treatment completion. Safety data were also collected. The median PFS was significantly longer in the RAB group compared to placebo (82 vs 21 days; P < .0001, HR 6.265 [95% CI 3.947-9.945]). The BORR for RAB-treated dogs was 73.2% (50.9% complete response [CR], 22.3% partial response [PR]) and 5.6% (0% CR, 5.6% PR) for placebo-treated dogs (P < .0001). One month after the last treatment, 37 RAB-treated dogs (33%) were progression free compared with no placebo-treated dogs (P < .0001). The most common adverse events observed in the RAB group were diarrhea (87.5%), decreased appetite (68.3%), and vomiting (68.3%) and were generally low grade and reversible. Serious adverse events were reported in 24 RAB-treated (20%) and 5 placebo-treated dogs (13%). Rabacfosadine demonstrated statistically significant antitumor efficacy in dogs with lymphoma when administered every 21 days for up to 5 treatments as compared to placebo.


[Infantile cryptosporidiosis in Sousse area, Tunisia].
The aim of this study was to evaluate infantile cryptosporidiosis prevalence in central Tunisia. Stool samples from 34,020 immunocompetent children were investigated for oocysts through a 12-year study. Cryptotosporidia were detected in 0.32% (108) of samples. Ninety three per cent of children were less than five years old. Incidence was much higher in summer and autumn. Leading clinical symptoms were diarrhea, fever and vomiting. Symptoms spontaneously resolved in all patients. In three cases, infection was asymptomatic. Data analysis indicate that cryptosporidiosis is not uncommon in diarrheic central Tunisian children.


Are signal intensity and homogeneity useful parameters for distinguishing between benign and malignant soft tissue masses on MR images? Objective evaluation by means of texture analysis.
To objectively identify possible differences in the signal characteristics of benign and malignant soft tissue masses (STM) on magnetic resonance (MR) images by means of texture analysis and to determine the value of these differences for computer-assisted lesion classification. Fifty-eight patients with histologically proven STM (benign, n=30; malignant, n=28) were included. STM texture was analyzed on routine T1-weighted, T2-weighted and short tau inversion recovery (STIR) images obtained with heterogeneous acquisition protocols. Fisher coefficients (F) and the probability of classification error and average correlation coefficients (POE+ACC) were calculated to identify the most discriminative texture features for separation of benign and malignant STM. F>1 indicated adequate discriminative power of texture features. Based on the texture features, computer-assisted classification of the STM by means of k-nearest-neighbor (k-NN) and artificial neural network (ANN) classification was performed, and accuracy, sensitivity and specificity were calculated. Discriminative power was only adequate for two texture features, derived from the gray-level histogram of the STIR images (first and 10th gray-level percentiles). Accordingly, the best results of STM classification were achieved using texture information from STIR images, with an accuracy of 75.0% (sensitivity, 71.4%; specificity, 78.3%) for the k-NN classifier, and an accuracy of 90.5% (sensitivity, 91.1%; specificity, 90.0%) for the ANN classifier. Texture analysis revealed only small differences in the signal characteristics of benign and malignant STM on routine MR images. Computer-assisted pattern recognition algorithms may aid in the characterization of STM, but more data is necessary to confirm their clinical value.


Engineered structures for use in disposable incontinence products.
The background and evolution of absorbent disposable hygiene products is discussed. The current technology used to produce disposable hygiene products such as baby diapers, feminine hygiene products and adult incontinence management products is shown to have a number of manufacturing and in-use problems. Alternative technologies, such as multilayer composite webs offer the opportunity to achieve better product weight control, and therefore better control over the other related properties, reduced raw material waste and improved functional characteristics. There are still problems to be resolved when using such composite materials, but the potential of these new technologies has now been established.


Thinking outside the box: a review of gastrointestinal symptoms and complications in cystic fibrosis.
Gastrointestinal (GI)-related symptoms, complications, and comorbidities in cystic fibrosis (CF) are common and research to reduce their burden is a priority for the CF community. To enable future research, this review aimed to summarize the range of GI symptoms, complications and comorbidities seen in CF, the underlying pathophysiology, and treatments. This was a rapid systematic review undertaken using the recommendations from the Cochrane Rapid Reviews Methods Group. We searched databases including PubMed, Embase, Medline and the Cochrane database and identified those studies reporting GI-related symptoms, complications, or comorbidities in CF or their treatment. Our searches identified 2,930 studies and a total 119 studies met our inclusion criteria. Where a prevalence could be determined, GI symptoms were reported in 33.7% of study participants. The range of symptoms reported was broad and the highest median prevalence included flatulence (43.5%), bloating and abdominal distension (36%), and fatty stool (36%). Meconium ileus was reported in 12% and distal intestinal obstruction syndrome in 8.5. GI-related symptoms, complications, and comorbidities in CF are common. More consistent characterization and recording of these symptoms in clinical studies may help achieve the priority of reducing the burden of GI disease in CF.


Childhood Infectious Encephalitis: An Overview of Clinical Features, Investigations, Treatment, and Recent Patents.
Infectious encephalitis is a serious and challenging condition to manage. This overview summarizes the current literature regarding the etiology, clinical manifestations, diagnosis, management, and recent patents of acute childhood infectious encephalitis. We used PubMed Clinical Queries as a search engine and used keywords of "encephalitis" AND "childhood" Patents were searched using the key term "encephalitis" in google.patents.- com and patentsonline.com. Viral encephalitis is the most common cause of acute infectious encephalitis in children. In young children, the clinical manifestations can be non-specific. Provision of empiric antimicrobial therapy until a specific infectious organism has been identified, which in most cases includes acyclovir, is the cornerstone of therapy. Advanced investigation tools, including nucleic acid-based test panel and metagenomic next-generation sequencing, improve the diagnostic yield of identifying an infectious organism. Supportive therapy includes adequate airway and oxygenation, fluid and electrolyte balance, cerebral perfusion pressure support, and seizure control. Recent patents are related to the diagnosis, treatment, and prevention of acute infectious encephalitis. Viral encephalitis is the most common cause of acute infectious encephalitis in children and is associated with significant morbidity. Recent advances in understanding the genetic basis and immunological correlation of infectious encephalitis may improve treatment. Third-tier diagnostic tests may be incorporated into clinical practice. Treatment is targeted at the infectious process but remains mostly supportive. However, specific antimicrobial agents and vaccines development is ongoing.


Geographical dimensions of terrestrial net and gross primary productivity.
The paper presents a comparative summary of previous attempts by the author to assess and map global primary productivity using environmental parameters as predictors. The individual components of the productivity process, net production, gross production, dark respiration as well as their regional rates are computed for 10 degree latitudinal belts. A new version of the Miami Model (Lieth, 1973, 1975) is presented predicting net primary productivity from an increased number of averages of temperature and precipitation. Net primary productivity values in form of dry matter accumulation and caloric energy equivalents are compared.


Molecular modelling and the biosynthesis of apolipoprotein B containing lipoproteins.
APOBEC-1 is the cytidine deaminase. We show by sequence alignment, molecular modelling and mutagenesis, that it is related in crystal structure to the cytidine deaminase of Escherichia coli (ECCDA). The two enzymes are both homodimers with composite active sites formed with loops from each monomer. In the sequence of APOBEC-1, three gaps compared to ECCDA match the size and contour of the minimal RNA substrate. We propose a model in which the asymmetric binding of one active site to the substrate cytidine which is positioned by the downstream binding of the product uridine and that this helps to target the other active site for deamination.


Aspects of the chemistry and toxicology of indole-diterpenoid mycotoxins involved in tremorganic disorder of livestock.
A method for the large-scale extraction ofNeotyphodium lolii (formerlyAcremonium lolii) infectedLolium perenne (perennial ryegrass) seed was optimized so as to efficiently obtain lolitrem B, the tremorgenic indole-diterpenoid compound thought to be the principal causative agent of the neurotoxic disorder ryegrass staggers. In a period of two weeks, 30 kg of seed could be processed yielding 125mg of pure, crystalline lolitrem B.In addition to lolitrem B, fifteen lolitrem analogues were isolated from the seed extracts and their structures determined by mass spectrometry and one- and two-dimensional NMR techniques. All but one of these analogues were previously unknown. Furthermore, three compounds related to paxilline, thought to be a precursor of lolitrem B were isolated fromPenicillium paxilli cultures.The isolation of the lolitrem and paxilline analogues provided much information on the likely pathways of lolitrem biosynthesis, and a detailed pathway is proposed. Paspaline was identified as the crucial intermediate in indole-diterpenoid biosynthesis, rather than paxilline, as previously thought. It is proposed that new endophyte incapable of biosynthesizing this substance will not produce any indole-diterpenoid tremorgens.Many of the lolitrem and paxilline derivatives isolated in the course of this study were tested for tremorgenic action in mice. These studies have identified a number of strucural features which are necessary for tremorgenic effect. Slow onset and long-duration tremors are characteristic of lolitrem compounds. For this effect, the acetal-linked isoprene unit and the stereochemistry at the A/B ring junction were identified as important. In contrast, paxilline compounds induce fast-onset and short-duration tremors. For this effect a C-13 α-orientated hydroxyl group is essential and the C-10 functionality is important. The extensive study of structure-activity relationships described in this thesis also suggests that lolitrem and paxilline compounds may exert their effects by binding to different target sites. Others have proposed that the more readily available paxilline be used as a model for the lolitrems in trials to select for animals resistant to ryegrass staggers, but the above observations suggest, however, that such an approach would not be successful.


Postnatal exposure to predator odor (TMT) enhances spatial learning in mice adulthood.
Adult behavioral and physiological responses are partly dependent on neonatal experiences. In several animal species, enriched/aprovished environments and stressful/appeasing events are crucial in the setting of adaptative behaviors. However, little is known about the effects of postnatal exposure to predator odor (as unconditioned fear-related stimulus) on spatial learning at adulthood. Thus, the aim of the present study was to investigate the effects of a postnatal exposure to 2,4,5-trimethylthiazoline (TMT, as a predator odor) on radial arm maze (RAM), Tolman maze (TM) and Morris water maze (MWM) in mice at adulthood. The results showed that a TMT group constituted by mice exposed postnatally during 3 weeks to TMT presented significantly better spatial learning achievements in adulthood compared to a water group, postnatally exposed to water only, as well as compared to a butanol group (butanol used as an odor without ecological significance) exposed postnatally to butanol during 3 weeks.


The role of ATP in the cytostructure of the hepatocytes.
We have previously described the preparation of hepatocytes from which the plasma membrane was removed by digitonin treatment. Such "nude" cells were found to be very stable in sucrose media containing above 50 mM NaCl or KCl, but they disintegrate near instantly in salt-free media, liberating nuclei, mitochondria, and other organelles. We show here that disintegration occurs at a physiologic pH and in the presence of oxygen. Disintegration was blocked by rotenone, oligomycin, KCN, and carboxyatractyloside, establishing that oxidative phosphorylation and ATP generation is essential for disintegration to occur. The addition of ATP, GTP, ITP, or ADP (but not AMP) in the presence of the inhibitors, induced breakdown. Taxol, an inhibitor of tubulin depolymerization and phalloidin, a drug that stabilizes actin fibers, prevented disintegration in salt-free media. The effect of these drugs was counteracted by the addition of ATP. Our results show that two conditions are essential to induce the disintegration of the nude cell: media of low ionic strength, and ATP generation. The ATP effect is likely to be of physiological significance, suggesting role of ATP generation in affecting polymerization of cytoskeletal elements.


Changes in the polynuclear aromatic hydrocarbon content of wheat grain and pasture grassland over the last century from one site in the U.K.
Crops harvested and stored from two long-term agricultural experiments started in the 1840-1850s at Rothamsted Experimental Station (U.K.) have been analyzed for polynuclear aromatic hydrocarbons (PAHs) because PAHs have increased four-to-five fold in the underlying 0-23 cm depth of soil over the last century due to atmospheric deposition. Bulked samples of herbage and wheat grain were analyzed for 16 compounds by gas chromatography-mass spectrometry for groups of years between 1860 and 1986. The sigma PAH (16 PAH) concentrations in herbage ranged between 110 and 6900 micrograms kg-1 dry weight, with fluoranthene, pyrene, benzofluoranthenes (b + j + k), chrysene and triphenylene consistently the most abundant. Benz[a]anthracene, benzo[ghi]perylene, benzo[a]pyrene, benzo[e]pyrene and indeno(1,2,3-cd)pyrene were also all important constituents. PAH concentrations in wheat grain ranged from 4 to 46 micrograms sigma PAH kg-1; the mixture of individual compounds was similar to that in herbage. Correcting for yield differences these corresponded to 37-1500 and 2.4-8.8 micrograms sigma PAH m-2 for herbage and wheat grain respectively. The lowest values were found in the most recent samples (1980s) and the highest for samples collected in 1879-81. Generally, there was a decline in the PAH burden of the vegetation with time. The temporal trends of PAHs in the samples are discussed in the context of possible sources of PAHs. Various lines of evidence indicate that the PAH concentrations in vegetation are an indication of atmospheric deposition directly onto the above-ground plant portions, and that uptake and translocation of soil-bound PAHs is of minor importance.


Family history predicts major adverse cardiovascular events (MACE) in young adults with psoriasis.
Patients with psoriasis may have increased risk of major adverse cardiovascular (CV) events (MACE), and a family history of CV disease (CVD) is an independent risk factor for MACE. We investigated the risk of first-time MACE in patients with psoriasis with or without a family history of CVD. Between January 1, 1997, and December 31, 2011, we identified 2,722,375 individuals, including 25,774 and 4504 patients with mild and severe psoriasis, through administrative registers. Incidence rate ratios were estimated by Poisson regression. Mean baseline age was 26.6 (SD 8.6) years. A family history of CVD was found among 16,080 (62.4%) and 3009 (66.8%) patients with mild and severe psoriasis, respectively. In patients with psoriasis and a family history of CVD, the adjusted incidence rate ratios (95% CI) of MACE were 1.28 (1.12-1.46) and 1.62 (1.14-2.30) for mild and severe disease, respectively. In patients with psoriasis but without a family history of CVD, there was no increased risk of MACE. Results may not apply to late-onset psoriasis. A family history of CVD predicted the risk of first-time MACE in young adults with psoriasis. The findings call for increased focus on a family history of CVD in CV risk assessment of patients with psoriasis.


Socio-demographic patterns in hospital admissions and accident and emergency attendances among young people using linkage to NHS Hospital Episode Statistics: results from the Avon Longitudinal Study of Parents and Children.
In England emergency hospital admissions among children are increasing and the under 25s are the most frequent attenders of A&E departments. Children of lower socio-economic status (SES) have poorer health outcomes and higher hospital admission rates. NHS Hospital Episode Statistics (HES) are increasingly being used for research but lack detailed data on individual characteristics such as SES. We report the results of an Avon Longitudinal Study of Parents and Children (ALSPAC) study that linked the data of 3,189 consenting participants to HES. We describe rates of hospital admission, emergency readmissions, and A&E attendances and examine socio-demographic correlates of these. Subjects were singletons and twins enrolled in ALSPAC who had provided consent for linkage to their health records by the study cut-off date (31.02.12). Linkage was carried out by the Health and Social Care Information Centre (now NHS Digital). We examined rates of admissions between birth and age 20 and A&E attendances between 14 and 20 years. Socio-demographic information collected in ALSPAC questionnaires during pregnancy were used to examine factors associated with admissions, emergency readmissions (an emergency admission within 30 days of discharge) and A&E attendances. Excluding birth records, we found at least one admission for 1,792/3,189 (56.2%) participants and 4,305 admissions in total. Admission rates were highest in the first year of life. Among males, admissions declined until about age 5 and then remained relatively stable; conversely, among females, they increased sharply from the age of 15. ICD 10 chapters for diseases of the digestive system and injury and poisoning accounted for the largest proportions of admissions (15.8 and 14.5%, respectively). Tooth decay was the highest single cause of admission for those aged 5-9 years. Overall, 1,518/3,189 (47.6%) of participants attended A&E at least once, with a total of 3,613 attendances between age 14 and 20 years. Individuals from more deprived backgrounds had higher rates of admissions, readmissions and A&E attendances. Linkage between cohort studies such as ALSPAC and HES data provides unique opportunities for detailed insights into socio-demographic and other determinants of hospital activity, which can inform secondary care demand management in the NHS.


Analysis of 1983 cases of malignant lymphoma in Thailand according to the World Health Organization classification.
Studying a large series of malignant lymphoma is important to increasing our understanding of this disease. Based on the World Health Organization classification system, 1983 cases of lymphoma at Siriraj Hospital were classified as either non-Hodgkin lymphoma (NHL) (92.1%) or Hodgkin lymphoma (HL) (7.9%). The NHL cases were 75% B cell type and 25% T cell type. Diffuse large B-cell lymphoma, unspecified peripheral T-cell lymphoma, follicular lymphoma, extranodal marginal zone B-cell lymphoma, precursor T lymphoblastic lymphoma, and Burkitt lymphoma accounted for 84.3% of all NHL cases found. Mixed cellularity and nodular sclerosis types constituted 77.7% of the HL cases found. An overall male preponderance was observed, but sex distribution differed among various types of lymphoma, and a female preponderance was observed in the elderly subjects. Changes in the frequency of B-cell NHL by age were characteristic: <50% in the first decade of life, a further decrease in the second decade, >60% in the third decade, and increases thereafter, reaching 90% after the seventh decade. High frequency of follicular lymphoma in Bangkok but low frequency in the Northeastern region and high frequency of HL in the Southern region were significant (P <0.05). Extranodal involvement was observed in 58.7% of NHLs, commonly affecting the upper aerodigestive tract and gastrointestinal tract, with some differences in geographical distribution. Higher frequencies of T-cell NHLs involving extranodal sites and of B-cell NHLs involving lymph nodes were significant (P <0.05). The distribution of various types of lymphoma and comparison with other large series of lymphoma further demonstrates the heterogeneity of this disease.


Identification and relative contributions of environmental driving factors for abundant and rare bacterial taxa to thermal stratification evolution.
The thermal stratification of reservoir affects water quality, and water quality evolution is largely driven by microorganisms. However, few studies have been conducted on the response of abundant taxa (AT) and rare taxa (RT) to thermal stratification evolution in reservoirs. Here, using high-throughput absolute quantitative techniques, we examined the classification, phylogenetic diversity patterns, and assembly mechanisms of different subcommunities during different periods and investigated the key environmental factors driving community construction and composition. The results showed that community and phylogenic distances of RT were higher than AT (P < 0.001), and community and phylogenic distances of the different subcommunities were significantly positively correlated with the dissimilarity of environmental factors (P < 0.001). Nitrate (NO3--N) was the main driving factor of AT and RT in the water stratification period, and Mn was the main driving factor in the water mixing period (MP) based on redundancy analysis (RDA) and random forest analysis (RF). The interpretation rate of key environmental factors based on the selected indicator species in RT by RF was higher than that of AT, and Xylophilus (10.5%) and Prosthecobacter (0.1%) had the highest average absolute abundance in AT and RT during the water stable stratification period (SSP), whereas Unassigned had the highest abundance during the MP and weak stratification period (WSP). The network of RT and environmental factors was more stable than that of AT, and stratification made the network more complex. NO3--N was the main node of the network during the SSP, and manganese (Mn) was the main node during the MP. Dispersal limitation dominated community aggregation, the proportion of AT was higher than that of RT. Structural Equation Model (SEM) showed that NO3--N and temperature (T) had the highest direct and total effects on β-diversity of AT and RT for the SP and MP, respectively.


Psilocybin-assisted therapy for depression: A systematic review and dose-response meta-analysis of human studies.
Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a dose-response meta-analysis to find the optimal dosage of psilocybin to reduce depression scores. Following our protocol (CRD 42022220190) multiple electronic databases were searched from their inception until February 2023, to identify double-blind randomized placebo-controlled (RCTs) fixed-dose trials evaluating the use of psilocybin for adult patients with primary or secondary depression. A one-stage dose-response meta-analysis with restricted cubic splines was used. Cochrane risk of bias was used to assess risk of bias. Our analysis included seven studies with a total of 489 participants. Among these, four studies focused on primary depression (N = 366), including one study with patients suffering from treatment-resistant depression. The remaining three studies examined secondary depression (N = 123). The determined 95% effective doses per day (ED95) were 8.92, 24.68, and 36.08 mg/70 kg for patients with secondary depression, primary depression, and both subgroups, respectively. We observed significant dose-response associations for all curves, each plateauing at different levels, except for the bell-shaped curve observed in the case of secondary depression. Additionally, we found significant dose-response associations for various side effects, including physical discomfort, blood pressure increase, nausea/vomiting, headache/migraine, and the risk of prolonged psychosis. In conclusion, we discovered specific ED95 values for different populations, indicating higher ED95 values for treatment-resistant depression, primary depression, and secondary depression groups. Further RCTs are necessary for each population to determine the optimal dosage, allowing for maximum efficacy while minimizing side effects.


[The place of patients and their families as healthcare stakeholders in Europe].
In the context of the Erasmus student exchange program, nursing students in the second year of their studies at the Institut de Formation en Soins Infirmiers Lionnois (Lionnois Nursing Care Training Institute) in Nancy undertook internships in different European countries. The place given to patients and their families as healthcare stakeholders takes on various forms. Some students share their experience and talk about the situations they encountered in Estonia, Italy and Romania.


An Investigation of the Relationship Between 18F-FDG PET/CT Parameters of Primary Tumors and Lymph Node Metastasis in Resectable Non-small Cell Lung Cancer.
Mediastinal lymph node metastasis is an important prognostic factor in non-small cell lung cancer (NSCLC) patients without distant metastases. 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) is recommended for detecting and staging lymph nodes and distant metastases in NSCLC patients. This study aims to investigate whether maximum standardized uptake (SUVmax), mean standardized uptake (SUVmean), metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG) values of the primary tumor measured by 18F-FDG PET/CT in resectable NSCLC can predict preoperative lymph node metastasis. This retrospective study included eighty NSCLC patients who underwent preoperative Positron Emission Tomography/Computed Tomography (PET/CT) for diagnosis and staging. The patients were stage I-III and had no distant metastases. Tumor metabolic parameters such as SUVmax, SUVmean, MTV, and TLG at PET/CT imaging were measured for preoperative diagnosis and staging, and the postoperative pathology results of the patients were examined. The pathology results divided patients into two groups; with and without lymph node metastasis. The groups were compared with student's t-test and chi-square test with regard to 18F-FDG PET/CT tumor metabolic parameters and other parameters. Fifteen (18.8%) patients were female, and 65 (81.3%) were male. According to the postoperative pathology results, while 30 (37.5%) patients had lymph node metastasis, 50 (62.5%) did not. There was a significant difference between the groups regarding tumor SUVmax and SUVmean values (p = 0.036, p = 0.045). Overall survival in the N0 group was significantly higher than in the N1 + N2 group (p = 0.034); median survival was 30.2 months in N0 group cases and 27.3 months in N1 and N2 groups. SUVmax and SUVmean values are significantly higher in patients with lymph node metastases than in patients without lymph node metastases, and this finding may provide useful information for predicting lymph node metastasis in patients with resectable NSCLC.


The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Use of mannitol.
There are two "class 1" studies, and one "class 2" study, and a large body of "Class 3" data, which can be used to support mannitol. The evidence supporting use of mannitol for ICP control is sufficiently strong to warrant guideline status. Mannitol is effective in reducing ICP, and its use is recommended as a guideline in the management of traumatic intracranial hypertension. Serum osmolalities >320 mOsm and hypovolemia should be avoided. There is some data to suggest that bolus administration is preferable to continuous infusion.


Correlation Between Parathyroid Hormone Levels with Urinary Magnesium Excretion in Patients with Non-Dialysis Dependent Chronic Kidney Disease.
Disorders of mineral metabolism occur in most patients with chronic kidney disease (CKD). The aim of this work was to correlate parathyroid hormone (PTH) levels with urinary magnesium excretion in patients with non-dialysis dependent CKD. Cross-sectional study. Concentrations of creatinine, magnesium, calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D] and alkaline phosphatase (ALP) were determined in blood samples. The assessment of urinary magnesium levels was performed by means of total daily excretion and by the excretion fraction (FEMg). The study evaluated 163 patients with a mean age of 60.7 ± 11.7 years and 51.0% were male. In the highest quartile of PTH (>89.5pg/mL), the mean levels of FEMg and ALP were higher (p<0.05). In the unadjusted regression analysis, the following variables were related to serum PTH levels: FEMg (odds ratio (OR) = 1.12; 95% confidence intervals (CI): 1.02-1.23), calcium (OR = 0.45; 95% CI: 0.22-0.90), ALP (OR = 1.02; 95% CI: 1.00-1.03) and eGFR (OR = 0.92; 95% CI: 1.00-1.03). After an adjusted analysis, only one FEMg and ALP will remain correlated with PTH. In patients with non-dialysis dependent CKD, FEMg and ALP were some variables that remained associated with PTH.


Comparative transcriptomic analysis reveals novel insights into the response to Cr(VI) exposure in Cr(VI) tolerant ectomycorrhizal fungi Pisolithus sp. 1 LS-2017.
Chromium (Cr) is one of the most toxic heavy metals and a health hazard to millions of people worldwide. Ectomycorrhizal (ECM) fungi can assist plants in phytoremediation of heavy metal contaminated soil. Cr tolerance differs among ECM fungal varieties, but the underlying molecular mechanisms of Cr tolerance in ECM fungi are not clear. This study identified, analysed and compared the Cr(VI)-induced transcriptional changes between Cr(VI)-tolerant strain (Pisolithus sp. 1 LS-2017) and Cr(VI)-sensitive strain (Pisolithus sp. 2 LS-2017) by de novo transcriptomic analysis. The results showed that 93,642 assembled unique transcripts representing the 22,353 (46.76%) unigenes matched the proteins we have known in the Nr database and 47,801 unigenes were got from the Pisolithus spp. For DEGs between the control and 10 mg/L Cr(VI) treatment, cyanoamino acid metabolic, type I diabetes mellitus metabolism, nitrogen metabolism and beta-Alanine metabolism pathways were significantly enriched (p < 0.05) in Pisolithus sp. 1 LS-2017. Two nitrate reductase family genes (nidD, niiA) provide Cr(VI) tolerance for Pisolithus sp. 1 LS-2017 by regulating Cr(VI) reduction. In addition, NO produced by nidD, niiA regulated denitrification can alleviate Cr(VI) induced oxidative stress. In Pisolithus sp. 2 LS-2017, the alcC, aldA and lcf2 gene may alleviate Cr(VI) induced oxidative stress by protecting SH groups and increasing secondary metabolism, reducing detoxify aldehydes to carboxylic acids and producing LCPUFAs respectively; .T gene regulate Cr(VI) induced wound healing by pigmentation and stability of melanin in spore; MKP2 gene accelerate Cr(VI) induced cell death and gpmA gene regulated Cr(VI) induced energy emergency.


Seeing double, being double: longing, belonging, recognition, and evasion in psychodynamic work with immigrants.
Psychically immigrants live double lives, simultaneously dwelling in the world they have left and the world in which they live, and into which most try to fit to avoid the alienating experience of being "other". Doubleness is not a conscious act, but it is a preconscious counterpoint to just about every social interaction. I argue that successful psychodynamic treatment allows immigrants to take the doubleness for granted, in effect seeing double and being double. In this way they come to effortlessly privilege one self-state over the other. The recognition and acceptance of competing self-states proves transformative in any treatment, but never more so than in working with immigrants who contend with several culturally competing selves in their daily lives and seek one relationship in which they can all be seen and heard. I describe treating an immigrant who, when I began to work with her, excelled at seeing double, but being double posed a terrifying dilemma. At least two self-states were engaged in a tug of war; she feared that the winner would take all.


Overview of the Common Core State Standard initiative and educational reform movement from the vantage of speech-language pathologists.
Educational reform is sweeping the country. The adoption and the implementation of the Common Core State Standards in almost every state are meant to transform education. It is intended to update the way schools educate, the way students learn, and to ultimately prepare the nation's next generation for the global workplace. This article will describe the Common Core State Standard initiative and the underlying concerns about the quality of education in the United States as well as the opportunities this reform initiative affords speech-language pathologists.


Detection of N-acetylcysteine, cysteine and their disulfides in urine by liquid chromatography with a dual-electrode amperometric detector.
A method for the determination of N-acetylcysteine, cysteine and their disulfides in urine is described. The thiols and disulfides are separated by reversed-phase ion-pair chromatography with octyl sodium sulfate as the ion-pairing reagent and detected with a dual-electrode amperometric detector using Au/Hg amalgam electrodes. Both the thiols and disulfides are detected with this system. In addition, dimers and mixed disulfides can be detected individually.


Asymmetric Catalytic Assembly of Triple-Columned and Multilayered Chiral Folding Polymers Showing Aggregation-Induced Emission (AIE).
Unprecedented chiral multilayer folding 3D polymers have been assembled and regulated by uniform and differentiated aromatic chromophore units between naphthyl piers. Screening catalysts, catalytic systems and monomers were proven to be crucial for asymmetric catalytic Suzuki-Miyaura polycouplings for this assembly. X-ray crystallography of the corresponding dimers and trimers revealed the absolute configuration and the intermolecular packing pattern. Up to 61 960 Mw /41 900 Mn and m/z 4317 for polymers and oligomers, as confirmed by gel permeation chromatography (GPC) and MALDI-TOF MS, indicated that these frameworks were composed of multiple stacked layers. The resulting multiple π-assemblies exhibited remarkable optical properties in aggregated states (photoluminescence in solids and aggregation-induced emission in solutions), as well as reversible redox properties in electrochemical performance.


Meta-analysis of seven heterogeneous studies on liraglutide add-on therapy in patients with type 2 diabetes mellitus treated with insulin.
Clinical trials indicate the efficacy of add-on therapy using incretin-related drugs to treat type 2 diabetes mellitus (DM) inadequately controlled by insulin. However, heterogeneity exists among these studies. Baseline body mass index (BMI) accounts for the heterogeneity of add-on therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors and the associated higher BMI with a lower efficacy. The efficacy of add-on therapy with glucagon-like peptide-1 (GLP-1) receptor agonists remains unclear. We performed a meta-analysis of randomized controlled trials of ≥12 weeks reporting the endpoint of adjusted mean change in hemoglobin A1c levels (AMΔHbA1c) or hypoglycemia incidence. Patients with type 2 DM treated with insulin alone or with metformin for at least 8 weeks before the study treatment were included. The intervention group received liraglutide co-administered with insulin or a fixed-dose combination. The control group received a placebo or insulin. Covariates included five baseline parameters (HbA1c, fasting plasma glucose, BMI, type 2 DM duration, and treatment duration). Seven studies (2067 patients) were selected. AMΔHbA1c was -1.00% (95% confidence interval [CI]: -1.21 to -0.78, I2 = 74.7%). The odds ratio for hypoglycemia incidence was 0.97 (95% CI: 0.50-1.87, I2 = 81.9%). Covariates did not account for the heterogeneity in AMΔHbA1c or hypoglycemia incidence. Liraglutide add-on therapy reduced HbA1c levels without increasing hypoglycemia incidence, independent of BMI, in insulin non-responders with type 2 DM. GLP-1 receptor agonists may be more suitable than DPP-4 inhibitors for add-on therapy in patients with high BMI. PROSPERO #CRD42021178888.


Effects of ACTH, benzodiazepines and 5-HT antagonists on escape from periaqueductal grey stimulation in the rat.
1. The effects of drugs has been studied on escape behaviour of rats following electrical stimulation of the periaqueductal grey, in order to assess the feasibility of using the latency to escape as a measure of experimental anxiety. 2. Escape latencies were decreased by methysergide and cyproheptadine, whilst lorazepam and chlordiazepoxide (CDP) increased the latencies. 3. ACTH marginally decreased escape latencies, and did not alter the response to lorazepam. 4. Difficulties associated with using this paradigm to detect anxiolytic or anxiogenic effects of drugs are discussed.


Complex Walking Tasks and Risk for Cognitive Decline in High Functioning Older Adults.
Performance on complex walking tasks may provide a screen for future cognitive decline. To identify walking tasks that are most strongly associated with subsequent cognitive decline. Community-dwelling older adults with Modified Mini-Mental State (3MS) >85 at baseline (n = 223; mean age = 78.7, 52.5% women, 25.6% black) completed usual-pace walking and three complex walking tasks (fast-pace, narrow-path, visuospatial dual-task). Slope of 3MS scores for up to 9 subsequent years (average = 5.2) were used to calculate a cognitive maintainer (slope ≥0) or decliner (slope <0) outcome variable. Logistic regression models assessed associations between gait speeds and being a cognitive decliner. A sensitivity analysis in a subsample of individuals (n = 66) confirmed results with adjudicated mild cognitive impairment (MCI) or dementia at 8-9 years post-walking assessment. Cognitive decliners were 52.5% of the sample and on average were slower for all walking tasks compared to maintainers. In models adjusted for demographic and health variables, faster fast-pace (OR = 0.87 per 0.1 m/s, 95% CI: 0.78, 0.97) and dual-task (OR = 0.84 per 0.1 m/s, 95% CI: 0.73, 0.96) gait speeds were associated with lower likelihood of being a cognitive decliner. Usual-pace gait speed was not associated (OR = 0.96 per 0.1 m/s, 95% CI: 0.85, 1.08). Results were nearly identical in analyses with adjudicated MCI or dementia as the outcome. Fast-pace and dual-task walking may provide simple and effective tools for assessing risk for cognitive decline in older individuals with high cognitive function. Such screening tools are important for strategies to prevent or delay onset of clinically meaningful change.


Family planning program activity and patient enrollment rates in the United States, 1969 and 1971.
The effects of demographic characteristics, socioeconomic conditions, health care, and family planning program activity on patient enrollment rates are estimated for 1969 and 1971. Two program activity variables (agencies and clinic locations) have significant, positive net effects in both years. The effect of agencies changed little between 1969 and 1971, and it is the strongest effect in both years. The effect of clinic locations more than doubled between 1969 and 1971, partly due to increased demand. The direct effects of the demographic, socioeconomic, and health care variables are not large, but many of the demographic and socioeconomic variables have substantial indirect effects via health care program activity.


Divergent Structural Responses to Pharmacological Interventions in Orbitofronto-Striato-Thalamic and Premotor Circuits in Obsessive-Compulsive Disorder.
Prior efforts to dissect etiological and pharmacological modulations in brain morphology in obsessive-compulsive disorder (OCD) are often undermined by methodological and sampling constraints, yielding conflicting conclusions and no reliable neuromarkers. Here we evaluated alteration of regional gray matter volume including effect size (Cohen's d value) in 95 drug-naïve patients (age range: 18-55) compared to 95 healthy subjects (age: 18-63), then examined pharmacological effects in 65 medicated (age: 18-57) and 73 medication-free patients (age: 18-61). Robustness of statistical outcomes and effect sizes was rigorously tested with Monte Carlo cross-validation. Relative to controls, both drug-naïve and medication-free patients exhibited comparable volumetric increases mainly in the left thalamus (d=0.90, 0.82, respectively), left ventral striatum (d=0.88, 0.67), bilateral medial orbitofrontal cortex (d=0.86, 0.71; 0.90, 0.73), and left inferior temporal gyrus (d=0.83, 0.66), and decreased volumes in left premotor/presupplementary motor areas (d=-0.83, -0.71). Interestingly, abnormalities in the thalamus and medial orbitofrontal cortex were present in medicated patients whereas entirely absent in premotor and ventral striatum. It suggests that pharmacotherapy elicited divergent responses in orbitofronto-striato-thalamic and premotor circuits, which warrants the design of longitudinal studies investigating the potential of these neuromarkers in stratified treatments of OCD.


Association between lipid peroxidation biomarkers and microRNA expression profiles.
In-vitro and animal studies demonstrate that epigenetic regulation may play an important role in lipid peroxidation. No human study to date has directly evaluated microRNAs (miRNAs), as epigenetic modulators, in relation to systemic levels of lipid peroxidation. To evaluate associations between systemic levels of lipid peroxidation and miRNA expression profiles in women. Included in the analysis were 92 women aged 40-70 years, a subset of the Shanghai Women's Health Study (SWHS). Lipid peroxidation was assessed by urinary markers F2-isoprostanes (F2-IsoPs), the products of free radical-catalyzed peroxidation of arachidonic acid, and its major metabolite after β-oxidation, 2,3-dinor-5,6-dihydro-15-F2t-IsoP (F2-IsoP-M), with GC/NICI-MS assays. Expression levels of 798 miRNAs were quantified in peripheral plasma with NanoString nCounter assays. A multivariable linear regression model was used to examine the association between lipid peroxidation and miRNA expression. After adjusting for potential confounders, 29 miRNAs and 213 miRNAs were associated with F2-IsoPs and F2-IsoP-M, respectively. When further controlling for multiple comparisons, none of these nominally significant associations with F2-IsoPs was retained, whereas 71 of 213 miRNAs associated with F2-IsoP-M remained. The predicted targets of the F2-IsoP-M associated miRNAs were enriched for several lipid peroxidation-related processes such as PI3K/AKT, MAPK, FOXO and HIF-1 signaling pathways. Moreover, 10 miRNAs (miR-93-5p, miR-761, miR-301b-3p, miR-497-5p, miR-141-3p, miR-186-5p, miR-126-3p, miR-200b-3p, miR-520d-3p, and miR-363-3p) exhibited functional interactions with 50 unique mRNAs targets involved in the regulation of β-oxidation. To our knowledge, this study, for the first time, provides human data suggesting that miRNA expression may be linked to lipid peroxidation products and their metabolism.


Administrative Databases and Diagnostic Therapeutic and Assistance Paths -PDTA- in the Monitoring Treatment of Rheumatoid Arthritis: The Experience of ATS Pavia.
The current flows of the SSN represent the set of interest whose interconnection alone justifies the current study. These flows can be interconnected with other sources, institutional or otherwise, in order to answer well-defined questions. The objective of the study is to verify, through the analysis of administrative databases, any differences in the consumption of health resources between biological off-patent originator drugs and biosimilars in real clinical practice, with particular reference to the rheumatology area. Through the use of assisted databases (BDA) of ATS Pavia we evaluated the differences in terms of consumption of health resources related to the different drugs under analysis. Annual and daily costs were calculated by total patient cost, stratified for different treatments, considering the sum of total costs for the prescriptions of drugs subject to the analysis. Another objective was to evaluate the adherence of the drugs of interest, by utilizing specific indicators (MPR). A total of 145 patients were analyzed. Among enrolled patients, 26.9% of users were treated with a biosimilar drug, while 73.1% with a biologic originator. Adherence is higher if it is considered the population treated with biosimilar drugs (82.1%). Total cost (including drug prescriptions, hospitalizations, outpatient services, tests for any cause) during the observation period of 1 year is 14,274.08. 87.7% of the total is attributable to drugs. Non-hospitalized patients are the least expensive, whether they were treated with biologics or biosimilars. In our sample, biosimilar drugs tend to be underused: the treatment of a patient with a chronic autoimmune disease is a clinical process that involves many health professionals, and a criticality could also derive from the difficult communication between the various professional figures who get involved with the whole patient treatment.


Immunosuppressive treatment of HBsAg-positive chronic liver disease: significance of HBeAg.
In a randomized clinical trial in 148 patients of azathioprine vs. prednisone treatment of chronic aggressive hepatitis and/or nonalcoholic cirrhosis, 20 were HBsAg positive on entry. In this subgroup sequential serum samples were investigated for HBs and HBe markers by radioimmunoassay. At the time of evaluation, 13 patients were still alive; their median age was 53 years (25 to 72) and median follow-up time was 46 months (23 to 82). Of 16 patients with cirrhosis, 5 of 7 with persistence of HBeAg died, compared with 2 of 9 with anti-HBe. In three patients with anti-HBe, HBeAg reappeared several times with simultaneous rise in transaminase values. The overall survival was 65% after 5 years. The prognosis of HBsAg-positive chronic liver disease seemed to depend on the presence of cirrhosis and HBeAg rather than on improvement in biochemical activity during immunosuppressive treatment.


A clinically practical model for the preoperative prediction of lymph node metastasis in bladder cancer: a multicohort study.
The aim of this study was to construct a clinically practical model to precisely predict lymph node (LN) metastasis in bladder cancer patients. Four independent cohorts were included. The least absolute shrinkage and selection operator regression with multivariate logistic regression were applied. The diagnostic efficacy of LN score and CT/MRI was compared by accuracy, sensitivity, specificity, and area under curve (AUC). A total of 606 patients were included to develop a basic prediction model. After multistep gene selection, the LN metastasis prediction model was constructed with 5 genes. The model can accurately predict LN metastasis with an AUC of 0.781. For clinically practical use, we transformed the model into a Fast LN Scoring System using the SYSMH cohort (n = 105). High LN score patients exhibited a 72.2% LN metastasis rate, while low LN score patients showed a 3.4% LN metastasis rate. The LN score achieved a superior accuracy than CT/MRI (0.882 vs. 0.727). Application of LN score can correct the diagnosis of 88% (22/25) patients who were misdiagnosed by CT/MRI. The clinically practical LN score can precisely, rapidly, and conveniently predict LN status, which will assist preoperative diagnosis for LN metastasis and guide precise therapy.


N-Channel field-effect transistors with floating gates for extracellular recordings.
A field-effect transistor (FET) for recording extracellular signals from electrogenic cells is presented. The so-called floating gate architecture combines a complementary metal oxide semiconductor (CMOS)-type n-channel transistor with an independent sensing area. This concept allows the transistor and sensing area to be optimised separately. The devices are robust and can be reused several times. The noise level of the devices was smaller than of comparable non-metallised gate FETs. In addition to the usual drift of FET devices, we observed a long-term drift that has to be controlled for future long-term measurements. The device performance for extracellular signal recording was tested using embryonic rat cardiac myocytes cultured on fibronectin-coated chips. The extracellular cell signals were recorded before and after the addition of the cardioactive isoproterenol. The signal shapes of the measured action potentials were comparable to the non-metallised gate FETs previously used in similar experiments. The fabrication of the devices involved the process steps of standard CMOS that were necessary to create n-channel transistors. The implementation of a complete CMOS process would facilitate the integration of the logical circuits necessary for signal pre-processing on a chip, which is a prerequisite for a greater number of sensor spots in future layouts.


Does ADT Influence the Risk of Suicidal Ideation among US Veteran Prostate Cancer Patients Pre-Exposed to PTSD?
Post-traumatic stress disorder (PTSD) is defined as a mental health disease that has a high probability of developing among individuals who have experienced traumatic events [...].


Hydrolyzed lactalbumin-based oral rehydration solution for acute diarrhoea in infants.
The addition of different organic substrates to standard glucose oral rehydration solution (G-ORS) has been shown to improve the intestinal absorption of sodium and water, and thereby decrease stool losses. Therefore, we evaluated, in infants with acute diarrhoea, the safety and efficacy of three oral rehydration solutions (ORS) which had the same concentrations of electrolytes (with sodium 60 mmol/l) but different substrates of proteins and carbohydrates. One solution (LAD-ORS) contained hydrolyzed lactalbumin (LAD) with maltodextrin and sucrose, a second (MS-ORS) was identical but without LAD and a third (G-ORS) was standard glucose ORS. The three solutions were compared in a double-blind, randomized trial in 74 hospitalized well-nourished children in Panama and the United States. All three oral rehydration solutions were equally efficacious and safe in these children, 54% of whom were infected with rotavirus. There was no suggestion that hydrolyzed lactalbumin or maltodextrin provided any advantage over glucose-ORS in terms of stool output or in duration of diarrhoea. We conclude that all three solutions are efficacious in the therapy of acute diarrhoea in infants.