Influence of retinoic acid on adhesion complexes in human hepatoma cells: a clue to its antiproliferative effects.
Retinoic acid exerts antiproliferative and differentiative effects in normal and transformed in vitro hepatocytes. In order to verify whether these effects are related to a modulation of adhesion molecules, we used Western blot analysis and immunofluorescence microscopy to investigate the E-cadherinl/beta-catenin complex, the main system of adherens junctions, and the occludin/ZO-1 complex present in the tight junctions in HepG2 cells cultured in the presence or absence of retinoic acid. Results showed that retinoic acid treatment increases the amount of beta-catenin bound to E-cadherin by decreasing its tyrosine-phosphorylation level. Similar results were obtained with the tight junction system, in which the amount of occludin/ZO-1 complex is increased by a similar mechanism that reduced the level of ZO-1 phosphorylation on tyrosine. Immunofluorescence images also confirm these results, showing the localization on the cell surface of both adhesion complexes. Their insertion into the plasma membrane could be suggestive of an optimal reassembly and function of adherens and tight junctions in hepatoma cells, indicating that retinoic acid, besides inhibiting cell proliferation, improves cell-cell adhesion, sustaining or inducing the expression of a more differentiated phenotype.


Urinary iron excretion for evaluating iron chelation efficacy in children with thalassemia major.
In patients with thalassemia major, examination routinely used for the evaluation of iron load in Indonesia is serum ferritin, but it is strongly influenced by other factors such as infections, inflammation and vitamin C levels. Evaluation of urinary iron excretion is an important and easy method to indicate iron chelation efficacy. To determine the efficacy of iron chelation therapy by urinary iron examination and to evaluate its correlation with the time of transfusion, serum ferritin level, transferrin saturation and T2* MRI. Prospective cohort study was conducted in children with thalassemia major aged 7-<18 years old who received DFP therapy. Twenty-four-hour urine collections were examined through inductively coupled plasma - mass spectrometry (ICP-MS). Patient's serum ferritin, transferrin saturation, peripheral blood, differential count and T2* MRI was documented during the study. Data analysis is based on urine iron level, body iron balance and the correlation between urine iron level, serum ferritin, transferrin saturation and T2* MRI and dosage of DFP. Thirty (55%) subjects showed a higher urine iron level on the day prior to transfusion (mean: 12,828 SD ±12,801 μg/24 h) in comparison to post transfusion (mean: 10,985 SD ±10,023 μg/24 h). All subjects had positive iron balance (mean 524 SD ±230 mg). There were positive correlation between urine iron level and transferrin saturation (r = 0.559, p = 0.01) and serum ferritin (r = 0.291, p = 0.03), no correlation found with T2* MRI results. There is a relationship to urinary iron excretion in response to chelation therapy and the degree of iron load.


Gender differences in susceptibility to smoking among patients with lung cancer.
To determine whether female smokers are more or less susceptible to the detrimental pulmonary-function effects of smoking when compared to male smokers among patients with lung cancer. Pack-years and pulmonary function indices were compared between 1,594 men and women with lung cancer who were smokers or had a history of smoking. Differences in individual susceptibility to smoking were estimated using a susceptibility index formula. Of the patients, 959 (92.8%) men and 74 (7.2%) women were current smokers. Common histological types of lung cancer were squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, among others. Women had a lower number of pack-years, forced expiratory volume in 1 second (FEV(1), liters), forced vital capacity (FVC, liters), and total lung capacity (TLC, liters) compared to those of men (25.0 ± 19.2 vs. 42.9 ± 21.7 for pack-years; 1.4 ± 0.5 vs. 2.0 ± 0.6 for FEV(1); 3.0 ± 0.7 vs. 2.0 ± 0.6 for FVC; 4.5 ± 0.8 vs. 5.7 ± 1.0 for TLC; all p < 0.001). The susceptibility index for women was significantly higher compared to that of men (1.1 ± 4.1 vs. 0.7 ± 1.1; p = 0.001). A significant inverse association was shown between the susceptibility index and TLC and FVC (r = -0.200 for TLC, -0.273 for FVC; all p < 0.001). The results suggest that the detrimental effects of smoking on pulmonary function are greater in women, as compared to those in men, among patients with lung cancer.


[Role of duodenum in regulation of plasma ghrelin level and body mass index after subtotal gastrectomy].
To investigate the role of duodenum in regulation of ghrelin and body mass index (BMI) and the correlation between ghrelin and BMI after subtotal gastrectomy. Forty-two patients with T(0-1)N(0-1)M(0) gastric cancer were divided into two groups after gastrectomy according to digestive reconstruction pattern, Billroth I group (n=23) and Billroth II group (n=19) respectively. Plasma ghrelin levels were determined by radioimmunoassay (RIA) before and at day 1, 7, 30 and 360 after gastrectomy,and BMIs were also measured. Two groups had identical postoperative trends in ghrelin alterations during the early stage, both dropping to nadir at day 1 (36.7% vs 35.7%), then markedly increasing at day 7 (51.0% vs 51.1%). At day 30, ghrelin level of Billroth I group was slightly higher than that of Billroth II group. At day 360, ghrelin level of Billroth I group recovered to 93.6%, approaching though lower than preoperative level and no significant difference was displayed, while ghrelin level of Billroth II group recovered only to 81.6% of preoperational level and significant difference existed (P=0.033). Compared with preoperative levels, ghrelin of two groups decreased by 6.9% and 18.4% while BMI by 3.3% and 6.4% respectively, liner regression correlations were revealed in both groups between decrease magnitudes(R(1)(2)=0.297,P=0.00;R(2)(2)=0.559,P<0.001). Anatomico-physiological duodenum compensatively promotes ghrelin recovery, accordingly enhances BMI after gastrectomy. Regarding patients with insufficient ghrelin secretion, ghrelin is positively correlated with BMI.


[Technical improvement of mechanical suture of bronchial stumps in pneumonectomy].
To prevent or reduce such postoperative complications of pneumonectomy as bronchopleural fistula and promote the curative effect of the surgery by improving the technique for handling the bronchial stumps. In 107 patients, bronchial stapler was adopted for closure of the bronchial stump and pneumonectomy was subsequently performed on the side of the staples. A 1-0 polyester suture was used to for suture in the shape of "U" deep in the mechanical suture on the bronchial stump. The postoperative complications were observed. The operations were performed easily and the bronchial stumps were short and sutured firmly. No fluid retention or granuloma occurred in the stumps after the operation, nor were the complications such as intractable cough and infection of thoracic cavity observed. No bronchopleural fistula was found in these patients. This new method is safe and effective for treatment of the bronchial stumps.


Salt-Mediated Organic Solvent Precipitation for Enhanced Recovery of Peptides Generated by Pepsin Digestion.
Conventional solvent-based precipitation makes it challenging to obtain a high recovery of low mass peptides. However, we previously demonstrated that the inclusion of salt ions, specifically ZnSO4, together with high concentrations of acetone, maximizes the recovery of peptides generated from trypsin digestion. We herein generalized this protocol to the rapid (5 min) precipitation of pepsin-digested peptides recovered from acidic matrices. The precipitation protocol extended to other organic solvents (acetonitrile), with high recovery from dilute peptide samples permitting preconcentration and purification. Mass spectrometry profiling of pepsin-generated peptides demonstrated that the protocol captured peptides as small as 800 u, although with a preferential bias towards recovering larger and more hydrophobic peptides. The precipitation protocol was applied to rapidly quench, concentrate, and purify pepsin-digested samples ahead of MS. Complex mixtures of yeast and plasma proteome extracts were successfully precipitated following digestion, with over 95% of MS-identified peptides observed in the pellet fraction. The full precipitation workflow-including the digestion step-can be completed in under 10 min, with direct MS analysis of the recovered peptide pellets showing exceptional protein sequence coverage.


Dissociating the conditioning and the anorectic effects of estradiol in female rats.
The present series of experiments challenges the ability of the hormone estradiol to act as an unconditioned stimulus in the conditioned taste avoidance (CTA) learning paradigm. We hypothesize that reductions in sucrose consumption observed after pairing it with estradiol are not indicative of associative learning, but due to the unconditioned expression of estradiol's anorectic effects during the time of CTA assessment. Three experiments in which a sucrose solution was paired with estradiol were conducted to test this hypothesis. Experiment 1 demonstrated that female rats expressed a reduction in post-pairing sucrose consumption even though the anorectic effects of estradiol had subsided. Experiment 2 showed that although a low dose of estradiol produced anorexia, it did not elicit post-pairing reductions in sucrose consumption. Experiment 3 revealed that contingent pairing was a requirement for post-pairing reduction in sucrose consumption even when testing was done at a time when anorexia is expressed. These findings demonstrate the dissociability of the conditioning and anorectic effects of estradiol, providing evidence against the hypothesis. The results are discussed in terms of independent neural mechanisms underlying the disparate behaviors.


Attentional function in secondary school students receiving isoniazid prophylaxis for tuberculosis infection.
Reports have suggested that isoniazid treatment may be associated with poor concentration and subtle reduction in memory. This study examines attentional function and processing speed in a group of 25 adolescents who received isoniazid prophylaxis for at least 6 months. As adolescents often face major educational assessment milestones, such cognitive side effects may have important implications. Participants were assessed before treatment, 1 month into treatment and at least 1 week after treatment cessation. Measures included the Paced Auditory Serial Addition Test and subtests of the appropriate Wechsler scale sensitive to attention and speed of information processing. Isoniazid does not appear to cause significant adverse effects on attentional function in adolescents.


Selection and amplification of heterologous genes encoding adenosine deaminase in mammalian cells.
We demonstrate that an adenosine deaminase (ADA) cDNA gene can function as a dominant selectable and amplifiable marker for gene transfer experiments in mammalian cells. Cells that incorporate the gene can be selected by growth in the presence of low concentrations of the ADA inhibitor 2'-deoxycoformycin with cytotoxic concentrations of adenosine or its analogue 9-beta-D-xylofuranosyl adenine. The DNA copy number of the transfected ADA minigene in the isolated transformants of Chinese hamster ovary cells can be amplified greater than 100-fold by growth in ADA selection media and increasing concentrations of 2'-deoxycoformycin. This selection scheme may allow for the introduction and subsequent amplification of heterologous DNA in a variety of mammalian cells.


Presynaptic effectors contributing to cAMP-induced synaptic potentiation in Drosophila.
cAMP analogs and activation of adenylyl cyclase by forskolin strongly potentiate synaptic transmission at the Drosophila neuromuscular junction. These effects are generally attributed to activation of cAMP-dependent protein kinase. Recent reports on crustacean and mammalian synapses have implicated other cAMP-dependent effectors in synaptic potentiation. Drosophila neuromuscular junctions were tested for effects of two known cAMP-dependent effectors: hyperpolarization-activated, cyclic nucleotide-regulated channels (HCNCs) and guanine nucleotide exchange protein activated by cAMP (Epac). Forskolin-induced enhancement of synaptic transmission was drastically reduced by a blocker of HCNCs, but not completely eliminated. A specific agonist for Epac modestly enhanced synaptic potentials. This agonist also stabilized their amplitudes in the presence of a blocker of HCNCs. The observations implicate HCNCs and Epac in cAMP-dependent potentiation that does not require cAMP-dependent protein kinase, indicating that additional previously unexplored factors contribute to synaptic plasticity in Drosophila. Genetic and molecular techniques available for Drosophila can be used to define the underlying molecular basis for cAMP-dependent synaptic potentiation.


[Binding characteristics of chemosynthetic Ac-SDKP analogue FAM-Aca-SDKP to hepatic stellate cell-T6 cells].
To investigate the binding of the chemosynthetic analogue of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) FAM-Aca-SDKP to hepatic stellate cell-T6 (HSC-T6) cells and basic physical characteristics. The Ac-SDKP analogue short-peptide FAM-Aca-SDKP carrying green fluorescence was synthesized chemically. Quantitative real-time PCR was used to evaluate its effect on the secretion of HSC collagen and verify the consistency in the biological effect between FAM-Aca-SDKP and Ac-SDKP. A fluorescence microscope was used to observe the binding between FAM-Aca-SDKP and HSC-T6, and flow cytometry was used to evaluate the time-concentration effect of the binding between FAM-Aca-SDKP and HSC-T6. The t-test or rank sum test was used for the statistical analysis of different types of data. After HSC-T6 was incubated with Ac-SDKP or FAM-Aca-SDKP for 24 hours, the expression of type I collagen in HSC-T6 was increased, when the action time was 0.5 hour, Ac-SDKP and FAM-Aca-SDKP caused a 30%-50% reduction in the expression of type I collagen. After HSC-T6 was incubated with FAM-Aca-SDKP, strong green fluorescence was observed on cell surface under a fluorescence microscope, and after Ac-SDKP was added, Ac-SDKP significantly reduced the fluorescence intensity on cell surface due to competitive inhibition. Flow cytometry showed that when the concentration of FAM-Aca-SDKP was 0-50μmol/L, the rate of fluorescence-positive cells rapidly increased from 0 to 12%; when the concentration was 50-100μmol/L, the rate of fluorescence-positive cells only increased from 12% to 14%; co-incubation with Ac-SDKP significantly reduced the rate of fluorescence-positive cells. The number of positive cells reached the peak at the 45-minute point of the incubation and then decreased gradually. FAM-Aca-SDKP can bind to the surface of HSC-T6 cells, and this process has ligand-receptor binding characteristics such as competitive inhibition, saturability, and time-concentration effect.


Emergence of antiretroviral therapy resistance-associated primary mutations among drug-naive HIV-1-infected individuals in rural western Cameroon.
The prevalence of antiretroviral therapy (ART) resistance-associated mutations among HIV-1 strains in western Cameroon was evaluated by genotypically analyzing strains isolated from drug-naive individuals. Proviral DNA was extracted from 54 blood samples and amplified by polymerase chain reaction of protease, reverse transcriptase, integrase, and envelope genes. At least 4 clones per sample were analyzed. Of 54 HIV-1 strains, 45 (83.3%) had a concordant subtype or circulating recombinant form (CRF) designation: 40 CRF02_AG, 2 subtype A1, 2 G, and 1 F2. The remaining 9 (16.7%) had a discordant subtype: 6 subtype A1/CRF02_AG, 2 D/CRF02, and 1 G/CRF02. Protease inhibitor-associated primary resistance mutations were found in 4 (7.4%) cases: M46L with full clones in 1 case, and M46I, M46L, and V82A as minor populations in 1 case each. Reverse transcriptase inhibitor-associated primary resistance mutations were found in 5 (9.8%) samples: Y188C in 2 cases, and L100I, M184V, and V75I in 1 case each, although all of these mutations were found as minor populations. This is one of the first reports of the emergence of primary ART resistance mutations among drug-naive, non-B subtype HIV-1-infected individuals in Cameroon. Follow-up studies should be conducted to assess whether these drug-resistant mutants found as minor populations might impact future ART.


Electrophysiological markers of covert face recognition in developmental prosopagnosia.
To study the existence and neural basis of covert face recognition in individuals with developmental prosopagnosia, we tested a group of 12 participants with developmental prosopagnosia in a task that required them to judge the familiarity of successively presented famous or non-famous faces. Electroencephalography was recorded during task performance, and event-related brain potentials were computed for recognized famous faces, non-recognized famous faces and non-famous faces. In six individuals with developmental prosopagnosia, non-recognized famous faces triggered an occipito-temporal N250 component, which is thought to reflect the activation of stored visual memory traces of known individual faces. In contrast to the N250, the P600f component, which is linked to late semantic stages of face identity processing, was not triggered by non-recognized famous faces. Event-related potential correlates of explicit face recognition obtained on those few trials where participants with developmental prosopagnosia classified famous faces as known or familiar, were similar to the effects previously found in participants with intact face recognition abilities, suggesting that face recognition mechanisms in individuals with developmental prosopagnosia are not qualitatively different from that of unimpaired individuals. Overall, these event-related potential results provide the first neurophysiological evidence for covert face recognition in developmental prosopagnosia, and suggest this phenomenon results from disconnected links between intact identity-specific visual memory traces and later semantic face processing stages. They also imply that the activation of stored visual representations of familiar faces is not sufficient for conscious explicit face recognition.


Enzymology of the hair follicle.
Androgenetic alopecia (AGA) is the most common type of hair loss in men and women. This continuous process results in a type of alopecia that follows a definite pattern in those individuals who are genetically predisposed. A genetic predisposition is a feature of AGA, but the predisposing genes are still unknown. Our understanding, however, of the hormonal effects on hair growth is far move advanced, and human hair follicles are not only targets for androgens, but also reveal an active androgen metabolism, with the ability to convert several androgens by different steroidogenic enzymes. Recent results suggest that the dermal papilla of the hair follicle expresses abundant type 2 5a-reductase, 3b-HSD and steroid sulfatase activity. Therefore, current information about the androgen metabolism in hair follicles is reviewed and the potential impact on future therapeutic approaches is discussed.


Comparison of clinical and laboratory features in coronavirus disease 2019 and pediatric multisystem inflammatory syndrome patients.
The coronavirus disease 2019 (COVID-19) and pediatric multisystem inflammatory syndrome (PIMS) are a major public health issue affecting many people worldwide. Although there are new studies in children, little is known about these two new conditions. The aim of this study was to evaluate and compare the clinical and laboratory features of children with COVID-19 and PIMS. We conducted a prospective, single-center study of pediatric COVID-19 and PIMS at a tertiary care hospital in Turkey between November 2020 and March 2021. A total of 115 patients with COVID-19 and PIMS were examined during the study period. The median age was 60 (range, 1-215) months and 64% of the patients were male. The most common clinical symptoms were fever (70%) and cough (43%). Conjunctivitis and skin rash were not seen in PIMS patients. Of all patients, 64% had a history of close contact in household. Lymphopenia was present in 34/115 (30%) patients. Acute phase reactants were significantly higher in PIMS patients. Abnormal chest computed tomography scan findings were detected in 68% of the patients, while 36% had abnormal echocardiographic findings. In multivariate analysis, longer duration of fever, diarrhea, lower thrombocyte and higher neutrophil count were significantly associated with diagnosis of PIMS. The treatment included antibiotics, favipiravir, intravenous immunoglobulin, corticosteroids, interleukin-1 blockade. and supportive therapy. Seven patients (6%) required intensive care support. All patients were discharged without any complications, except one who died. Longer duration of fever, diarrhea, lower thrombocyte, and higher neutrophil count can warn clinicians for diagnosis of PIMS.


Social interaction modulates autonomic, inflammatory, and depressive-like responses to cardiac arrest and cardiopulmonary resuscitation.
Psychological factors, including depression and social isolation, are important determinants of cardiovascular health. The current study uses a well-validated mouse model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR) to examine the effect of social environment on several pathophysiological and behavioral responses to cerebral ischemia. Male experimental mice were either housed in pairs with an ovariectomized female or socially isolated for the duration of the experiment. Cardiac arrest increased the mRNA expression of the proinflammatory cytokines TNF-α, IL-1β, and IL-6, as well as the microglia marker MAC-1; expression of each of these factors, except IL-6, was further increased among socially isolated mice. Furthermore, socially isolated animals exposed to the CA/CPR procedure displayed significantly higher levels of neuronal cell death and microglia staining within the hippocampus at 7 d following surgery. Social isolation also exacerbated CA/CPR-induced depressive-like behavior and cardiac autonomic dysregulation. In the absence of ischemic damage, social environment had no significant effect on the expression of neuronal cell death, autonomic cardiac control, or behavior. Together, these data suggest that social factors influence the pathophysiological trajectory following cardiac arrest.


Tryptophan, kynurenine pathway, and diabetic ketoacidosis in type 1 diabetes.
Diabetic ketoacidosis (DKA) is a serious complication of complete insulin deficiency and insulin resistance in Type 1 diabetes (T1D). This results in the body producing high levels of serum ketones in an attempt to compensate for the insulin deficiency and decreased glucose utilization. DKA's metabolic and immunologic dysregulation results in gradual increase of systemic and cerebral oxidative stress, along with low grade systemic and cerebral inflammation and the development of pretreatment subclinical BE. During treatment the early progression of oxidative stress and inflammation is hypothesized to advance the possibility of occurrence of crisis of clinical brain edema (BE), which is the most important cause of morbidity and mortality in pediatric DKA. Longitudinal neurocognitive studies after DKA treatment show progressive and latent deficits of cognition and emphasize the need for more effective DKA treatment of this long-standing conundrum of clinical BE, in the presence of systemic osmotic dehydration, metabolic acidosis and immune dysregulation. Candidate biomarkers of several systemic and neuroinflammatory pathways prior to treatment also progress during treatment, such as the neurotoxic and neuroprotective molecules in the well-recognized tryptophan (TRP)/kynurenine pathway (KP) that have not been investigated in DKA. We used LC-MS/MS targeted mass spectrometry analysis to determine the presence and initiation of the TRP/KP at three time points: A) 6-12 hours after initiation of treatment; B) 2 weeks; and C) 3 months following DKA treatment to determine if they might be involved in the pathogenesis of the acute vasogenic complication of DKA/BE. The Trp/KP metabolites TRP, KYN, quinolinic acid (QA), xanthurnenic acid (XA), and picolinic acid (PA) followed a similar pattern of lower levels in early treatment, with subsequent increases. Time point A compared to Time points B and C were similar to the pattern of sRAGE, lactate and pyruvic acid. The serotonin/melatonin metabolites also followed a similar pattern of lower quantities at the early stages of treatment compared to 3 months after treatment. In addition, glutamate, n-acetylglutamate, glutamine, and taurine were all lower at early treatment compared to 3 months, while the ketones 3-hydroxybutaric acid and acetoacetate were significantly higher in the early treatment compared to 3 months. The two major fat metabolites, L-carnitine and acetyl-L-carnitine (ALC) changed inversely, with ALC significantly decreasing at 2 weeks and 3 months compared to the early stages of treatment. Both anthranilic acid (AA) and 3-OH-anthranilic acid (3OH-AA) had overall higher levels in the early stages of treatment (A) compared to Time points (B and C). Interestingly, the levels of AA and 3OH-AA early in treatment were higher in Caucasian females compared to African American females. There were also differences in the metabolite levels of QA and kynurenic acid (KA) between genders and between races that may be important for further development of custom targeted treatments. We hypothesize that the TRP/KP, along with the other inflammatory pathways, is an active participant in the metabolic and immunologic pathogenesis of DKA's acute and chronic insults.


Transluminal angioplasty for middle cerebral artery stenosis in patients with acute ischemic stroke.
Precutaneous transluminal angioplasty (PTA) is currently performed to treat supraaortic atherosclerotic lesions. Our purpose was to evaluate the safety and efficacy of PTA for middle cerebral artery (MCA) stenosis in patients with acute ischemic stroke. We performed PTA with the use of a microballoon (2-2.5 mm in diameter and 10-13 mm in length) in 10 consecutive patients (mean age, 48 years) who met the following criteria: high-grade M1 stenosis (> 70%) and mild neurologic deficits (NIH stroke scale < 4) and/or recurrent transient ischemic attacks (TIAs) resistant to anticoagulation, or a large area of hypoperfusion in the MCA territory on brain perfusion SPECT scans. During follow-up, we administered antiplatelet agents and evaluated the status of restenosis by angiography (n = 2), brain perfusion SPECT (n = 4), and/or transcranial Doppler sonography (TCD) (n = 7). Stenotic arteries were successfully dilated in nine of 10 patients. Angioplasty failed in one patient because the balloon could not pass through the tortuous cavernous internal carotid artery. None of the patients experienced either peri- or postangioplasty complications. Residual stenosis was less than 50%, and clinical improvement, including elimination of TIAs in four patients who had suffered resistant TIAs, was observed in all patients; improvement of the cerebral perfusion was also noted in two patients with a large hypoperfusion area in the MCA territory. The average follow-up period was 11 months (range, 2 to 36 months). None experienced recurrent stroke during the follow-up period. TCD revealed decreased flow velocity of the MCA after angioplasty in seven patients. PTA of the proximal portion of the MCA seems to be a safe and effective therapeutic technique for the prevention of secondary ischemic stroke.


PTH Reloaded: A New Evolutionary Perspective.
The parathyroid hormone (PTH) family is a group of structurally-related secreted peptides involved in bone mineral homeostasis and multitude of developmental processes in vertebrates. These peptides mediate actions through PTH receptors (PTHRs), which belong to the transmembrane G protein-coupled receptor group. To date, genes encoding for PTH and PTHR have only been identified in chordates, suggesting that this signaling pathway may be an evolutionary innovation of our phylum. In vertebrates, we found up to six PTH and three PTHR different paralogs, varying in number between mammals and teleost fishes due to the different rounds of whole-genome duplication and specific gene losses suffered between the two groups of animals. The diversification of the PTH gene family has been accompanied by both functional divergence and convergence, making sometimes difficult the comparison between PTH peptides of teleosts and mammals. Here, we review the roles of all Pth peptides in fishes, and based on the evolutionary history of PTH paralogs, we propose a new and simple nomenclature from PTH1 to PTH4. Moreover, the recent characterization of the Pth4 in zebrafish allows us to consider the prominent role of the brain-to-bone signaling pathway in the regulation of bone development and homeostasis. Finally, comparison between PTH peptides of fish and mammals allows us to discuss an evolutionary model for PTH functions related to bone mineral balance during the vertebrate transition from an aquatic to a terrestrial environment.


Vesicle budding induced by a pore-forming peptide.
We describe, in a system whose uniqueness is that the presence of pores allows the volume to vary as budding proceeds, how phase separation on the surface of spheres extrudes material in the process called "budding". The system is giant phospholipid vesicles (GUVs) containing phase-separated regions of DOPC (soft, liquid) and DPPC (stiff, gel), with cholesterol and without it. Budding is triggered by adding the cationic pore-forming peptide, melittin. Without cholesterol, fluorescence experiments show that melittin selectively binds to the liquid domains, inducing them to form mainly exocytotic monodisperse smaller vesicle buds of this same material, causing the parent GUV to shrink. The effect of cholesterol is to produce just a few large buds following domain coalescence, rather than numerous smaller monodisperse ones. Line tension is experimentally shown to be essential for budding in this multicomponent membrane.


Transcatheter aortic valve implantation in high-risk patients with severe aortic stenosis.
Although surgery is the gold standard for severe aortic stenosis (AS) treatment, it is considered high risk in elderly patients because of high complication rates, which leads to substantial hesitation in submitting such patients to surgery. With the growing need to treat elderly patients with severe AS, percutaneous transcatheter aortic valve implantation (TAVI) was pioneered in 2001, followed by implantation of a self-expanding percutaneous aortic valve in 2005. As of April 2010, these 2 methods of TAVI have been used in more than 15,000 patients throughout the world. The acute success rate of this procedure is now increasing up to 95.4% by the transfemoral approach and 92.7% by the transapical approach with regard to Edwards SAPIEN valve implantation. In terms of the Corevalve ReValving system, it is reported as 98.2% in an expert's hands. This article reviews the methods of TAVI and the devices, not yet been approved in Japan but are expected to be available in a few years.


Gut γδ T cells as guardians, disruptors, and instigators of cancer.
Colorectal cancer is the third most common cancer worldwide with nearly 2 million cases per year. Immune cells and inflammation are a critical component of colorectal cancer progression, and they are used as reliable prognostic indicators of patient outcome. With the growing appreciation for immunology in colorectal cancer, interest is growing on the role γδ T cells have to play, as they represent one of the most prominent immune cell populations in gut tissue. This group of cells consists of both resident populations-γδ intraepithelial lymphocytes (γδ IELs)-and transient populations that each has unique functions. The homeostatic role of these γδ T cell subsets is to maintain barrier integrity and prevent microorganisms from breaching the mucosal layer, which is accomplished through crosstalk with enterocytes and other immune cells. Recent years have seen a surge in discoveries regarding the regulation of γδ IELs in the intestine and the colon with particular new insights into the butyrophilin family. In this review, we discuss the development, specialities, and functions of γδ T cell subsets during cancer progression. We discuss how these cells may be used to predict patient outcome, as well as how to exploit their behavior for cancer immunotherapy.


Growth under Red Light Enhances Photosystem II Relative to Photosystem I and Phycobilisomes in the Red Alga Porphyridium cruentum.
Acclimation of the photosynthetic apparatus to light absorbed primarily by photosystem I (PSI) or by photosystem II (PSII) was studied in the unicellular red alga Porphyridium cruentum (ATCC 50161). Cultures grown under green light of 15 microeinsteins per square meter per second (PSII light; absorbed predominantly by the phycobilisomes) exhibited a PSII/PSI ratio of 0.26 +/- 0.05. Under red light (PSI light; absorbed primarily by chlorophyll) of comparable quantum flux, cells contained nearly five times as many PSII per PSI (1.21 +/- 0.10), and three times as many PSII per cell. About 12% of the chlorophyll was attributed to PSII in green light, 22% in white light, and 39% in red light-grown cultures. Chlorophyll antenna sizes appeared to remain constant at about 75 chlorophyll per PSII and 140 per PSI. Spectral quality had little effect on cell content or composition of the phycobilisomes, thus the number of PSII per phycobilisome was substantially greater in red light-grown cultures (4.2 +/- 0.6) than in those grown under green (1.6 +/- 0.3) or white light (2.9 +/- 0.1). Total photosystems (PSI + PSII) per phycobilisome remained at about eight in each case. Carotenoid content and composition was little affected by the spectral composition of the growth light. Zeaxanthin comprised more than 50% (mole/mole), beta-carotene about 40%, and cryptoxanthin about 4% of the carotenoid pigment. Despite marked changes in the light-harvesting apparatus, red and green light-grown cultures have generation times equal to that of cultures grown under white light of only one-third the quantum flux.


A novel serine/threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes.
We previously reported the cloning of a serine/threonine kinase, PAK (for p21 (Cdc42/Rac)-activated kinase), which binds to the Ras-related GTPases Cdc42Hs and Rac1 (Manser, E., Leung, T., Salihuddin, H., Zhao, Z-s., and Lim, L. (1994) Nature 367, 40-46). These p21 proteins together with RhoA comprise the Rho subfamily of proteins that are involved in morphological events. We now report the isolation of a rat cDNA encoding a 150-kDa protein, which specifically binds RhoA in its GTP form and contains an N-terminal serine/threonine kinase domain highly related to the human myotonic dystrophy kinase and a cysteine-rich domain toward the C terminus. The RhoA binding domain is unrelated to other p21 binding domains. Antibody raised against the kinase domain of the predicted protein, termed ROK alpha (for ROK alpha, RhoA-binding kinase), recognized a ubiquitous 150-kDa protein. The brain p150 purified by affinity chromatography with RhoA exhibited serine/threonine kinase activity. In cultured cells, immunoreactive p150 was recruited to membranes upon transfection with dominant positive RhoAV14 mutant and was localized with actin microfilaments at the cell periphery. These results are consistent with a role for the kinase ROK alpha as an effector for RhoA.


Successful treatment with ganciclovir of a HIV endstage patient with adrenal insufficiency.
We report on a 31-year-old AIDS patient who presented with rapid progressive fatigue, weakness, weight loss and hyperpigmentation. Endoscopy showed an ulcerous CMV gastritis with the histological hallmarks of this disease. In addition, laboratory tests revealed the constellation of an adrenal insufficiency with low plasma levels of sodium and increased levels of potassium and ACTH. After initiation of ganciclovir treatment, the CMV gastritis healed and the electrolyte abnormalities were resolved within 2 weeks. We assume that a CMV adrenalitis was treated in a reversible stage. The literature on CMV adrenalitis is reviewed to support this conclusion.


Fibular and metatarsal osteosynthesis in a southern brown howler monkey (Alouatta guariba clamitans).
Here we describe a successful surgical management of a distal fibular fracture combined with a tarsocrural luxation and multiple metatarsal fractures in the left foot of a southern brown howler monkey (Alouatta guariba clamitans). We achieved satisfactory outcome by applying intramedullary pinning for each of the bone fractures and closed reduction of joint luxation-kept in place only by bone alignment, without further ligament reconstruction. Bone healing occurred uneventfully within eight weeks and the monkey's foot regained its normal function. Therefore, we could properly release the patient back into the wild.


Multifunctional Silicone Rubber Nanocomposites by Controlling the Structure and Morphology of Graphene Material.
Multifunctional elastomer nanocomposites have been applied in several high-tech fields. The design of materials with tailored properties capable of tuning their performance is a topical challenge. Here, we demonstrate that it is possible to modulate the mechanical and transport properties of silicone rubber nanocomposites by controlling the structure, chemical composition and morphology of the graphene material. Intrinsic graphene properties, such as remaining oxygen groups, specific surface area, and aspect ratio, among others, have a profound effect on the final properties of the nanocomposite. Thus, the thermal conductivity benefits from larger filler size and high aromatic restoration. Whereas mechanical properties and electrical conductivity require a proper balance between filler/polymer matrix interaction and a partial aromatic restoration.


Treatment of depressive symptoms in diverse, rural, and vulnerable older adults.
We examined the effects of home-delivered cognitive-behavior therapy (CBT) on depressive symptoms among rural, diverse, and vulnerable older adults. Furthermore, we differentiated depression into its two salient aspects: psychological and somatic. Data came from a randomized controlled experiment of CBT on 134 individuals residing in rural Alabama. Cognitive-behavior therapy resulted in significantly lower depressive symptom severity scores. When depressive symptoms were categorized as psychological or somatic, CBT was found to significantly improve the former but not the latter. Notably, there was a trend toward somatic symptom improvement. Cognitive-behavior therapy can be an effective treatment for depression in a hard-to-reach group of older adults. Home delivery affords advantages but is also an expensive delivery modality. Diverse older adults responded to the CBT intervention.


External fixation of distal radius fractures.
Fractures of the distal radius are the most common fractures that occur in patients between ages 15 and 75 years. Many methods for treating displaced distal radius fractures are available. All forms of treatment involve obtaining fracture reduction, which may then be maintained by casting, functional bracing, external fixation, percutaneous pinning, internal fixation, or a combination of these methods. This article discusses the indications and technique of fracture treatment with external fixation and, when required, adjuvant percutaneous pins.


Ratio analysis nuclear magnetic resonance spectroscopy for selective metabolite identification in complex samples.
Metabolite identification in the complex NMR spectra of biological samples is a challenging task due to significant spectral overlap and limited signal-to-noise. In this study we present a new approach, RANSY (ratio analysis NMR spectroscopy), which identifies all the peaks of a specific metabolite on the basis of the ratios of peak heights or integrals. We show that the spectrum for an individual metabolite can be generated by exploiting the fact that the peak ratios for any metabolite in the NMR spectrum are fixed and proportional to the relative numbers of magnetically distinct protons. When the peak ratios are divided by their coefficients of variation derived from a set of NMR spectra, the generation of an individual metabolite spectrum is enabled. We first tested the performance of this approach using one-dimensional (1D) and two-dimensional (2D) NMR data of mixtures of synthetic analogues of common body fluid metabolites. Subsequently, the method was applied to (1)H NMR spectra of blood serum samples to demonstrate the selective identification of a number of metabolites. The RANSY approach, which does not need any additional NMR experiments for spectral simplification, is easy to perform and has the potential to aid in the identification of unknown metabolites using 1D or 2D NMR spectra in virtually any complex biological mixture.


Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalomyelitis.
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a neuro-immune disease of uncertain pathogenesis. Human parvovirus B19 infection has been shown to occur just prior to development of the onset of CFS/ME in several cases, although B19 seroprevalence studies do not show any significant differences between CFS/ME and controls. In this study, we analysed parvovirus B19 markers in CFS/ME patients (n=200), diagnosed according to Fukuda CDC criteria, and normal blood donors (n=200). Serum from each subject was tested for anti-B19 VP2 IgM and IgG (by Biotrin ELISA), anti-B19 NS1 IgM and IgG (by immunofluorescence), and B19 DNA (by real-time PCR). CFS/ME patients and normal blood donors had a similar B19 seroprevalence (75 % versus 78 %, respectively). Eighty-three CFS patients (41.5 %) as compared with fourteen (7 %) normal blood donors tested positive for anti-B19 NS1 IgG (chi(2)=64.8; P<0.0001; odds ratio=9.42, CI 5.11-17.38). Of these 83 patients, 61 complained of chronic joint pain, while 22 did not. Parvovirus B19 DNA was detected in serum of 11 CFS patients and none of the controls by Taqman real-time PCR (chi(2)=9.35, P<0.002). Positivity for anti-B19 NS1 IgG was associated with higher expression levels of the human CFS-associated genes NHLH1 and GABPA. As NS1 antibodies are thought to indicate chronic or severe courses of B19 infection, these findings suggest that although the seroprevalence of B19 in CFS patients is similar to controls, the immune control of the virus in these patients may not be efficient.


[Morphological and molecular identification of Cysticercus fasciolaris isolated from rodent hosts (Rattus norvegicus) in Buenos Aires province (Argentina)].
In a rodent (Rattus norvegicus) survey in Buenos Aires province, metacestodes of tapeworms were found encysted in the liver of the host. The aim of this work was the morphological and molecular identification of this parasite. To achieve the molecular characterization of the parasite, ribosomal (28S) and mitochondrial (COI) DNA were amplified and sequenced. Based on both morphological and molecular data using bioinformatic tools, the metacestode was identified as Cysticercus fasciolaris. The adult form of this tapeworm (Taenia taeniaeformis) commonly infects felid and canid mammalian hosts. This is the first report on the molecular identification of Cysticercus fasciolaris in Buenos Aires province (Argentina).


Metabolomic profiling of liver tissues after acute administration of vardenafil in rats.
Erectile dysfunction (ED) diseases have almost affected 100 million men all over the world. Orally administered phosphodiesterase 5 (PDE 5) inhibitors are the most used pharmaceutical formulations for the treatment of ED. In this study, it is aimed to investigate the metabolomics feature of orally administered vardenafil in rats. To carry out the experimental procedure eight male Wistar albino rats were used. Their livers were gently removed and metabolomics profiles of each sample were determined by UPLC Q-TOF MS. Identification of metabolites was achieved by the METLIN database. Cluster analysis was also performed via Principle Component Analysis. Several metabolites were identified and results were evaluated by XCMS software. UPLC Q-TOF MS could be successfully applied to profile biomarkers and help us understand the molecular mechanisms of vardenafil usage. It was concluded that the level of some metabolites, responsible for the collagen synthesis and Kreb's cycle, has been statistically significant after the vardenafil administration.


[Androgen receptor in hepatocellular carcinoma and the surrounding liver tissues in China].
To investigate the reasons why primary liver cancer (hepatocellular carcinoma, HCC) is prevalent in male, androgen receptors (AR) in cytoplasm and nucleus were quantitatively detected in tumor tissue and tumor-adjacent tissue of 23 patients with HCC and liver tissue of normal livers by means of receptor radio-ligand binding assay. The concentrations of AR in cytoplasm and nucleus were as follows: 0.20-5.30, 1.91-6.50 fmol/mg protein in normal liver tissue; 5.12-27.62, 10.73-47.18 fmol/mg protein in tumor tissue; and 3.18-14.98, 5.15-36.32 fmol/mg protein in tumor-surrounding tissue. The mean concentrations of AR in cytoplasm or nucleus decreased in the order of tumor tissue, tumor-surrounding tissue and normal liver tissue, and the differences among them were statistically significant. The concentration of AR in tumor tissue and tumor-adjacent tissue had no direct or indirect association with sex, age, abuse of alcohol, HBsAg, HBcAb, AFP, pathological type of tumor, differentiation degree of tumor cells and the underlying liver disease. The result suggests that the prevalence of HCC in male over in female in China may be somehow related to the expression of AR in tumor cells.


Effects of spinach nitrate on insulin resistance, endothelial dysfunction markers and inflammation in mice with high-fat and high-fructose consumption.
Insulin resistance, which is associated with an increased risk of cardiovascular morbidity and mortality, has become a leading nutrition problem. Inorganic nitrate enriched in spinach has been demonstrated to reverse the pathological features of insulin resistance and endothelial dysfunction. However, the effects of a direct intake of nitrate-enriched spinach on insulin resistance and endothelial dysfunction have not been studied. To investigate the effects of spinach nitrate on insulin resistance, lipid metabolism, endothelial function, and inflammation in mice fed with a high-fat and high-fructose diet. A diet intervention of spinach with or without nitrate was performed in mice. A high-fat and high-fructose diet was used to cause insulin resistance, endothelial dysfunction, and inflammation in mice. The impacts of spinach nitrate on lipid profile, insulin resistance, markers of endothelial function, and inflammation were determined in mice. Spinach nitrate improved the vascular endothelial function of the mice with high-fat and high-fructose consumption, as evidenced by the elevated plasma nitrite level, increased serum nitric oxide (NO) level and decreased serum ET-1 level after spinach nitrate intervention. Spinach nitrate also reduced serum triglycerides, total cholesterol, and low-density lipoprotein-cholesterol levels and elevated serum high-density lipoprotein-cholesterol levels in the mice fed with a high-fat and high-fructose diet. Mice receiving spinach with 60 mg/kg of nitrate (1.02±0.34) showed a significantly low homeostasis model assessment-insulin resistance index as compared with the model mice (2.05±0.58), which is indicating that spinach nitrate could effectively improve the insulin resistance. In addition, spinach nitrate remarkably decreased the elevated serum C-reactive protein, tumor necrosis factor α, and interleukin-6 levels induced by a high-fat and high-fructose diet. The intake of spinach nitrate can augment NO status, improve lipid homeostasis, relieve inflammation, and enhance endothelial function, suggesting that spinach is promising dietary supplements for insulin resistance prevention.


Cigarette smoking and pancreas cancer risk: an evaluation based on a systematic review of epidemiologic evidence in the Japanese population.
Cigarette smoking has been recognized as an important risk factor for pancreas cancer, but the magnitude of the association may vary among geographical areas. Therefore, we reviewed epidemiologic studies on the association between cigarette smoking and pancreas cancer in the Japanese population. Original data were obtained from MEDLINE searched using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient') and the magnitude of association ('strong', 'moderate', 'weak' or 'no association'), together with biological plausibility as previously evaluated by the International Agency of Research on Cancer. We identified four cohort studies and three case-control studies. All cohort studies consistently showed positive associations between pancreas cancer and cigarette smoking, although statistical significance in each study is variable. Most of the cohort studies consistently showed that cigarette smoking had a dose-response relationship with pancreas cancer. One case-control study showed a strong positive association, but the rest did not show any association. Meta-analysis of seven studies indicated that a summary estimate for ever smoking relative to never smoking was 1.68 (95% confidence interval: 1.38-2.05). We conclude that there is convincing evidence that cigarette smoking moderately increases the risk of pancreas cancer in the Japanese population.


Membranous nephropathy due to chronic mercury poisoning from traditional Indian medicines: report of five cases.
Mercury contained in traditional medicines can cause chronic poisoning, which can cause membranous nephropathy (MN). We report five cases of nephrotic syndrome caused by MN with evidence of chronic mercury poisoning due to consumption of traditional Indian medicines such as Siddha and Ayurveda, which to our knowledge are the first such reports. All patients were seronegative for antibodies against phospholipase A2 receptor (PLA2R). Two patients, who had severe nephrotic syndrome, had received Siddha medicine for prolonged period and oral chelation with dimercaptopropane-1-sulfonic acid was successful in eliminating mercury, resulting in an improvement in nephrotic state in these patients. We suggest that mercury poisoning should be entertained in patients with anti-PLA2R antibody-negative MN, with history of consumption of traditional Indian medicines.


[MxyR of Mycobacterium tuberculosis Responds to Xylan; an Unusual Ligand for a MarR Family Transcriptional Regulator].
Among the repertoire of MarR family transcriptional regulators in Mycobacterium tuberculosis, gene rv3095 (mxyR) encodes Mycobacterial Xylan Regulator, MxyR. Gene mxyR is divergently oriented from a hydrolase (rv3094c), oxidoreductase (rv3093c) and an ABC transporter (rv3092c) and convergently oriented with xylanase (rv3096). Xylanase is commonly used by plant pathogenic microbes where they degrade xylan, the major component of hemicellulose. We have purified the transcriptional regulatory protein encoded by rv3095 and its molecular interactions were studied in detail using electrophoretic mobility shift assay. MxyR interacts with its upstream intergenic region mxyO with high specificity and at a dissociation constant of 5.01 ± 0.017 nM. Notably, this binding is attenuated by specific carbohydrate ligands such as xylan, L-Arabinose and D-Galactose with an IC50 values of 22.7 ± 1.02 ng/μL, 360.8 ± 24.25 ng/μL and 2320.0 ± 96.97 μg/μL, respectively. Consequently, it is evident that this association changes the conformation of the DNA binding helix α4 making the transcriptional regulator incompatible with binding to its cognate DNA, allowing xylanase and other genes to be transcribed. This study establishes the natural ligands of MxyR of M. tuberculosis providing insight on metabolic regulation of the carbohydrate, xylan.


Dazl protein expression in adult rat testis is up-regulated at meiosis and not hormonally regulated.
The Y-chromosomal DAZ (deleted in azoospermia) gene and the autosomal Dazl (deleted in azoospermia-like) gene are two crucial factors for the achievement and maintenance of spermatogenesis. Whereas Y-chromosomal DAZ is present in certain primates, it is lacking in rodents and other species. We have investigated the expression of Dazl protein during spermatogenesis in the adult rat testis using immunohistochemistry. Dazl immunoreactivity was found predominantly in the cytosol of primary pachytene spermatocytes. A weaker but clearly detectable signal was present in intermediate and B spermatogonia and in early spermatocytes from preleptotene to zygotene. The highest expression patterns were observed between stages IV and VIII during the spermatogenic cycle when spermatocytes prepare for the first meiotic division. Specific staining could also be observed in step 11-19 elongating spermatids in the acrosome region. Treatment for 42 days with a potent GnRH-antagonist abolished gonadotrophin secretion and led to a regressed testis, lacking most of the advanced germ cell types such as spermatids but still bearing spermatogonia and spermatocytes. No difference in staining pattern for Dazl protein was observed in GnRH antagonist-treated rats despite the lack of gonadotrophins and substantial impairment of the spermatogenic process, indicating that Dazl expression is clearly hormone-independent. The localization and level of Dazl expression suggests an important role in the regulation of the first meiotic stages of spermatogenesis. The hormone independent onset of expression points to an autonomous cell-cycle event in which Dazl seems to be essential for the entry into meiosis. The presence of Dazl in the acrosome region of elongating spermatids might reflect an unknown role of Dazl as a morphogenetic factor during spermiogenesis.


Incidence and Severity of Drug Interactions Before and After Switching Antiretroviral Therapy to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Treatment-Experienced Patients.
Switching antiretroviral therapy (ART) in people with HIV (PWH) can influence their risk for drug-drug interactions (DDIs). The purpose of this study was to assess changes in the incidence and severity of DDIs among PWH who switched their ART to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). This was a multicenter retrospective cohort study of PWH on ART and at least 1 concomitant medication (CM) who switched to BIC/FTC/TAF between 3/2018 and 6/2019. Using the University of Liverpool's HIV Drug Interaction Database, 2 DDI analyses were performed for each patient. The first assessed patients' preswitch ART regimens with their CM list. The second assessed the same CM list with BIC/FTC/TAF. Each ART-CM combination was given a score of 0 (no or potential weak interaction), 1 (potential interaction), or 2 (contraindicated interaction). A paired t test analyzed changes in total DDI scores following ART switches, and linear regression examined factors contributing to DDI score reductions. Among 411 patients, 236 (57%) had at least 1 DDI present at baseline. On average, baseline DDI scores (SD) were 1.4 (1.8) and decreased by 1 point (95% CI, -1.1 to -0.8) after patients switched to BIC/FTC/TAF (P < .0001). After adjusting for demographics, baseline ART, and CM categories, switching to BIC/FTC/TAF led to significant DDI score reductions in patients receiving CMs for cardiovascular disease, neurologic/psychiatric disorders, chronic pain, inflammation, gastrointestinal/urologic conditions, and conditions requiring hormonal therapy. Treatment-experienced PWH eligible to switch their ART may experience significant declines in number and severity of DDIs if switched to BIC/FTC/TAF.


Polypectomy and advanced endoscopic resection.
Most colorectal cancers evolve from colorectal adenomatous polyps in a pathway known as the adenoma to carcinoma sequence. Early detection and removal of colorectal adenomas can prevent the development of colorectal cancer. The vast majority of these polyps can be resected endoscopically. Advances in endoscopic resection techniques have led to expanded indications for endoscopic polypectomy, whereby giant polyps, scarred lesions and early cancers may be cured. We will outline conventional endoscopic mucosal resection techniques as well as more complex resection methods such as endoscopic submucosal dissection, full thickness resection and the use of combined endoscopic and laparoscopic assisted approaches to resection. We will also explore the role of a virtual multidisciplinary team to aid decision-making when managing large and complex colorectal polyps. This review will provide an update on the endoscopic management of colorectal polyps and highlight exciting new developments in this ever-expanding field.


Urinary N-acetyl-beta-D-glucosaminidase and neopterin aid in the diagnosis of rejection and acute tubular necrosis in initially nonfunctioning kidney grafts.
The study aimed at investigating urinary neopterin, a marker of cellular immune response, and urinary N-acetyl-beta-D-glucosaminidase (NAG), a marker of tubular damage, as noninvasive means to differentiate between acute tubular necrosis (ATN) and rejection in initially nonfunctioning (INF) human renal transplants. Seventy-two renal transplant patients were studied. Forty-five of them experienced an uncomplicated early posttransplant course, 27 patients suffered from INF. Twenty-two patients experienced ATN, 5 patients had a total of six biopsy-proven rejections. The NAG activity was measured by a colorimetric assay, neopterin by high-performance liquid chromatography. Receiver operating characteristics (ROC) analysis was applied to compute diagnostic performance and an optimal discriminating threshold. Demographic characteristics (age, gender, cold and warm ischemia periods, HLA mismatches) and posttransplant urinary NAG and neopterin excretions did not differ between ATN and rejection groups. Both urinary NAG and neopterin excretions were lower in the control group (NAG 1.8 +/- 1.0 U/mmol urinary creatinine; neopterin 270 +/- 126 nmol/mmol urinary creatinine; mean +/- SD) as compared with the ATN group (NAG 12 +/- 10 U/mmol, p < 0.001 vs. control group; neopterin 303 +/- 195 nmol/mmol, n.s.) and the rejection group (NAG 7 +/- 8 U/mmol, p < 0. 01; neopterin 508 +/- 419 nmol/mmol, p < 0.01). The ratio of urinary neopterin to NAG excretion (uNNR; dimension nmol neopterin/U NAG activity) increased during rejections as compared with ATN (139 +/- 74 vs. 50 +/- 38 nmol/U, p < 0.01). The area under the ROC curve for uNNR was 0.88 +/- 0.07 (p < 0.001). Applying a ROC-estimated optimal discriminator of uNNR (80 nmol/U), 16 patients with ATN and all six rejection episodes were classified correctly. The uNNR provides a noninvasive means to aid in the differential diagnosis of rejection and ATN in INF human renal transplants.


Association of haplotypes in the beta-chemokine locus with multiple sclerosis.
Linkage studies in multiple sclerosis (MS) identified several susceptibility loci. One of these regions includes chromosome 17q11 where a meta-analysis of data from three genome scans suggested linkage. This region encodes a cluster of genes for beta-chemokines or CC chemokine ligands (CCLs), which may be involved in the development of MS lesions. Here we aimed to test if CCL alleles and haplotypes are associated with MS. Using methods of linkage and association, we observed deviations from the expected 50% transmission of haplotypes from unaffected parents to their affected children at CCL2, CCL11-CCL8-CCL13 and CCL3 within the investigated 1.85 MB chromosomal segment. Analyses of the linkage disequilibrium map support that variants with possible relevance to MS can be located within these subregions. Identification of MS associated CCL variants may have direct clinical significance, as it can lead to the design of small competitive antagonists of these molecules with beneficial effects in the treatment of patients with early and active disease.


[Transgenic bioinsecticides inimical to parasites, but imical to environment].
Identification of Bacillus thuringiensis (Bt) parasporal crystalline inclusions composed of Cry proteins (=delta-endotoxins) resulted in introduction of microbial pesticides for biological control of some parasites. Delta-endotoxins are encoded by cry genes and are active against pest and nuisance insects (mostly mosquitoes and black flies--vectors of still important infectious diseases). The recent significant progress in DNA recombination technique may overcome limitations (a short residual persistence and a narrow spectrum of activity) associated with application of Bt conventional products. An introduction of cry genes from mosquitocidal subspecies B. th. israelensis (Bti) to the aquatic microorganisms inhabiting the same water bodies as mosquito and fly larvae (Diptera), has considerably improved the toxin delivery system to target insects. However, in the first experiments, in which Bti genes were cloned in cyanobacteria (Agmenellum quadruplicatum, Synechocystis PCC6803), a low gene expression was observed. Thus, it was necessary to integrate cry genes with strong promoters or to increase the number of vector-introduced copies. To overcome the obstacles of low gene expression and regulatory restriction for recombinant organisms, Bti spore/crystal formulations were encapsulated in the aquatic protozoan, Tetrahymena pyriformis. Large numbers of crystals (180 to 240/cell) were accumulated in its food vacuoles. This system resulted also in an increase in toxin persistence from 24 to 71 h. Cloning Bti genes in B. sphaericus (which also produces mosquitocidal proteins) was another way of an increasing Bt crystal residual activity. In this case, the crystals were additionally protected by B. sphaericus exosporium. These transgenic bacteria produced large amounts of delta-endotoxins that remained under water surface longer than the wild B. sphaericus strains. Moreover, they had a broader spectrum of insecticidal activity, because B. sphaericus is toxic mostly to Culex and Anopheles, and Bti--mostly to Culex, Aedes and some Simmulidae. Gram-negative bacteria (Asticcacaulis excentricus, Caulobacter crescentus and Ancylobacter aquaticus) turned out also to be effective delta-endotoxin producers. They grow on simple media and do not contain proteases which could degrade Cry proteins. In some cases, 100% mosquito larvae mortality was observed as a result of an exposure to transgenic microorganisms containing Bti genes. However, transgenic techniques are still not very popular in the world, despite their efficacy in biological control of insects. The transgenic organism construction is expensive and time-consuming. Genetic engineering is still raising a lot of anxieties and doubts concerning inappropriate use of modified organisms. On the other hand, this technology could solve many problems associated with vectors of important diseases, which are still unapproachable to contemporary medicine.


Human alpha-thrombin inhibition by the active site titrant N alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester: a comparative kinetic and X-ray crystallographic study.
Kinetics for the hydrolysis of the chromogenic active site titrant N alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester (Dmc-azaLys-ONp) catalyzed by bovine beta-trypsin, bovine alpha-thrombin, human alpha-thrombin, human Lys77-plasmin, human urinary kallikrein, the M(r) 33,000 and M(r) 54,000 species of human urokinase, as well as by porcine pancreatic beta-kallikrein-A and B have been obtained between pH 6.0 and 8.0, at 21.0 degrees C. Moreover, the three dimensional structure of the human alpha-thrombin-(hirugen).Dmc-azaLys acyl.enzyme complex has been analyzed and refined by X-ray crystallography at 2.0 A resolution (R-factor = 0.168). As observed for bovine beta-trypsin, the acylating inhibitor molecule is covalently bound to the Ser195 catalytic residue, filling the human alpha-thrombin S1 primary specificity subsite with its lysyl side-group. However, the carbonyl group of the scissile human alpha-thrombin.Dmc-azaLys acyl bond does not occupy properly the oxyanion binding hole. At variance from the bovine beta-trypsin.Dmc-azaLys acyl.enzyme structure, a second, not covalently bound, inhibitor molecule, partly shielded by the 60-insertion loop of human alpha-thrombin, is contacting the enzyme "aryl-binding site".


Facile Fabrication and Characterization of Improved Proton Conducting Sulfonated Poly(Arylene Biphenylether Sulfone) Blocks Containing Fluorinated Hydrophobic Units for Proton Exchange Membrane Fuel Cell Applications.
Sulfonated poly(arylene biphenylether sulfone)-poly(arylene ether) (SPABES-PAE) block copolymers by controlling the molar ratio of SPABES and PAE oligomers were successfully synthesized, and the performances of SPABES-PAE (1:2, 1:1, and 2:1) membranes were compared with Nafion 212. The prepared membranes including fluorinated hydrophobic units were stable against heat, nucleophile attack, and physio-chemical durability during the tests. Moreover, the polymers exhibited better solubility in a variety of solvents. The chemical structure of SPABES-PAEs was investigated by ¹H nuclear magnetic resonance (¹H NMR), Fourier transform infrared spectroscopy (FT-IR), and gel permeation chromatography (GPC). The membrane of SPABES-PAEs was fabricated by the solution casting method, and the membranes were very flexible and transparent with a thickness of 70⁻90 μm. The morphology of the membranes was observed using atomic force microscope and the ionic domain size was proved by small angle X-ray scattering (SAXS) measurement. The incorporation of polymers including fluorinated units allowed the membranes to provide unprecedented oxidative and dimensional stabilities, as verified from the results of ex situ durability tests and water uptake capacity, respectively. By the collective efforts, we observed an enhanced water retention capacity, reasonable dimensional stability and high proton conductivity, and the peak power density of the SPABES-PAE (2:1) was 333.29 mW·cm-2 at 60 °C under 100% relative humidity (RH).


Extracting diagnostic stromal organization features based on intrinsic two-photon excited fluorescence and second-harmonic generation signals.
Intrinsic two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) signals are shown to differentiate between normal and neoplastic human esophageal stroma. It was found that TPEF and SHG signals from normal and neoplastic stroma exhibit different organization features, providing quantitative information about the biomorphology and biochemistry of tissue. By comparing normal with neoplastic stroma, there were significant differences in collagen-related changes, elastin-related changes, and alteration in proportions of matrix molecules, giving insight into the stromal changes associated with cancer progression and providing substantial potential to be applied in vivo to the clinical diagnosis of epithelial precancers and cancers.


Identification of a calcium-controlled negative regulatory system affecting Vibrio cholerae biofilm formation.
Vibrio cholerae's capacity to cause outbreaks of cholera is linked to its survival and adaptability to changes in aquatic environments. One of the environmental conditions that can vary in V. cholerae's natural aquatic habitats is calcium (Ca(+2)). In this study, we investigated the response of V. cholerae to changes in extracellular Ca(2+) levels. Whole-genome expression profiling revealed that Ca(2+) decreased the expression of genes required for biofilm matrix production. Luria-Bertani (LB) medium supplemented with Ca(2+) (LBCa(2+)) caused V. cholerae to form biofilms with decreased thickness and increased roughness, as compared with biofilms formed in LB. Furthermore, addition of Ca(2+) led to dissolution in biofilms. Transcription of two genes encoding a two-component regulatory system pair, now termed calcium-regulated sensor (carS) and regulator (carR), was decreased in cells grown in LBCa(2+). Analysis of null and overexpression alleles of carS and carR revealed that expression of vps (Vibriopolysaccharide) genes and biofilm formation are negatively regulated by the CarRS two-component regulatory system. Through epistasis analysis we determined that CarR acts in parallel with HapR, the negative regulator of vps gene expression.


Predictive factors of excessive online poker playing.
Despite the widespread rise of online poker playing, there is a paucity of research examining potential predictors for excessive poker playing. The aim of this study was to build on recent research examining motives for Texas Hold'em play in students by determining whether predictors of other kinds of excessive gambling apply to Texas Hold'em. Impulsivity, negative mood states, dissociation, and boredom proneness have been linked to general problem gambling and may play a role in online poker. Participants of this study were self-selected online poker players (N = 179) who completed an online survey. Results revealed that participants played an average of 20 hours of online poker a week and approximately 9% of the sample was classified as a problem gambler according to the Canadian Problem Gambling Index. Problem gambling, in this sample, was uniquely predicted by time played, dissociation, boredom proneness, impulsivity, and negative affective states, namely depression, anxiety, and stress.


Effective Face Detector Based on YOLOv5 and Superresolution Reconstruction.
The application of face detection and recognition technology in security monitoring systems has made a huge contribution to public security. Face detection is an essential first step in many face analysis systems. In complex scenes, the accuracy of face detection would be limited because of the missing and false detection of small faces, due to image quality, face scale, light, and other factors. In this paper, a two-level face detection model called SR-YOLOv5 is proposed to address some problems of dense small faces in actual scenarios. The research first optimized the backbone and loss function of YOLOv5, which is aimed at achieving better performance in terms of mean average precision (mAP) and speed. Then, to improve face detection in blurred scenes or low-resolution situations, we integrated image superresolution technology on the detection head. In addition, some representative deep-learning algorithm based on face detection is discussed by grouping them into a few major categories, and the popular face detection benchmarks are enumerated in detail. Finally, the wider face dataset is used to train and test the SR-YOLOv5 model. Compared with multitask convolutional neural network (MTCNN), Contextual Multi-Scale Region-based CNN (CMS-RCNN), Finding Tiny Faces (HR), Single Shot Scale-invariant Face Detector (S3FD), and TinaFace algorithms, it is verified that the proposed model has higher detection precision, which is 0.7%, 0.6%, and 2.9% higher than the top one. SR-YOLOv5 can effectively use face information to accurately detect hard-to-detect face targets in complex scenes.


Role of Forkhead Box O Transcription Factors in Oxidative Stress-Induced Chondrocyte Dysfunction: Possible Therapeutic Target for Osteoarthritis?
Chondrocyte dysfunction occurs during the development of osteoarthritis (OA), typically resulting from a deleterious increase in oxidative stress. Accordingly, strategies for arresting oxidative stress-induced chondrocyte dysfunction may lead to new potential therapeutic targets for OA treatment. Forkhead box O (FoxO) transcription factors have recently been shown to play a protective role in chondrocyte dysfunction through the regulation of inflammation, autophagy, aging, and oxidative stress. They also regulate growth, maturation, and matrix synthesis in chondrocytes. In this review, we discuss the recent progress made in the field of oxidative stress-induced chondrocyte dysfunction. We also discuss the protective role of FoxO transcription factors as potential molecular targets for the treatment of OA. Understanding the function of FoxO transcription factors in the OA pathology may provide new insights that will facilitate the development of next-generation therapies to prevent OA development and to slow OA progression.


Preoperative factors affecting the outcome of unruptured posterior circulation aneurysm surgery.
We retrospectively investigated preoperative variables contributing to adverse surgical outcome for repair of unruptured posterior circulation aneurysms on data collected prospectively between October 1989 and March 2010. Putative risk factors including age, sex, smoking status, positive family history, modified Rankin Score prior to the surgery, size of the aneurysm, specific site (basilar caput and trunk, vertebral artery and posterior inferior cerebellar artery), midline location, presence of calcium, thrombus or irregularity in the aneurysm on preoperative imaging, associated arteriovenous malformation and preoperative coiling were investigated using regression analyses. In a total of 121 operations, surgical mortality and morbidity was 16.3%. For patients with aneurysms less than 9mm this rate was 3.2%. Among the investigated variables we found that size, calcification of the aneurysm and age were each predictors of surgical outcome of unruptured posterior circulation aneurysms.


Memory deficits after resection from left or right anterior temporal lobe in humans: a meta-analytic review.
Memory deficits in epileptic patients have been found in some, but not all studies assessing the effects of side of seizures and resection from a temporal lobe on cognitive performance. The purpose of this study was to provide a quantitative review of previous studies on this issue. Based on conventional meta-analytic procedures, we identified 33 studies that assessed verbal and nonverbal memory performance before and after anterior temporal lobectomy. The Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale were used. These studies were then subjected to two levels of analyses: (a) vote-counting procedure, and (b) effect-size calculations and comparisons. Overall, the data confirmed previous findings that verbal memory tasks are sensitive to left hemisphere dysfunction. The efficacy of a "nonverbal" task for tapping function in the nondominant (right) hemisphere was not confirmed, although a trend supporting this speculation was observed. With regard to the comparison of changes in verbal and nonverbal memory before and after resection from a temporal lobe, a clear trend was observed for decline in verbal memory function after resection from the left, especially significant for immediate verbal recall. A trend for contralateral improvement on nonverbal memory also was observed. The pattern of memory change after resection from the right temporal lobe was less clear. The findings of this study suggest that side of epileptic seizure and surgical resection from a temporal lobe affect verbal memory functions. The relations between the laterality of epileptic seizure, surgical resection from the temporal lobe, and nonverbal memory are to be verified by further research.


Tunneled hemodialysis catheter-related bloodstream infections: a prospective multicenter cohort study from Spain.
Catheter-related bloodstream infections (CRBSI) are common among patients undergoing long-term hemodialysis (HD) worldwide. The aim of this study was look into the incidence, epidemiology, and risk factors for CRBSI in four medical centers and Spanish dialysis facilities following a common protocol for insertion and management of tunneled hemodialysis catheters (THCs). Prospective study including all THCs inserted from September-04 to October-05. Follow-up was from THC insertion to its withdrawal, onset of CRBSI or end of study. Data of all THCs, CRBSI episodes, and catheter complications were collected. A descriptive analysis of CRBSI incidence and etiology and multivariate Cox regression to identify risk factors for CRBSI was performed. A total of 130 THCs in 123 patients were inserted. There were 34 879 catheter-days. Twelve CRBSI in 11 patients with a CRBSI rate of 0.34/1000 catheter-days were recorded. CRBSI was caused by gram-positive coccus in 91.7% of the cases. Vascular cause of renal disease (HR 25.5 CI95% 5.5-117.2), and a previous THC (HR 5.1 CI95% 1.3-19.1) were identified as risk factors for CRBSI. CRBSI were satisfactorily resolved in 83.3% of the cases. Overall mortality was 14.6% (18/123), in two cases (2/11) death occurred within 30 days after CRBSI onset. Although some factors, such as vascular cause of renal disease and previous THC medical history, have been related to the onset of tunneled catheter-related bloodstream infections, the incidence of these bacteremia, mainly produced by gram-positive coccus, is low among hemodialysis patients and the mortality rate is not high.


Uniform chitosan microspheres for potential application to colon-specific drug delivery.
Uniform chitosan microspheres have been fabricated and weakly crosslinked for potential applications in colon-specific drug delivery. The effects of microsphere size, crosslinking density and electrostatic interactions between the drug and chitosan on drug release were studied, employing model drugs of different acidities. When the drug was basic, all chitosan spheres exhibited 100% release within 30 min. As the acidity of the drug increased, the release slowed down and depended on the crosslinking density and microsphere size. The release of weakly acidic drug was most suppressed for large spheres (35-38 microm), while the small spheres (23-25 microm) with higher crosslinking exhibited the most retention of highly acidic drug, indicating that they are a promising candidate for colon-specific delivery.


The use of non-linear analysis for differentiating the biomagnetic activity in ovarian lesions.
In this study we investigated the biomagnetic activity measured with the superconducting quantum interference device (SQUID) in benign and malignant ovarian lesions using non-linear analysis. We used a single channel biomagnetometer SQUID in order to measure the magnetic field emitted from benign and malignant ovarian lesions. We can differentiate such biomagnetic activities using non-linear analysis. Using the application of non-linear analysis in the ovarian lesions together with the use of dimensional calculations we have observed a clear saturation value for the dimension of malignant ovarian lesions and non-saturation for benign ovarian lesions. The biomagnetic measurements with the SQUID and the application of non-linear analysis in benign and malignant ovarian lesions, is a promising procedure in assessing and differentiating ovarian tumours.


Post-Anaesthetic Discharge Scoring System to assess patient recovery and discharge after colonoscopy.
To investigate whether discharge scoring criteria are as safe as clinical criteria for discharge decision and allow for earlier discharge. About 220 consecutive outpatients undergoing colonoscopy under sedation with Meperidine plus Midazolam were enrolled and assigned to 2 groups: in Control-group (110 subjects) discharge decision was based on the clinical assessment; in PADSS-group (110 subjects) discharge decision was based on the modified Post-Anaesthetic Discharge Scoring System (PADSS). Measurements of the PADDS score were taken every 20 min after colonoscopy, and patients were discharged after two consecutive PADSS scores ≥ 9. The investigator called each patient 24-48 h after discharge to administer a standardized questionnaire, to detect any delayed complications. Patients in which cecal intubation was not performed and those who were not found at follow-up phone call were excluded from the study. Thirteen patients (7 in Control-group and 6 in PADSS-group) were excluded from the study. Recovery from sedation was faster in PADSS-group than in Control-group (58.75 ± 18.67 min vs 95.14 ± 10.85 min, respectively; P < 0.001). Recovery time resulted shorter than 60 min in 39 patients of PADSS-group (37.5%), and in no patient of Control-group (P < 0.001). At follow-up phone call, no patient declared any hospital re-admission because of problems related to colonoscopy and/or sedation. Mild delayed post-discharge symptoms occurred in 57 patients in Control-group (55.3%) and in 32 in PADSS-group (30.7%). The most common symptoms were drowsiness, weakness, abdominal distension, and headache. Only 3 subjects needed to take some drugs because of post-discharge symptoms. The Post-Anaesthetic Discharge Scoring System is as safe as the clinical assessment and allows for an earlier patient discharge after colonoscopy performed under sedation.


New, sensitive fluorogenic substrates for human cathepsin G based on the sequence of serpin-reactive site loops.
Cathepsin G has both trypsin- and chymotrypsin-like activity, but studies on its enzymatic properties have been limited by a lack of sensitive synthetic substrates. Cathepsin G activity is physiologically controlled by the fast acting serpin inhibitors alpha1-antichymotrypsin and alpha1-proteinase inhibitor, in which the reactive site loops are cleaved during interaction with their target enzymes. We therefore synthesized a series of intramolecularly quenched fluorogenic peptides based on the sequence of various serpin loops. Those peptides were assayed as substrates for cathepsin G and other chymotrypsin-like enzymes including chymotrypsin and chymase. Peptide substrates derived from the alpha1-antichymotrypsin loop were the most sensitive for cathepsin G with kcat/Km values of 5-20 mM-1 s-1. Substitutions were introduced at positions P1 and P2 in alpha1-antichymotrypsin-derived substrates to tentatively improve their sensitivity. Replacement of Leu-Leu in ortho-aminobenzoyl (Abz)-Thr-Leu-Leu-Ser-Ala-Leu-Gln-N-(2, 4-dinitrophenyl)ethylenediamine (EDDnp) by Pro-Phe in Abz-Thr-Pro-Phe-Ser-Ala-Leu-Gln-EDDnp produced the most sensitive substrate of cathepsin G ever reported. It was cleaved with a specificity constant kcat/Km of 150 mM-1 s-1. Analysis by molecular modeling of a peptide substrate bound into the cathepsin G active site revealed that, in addition to the protease S1 subsite, subsites S1' and S2' significantly contribute to the definition of the substrate specificity of cathepsin G.


Unraveling the mystery of pain in chronic pancreatitis.
Chronic pancreatitis is typically a painful condition and it can be associated with a severe burden of disease. The pathogenesis of pain in this disorder is poorly understood and its treatment has been largely empirical, often consisting of surgical or other invasive methods, with an outcome that is variable and frequently unsatisfactory. Human and experimental studies have indicated a critical role for neuronal mechanisms that result in peripheral and central sensitization. The pancreatic nociceptor seems to be significantly affected in this condition, with increased excitability associated with downregulation of potassium currents. Some of the specific molecules implicated in this process include the vanilloid receptor, TRPV1, nerve growth factor, the protease activated receptor 2 and a variety of others that are discussed in this Review. Studies have also indicated novel therapeutic targets for this condition.


[Research progress of Baizhu Shaoyao powder in treating ulcerative colitis].
Ulcerative colitis is a chronic, nonspecific and complex intestinal disease. The current clinical treatment guideline of this disease recommends a variety of options with oral western medicines, such as aminosalicylic acids, glucocorticosteroids, and immunosuppressors. However, due to their unstable therapeutic effects, high toxicities, and strong drug dependence, they are not suitable for long-term administration. Baizhu Shaoyao powder, a traditional Chinese medicinal prescription, is clinically and commonly used for tonifying spleen and softening liver as well as eliminating dampness and relieving diarrhea. Recent researches suggest that Baizhu Shaoyao powder has significant effect in the treatment of ulcerative colitis. This article reviewed the research progress on the curative effect and action mechanism of Baizhu Shaoyao powder in treating ulcerative colitis, and provided the ideas and directions for its further research in future.


Adsorption of the compounds encountered in monosaccharide dehydration in zeolite beta.
A comprehensive study of the adsorption of the compounds involved in the reaction of dehydration of fructose to 5-hydroxymethyl furfural (HMF) on the zeolite H-BEA with SiO2/Al2O3 = 18 has been carried out. Furthermore, a method for the estimation of the real adsorption loading from the experimentally measured excess adsorption is developed and applied to calculate the adsorption isotherms both in the case of single-solute and multisolute mixtures. It was found that zeolite H-BEA adsorbs HMF and levulinic acid from water mixtures to greater extent than sugars and formic acid, which prefer to partition in the aqueous phase. HMF and levulinic acid adsorption isotherms could be fitted in a Redlich-Peterson isotherm model, while the adsorption of formic acid is better fitted using the Freundlich model and sugars via the Henry model. Adsorption loadings decreased with increasing temperature (0, 25, and 40 °C), which is characteristic of an exothermic process. From the temperature dependence of the isotherms, the limiting heat of adsorption at zero coverage was determined using van't Hoff equation. Given the importance and the complexity of multicomponent systems, several experiments of adsorption of multisolute solutions have been carried out. In most of the cases, the ideal adsorbed solution theory (IAST) has been proven to satisfactorily predict adsorption from multisolute mixtures using as input the single-solute isotherms.


A Novel Case of Severe Respiratory Symptoms and Persistent Pulmonary Hypertension in a Saudi Neonate With SARS-CoV-2 Infection.
Coronavirus disease 2019 (COVID-19) is an emergent disease that has spread rapidly to infect more than 210 countries across the world. With the increasing number of infected pregnant women, many physicians hypothesized the perinatal transmission as a potential route of transmission. Some cases of perinatal transmission have been described, but it is unclear if these occurred via the transplacental or the transcervical routes or through environmental exposure. In this report, we described a case of a female infant who was delivered by caesarean section at 34 weeks' gestation to an infected mother. The neonate was transferred into the Neonatal Intensive Care Unit (NICU) Level 3, with the precaution of airborne and contact isolation. All required investigations were performed, including blood gases, nasopharyngeal swab, chest x-ray, and echocardiogram. On the fifth day of delivery, her investigations demonstrated a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite applying all recommended guidelines and following the treatment protocol, she developed severe respiratory symptoms with persistent pulmonary hypertension, which progressed significantly to her death.


Single-center phase II trial of transarterial chemoembolization with drug-eluting beads for patients with unresectable hepatocellular carcinoma: initial experience in the United States.
This prospective phase II pilot study evaluated safety and efficacy of transarterial chemoembolization (TACE) with drug-eluting beads (DEBs) loaded with doxorubicin in patients with unresectable hepatocellular carcinoma (HCC). Twenty patients with unresectable HCC (75% Child's A, 95% Eastern Cooperative Oncology Group performance status 0 to 1, 60% Barcelona Clinic Liver Cancer C, tumor size 6.9 cm) underwent 34 DEB-TACE sessions. Primary endpoints were tumor response, assessed by contrast-enhanced magnetic resonance imaging at 1 month after treatment, using size (response evaluation criteria in solid tumors [RECIST]), contrast-enhancement (European Association for the Study of the Liver) and apparent diffusion coefficient values, and safety assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Secondary endpoints included feasibility, progression-free survival, and overall survival. DEB-TACE was successfully performed in 34 sessions and demonstrated a favorable safety profile. On initial (1 month) postprocedural magnetic resonance imaging, treated lesions had a mean decrease in size of 4% (P = 0.1129). Using RECIST, partial response was achieved in 2 patients (10%), and 18 patients (90%) had stable disease. Treated tumors demonstrated a mean decrease in contrast enhancement of 64% (P < 0.0001). By European Association for the Study of the Liver criteria, 12 patients (60%) had objective tumor response, and 8 (40%) had stable disease. No patients had progression of a treated lesion while undergoing treatment. At 6 months, the disease control rate was 95% using RECIST. Overall survival rates at 1 and 2 years were 65% and 55%, respectively; median overall survival was 26 months. DEB-TACE is safe and effective in achieving local tumor control in patients with unresectable HCC.


The effect of parents' alcohol problems on children's behaviour as reported by parents and by teachers.
Associations between parents' alcohol problems when children were aged 9 and children's behaviour at ages 9 and 13 as reported by parents and teachers were investigated. The sample consisted of participants in a multidisciplinary longitudinal study, data were collected by face-to-face interview. When compared to children with no or mild parental alcohol problems, children classified as having severe parental alcohol problems were more likely to display high levels of problem behaviour at age 9 as reported by teachers and at age 13 as reported by parents. Poorer family relationships, lower verbal and reading proficiency and being male were also associated with high levels of behaviour problems.


[Benefits and limits of minimally invasive techniques in thyroid surgery].
The present study was designed to investigate the potential benefits and limits of two minimally invasive thyroidectomy procedures, namely minimally invasive video-assisted thyroidectomy (MIVAT) and open minimal-incision thyroidectomy (MIT). From May 2000 to June 2006, a prospective, non-randomised study was performed on 957 consecutive patients undergoing thyroid surgery. Fifty-six (5.8%) underwent MIVAT, 214 (22.4%) MIT and 687 (71.8%) conventional thyroidectomy (CT). Patients were selected for MIVAT when total thyroid volume was < or = 30 mL and for MIT when total thyroid volume was > 30 but < or = 80 mL, as determined by ultrasonography. The length of the central neck skin incision was 1.5-2 cm for MIVAT, 2.5-3.5 cm for MIT and 6-10 cm for CT. The incidence of definitive hypoparathyroidism or recurrent laryngeal palsy after MIVAT or MIT was comparable to that occurring after CT. Patients undergoing MIVAT or MIT experienced significantly less postoperative pain than those undergoing CT. Less pain was also registered in the MIVAT patient cohort as compared to the MIT group. Patients undergoing MIVAT or MIT were more satisfied with the cosmetic result as compared to those undergoing CT, whereas no significant differences were found between the MIVAT and MIT groups. As compared to CT, MIVAT and MIT provided a significant improvement in terms of cosmetic results and postoperative pain. Nevertheless, the main limiting factor for minimally invasive thyroid surgery still remains the size of the thyroid.


Ductal carcinoma in situ of the breast: a comparative analysis of histology, nuclear area, ploidy, and neovascularization provides differentiation between low- and high-grade tumors.
Ductal carcinoma in situ (DCIS) is a heterogeneous group of lesions that has been subdivided into three types: well differentiated (grade I), moderately differentiated (grade II), and poorly differentiated (grade III). Forty-five cases of DCIS were analyzed for image analysis: nuclear area, DNA ploidy, and vascularization in order to establish a more precise correlation between the histologic grade and these morphometric parameters. Our results confirm that the mean nuclear area, DNA ploidy, and microvessel density (MVD) progressively increased from DCIS grade I to DCIS grade III. The analysis of the nuclear area in relationship to DCIS grading demonstrated a progressive increase of values between grades I/II to grade III, but these data have no statistical significance. An analysis of DNA ploidy demonstrated significant differences between grades I/III (p < 0.05), but there was no statistical significance between grades I/II, grades II/III, or both (p > 0.005). The analysis of MVD was extremely significant between grades I/III (p < 0.001) and grades II/III (p < 0.001), but between grades I/II, these values showed no significant differences (p > 0.05). Based on this study, it can be concluded that image analysis techniques confirm how DCIS presents morphometric values that increase from DCIS grade I to DCIS grade III and that within this spectrum, DCIS grade III can be identified as a group of tumors presenting a large nuclear area, aneuploid DNA, and abundant vascular neogenesis, confirming that this neoplasm displays more aggressive patterns than the other two types. These criteria should justify a higher rate of tumor progression to DCIS grade III.


Blockade of purinergic 2 receptors attenuates the mechanoreceptor component of the exercise pressor reflex.
The finding that pyridoxalphosphate-6-azophenyl-2,4-disulfonic acid (PPADS), a P2 antagonist, attenuated the pressor response to calcaneal tendon stretch, a purely mechanical stimulus, raises the possibility that P2 receptors sensitize mechanoreceptors to static contraction of the triceps surae muscles. The mechanical component of the exercise pressor reflex, which is evoked by static contraction, can be assessed by measuring renal sympathetic nerve activity during the first 2-5 s of this maneuver. During this period of time, group III mechanoreceptors often discharge explosively in response to the sudden tension developed at the onset of contraction. In decerebrated cats, we, therefore, examined the effect of PPADS (10 mg/kg) injected into the popliteal artery on the renal sympathetic and pressor responses to contraction and stretch. We found that PPADS significantly attenuated the renal sympathetic response to contraction, with the effect starting 2 s after its onset and continuing throughout its 60-s period. PPADS also significantly attenuated the renal sympathetic nerve response to stretch, but did so after a latency of 10 s. Our findings lead us to conclude that P2 receptors sensitize group III muscle afferents to contraction. The difference in the onset latency between the PPADS-induced attenuation of the renal sympathetic response to contraction and the renal sympathetic response to stretch is probably due to the sensitivities of different populations of group III afferents to ATP released during contraction and stretch.


Trihalomethane determination and removals from the main discharge channel of Konya City (Turkey).
Konya Main Discharge Channel is a very important environmental problem due to carrying the domestic waste water of Konya city centre as well as industrial waste water. Lowest flow rate of the channel was observed in October about 2 10(4) m3d(-1). In this period, channel water is not only waste water but includes more rain water coming from Gölyazi region. Discharge channel water can only reach to Tuz Lake for three months in a year. At other times of the year, water cannot reach the lake because of high evaporation, infiltration and usage of the water for irrigation. The land irrigated with the waste water tends to lose its productivity. In this study, water samples were collected and analysed from one hourly period for 2 days (24 x 2 = 48), daily period for 3 weeks (7 x 3 = 21) and monthly samples for a year (9 months). The samples were analysed as to whether these contained trihalomethanes or not, also results were compared with disinfection method that is used for drinking water, and samples were collected from ten different points on the channel. Pollution level of the channel water was controlled in accordance with the Turkish Water Pollution Control Law. In addition to trihalomethanes analysis, the effect of aeration on trihalomethanes was investigated. Collected samples (given above) were analysed for trihalomethanes compounds, and the relationship between disinfection type and dosage method on trihalomethanes formation was compared in this study.


Relationship between gamma-glutamyl transpeptidase and mean urinary alcohol levels in alcoholics while drinking and after alcohol withdrawal.
In 42 patients with alcoholic liver disease in whom daily urinary ethanol concentrations were measured for 3 months, after an abstinence of at least 1 month, serum gamma-glutamyl transpeptidase (GGT) activity was found to correlate (r = 0.69; p less than 0.0001) with mean urinary alcohol levels. The half-life of serum GGT decay in 32 patients who remained abstinent for an 8-week period was calculated to be 26 days. This prolonged half-life can result in high serum GGT levels in patients abstinent for prolonged periods, in whom serum GGT baselines before abstinence were very high. Individual variations in serum GGT levels should be interpreted in relation to continued alcohol consumption, keeping in mind the long half-life for this enzyme in these patients.


[Advancing public mental health research in Latin America].
This special issue on Mental Health of the Journal of the School of Medicine, represents a significant contribution to the advance of public mental health research and training in Latin America. The editors (as well as the authors) deserve much credit for having conceived and implemented the joint publication of these papers. In this brief introduction, I draw attention to four ways in which their effort is likely to accelerate progress in this field.