Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P2Y- and facilitatory A2A-purinoceptors.
1. The effects of analogues of adenosine and ATP on noradrenaline release elicited by electrical stimulation (5 Hz, 2700 pulses) were studied in superfused preparations of rat tail artery. The effects of purinoceptor antagonists, of adenosine deaminase and of adenosine uptake blockade were also examined. Noradrenaline was measured by h.p.l.c. electrochemical detection. 2. The A1-adenosine receptor agonist, N6-cyclopentyladenosine (CPA; 0.1-100 nM) reduced, whereas the A2A-receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 3-30 nM) increased evoked noradrenaline overflow. These effects were antagonized by the A1-adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 20 nM) and the A2-adenosine receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX; 100 nM), respectively. The P2Y-purinoceptor agonist, 2-methylthio-ATP (1-100 microM) reduced noradrenaline overflow, an effect prevented by the P2-purinoceptor antagonist, cibacron blue 3GA (100 microM) and suramin (100 microM). 3. Adenosine deaminase (2 u ml-1), DMPX (100 nM) and inhibition of adenosine uptake with S-(p-nitrobenzyl)-6-thioinosine (NBTI; 50 nM) decreased evoked noradrenaline overflow. DPCPX alone did not change noradrenaline overflow but prevented the inhibition caused by NBTI. The P2Y-purinoceptor antagonist, cibacron blue 3GA (100 microM) increased evoked noradrenaline overflow as did suramin, a non-selective P2-antagonist. 4. It is concluded that, in rat tail artery, inhibitory (A1 and P2Y) and facilitatory (A2A) purinoceptors are present and modulate noradrenaline release evoked by electrical stimulation. Endogenous purines tonically modulate noradrenaline release through activation of inhibitory P2Y and facilitatory A2A purinoceptors, whereas a tonic activation of inhibitory A1 purinoceptors seems to be prevented by adenosine uptake.


Increased lipid peroxidation by graphene quantum dots induces ferroptosis in macrophages.
Graphene quantum dots (GQDs) are an excellent tool for theranostics, and are widely used in nanomedical applications. The biosafety of GQDs has received abundant attention, but their latent toxicological mechanisms remain inadequately understood. To investigate the cellular and molecular mechanisms underlying graphene-mediated changes, quantitative proteomics and untargeted lipidomics were integrated. We discovered that glutathione peroxidase 4 as a key regulator of ferroptosis, was down-regulated at the protein level by GQDs. Lipidomics profiling with features of ferroptosis was identified in GQDs-treated RAW264.7 macrophages. Furthermore, GQDs exposure was associated with reduced levels of GSH and increased lipid peroxidation. Overexpression of GPX4 in RAW264.7 cells and pre-treatment of a ferroptosis inhibitor Ferrostatin-1 (Fer-1) not only suppressed cell death, but also alleviated lipid peroxidation. Taken together, our results indicated that GQDs exposure induced ferroptosis in RAW264.7 macrophages, and provided essential data for biosafety evaluations of GQDs.


Prostaglandins stimulate serotonin acetylation in chick pineal cells: involvement of cyclic AMP-dependent and calcium/calmodulin-dependent mechanisms.
The effects of prostaglandins (PGs) on the activity of the rate-limiting enzyme of melatonin biosynthesis, arylalkylamine-N-acetyltransferase (NAT) were investigated on primary cultures of dispersed chick pineal cells. In indomethacin-treated cells, PGs caused a four-fold increase in NAT activity. This response was associated with an eight-fold increase in cyclic AMP (cAMP) levels. The potency order of PGs was the same for NAT and for cAMP responses (PGE1 > PGE2 > PGF2 alpha >> cloprostenol). However, each PG tested was 30- to 200-fold more potent to increase NAT activity than to stimulate cAMP accumulation. As a result, half-maximal stimulation of NAT by PGs was not associated with an increase in cAMP levels. Half-maximal stimulation of NAT by PGE1 was highly sensitive to inhibition by a calcium/calmodulin antagonist (W-7). In contrast, maximal stimulation of NAT by PGE1 as well as stimulations evoked by either forskolin or 8-bromo-cAMP were poorly sensitive to inhibition by W-7. These results indicate that an increase in cAMP levels may be responsible for the maximal stimulation of NAT evoked by PGs, whereas half-maximal stimulation of NAT by PGs would rely principally on a calcium/calmodulin-dependent mechanism.


Phosphorylation of the Epstein-Barr virus BZLF1 immediate-early gene product ZEBRA.
Expression of the Epstein-Barr virus (EBV) BZLF1 gene product ZEBRA is a first step in the cascade of the virus-productive cycle. ZEBRA protein was detected by immunoblotting as a single band at 38 kDa in Akata cells after crosslinkage of membrane immunoglobulin G (IgG) with anti-IgG antibody. Immunoprecipitation of [32P]phosphate-labeled, anti-IgG-stimulated Akata cells with anti-ZEBRA antibody showed that ZEBRA was phosphorylated. Phosphoamino acid analysis demonstrated phosphorylation of serine, but not threonine or tyrosine, and tryptic-peptide mapping showed multiple phosphorylated peptides of ZEBRA. Treatment with 8-bromo cAMP and blockage of phosphodiesterase by theophylline in anti-IgG-stimulated cells increased the phosphorylation of three ZEBRA peptides. Incubation with 12-O-tetradecanoylphorbol-13-acetate (TPA) reduced the phosphorylation of these three ZEBRA peptides, while treatment with staurosporine, a protein kinase C (PKC) inhibitor, enhanced their phosphorylations. These data suggest that activation of PKC with TPA induces the ZEBRA dephosphorylation and that activation of cAMP-dependent protein kinase A enhances the ZEBRA phosphorylation at the specific sites.


Intravitreal aflibercept for macular oedema secondary to central retinal vein occlusion in patients with prior treatment with bevacizumab or ranibizumab.
PurposeTo report the visual and anatomic outcomes in eyes with macular oedema (MO) secondary to central retinal vein occlusion (CRVO) that were switched from either intravitreal bevacizumab or ranibizumab to intravitreal aflibercept.MethodsTwo-center retrospective chart review. Eyes with MO secondary to CRVO that received a minimum of three intravitreal injections of bevacizumab or ranibizumab and were switched to intravitreal aflibercept for persistent or recurrent MO not responding to either bevacizumab and/or ranibizumab.ResultsIn all 42 eyes of 42 patients were included in the study. The median visual acuity before the switch was 20/126, 1 month after the first injection of aflibercept 20/89 (P=0.0191), and at the end of the follow-up 20/100 (P=0.2724). The median CRT before the switch was 536 μm, 1 month after the first injection of aflibercept 293.5 μm (P=0.0038), and at the end of the follow-up 279 μm (P=0.0013 compared to before the switch). The median number of weeks between injections before the switch was 5.6 and after the switch was 7.6 (P<0.0001).ConclusionConverting eyes with refractory MO due to CRVO to aflibercept can result in stabilization of the vision, improved macular anatomy, and extension of the injection interval.


Heart failure in China: a review of the literature.
Heart failure (HF) is a serious disease associated with high morbidity and mortality. In China, as in other countries, it is a common cause for hospital admission; however, as yet there are few data documenting the epidemiology and management of HF in China, or quality of life-related considerations in this population. This review aims to identify relevant Chinese and English language publications that discuss the causes, risks, treatment, and health outcomes (costs, health-related quality of life) of HF in China (excluding Taiwan and Hong Kong). The prevalence of HF in China appears to be lower than that reported in many Western countries, including the US. Hypertension and coronary heart disease are the leading causes of HF in China, as they are in many Western nations, potentially highlighting the improvement in socioeconomic conditions in China. Evidence suggests that use of newer pharmacological agents for the treatment of HF is increasing; however, it is still believed that there is a lack of physician knowledge regarding newer, more effective treatment options, with rural (poor) areas appearing to be the most reliant on older, less expensive, medications. Interest in Chinese quality of life measures for HF has risen recently, with the development of valid and reliable rating scales in the Chinese population. Although the amount of available literature on HF in China is improving, there remain significant gaps in our understanding of the issue, and further research is needed to provide a reliable Chinese evidence base for the improvement of clinical practice.


Determination of transcription factors and their possible roles in the regulation of Pax3 gene expression in the mouse B16 F1 melanoma cell line.
The objective of this study was to determine which transcription factors regulate the expression of the Pax3 gene in the mouse B16 F1 melanoma cell line. The results showed that the -14 kilobase pair (kbp) Pax3 promoter, but not the -1.6 kbp Pax3 promoter, promoted Pax3 gene expression in B16 cells. Comparison of the sequence of the -14 kbp human Pax3 promoter with mouse Pax3 promoters indicated that homology sequences were located between -6.9 and -5.8 kbp, and also that the 1.1 kbp fragment (between -6.9 and -5.8 kbp), linked -1.6 kbp proximal to the Pax3 promoter [plasmid PGPax3PIV (N6.9/5.8) delta SST Lacz], could mimic the functions of plasmid PGPax3 -14(N-1.6) Lacz. Mutations of the core binding elements of either Pax3 site I or II or both sites I and II reduced significantly the beta-galactosidase (beta-gal) activity in the cells. However, mutations of the core binding sequences of site A or B increased significantly the beta-gal activity in the cells. Biochemistry analysis demonstrated that POU transcription factors (Oct-1 and Brn-2) bind to the specific binding elements of both sites I and II to stimulate Pax3 gene expression, whereas the TALE homeodomain-containing proteins (Pbx and Prep1) bind with the core binding sequences of sites A and B to repress the expression of the Pax3 gene in B16 cells.


Superficial leiomyosarcoma of the glans: report of a case and literature review.
Primary leiomyosarcomas of the penis are rare. Clinically and pathologically, these tumors fall into two groups: superficial and deep. Superficial lesions usually are low grade and show a limited tendency toward distant metastasis. In contrast, deep-seated tumors usually show a more aggressive behavior associated with a poor prognosis. A 62-year-old man with a superficial leiomyosarcoma of the glans penis is reported.


Microorganisms as Shapers of Human Civilization, from Pandemics to Even Our Genomes: Villains or Friends? A Historical Approach.
Universal history is characterized by continuous evolution, in which civilizations are born and die. This evolution is associated with multiple factors, among which the role of microorganisms is often overlooked. Viruses and bacteria have written or decisively contributed to terrible episodes of history, such as the Black Death in 14th century Europe, the annihilation of pre-Columbian American civilizations, and pandemics such as the 1918 Spanish flu or the current COVID-19 pandemic caused by the coronavirus SARS-CoV-2. Nevertheless, it is clear that we could not live in a world without these tiny beings. Endogenous retroviruses have been key to our evolution and for the regulation of gene expression, and the gut microbiota helps us digest compounds that we could not otherwise process. In addition, we have used microorganisms to preserve or prepare food for millennia and more recently to obtain drugs such as antibiotics or to develop recombinant DNA technologies. Due to the enormous importance of microorganisms for our survival, they have significantly influenced the population genetics of different human groups. This paper will review the role of microorganisms as "villains" who have been responsible for tremendous mortality throughout history but also as "friends" who help us survive and evolve.


Predicting and remembering the behaviors of social targets: how prediction accuracy affects episodic memory.
Decades of research has investigated the relationship between memory and future thinking. Although some of this work has shown that memory forms the basis of making predictions about the future, less work has investigated how the outcome of those predictions (whether consistent or inconsistent with what one predicts) is later remembered. Limited past works suggests that memory for outcomes that are consistent with what one predicts are better remembered that predictions that are inconsistent. To advance understanding of the relationship between episodic memory and future thinking, the current investigation examines how the outcome of predictions affects memory after the predicted events takes place. In this experiment, participants first learned trait information about social targets. Then, participants imagined scenarios involving targets and the self (i.e., the participant) and made predictions about which behaviors targets would perform based on the trait information associated with targets participants learned earlier. Participants were then told the behaviors the targets actually performed (i.e., prediction outcome), which was either consistent or inconsistent with predictions, before then taking a memory test for prediction outcomes (what the social target actually did). Results showed memory for prediction-consistent outcomes was better than for prediction-inconsistent outcomes, suggesting people exhibit enhanced memory for events that are in line with predictions based on existing contents of memory (e.g., what one knows; schemas), which is in line with the limited past work in this domain. Overall, finding better memory for prediction-consistent outcomes may reflect an adaptive function in memory, where people show enhanced memory for episodes when they play out as predicted, and aligned with the current contents of memory.


Urban-regional patterns of food purchasing behaviour: a cross-sectional analysis of the 2015-2016 Australian Household Expenditure Survey.
In many high-income countries people living in regional (rural) areas have higher rates of chronic disease compared to people living in urban areas. Food purchasing behaviour provides a potential pathway linking residential location with dietary intake and health outcomes. This study examined the relationship between geographic location and food expenditure on a range of foods. Data from the 2015-2016 Australian Household Expenditure Survey (number of households = 9827) were used to examine weekly household food expenditure and proportion of total food expenditure on 14 categories of food items. Foods were classified using the Australian Guide to Healthy Eating. Two-part models and zero-one inflated beta regression models were used to assess the association between geographic area and food expenditure. Average proportion of total food expenditure on fruit was estimated to be more for households located in major cities compared to households located in inner and outer regional areas. Households located in inner and outer regional areas allocated less to fresh fruit, fish and meals out compared to households in major cities. Households located in inner regional areas allocated a greater proportion of their food budget to sweet cakes, biscuits, puddings, desserts, chocolate and ice-cream compared to households in major cities and outer regional areas. The geographic patterns in food purchasing suggest those in regional areas may be at risk of diets less aligned with healthy guidelines. Given the findings of this study suggesting geographic differences in food purchasing, further research is warranted to enhance contextual understanding of food purchasing behaviours in regional areas.


1H, 13C, and 15N backbone and side-chain chemical shift assignments for the 31 kDa human galectin-7 (p53-induced gene 1) homodimer, a pro-apoptotic lectin.
Galectins are multifunctional proteins with carbohydrate/protein-binding properties and distinct expression profiles. Homodimeric galectin-7 (p53-induced gene 1) is a potent pro-apoptotic effector with clinical relevance. Here, we report (1)H, (13)C, and (15)N chemical shift assignments for human galectin-7 dimer as determined by using heteronuclear, triple resonance NMR spectroscopy.


The diagnostic quandary of magnetic resonance imaging-negative Hirayama disease: a case report.
Magnetic resonance imaging (MRI) features are typical findings in Hirayama disease (HD) and are useful diagnostic entities but may not be present in all patients. We present the case of a 22-year-old Nepalese man who presented with insidious onset of weakness of his right upper limb of more than 5 years duration. His weakness was progressive for the first 3 years, and then remained static. On examination, weakness of the interossei, thenar, hypothenar, flexor, and extensor muscles were present in his right upper limb, power was normal in his left upper and bilateral lower limbs. Minipolymyoclonus was present in both upper limbs, less prominent on the left side. Electrophysiological findings showed motor axonal neuropathy in his right upper limb, neurogenic discharges and fibrillations, and fasciculations in both upper limbs. Contrast magnetic resonance imaging (MRI) of his cervical spine in flexion was normal. Our patient was diagnosed with HD based on clinical and electrophysiological findings. Our patient was advised to use a cervical collar and regular physiotherapy and was found to have subjective benefit. A normal cervical MRI does not rule out HD and the diagnosis can also be made based on clinical and electrophysiological studies. Progressive distal upper limb weakness or tremor in young patients should be evaluated for HD, because early diagnosis and intervention might halt the progression.


Computational fluid dynamics investigations over conventional and modified Savonius wind turbines.
Wind turbines are devices that convert the kinetic energy present in the wind into clean, sustainable, and effectively renewable energy that could be used to generate electricity. A Savonius wind turbine is a drag-based vertical axis wind turbine (VAWT) that is known to have low noise levels and good starting characteristics even at low wind speeds. Its disadvantage lies in its low efficiency or low coefficient of performance. Exploring ways to increase the coefficient of performance, numerical investigations were carried out on different modified Savonius VAWT configurations, having different curvatures, different overlap percentages, added mini blades, and fitted out with extended surfaces. These investigations were computationally executed on Ansys Fluent™ using the sliding mesh technique. Two-dimensional simulations, on a Bach blade curvature with zero overlap as well as a half-circle and a polynomial curvature with overlap, showed that for a wind speed of 5 m/s and a tip speed ratio of 0.8, the half-circle blade curvature having an overlap of 20% performs best, yielding the highest net (average) coefficient of moment, equal to 0.3065. Results also show that the addition of mini blades to this optimal configuration produces a slight improvement in the coefficient of moment. However, the addition of extended surfaces onto the blades caused the minimum coefficient of moment to be a substantial negative value and thus resulting in a much lower value for the turbine's average coefficient of moment.


Nonalcoholic Fatty Liver Disease Is an Independent Risk Factor for Nephrolithiasis in Women: Findings from NHANES III.
Objective: To determine if radiologically diagnosed nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for nephrolithiasis using data from National Health and Nutrition Examination Survey III (NHANES III). Patients and Methods: NHANES III participants aged 20-74 years who underwent hepatobiliary ultrasound were classified as with NAFLD (moderate or severe hepatic steatosis in absence of other known causes of liver disease; n = 2498) or without NAFLD (controls; n = 9361). Risk of nephrolithiasis caused by NAFLD was estimated using logistic regression with propensity score adjustment. Secondary outcomes included medical stone management, lithotripsy, and surgical stone removal. Results: Participants with NAFLD were older (48.7 ± 0.4 vs 43.3 ± 0.3 years, p < 0.001) and exhibited greater prevalence of all components of metabolic syndrome: obesity (48% vs 21%), impaired glucose tolerance (17% vs 11%), diabetes mellitus (15% vs 6%), hypertension (36% vs 24%), and gout (4% vs 2%) (all p < 0.001). After adjusting for demographic, lifestyle, and metabolic factors, NAFLD was associated with increased risk nephrolithiasis (odds ratio [OR] = 1.29, 95% confidence interval [CI] [1.02-1.61], p = 0.03). The association persisted in women (OR = 1.65, 95% CI [1.17-2.32], p = 0.004) but not in men (OR = 1.04, 95% CI [0.77-1.40], p = 0.80). NAFLD was not associated with increased occurrence of medical management (OR = 1.31, 95% CI [0.84-2.05], p = 0.24), lithotripsy (OR = 1.61, 95% CI [0.83-3.33], p = 0.20), or surgical stone removal (OR = 0.83, 95% CI [0.48-1.44], p = 0.52). Conclusions: In a large U.S. population-based cross-sectional analysis, NAFLD was found to be associated with increased risk of nephrolithiasis in women after adjusting for demographic, clinical, and metabolic factors.


Novel 2H-chromen-2-one derivatives of resveratrol: Design, synthesis, modeling and use as human monoamine oxidase inhibitors.
Using a fragment-based drug design strategy, two biomedical interesting fragments, resveratrol and coumarin were linked to design a series of novel human monoamine oxidase (hMAO) inhibitors with a scaffold of 3-((E)-3-(2-((E)-styryl)phenyl)acryloyl)-2H-chromen-2-one, which demonstrated a very interesting selectivity profile against hMAO-A and hMAO-B: some compounds with this scaffold are selective hMAO-A inhibitors, whereas some are selective hMAO-B inhibitors. The small changes in the substituents of the coumarin moiety led to this interesting selectivity profile. The most potent selective hMAO-B inhibitor D7 has a selectivity ratio of 20.93, with an IC₅₀ value of 2.78 μM, similar or better than selegiline (IC₅₀ = 2.89 μM), a selective hMAO-B inhibitor currently in the market for the treatment of Parkinson's disease. Our modeling study indicates that Tyr 326 of hMAO-B (or corresponded Ile 335 of hMAO-A) may be the determinant for the specificity of these compounds. The selectivity profile of compounds reported herein suggests that we can further develop both selective hMAO-A and hMAO-B inhibitors based on this novel scaffold.


Selective activation of Lyt 2+ precursor T cells by ligation of the antigen receptor.
Resting T lymphocytes may be activated either physiologically, by the specific recognition of antigen in association with molecules encoded by the major histocompatibility complex (MHC), or non-physiologically using mitogens such as concanavalin A (Con A). The former activation process is difficult to analyse because resting precursor T cells specific for a particular antigen-MHC combination can only be isolated in the presence of a large excess of bystander cells of irrelevant specificity; clonal populations of uniform specificity are not useful for studying the activation of naive T cells because there is no reason to believe that such cloned cells ever return to the state of resting precursors. Mitogens may activate a large fraction of resting T cells, but analysis is again complicated because the target molecule(s) of most mitogens is unknown and the relationship of this kind of activation to physiological induction by antigen plus MHC molecules remains unclear. By using a monoclonal antibody specific for the antigen receptors on approximately 25% of all T cells of both Lyt 2+ and Lyt 2- subsets, we have studied the induction of lymphokine responsiveness in resting normal T cells. This antibody, immobilized on Sepharose beads, is sufficient to activate Lyt 2+ T cells, but not Lyt 2- T cells, to clonal expansion in the presence of a mixture of lymphokines (10% rat spleen Con A supernatant). We report here that clonal growth of the T cells obeys single-hit kinetics in limiting-dilution microcultures, suggesting that a single cell type is limiting. We conclude that cytotoxic T-lymphocyte (Tc) precursors require only ligation of the antigen receptor before they become responsive to lymphokines, whereas helper T-lymphocyte (Th) precursors require additional signals.


Molecular cloning of major histocompatibility complex class II B gene cDNA from the Bengalese finch Lonchura striata.
The only avian major histocompatibility complex (Mhc) genes thus far identified are from species of the relatively small order of Galliformes, while by far the largest order of Passeriformes (songbirds), containing some 60% of extant bird species, has not been studied at all in this regard. The Galliformes emerged more than 55 million years (my) ago, the Passeriformes some 25 my ago. Because of the potential for the use of Mhc genes as markers in the study of songbird populations, an attempt was made to clone class II B genes of a passeriform species, the Bengalese finch Lonchura striata acuticauda. Using a set of primers designed on the basis of known sequences, a probe corresponding to part of exon II was obtained by the polymerase chain reaction. The probe was then used to screen a Bengalese finch cDNA library and to isolate and sequence two nearly full-length clones. The sequences reveal the presence of one presumably functional class II B locus in this bird species.


Antiproliferative properties of piperidinylchalcones.
Methoxylated chalcones bearing N-methylpiperidinyl substituents on ring A inhibited the growth of human tumour cell lines (MCF, HCT 116, and Jurkat) at IC50 values of <5 microM. Investigations on a representative member (12) showed that antiproliferative activity was linked to the disruption of the cell cycle at G1 and G2/M phases. The effect was concentration dependent and was evident at the approximate IC50 of 12. Down regulation of cell cycle regulatory components (CDK4, cyclin B, E2F, and phosphorylated Rb) were observed under similar conditions. Methoxylated chalcones without the piperidinyl substituent were found to exert equally potent and selective antiproliferative activity against HCT 116 tumour cells but did not interfere with cell cycle progression at their IC50 concentrations. The presence of the piperidinyl substituent in the chalcone template is proposed to lend specificity to the mechanism of antiproliferative activity, in addition to promoting a more desirable physicochemical profile.


Nitric oxide inhibits hypoxia-induced impairment of human RBC deformability through reducing the cross-linking of membrane protein band 3.
Nitric oxide (NO) prevents the decline of RBC deformability under high altitude and other ischemic and hypoxic conditions, but the clear mechanisms remain unknown. Here, we have carried out a systematic study to find the mechanisms of NO-induced regulation of RBC deformability under hypoxia. NO levels, RBCs membrane elongation index (EI), membrane protein band 3 methemoglobin (MetHb) were determined during hypoxia (0 to 120 minutes). To validate the role of NO in regulating RBC deformability, tests were also performed with a NO donor (sodium nitroprusside) or a NO synthase inhibitor (l-nitro-arginine methylester) under 60 minutes hypoxia. Hypoxia for 45 minutes increased NO levels from 25.65 ± 1.95 to 35.26 ± 2.01 μmol/L, and there was a plateau after 60 minutes hypoxia. The EI did not change before 45 minutes hypoxia, but decreased from 0.567 ± 0.019 to 0.409 ± 0.042 (30 Pa) after 60 minutes hypoxia. The cross-linking of band 3 and phosphotyrosine increased after 45 minutes hypoxia. All can be alleviated by supplement NO and aggregated by inhibiting NOS. However, the MetHb was not present this trend. NO may prevent decreased of RBCs deformability through reducing the cross-linking of membrane band 3 under hypoxia; this helps microvascular perfusion of RBCs during ischemic and hypoxic disease states.


Expanding the Evidence on the Safety and Efficiency of 2-Way Text Messaging-Based Telehealth for Voluntary Medical Male Circumcision Follow-up Compared With In-Person Reviews: Randomized Controlled Trial in Rural and Urban South Africa.
There is a dearth of high-quality evidence from digital health interventions in routine program settings in low- and middle-income countries. We previously conducted a randomized controlled trial (RCT) in Zimbabwe, demonstrating that 2-way texting (2wT) was safe and effective for follow-up after adult voluntary medical male circumcision (VMMC). To demonstrate the replicability of 2wT, we conducted a larger RCT in both urban and rural VMMC settings in South Africa to determine whether 2wT improves adverse event (AE) ascertainment and, therefore, the quality of follow-up after VMMC while reducing health care workers' workload. A prospective, unblinded, noninferiority RCT was conducted among adult participants who underwent VMMC with cell phones randomized in a 1:1 ratio between 2wT and control (routine care) in North West and Gauteng provinces. The 2wT participants responded to a daily SMS text message with in-person follow-up only if desired or an AE was suspected. The control group was requested to make in-person visits on postoperative days 2 and 7 as per national VMMC guidelines. All participants were asked to return on postoperative day 14 for study-specific review. Safety (cumulative AEs ≤day 14 visit) and workload (number of in-person follow-up visits) were compared. Differences in cumulative AEs were calculated between groups. Noninferiority was prespecified with a margin of -0.25%. The Manning score method was used to calculate 95% CIs. The study was conducted between June 7, 2021, and February 21, 2022. In total, 1084 men were enrolled (2wT: n=547, 50.5%, control: n=537, 49.5%), with near-equal proportions of rural and urban participants. Cumulative AEs were identified in 2.3% (95% CI 1.3-4.1) of 2wT participants and 1.0% (95% CI 0.4-2.3) of control participants, demonstrating noninferiority (1-sided 95% CI -0.09 to ∞). Among the 2wT participants, 11 AEs (9 moderate and 2 severe) were identified, compared with 5 AEs (all moderate) among the control participants-a nonsignificant difference in AE rates (P=.13). The 2wT participants attended 0.22 visits, and the control participants attended 1.34 visits-a significant reduction in follow-up visit workload (P<.001). The 2wT approach reduced unnecessary postoperative visits by 84.8%. Daily response rates ranged from 86% on day 3 to 74% on day 13. Among the 2wT participants, 94% (514/547) responded to ≥1 daily SMS text messages over 13 days. Across rural and urban contexts in South Africa, 2wT was noninferior to routine in-person visits for AE ascertainment, demonstrating 2wT safety. The 2wT approach also significantly reduced the follow-up visit workload, improving efficiency. These results strongly suggest that 2wT provides quality VMMC follow-up and should be adopted at scale. Adaptation of the 2wT telehealth approach to other acute follow-up care contexts could extend these gains beyond VMMC. ClinicalTrials.gov NCT04327271; https://www.clinicaltrials.gov/ct2/show/NCT04327271.


Alcian blue staining intestinal goblet cell antigen (GOA): a marker for gastric signet ring cell and colonic colloidal carcinoma.
An Alcian blue staining, perchloric acid-soluble, antigenic acidic mucosubstance (GOA) was purified from human gastric signet ring cell carcinoma with DEAE-cellulose chromatography, Seqhadex G-200 and preparative polycrylamide gel electrophoresis. Specific antisera were raised which reacted in indirect immunoenzyme histology with normal goblet cells of the small and large intestine and with goblet cells of intestinalized gastric mucosa. In surgical resection specimens of the stomach (n = 100) and of the colon (n = 19) 3 gastric signet ring cell carcinomas and 3 colonic colloidal adenocarcinomas stained for GOA, demonstrating an immunochemical relationship with normal intestinal goblet cells.


Widespread intranuclear neuronal corpuscles (Marinesco bodies) associated with a familial spinal degeneration with cranial and peripheral nerve involvement.
Widespread intranuclear, paranucleolar, acidophilic corpuscles, known as Marinesco bodies, were found in association with degeneration of the posterior columns of ting at the age of 45 years. Neurological examination of his sister (aged 51 years) inciates that she is suffering from the same diseases. The cases appear to belong to the predominantly spinal form of spino-cerebellar degenerations or Friedreich's ataxia. This report, which includes an electron microscope examination, considers the pathological significance of Marinesco bodies.


Comparative penetration of lomefloxacin and other quinolones into human phagocytes.
The penetration of lomefloxacin into human polymorphonuclear leukocytes (PMNs) and peritoneal macrophages (PMphis) was evaluated using a fluorometric assay. Lomefloxacin reached high intracellular concentrations into PMNs at extracellular concentrations of 2 and 5 mg/L (cellular to extracellular concentration ratio [C/E] greater than 4). At the same conditions (20 minutes incubation; extracellular concentrations: 2 mg/L) lomefloxacin uptake by human PMNs (C/E: 7.9 +/- 2.6) was slightly higher than those of norfloxacin (C/E 5.1 +/- 1.8), ciprofloxacin (C/E: 6.2 +/- 2.0), and ofloxacin (C/E 7.1 +/- 2.6). Lomefloxacin penetration into human PMphis was significantly lower than PMNs but still with C/E ratios greater than 4. Entry of lomefloxacin into phagocytes was not affected by cell viability but was environmental-temperature dependent. It is concluded that lomefloxacin and the other quinolones evaluated reach high intracellular concentrations in human phagocytic cells.


Direct measurement of dynamic attractant gradients reveals breakdown of the Patlak-Keller-Segel chemotaxis model.
Chemotactic bacteria not only navigate chemical gradients, but also shape their environments by consuming and secreting attractants. Investigating how these processes influence the dynamics of bacterial populations has been challenging because of a lack of experimental methods for measuring spatial profiles of chemoattractants in real time. Here, we use a fluorescent sensor for aspartate to directly measure bacterially generated chemoattractant gradients during collective migration. Our measurements show that the standard Patlak-Keller-Segel model for collective chemotactic bacterial migration breaks down at high cell densities. To address this, we propose modifications to the model that consider the impact of cell density on bacterial chemotaxis and attractant consumption. With these changes, the model explains our experimental data across all cell densities, offering new insight into chemotactic dynamics. Our findings highlight the significance of considering cell density effects on bacterial behavior, and the potential for fluorescent metabolite sensors to shed light on the complex emergent dynamics of bacterial communities.


Direct Oral Anticoagulants: Navigating Through Clinical Challenges.
Direct oral anticoagulants (DOACs) have been approved, for over a decade, by both European and American medicine agencies, for treatment and prevention of several cardiovascular conditions. Since then, an increasing amount of data has been added to the medical literature day by day, resulting in a dichotomy in selection of the appropriate agent, dosage, and duration of treatment for special populations with multiple comorbidities. Considering these issues, we have prepared a comprehensive review for the clinical practitioner, to optimize the DOAC utilization in clinical practice. A thorough literature search and review was conducted, concerning mainly the last decade. Our review focused on the current guidelines and the most recently published studies in PubMed, Science Direct Scopus, and Google Scholar to date. The purpose of this study is to provide guidance for healthcare professionals for making proper decisions when confronted with clinical challenges. Nevertheless, further research is required to establish DOAC superiority in complicated cases, where there is clinical uncertainty.


Betulin and Crinum asiaticum L. bulbs extract attenuate pulmonary fibrosis by down regulating pro-fibrotic and pro-inflammatory cytokines in bleomycin-induced fibrosis mice model.
Pulmonary fibrosis (PF) is a lung disease characterized by scaring of lung tissue that impairs lung functions. The estimated survival time of patients with pulmonary fibrosis is 3-5 years. Bleomycin (BLM) is used clinically in the treatment of Hodgkin lymphoma and testicular germ-cell tumors. Bleomycin's mechanism of action is the inhibition of DNA and protein synthesis. This happens when leukocytes induce the release of cytokines and chemokines which increase the pro-fibrotic and pro-inflammatory cytokines such as IL-6, TNF-alpha, IL-13, IL-1β and transforming growth factor-beta 1 (TGF-β). Crinum asiaticum L. bulbs (CAE) are widely found in parts of Africa, Asia and Indian Ocean Island. It is also prevalent in southern part of Ghana and traditionally used by the indigenes to treat upper respiratory tract infections, and for wound healing. Betulin (BET) is found in the bulbs of Crinum asiaticum L. but widely isolated from the external bark of birches and sycamore trees. Betulin as a lupine type triterpenes has been researched for their pharmacological and biological activities including anticancer, anti-inflammatory, antimicrobial activities and anti-liver fibrosis effects.Aim of the study: The aim was to study the anti-pulmonary fibrosis effect of Crinum asiaticum L. bulbs extract and betulin in bleomycin-induced pulmonary fibrosis in mice. There was a single oropharyngeal administration of bleomycin (80 mg/kg) in mice followed by the treatment of CAE and BET after 48 h of exposure to BLM. There was increased survival rate in CAE and BET treatment groups compared to the BLM induced group. There was a marked decreased in the levels of hydroxyproline, collagen I and III in the CAE and BET treatment groups compared to BLM-treated group. The treatment groups of CAE and BET significantly down regulated the levels of pro-fibrotic and pro-inflammatory cytokines concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increased in the BLM treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM induced pulmonary fibrosis in mice, the study showed improved lung functions with wide focal area of viable alveolar spaces and few collagen fibers deposition on lungs of treatment groups. CAE and BET attenuated pulmonary fibrosis by down regulating pro-fibrotic and pro-inflammatory cytokines as well as improving lung function. This could be a lead in drug discovery where compounds with anti-fibrotic effects could be developed for the treatment of lung injury.


Environmental quality induced predicted by evolutionary theory.
The use of evolutionary theory to understand and predict environmental quality indices has been described. Three specific examples concerning the environmental health implications of black skin, heat stress adaptation, and G-6-PD deficiency have been discussed in which evolutionary theory provides the conceptual framework for novel insights and reasonable predictions of environment, pollutant and human interactions. The use of the evolutionary paradigm in the development of environmental quality indices offers a clear alternative to trial and error research efforts.


A new vanadium (III) complex of 2,6-bis(3,5-diphenylpyrazol-1-ylmethyl)pyridine as a catalyst for ethylene polymerization.
The tridentate ligand 2,6-bis(3,5-diphenylpyrazol-1-ylmethyl)pyridine, abbreviated as 2,6-[(3,5-ph₂pz-CH₂)₂-py], a new pyridine-pyrazole derivative, was prepared from 2,6-bis(bromomethyl)pyridine and 3,5-diphenylpyrazole. The ligand was characterized by means of elemental analyses, ATR-IR, ¹H- and ¹³C-NMR spectroscopy and single crystal X-ray crystallography. Using this ligand, a new mononuclear vanadium (III) complex, {2,6-[(3,5-ph₂pz)CH₂]₂py}VCl₃ was prepared and characterized by elemental analysis, ATR-IR and HR-MS. The complex was investigated as a catalyst for ethylene polymerization and compared with 2,6-[(3,5-Me₂pz)CH₂]₂py}VCl₃ to explore the effect of the substituent on the pyrazolyl rings on ethylene polymerization. High catalytic activity was observed at ambient temperature. After treatment with AlEtCl₂, these complexes showed high activity for ethylene polymerization converting ethylene to highly linear polyethylene and affording high molecular weight polymers (up to 1.0 × 10⁶ g/mol) with unimodal molecular weight distributions.


No Effect of Isolated Anthocyanins from Bilberry Fruit and Black Rice on LDL Cholesterol or other Biomarkers of Cardiovascular Disease in Adults with Elevated Cholesterol: A Randomized, Placebo-Controlled, Cross-Over Trial.
Some dietary interventions with berry fruits, berry fruit extracts, and purified anthocyanins have been reported to beneficially alter lipoprotein profiles in hyperlipidemic participants. The major anthocyanins in human diets are glycosides of cyanidin and delphinidin, and structure can influence both absorption and bioactivity. The aim of this study is to determine the effects of two major types of anthocyanins on low-density lipoprotein cholesterol and other cardiometabolic markers for cardiovascular disease (CVD) risk in hyperlipidemic individuals. Fifty-two hyperlipidemic participants complete this randomized, placebo-controlled, double-blind, three arm crossover trial. Participants ingest capsules containing 320 mg of anthocyanins (bilberry trihydroxy-type or black rice dihydroxy-type) or placebo once daily for 28 days. Biomarkers of CVD risk are measured before and after the intervention period. Compared to the placebo, neither anthocyanin treatment significantly (p < 0.05) changes circulating levels of lipoproteins (total-/high-density lipoprotein (HDL)-/low-density lipoprotein (LDL)-cholesterol, triglycerides, Apolipoprotein B (ApoB)), biomarkers of glycemic control (fasting glucose, fructosamine), biomarkers of HDL function (ApoA1, HDL3, paraoxonase-1 (PON1) arylesterase, and lactonase activities), or plasma bile acids. These data do not support the notion that regular consumption of anthocyanins beneficially affects glycemic control or lipoprotein profiles or functions. It is possible the no effect observation is due to the relatively short duration of treatments.


[FIDUSweb version 2.0 : An electronic platform to establish a cooperative university eye network].
Due to the increasing digitalization in ophthalmology, increasingly more documentation and diagnostic data are becoming electronically available. In order to improve patient care beyond sectoral boundaries, electronic cooperation portals were introduced in Münster and Homburg, which serve the networking with ophthalmologists in private practice. This article reports on the implementation of an electronic cooperation portal at the University Eye Hospitals in Münster and Homburg in 2015 and 2016. The FIDUSweb represents a data protection-compliant cooperation portal that can be easily set up. By implementing it as a web portal all terminal equipment and also electronic patient files can be networked. Particularly important functions are the transmission of medical reports in real time, appointment booking functions, the transmission of imaging data and shared treatment documentation. Cross-sectoral care can greatly benefit from the use of the FIDUSweb, especially in digital and multimodal ophthalmology.


Prognostic impact of additional HPV diagnostics in 102 patients with p16-stratified advanced oropharyngeal squamous cell carcinoma.
p16 overexpression was considered as surrogate marker to identify human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCCs). 102 patients with advanced stage OPSCCs treated primarily by transoral lasermicrosurgery were included. Prognostic associations of p16- and HPV-status were analyzed separately and combined. In contrast to p16, the HPV-status resulted in no significant survival discrepancies (5-year overall survival (OS) HPV-positive 64.9%, HPV-negative 78.7%). Combining both markers, p16-positive (p16-positive/HPV-positive, p16-positive/HPV-negative) and p16-negative/HPV-negative groups demonstrated comparable high survival (OS 78.1% vs. 85.6% vs. 73.6%). Lowest survival was observed for patients with p16-negative/HPV-positive OPSCCs (OS 40.8%). Never smoking patients with p16-positive OPSCCs demonstrated the highest survival, whereas within former/current smokers with p16-positive and p16-negative disease it was comparable low (OS 90.0% vs. 63.0% vs. 57.4%). p16- and HPV-status should not be considered as equivalent markers for a better prognosis. Furthermore, they should not generally predominate patient associated factors like smoking.


Opioids for the management of dyspnea in cancer patients: a systematic review and meta-analysis.
Dyspnea is a prevalent symptom that significantly reduces quality of life of cancer patients. Palliative treatment is necessary when the symptoms do not respond to treatment for their cause. Opioids are widely used as pharmacological therapy, but evidence for individual agents is inconsistent. The purpose of this study was to evaluate the efficacy and safety of opioids for dyspnea in cancer patients. We searched the CENTRAL, MEDLINE, EMBASE, and ICHUSHI for studies using opioids for dyspnea in adult cancer patients reported by September 2019. Screening of the retrieved literature and assessment of risk of bias and outcomes were performed by two independent authors. A meta-analysis was performed on the primary endpoint, relief of dyspnea, and secondary endpoints including quality of life, somnolence as a side effect, and serious adverse events. Twelve randomized controlled trials were evaluated regarding relief of dyspnea. Somnolence and serious adverse events were evaluated in seven and four randomized controlled trials, respectively, but no randomized controlled trials were evaluable for quality of life. Overall, opioids were more effective than placebo for dyspnea (standardized mean difference - 0.43, 95% confidence interval [CI] - 0.75 to - 0.12). Although significant difference was found between systemic morphine and placebo in the drug-specific analysis, no significant difference could be detected in the other analyses. Systemic administration of opioids is more effective than placebo in relieving dyspnea in cancer patients. Robust evidence on the efficacy and safety of opioids on dyspnea in cancer patients is lacking, and further studies are needed.


Endocytic myosin-1 is a force-insensitive, power-generating motor.
Myosins are required for clathrin-mediated endocytosis, but their precise molecular roles in this process are not known. This is, in part, because the biophysical properties of the relevant motors have not been investigated. Myosins have diverse mechanochemical activities, ranging from powerful contractility against mechanical loads to force-sensitive anchoring. To better understand the essential molecular contribution of myosin to endocytosis, we studied the in vitro force-dependent kinetics of the Saccharomyces cerevisiae endocytic type I myosin called Myo5, a motor whose role in clathrin-mediated endocytosis has been meticulously studied in vivo. We report that Myo5 is a low-duty-ratio motor that is activated ∼10-fold by phosphorylation and that its working stroke and actin-detachment kinetics are relatively force-insensitive. Strikingly, the in vitro mechanochemistry of Myo5 is more like that of cardiac myosin than that of slow anchoring myosin-1s found on endosomal membranes. We, therefore, propose that Myo5 generates power to augment actin assembly-based forces during endocytosis in cells.


Brown-headed cowbirds (Molothrus ater) harbor Sarcocystis neurona and act as intermediate hosts.
We tested the hypothesis that brown-headed cowbirds (Molothrus ater) harbor Sarcocystis neurona, the agent of equine protozoal myeloencephalitis (EPM), and act as intermediate hosts for this parasite. In summer 1999, wild caught brown-headed cowbirds were collected and necropsied to determine infection rate with Sarcocystis spp. by macroscopic inspection. Seven of 381 (1.8%) birds had grossly visible sarcocysts in leg muscles with none in breast muscles. Histopathology revealed two classes of sarcocysts in leg muscles, thin-walled and thick-walled suggesting two species. Electron microscopy showed that thick-walled cysts had characteristics of S. falcatula and thin-walled cysts had characteristics of S. neurona. Thereafter, several experiments were conducted to confirm that cowbirds had viable S. neurona that could be transmitted to an intermediate host and cause disease. Specific-pathogen-free opossums fed cowbird leg muscle that was enriched for muscle either with or without visible sarcocysts all shed high numbers of sporocysts by 4 weeks after infection, while the control opossum fed cowbird breast muscle was negative. These sporocysts were apparently of two size classes, 11.4+/-0.7 microm by 7.6+/-0.4 microm (n=25) and 12.6+/-0.6 microm by 8.0+/-0 microm (n=25). When these sporocysts were excysted and introduced into equine dermal cell tissue culture, schizogony occurred, most merozoites survived and replicated long term and merozoites sampled from the cultures with long-term growth were indistinguishable from known S. neurona isolates. A cowbird Sarcocystis isolate, Michigan Cowbird 1 (MICB1), derived from thin-walled sarcocysts from cowbirds that was passaged in SPF opossums and tissue culture went on to produce neurological disease in IFNgamma knockout mice indistinguishable from that of the positive control inoculated with S. neurona. This, together with the knowledge that S. falcatula does not cause lesions in IFNgamma knockout mice, showed that cowbird leg muscles had a Sarcocystis that fulfills the first aim of Koch's postulates to produce disease similar to S. neurona. Two molecular assays provided further support that both S. neurona and S. falcatula were present in cowbird leg muscles. In a blinded study, PCR-RFLP of RAPD-derived DNA designed to discriminate between S. neurona and S. falcatula showed that fresh sporocysts from the opossum feeding trial had both Sarcocystis species. Visible, thick-walled sarcocysts from cowbird leg muscle were positive for S. falcatula but not S. neurona; thin-walled sarcocysts typed as S. neurona. In 1999, DNA was extracted from leg muscles of 100 wild caught cowbirds and subjected to a PCR targeting an S. neurona specific sequence of the small subunit ribosomal RNA (SSU rRNA) gene. In control spiking experiments, this assay detected DNA from 10 S. neurona merozoites in 0.5g of muscle. In the 1999 experiment, 23 of 79 (29.1%) individual cowbird leg muscle samples were positive by this S. neurona-specific PCR. Finally, in June of 2000, 265 cowbird leg muscle samples were tested by histopathology for the presence of thick- and thin-walled sarcocysts. Seven percent (18/265) had only thick-walled sarcocysts, 0.8% (2/265) had only thin-walled sarcocysts and 1.9% (5/265) had both. The other half of these leg muscles when tested by PCR-RFLP of RAPD-derived DNA and SSU rRNA PCR showed a good correlation with histopathological results and the two molecular typing methods concurred; 9.8% (26/265) of cowbirds had sarcocysts in muscle, 7.9% (21/265) had S. falcatula sarcocysts, 1.1% (3/265) had S. neurona sarcocysts, and 0.8% (2/265) had both. These results show that some cowbirds have S. neurona as well as S. falcatula in their leg muscles and can act as intermediate hosts for both parasites.


Complications associated with Dermabond® during head and neck surgery: MAUDE and literature review.
Dermabond® is a liquid surgical sealant containing 2-octyl-cyanoacrylate that has been widely used during head and neck surgeries. This study aims to provide a summary of adverse events related to Dermabond® in head and neck procedures as reported in the MAUDE database, and to report a complete overview of all documented adverse events related to Dermabond® use in current literature. The US Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database was queried for reports of adverse events related to Dermabond® use from January 1, 2010, to February 1, 2020. Data were extracted from reports pertaining to head and neck procedures. In addition, literature review was performed from January 1970 to January 2021. Various adverse events related to Dermabond® were included in the study. We identified 32 adverse events, from which 29 (90.6%) were patient-related events and 3 (9.4%) were operator-related events. Of the patient-related events, contact dermatitis (CD) (20 [69.0%]) was the most common, followed by wound dehiscence (4 [13.8%]). All of the operator-related events were from inadvertent cut injury (3 [100%]). Following the literature review, adverse events of Dermabond® were categorized into CD, wound dehiscence, infection, and cut injury. Dermabond® demonstrated utility in various surgical procedures including head and neck surgeries but are associated with risks. This study identified adverse events associated with Dermabond®. Further studies are needed to establish the causation of contact dermatitis in certain populations.


Technical approaches to the optimisation of CT.
This paper reviews current technical approaches to the optimisation of CT practice, i.e. approaches to reduce patient dose to the necessary minimum. The most important step towards this goal appears to be the technology of tube current modulation (TCM), which came into practice in the early 2000s and has become the standard approach recently. Anatomy- or attenuation-based TCM allows for a dose reduction between 10 and 60% as compared to scans with constant tube current. Automatic exposure control (AEC) approaches are the next step; based on TCM technology, AEC adapts the tube current both with the rotation angle alpha (alpha-modulation) and along the z-axis (z-modulation) to achieve a pre-selected image quality level at minimal dose. To pre-select the image quality level, i.e. primarily the pixel noise level, tools for simulation are important to investigate the necessary noise levels pro- and retrospectively for given cases and diagnostic tasks. Respective "dose tutor" approaches have become available recently and are presented. The most recent technical innovation which may lead to substantial dose reduction is the investigation of optimal spectra taking the type of contrast and 3D dose distributions into account. A high potential has been shown especially for pediatric CT and for thoracic CT where dose reduction of a factor of 2 and more is possible when using reduced tube voltages.


The glutathione peroxidase 8 (GPX8)/IL-6/STAT3 axis is essential in maintaining an aggressive breast cancer phenotype.
One of the emerging hallmarks of cancer illustrates the importance of metabolic reprogramming, necessary to synthesize the building blocks required to fulfill the high demands of rapidly proliferating cells. However, the proliferation-independent instructive role of metabolic enzymes in tumor plasticity is still unclear. Here, we provide evidence that glutathione peroxidase 8 (GPX8), a poorly characterized enzyme that resides in the endoplasmic reticulum, is an essential regulator of tumor aggressiveness. We found that GPX8 expression was induced by the epithelial-mesenchymal transition (EMT) program. Moreover, in breast cancer patients, GPX8 expression significantly correlated with known mesenchymal markers and poor prognosis. Strikingly, GPX8 knockout in mesenchymal-like cells (MDA-MB-231) resulted in an epithelial-like morphology, down-regulation of EMT characteristics, and loss of cancer stemness features. In addition, GPX8 knockout significantly delayed tumor initiation and decreased its growth rate in mice. We found that these GPX8 loss-dependent phenotypes were accompanied by the repression of crucial autocrine factors, in particular, interleukin-6 (IL-6). In these cells, IL-6 bound to the soluble receptor (sIL6R), stimulating the JAK/STAT3 signaling pathway by IL-6 trans-signaling mechanisms, so promoting cancer aggressiveness. We observed that in GPX8 knockout cells, this signaling mechanism was impaired as sIL6R failed to activate the JAK/STAT3 signaling pathway. Altogether, we present the GPX8/IL-6/STAT3 axis as a metabolic-inflammatory pathway that acts as a robust regulator of cancer cell aggressiveness.


Microbiota-derived short chain fatty acids in fermented Kidachi Aloe promote antimicrobial, anticancer, and immunomodulatory activities.
Fermented Aloe leaf juice is a commonly used food supplement in Japan. In a previous study, fermentation of A. arborescence juice was performed and the presence of short-chain fatty acids (SCFAs) was confirmed and quantified. Samples were collected before and after the fermentation process to be subjected, in the present study, to DNA extraction, 16S rRNA gene (V3-V4 regions) amplification, and sequencing by the next-generation Illumina MiSeq sequencer. Our work aims to analyze the sequences to assess the bacterial diversity in the juice before and after fermentation, identify the beneficial microbes responsible for the production of SCFAs, and evaluate some of the biological activities of the fermented juice. Data revealed the richness and diversity of the bacterial community in the fermented juice compared to the unfermented control. Relative abundance of bacterial phyla showed that the majority of the microbial community in the test samples corresponded to Pseudomonadota (unfermented; 10.4%, fermented; 76.36%), followed by Bacillota (unfermented; 4.71%, fermented; 17.13%) and then Bacteroidota (unfermented; 0.57%, fermented; 1.64%). For the fermented sample, 84% of Bacillota were lactobacilli. A hierarchically clustered heatmap revealed that Lactobacillus was the most abundant genus in both samples suggesting its involvement in the production of SCFAs. To assess potential health benefits, the anticancer efficacy of the fermented product of A. arborescens was investigated against colorectal cancer (IC50 = 3.5 µg/ml) and liver cancer (IC50 = 6.367 µg/ml) compared to the normal peripheral blood mononuclear cells (PBMCs). Flow cytometric analysis of the cell cycle pattern revealed remarkable population arrest in G0 and G1, however, the highest percentages were mainly in the G1 phase for Hep-G2 (40.1%) and HCT-116 (53.2%) cell lines. This effect was accompanied by early apoptotic profiles of HCT-116 (36.9%) and late apoptosis for Hep-G2 (17.3%). Furthermore, immunomodulatory properties demonstrated a significantly (p < 0.001) reduced percentage of induced TNF-α while enhancing IFN-γ dramatically. For antimicrobial activities, marked broad-spectrum activities were recorded against some bacterial and fungal pathogens (17-37 mm inhibition zone diameter range). Therefore, this study affords the basis of bacterial community composition in fermented A. arborescens juice as well as its potential biological benefits.


Nigral involvement in atypical parkinsonisms: evidence from a pilot study with ultra-high field MRI.
Ten healthy subjects (HS) and 15 patients with atypical parkinsonisms underwent 7-T susceptibility-weighted-imaging MR to evaluate substantia nigra (SN). All HS were judged "normal". Twelve out of 15 patients exhibited bilateral abnormal SN while three patients with corticobasal degeneration (CBD) showed bilateral normal aspect of SN. Anatomical changes of SN at 7 T occur in multiple system atrophy and progressive supranuclear palsy as previously reported in Parkinson's disease. Preserved SN in CBD confirms the pathological heterogeneity of this disease.


Characterization of the lipopolysaccharide of Escherichia coli 126.
The lipopolysaccharide (LPS) of Escherichia coli 126 was isolated and studied. The lipid A fatty acid composition of the investigated LPS was similar to that of other members of the family Enterobacteriaceae. The E. coli 126 LPS was more toxic than the LPSs of previously studied E. coli strains and of other members of the Enterobacteriaceae (Budvicia aquatica and Pragia fontium), and was less pyrogenic than pyrogenal. SDS-PAG electrophoresis showed a bimodal distribution typical of S-form LPSs. The LPS of E. coli 126 decreased the adhesive index indicating a possible competition between LPS molecules of E. coli 126 and adhesins of E. coli F-50 on rabbit erythrocytes. The LPS of E. coli 126 in a homologous system showed antigenic activity in the reactions of double immunodiffusion in agar by Ouchterlony. No serological cross-reaction of the LPS of other E. coli strains, as well as of that of the B. aquatica type strain, with the antiserum to E. coli 126 was observed. The structural components of the lipopolysaccharide obtained by mild acid hydrolysis were lipid A, the core oligosaccharide, and the O-specific polysaccharide. Based on the data of monosaccharide analysis and 1H and 13C NMR spectroscopy it was found that the O-specific polysaccharide had the structure characteristic of the representatives of E. coli serogroup O15.


Enlargement of the anterior horn of the lateral ventricle in schizophrenic patients: chronological and morphometrical studies.
The anterior horn and lateral ventricular sizes of the brain CT were selected for measurement and comparison between 47 schizophrenic patients and 48 neurotic cases, which constituted the control subjects. The ventricular brain ratio (VBR) and the linear ratio (LR 1-6) in multiple age groups were calculated, analyzed and compared using the Student's t test, the two-way ANOVA and Bonferroni's methods. It was found that the VBR of the anterior horn and modified bicaudate cerebroventricular index of the teenage schizophrenics were significantly greater than those of the teenage controls (p less than 0.01) and the ventricular sizes were not associated with the different stages of age except for the cases of the teenage group. These results support the hypothesis of previous investigators that the ventricular enlargement is present early in the course of schizophrenia and provide additional evidence that in teenage schizophrenic patients there is a tendency of the enlargement of the anterior horn of the lateral ventricle which may be related with a morphological vulnerability in the prefrontal cortex.


Mesenchymal Stromal Cells: a Possible Reservoir for HIV-1?
The introduction of antiretroviral therapy (ART) and highly active antiretroviral therapy (HAART) has transformed human immunodeficiency virus (HIV)-1 into a chronic, well-managed disease. However, these therapies do not eliminate all infected cells from the body despite suppressing viral load. Viral rebound is largely due to the presence of cellular reservoirs which support long-term persistence of HIV-1. A thorough understanding of the HIV-1 reservoir will facilitate the development of new strategies leading to its detection, reduction, and elimination, ultimately leading to curative therapies for HIV-1. Although immune cells derived from lymphoid and myeloid progenitors have been thoroughly studied as HIV-1 reservoirs, few studies have examined whether mesenchymal stromal/stem cells (MSCs) can assume this function. In this review, we evaluate published studies which have assessed whether MSCs contribute to the HIV-1 reservoir. MSCs have been found to express the receptors and co-receptors required for HIV-1 entry, albeit at levels of expression and receptor localisation that vary considerably between studies. Exposure to HIV-1 and HIV-1 proteins alters MSC properties in vitro, including their proliferation capacity and differentiation potential. However, in vitro and in vivo experiments investigating whether MSCs can become infected with and harbour latent integrated proviral DNA are lacking. In conclusion, MSCs appear to have the potential to contribute to the HIV-1 reservoir. However, further studies are needed using techniques such as those used to prove that cluster of differentiation (CD)4+ T cells constitute an HIV-1 reservoir before a reservoir function can definitively be ascribed to MSCs. MSCs may contribute to HIV-1 persistence in vivo in the vasculature, adipose tissue, and bone marrow by being a reservoir for latent HIV-1. To harbour latent HIV-1, MSCs must express HIV-1 entry markers, and show evidence of productive or latent HIV-1 infection. The effect of HIV-1 or HIV-1 proteins on MSC properties may also be indicative of HIV-1 infection.


Molecular phylogeny as a basis for the classification of transport proteins from bacteria, archaea and eukarya.
Although enzymes catalyzing chemical reactions have long been classified according to the system developed by the Enzyme Commission (EC), no comparable system has been developed or proposed for transport proteins catalyzing transmembrane vectorial reactions. We here propose a comprehensive system, designated the Transport Commission (TC) system, based both on function and phylogeny. The TC system initially categorizes permeases according to mode of transport and energy coupling mechanism, and each category is assigned a one-component TC number (W). The secondary level of classification corresponds to the phylogenetic family (or superfamily) to which a particular permease is assigned, and each family is assigned a two-component TC number (W.X). The third level of classification refers to the phylogenetic cluster within a family (or the family within a superfamily) to which the permease belongs, and each cluster receives a three-component TC number (W.X.Y). Finally, the last level of categorization is based on substrate specificity and polarity of transport, and each entry is assigned a four component TC number (W.X.Y.Z). This system is based on the observation that mode of transport and energy coupling mechanism are fundamental properties of transport systems that very seldom transcend familial lines, but substrate specificity, being readily alterable by point mutations, is a superficial characteristic that often transcends familial lines. The proposed system has the potential to include all known permeases for which sequence data are available and has the flexibility to accommodate the multitude of permeases likely to be revealed by future genome sequencing and biochemical analysis. Major conclusions resulting from our classification efforts are described. The classification system, which will be continuously updated, is available on our World Wide Web site (http:/(/)www-biology.ucsd.edu/ approximately msaier/transport/titlepage.html).


Distribution of vinculin in the Z-disk of striated muscle: analysis by laser scanning confocal microscopy.
Vinculin is a major cytoskeletal component in striated muscle, where it has been reported to form a rib-like structure between the cell membrane and the Z-disk termed a costamere. This arrangement of vinculin has been purported to be involved in the alignment of the myofibrils. However, the three-dimensional arrangement of vinculin in relation to the Z-disk of the myofibril was not known. In the present study, we examined the distribution of vinculin in striated muscle with monospecific antibodies using immunofluorescence and laser scanning confocal microscopy. Isolated cardiac and skeletal muscle cells from a variety of species, tissue sections, and neonatal myocytes with developing myofibrils were examined. Optical sectioning in the X-Y and X-Z planes demonstrated that vinculin immunoreactivity was heaviest at the periphery of the cell; however, the immunoreactivity was also distributed within the Z-disk although at a relatively reduced level. This distribution is potentially significant in understanding the physiological significance of vinculin in striated muscle function and in myofibrillogenesis.


Muscle hypertrophy in bodybuilders.
Muscle biopsy samples were obtained from m. vastus lateralis and m. deltoideus of three high caliber bodybuilders. Tissue specimens were analysed with respect to relative distribution of fast twitch (FT) and slow twitch (ST) fiber types and different indices of fiber area. In comparison to a reference group of competitive power/weight-lifters the following tendencies were observed: the percentage of FT fibers was less, mean fiber area was smaller and selective FT fiber hypertrophy was not evident. Values for fiber type composition and fiber size were more similar to values reported for physical education students and non-strength trained individuals. The results suggest that weight training induced muscle hypertrophy may be regulated by different mechanisms depending upon the volume and intensity of exercise.


MLH1 promoter hypermethylation: are you absolutely sure about the absence of MLH1 germline mutation? About a new case.
Lynch syndrome accounts for 3-5% of colorectal cancers and is due to a germline mutation in one of the mismatch repair genes MLH1, MSH2, MSH6, and PMS2. Somatic hypermethylation of the MLH1 promoter is commonly associated to sporadic cases. Strategies have been developed to identify patients with Lynch Syndrome based on clinical findings, tumoral phenotype, family history and immunohistochemistry analysis. However, there still are some pitfalls in this strategy, possibly responsible for an underdiagnosis of Lynch syndrome. Here we report the case of a 37 years-old man presenting with two concomitant tumors located in the rectosigmoid and in the ileocecal angle. Both tumors were microsatellites instability-high (MSI-H) and showed a loss of MLH1 and PMS2 protein expression, but only one had MLH1 promoter hypermethylation. Constitutional analysis of mismatch repair genes could not be performed from a blood sample, because of the early death of the patient. However, tumoral tissue analyses revealed in both tumors a pathogenic variant in the MLH1 gene. Further analysis of the surrounding tumor-free tissue also showed the presence of this alteration of the MHL1 gene. Finally, the same pathogenic variant was present constitutionally in one of the siblings of the patient, confirming its hereditary nature. This new case of concomitant presence of MLH1 promoter hypermethylation and MLH1 germline mutation demonstrates that the presence of MLH1 promoter hypermethylation should not rule out the diagnosis of Lynch Syndrome.


Cloning and characterization of Planctomyces limnophilus rpoN: complementation of a Salmonella typhimurium rpoN mutant strain.
The rpoN gene, which encodes the alternative sigma factor sigma 54, was cloned from the budding, peptidoglycan-less bacterium Planctomyces limnophilus. P. limnophilus rpoN complemented the Ntr- phenotype of a Salmonella typhimurium rpoN mutant strain. The P. limnophilus rpoN gene encoded a predicted polypeptide that was 495 residues in length and shared a significant homology with other members of the sigma 54 family. The protein sequence displayed all of the characteristic motifs found in members of this family, including the C-terminal helix-turn-helix motif and the well-conserved RpoN box. A potential sigma 54-dependent activator was also identified in P. limnophilus. These findings extend the range of phylogenetic groups within the Domain Bacteria that are known to contain sigma 54.


Genetic diversity of avocado from the southern highlands of Tanzania as revealed by microsatellite markers.
Avocado is an important cash crop in Tanzania, however its genetic diversity is not thoroughly investigated. This study was undertaken to explore the genetic diversity of avocado in the southern highlands using microsatellite markers. A total of 226 local avocado trees originating from seeds were sampled in eight districts of the Mbeya, Njombe and Songwe regions. Each district was considered as a population. The diversity at 10 microsatellite loci was investigated. A total of 167 alleles were detected across the 10 loci with an average of 16.7 ± 1.3 alleles per locus. The average expected and observed heterozygosity were 0.84 ± 0.02 and 0.65 ± 0.04, respectively. All but two loci showed a significant deviation from the Hardy-Weinberg principle. Analysis of molecular variance showed that about 6% of the variation was partitioned among the eight geographic populations. Population FST pairwise comparisons revealed lack of genetic differentiation for the seven of 28 population pairs tested. The principal components analysis (PCA) and hierarchical cluster analysis showed a mixing of avocado trees from different districts. The model-based STRUCTURE subdivided the trees samples into four major genetic clusters. High diversity detected in the analysed avocado germplasm implies that this germplasm is a potentially valuable source of variable alleles that might be harnessed for genetic improvement of this crop in Tanzania. The mixing of avocado trees from different districts observed in the PCA and dendrogram points to strong gene flow among the avocado populations, which led to population admixture revealed in the STRUCTURE analysis. However, there is still significant differentiation among the tree populations from different districts that can be utilized in the avocado breeding program.


The effects of chronic intracochlear electrical stimulation on inferior colliculus spatial representation in adult deafened cats.
Previous studies have shown that chronic electrical stimulation through a cochlear implant causes significant alterations in the central auditory system of neonatally deafened cats. The goal of this study was to investigate the effects of chronic stimulation in the mature auditory system. Normal hearing adult animals were deafened by ototoxic drugs and received daily electrical stimulation over periods of 4-6 months. In terminal physiology experiments, response thresholds to pulsatile and sinusoidal signals were recorded within the inferior colliculus (IC). Using previously established methods, spatial tuning curves (STCs; threshold vs. IC depth functions) were constructed, and their widths measured to infer spatial selectivity. The IC spatial representations were similar for pulsatile and sinusoidal stimulation when phase duration was taken into consideration. However, sinusoidal signals consistently elicited much lower thresholds than pulsatile signals, a difference not solely attributable to differences in charge/phase. The average STC width was significantly broader in the adult deafened/stimulated animals than in controls (adult deafened/unstimulated cats), suggesting that electrical stimulation can induce spatial expansion of the IC representation of the chronically stimulated cochlear sector. Further, results in these adult animals were not significantly different from results in neonatally deafened, early stimulated animals, suggesting that a similar degree of plasticity was induced within the auditory midbrains of mature animals.


Mapping O-glycosylation of apolipoprotein C-III in MALDI-FT-ICR protein profiles.
Ultrahigh resolution MALDI-FT-ICR profiles were obtained from human serum samples that were processed using a fully automated RPC18-based magnetic bead method. Proteins were profiled from m/z value 6630 with a resolving power of 73 000 up to m/z value 12 600 with a resolving power of 37 000. In this study, a detailed evaluation was performed of the isoforms of apolipoprotein C-III, i.e. the different mucin-type core 1 O-glycans with the addition of one or two sialic acid residues. The MALDI-FT-ICR profiles are discussed with regard to reproducibility of the signal intensities as well as the accurate mass measurements. ESI-FT-ICR-MS/MS analyses of the same serum samples were performed to confirm the identity of apolipoprotein C-III glycoforms.


Correlation of fetal DNA levels in maternal plasma with Doppler status in pathological pregnancies.
To evaluate whether intrauterine growth restriction (IUGR) as seen in preeclampsia is associated with high levels of fetal DNA in maternal circulation, and whether fetal DNA is related to altered uterine and/or umbilical artery Doppler velocimetry. Fetal DNA quantification was performed by real-time PCR on SRY sequences in 64 male-bearing pregnant women with IUGR and/or preeclampsia and 89 controls. Fetal DNA content was significantly elevated in IUGR pregnancies similar to preeclampsia and correlated with altered umbilical Doppler velocimetry, while no correlation was found with uterine Doppler status. Increased fetal DNA levels in maternal plasma may be a sign of placental or fetal pathology even in the presence of normal uterine Doppler velocimetry, allowing a more precise diagnostic evaluation. The finding that elevated fetal DNA in IUGR pregnancies correlates with abnormal umbilical Doppler velocimetry suggests that fetal DNA release is associated more with fetal chronic hypoxia than with fetal size.


An improved system for surgical excision of needle-localized nonpalpable breast lesions.
A technique for improved localization and surgical excision of nonpalpable breast lesions is described. The method employs an atraumatic outer stiffening cannula which is available in a variety of lengths and eliminates several of the technical difficulties encountered during these procedures. Successful initial excision of over 50 consecutive nonpalpable breast lesions has been obtained with this technique.


The interrelationship between atrial fibrillation and atrial flutter.
For a long time, it has been known that atrial fibrillation and atrial flutter have a close clinical interrelationship. Recent electrophysiological studies, especially mapping studies, have significantly advanced our understanding of this interrelationship. Regarding the relationship of atrial fibrillation with atrial flutter: Atrial fibrillation of variable duration precedes the onset of atrial flutter in almost all instances. During the atrial fibrillation, the functional components needed to complete the atrial flutter reentrant circuit, principally a line of block between the venae cavae, are formed. If this line of block does not form, classical atrial flutter does not develop. If this line of block shortens or disappears, classical atrial flutter disappears. In fact, it is fair to say that the major determinant of whether atrial fibrillation persists or classical atrial flutter develops is whether a line of block forms between the venae cavae. Regarding the relationship of atrial flutter with atrial fibrillation: Studies in experimental models and now in patients have demonstrated that a driver (a rapidly firing focus or a reentrant circuit of very short cycle length) can cause atrial fibrillation by producing fibrillatory conduction to the rest of the atria. When the driver is a stable reentrant circuit of very short cycle length, it is, in effect, a very fast form of atrial flutter. There probably is a spectrum of reentrant circuits of short cycle length, i.e., "atrial flutter," that depend, in part, on where the reentrant circuit is located. When the cycle length of the reentrant circuit is so short that it will only activate small portions of the atria in a 1:1 manner, the rest of the atria will be activated rapidly but irregularly, i.e., via fibrillatory conduction, resulting in atrial fibrillation. In short, there are probably several mechanisms of atrial fibrillation, one of which is due to a very rapid atrial flutter circuit causing fibrillatory conduction. In sum, atrial fibrillation and atrial flutter have an important interrelationship.


Haplotype-resolved genomes of wild octoploid progenitors illuminate genomic diversifications from wild relatives to cultivated strawberry.
Strawberry is an emerging model for studying polyploid genome evolution and rapid domestication of fruit crops. Here we report haplotype-resolved genomes of two wild octoploids (Fragaria chiloensis and Fragaria virginiana), the progenitor species of cultivated strawberry. Substantial variation is identified between species and between haplotypes. We redefine the four subgenomes and track the genetic contributions of diploid species by additional sequencing of the diploid F. nipponica genome. We provide multiple lines of evidence that F. vesca and F. iinumae, rather than other described extant species, are the closest living relatives of these wild and cultivated octoploids. In response to coexistence with quadruplicate gene copies, the octoploid strawberries have experienced subgenome dominance, homoeologous exchanges and coordinated expression of homoeologous genes. However, some homoeologues have substantially altered expression bias after speciation and during domestication. These findings enhance our understanding of the origin, genome evolution and domestication of strawberries.


Auditory, visual, and cross-modal negative priming.
Auditory, visual, and cross-modal negative priming was investigated using a task in which participants judged whether stimuli were animals or musical instruments. Negative priming was observed, but only if the attended and the ignored primes evoked different responses. This pattern--negative priming after conflict, but not after nonconflict, primes--was demonstrated with visual stimuli and replicated with auditory stimuli, as well as across modalities, both auditory to visual and visual to auditory. Implications for theories of negative priming are discussed.


Distribution in the visual field of the costs of voluntarily allocated attention and of the inhibitory after-effects of covert orienting.
By using a simple reaction time (RT) paradigm we have investigated the spatial distribution of the benefits and costs of voluntarily directed attention and of the inhibitory after-effects of covert orienting. In the first experiment subjects deliberately allocated attention to each one of five stimulus positions disposed along the horizontal meridian, while at the same time fixing their eyes on the central position. The separation in visual angle between the central position and the two nearest positions, one on the left and the other on the right, was 10 degrees; that between the central position and the two most eccentric positions was 30 degrees. By comparing RT to brief flashes of light presented at each position during directed attention with RT to identical flashes at the same position during diffuse attention (i.e. in a condition in which subjects paid equal attention to all five positions), it was possible to determine that benefits, that is RT decreases relative to the diffuse-attention condition, were strictly limited to the attended position. Costs, i.e. RT increases relative to the diffuse-attention condition, showed a more diffuse and complex spatial pattern. When attention was directed to one of the noncentral positions, costs were apparent at the two contralateral positions and at the central position, but not at the ipsilateral position. When attention was directed to the central position, costs occurred at all other positions. This suggests a special role for the vertical meridian in delimiting the area of costs when one covertly orients towards the opposite right or left visual half field. Work of others and our preliminary evidence indicate that the area of costs is similarly limited by the horizontal meridian when one orients toward the opposite upper or lower visual field. In the second experiment we studied the inhibitory after-effect of covert orienting. Orienting to a light stimulus without moving the eyes to it may induce a short-lived facilitation of the speed of response to a second stimulus presented at the same position, but this facilitation is followed by a profound and prolonged RT retardation. By using a two-flashes paradigm we observed this RT retardation not only when the two stimuli appeared at the same position, but also when they occurred at different locations in the same altitudinal or lateral visual hemifield. There were no inhibitory after-effects when the two stimuli appeared on opposite sides of the vertical or horizontal meridian.(ABSTRACT TRUNCATED AT 400 WORDS)


ESR determinations of membrane permeability in a yeast sterol mutant.
Yeast sterol mutants were subjected to ESR analysis in an attempt to elucidate how altered sterol composition correlates with membrane permeability. The technique requires spin labeling the intact yeast cells with a small, water-soluble nitroxide probe (2,2,5,5 tetramethyl-3-pyrrolin-1-oxyl-3-carboxylic acid, PCA), suspending cells in a NiCl2 solution, and measuring the extent of Ni2+ entry through the membrane by its magnetic dipolar line broadening effect on the PCA signal. The wild type, A184D, was found to be impermeable to Ni2+ during all growth phases while the sterol mutant erg 6/2 was readily permeable to Ni2+. Other sources of line broadening such as increased rotational correlation time and cell nonviability are shown to be neglibible. Internal Ni2+ concentrations for erg 6/2 and kinetics of Ni2+ entry were determined.


Infection caused by Sporothrix schenckii: an autochthonous case in Bari, Southern Italy.
An autochthonous case of lymphocutaneous sporotrichosis caused by Sporothrix schenckii is reported. The patient developed skin lesions localized along the lymphatics that appeared after he suffered an injury while collecting wicker canes in marshy water. The fungus was identified as Sporothrix schenckii by MALDI-TOF and sequencing. Phylogenetic analysis was also performed. Low MIC values were detected for all tested echinocandins and azoles except for fluconazole. The patient was treated with itraconazole without significant improvement. A regression of lesions was observed after 3 months of therapy with voriconazole. Few cases of sporotrichosis have been reported in Europe. However, several cases of sporotrichosis have been described in Italy. The incidence of sporotrichosis in Italy may be underestimated and microbiologists, and clinicians must be aware of this fungal infection.


Sex differences in smoking cue reactivity: craving, negative affect, and preference for immediate smoking.
Female smokers have greater difficulty quitting, possibly due to increased reactivity to smoking-related cues. This study assessed sex differences in craving, affect, and preference for immediate smoking after cue exposure. Regular smokers (n = 60; 50% female) were exposed to smoking and neutral cues in separate, counterbalanced sessions. Outcomes included changes in craving and affect and preference for immediate smoking following cue exposure. Findings indicated that women exhibited greater preference for immediate smoking (p = .004), and reported greater cue-induced increases in cigarette craving (p = .046) and negative affect (p = .025). These data suggest that women may have greater difficulty inhibiting smoking after cue exposure, possibly as a consequence of greater increases in craving and negative affect. Findings suggest a mechanism that may contribute to greater cessation failure among female smokers.


[Suicidal behaviors in migrant youths: Male experiences].
Suicide is the second leading cause of death among adolescents. Boys are more affected than girls, although they report fewer suicide attempts and rely less on care. Few studies have examined the experience of suicidal thoughts and behavior among young boys. In order to improve their health care, it is necessary to consider the socio-cultural aspects and the construction of the meaning given by adolescent boys to suicidal behaviors in France. This is a qualitative, complementary and inductive study. All teens included have presented suicidal thoughts in the months preceding the inclusion. The existence of self-mutilation and/or suicidal act is sought but is not included within the criteria of inclusion, the various contexts will enrich the data. Semi-structured interviews are transcribed and analyzed by the Interpretative Phenomenological Analysis. Ten adolescents between 14 and 20 years old were included in the study. Three axes of experience emerge: the relationship to oneself, the relationship to the other, the relationship to death. Some themes are common to experiences of both boys and girls, others are more specific to the boys' experience. The inner struggle, testing one's limits and an isolating unspeakable are thus common, highlighting the difficulty for adolescents to mentalize and verbalize emotions and feelings. Difficulties in connecting with others, and feelings of loneliness and isolation, are at the core of the participants' experience. However, the experience of boys appears specific in the difficulty to represent the irreversibility of death which can lead to suicidal behavior without direct intentionality. The narrative of suicidal acts, in its formulation, is quite different from that of young girls. One can assume that the difficulty of expressing suffering could lead young boys to develop a discourse that overshadows the question of their death, or in contrast magnifies it in a rewarding stage from which they pride themselves. The fear of being isolated or rejected seems almost insurmountable for the boys interviewed. The fear of the judgment of peers or the family is mixed with the imperative to face the problem by oneself and reinforces the feeling of isolation in a retroactive loop. The story of the suicidal act can take a positive and enriching tone in the participant's stories. This only applies to adolescents with a history of suicidal gesture. The experience of acting out and its consequences seems to be integrated by the adolescent as elements which participate to a certain extent to the construction of their identity. This ameliorative feature can be compared to the hegemonic social models of masculinity. The sociological notion of gender identity makes it possible to think of this construction in a dynamic way and to propose adaptations of the caregivers' attitude during the first interviews with a suicidal teenager. During the first meetings, the caregiver should explore the adolescent's representations of the suicidal crisis in a neutral, self-interested, and unbiased way, including when the representations are disturbing or shocking for the caregiver. For example, when the patient values or glorifies suicidal behavior or when care is experienced as a sign of weakness and vulnerability. Respect of these proposals can indeed support weakened narcissistic foundations and favor encounter and alliance. This can only be done with the conviction that these representations are not frozen, but in construction, and that they can be secondarily mobilized in the therapeutic relationship. For that purpose, a work of elaboration on the representations of the masculinity will be able to lead the young person to reconsider his perception of care and suicidal behaviors. Reflexivity on the part of the caregiver about his own representations of masculinity seems necessary. Therapeutic management must explore and respect the adolescent's representations of masculinity and then mobilize them to bring the young person to reconsider his perception of care and suicidal behavior.


Determination of the isoniazid acetylator phenotype in a West African population.
The concentration of isoniazid in plasma after an oral dose of 10 mg/kg was estimated in 120 Nigerians (39 normal, 81 tuberculous). The concentrations were bimodally distributed giving a good discrimination between slow and rapid acetylators. The proportion of rapid to slow acetylators in the whole group was 60:40. This is similar to the results of the only other study of acetylator phenotype in West Africans.


Acute treatment with tumour necrosis factor-alpha induces changes in protein metabolism in rat skeletal muscle.
Acute treatment of rats with recombinant tumour necrosis factor (TNF-alpha) caused an enhanced proteolytic rate--measured as tyrosine released in the presence of cycloheximide-in soleus muscle (34%). The cytokine treatment also decreased the rate of protein synthesis in this muscle (22%) while it had no effect upon the same parameter in extensor digitorum longus (EDL) (26%) muscle. In addition, treatment of rats with TNF-alpha increased amino acid uptake by transport system A in the incubated muscles both in soleus (45%) and EDL (99%) in the presence of insulin in the incubating medium. This effect was not associated with a direct action of TNF on muscle since the addition of different concentrations of the cytokine to the preparations did not alter the uptake of alpha(methyl)-aminoisobutyric acid by the incubated muscles. It can be concluded that acute TNF-alpha treatment causes changes in protein metabolism in red-type muscles-such soleus-while little effects are seen in white-type muscles-such as EDL. The results presented may, to some extent, be related to the cachectic response associated with cancer and inflammation.


Torulopsis glabrata urinary infections: a review.
During a 12-year prospective period 9 referral patients were treated for proved Torulopsis urinary infections. Of the 9 patients 7 had irritative voiding symptoms and pyuria was present in 8. To estimate incidence of infection, a retrospective review was performed between January 1982 and December 1983. A total of 105 urine specimens from 57 hospitalized patients yielded Torulopsis glabrata. Two patients suffered symptomatic invasive infections. Patients were treated with antifungal therapy only when invasive symptomatic infections persisted despite elimination of predisposing factors. 5-Fluorocytosine eradicated Torulopsis funguria in 4 of 6 patients in whom it was used. Prolonged therapy with ketoconazole was also successful. Surgical removal of associated stones or fungal coagulum was sometimes required.


Correction to: How the 2018 US Physical Activity Guidelines are a Call to Promote and Better Understand Acute Physical Activity for Cognitive Function Gains.
The article How the 2018 US Physical Activity Guidelines are a Call to Promote and Better Understand Acute Physical Activity for Cognitive Function Gains, written by Yu-Kai Chang, Kirk I. Erickson, Emmanuel Stamatakis and Tsung-Min Hung, was originally published Online First without Open Access. After publication in volume 49, issue 11, pages 1625-1627 [#-#] the author decided to opt for Open Choice and to make the article an Open Access publication.


Using structural equation modeling to understand family and psychological factors of childhood obesity: from socioeconomic disadvantage to loss of control eating.
Current study aimed to empirically test the Hemmingsson's theoretical model of childhood obesity which emphasizing the importance of family environment and the emotional distress of parents as influential variables in the emotional distress of the child and subsequent weight gain. This study also tested the hypothesis that the emotional distress of the child triggers a weight gain-inducing behavior (loss of control eating) to suppress negative emotions. Families of 220 Spanish children participated in the study (28.2% normal, 35.1% overweight and 32.2% obesity), aged between 8 and 12. The evaluation included a clinical interview and a battery of questionnaires. Structural equation models were computed according to the steps proposed by theoretical model. Fit indices were acceptable suggesting that the data adequately fit the hypothesized model. Path coefficients in the final model were statistically significant showing a relationship between socioeconomic status, the emotional distress of parents, family environment, the emotional distress of children, loss of control eating and child's BMI Z-score. Considering this relation between emotional distress and child weight status, childhood obesity intervention programs may benefit from targeting family environment and the potential role that food is playing in the regulation of children's distress. Level III: Cohort analytic study.


18F-Radiolabeling and Preliminary Evaluation of a HSP90 ligand.
With the ambition of improving the management of pancreatic neuroendocrine tumors (P-NETs), we developed and preliminary validated a novel fluorine-18 labelled HSP90 ligand. A precursor containing methoxymethyl ethers protecting groups and a tosyl as leaving group was synthesized. The target compound was labeled with nucleophilic 18F-fluoride and the protecting groups was subsequently removed with hydrochloric acid before purification. In vitro cell- and frozen section autoradiography and in vivo animal studies were performed. The precursor was successfully synthesized and utilized in the 18F-radiolabeling giving 0.5-1.0 GBq of pure product with a synthesis time of 70 min. In vitro experiments indicated a high specific binding, but in vivo studies showed no tumor uptake due to fast hepatobiliary metabolism and excretion. Despite the unfavorable in vivo properties of the tracer, the promising results from in vitro autoradiography experiments in frozen sections of P-NETs from surgical resection encourage us to continue the project aiming the improvement of in vivo properties of the tracer.


Inclusion of celecoxib into fibrous ordered mesoporous carbon for enhanced oral bioavailability and reduced gastric irritancy.
Fibrous ordered mesoporous carbon (FOMC) was developed as a new drug delivery system for loading an insoluble drug, designed to be orally administered, and then to enhance the drug loading capacity, improve the dissolution rate, enhance the oral bioavailability and reduce the gastric damage. Celecoxib (CEL) was chosen as a model drug. The nanostructures and effect of different pore sizes (4.4-7.0 nm) on drug loading and release properties were studied. The results showed that FOMC has a high drug loading capacity (0.599 g/g, drug weight/carrier weight) and the dissolution rate of CEL from FOMC was much faster than pure crystalline CEL using buffer (pH 6.8) as a dissolution medium. Moreover, the oral bioavailability of CEL loaded into FOMC was significantly improved compared with that of CEL capsules and the gastric damage caused by CEL which was loaded in FOMC was also reduced, demonstrating the protective effect of FOMC.