Watermelon and dietary advice compared to dietary advice alone following hospitalization for hyperemesis gravidarum: a randomized controlled trial.
Hyperemesis gravidarum (HG) affects about 2% of pregnancies and is at the severe end of the spectrum of nausea and vomiting of pregnancy. HG causes severe maternal distress and results in adverse pregnancy outcomes long after the condition may have dissipated. Although dietary advice is a common tool in management, trial evidence to base the advice on is lacking. A randomized trial was conducted in a university hospital from May 2019 to December 2020. 128 women at their discharge following hospitalization for HG were randomized: 64 to watermelon and 64 to control arm. Women were randomized to consume watermelon and to heed the advice leaflet or to heed the dietary advice leaflet alone. A personal weighing scale and a weighing protocol were provided to all participants to take home. Primary outcomes were bodyweight change at the end of week 1 and week 2 compared to hospital discharge. Weight change (kg) at end of week 1, median[interquartile range] -0.05[-0.775 to + 0.50] vs. -0.5[-1.4 to + 0.1] P = 0.014 and to the end of week 2, + 0.25[-0.65 to + 0.975] vs. -0.5[-1.3 to + 0.2] P = 0.001 for watermelon and control arms respectively. After two weeks, HG symptoms assessed by PUQE-24 (Pregnancy-Unique Quantification of Emesis and Nausea over 24 h), appetite assessed by SNAQ (Simplified Nutritional Appetite Questionnaire), wellbeing and satisfaction with allocated intervention NRS (0-10 numerical rating scale) scores, and recommendation of allocated intervention to a friend rate were all significantly better in the watermelon arm. However, rehospitalization for HG and antiemetic usage were not significantly different. Adding watermelon to the diet after hospital discharge for HG improves bodyweight, HG symptoms, appetite, wellbeing and satisfaction. This study was registered with the center's Medical Ethics Committee (on 21/05/2019; reference number 2019327-7262) and the ISRCTN on 24/05/2019 with trial identification number: ISRCTN96125404 . First participant was recruited on 31/05/ 2019.


Co-adsorption of phosphate and zinc(II) on the surface of ferrihydrite.
Ferrihydrite (Fh) is of great importance in affecting the migration and transformation of heavy-metal cations and oxyanions. To advance the understanding of co-adsorption reactions on Fh surface, the co-adsorption of phosphate and Zn(II) from aqueous solution to a synthesized Fh was determined. The batch experiments demonstrated a synergistic adsorption of phosphate and Zn(II) on Fh. In the pH range of 3.5-6, the adsorption of the two contaminants showed strong pH dependence in the single solute adsorption systems, but the dependence alleviated in the simultaneous adsorption system. X-ray photoelectron spectroscopy (XPS) revealed that the chemical shifts of Zn 2p1/2 and Zn 2p3/2 binding energies were more significant than that of P 2p in the single and simultaneous adsorption systems. On the other side, in situ attenuated total reflectance Fourier transform infrared (ATR-FTIR) observed increased formation of outer- and inner-sphere complexes of phosphate in the simultaneous system. Thus, the synergistic adsorption of the two contaminants could be attributed to the formation of ternary complexes as well as electrostatic interactions, while surface precipitation could not be completely ruled out. On the basis of the results from both the batch adsorption experiments and structural characterization, these two contaminants were likely to form phosphate-bridged ternary complexes (≡Fe-P-Zn) in the simultaneous adsorption system.


Anti-PDGF receptor β antibody-conjugated squarticles loaded with minoxidil for alopecia treatment by targeting hair follicles and dermal papilla cells.
This study developed lipid nanocarriers, called squarticles, conjugated with anti-platelet-derived growth factor (PDGF)-receptor β antibody to determine whether targeted Minoxidil (MXD) delivery to the follicles and dermal papilla cells (DPCs) could be achieved. Squalene and hexadecyl palmitate (HP) were used as the matrix of the squarticles. The PDGF-squarticles showed a mean diameter and zeta potential of 195 nm and -46 mV, respectively. Nanoparticle encapsulation enhanced MXD porcine skin deposition from 0.11 to 0.23 μg/mg. The antibody-conjugated nanoparticles ameliorated follicular uptake of MXD by 3-fold compared to that of the control solution in the in vivo mouse model. Both vertical and horizontal skin sections exhibited a wide distribution of nanoparticles in the follicles, epidermis, and deeper skin strata. The encapsulated MXD moderately elicited proliferation of DPCs and vascular endothelial growth factor (VEGF) expression. The active targeting of PDGF-squarticles may be advantageous to improving the limited success of alopecia therapy. Topical use of minoxidil is only one of the very few treatment options for alopecia. Nonetheless, the current delivery method is far from ideal. In this article, the authors developed lipid nanocarriers with anti-platelet-derived growth factor receptor ? antibody to target dermal papilla cells, and showed enhanced uptake of minoxidil.


EmBody/EmFace as a new open tool to assess emotion recognition from body and face expressions.
Nonverbal expressions contribute substantially to social interaction by providing information on another person's intentions and feelings. While emotion recognition from dynamic facial expressions has been widely studied, dynamic body expressions and the interplay of emotion recognition from facial and body expressions have attracted less attention, as suitable diagnostic tools are scarce. Here, we provide validation data on a new open source paradigm enabling the assessment of emotion recognition from both 3D-animated emotional body expressions (Task 1: EmBody) and emotionally corresponding dynamic faces (Task 2: EmFace). Both tasks use visually standardized items depicting three emotional states (angry, happy, neutral), and can be used alone or together. We here demonstrate successful psychometric matching of the EmBody/EmFace items in a sample of 217 healthy subjects with excellent retest reliability and validity (correlations with the Reading-the-Mind-in-the-Eyes-Test and Autism-Spectrum Quotient, no correlations with intelligence, and given factorial validity). Taken together, the EmBody/EmFace is a novel, effective (< 5 min per task), highly standardized and reliably precise tool to sensitively assess and compare emotion recognition from body and face stimuli. The EmBody/EmFace has a wide range of potential applications in affective, cognitive and social neuroscience, and in clinical research studying face- and body-specific emotion recognition in patient populations suffering from social interaction deficits such as autism, schizophrenia, or social anxiety.


Assumptions of the QALY procedure.
The Quality Adjusted Life Year (QALY) has been proposed as a useful index for those managing the provision of health care because it enables the decision-maker to compare the 'value' of different health care programmes and in a way which, potentially at least, reflects social preferences about the appropriate pattern of provision. The index depends on a combination of a measure of morbidity and the risk of mortality. Methodological debate has tended to concentrate on the technicalities of producing a scale of health; and philosophical argument has concentrated on the ethics of interpersonal comparison. There is little recognition of the fragility of the theoretical assumptions underpinning the proposed combination of morbidity and risk of mortality. The context in which the proposed indices are being developed is examined in Section 2. Whilst most working in the field of health measurement eschew over-simplification, it is clear that the application of micro-economics to management is greatly facilitated if a single index can be agreed. The various approaches to combining morbidity and mortality are described in Section 3. The crucial assumptions concern the measurement and valuation of morbidity; the procedures used for scaling morbidity with mortality; and the role of risk. The nature of the valuations involved are examined in Section 4. It seems unlikely that they could ever be widely acceptable; the combination with death and perfect health poses particular problems; and aggregation across individuals compounds the problem. There are also several technical difficulties of scaling and of allowing for risk which have been discussed elsewhere and so are only considered briefly in Section 5 of this paper.(ABSTRACT TRUNCATED AT 250 WORDS)


Inhibition of NLRP3 inflammasome-mediated neuroinflammation alleviates electroconvulsive shock-induced memory impairment via regulation of hippocampal synaptic plasticity in depressive rats.
Electroconvulsive shock has been considered one of the most effective treatment modalities for major depressive disorder. The association of acute transitory neuroinflammation in the hippocampus following electroconvulsive therapy with transient learning and memory impairment limits its clinical application. Whereas the NLRP3 inflammatory pathway is deemed to serve a key role in neuroinflammatory regulation, we aimed to examine if NLRP3 inflammasome activation was linked to electroconvulsive shock (ECS)-induced neuroinflammation and cognitive deficits. The depressed rats were modeled with chronic unpredictable mild stress. Their depression-like behaviors and cognitive performance were evaluated via sucrose preference test, forced swim test, open field test, and Morris water maze test. The NLRP3 expression was determined by western blot. The hippocampal CA1 region was immunohistochemically and electron-microscopically examined, respectively, for the activation of Iba-1 positive microglia and the ultrastructure of synapses. In this work, we found that ECS induced microglial activation in the rat hippocampal CA1 region. Pharmacological inhibition of NLRP3 inflammasome with MCC950 (NLRP3 inhibitor) in vivo significantly alleviated ECS-induced spatial learning and memory impairment, partially reversed neuroinflammation, and synaptic structural plasticity in the damaged hippocampal CA1 region, and reduced synapse associated protein expression and microglial activation. It offers a potential new approach for the prevention and treatment of cognitive decline following electroconvulsive therapy.


Novel multi-linear quantitative brain volume formula for manual radiological evaluation of brain atrophy.
The brain atrophy commonly occurs in elderly and in some childhood conditions making the techniques for quantifying brain volume needful. Since the automated quantitative methods of brain volume assessment have limited availability in developing countries, it was the purpose of this study to design and test an alternative formula that is applicable to all healthcare levels. The multi-linear diagonal brain fraction formula (DBF) was designed from dimensions of brain relative to skull and ventricles. To test a developed formula, a total of 347 subjects aged between 0 and 18 years who had brain CT scans performed recruited and subjected to a systematic measurement of their brains in a diagonal brain fashion. Out of 347 patients evaluated, 62 subjects (17.8 %) were found to be cases of brain atrophy. The three radiological measurements which included sulcal width (SW), ventricular width (VW) and Evans Index (EI) were concurrently performed. SW and VW showed good age correlation. Similar tests were extended to diagonal brain fraction (DBF) and skull vertical horizontal ratio (VHR) in which DBF showed significant age correlation. The DBF formula shows significant ability of differentiating changes of brain volume suggesting that it can be utilized as an alternative brain fraction quantification method bearing technical simplicity in assessing gross brain volume. The designed formula is unique in that it captures even the possible asymmetrical volume loss of brain through diagonal lines. The proposed scores being in term of ratios give four grades of brain atrophy.


Potential applications of enzymes immobilized on/in nano materials: A review.
Several new types of carriers and technologies have been implemented in the recent past to improve traditional enzyme immobilization which aimed to enhance enzyme loading, activity and stability to decrease the enzyme biocatalyst cost in industrial biotechnology. These include cross-linked enzyme aggregates, microwave-assisted immobilization, click chemistry technology, mesoporous supports and most recently nanoparticle-based immobilization of enzymes. The union of the specific physical, chemical, optical and electrical properties of nanoparticles with the specific recognition or catalytic properties of biomolecules has led to their appearance in myriad novel biotechnological applications. They have been applied time and again for immobilization of industrially important enzymes with improved characteristics. The high surface-to-volume ratio offered by nanoparticles resulted in the concentration of the immobilized entity being considerably higher than that afforded by experimental protocols based on immobilization on planar 2-D surfaces. Enzymes immobilized on nanoparticles showed a broader working pH and temperature range and higher thermal stability than the native enzymes. Compared with the conventional immobilization methods, nanoparticle based immobilization served three important features; (i) nano-enzyme particles are easy to synthesize in high solid content without using surfactants and toxic reagents, (ii) homogeneous and well defined core-shell nanoparticles with a thick enzyme shell can be obtained, and (iii) particle size can be conveniently tailored within utility limits. In addition, with the growing attention paid to cascade enzymatic reaction and in vitro synthetic biology, it is possible that co-immobilization of multi-enzymes could be achieved on these nanoparticles.


Processing of Toxoplasma ROP1 protein in nascent rhoptries.
Secretion in the obligate intracellular parasite, Toxoplasma gondii, occurs through a number of regulated compartments. Among these are the apical organelles known as rhoptries which release their contents as part of the invasion process. We are interested in the processing, targeting and ultimate function of rhoptry proteins (and have focused our analyses on rhoptry protein 1 (ROP1). In this paper, we address the issue of processing: using a number of engineered forms of the ROP1 gene (introduced into a ROP1- background), we show that ROP1 is synthesized as a pre-pro-protein that is subject to proteolytic cleavages to remove the pre-sequence and the 'pro' region, at the N-terminus. Using brefeldin A (BFA) and reduced temperature we show that this processing occurs late in the secretory pathway of the parasite. Immunolocalization studies with epitope-tagged constructs indicate that processing is apparently occurring in the nascent rhoptries of dividing parasites. The results are discussed in the context of the targeting and possible function of the ROP1 protein.


Compatibility of PiC Insupen Needles with a Broad Range of Pens for the Injection of Subcutaneously Administered Drugs for Diabetes.
To test the compatibility of PiC Insupen needles with a broad range of pens produced by different manufacturers for the injection of subcutaneously administered drugs. The "extreme" products in PiC pen needles range were considered (G33x4 mm and G29x12 mm), to verify that the compatibility was not affected by the cannula diameter and length. Following the launch of the G34x3.5mm needle, additional tests were performed comparing G33x4 and G34x3.5 pen needles. A test medium with viscosity similar to insulin was used. Additional tests were performed with a liquid with a much higher viscosity. All the requirements of the technical standard ISO 11608-2 were satisfied, and the differences between G29, G33 and G34 were negligible. Therefore, the PiC Insupen needle G33x4mm was chosen as representative of the PiC pen needles. Dose accuracy and needle hub torque were assessed, according to the ISO 11608-2:2012 norms. For pens with variable volume, two different volumes were tested (Vlow and Vhigh) in random order, testing 60 needles with Vlow and 60 with Vhigh. Overall, 50 different pens were tested. Dose accuracy acceptance criteria were met for all the pens tested, with the only exception of Vhigh for Berlipen Precision pen. The removal torque was adequate for all pens, with the only exception of Berlipen 301 and Berlipen 302 pens. We documented that Pikdare needles are compatible with a large array of different pens for the injection of insulin and other drugs administered subcutaneously.


Large lipomas in the deep palmar space.
Lipoma in the deep palmar space of the hand is an unusual tumor. Our experience with seven of these tumors indicates that they can be unusually large at initial examination, can first be seen with paresthesias in branches of the median nerve, and can be difficult to surgically expose. Marginal resection of this tumor is curative.


The association of dysmenorrhea with noncyclic pelvic pain accounting for psychological factors.
The factors that underlie pelvic pain are poorly understood. Specifically, the relative influence of dysmenorrhea and psychological factors in the etiology of noncyclic pelvic pain conditions, such as interstitial cystitis and irritable bowel syndrome, is unknown. To further characterize pelvic pain, we compared the frequency of menstrual, somatosensory, and psychological risk factors between women with and without severe noncyclic pelvic pain symptoms. A total of 1012 reproductive-aged women completed a 112-item questionnaire with domains including mood, fatigue, physical activity, somatic complaint, and pain. Questionnaire items included existing items for menstrual distress and newly written items derived from qualitative interviews. The relationship of dysmenorrhea and noncyclic pelvic pain complaints (dyspareunia, dyschezia, or dysuria) was modeled using quantile regression. Among women who menstruate regularly, those with dysmenorrhea had disproportionally more severe noncyclic pelvic pain (54/402, 13%) than women without dysmenorrhea (5/432, 1%; odds ratio, 13; 95% confidence interval, 5-33). In a multivariate-adjusted model, dysmenorrhea (β = .17), activity capability (β = .17), somatic complaint (β = .17), and bodily pain (β = .12) were the primary predictors of noncyclic pelvic pain. Depression (β = .03) and anxiety (β = .01) were not significantly predictive. The presence of dysmenorrhea, somatic complaint, and low activity capability predicted 90% of the cases of women with noncyclic pelvic pain. The association between dysmenorrhea and noncyclic pelvic pain suggests that menstrual pain is an etiological factor in noncyclic pelvic pain, whereas depression and anxiety may be secondary effects. Longitudinal studies are needed to determine whether dysmenorrhea causally influences development of noncyclic pelvic pain or shares common underlying neural mechanisms.


Evidence for autoinhibitory regulation of the c-src gene product. A possible interaction between the src homology 2 domain and autophosphorylation site.
In the previous study (Sato, K., Miki, S., Tachibana, H., Hayashi, F., Akiyama, T., and Fukami, Y. (1990) Biochem. Biophys. Res. Commun. 171, 1152-1159), we found a synthetic peptide, termed peptide A, that inhibited the kinase activity of p60v-src. The peptide A sequence corresponds to residues 137 to 157 of p60v-src which are included in the amino-terminal portion of the src homology 2 domain. In this study, we attempted to specify the inhibitory sequence in this domain and to identify its target site. The most potent peptide A derivative was one that corresponds to residues 140 through 157. The target site of peptide A was assumed to reside in the autophosphorylation site of p60v-src, since synthetic peptides containing the sequence Phe424-Pro-Ile-Lys-Trp428 which is present downstream of the autophosphorylated Tyr416 partially counteracted the inhibitory effect of peptide A. An antibody was prepared against one of such target peptides, termed pepY. Cross-linking experiments showed that 125I-labeled peptide A could bind to p60v-src blotted on a membrane, and the binding was blocked by the anti-pepY antibody but not by other anti-p60v-src antibodies. Conversely, immunoblotting of p60v-src with anti-pepY antibody was blocked by the cross-linking of peptide A to p60v-src. To our surprise, anti-pepY antibody did not affect the p60v-src activity. Furthermore, p60c-src was activated 2- to 6-fold by this antibody. These results suggest that the pepY region in the catalytic domain of p60v-src or of p60c-src is not essential for the catalytic activity but rather is involved in the negative regulation of the kinase activity of p60c-src.


Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer.
Mounting evidence has demonstrated the vital importance of tumor-associated macrophages (TAMs) and exosomes in the formation of the premetastatic niche. However, the molecular mechanisms by which tumor-derived exosomal miRNAs interact with TAMs underlying premetastatic niche formation and colorectal cancer liver metastasis (CRLM) remain largely unknown. Transmission electron microscopy and differential ultracentrifugation were used to verify the existence of exosomes. In vivo and in vitro assays were used to identify roles of exosomal miR-934. RNA pull-down assay, dual-luciferase reporter assay, etc. were applied to clarify the mechanism of exosomal miR-934 regulated the crosstalk between CRC cells and M2 macrophages. In the present study, we first demonstrated the aberrant overexpression of miR-934 in colorectal cancer (CRC), especially in CRLM, and its correlation with the poor prognosis of CRC patients. Then, we verified that CRC cell-derived exosomal miR-934 induced M2 macrophage polarization by downregulating PTEN expression and activating the PI3K/AKT signaling pathway. Moreover, we revealed that hnRNPA2B1 mediated miR-934 packaging into exosomes of CRC cells and then transferred exosomal miR-934 into macrophages. Interestingly, polarized M2 macrophages could induce premetastatic niche formation and promote CRLM by secreting CXCL13, which activated a CXCL13/CXCR5/NFκB/p65/miR-934 positive feedback loop in CRC cells. These findings indicate that tumor-derived exosomal miR-934 can promote CRLM by regulating the crosstalk between CRC cells and TAMs. These findings reveal a tumor and TAM interaction in the metastatic microenvironment mediated by tumor-derived exosomes that affects CRLM. The present study also provides a theoretical basis for secondary liver cancer.


Distribution of Phlebotomine Sandflies in the Cave Area of Satun Province, Thailand.
Leishmaniasis, a sandfly-transmitted protozoan infection, is a neglected health threat in Thailand and the information on its vector is scarce. This study aimed to identify sandfly distribution, abundance, and environmental conditions of natural breeding sites in the cave areas of Satun Province, where previous cases of leishmaniasis were reported. Sandflies were collected during a six-month period using CDC light traps and modified emergence traps. Species distribution, relative abundance, and environmental conditions of potential breeding sites were determined. Our survey of 12,790 sandflies found the highest female abundance in April-May. We identified six known species, the most prevalent being Sergentomyia anodontis. We also found S. barraudi, a potential Leishmania spp. vector, distributing in this area. Most male sandflies had partially rotated genitalia, indicating the breeding site proximity to our trap locations. Potential resting/breeding sites were discovered outside the cave during February-March, and inside during May-June. The environmental parameters showed warm climate, moderate humidity, moderately alkaline pH, moderate-to-high macronutrients, and low-to-high organic matters. In summary, our study provided the spatiotemporal distribution and environmental condition of sandfly potential breeding sites in the cave areas of Satun Province. This data may contribute to more effective vector surveillance programs in the future.


The balance of serum matrix metalloproteinase-8 and its tissue inhibitor in acute coronary syndrome and its recurrence.
Matrix metalloproteinase-8 (MMP-8) is involved in the breakdown of the extracellular matrix increasing the vulnerability of atherosclerotic lesions. We analysed the diagnostic value of serum MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in acute coronary syndrome (ACS) and their prognostic value in ACS recurrence. The population comprised 343 patients with ACS [including 108 unstable angina pectoris and 235 acute myocardial infarctions (AMI)] and 326 healthy controls. Additionally, 157 (45.8%) patients were resampled during the recovery. The ACS patients were followed up for 6 years. MMP-8, TIMP-1, and their molar ratio distinguished the cases from the controls; C-statistic of the multivariate model (95% CI, p-value) including the MMP-8/TIMP-1 ratio regarding its discriminating ability for AMI was 0.922 (0.893-0.950, p<0.001). After the acute phase of ACS, median MMP-8 and TIMP-1 concentrations decreased (p<0.001) by 34.5 and 28.7%, respectively, but ended up on a different level than those found in the controls. In the follow-up, acute phase and recovery period TIMP-1 concentrations associated with cardiovascular death with hazard ratios 4.31 (2.00-9.26, p<0.001) and 4.69 (1.10-20.01, p=0.037), respectively. The increase of serum MMP-8 and TIMP-1 concentrations may reflect plaque instability and tissue damage. TIMP-1 concentrations are associated with poor outcome in patients with ACS. The findings may have practical implications in both diagnostics and therapeutics.


Characteristics of sulfur response in a micro-flame photometric detector.
A recently reported micro-flame photometric detector (microFPD) has been examined in greater detail for its sulfur response characteristics. While supporting an "upside down" flame on a stainless steel capillary burner (delivering oxygen) in a counter flowing stream of premixed hydrogen and oxygen, the extremely small flame of the muFPD (30 nL) was observed to produce linear sulfur emission as HSO(*). In this mode, linear sulfur response was obtained over four orders of magnitude with a minimum detectable flow of 2 x 10(-10) g S/s. Additionally, a broad series of sulfur compounds ranging in chemical structure were examined in the microFPD in order to determine the extent of equimolarity and reproducibility of response toward this element. Results of exploring both the linear (HSO(*)) and quadratic (S(2)(*)) modes indicate that the %RSD and equimolarity of sulfur response are comparable between that of the microFPD and a conventional flame photometric detector (FPD).


Tibetan Herbal Tea Agar-35 Reduces Negative Affect and Anxiety: A Placebo-Controlled Pilot Study.
Herbal medicine and other forms of complementary and alternative medicine (CAM) are used to treat symptoms of psychiatric disorders in the United States, including anxiety and mood problems. In Traditional Tibetan Medicine anxiety and depression are commonly treated with an herbal compound known as Agar-35. The objective of this pilot study was to explore whether Agar-35 tea would improve anxiety, affect, stress, and rumination. Undergraduate psychology students (N=14) were randomized to drink either Agar-35 tea (n=6) or placebo tea (n=8) for 7 nights. The results indicated that Agar-35 significantly reduced participants' negative affect compared to placebo, U = 6.0, p = .019, effect size, r = .63. Further, Agar-35 also reduced anxiety (trending toward significance), U = 10.0, p = .071, effect size, r = .48. In accordance with its use in Tibetan Medicine, these preliminary findings suggest that Agar-35 may benefit aspects of psychological health.


Lateral hypothalamic region excites the activity of vasopressin neurons in the supraoptic nucleus through subfornical organ neurons.
In urethane-anesthetized male rats, microinjection of angiotensin II into the lateral hypothalamic area excited the activity of about half (N = 7) of subfornical organ neurons (N = 15) antidromically identified as projecting to the hypothalamic supraoptic nucleus. Microinjection of angiotensin II also excited the activity of approximately one-quarter (N = 8) of putative vasopressin-secreting neurons (N = 28) in the hypothalamic supraoptic nucleus and these excitatory responses of putative vasopressin-secreting neurons were blocked (N = 3) or attenuated (N = 3) by pretreatment with the angiotensin II antagonist saralasin, but not by isotonic saline (N = 2), in the subfornical organ.


Tonic GABA(A) receptor-mediated signalling in temporal lobe epilepsy.
The tonic activation of extrasynaptic GABAA receptors by extracellular GABA provides a powerful means of regulating neuronal excitability. A consistent finding from studies that have used various models of temporal lobe epilepsy is that tonic GABAA receptor-mediated conductances are largely preserved in epileptic brain (in contrast to synaptic inhibition which is often reduced). Tonic inhibition is therefore an attractive target for antiepileptic drugs. However, the network consequences of a commonly used approach to augment tonic GABAA receptor-mediated conductances by global manipulation of extracellular GABA are difficult to predict without understanding how epileptogenesis alters the pharmacology and GABA sensitivity of tonic inhibition, and how manipulation of tonic conductances modulates the output of individual neurons. Here we review the current literature on epilepsy-associated changes in tonic GABAA receptor-mediated signalling, and speculate about possible effects they have at the network level. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.


Structure-activity relationships of a series of 1-substituted-4-methylbenzimidazole neuropeptide Y-1 receptor antagonists.
The characterization of a novel series of NPY-1 receptor antagonists derived from the 4-methylbenzimidazole 4 is described. Appropriate substitution on the piperidyl nitrogen of 4 led to systematic increases in Y-1 receptor affinity, to approximately 50-fold, and to the discovery of the importance of a second basic substituent.


[Retrospective Study of Laryngeal Preservation Treatment for Hypopharyngeal Carcinoma with Transoral Resection or Induction Chemotherapy].
We have performed transoral surgical resection for patients with T1/T2 hypopharyngeal cancer and induction chemotherapy with docetaxel for patients with T2/T3 disease. The patients were analyzed in order to determine the current situation of larynx preservation in patients with hypopharyngeal cancer. The data of a total of 83 patients with hypopharyngeal cancer were analyzed retrospectively. The primary subsites were : pyriform sinus (PS) in 61 patients, posterior wall (PW) in 13 patients, and postcricoid (PC) in 9 patients. The number of patients classified as having T1, T2, T3 and T4 disease were 14, 29, 23 and 17, respectively. The main therapies employed in the patients were as follows: transoral surgical resection plus radiation therapy for T1 disease, radiation therapy, induction chemotherapy, and partial resection for T2 disease, induction chemotherapy, radiation therapy, and pharyngo-laryngoesophagectomy for T3 disease, and pharyngo-laryngoesophagectomy plus induction chemotherapy for T4 disease. The 5-year larynx preservation rates in the patients with T1, T2, T3 and T4 disease were 100%, 73%, 39% and 35%, respectively. Our method was able to improve the larynx preservation rate without having any adverse effect on the survival rate. However, the strength of treatment for T 3 disease needs to be improved, because a large number of recurrences and deaths due to the primary disease were encountered in this patient group.


Stud attachments for the mandibular implant-retained overdentures: Prosthetic complications. A literature review.
A plethora of attachment systems for mandibular two-implant overdentures is currently available often without evidence-based support. Technical aspects are now parameters considered when choosing the appropriate attachment. Despite the increasing use of the Locator attachments, studies regarding their properties remain scarce. Peer reviewed articles published in English up to 2011, were identified through a MEDLINE search (Pubmed and Elsevier) and a hand search of relevant textbooks and annual publications. Emphasis was made on the technical complications as well as the loss of retention related to the attachments in implant-retained overdentures, primarily the Locator attachment. The evaluation of the long-term outcome of implant overdentures and complications associated with different attachment systems may provide useful guidelines for the clinician in selecting the type of attachment system and overdenture design.


The first general route for efficient synthesis of 18O labelled alcohols using the HOF·CH3CN complex.
A mild and very efficient method for converting boronic acids to alcohols has been developed using the acetonitrile complex of hypofluorous acid HOF·CH3CN. Employing (18)O-labeled water results in alcohols containing a heavy oxygen isotope. The reactions were performed at room temperature, within a few minutes and in excellent yields.


Ulnar nerve strains at the elbow.
Twenty unembalmed intact cadavers had strain measurements taken of the ulnar nerve at 5 positions around the elbow and at varying degrees of elbow flexion. A microstrain gauge was implanted directly into the nerve through a superficial incision. Maximum strains in the ulnar nerve occurred at maximum elbow flexion and directly behind the medial epicondyle; meaningfully less strain was seen at lesser degrees of flexion and positions distal and proximal to the epicondyle. A wide range of maximal strains (0% to 14%) was found. Twenty-five percent of the ulnar nerves showed strains of greater than 10% with maximum elbow flexion behind the medial epicondyle. Cubital tunnel syndrome may be at least in part a traction neuropathy.


On-chip potential gradient detection with a portable capillary electrophoresis system.
A portable chip-CE system with potential gradient detection (PGD) was developed and applied to the determinations of alkali metals and alkaloids. The separation efficiency appeared to be satisfactory and nonaqueous capillary electrophoresis (NACE) proved to be applicable to PGD or conductivity detection. The power supplies, separation and detection were built on a device of 3 kg in weight. A branch channel near the end of the separation channel was designed to perform PGD and make the application of relatively high field strength possible. The study is the first report on the application of PGD on the microchip platform. The design of the chip-CE system shows several advantages, such as simplicity, miniaturization and wide applicability.


Optimum design of reference points distribution in three-dimensional reconstruction of dental model in intercuspal position.
The scanning of plaster models for three-dimensional (3D) construction requires their rigid fixation in the intercuspal position. Factors such as installation, motion, and scanning procedures influenced the accuracy of this method, which ultimately influence the results. Therefore, the present study attempted to provide an optimal and accurate method with less complex procedures and a more accessible equipment for determining the intercuspal relation in the 3D occlusal construction of dental models. A pair of plastic mounting plates that could be directly attached to a mechanical articulator was designed and 3D printed. Nine axial hemispherical concaves were introduced on the axial surface of each plate. The rigidly fixed maxillary and mandibular dental models were scanned directly. The distances DR between nine pairs of concaves on both mounting plates adhered to the maxillary and mandibular sections of the articulator were measured using the three-coordinate measuring machine Faro Edge as the reference. The present study comprised seven test groups varying in number and location. Assessing the reference points from each of the seven groups performed the 3D construction. The Geomagic Studio software was used to construct the concaves of digital casts, and the distances DM between the pairs of concaves were measured as test values. Variable differences between DR and DM were analyzed. An optimum distribution scheme was obtained for reference point registration by quantitatively evaluating accuracy levels of the 3D constructions of different reference point distribution patterns. This scheme can serve as a reference for related studies and dental clinic operations. Three-dimensional construction of the intercuspal relation during scanning of the maxillary and mandibular models with an accuracy of 0.046 mm ± 0.009 mm can be achieved using the improved design of mounting plates.


Effect of High-pressure Processing on the Quality Characteristics and Shelf-life Stability of Hanwoo Beef Marinated with Various Sauces.
The effects of high-pressure processing (HPP) treatment on the quality characteristics of low graded Hanwoo beef marinated with five different sauces (soy, fish, fish-soy, soy-fish and fish-soy-meat sauces) obtained from Asian countries were studied. The Hanwoo beef striploins were marinated with the aforementioned sauces (at ratio: 3:1 w/w) for 3 days at 4℃ before they were treated with HPP at 550 MPa for 5 min at 10℃. All the sauces used were equalized to a same salt level of 12.5%, and the samples marinated with a 12.5% brine solution were served as a control. After treating with the HPP, all the samples were stored for further 7 days at 4℃ for analyses. Results revealed that HPP treatments showed some effects on technological quality traits (pH, cooking loss and color) but had no effect on the collagen contents of the marinated beef. Noticeably, the HPP treatment led to the increases in amounts of free amino acids associated with monosodium glutamate-like taste and sweet taste in the samples marinated with fish sauce or soy-fish sauce, fish-soy sauce and fish-soy-meat sauce whereas, it only reduced these amino acids in the samples marinated with soy sauce or control. Furthermore, the total bacteria count in all the marinated beef samples treated with HPP were significantly (p<0.05) lower than those of the non-HPP-treated samples throughout the storage periods. It is concluded that HPP could be applied for enhancing the taste-active compounds production such as free amino acids, and improving the shelf-life stability of the marinated beef.


MDCT evaluation of Dorsal Pancreatic Artery and Intrapancreatic arcade anatomy.
The purpose of the study was to analyze the anatomy and variations in the origin of the dorsal pancreatic artery, greater pancreatic artery and to study the various types of arterial arcades supplying the pancreas on multidetector CT (MDCT). A retrospective analysis of 747 MDCT scans was performed in patients who underwent triple phase or dual phase CT abdomen between December 2020 and October 2022. Variations in origin of Dorsal pancreatic artery (DPA), greater pancreatic artery (GPA), uncinate process branch were studied. Intrapancreatic arcade anatomy was classified according to Roman Ramos et al. into 4 types-small arcades (type I), small and large arcades (type II), large arcades (type III) and straight branches (type IV). The DPA was visualized in 65.3% (n = 488) of cases. The most common origin was from the splenic artery in 58.2% (n = 284) cases. The mean calibre of DPA was 2.05 mm (1.0-4.8 mm). The uncinate branch was seen in 21.7% (n = 106) with an average diameter of 1.3 mm. The greater pancreatic artery was seen in 57.3% (n = 428) predominantly seen arising from the splenic artery. The most common arcade anatomy was of Type II in 52.1% (n = 63) cases. Pancreatic arterial variations are not very uncommon in daily practice. Knowledge of these variations before pancreatic surgery and endovascular intervention procedure is important for surgeons and interventional radiologist.


Fasciola hepatica and Schistosoma mansoni: immunofluorescent antigen localization and cross-reactivity.
In an attempt to identify the tissue sources of biochemically purified antigenic fractions of Fasciola hepatica and Schistosoma mansoni, antisera were tested against plastic-embedded sections of worms of various ages by an indirect fluorescent-antibody-labeling technique. Antibodies prepared against antigens purified by chromatography of F. hepatica whole worm extract through concanavalin A-Sepharose 4B labeled the parenchyma and tegument of adult F. hepatica strongly while antibodies developed against antigens purified by antibody-affinity chromatography against antibodies of S. mansoni labeled only the parenchyma. Antigens common to these two groups clearly originated from F. hepatica parenchyma. Certain of these common antigens are known to provide significant protection in mice to challenge with S. mansoni cercariae, and in the present study antisera against F. hepatica extracts cross-labeled S. mansoni adult male parenchyma. Reciprocal cross-reactions between antisera against S. mansoni and the parenchyma of adult F. hepatica were also noted. FhFIIb, an extract of F. hepatica which Tailliez described as not cross-reacting with S. mansoni, was found to contain no F. hepatica parenchymal antigens. Antigenic fractions of F. hepatica and S. mansoni collected from the surface of worms after incubation in nonionic detergent were unexpectedly found to contain much parenchymal antigen, suggesting leakage of internal components into the supernatant during preparation. Antisera to F. hepatica developed during a natural infection in rabbits labeled tegumental components and gut strongly but did not react with parenchymal tissue. Antisera against extracts of adult schistosomes labeled the parenchyma of male worms and the glycocalyx of the cercarial tegument, indicating the presence of common antigens in the adult and the cercarial stage. Reciprocal reactions between anticercarial sera and adult sections provided further evidence of shared antigenicity. Antisera against S. mansoni egg antigens strongly labeled sections of eggs in liver tissue and cross-reacted with cercarial glycocalyx, indicating the existence of common antigens between these two stages. The antisera also cross-reacted with what appeared to be non-membrane-bound protein in the tegument of F. hepatica. The soluble egg antigen extract shared antigenicity with the parenchyma of both S. mansoni and F. hepatica but circumoval precipitin had no cross-reactivity with this tissue. Thus S. mansoni eggs contain nondiffusable components sharing antigenic specificity with adult parenchymal tissue.(ABSTRACT TRUNCATED AT 400 WORDS)


Bone microenvironment signals in osteosarcoma development.
The bone is a complex connective tissue composed of many different cell types such as osteoblasts, osteoclasts, chondrocytes, mesenchymal stem/progenitor cells, hematopoietic cells and endothelial cells, among others. The interaction between them is finely balanced through the processes of bone formation and bone remodeling, which regulates the production and biological activity of many soluble factors and extracellular matrix components needed to maintain the bone homeostasis in terms of cell proliferation, differentiation and apoptosis. Osteosarcoma (OS) emerges in this complex environment as a result of poorly defined oncogenic events arising in osteogenic lineage precursors. Increasing evidence supports that similar to normal development, the bone microenvironment (BME) underlies OS initiation and progression. Here, we recapitulate the physiological processes that regulate bone homeostasis and review the current knowledge about how OS cells and BME communicate and interact, describing how these interactions affect OS cell growth, metastasis, cancer stem cell fate and therapy outcome.


IMP2 regulates differentiation potentials of mouse neocortical neural precursor cells.
Neural precursor cells (NPCs) in the mammalian neocortex generate various neuronal and glial cell types in a developmental stage-dependent manner. Most neocortical NPCs lose their neurogenic potential after birth. We have previously shown that high-mobility group A (HMGA) proteins confer the neurogenic potential on early-stage NPCs during the midgestation period, although the underlying mechanisms are not fully understood. In this study, we found that HMGA2 promotes the expression of insulin-like growth factor 2 mRNA-binding protein 2 (IMP2, Igf2bp2) in neocortical NPCs. The level of IMP2 was indeed high in early-stage NPCs compared with that in late-stage NPCs. Importantly, over-expression of IMP2 increased the neurogenic potential and suppressed astrocytic differentiation of late-stage NPCs, whereas knockdown of IMP2 promoted astrocytic differentiation and reduced the neurogenic potential of early-stage neocortical NPCs without overtly affecting cell proliferation. Our results thus identified IMP2 as a developmental stage-dependent regulator of the differentiation potentials of NPCs in the mouse neocortex.


Intestinal bacteria flora changes in patients with Mycoplasma pneumoniae pneumonia with or without wheezing.
Mycoplasma pneumoniae (MP) infection is a common cause of community-acquired pneumonia in children. Furthermore, many children with Mycoplasma pneumoniae pneumonia (MPP) have recurrent wheezing and reduced small airway function after their clinical symptoms have resolved, eventually leading to asthma. MPP can trigger immune disorders and systemic inflammatory responses. Hence, the intestine is the largest immune organ of the body. Therefore, we sought to investigate whether the alteration of intestinal flora is correlated with the development of wheezing in children with MPP. We collected 30 healthy children as group A, 50 children with nonwheezing MPP as group B, and 50 children with wheezing MPP as group C. We found that the percentage of eosinophil cells (EC) was significantly higher in group C than that in group B for routine blood tests and serum inflammatory factors. The serum cytokines, including IL-4, IL-17, TNF-α, and TGF-β, were significantly higher in group C than in group B. In addition, the level of IL-10 was significantly lower in group C than in group B. The distribution characteristics of intestinal flora strains in children with MPP were detected by sequencing of 16S rRNA gene amplicon sequencing. There were differences in the abundance of intestinal flora between children with MPP and healthy children, with lower abundance of Ruminococcus flavefaciens, Clostridium butyricum, Lactobacillus, and Bifidobacterium in the intestine of children with MPP compared to healthy children. The abundance of Ruminococcus flavefaciens and Clostridium butyricum was significantly lower in the intestine of children with wheezing MPP compared to children without wheezing MPP. In the correlation analysis between children with MPP and inflammatory factors, Ruminococcus flavefaciens was found to be negatively correlated with IL-17. Clostridium butyricum was negatively correlated with L-4, IL-17, TNF-α, and TGF-β; however, it positively correlated with IL-10. Thus, it was concluded that alterations in intestinal flora play a crucial role in the immune response to MPP, where a significant decline in intestinal Ruminococcus flavefaciens and Clostridium butyricum leads to an exacerbation of the inflammatory responses, which may promote the development of children with wheezing MPP.


Intraocular pressure as a risk factor for visual field loss in pseudoexfoliative and in primary open-angle glaucoma.
To analyze the relationship between intraocular pressure (IOP) and visual field loss in patients with primary open-angle glaucoma (POAG) and in those with pseudoexfoliative glaucoma (PEXG). A cross-sectional, observational study. Thirty-one patients with PEXG and 31 patients with POAG that was newly diagnosed were included in this study. The authors recorded the untreated IOP and the amount of the visual field loss, at presentation, in both study groups. The authors found a significant relationship between IOP and visual field mean deviation (MD) index (P = 0.0001, r = 0.68) in PEXG but not in POAG eyes (P = 0.7). The authors found that untreated IOP levels can explain the amount of visual field loss, as measured by the MD index, much better in patients with PEXG than in comparable patients with POAG. Thus, vulnerability of the optic nerve head to increased IOP appears to be different in these two diagnostic categories.


Analysis of chromosomes of workers exposed to acrylonitrile.
Examination of 18 workers who had been exposed to acrylonitrile for 15.3 years on average and 18 workers who had not been exposed to acrylonitrile showed no difference in the incidence of chromosome aberrations; for each person concerned 100 metaphases were evaluated.


A computational procedure for identifying master regulator candidates: a case study on diabetes progression in Goto-Kakizaki rats.
We have recently identified a number of active regulatory networks involved in diabetes progression in Goto-Kakizaki (GK) rats by network screening. The networks were quite consistent with the previous knowledge of the regulatory relationships between transcription factors (TFs) and their regulated genes. To study the underlying molecular mechanisms directly related to phenotype changes, such as diseases, we also previously developed a computational procedure for identifying transcriptional master regulators (MRs) in conjunction with network screening and network inference, by effectively perturbing the phenotype states. In this work, we further improved our previous method for identifying MR candidates, by listing them in a more reliable manner, and applied the method to reveal the MR candidates for diabetes progression in GK rats from the active networks. Specifically, the active TF-gene pairs for different time periods in GK rats were first extracted from the networks by network screening. Another set of active TF-gene pairs was selected by network inference, by considering the gene expression signatures for those periods between GK and Wistar-Kyoto (WKY) rats. The TF-gene pairs extracted by the two methods were then further selected, from the viewpoints of the emergence specificity of TF in GK rats and the regulated-gene coverage of TF in the expression signature. Finally, we narrowed all of the genes down to only 5 TFs (Etv4, Fus, Nr2f1, Sp2, and Tcfap2b) as the candidates of MRs, with 54 regulated genes, by merging the selected TF-gene pairs. The present method has successfully identified biologically plausible MR candidates, including the TFs related to diabetes in previous reports. Although the experimental verifications of the candidates and the present procedure are beyond the scope of this study, we narrowed down the candidates to 5 TFs, which can be used to perform the verification experiments relatively easily. The numerical results showed that our computational method is an efficient way to detect the key molecules responsible for biological phenomena.


Asociación de síndrome de Fitz-Hugh-Curtis en fase crónica y quiste mesotelial simple en un hombre adulto. Presentación de un caso.
Presentation of a case little reported in the literature of Fitz-Hugh-Curtis Syndrome regarding gender and its association with simple intra-abdominal mesothelial cyst. A bibliographic source was compiled regarding the unusual presentation of the syndrome in males and its association with the simple mesothelial cyst. The affectation in men is infrequent, with only 10 reported cases. The simple peritoneal mesothelial cyst has an approximate incidence of 1/1,000,000. We are faced with an unusual presentation in terms of pathology and association, so it is important to carry out the case report.


Naphthalene Structures Derived from Lignins During Phenolation.
Phenolation is a commonly used method to improve the reactivity of lignin for various applications. In this study, resinol lignin models (syringaresinol and pinoresinol) and eucalyptus alkali lignin were treated under acid-catalyzed phenolation conditions to investigate the products derived from resinol (β-β) structures of lignins. The phenolation products were characterized by means of GC-MS and NMR spectroscopy following separation using flash chromatography and thin-layer chromatography. A series of new naphthalene products were identified from phenolation of syringaresinol, and the corresponding guaiacyl analogs were also identified by GC-MS. The C1-Cα bond of these resinol compounds was cleaved to release syringol or guaiacol during phenolation. In addition, diphenylmethane products formed from phenol or phenol and syringol/guaiacol were found in the phenolation products. Comparatively, more naphthalene products were obtained by phenolation from syringaresinol than those obtained from pinoresinol. HSQC NMR characterization of the phenolated alkali lignin revealed that naphthalene structures formed in the phenolated lignin.


Oculomotor abnormalities in Friedreich's ataxia.
A clinical neuro-ophthalmological and electro-oculographic study was made on fourteen patients with Friedreich's ataxia. None had evidence of optic nerve dysfunction. No patient complained of oscillopsia although all had ocular motor deficits of varying degrees, which appeared to be related to the severity of the general manifestations of the disease. The defects comprised square wave jerks, jerky pursuit with inability to maintain eccentric gaze resulting in gaze paretic nystagmus and rebound nystagmus. There was failure to suppress by fixation the vestibulo-ocular reflex. The slow phase velocity of caloric nystagmus was always of reduced velocity. There was inability to augment the slow phase velocity of optokinetic nystagmus with increasing stimulus velocity. Abnormalities of the saccadic system were manifest particularly as hypermetria. These signs in combination are suggestive of disease involving the cerebellar flocculus and vermis or their brain stem connections. No abnormalities were found in 17 parents or siblings.


[Evaluation of hand hygiene compliance in a Primary Health Care area of Madrid].
Hand hygiene is the most effective measure for preventing infections related to healthcare. This study aims to evaluate the Hand hygiene compliance in Primary Health Care. A cross-sectional study was carried out, collecting socio-demographic data and the hand hygiene compliance from 198 Primary Health Care workers. Their hand hygiene compliance was evaluated according to WHO criteria. The level of hand hygiene compliance was 8.1% (95% CI 6.2-10.1). Employment experience of over 20 years was significantly associated with low levels of compliance. Primary Health Care workers have a low hand hygiene compliance. Training programs need to be introduced to increase compliance and facilitate access to hydro-alcoholic solutions.


Screening for Cushing's syndrome using early morning urine samples.
Urinary free 11-hydroxycorticosteroid/creatinine ratios (UFC/Cr)were determined in early morning urine samples from 138 obese subjects attending endocrine clinics in the Glasgow area. The majority of patients (128) had UFC/Cr ratios within the normal range for non-obese subjects (5-55 mumol/mol). Of those with elevated UFC/Cr ratios, further investigations of the hypothalamic-pituitary-adrenal axis confirmed a diagnosis of Cushing's syndrome due to bilateral adrenal hyperplasia in six of the cases and adrenal tumours in a further two patients. In the remaining two patients there was evidence of intermittent adrenal hyperactivity with inconsistent responses to insulin-induced hypoglycaemia tests.


Pressure transmission through ureteric stents: a novel in vivo human study.
To document, in an in vivo study, the pressure transmission from the urinary bladder to the upper tract through ureteric stents in human patients. Stents have acquired special importance in the urological armamentarium. Flank pain and hydronephrosis are associated with stenting in 50% and 18% of cases, respectively. Pressure transmission from urinary bladder to the upper tract through the stent is the logical explanation for loin pain and hydronephrosis. This study was conducted in a prospective manner. We did not select patients or modify their management; instead, we studied patients who, during the course of urological management of some upper tract disease, are left with both a ureteric stent and a nephrostomy tube. Twenty patients fulfilled our criteria. After written consent, a pressure-flow study was done monitoring pressure changes in the renal pelvis during different phases of bladder filling in sitting and recumbent positions. Pressure-flow curves showed almost equal transmission of pressure from the bladder to the renal pelvis throughout all phases of bladder filling and emptying. Any voluntary and involuntary rise of pressure in the bladder was instantly and almost equally transmitted to the renal pelvis. A subgroup of patients with infravesical obstruction resulting from benign prostatic hyperplasia also showed equal transmission of the elevated intravesical pressure during voiding to the renal pelvis. Pressure from the lower urinary tract is transmitted to the upper tract through the stent, posing a threat to the renal parenchyma and function. Stent placement, when indicated, should be used for the shortest period possible, in sterile urine.


[Hemihepatectomy].
Controlled right hemi-hepatectomy is a major operation reserved for primary or secondary malignant tumours, a few very large benign tumour and, more rarely, rupture of the right lobe of the liver. The surgical technique of hemi-hepatectomy respects several general rules concerning positioning of the patient, the surgical incision, haemostasis of the various pedicles, biliary stasis and drainage. Six technical variants are discussed together with their advantages and disadvantages and respective indications according to the size, nature and situation of the lesion in relation to the glissonian and hepato-caval pedicles. On the basis of this very detailed basic technique, tactical modalities according to the features of the lesion are proposed: extra or intra-hepatic control of the pedicles, initial or terminal opening of the median fissure, initial or terminal mobilisation of the right hemi-liver, total vascular exclusion. Controlled left hemi-hepatectomy is a less complicated technique which can be performed according to tactical variant identical to those described for right hemi-hepatectomy, but total vascular exclusion is rarely essential.


Stimulation of gastric acid secretion by dimaprit in unanesthetized rats.
In unanesthetized rats, dimaprit and histamine given by intravenous infusion were about equipotent in stimulating gastric acid secretion. The maximal rate of acid secretion in response to dimaprit was significantly greater than to histamine but not significantly different from the response to pentagastrin.


Numerical research on the anisotropic transport of thermal neutron in heterogeneous porous media with micron X-ray computed tomography.
The anisotropic transport of thermal neutron in heterogeneous porous media is of great research interests in many fields. In this paper, it is the first time that a new model based on micron X-ray computed tomography (CT) has been proposed to simultaneously consider both the separation of matrix and pore and the distribution of mineral components. We apply the Monte Carlo method to simulate thermal neutrons transporting through the model along different directions, and meanwhile detect those unreacted thermal neutrons by an array detector on the other side of the model. Therefore, the anisotropy of pore structure can be imaged by the amount of received thermal neutrons, due to the difference of rock matrix and pore-filling fluids in the macroscopic reaction cross section (MRCS). The new model has been verified by the consistent between the simulated data and the pore distribution from X-ray CT. The results show that the evaluation of porosity can be affected by the anisotropy of media. Based on the research, a new formula is developed to describe the correlation between the resolution of array detectors and the quality of imaging. The formula can be further used to analyze the critical resolution and the suitable number of thermal neutrons emitted in each simulation. Unconventionally, we find that a higher resolution cannot always lead to a better image.


Implementation fidelity of a Brazilian drug use prevention program and its effect among adolescents: a mixed-methods study.
Based on the US DARE-kiR, a version of the Keepin' it REAL program, the Drug and Violence Resistance Educational Program (PROERD) is the most widely implemented Brazilian prevention program. It originates from the translation of the DARE-kiR, a version of the Keepin' it REAL program. Previous results suggest its inefficiency in preventing drug use among Brazilian adolescents. Since kiR fidelity can impact program outcomes, this mixed-methods study evaluates the PROERD implementation fidelity and its effects on preventing drug use among adolescents. Data from two cluster randomized controlled trials (cRCTs) with 4,030 students from 30 public schools in São Paulo (1,727 fifth graders and 2,303 seventh graders), assessed at two-time points, were analyzed quantitatively. After implementing each lesson during the cRCT, 19 PROERD instructors answered fidelity forms. The effect of PROERD fidelity on alcohol, cigarettes, marijuana, inhalant, and cocaine use (the last two only among seventh graders) in the six months prior to follow-up assessment was analyzed by logistic regressions for fifth grade and mixed effect models for seventh graders. For qualitative analysis, semi-structured interviews were conducted with PROERD instructors and investigated by thematic analysis. Quantitative analysis showed that PROERD implementation fidelity had no impact on drug use among fifth and seventh graders. Conversely, the qualitative analysis revealed important aspects that may influence implementation fidelity and consequently program effectiveness, such as adaptations made by instructors, school infrastructure, among others, besides program application. PROERD requires cultural adaptation to improve its implementation in Brazilian public schools.


"The Circle" Predicts Extent of Fusion for Surgical Correction of Cervical Spinal Kyphotic Deformities: Proof of Concept.
Correction of kyphotic deformities of the spine is a common problem faced by spine surgeons. Unfortunately, there are no clear published guidelines available regarding the extent of spinal fusion required to achieve and maintain lasting deformity correction. We aim to share a set of novel radiographic parameters ("the Circle") that can be used as a guideline for determining the extent of fusion required in surgical correction of spinal kyphotic deformity. A Google forms survey was distributed among spine surgeons and trainees to evaluate differences in recommended extent of posterior-approach fusions for cervical spinal kyphotic deformities before and after introduction to the Circle. Extent of fusion before and after use of the Circle were qualitatively and quantitatively analyzed. Data were anonymized and stored in a secure database. Twenty-seven neurosurgical attendings (n = 14), residents (n = 9), and fellows (n = 3) responded to the survey. Variance between predicted upper and lower instrumented vertebrae, and length of construct, was statistically significantly decreased after application of the Circle in almost all cases. Respondents rated the ease of use of the Circle an average of 4.2 out of 5 (5 = the most ease). The majority of participants (92 [6%]; n = 25 of 27) stated that they would or would likely use the Circle as a radiographic tool in the surgical planning for correction of cervical spinal kyphotic deformities in the future. The Circle is a novel set of radiographic parameters that may be used to educate and guide surgical plans and extent of fusion when aiming to correct spinal kyphotic deformities.


Do Chronic Low Back Pain and Chronic Widespread Pain differ in their association with Depression Symptoms in the 1958 British Cohort?
Depression frequently coexists with chronic pain. Contemporary models suggest that these conditions share pathobiological mechanisms, prompting a need to investigate their temporal association. This investigation aimed to explore two distinctly different chronic pain conditions, and their cross-sectional and prospective associations with depression. Self-reported information was available on chronic widespread pain (CWP), chronic low back pain (CLBP) (45 years), and depression symptoms (45 and 50 years) from up to 9,377 participants in the 1958 British cohort. Depression symptom outcomes were derived by "Clinical Interview Schedule-Revised" (45 years) and "Short Form-36" (50 years). Relationships between both chronic pain conditions and depression symptoms were investigated by fitting four separate logistic regression models, each with varying levels of covariate adjustment, including depression at baseline. CWP was associated with depression symptoms cross-sectionally (odds ratio [OR] = 2.04, 95% confidence interval [CI] 1.65, 2.52; P < 0.001, n = 7,629), and prospectively when fully adjusted for baseline, sociodemographic, lifestyle, and health covariates (OR = 1.45, 95% CI 1.17, 1.80; P = < 0.001, n = 6,275). CLBP was associated with depression symptoms prospectively (full model: OR = 1.28, 95% CI 1.01, 1.61; P = 0.04, n = 6,288). In fully adjusted models the prospective association of CWP with depression symptoms was more heavily influenced by our covariates than CLBP with depression symptoms. Pain may be a stressor from which depression can arise. Development of depression may be differentially dependant upon the type of pain experienced. Screening for depression symptoms among individuals with both chronic pain conditions is indicated and should be repeated over time.


Involvement of organic anion transporting polypeptide 1a5 (Oatp1a5) in the intestinal absorption of endothelin receptor antagonist in rats.
To assess the contribution of organic anion transporting polypeptide 1a5 (Oatp1a5/Oatp3) in the intestinal absorption of an orally active endothelin receptor antagonist, (+)-(5S,6R,7R)-2-butyl-7-[2-((2S)-2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylene-dioxyphenyl)cyclopenteno[1,2-b]pyridine-6-carboxylic acid (compound-A) in rats. Uptakes of [(14)C]compound-A by Oatp1a5-expressing Xenopus laevis oocytes and isolated rat enterocytes were evaluated. The uptake of compound-A by Oatp1a5-expressing oocytes was significantly higher than that by water-injected oocytes and Oatp1a5-mediated uptake was saturable with K(m) value of 116 microM. Compound-A was taken up into isolated enterocytes in time- and concentration-dependent manners and the estimated K(m) value was 83 microM, which was close to that for the Oatpt1a5-mediated uptake in oocytes. Both uptakes of compound-A by Oatp1a5-expressing oocytes and enterocytes were pH-sensitive with significantly higher uptake at acidic pH than those at neutral pH. Uptakes of compound-A into Oatp1a5-expressing oocytes and enterocytes were significantly decreased in the presence of Oatp1a5 substrates such as bromosulfophthalein and taurocholic acid. These results consistently suggested that Oatp1a5 is contributing to the intestinal absorption of compound-A at least in part, and the transporter-mediated absorption seems to be maximized at the acidic microenvironment of epithelial cells in the small intestine in rats.


Blue carbon assessments of seagrass and mangrove ecosystems in South and Southeast Asia: Current progress and knowledge gaps.
Coastal blue carbon ecosystems can be an important nature-based solution for mitigating climate change, when emphasis is given to their protection, management, and restoration. Globally, there has been a rapid increase in blue carbon research in the last few decades, with substantial investments on national scales by the European Union, the USA, Australia, Seychelles, and Belize. Blue carbon ecosystems in South and Southeast Asia are globally diverse, highly productive and could represent a global hotspot for carbon sequestration and storage. To guide future efforts, we conducted a systematic review of the available literature on two primary blue carbon ecosystems-seagrasses and mangroves-across 13 countries in South and Southeast Asia to assess existing national inventories, review current research trends and methodologies, and identify existing knowledge gaps. Information related to various aspects of seagrass and mangrove ecosystems was extracted from 432 research articles from 1967 to 2022. We find that: (1) blue carbon estimates in several countries have limited data, especially for seagrass meadows compared to mangrove ecosystems, although the highest reported carbon stocks were in Indonesia and the Philippines with 4,515 and 707 Tg within mangrove forest and 60.9 and 63.3 Tg within seagrass meadows, respectively; (2) there is a high difference in the quantity and quality of data between mangrove and seagrass ecosystems, and the methodologies used for blue carbon estimates are highly variable across countries; and (3) most studies on blue carbon stocks are spatially biased towards more familiar study areas of individual countries, than several lesser-known suspected blue carbon hotspots. In sum, our review demonstrates the paucity and variability in current research in the region, and highlights research frontiers that should be addressed by future research before the robust implementation of these ecosystems into national climate strategies.


Diversifying stem cell debates: Including Muslim contexts and perspectives.
Greater transcultural and transdisciplinary engagement within Muslim contexts and deliberate inclusion of diverse Muslim voices in the development of international guidelines is required to improve understanding of the state of stem cell science, strengthen thinking about attendant ethical complexities, enhance compliance, deepen public deliberation, increase trust, and strengthen practice standards.


Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues.
Clostridium difficile causes life-threatening diarrhea and is the leading cause of healthcare-associated bacterial infections in the United States. TcdA and TcdB bacterial toxins are primary determinants of disease pathogenesis and are attractive therapeutic targets. TcdA and TcdB contain domains that use UDP-glucose to glucosylate and inactivate host Rho GTPases, resulting in cytoskeletal changes causing cell rounding and loss of intestinal integrity. Transition state analysis revealed glucocationic character for the TcdA and TcdB transition states. We identified transition state analogue inhibitors and characterized them by kinetic, thermodynamic and structural analysis. Iminosugars, isofagomine and noeuromycin mimic the transition state and inhibit both TcdA and TcdB by forming ternary complexes with Tcd and UDP, a product of the TcdA- and TcdB-catalyzed reactions. Both iminosugars prevent TcdA- and TcdB-induced cytotoxicity in cultured mammalian cells by preventing glucosylation of Rho GTPases. Iminosugar transition state analogues of the Tcd toxins show potential as therapeutics for C. difficile pathology.


In vivo drug release behavior in dogs from a new colon-targeted delivery system.
The colon-targeted delivery capsule (CTDC), a new capsule-type dosage form for colonic delivery of drugs, was investigated for the in vivo drug release behavior in dogs. A CTDC formulation with prednisolone as a model drug and theophylline as a marker substance for gastric emptying was prepared for this study. The enteric-coated capsule (ECC) formulation with a similar composition was also prepared as the reference. Both formulations were administered to four beagle dogs, and the drug release behavior thereof was compared. Under fasted condition, ECC released prednisolone and theophylline at the same time within 1 h after the gastric emptying. On the other hand the CTDC released prednisolone at 3.2 h after the gastric emptying. Such release behavior of CTDC was approximately consistent with the results obtained from the in vitro dissolution study, suggesting that the pH-sensing and timed-release functions imparted to the CTDC can work in the gastrointestinal tract of dogs as programmed. Under non-fasted condition, however, the gastric emptying of CTDC was found to be considerably delayed, up to about 14 h, and in this case the in vivo dissolution lag time of prednisolone at the small intestine was shortened to about 1.5 h.


Intravenous myocardial imaging performed serially early and late after acute myocardial infarction.
The accuracy and sensitivity of myocardial imaging using intravenous Rb-81 in delineating the extent and subsequent changes in regional myocardial perfusion abnormalities were examined serially in 12 patients one to 510 days after an acute myocardial infaraction. Definite regions of decreased Rb-81 uptake were noted in 10 patients with transmural infarction. There was excellent correlation between the site of perfusion abnormalities, the electrocardiographic infarct location and the region of segmental wall motion disorders. Follow-up studies revealed in 8 of 11 patients a decrease in the extent of the perfusion defect, which was associated with an improvement in the extent and/or severity of regional wall motion disorders. Conversly, wall motion abnormalities did not change in the remaining three patients in whom perfusion abnormalities persisted unchanged. We conclude that intravenous myocardial imaging permits visualization of myocardial perfusion abnormalities early after acute myocardial infaraction. Serial imaging allows detection of changes in the extent of perfusion abnormalities, and, thus, might provide useful information with respect to the patient's prognosis and the effects of therapeutic interventions.


Investigations into the role of calcium ions in the control of steroid production by isolated adrenal zona glomerulosa cells of the rat.
An increase in the concentration of extracellular potassium from 3.6 to 8.4 mmol/1 had only a small delayed effect on the uptake of radioactive calcium by isolated adrenal glomerulosa cells. However, the same stimulus had a rapid and highly significant effect on the efflux of radioactive calcium from glomerulosa cells preloaded with 45Ca2+. Cells incubated in medium containing 8.4 mmol potassium/1 had retained approximately 15% more radioactivity than conrol cells after 2.5 min and this difference was maintained for up to 90 min. There was an increase in the production of steroids by the glomerulosa cells in the presence of 8.4 mM-potassium. No effect on calcium efflux was observed in similar experiments with isolated fasciculata cells; it has been established that this concentration of potassium does not affect steroidogenesis in fasciculata cells, indicating that the effect on glomerulosa cells may be causally linked to steroidogenesis. There was no significant change in the total calcium content of glomerulosa cells in the presence of 8.4 mM-potassium. Exchangeable calcium in these cells was found to be 60% of the total calcium content.


Intravascular Lithotripsy for Acute Stent Under-Expansion and In-Stent Restenosis: A Case Series.
Coronary in-stent restenosis (ISR) has an incidence of about 10% of percutaneous coronary interventions (PCIs) performed in the United States. Traditional management strategies for ISR include balloon angioplasty with non-compliant or use of cutting/scoring balloons or atheroablative therapies (like laser and rotational atherectomy), all of which are inherently limited in their ability to treat stent under-expansion or calcification around the stent. Shockwave intravascular lithotripsy (IVL) has recently demonstrated safe and efficacious treatment of severely calcified coronary stenoses with reported cases of treating ISR as an off-label use. In this case series, we describe the successful use of IVL for 6 cases of ISR and 1 case of stent under-expansion using 40-80 IVL pulses per lesion. Angiographic success was obtained in all seven patients, and there were no intra-procedural complications or adverse cardiac events at a mean follow-up of 200 days. Our report indicates that IVL can be safely and effectively used to treat ISR and stent under-expansion.


Deep learning model to predict Epstein-Barr virus associated gastric cancer in histology.
The detection of Epstein-Barr virus (EBV) in gastric cancer patients is crucial for clinical decision making, as it is related with specific treatment responses and prognoses. Despite its importance, the limited medical resources preclude universal EBV testing. Herein, we propose a deep learning-based EBV prediction method from H&E-stained whole-slide images (WSI). Our model was developed using 319 H&E stained WSI (26 EBV positive; TCGA dataset) from the Cancer Genome Atlas, and 108 WSI (8 EBV positive; ISH dataset) from an independent institution. Our deep learning model, EBVNet consists of two sequential components: a tumor classifier and an EBV classifier. We visualized the learned representation by the classifiers using UMAP. We externally validated the model using 60 additional WSI (7 being EBV positive; HGH dataset). We compared the model's performance with those of four pathologists. EBVNet achieved an AUPRC of 0.65, whereas the four pathologists yielded a mean AUPRC of 0.41. Moreover, EBVNet achieved an negative predictive value, sensitivity, specificity, precision, and F1-score of 0.98, 0.86, 0.92, 0.60, and 0.71, respectively. Our proposed model is expected to contribute to prescreen patients for confirmatory testing, potentially to save test-related cost and labor.


Inhibition of aflatoxins on UDP-glucuronosyltransferases (UGTs).
Aflatoxins have been recognized as the most harmful mycotoxins leading to various toxic effects. The present study aims to determine the inhibition behavior of aflatoxins on the activity of the important phase II metabolizing enzymes, UDP-glucuronosyltransferases (UGTs), based on in vitro incubation system of recombinant human UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU). 100 μM AFB1 and AFG1 exhibited extensive inhibition towards UGT isoforms especially UGT1A7 and UGT1A8, with the inhibition ratios to be 71.38%, 72.95% and 72.79% for AFB1 to UGT1A7, AFB1 to UGT1A8 and AFG1 to UGT1A8, respectively. Molecular docking results showed that hydrogen bonds and hydrophobic contacts of the particular structure consisting of double furan ring with double bond contributed to the interaction of aflatoxins and UGTs. Kinetics analysis, including inhibition types and kinetics parameters (Ki), and in vitro-in vivo extrapolation (IVIVE) indicated that there might be a medium possibility of inhibition on UGTs by aflatoxins in vivo. In conclusion, the present study indicated that aflatoxins could possibly disturb endogenous metabolism by inhibiting the activity of UGTs so as to exhibit toxic effects.


The preparation of carbon-11 labelled proline for positron emission tomography. Preliminary distribution studies in rats with Walker 256 carcinosarcoma.
DL-[1-11C]Proline has been synthesized by carboxylation of alpha-lithiopyrrolidyl-N-tert-butyl-formamidine with a radiochemical yield of up to 18% without correction for decay. The total synthesis time is 45 min. Accumulation of DL-[1-11C]proline has been shown in Walker 256 carcinosarcoma transplanted in rats. A tumor/non-tumor ratio of 5.9 was found at 45 min after i.v. injection.


[Treatment of systemic lupus erythematosus: myths, certainties and doubts].
Systemic lupus erythematosus (SLE) is a complex disease with different clinical forms of presentation, including a wide range of severity and organic involvement. Such circumstance, along with the fact of the uncommon nature of the disease and the absence of clinically representative response criteria, make it difficult to design controlled clinical trials in SLE patients. As a result, observational studies have a special relevance, being a source of valuable information of SLE prognosis and outcome as well as of the efficacy and adverse effects of the different therapies. Herein we update some of the main treatments used in SLE. Steroids may have more risks than benefits if used at high doses. New mechanisms of action have been described, supporting the use of lower doses, possibly with the same efficacy and less adverse effects. Intravenous pulses of cyclophosphamide still have a role in the treatment of proliferative lupus nephritis and other serious SLE manifestations. Mycophenolate mofetil has shown its efficacy both as induction and maintenance therapy of selected cases of lupus nephritis. Biological therapies have emerged as new promising options. Although clinical trials have not confirmed a clear superiority of rituximab in SLE, observational studies have shown good response rates in severe SLE manifestations or refractory forms. Belimumab has recently been added to the therapeutic armamentarium of SLE; although its place in clinical practice is not well-defined, it may be recommended in active patients with no response or good tolerance to standard therapies. Hydroxichloroquine improves survival, decreases the risk of thrombosis and flares and is safe in pregnancy, and should be considered the baseline therapy in most SLE patients.


Plasma potassium in hypertensive Africans on frusemide.
The effects of potassium chloride (as Slow-K 600 mg three times daily) and spironolactone (as Aldactone A 25 mg four times daily) were compared in hypertensive African patients on frusemide. Mean plasma-potassium levels in patients on frusemide plus Slow-K and frusemide plus Aldactone-A rose from 3.6 to 3.8 mOsm/L whilst on frusemide alone mean plasma-potassium fell from 3.7 to 3.6 mOsm/L. The mean blood pressure, both systolic and diastolic, was significantly reduced in the frusemide plus Aldactone-A group when compared with patients on frusemide alone or on frusemide plus Slow-K.


Evaluation of the efficiency of simvastatin loaded PLGA nanoparticles against acute paraquat-intoxicated rats.
Here, we reported a novel nanotherapeutic platform for paraquat (PQ)-induced acute lung injury in animal models using simvastatin (SV) loaded into Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). In this way, Male Wistar rats orally received PQ (120 mg / kg) plus saline, SV (20 mg / kg) or PLGA-SV NPs containing 5, 10 and 20 mg SV/ kg. The levels of TNFα, IL-1β, IL-6 and glutathione content were evaluated. In addition, the pathological changes in the lung were monitored. Our results indicated that PQ (120 mg/kg) significantly reduced the body weight of rats compared to the control group. The most decrease in the level of inflammatory cytokines, bleeding, alveolar destruction as well as lymphocytic infiltration in the lung was observed at group treated with PLGA-SV NPs (10 mg). Free SV (20 mg) as well as PLGA-SV NPs (5 mg) modulated the inflammatory factors and glutathione content, however, they could not prevent tissue damage of PQ. Interestingly, PLGA-SV NPs (20 mg) could not improve the PQ- induced pulmonary damage. In conclusion, PLGA-SV NPs (10 mg) attenuated PQ-induced lung injury. The underlying mechanism may be relevant to increasing glutathione levels and inhibition of the production of inflammatory factors.


Thymus dependence and independence of intestinal pathology in a Trichinella spiralis infection: a study in congenitally athymic (nude) mice.
The hypothesis that non-specific histopathological gut changes are thymus-dependent was tested in a helminth infection--the nematode Trichinella spiralis. The study was performed in congenitally athymic (nu/nu) mice and their thymus-bearing heterozygous litter-mates (+/mu). The non-specific histopathological changes of the small intestine were judged on villus/crypt ratio and mitotic index; for the specific (= immunological) reaction the number of pyroninophilic cells in the small intestine was used as criterion. T. spiralis induced non-specific histopathological reactions both in nu/nu and +/nu mice, whereas the number of pyroninophilic cells was only increased in +/nu mice. It was concluded that the immunological reaction was dependent on the immune status of the host, whereas the non-specific histopathological changes were not, i.e. they were thymus-independent.


Modelling the impacts of climate change on faba bean (Vicia faba L.) production in Welmera area, central Ethiopia.
Climate change is affecting agricultural production and other aspects of life but only limited number of studies took interest in characterizing and projecting climate and its impact on crop production at local level. The threat to agricultural sector is more serious in Ethiopia, where climate is influenced by diverse topography and varying landscape features. This study was conducted in Welmera area to model the impacts of climate change on production of two faba bean (Vicia faba L.) varieties (Tums and Gora). Historical climate and crop yield data were obtained from the National Meteorological Agency of Ethiopia and Holeta Agricultural Research Center, respectively. Future climate data were downscaled by an average ensemble of four GCMs (BSS-CSM1-1, HadGEM2-ES, MIROC-ESM, NorESM1-M) in near- and mid-century (2030s and 2050s) under both RCP 4.5 and RCP 8.5. Rainfall by near-century will increase by up to 50% depending on the concentration pathway considered compared to the baseline period (1988-2017). The projected average rainfall total of belg season (FMAM) will increase by 88.17% under RCP 4.5 scenario and 95.38% under RCP 8.5 scenario in near-century. The future projection revealed that the highest mean monthly rainfall and temperature changes will occur in July (147.3 mm/month) and August (0.24 °C/month) under RCP8.5. However, in August and September mean monthly rainfall will decrease dramatically by 50.85 % and 31.05% from 2020 to 2079 under RCP 8.5 and RCP 4.5, respectively. The yield of Tumsa variety will decrease by up to 24.19% under RCP8.5 in mid-century. Gora variety will see an increase of yield by 18.24% under RCP 4.5 in mid-century and 28.03% under RCP 8.5 in near-century. Overall, the area will experience an increase and a decrease in faba bean yield for both varieties in the upcoming decades in the study area. Performance evaluation of the models showed that they were able to predict future yield faba bean varieties in the area with acceptable accuracy. Inconsistency of future climate variables and impact on fababean production underscores the need to develop location-specific adaptation strategies. Further studies that consider wider area could be necessary to better understand the impact of future climate on faba bean production in the study area and similar agroecologies in the country.


Senescence-induced alteration in cell surface carbohydrates correlated using proton NMR spectroscopy and a lectin-based affinity-binding assay.
Changes in the cell surface oligosaccharides in human fetal lung fibroblasts (IMR-90) are studied as the cells progress to senescence using nuclear magnetic resonance spectroscopy (NMR) and a biochemical assay. A lectin-based affinity-binding technique is used which measures the organization of carbohydrates on the cell surface. Proton NMR studies of the water in samples of frozen cell suspensions of young and old cells provide information on the local dynamics of the cell surface by monitoring the motion of bound water. Changes in the lectin binding density and affinity class distribution correlate with a decrease in the water proton linewidth in frozen cells. These observations reflect alterations in the conformation or structure of the cell surface oligosaccharides and local constituent water.


Clinical and radiological characteristics of neuromyelitis optica spectrum disorder in the North Egyptian Nile Delta.
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disorder of the central nervous system that was previously thought to be a subtype of multiple sclerosis (MS). Epidemiology studies of NMOSD are rare in both Middle East and North African countries. To our knowledge, there are no such studies in Egypt. Herein, we describe a case series of NMOSD patients from North Egyptian Nile Delta region and compare them to NMOSD in other parts in the Middle East and the world. This is a case series study of NMOSD patients who were seen at the neuroimmunology clinic, Elhadara Hospital, University of Alexandria, Egypt, from January 2017 to January 2018. We describe their clinical, serological and radiological features. Our study identified twenty Egyptian patients, all of who fulfilled the 2015 international NMOSD diagnostic criteria. Ten tested positive for AQP4 antibodies in the serum while the other ten were seronegative. The mean age at onset was 27.8 years with an average disease duration of 6.8 years. There was a strong female predominance with a ratio of 5.6:1. We identified clinical features of the cohort that differ from those reported in other worldwide studies. This is the first NMOSD case series in Egypt. Despite some limitation in testing and access to care, there are features of our NMOSD cases that appear to be different from other worldwide cohorts reported in the literature.


Sexually dimorphic legs in a neotropical harvestman (Arachnida, Opiliones): ornament or weapon?
The evolution of sexually dimorphic traits has been the focus of much theoretical work, but empirical approaches to this topic have not been equally prolific. Males of the neotropical family Gonyleptidae usually present a strong fourth pair of legs armed with spines, but their functional significance is unknown. We investigated the putative functions of the leg armature in the harvestman Neosadocus maximus. Being a non-visual species, the spines on male legs can only be perceived by females through physical contact. Thus, we could expect females to touch the armature on the legs of their mates if they were to evaluate it. However, we found no support for this hypothesis. We did show that (1) leg armature is used as a weapon in contests between males and (2) spines and associated sensilla are sexually dimorphic structures involved in "nipping behavior", during which a winner emerged in most fights. Finally, we demonstrate that five body structures directly involved in male-male fights show positive allometry in males, presenting slopes higher than 1, whereas the same structures show either no or negative allometry in the case of females. In conclusion, leg armature in male harvestmen is clearly used as a device in intrasexual contests.


[Is mild hyperhomocysteinemia an additional risk factor of the metabolic syndrome?].
Metabolic syndrome is a cardiovascular risk factors cluster and hyperhomocysteinemia an obvious independant risk factor. To ascertain if hyperhomocysteinemia is associated with the metabolic syndrome. "Epimil" is a prospective epidemiologic survey, which began by a cross-sectionnal study of cardiovascular risk factors in a French population, which then will be followed for ten years for supervision and intervention. Initial data collection, blood pressure measurement, ECG and blood samples (biology and DNA) have been performed. For the metabolic syndrome, we used the criterias of the third report of the national cholesterol education program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (NCEP ATP III). Out of 2045 men aged from 20 to 58 years (37.7+/-8.7 years), 185 (9%) have metabolic syndrome (at least three criterias), 587 (29%) a blood homocysteine>or=12 micromol/L and 202 (10%)>or=15 micromol/L. Homocysteinemia is 10.97+/-5.01 micromol/L for the whole population and doesn't differ with (11.4+/-6 micromol/L) or without (10.9+/-5 micromol/L) the metabolic syndrome, as does its values distribution. It's not correlate with the body mass index, waist and hip measurements, nor with glycemia, HbA1c, insulin resistance and cardiovascular risk markers (CRPus, microalbuminuria). It weakly correlates with systolic and diastolic blood pressure, creatinine clearance, tobacco use, cholesterolemia, triglycerides and free fatty acids but not with HDL and LDL fractions, nor lipoprotein (a). Among this population, it slightly contributes to the ten years vascular risk evaluated according to Framingham equations or Score system. Homocysteinemia and the prevalence of hyperhomocysteinemia don't differ with or without the metabolic syndrome and doesn't correlate its main criterias.


Perioperative SARS-CoV-2 infection among women undergoing major gynecologic cancer surgery in the COVID-19 era: A nationwide, cohort study from Turkey.
The objective of this study was to determine the rate of perioperative SARS-CoV-2 infection among gynecologic cancer patients undergoing major surgery. The database of the Turkish Ministry of Health was searched in order to identify all consecutive gynecologic cancer patients undergoing major surgery between March 11, 2020 and April 30, 2020 for this retrospective, nationwide, cohort study. The inclusion criteria were strictly founded on a final histopathological diagnosis of a malignant gynecologic tumor. COVID-19 cases were diagnosed by reverse transcriptase- polymerase chain reaction testing for SARS-CoV-2. The rate of perioperative SARS-CoV-2 infection and the 30-day mortality rate of COVID-19 patients were investigated. During the study period, 688 women with gynecologic cancer undergoing major surgery were identified nationwide. The median age of the patients was 59 years. Most of the surgeries were open (634/688, 92.2%). There were 410 (59.6%) women with endometrial cancer, 195 (28.3%) with ovarian cancer, 66 (9.6%) with cervical cancer, 14 (2.0%) with vulvar cancer and 3 (0.4%) with uterine sarcoma. The rate of SARS-CoV-2 infections confirmed within 7 days before or 30 days after surgery was 46/688 (6.7%). All but one woman was diagnosed postoperatively (45/46, 97.8%). The rates of intensive care unit admission and invasive mechanical ventilation were 4/46 (8.7%) and 2/46 (4.3%), respectively. The 30-day mortality rate was 0%. In the COVID-19 era, gynecologic cancer surgery may be performed with an acceptable rate of perioperative SARS-CoV-2 infection if the staff and the patients strictly adhere to the established infection control measures.


On the relationship between human all-cause mortality and age.
Many equations can be used to study the relationship between mortality rates and age: Gompertz, Weibull, logistic, polynomial and age-period-cohort equations a.o. All these equations result in highly significant correlations between ln mortality rates and age in the age range 35-84 years. This applies to all developed countries and is independent of the differences in causes of death between populations. The best fit is obtained by a second-degree polynomial equation (R2 > 0.99), closely followed by the Gompertz equation. This equation is preferred in view of its extreme simplicity. A highly significant correlation exists between the intercept and the slope of the Gompertz equations, pointing to a crossing-over age. Beyond that age, around 85 years, populations with high mortality rates have a lower mortality, due to selective survival of the strongest individuals. The polynomial age 2 term may be positive or negative, an expression of the acceleration or de-acceleration of mortality at higher ages and is significantly more often positive in women. The equations used are very useful for the study of the aging process and for examining the relationship between possible causal factors and mortality rates in populations.


Biomarkers of dietary fat composition in young adults with a parental history of premature coronary heart disease compared with controls. The EARS Study.
The European Atherosclerosis Research Study (EARS) is a study of the biological expression of a paternal history of premature coronary heart disease. The study was carried out in 14 centres in 11 European countries, where the offspring of fathers who suffered a documented myocardial infarction before the age of 55 years (cases) were compared with age- and sex-matched controls. In this paper we describe the measurement of plasma cholesteryl esters as biomarkers for the fatty acid composition of the diet in the cases and controls. No significant differences were found. Cholesteryl palmitate, oleate, linoleate and arachidonate were measured in plasma and correlated with plasma lipids and lipoproteins and with life-style variables including body-mass index, alcohol consumption, tobacco and physical activity. The strongest correlations were observed between cholesteryl esters and triglycerides, which are positively correlated with cholesteryl oleate and negatively with cholesteryl linoleate. Apo B was negatively correlated with cholesteryl linoleate and positively with palmitate. Among the other variables, alcohol was positively correlated with cholesteryl oleate and negatively with linoleate, both in males and in females. Furthermore, there are differences between regions, with the highest percentages of saturated cholesteryl palmitate measured in Finnish students, the highest percentage of cholesteryl linoleate in Belgium and of cholesteryl arachidonate in Southern Europe.


How Challenge Demands Have Offsetting Effects on Job Performance: Through the Positive and Negative Emotions.
By combining the broaden-and-build theory of positive emotions (Fredrickson, 2001) and the transactional theory of stress (Lazarus and Folkman, 1984), this study examines how challenge demands (i.e., task complexity and time pressure) have dual effects on employees' job performance through the mediating effects of positive and negative emotions. We collected data from 414 employees from three firms located in China, including two hi-tech firms and one financial firm. The results indicated that challenge demands (i.e., task complexity and time pressure) have an overall positive effect on employees' job performance (i.e., task performance and contextual performance) by offsetting positive indirect effects with negative indirect effects. The theoretical and practical implications are also discussed.