Entropy formula of N-body system.
We prove a proposition that the entropy of the system composed of finite N molecules of ideal gas is the q-entropy or Havrda-Charvát-Tsallis entropy, which is also known as Tsallis entropy, with the entropic index [Formula: see text] in D-dimensional space. The indispensable infinity assumption used by Boltzmann and others in their derivation of entropy formulae is not involved in our derivation, therefore our derived formula is exact. The analogy of the N-body system brings us to obtain the entropic index of a combined system [Formula: see text] formed from subsystems having different entropic indexes [Formula: see text] and [Formula: see text] as [Formula: see text]. It is possible to use the number N for the physical measure of deviation from Boltzmann entropy.


Systemic inflammatory response and thrombosis due to alterations in the gut microbiota in COVID-19.
We thank Dr. Cienfuegos and colleagues for their comments on our recent publication "COVID-19, Coronavirus, SARS-CoV-2 and the small bowel". Cienfuegos et al. have treated several COVID-19 patients with thromboembolic complications, including bowel ischemia. The authors correctly highlight the importance of this complication in COVID-19 patients, which has also been documented in autopsy studies.


Hair casts: classification, staining characteristics, and differential diagnosis.
Considerable confusion exists in the literature regarding hair casts. A variety of different disorders have been grouped and reported as if they were a single entity. This nonspecificity in terminology accounts for the vast discrepancy in their reported incidence, size, configuration, etc. A specific classification for hair casts is proposed to clarify the situation. This article presents a practical staining technic, which readily differentiates peripilar keratin casts from other hair disorders. Clinical and microscopic characteristics of peripilar keratin casts and peripilar nonkeratin casts are illustrated.


Responses of midbrain dorsal raphe neurons to ethanol studied in brainstem slices.
The effects of ethanol on midbrain dorsal raphe (DR) neurons were studied using the brainstem slice preparations. Ethanol in low doses (100 mg% and 200 mg%) exerted more excitation than inhibition on DR cells. Higher doses of ethanol produced inhibition in the majority of DR neurons. The present data indicate that the effects of ethanol were biphasic with low concentrations tending to excite and high concentrations to inhibit DR neurons.


Quantitative determination of morphine in biological samples by gas-liquid chromatography and electron-capture detection.
A highly sensitive method for the determination of morphine in plasma and brain samples down to 500 pg ml-1 in plasma and 100 pg in 30 mg of brain tissue is described. This sensitivity is in the range of that described for radioactive and radioimmunological tehcniques. The samples (50-500 mu-l) are extracted with toluene-butanol (9:1) at pH 8.9 and then re-extracted into 0.1 N sulphuric acid and back extracted to a toluene-butanol phase at pH 8.9. The pentafluoropropionic anhydride derivatives of morphine and the internal standard nalorphine were quantitatively determined by gas-liquid chromatography with a 3-H electron capture detector.


Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests.
Cutaneous melanomas are characterized by a range of histological appearances, and several morphological variants have been described. In this study, we report a variant of superficial spreading melanoma that is characterized by large, irregular junctional melanocytic nests. The junctional nests varied in shape and size, showed focal tendency to confluence, and were often surrounded by a cuff of epidermal keratinocytes. The melanocytes comprising the nests showed variable cytological atypia. In most of the cases, scant intraepidermal or junctional single melanocytes were seen, and other well-documented diagnostic criteria for melanoma were lacking, and as a result, histological recognition of these tumors as melanoma was difficult. Some cases were associated with an invasive dermal component or showed evidence of sun damage. To provide supporting evidence for malignancy, we analyzed these tumors for genomic aberrations. Using array comparative genomic hybridization (aCGH), we identified multiple genomic aberrations in all analyzed cases. A similar pattern of genomic aberrations was seen in a control group of bona fide superficial spreading melanomas, suggesting that these 'melanomas composed exclusively or predominantly of large nests' are indeed variants of superficial spreading melanoma. Fluorescence in-situ hybridization (FISH) was positive in 40% of the cases. However, using aCGH, the FISH-negative cases showed multiple genomic aberrations in regions that are not covered by FISH. The low sensitivity of the FISH test can be explained by the fact that FISH only evaluates four genomic loci for aberrations, whereas aCGH surveys the entire genome. In summary, we present histological and molecular genetic evidence for a morphological variant of superficial spreading melanoma. Awareness of the histological features will aid in their correct diagnosis as melanoma, and in difficult cases, judicious application of ancillary tests such as aCGH (rather than FISH) will assist accurate diagnosis.


A comparison between scalpel and electrocautery in modified radical mastectomy.
To compare the effects of a conventional cold scalpel and electrocautery in modified radical mastectomy. A non-randomised controlled trial. Teaching hospital in Southern Taiwan. 101 consecutive patients with primary breast cancer who underwent modified radical mastectomy between July 1987 and June 1989. The 44 patients during the first year were allocated to have skin flaps fashioned conventionally with a cold scalpel and the 57 patients during the second year, by electrocautery. Morbidity and mortality among the 101 patients who underwent modified radical mastectomy. The groups were comparable in regard to age, menopause, cancer stage, weight of specimen and histological type of cancer. The mean blood loss was 567 ml when scalpel was used and 150 ml when electrocautery was used (p < 0.001). The postoperative fall in packed cell volume was significantly greater in the scalpel group (0.75 [0.26] compared with 0.28 [0.15], p < 0.001) and more patients in this group required transfusion (9 compared with 0, p < 0.01). There were no deaths in either group. There were no significant differences in operation time, total post-operative Hemovac drainage, postoperative hospital stay, the number of lymph nodes removed, the number of metastatic lymph nodes, and postoperative complications between the groups. Electrocautery is a safe, convenient and rational method for constructing skin flaps in modified radical mastectomy, and patients do not need blood transfusions.


[Enhancing effect of danggui injection on immunologic function].
Experiments have shown that Danggui injection enhances phagocytic function of macrophage in normal mice, and antagonizes the immunosuppressive activity of macrophage by cytoxan. The injection may increase the function of B cells and the activity of serum lysozyme, thus increasing the function of humoral immunity and nonspecific immunity.


STEMSIM: a simulator of within-strain short-term evolutionary mutations for longitudinal metagenomic data.
As the resolution of metagenomic analysis increases, the evolution of microbial genomes in longitudinal metagenomic data has become a research focus. Some software has been developed for the simulation of complex microbial communities at the strain level. However, the tool for simulating within-strain evolutionary signals in longitudinal samples is still lacking. In this study, we introduce STEMSIM, a user-friendly command-line simulator of short-term evolutionary mutations for longitudinal metagenomic data. The input is simulated longitudinal raw sequencing reads of microbial communities or single species. The output is the modified reads with within-strain evolutionary mutations and the relevant information of these mutations. STEMSIM will be of great use for the evaluation of analytic tools that detect short-term evolutionary mutations in metagenomic data. STEMSIM and its tutorial are freely available online at https://github.com/BoyanZhou/STEMSim.


Prevalence of severe depressive symptoms increases as death approaches and is associated with disease burden, tangible social support, and high self-perceived burden to others.
Terminally ill cancer patients experience progressive functional decline, accelerating symptom severity, deteriorating social support, and self-perceived burden to others (SPB), predisposing them to depressive symptoms. However, changes in the prevalence of severe depressive symptoms as death approaches and the unique roles of these four variables have not been adequately studied. This study explored longitudinal changes in and associations of symptom distress, functional dependence, social support, and SPB with prevalence of severe depressive symptoms in the last year of life. A convenience sample of 325 cancer patients was longitudinally followed until death. Prevalence of severe depressive symptoms (score ≥11 on the depression subscale of the Hospital Anxiety and Depression Scale) was examined by multivariate logistic regression modeling with the generalized estimating equation. The prevalence of severe depressive symptoms increased as death approached. The likelihood of severe depressive symptoms was significantly higher in patients who had higher levels of symptom distress and functional dependence, received greater tangible support, and reported high SPB, but lower for patients reporting a higher level of affectionate support and positive social interactions with their supportive network. Prevalence of severe depressive symptoms increased as death approached and was associated with several modifiable factors. Healthcare professionals should become familiar with these factors to identify vulnerable patients. To decrease the likelihood of terminally ill cancer patients' severe depressive symptoms, they should receive effective interventions to manage their symptoms, appropriately foster social support to restore their fragile self-esteem due to depending on others, and lighten their SPB.


New classification for correction of alar retraction using the alar spreader graft.
Identifying the cause of alar retraction is essential for proper correction of this deformity. In secondary surgery, aimed primarily at cephalic orientation and medialization of the lateral crus, corrections involving spreading and lateralization of the lateral crus can achieve a more horizontal orientation. In their clinic, the authors have practiced the use of an alar spreader graft to support the spread of the lateral crus. For the lateral crus to move freely without any resistance, it is critical to release the nasal hinge and pyriform ligament. A frontal view of the alar notching and the direction of the lateral crus are highly important factors needed to determine the cause of alar retraction. This report describes a new classification system for alar retractions viewed from the front to aid in determining the cause of the retraction and the surgical management. From March 2008 to July 2010, 31 alar retractions were corrected using alar spreader grafts for patients showing clear alar retractions in frontal views. Satisfactory results without severe complications were obtained in 30 cases, with undercorrection in only 1 case. The alar cartilage was completely released to facilitate lateralization and caudal mobilization. An alar spreader graft then was used to support the lateral crus until a biologic scar cast was formed. The use of alar spreader grafts to correct alar retractions provided consistently good results. The attempt also was made to enhance the treatment strategy based on this classification system derived from frontal views of alar retraction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266 .


Molecular modelling of co-receptor CD8 alpha alpha and its complex with MHC class I and T-cell receptor in sea bream (Sparus aurata).
T-cells are the main actors of cell-mediated immune defence; they recognize and respond to peptide antigens associated with MHC class I and class II molecules. In this paper, we investigated by molecular modelling methods in the teleost sea bream (Sparus aurata) the interaction among the molecules of the tertiary complex CD8/MHC-I/TCR, which determines the T-cell-mediated immunological response to foreign molecules. First, we predicted the three-dimensional structure of CD8 alpha alpha dimer and MHC-I, and, successively, we simulated the CD8 alpha alpha/MHC-I complex. Finally, the 3D structure of the CD8/MHC-I/TCR complex was simulated in order to investigate the possible changes that can influence TCR signalling events.


Efflux systems in bacteria and their metabolic engineering applications.
The production of valuable chemicals from metabolically engineered microbes can be limited by excretion from the cell. Efflux is often overlooked as a bottleneck in metabolic pathways, despite its impact on alleviating feedback inhibition and product toxicity. In the past, it has been assumed that endogenous efflux pumps and membrane porins can accommodate product efflux rates; however, there are an increasing number of examples wherein overexpressing efflux systems is required to improve metabolite production. In this review, we highlight specific examples from the literature where metabolite export has been studied to identify unknown transporters, increase tolerance to metabolites, and improve the production capabilities of engineered bacteria. The review focuses on the export of a broad spectrum of valuable chemicals including amino acids, sugars, flavins, biofuels, and solvents. The combined set of examples supports the hypothesis that efflux systems can be identified and engineered to confer export capabilities on industrially relevant microbes.


Resveratrol protects myocardial ischemia-reperfusion injury through both NO-dependent and NO-independent mechanisms.
We previously showed that resveratrol (3,4',5-trihydroxystilbene) stimulates NO production and is cardioprotective in rat heart subjected to ischemia-reperfusion (I/R rat heart). We now show that in I/R rat heart, inducible nitric oxide synthase (iNOS) expression is markedly induced, while expression of endothelial nitric oxide synthase (eNOS) and nueronal nitric oxide synthase (nNOS) is unchanged. In animals preconditioned with resveratrol (0.5 to 1 mg/kg body wt), I/R-induced iNOS induction is abrogated; however, expression of eNOS and nNOS is greatly upregulated. The protective effects of resveratrol on I/R rat heart include reduced rhythm disturbances, reduced cardiac infarct size, and decreased plasma levels of lactate dehydrogenase (LDH) and creatine kinase (CK). Among these, the reductions in LDH/CK levels and infarct size are NO-dependent as the coadministration of N(omega)-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg body wt) with resveratrol abolishes the resveratrol effect. In contrast, the reductions in the severity of ventricular arrhythmia and mortality rate are not affected by L-NAME coadministration, suggesting that a NO-independent mechanism is involved.


Geographic distribution of malignant mesothelioma incidence and survival in Australia.
To understand the geographic distribution of and area-level factors associated with malignant mesothelioma incidence and survival in Australia. Generalised linear models and Bayesian spatial models were fitted using population registry data. Area-level covariates were socioeconomic quintile, remoteness category and state or territory. The maximised excess events test was used to test for spatial heterogeneity. There was strong evidence of spatial differences in standardised incidence rates for malignant mesothelioma but survival was uniformly poor. Incidence rates varied by state or territory and were lower in remote areas. Patterns in the geographic distribution of modelled incidence counts for malignant mesothelioma differed substantially from patterns of standardised incidence rates. Geographic variation in the modelled incidence counts of malignant mesothelioma demonstrates varying demand for diagnostic and management services. The long latency period for this cancer coupled with migration complicates any associations with patterns of exposure, however some of the geographic distribution of diagnoses can be explained by the location of historical mines and asbestos-related industries.


Antibiotic choice for the management of preterm premature rupture of membranes in Taiwanese women.
Preterm premature rupture of membranes (PPROM) is one of the most common causes of preterm birth. Antibiotic treatment is recommended to prolong the pregnancy course and reduce fetal morbidity in women with PPROM. However, the guidelines for antibiotic selection are based on studies done years ago, mostly in Western countries, which may not reflect the geographic, temporal, and ethnic variation in microbial colonization and infection in other parts of the world. We aimed to understand whether the antibiotics recommended by the current guidelines were sufficient to eradicate the majority of pathogens involved. This is a single-center retrospective study at a tertiary medical center in Taiwan with patients recruited from January 1, 2017, to December 31, 2019. All patient included had a confirmed diagnosis of PPROM. In this study, we aimed to investigate which broad-spectrum antibiotic was most suitable for PPROM cases in Taiwan. 133 women were included, and 121 women had positive culture results. Most of the pregnant women had one positive result (35.5%). The most common pathogen was Lactobacillus species (27.8%), followed by Streptococcus species (12.9%) and Staphylococcus species (12.09%). The most appropriate antibiotic therapy for PPROM was a combination of 1 g azithromycin given orally on admission plus a third-generation cephalosporin administered intravenously in the first 48 hours and followed by amoxicillin 500 mg per os for another five days. This recommended antibiotic regimen for women with PPROM needs further study under a randomized clinical trial with a larger study population to evaluate its efficacy.


Macrophages orchestrate the expansion of a proangiogenic perivascular niche during cancer progression.
Tumor-associated macrophages (TAMs) are a highly plastic stromal cell type that support cancer progression. Using single-cell RNA sequencing of TAMs from a spontaneous murine model of mammary adenocarcinoma (MMTV-PyMT), we characterize a subset of these cells expressing lymphatic vessel endothelial hyaluronic acid receptor 1 (Lyve-1) that spatially reside proximal to blood vasculature. We demonstrate that Lyve-1+ TAMs support tumor growth and identify a pivotal role for these cells in maintaining a population of perivascular mesenchymal cells that express α-smooth muscle actin and phenotypically resemble pericytes. Using photolabeling techniques, we show that mesenchymal cells maintain their prevalence in the growing tumor through proliferation and uncover a role for Lyve-1+ TAMs in orchestrating a selective platelet-derived growth factor–CC–dependent expansion of the perivascular mesenchymal population, creating a proangiogenic niche. This study highlights the inter-reliance of the immune and nonimmune stromal network that supports cancer progression and provides therapeutic opportunities for tackling the disease.


Reduction of erythrocyte (Na(+)-K+) ATPase activities in non-insulin-dependent diabetic patients with hyperkalemia.
To elucidate the mechanism of hyperkalemia in diabetic patients without renal failure, we investigated (Na(+)-K+) adenosine triphosphatase (ATPase) activity in erythrocyte membrane, erythrocyte Na+ and K+ content, and plasma endogenous digitalis-like substance in control subjects (n = 16) and non-insulin-dependent diabetes mellitus (NIDDM) patients (n = 62). NIDDM patients were divided into normokalemic patients (NKDM, n = 48) and hyperkalemic patients (HKDM, n = 14). There was no difference in plasma glucose or hemoglobin A1c (HbA1c) levels, plasma renin activity (PRA), and plasma aldosterone concentrations (PAC) between NKDM and HKDM patients. (Na(+)-K+)ATPase activities in NIDDM patients were significantly reduced compared with those in control subjects (0.336 +/- 0.016 mumol-inorganic phosphate [Pi]/mg protein/h, mean +/- SEM, P less than .05), and (Na(+)-K+)ATPase activities in HKDM patients (0.243 +/- 0.015 mumol Pi/mg protein/h) were significantly reduced compared with those in NKDM patients (0.295 +/- 0.008 mumol Pi/mg protein/h, P less than .01). Plasma K+ content had a significant negative correlation with (Na(+)-K+)ATPase activity in diabetic patients (r = -.365, P less than .01). Erythrocyte Na+ content had a significant negative correlation with (Na(+)-K+)ATPase activity in control subjects (r = -.619, P less than .05). There was no difference in plasma endogenous digitalis-like substance among the three groups. (Na(+)-K+)ATPase activity was not significantly correlated with plasma endogenous digitalis-like substance in control subjects and diabetic patients. These findings suggest that the reduction of (Na(+)-K+)ATPase activity, which was not related to plasma digitalis-like substance, may be partly responsible for hyperkalemia in diabetic patients.


A comparison of postoperative recovery times between isoflurane and enflurane for pediatric dental outpatient anesthesia.
Isoflurane is a volatile liquid anesthetic agent reported to have recovery times shorter than many anesthetic agents in current use. This study compared postoperative recovery times in pediatric patients receiving dental treatment under isoflurane to those receiving enflurane anesthesia. The study consisted of a retrospective review of anesthesia records for pediatric patients receiving isoflurane anesthesia. These patients were then matched to patients receiving enflurane anesthesia for age, weight, sex, race, and treatment time. A total of nine matched pairs were available for review. The average recovery time (as measured from extubation to discharge) for isoflurane was 53 minutes and for enflurane, 46 minutes. When the matched cases were analyzed by paired t-text, no statistically significant difference in recovery times was demonstrated at the 0.05 level. These findings suggest that there is no significant difference in postoperative recovery times between isofluane and enflurane in pediatric dental outpatients undergoing general anesthesia.


Monitoring the assembly of antibody-binding membrane protein arrays using polarised neutron reflection.
Protein arrays are used in a wide range of applications. The array described here binds IgG antibodies, produced in rabbit, to gold surfaces via a scaffold protein. The scaffold protein is a fusion of the monomeric E. coli porin outer membrane protein A (OmpA) and the Z domain of Staphylococcus aureus protein A. The OmpA binds to gold surfaces via a cysteine residue in a periplasmic turn and the Z domain binds immunoglobulins via their constant region. Polarised Neutron Reflection is used to probe the structure perpendicular to the gold surface at each stage of the assembly of the arrays. Polarised neutrons are used as this provides a means of achieving extra contrast in samples having a magnetic metal layer under the gold surface. This contrast is attained without resorting to hydrogen/deuterium exchange in the biological layer. Polarised Neutron Reflection allows for the modelling of many and complex layers with good fits. The total thickness of the biological layer immobilised on the gold surface is found to be 187 A and the layer can thus far be separated into its lipid, protein and solvent parts.


The second will be first: competition on directed networks.
Multiple sinks competition is investigated for a walker diffusing on directed complex networks. The asymmetry of the imposed spatial support makes the system non transitive. As a consequence, it is always possible to identify a suitable location for the second absorbing sink that screens at most the flux of agents directed against the first trap, whose position has been preliminarily assigned. The degree of mutual competition between pairs of nodes is analytically quantified through apt indicators that build on the topological characteristics of the hosting graph. Moreover, the positioning of the second trap can be chosen so as to minimize, at the same time, the probability of being in turn shaded by a thirdly added trap. Supervised placing of absorbing traps on a asymmetric disordered and complex graph is hence possible, as follows a robust optimization protocol. This latter is here discussed and successfully tested against synthetic data.


Species-specific metabolites mediate host selection and larval recruitment of the symbiotic seastar shrimp.
In marine environments, host selection, defining how symbiotic organisms recognize and interact with their hosts, is often mediated by olfactory communication. Although adult symbionts may select their hosts detecting chemosensory cues, no information is available concerning the recruitment of symbiotic larvae which is a crucial step to sustain symbioses over generations. This study investigates the olfactory recognition of seastar hosts by adult Zenopontonia soror shrimps and the recruitment of their larvae. We examine the semiochemicals that influence host selection using chemical extractions, behavioural experiments in olfactometers, and mass spectrometry analyses. After describing the symbiotic population and the embryonic development of shrimps, our results demonstrate that asterosaponins, which are traditionally considered as chemical defences in seastars, are species-specific and play a role in attracting the symbiotic shrimps. Adult shrimps were found to be attracted only by their original host species Culcita novaeguineae, while larvae were attracted by different species of seastars. This study provides the first chemical identification of an olfactory cue used by larvae of symbiotic organisms to locate their host for recruitment. These findings highlight the importance of chemical communication in the mediation of symbiotic associations, which has broader significant implications for understanding the ecological dynamics of marine ecosystems.


Investigating MIF in Mouse Model of Gout.
Mice are widely used to assess the pathogenesis of diseases. An experimental model of gout consists of the injection of uric acid crystals into joints of mice, which reproduce inflammation and functional changes of the human disease. Uric acid crystals activate synoviocytes culminating in the release of IL-1β and neutrophil recruitment, key inflammatory elements in gouty arthritis. Since MIF plays an important role in orchestrating gout inflammation, we detail valuable procedures to investigate uric acid crystal-induced joint inflammation in mice and give options for further understanding the functions of MIF in gouty arthritis in vivo and in vitro.


Electrophysiological Investigation of NMDA Current Properties in Brain Slices.
Analysis of electrophysiological properties of NMDARs and NMDAR-mediated synaptic transmission in identified neurons and synapses in brain slices is a major step in understanding their function in normal and pathological neuronal brain networks. In many central synapses excitatory postsynaptic currents (EPSCs) are mediated by excitatory neurotransmitter glutamate that activates colocalized AMPAR and NMDAR generating a complex EPSC. Here, we describe the methods commonly used in brain slices to study the electrophysiological properties of NMDAR-mediated component of spontaneous or evoked EPSCs by extracellular stimulation or by stimulating synaptically connected neurons. This approach is based on whole-cell patch-clamp recordings, pharmacological tools, and the analysis of the difference in temporal parameters between the AMPA and NMDA receptors. It allows pinpointing of the basic functional properties of NMDARs that are specific to identified brain regions, neurons, and synapses of wild-type or genetically manipulated mice.


Detection of penicillin-binding protein 2b gene alteration in Streptococcus mitis by polymerase chain reaction.
Three isolates of beta-lactam-resistant streptococci from the saliva of healthy adults were identified as Streptococcus mitis. Minimum inhibitory concentrations (MICs) were 2 to 4 micro g/ml for ampicillin (ABPC) and 64 to more than 128 micro g/ml for cefaclor (CCL). To determine the position of base alterations of the penicillin-binding protein 2b ( pbp2b) gene, upstream primers containing possible mutation points were designed, and used for polymerase chain reaction (PCR), together with a downstream primer. Alterations adjacent to the conserved motifs of the pbp2b gene were apparent. DNA sequencing data indicated replacements in deduced amino acid sequences in all resistant isolates: from threonine to alanine just after the serine-serine-asparagine (SSN) motif, and from alanine to glycine two residues downstream of the lysine-threonine-glycine (KTG) motif. These changes were the same as those in penicillin-resistant Streptococcus pneumoniae (PRSP), suggesting importance for the enzymatic activity of the protein. Thus, Beta-lactam susceptibility of S. mitis may be partially predicted by PCR using our primer set for pbp2b.


Substrate selectivity of diacylglycerol kinase in guinea pig brain.
The present study was conducted to test the selectivity of the microsomal diaclyglycerol kinase (ATP:1,2-diacyl-sn-glycerol-phosphotransferase) from guinea pig brain towards different, 1,2-diacyl-sn-glycerols. The molecular species added to the incubation medium as substrates were a mixture of the 1-[3H]palmitoyl plus 1-[14C]stearoyl homologs of either the monoenoic (2-oleoyl), dienoic (2-linoleoyl), tetraenoic (2-arachidonoyl), or hexaenoic (2-docosahexaenoyl) diacylglycerols. Rates of phosphatidic acid synthesis (1-palmitoy plus 1-stearoyl homologs) with each of the four classes of unsaturated diacylglycerols were not greatly different, although they were moderately higher in the case of the monoenes. No marked enzyme selectivity for either the 1-palmitoyl or 1-stearoyl homolog of the various 1-saturated 2-unsaturated diacylglycerols was apparent. Generally similar results were obtained with the diacylglycerol kinase in rat brain microsomes.


Cardioselective beta-adrenergic blocking agents. 1. 1-((3,4-Dimethoxyphenethyl)amino)-3-aryloxy-2-propanols.
A series of 1-amino-3-aryloxy-2-propanols has been synthesized and examined for cardioselective beta-blockade. The introduction of the (3,4-dimethoxyphenethyl)amino group lead to the most cardioselective agents. Structure-activity relationships are discussed. Of the compounds tested 1-[(3,4-dimethoxyphenethyl)amino]-3-(m-tolyloxy)-2-propanol was selected for clinical trial because of optimal potency and selectivity.


Tumor-specific outcome of metachronous uterine malignancy after pelvic irradiation for cervical cancer.
To examine survival of women who develop metachronous uterine malignancy after definitive pelvic radiotherapy for cervical cancer. This retrospective observational study examined the Surveillance, Epidemiology, End Results Program between 1973 and 2013. Women with cervical cancer who received definitive radiotherapy without hysterectomy were examined for the diagnosis of metachronous uterine malignancy (n = 5277). Survival was compared between metachronous and non-metachronous uterine malignancies according to tumor factors. The 10- and 20-year cumulative incidences of metachronous uterine malignancy were 0.6% and 1.2%, respectively. When compared to non-metachronous uterine malignancy, metachronous tumor were more likely to be non-endometrioid and advanced-stage (both, P < 0.001). As a whole cohort, metachronous uterine malignancy was significantly associated with decreased overall survival (OS) compared to non-metachronous tumors (hazard ratio [HR] 4.22, P < 0.001). OS was significantly worse in metachronous compared to non-metachronous malignancies, although the magnitude of statistical significance was greater for endometrioid tumors (HRs for endometrioid versus non-endometrioid: 6.17 versus 1.92). For grade 1-2 endometrial cancer, metachronous cases had significantly decreased OS compared to non-metachronous cases, a larger difference than that seen in higher grade tumors (HRs for grade 1-2 versus 3: 7.79 versus 2.15). Similarly, in early-stage endometrial cancer, metachronous cases had significantly decreased OS, with a greater HR compared to advanced-stage disease (HRs for stage I-II versus III-IV: 5.29 versus 2.29). Radiotherapy-associated metachronous uterine malignancy after cervical cancer is rare but commonly presents with aggressive tumor characteristics. The impact on survival is considerably high when metachronous uterine malignancy is endometrioid, low-grade, and early-stage.


Synthesis of serum and cytosol vitamin D-binding proteins by rat liver and kidney.
The synthesis of vitamin D-binding proteins in rat was examined using liver and kidney slices, isolated hepatocytes, and isolated renal tubules. Rat liver synthesized both serum vitamin D-binding protein (DBP) and a tissue DBP-binding component and secreted serum DBP. Rat kidney also synthesized a tissue DBP-binding component and cytosol vitamin D-binding protein (CDBP) which was immunologically related to serum DBP, but secretion of renal CDBP was not observed. Renal CDBP had a higher molecular weight (approximately 65,000) than that of serum DBP (54,000) and was heat-labile, while serum DBP was heat-stable (60 degrees C, 60 min). Renal CDBP was considered to exist in cytosol, forming a complex with a tissue DBP-binding component. These results indicate that liver is a site of synthesis of serum DBP and that CDBP, which is immunologically related to but physicochemically different from serum DBP, is synthesized in situ in kidney.


Effect of PLGA hydrophilia on the drug release and the hypoglucemic activity of different insulin-loaded PLGA microspheres.
The effects of viscosity and hydrophilic characteristics of different PLGA polymers on the microencapsulation of insulin have been studied in vitro and in vivo after subcutaneous administration to hyperglycemic rats. Hydrophilic PLGA polymers produced a higher burst effect than the hydrophobic ones. Moreover, an incomplete insulin release was observed with the hydrophilic PLGA polymers in comparison with the hydrophobic ones. An explanation for that incomplete release can be the development of polymer-insulin interactions associated to the polymer hydrophilic/hydrophobic character, as detected by DSC analysis. Differences in the release rate of microsphere formulations lead to differences in the hypoglycemic action and the weight of animals. Hydrophobic PLGA was able to prolong the hypoglycemic action up to 4 weeks which is at least double than that obtained with hydrophilic PLGA of a similar viscosity. Comparing insulin microspheres with an immediate release formulation, microspheres can increase insulin relative bioavailability up to four times.


Incidence, Clinical Characteristics, and Impact of Absent Echocardiographic Signs in Patients With Infective Endocarditis After Transcatheter Aortic Valve Implantation.
Echocardiography is the primary imaging modality for diagnosis of infective endocarditis (IE) in prosthetic valve endocarditis (PVE) including IE after transcatheter aortic valve implantation (TAVI). This study aimed to evaluate the characteristics and clinical outcomes of patients with absent compared with evident echocardiographic signs of TAVI-IE. Patients with definite TAVI-IE derived from the Infectious Endocarditis after TAVI International Registry were investigated comparing those with absent and evident echocardiographic signs of IE defined as vegetation, abscess, pseudo-aneurysm, intracardiac fistula, or valvular perforation or aneurysm. Among 578 patients, 87 (15.1%) and 491 (84.9%) had absent (IE-neg) and evident (IE-pos) echocardiographic signs of IE, respectively. IE-neg were more often treated via a transfemoral access with a self-expanding device and had higher rates of peri-interventional complications (eg, stroke, major vascular complications) during the TAVI procedure (P < .05 for all). IE-neg had higher rates of IE caused by Staphylococcus aureus (33.7% vs 23.2%; P = .038) and enterococci (37.2% vs 23.8%; P = .009) but lower rates of coagulase-negative staphylococci (4.7% vs 20.0%, P = .001). IE-neg was associated with the same dismal prognosis for in-hospital mortality in a multivariate binary regression analysis (odds ratio: 1.51; 95% confidence interval [CI]: .55-4.12) as well as a for 1-year mortality in Cox regression analysis (hazard ratio: 1.10; 95% CI: .67-1.80). Even with negative echocardiographic imaging, patients who have undergone TAVI and presenting with positive blood cultures and symptoms of infection are a high-risk patient group having a reasonable suspicion of IE and the need for an early treatment initiation.


Pharmacological characterisation of dopamine overflow in the striatum of the normal and MPTP-treated common marmoset, studied in vivo using fast cyclic voltammetry, nomifensine and sulpiride.
The in vivo measurement of electrically-evoked dopamine overflow was measured for the first time in the striatum of control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets using fast cyclic voltammetry at untreated carbon-fibre microelectrodes, (7 microm, o.d.). The identity of dopamine was confirmed using electrochemical, pharmacological and histological criteria and complied with rat data from earlier studies. Dopamine overflow depended on the intensity, number of pulses, and frequency of the applied stimuli. Maximum dopamine overflow occurred using 1.0-2.0 mA, 200 micros pulse width, 150-200 pulses at 80-120 Hz stimulation of the medial forebrain bundle. Evoked dopamine overflow in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated marmosets showed a similar electrochemical and pharmacological profile compared to healthy controls, albeit the concentration detected was significantly reduced. The catecholamine uptake blocker, nomifensine, significantly increased the dopamine signal in control marmosets. However, in contrast, nomifensine had no significant effect on evoked dopamine overflow in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated marmosets. Apart from demonstrating that fast cyclic voltammetry with electrical stimulation can be reliably used to monitor dopamine overflow within the primate brain, our results describe for the first time the technical prerequisites for the fast cyclic voltammetric technique in the non-human primate brain.


Detection of hepatitis C virus by polymerase chain reaction and response to interferon-alpha therapy: relationship to genotypes of hepatitis C virus.
To investigate the relationship between genotypes of hepatitis C virus and response to interferon-alpha therapy, hepatitis C virus RNA was assayed by polymerase chain reaction with three sets of primers and probes in 70 patients with non-A, non-B chronic hepatitis who received interferon-alpha. Twenty-four patients sustained long-term remissions (complete responders). Polymerase chain reaction for 5'-terminal noncoding region detected hepatitis C virus RNA in 94.3% (66 of 70) of the patients. Polymerase chain reaction for nonstructural region 3, in which primers and a probe were synthesized to be identical to hepatitis C virus-J, detected hepatitis C virus RNA in 40 patients. Polymerase chain reaction for nonstructural region 5-in which sequences of primers and a probe were derived from hepatitis C virus-K2, a genotype different from hepatitis C virus-J--detected hepatitis C virus RNA in 17 patients. Only one patient was positive on both nonstructural region 3 and nonstructural region 5 polymerase chain reaction. Nucleotide sequence of clones obtained from 5' terminal noncoding region polymerase chain reaction products of two patients positive on polymerase chain reaction for nonstructural region 3 and negative on polymerase chain reaction for nonstructural region 5 (group 1) corresponded to that of the hepatitis C virus-J group, and those of clones from two patients negative on polymerase chain reaction for nonstructural region 3 and positive on polymerase chain reaction for nonstructural region 5 (group 2) corresponded to that of hepatitis C virus-K2.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of luteoin in delaying cataract in STZ-induced diabetic rats.
Luteolin, a flavonoid rich in many plants, has shown various pharmacological effects including anti-inflammation, anti-oxidant, anti-tumor, cardioprotective and neuroprotective properties. At present, inflammation and oxidative stress have been recognized to be two important contributing factors to the development of diabetic cataract. The aim of this study is to investigate the effects of luteolin on diabetes-induced oxidative stress and inflammation in the lens of rats. A diabetic rat model was induced by intraperitoneally giving streptozotocin at a dosage of 60 mg/kg, and then the rats were treated by orally administration of luteolin 25, 50 and 100 mg/kg for 12 weeks. The results showed that luteolin administration could increase the antioxidant capacity such as glutathione (GSH) and glutathione peroxidase (GPx) activity, and decreased malondialdehyde (MDA) level in the lens of diabetic rats. Luteolin also inhibited diabetes-induced elevation of interleukin-1 beta (IL-1β), vascular endothelial growth factor and nuclear factor-κB (NF-κB) mRNA and protein expression in lens. Moreover, in the high dose group (100 mg/kg), lens GSH level was decreased to normal compared to control group. The degree of oxidative and inflammatory damage was significantly reduced in luteolin-treated rats. These data suggested that luteolin can be an effective protection candidate of diabetes-induced lens neurodegeneration by inhibiting the levels of inflammatory mediators and oxidative stress.


Assembly of Poly(vinylphosphonic acid)-Based Double Hydrophilic Block Copolymers by Gadolinium Ions for the Formation of Highly Stable MRI Contrast Agents.
Mixing double-hydrophilic block copolymers containing a poly(vinylphosphonic acid) block with gadolinium ions in water leads to the spontaneous formation of polymeric nanoparticles. With an average diameter near 20 nm, the nanoparticles are stable after dilution or change of pH and ionic strength. High magnetic relaxivities were measured in vitro, and in vivo magnetic resonance imaging on rats demonstrates the high potential of such polymeric assemblies.


Vessel Anatomical Features of 'Picual' and 'Frantoio', Two Olive Cultivars Different in Resistance against Verticillium Wilt of Olive.
The olive tree (Olea europaea), a non-tropical woody crop that occupies the largest area in the world, is severely affected by the fungus Verticillium dahliae worldwide. In this regard, there is currently detailed information on the level of resistance to this pathogen in the main olive varieties. However, there is little information on quantitative aspects of its anatomy and on the existence of anatomical differences between varieties that could be related to the differential resistance response observed. In the present work, a quantitative study of the xylem of 'Picual', susceptible, and 'Frantoio', resistant, to V. dahliae is carried out. This study also provides quantitative data on the xylem in different areas of the plant, an aspect on which there is not much information for the olive tree. Among the parameters evaluated, it is probably the greater conductive capacity in the xylem tissue that 'Frantoio' presents, mainly due to the greater density of its vessels, which has a more relevant role in the resistance and natural recovery that this cultivar manifests to the disease. In any case, these constitutive anatomical differences, and those others that can be induced in plants during infections, should be investigated in future work that includes inoculation with the pathogen.


Growth/differentiation factor 3 signals through ALK7 and regulates accumulation of adipose tissue and diet-induced obesity.
Growth/differentiation factor 3 (GDF3) is highly expressed in adipose tissue, and previous overexpression experiments in mice have suggested that it may act as an adipogenic factor under conditions of high lipid load. GDF3 has been shown to signal via the activin receptor ALK4 during embryogenesis, but functional receptors in adipose tissue are unknown. In this study, we show that Gdf3(-/-) mutant mice accumulate less adipose tissue than WT animals and show partial resistance to high-fat diet-induced obesity despite similar food intake. We also demonstrate that GDF3 can signal via the ALK4-homolog ALK7 and the coreceptor Cripto, both of which are expressed in adipose tissue. In agreement with a role for ALK7 in GDF3 signaling in vivo, mutant mice lacking ALK7 also showed reduced fat accumulation and partial resistance to diet-induced obesity. We propose that GDF3 regulates adipose-tissue homeostasis and energy balance under nutrient overload in part by signaling through the ALK7 receptor.


Circular RNA PRMT5 confers cisplatin-resistance via miR-4458/REV3L axis in non-small-cell lung cancer.
Multifactor and multistep processes were elucidated to participate in the progression of non-small-cell lung cancer (NSCLC). Circular RNA 0031250 (circ-PRMT5) was a vital factor in NSCLC. However, the role of circ-PRMT5 in cisplatin (DDP)-resistance needed to be further highlighted. Expression profiles of circ-PRMT5, microRNA (miR)-4458, and EV3-like DNA-directed polymerase ζ catalytic subunit (REV3L) were detected using quantitative real-time polymerase chain reaction. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and transwell assays were performed to determine the half-maximal inhibitory concentration of DDP, cell viability, apoptosis, and invasion in vitro. Besides, the protein levels of REV3L and indicated proteins were examined by adopting western blot. Dual-luciferase reporter assay was performed to analyze the interaction between miR-4458 and circ-PRMT5 or REV3L. The functional role of circ-PRMT5 was explored using a xenograft tumor model. Levels of circ-PRMT5 and REV3L were markedly increased, while miR-4458 was downregulated in resistant tissues and cells. Knockdown of circ-PRMT5 enhanced cell apoptosis, DDP-sensitivity, and declined metastasis in NSCLC with DDP resistance. Besides, miR-4458 inhibition or REV3L upregulation could revert circ-PRMT5 absence-mediated effect on DDP-sensitivity in vitro. Mechanically, circ-PRMT5 was a sponge of miR-4458 to regulate REV3L. Importantly, circ-PRMT5 silencing could interact with DDP treatment expedite the decrease of tumor growth in vivo. Circ-PRMT5 promoted DDP resistance via REV3L by sponging miR-4458 in NSCLC, thus providing a novel therapeutic strategy for patients with NSCLC.


Efficacy and safety of coadministration of sitagliptin with insulin glargine in type 2 diabetes.
The aim of the randomized present study was to compare the therapeutic efficacy and safety of a combination of sitagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, plus insulin glargine (GL + sita) with that of premixed insulin aspart 30 (NOV) for type 2 diabetes (T2D) patients controlled with oral hypoglycemic drugs (HbA1c 7 %-9 %). Sixty-five patients were randomized (1: 1) to the GL + sita (n = 33) and NOV (n = 32) groups and were treated with the combination regimen or premixed insulin twice a day for 16 weeks. The primary endpoint was mean change in HbA1c. Secondary endpoints included fasting blood glucose, blood glucose profiles (seven time points), rate of achieving target HbA1c (<7 % or ≤6.5 %), insulin dose, incidence of hypoglycemia, and body weight. After 16 weeks, there was no significant difference in HbA1c between the two groups, although more patients achieved HbA1c <7.0 % in the GL + sita group. There was a significant difference in body weight changes between the GL + sita and NOV groups (-0.45 vs 1.52 kg, respectively; P < 0.001). Mean plasma glucose and the mean amplitude of glycemic excursion were significantly lower in the GL + sita than NOV group (P < 0.005), as was the incidence of symptomatic hypoglycemia (2.85 % vs. 13.3 %, respectively; P < 0.001). The combination of GL + sita greatly improved HbA1c in T2D patients (HbA1c 7 %-9 %) with an efficacy that was equal to that of premixed insulin. Thus, GL + sita treatment is a viable option for patients who fail to achieve glycemic control using oral hypoglycemic drugs.


Feline non-flea induced hypersensitivity dermatitis: clinical features, diagnosis and treatment.
Hypersensitivity dermatitis (HD) is often suspected in cats and is mostly caused by insect bites, food or environmental allergens. Cats with non-flea induced HD are reported to present frequently with one or more of the following cutaneous reaction patterns: miliary dermatitis, eosinophilic dermatitis, self-induced symmetrical alopecia or head and neck excoriations/pruritus. None of the above patterns are, however, pathognomonic for non-flea induced HD and the diagnosis of this condition is based on exclusion of diseases presenting similarly and an adequate response to treatment. Therapeutic approaches to affected cats include use of immunomodulatory drugs (ciclosporin, glucocorticoids, antihistamines), hypoallergenic diets and allergen-specific immunotherapy. This review provides an update on the clinical signs, diagnosis and treatment of feline non-flea induced HD. It draws on the findings of a recent large-scale study that described the clinical signs of numerous cats with non-flea HD and has proposed criteria to facilitate the diagnosis of the condition.


Catching the asthma: family care for school-aged children with asthma.
The purpose of this study was to explore how families with school-aged children diagnosed with asthma incorporate asthma care into their daily lives. Twelve families with a school-aged child who had asthma participated in this study. Data collection involved a series of three in-depth interviews with family members in which the process of catching the asthma before it gets out of hand was uncovered, clarified, and validated. Learning the ropes, dealing with asthma, and coming to terms with asthma are the tasks engaged in by parents and their children to catch the asthma.


In vitro regeneration of adult rat ganglion cell axons from retinal explants.
The potential for regeneration of adult rat ganglion cell (RGC) axons was investigated in vitro. Explants from RITC (rhodamine-B-isothiocyanate) retrogradely labeled and in vivo axotomized retinae were placed on dishes coated with various substrates. The retinal pieces were cultivated in a serum-free medium and incubated under 50 to 80% O2-enriched and 5% CO2-containing atmosphere. Under these conditions, massive outgrowth of fibers was observed as early as 24 h after explantation and over a period of time extending up to 7 days in culture. By various criteria, two main types of processes could be characterized: (1) Short, thick processes emerged from either migrated flat cells or from cells inside the retinal explant, and (2) long and thin processes emerged from cells in the ganglion cell layer (GCL). By immunohistochemistry, the short processes and the cells from which they had emerged, appeared to be glial acidic fibrillary protein (GFAP)-positive Thy 1 and L 1-negative, suggesting their glial nature. The second type of long, thin processes appeared to be GFAP-negative, L1- and Thy 1-positive, indicating that they were neuronal, probably RGC processes. Proof that long fibers emerged from RGCs was provided by retrograde labeling of RGCs with RITC prior to explanation. Numerous RITC-filled RGCs survived in vitro. Regrowing axons retransported part of the accumulated fluorescent dye in the orthograde direction and thus unequivocally permitted their identification as RGC axons. The fact that adult RGC axons can reelongate in vitro might provide a useful bioassay for investigations on the factors that either support or inhibit regrowth of axons from CNS neurons.


Bicuspid Aortic Insufficiency With Aortic Root Aneurysm: Root Reimplantation Versus Bentall Root Replacement.
In patients with a bicuspid aortic valve presenting with aortic insufficiency (AI) and root aneurysm, we assessed whether outcomes with primary cusp repair with root reimplantation were equivalent to the gold standard Bentall procedures. From 2002 to 2014, 710 patients with bicuspid aortic valve underwent aortic root procedures. Of these, only patients presenting with noncalcified type I bicuspid aortic valve with AI (n = 165) were included to maintain anatomic and physiologic homogeneity between the groups. Aortic stenosis, endocarditis, redo root, and emergency cases were excluded. Patients undergoing valve-sparing root reimplantation (VSRR group, n = 45) were retrospectively compared with those undergoing Bentall root replacement (Bentall group, n = 120). Patients in the Bentall group were older (52 ± 13 vs 46 ± 12 years; p ≤ 0.01) and had a lower ejection fraction (0.53 ± 0.12 versus 0.58 ± 0.08; p < 0.01), but left ventricular diastolic diameter was similar (58 ± 10 mm versus 57 ± 9 mm; p = 0.5). Thirty-day and in-hospital mortality was zero; in-hospital stroke rate was 0.8% (n = 1) in the Bentall group (0 in the VSRR group; p = 0.54). Permanent pacemaker rate was 6% (n = 7) in the Bentall group (0 in the VSRR group; p = 0.2). On discharge echocardiography, AI grade ≤ 1+ (100%; p = 1) and transvalvular gradients (mean gradient 7 ± 3 versus 6 ± 3 mm Hg; p = 0.14) were similar. Mean follow-up was 7.5 ± 3.2 and 3.4 ± 2.9 years (p < 0.001). There were 14 transient ischemic attacks or stroke events in the Bentall group, and none in the VSRR group. One patient in each group exhibited AI ≥ 3+. Five-year actuarial survival (100% versus 98% ± 2%; p = 0.8) and freedom from aortic reoperation (98% ± 2% versus 100%; p = 0.8) were similar. In patients with bicuspid aortic valve AI with root aneurysm, primary cusp repair with root reimplantation achieves equivalent midterm outcomes compared with Bentall root replacement.


The protective role of parsley extract against vincristine mutagenicity in Drosophila melanogaster.
In this study, Drosophila melanogaster males were treated with parsley plant extract and the anticancer drug vincristine (VCR) singly and in combined treatments (pre, co and post-treatments) to detect the mutagenic effects by using sex-linked recessive lethal test (SLRL) and estimation of cholinesterase enzyme (ChE) activities in order to compare the sensitivity of the two test systems. A wild type strain Oregon-R (Or-R) male flies of D. melanogaster were reared on a medium containing one concentration of each of VCR and parsley (4 ml/100 ml medium) in each single and combined treatment. Also the activity of ChE was estimated in some insects of the two generations: F1 females, F2 bar eye females (heterozygous) and F2 wild types males. The results indicate that both of parsley and vincristine did not cause significant increases of SLRL test in either the single or combined treatments. In contrast, estimation of ChE activities showed significant increase in all the broods within single and combination treatments, except female of the second generation of spermatid brood which treated with parsley and VCR at the same time. It is concluded that enzyme estimation is more sensitive than SLRL test for detection the mutagenic effect for parsley's extract and vincristine.


1, 5-Bis (2-hydroxyacetophenone)thiocarbohydrazone: a novel colorimetric and fluorescent dual-mode chemosensor for the recognition of fluoride.
1,5-Bis (2-hydroxyacetophenone)thiocarbohydrazone (H4L) has been synthesized and characterized by means of spectroscopic and single crystal X-ray diffraction methods. Interactions of the H4L with a variety of anions were investigated using a combination of UV-visible and fluorescence spectroscopic methods in a biological competing solvent DMSO. The H4L has a high degree of selectivity for fluoride over other anions. (1)H NMR titration experiments indicate that a deprotonation process is involved in the chemo sensing process.


[A protocol for monitoring antimalarial treatment].
We are showing a protocol to survey the treatment by APS, with a computer equipment that enable us to examine very shortly the central field of vision and the ERG; but that least investigation can be EOG or a PEV, according to the toxic pathology we are studying.


Surgical management of endometriosis to optimize fertility.
Surgery is an integral element of treatment for infertility caused by endometriosis. This review summarizes the purported mechanisms of infertility in endometriosis, as well as the impacts of surgery for endometriosis on fertility, including pregnancy achieved spontaneously and with assisted reproductive technology (ART). Endometriosis' effect on fertility is multifactorial. The sequela of increased inflammation resulting from endometriosis causes alterations in ovarian, tubal, and uterine function. Removing or destroying these lesions reduces inflammation. Surgical treatment of both early-stage endometriosis and deeply infiltrating endometriosis improves spontaneous pregnancy rates and ART pregnancy rates. Conventional or robotic laparoscopy is the preferred surgical approach. Endometriosis has detrimental effects on fertility, including negative impacts on oocyte, tubal, and endometrial function. Laparoscopic surgery for endometriosis elevates both spontaneous and ART pregnancy rates above those achieved with expectant management alone. The resection or destruction of endometriosis implants reduces inflammation, which likely improves the multifactorial infertility related to endometriosis. This topic is complex and controversial; more research in the form of high-quality randomized control trials is needed.


Serrated polyposis syndrome; epidemiology and management.
Serrated colorectal polyps, long considered innocent, are currently recognized as the precursors to one-third of all colorectal cancers (CRC). Serrated polyposis syndrome (SPS), characterized by accumulation of multiple and/or large serrated polyps, symbolizes the highest expression of serrated pathway of carcinogenesis, leading to a high risk of CRC when it is not detected or treated on time. Although previously considered uncommon, SPS is now acknowledged as the most prevalent colorectal polyposis. This syndrome has attracted increasing interest over the past decade and has become a hot topic in the field of gastrointestinal oncology. Besides a small proportion of cases caused by germline mutations in RNF43, no clear genetic cause has been identified. Both epigenetic and environmental factors, especially smoking, have been related to this syndrome, but the etiology of SPS remains uncertain and diagnosis is based on endoscopic criteria. Recent studies on SPS have focused on identifying the underlying risk-factors for CRC, defining the best endoscopic techniques for surveillance and establishing optimal preventive strategies aimed at reducing CRC-incidence without exposing patients to unnecessary procedures. The purpose of this chapter is to review, from a practical perspective, current knowledge and future directions in the diagnosis and management of serrated polyposis syndrome.


Regional differences in the delayed rectifier current (IKr and IKs) contribute to the differences in action potential duration in basal left ventricular myocytes in guinea-pig.
To compare the properties of single myocytes isolated from different layers of the basal region of the left ventricle and to test the hypothesis that differences in the delayed rectifier current (IK) contribute to regional differences in action potential duration. Myocytes were isolated from basal sub-endocardial, mid-myocardial and sub-epicardial layers of the guinea-pig left ventricle. Membrane voltage and current were measured using the switch-clamp technique. Mean action potential duration measured at 90% repolarisation (APD90) was longer in sub-endocardial myocytes than in mid-myocardial and sub-epicardial myocytes [APD90 ms at 0.2 Hz: sub-endocardial 292 +/- 12 (n = 40), mid-myocardial 243 +/- 8 (n = 42) and sub-epicardial 227 +/- 9 (n = 36), P < 0.001, analysis of variance (ANOVA)]. The APD-rate relationship (stimulation frequencies 2, 1, 0.2 and 0.017 Hz) was steeper in sub-endocardial than in mid-myocardial or sub-epicardial myocytes (P < 0.001, ANOVA). The density of IK was greater in mid-myocardial (4.05 +/- 0.09 pA pF-1) and sub-epicardial (3.90 +/- 0.41 pA pF-1) than in sub-endocardial myocytes (2.74 +/- 0.27 pA pF-1, P < 0.01 ANOVA). The rapidly-activating (IKr) and slowly-activating (IKs) components of IK were significantly smaller in sub-endocardial than in mid-myocardial or sub-epicardial myocytes. D,L-Sotalol-induced prolongation of APD90 was similar in the three regions studied. There are significant transmural gradients in the electrophysiological properties of myocytes isolated from the base of the left ventricular free wall in guinea-pig. Sub-endocardial myocytes had a longer APD90 attributable in part to a significantly smaller IK density. We have been unable to identify M cells in the guinea-pig left ventricular free wall.


On a new trematode, Prohemistomum azimi n. sp. (Trematoda: Cyathocotylidae) from the Egyptian slit-faced bat.
Prohemistomum azimi n. sp. is described from one out of four Egyptian slit-faced bats, Nycteris thebaica Geffroy, 1910 captured from Giza, Egypt. The new species is compared with other related species of the genus and its specific diagnosis is outlined. The new species is the first record of the genus Prohemistomum Odhner, 1913 from Chiroptera.


Renal formulas pretreated with medications alters the nutrient profile.
Pretreating renal formulas with medications to lower the potassium and phosphorus content is common in clinical practice; however, the effect of this treatment on other nutrients is relatively unstudied. We examine whether nutrient composition is affected by pretreating renal formulas with sodium polystyrene sulfonate (SPS) suspension and sevelamer carbonate. Fixed medication doses and treatment times were utilized to determine changes in the nutrient composition of Suplena® and Similac® PM 60/40. The effect of simultaneously adding both medications (co-administration) to the formula on the nutrient composition of Suplena® was also evaluated. Pretreatment of Suplena® with SPS reduced the concentrations of calcium (11-38 %), copper (3-11 %), manganese (3-16 %), phosphorus (0-7 %), potassium (6-34 %), and zinc (5-20 %) and increased those of iron (9-34 %), sodium (89-260 %), and sulfur (19-45 %) and the pH (0.20-0.50 units). Pretreatment of Similac® PM 60/40 with SPS reduced the concentrations of calcium (8-29 %), copper (5-19 %), magnesium (3-26 %), and potassium (33-63 %) and increased those of iron (13-87 %) and sodium (86-247 %) and the pH (0.40-0.81 units). Pretreatment of both formulas with the SPS suspension led to significant increases in the aluminum concentration in both formulas (507-3957 %). No differences in potassium concentration were observed between treatment times. Unexpectedly, the levels of neither phosphorus nor potassium were effectively reduced in Suplena® pretreated with sevelamer carbonate alone or when co-administered with SPS. Pretreating formula with medications alters nutrients other than the intended target(s). Future studies should be aimed at predicting the loss of these nutrients or identifying alternative methods for managing serum potassium and phosphorus levels in formula-fed infants. The safety of pretreating formula with SPS suspension should also be examined.


Chronic pruritus--pathogenesis, clinical aspects and treatment.
Chronic pruritus is a major symptom in numerous dermatological and systemic diseases. Similar to chronic pain, chronic pruritus can have a dramatic impact on the quality of life and can worsen the general condition of the patient considerably. The pathogenesis of itch is diverse and involves a complex network of cutaneous and neuronal cells. In recent years, more and more itch-specific mediators and receptors, such as interleukin-31, gastrin-releasing peptide receptor or histamine H4 receptor have been identified and the concept of itch-specific neurons has been further characterized. Understanding of the basic principles is important for development of target-specific treatment of patients with chronic pruritus. In this review, we summarize the current knowledge about the pathophysiological principles of itch and provide an overview about current and future treatment options.


Effects of Exercise Programs on Functional Capacity and Quality of Life in People With Acquired Brain Injury: A Systematic Review and Meta-Analysis.
The aims of this systematic review and meta-analyses were to evaluate the effects of exercise on the functional capacity and quality of life (QoL) of people with acquired brain injury (ABI) and to analyze the influence of training variables. Five electronic databases (MEDLINE, Cochrane Library, CINAHL, SportDiscus, and Web of Science) were searched until October 2021 for clinical trials or experimental studies examining the effects of exercise on the functional capacity and QoL in adults with ABI and comparing exercise interventions with non-exercise (usual care). Thirty-eight studies were evaluated. A total sample of 2219 people with ABI (exercise, n = 1572; control, n = 647) were included in the quantitative analysis. A greater improvement was observed in walking endurance (z score = 2.84), gait speed (z score = 2.01), QoL physical subscale (z score = 3.42), and QoL mental subscale (z score = 3.00) was observed in the experimental group than in the control group. In addition, an improvement was also observed in the experimental group in the "Timed Up and Go" Test scores and balance without differences from the control group. Significant interactions were also observed between the rehabilitation phases, type, frequency and volume of training, and overall effects. The results suggest that exercise improves functional capacity and QoL regardless of model training, highlighting the effectiveness of long-term exercise that includes short sessions with components such as strength, balance, and aerobic exercise. The results shown in this systematic review with meta-analysis will allow physical therapists to better understand the effects of training on people with ABI.


Electrocardiographic biomarkers of ventricular repolarisation in a single family of short QT syndrome and the role of the Bazett correction formula.
The definition of the short QT syndrome (SQTS) is based on QT duration, but thorough QT- and T-wave evaluation has not been performed to date. To evaluate the influence of QT rate-correction formulas in SQTS diagnosis, 12-lead electrocardiograms (ECGs) were recorded in 27 subjects from a single family with SQTS. Based on QT duration corrected by Bazett formula (QTc), 4 men were considered to have SQTS (QTc <or=340 ms), and 16 were classified to have "suspected" SQTS (QT <or=320 ms and/or QTc <or=380 ms). Holter ECGs were recorded in the 4 patients with SQTS, 8 with suspected SQTS, and 62 healthy volunteers. We evaluated QT duration at each RR interval and calculated individual alpha coefficient of the QT/RR relation. The QT interval duration at the mean Holter heart rate was corrected using an individual approach and 5 "universal" correction formulas (Bazett, Fridericia, Sagie-Framingham, Hodges, Rautaharju). Patients with SQTS and controls had lower alpha coefficients of the QT/RR relation when compared with Bazett and Fridericia formulas. The QT rate-dependence was lower in patients with SQTS (alpha 0.146 +/- 0.070) when compared with control subjects (alpha 0.203 +/- 0.039, p <0.05). The universal correction-formulas consistently provided higher values of corrected QT interval duration at the mean Holter heart rate than a subject-specific correction formula (p <0.05), which induced false negative diagnoses. In conclusion, the Bazett correction formula is not appropriate for making a diagnosis of SQTS. The subject-specific correction formula may provide a better cut-off value definition for the diagnosis of SQTS.


Trainee participation does not adversely affect the safety of thyroid surgery: Systematic review and meta-analysis.
Surgical traineeship is essential but must be safe for patients. In thyroid surgery, surgeon volume correlates with improved clinical/economic outcomes. However, it is presently unclear how far does trainee participation affect post-thyroidectomy complication rates in real-world and randomized data. We systematically searched four databases for associations of trainee participation with any post-thyroidectomy outcome. We conducted univariate meta-analyses, sensitivity analyses, and assessed publication bias qualitatively and quantitatively. We included 1 randomized and 15 observational studies from 3755 records, comprising 34 774 thyroid surgical patients. Trainee participation was associated with 12 min longer operative time, but not higher complication rates (hypoparathyroidism, recurrent laryngeal nerve palsy, hematoma, blood loss, return to operating room, hospitalization duration, readmission, and mortality). Sensitivity, publication bias, and multivariate analyses did not change our findings. Real-world and limited randomized data suggest that trainee participation in thyroid surgery is safe, given adequate consultant supervision and appropriate case selection.


Underweight children older than 5 years with sickle cell anemia are at risk for early mortality in a low-resource setting.
Undernutrition is a risk factor for under-5 mortality and is also postulated to be a risk factor for mortality in older children and adults with sickle cell anemia (SCA). We tested the hypothesis that underweight is associated with mortality in children aged 5 to 12 years with SCA. We performed a secondary analysis of participants in the Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria trial, a double-blind, parallel-group randomized controlled trial for low-dose or moderate-dose hydroxyurea in children with abnormal transcranial Doppler velocities and a comparison group of participants with nonelevated transcranial Doppler velocities in northern Nigeria. Nutritional status was classified as underweight (weight-for-age z score), stunting (height-for-age z score), and wasting (body mass index z score) using the World Health Organization growth reference. The mean weight-for-age z score was lower in children who died during the study than in those who survived. Otherwise, the baseline characteristics of children who died during the study were not significantly different from those of the children who survived. A pooled analysis of participants demonstrated that a lower weight-for-age z score was associated with an increased hazard of death. Underweight participants (weight-for-age z score <-1) had a greater probability of death during follow-up than those who were not underweight. Underweight status in school-aged children with SCA is a previously unrecognized risk factor for early mortality in Nigeria and can be easily applied to screen children at risk for death. This trial was registered at www.clinicaltrials.gov as #NCT02560935.


Comparing donor site morbidity in osteocutaneous radial forearm versus fibula free flap for mandibular reconstruction.
The osteocutaneous radial forearm free flap has gained popularity as a less morbid option for oromandibular reconstruction compared to the fibular free flap. However, there is a paucity of data regarding direct outcome comparison between these techniques. Retrospective chart review of 94 patients who underwent maxillomandibular reconstruction intervened from July 2012-October 2020 at the University of Arkansas for Medical Sciences. All other bony free flaps were excluded. Endpoints retrieved encompassed demographics, surgical outcomes, perioperative data, and donor site morbidity. Continuous data points were analyzed using independent sample t-Tests. Qualitative data was analyzed using Chi-Square tests to determine significance. Ordinal variables were tested using the Mann-Whitney U test. The cohort was equally male and female, with a mean age of 62.6 years. There were 21 and 73 patients in the osteocutaneous radial forearm free flap and fibular free flap cohorts, respectively. Excluding age, the groups were otherwise comparable, including tobacco use, and ASA classification. Bony defect (OC-RFFF = 7.9 cm, FFF = 9.4 cm, p = 0.021) and skin paddle (OC-RFFF = 54.6 cm2, FFF = 72.21 cm2, p = 0.045) size were larger in the fibular free flap group. However, no significant difference was found between cohorts with respect to skin graft. There was no statistically significant difference between cohorts regarding the rate of donor site infection, tourniquet time, ischemia time, total operative time, blood transfusion, or length of hospital stay. No significant difference in perioperative donor site morbidity was found between patients undergoing fibular forearm free flap and osteocutaneous radial forearm flap for maxillomandibular reconstruction. Osteocutaneous radial forearm flap performance was associated with significantly older age, which may represent a selection bias.


Prognosis Prediction in Initially Diagnosed Multiple Myeloma Patients Using Intravoxel Incoherent Motion-Diffusion Weighted Imaging and Multiecho Dixon Imaging.
Multiparametric MRI provides complementary information for the diagnosis and management of multiple myeloma (MM). To evaluate the association of prognostic factors of MM and parameters derived from intravoxel-incoherent motion diffusion-weighted imaging (IVIM-DWI) and multiecho (ME) Dixon. Retrospective. In all, 78 MM patients. T1 -weighted turbo spin-echo sequences (TSE), IVIM-DWI, ME 3D gradient echo sequence with multistep adaptive fitting at 3T. The region of interest (ROI) on the vertebral body was independently measured on four parametric maps (Dslow , Dfast and perfusion fraction [f], and proton-density fat-fraction [Ff] maps) by two readers. All patients were categorized into three groups based on the International Staging System (ISS). Three groups were compared using analysis of variance (ANOVA) and post-hoc tests with Bonferroni correction. Logistic regression analysis was performed to predict the advancement of disease (early vs. advanced). Principal component analysis (PCA) was used to find the deterministic parameters. Dslow and Ff were significantly different among ISS-1 (n = 38), ISS-2 (n = 22), and ISS-3 (n = 18) groups in both readers: 0.36, 0.41, and 0.58 × 10-3 mm2 /s for Dslow (P < 0.05), and 46%, 30%, and 15% for Ff (P < 0.05) in reader 1; 0.34, 0.41, and 0.58 × 10-3 mm2 /s for Dslow (P < 0.05), 43%, 27%, and 13.2% for Ff (P < 0.05) in reader 2, respectively. Dfast between ISS-3 and the other groups was significantly different in one reader only: 2.03, 2.29, and 2.85 × 10-3 mm2 /s (P < 0.05). There was no significant difference in f among the groups in both readers. Logistic regression by stepwise selection indicated Ff as the single most significant factor for differentiating early and advanced stages of MM with an accuracy of 76% and area under the curve (AUC) of 0.83 (P < 0.05). PCA revealed Ff, and Dslow as the deterministic parameters, with a cumulative proportion of 0.84. D slow and Ff are associated with the prognostic factor of MM. Level of Evidence 3 Technical Efficacy Stage 5. J. MAGN. RESON. IMAGING 2021;53:491-501.


Cross-correlation between vagal afferent impulses from pulmonary mechanoreceptors and high-frequency inflation (HFI) and deflation (HFD) in rabbits.
The effects of high-frequency airway inflation (HFI) and high-frequency airway deflation (HFD) generated by a triangular pressure pulse generator on pulmonary mechanoreceptors were examined. The cross-correlograms between vagal afferent impulses from the slowly adapting (SAR) and the rapidly adapting receptors (RAR) and the HFI or the HFD pulses were analysed. HFI stimulated SAR and RAR and HFD stimulated RAR, but inhibited SAR. The time lag of the mode in the correlogram between SAR and HFI was shorter than that of the mode in the correlogram between RAR and HFI. The span of the mode and the trough of SAR was shorter than the span of the mode of RAR. This may indicate that the time to peak of the generator potential of RAR is longer than that of SAR.


Catalytic hydrothermal treatment of pulping effluent using a mixture of Cu and Mn metals supported on activated carbon as catalyst.
The present study was performed to investigate the performance of activated carbon-supported copper and manganese base catalyst for catalytic wet oxidation (CWO) of pulping effluent. CWO reaction was performed in a high pressure reactor (capacity = 0.7 l) at temperatures ranging from 120 to 190 °C and oxygen partial pressures of 0.5 to 0.9 MPa with the catalyst concentration of 3 g/l for 3 h duration. With Cu/Mn/AC catalyst at 190 °C temperature and 0.9 MPa oxygen partial pressures, the maximum chemical oxygen demand (COD), total organic carbon (TOC), lignin, and color removals of 73, 71, 86, and 85 %, respectively, were achieved compared to only 52, 51, 53, and 54 % removals during the non-catalytic process. Biodegradability (in terms of 5-day biochemical oxygen demand (BOD5) to COD ratio) of the pulping effluent was improved to 0.38 from an initial value of 0.16 after the catalytic reaction. The adsorbed carbonaceous fraction on the used catalyst was also determined which contributed meager TOC reduction of 3-4 %. The leaching test showed dissolution of the metals (i.e., Cu and Mn) from the catalysts in the wastewater during CWO reaction at 190 °C temperature and 0.9 MPa oxygen partial pressures. In the future, the investigations should focus on the catalyst reusability.


Neonatal bacterial meningitis.
Neonatal meningitis contributes substantially to neurological disability worldwide. Its incidence remains low but is significantly higher in neonates with documented sepsis, preterm infants, and when meningitis is nosocomial. Neonates are at higher risk of meningitis because of immaturity in humoral and cellular immunity, and the absence of specific clinical signs makes diagnosis of meningitis more difficult in neonates than in older children. Neonatal meningitis remains, therefore, a public health challenge for pediatricians. Mortality and long-term complications in survivors are observed in 10-15% and 20-50%, respectively, depending on term at diagnosis, type of identified organisms, and delay before treatment. Neurological deficits range from moderate-to-severe disabilities to more subtle problems including visual deficits, middle-ear disease, and cognitive and behavioral impairments. Intracerebral complications should be documented using magnetic resonance imaging. Treatment should be initiated once the diagnosis is suspected using a parenteral combination of bactericidal antibiotics adapted to pathogen sensitivity.


Use of an 8(1)3(2) asymmetrical factorial design for the in vitro evaluation of ondansetron permeation through human epidermis.
The in vitro permeation of ondansetron through human cadaver epidermis, as a preliminary step toward the development of a transdermal therapeutic system, was investigated. In vitro release studies were carried out using modified Franz diffusion cells and human epidermis, taken from cadaver skin by heat separation technique. To estimate the effect of the type and concentration of the penetration enhancers and the skin from different donors, an 8(1)3(2) asymmetrical factorial design was used. Formulations containing lauric acid and oleic acid as penetration enhancers, showed the largest Q values [amounts of ondansetron permeated per unit area of epidermal membrane (microg/cm2)] at 24, 48, and 72 hr, as well as steady-state flux values, among all formulations tested. The other enhancers increased the flux in the following order: lauryl alcohol>glycerol monooleate>Azone >cineole>oleyl alcohol>1-methyl-2-pyrrolidinone. Moreover, the concentration of the penetration enhancer and the type of the skin were proved to significantly affect the permeation rate of ondansetron through human epidermis. From the results obtained, it was shown that the formulations containing lauric acid or oleic acid at 5% or 10% could increase sufficiently the permeation of ondansetron. Therefore, the transdermal administration of ondansetron seems feasible.


Rapid leaf decay and nutrient release in a chinese tallow forest.
The Chinese tallow tree, Sapium sebiferum, was introduced to the Texas Gulf Coast in the early 1900's and has spread into coastal prairie habitats. Since coastal prairie contains few deciduous trees, we studied leaf fall dynamics, rate of decomposition, and the quantity and rate of nutrient input from decomposing tallow leaves. Among-year leaf fall averaged 382.6 g·m-2·yr-1, similar to other south temperat deciduous forests and about as predicted by Meentemeyer et al.'s (1982) AE-lignin model. Decay of tallow leaves (k=-4.33) was much more rapid than native black willow (k=-0.35) and than other temperate deciduous trees (k=-0.77). The ratio of lignin to initial nitrogen concentration, highly correlated with rate of decomposition for hardwood trees, was low for Chinese tallow and may contribute to rapid leaf decay. Taking AE and lignin content into account, Meentemeyer's (1984) model predicted k=-1.39 for Chinese tallow and k=-0.88 for black willow. Decay of tallow was much faster but decay of willow was slower than predicted, suggesting that decay on the coastal prairie may be controlled by factors other than lignin content and climate. N, P, and K characteristically accumulate as leaves decay. However, these elements did not accumulate as tallow leaves decayed, possibly because high densities of Armadillidium vulgare, a detritivore, reduced immobilization of elements by microbes. This would result in increased turnover of these elements. Accumulation of Al, Fe, Zn, and S in decaying tallow litter may be related to flood-drain cycles on coastel prairie clay soils. Ca, N, K, Mg, and S were added to forest soil in greatest amounts from decaying tallow leaves. Concentrations of P, K, NO3-N, Zn, Mn, and Fe were significantly higher and Mg and Na were significantly lower in forest than in prairie soil, raising the possibility that Chinese tallow trees altered the distribution of nutrients in the soil profile. We conclude that the Chinese tallow tree may enhance productivity in ecosystems to which it has been introduced by addition of nutrients from rapid decay of leaves.


Histological study of PIVKA-II expression in hepatocellular carcinoma and adenomatous hyperplasia.
Although serum concentration of protein induced vitamin K absence or antagonist II (PIVKA-II) has been widely used for diagnosing hepatocellular carcinoma (HCC), little information is available concerning tissue PIVKA-II as an immunohistochemical marker for liver histology. In this study, we examined the expression of PIVKA-II in precancerous nodules (adenomatous hyperplasia) and various differentiation grades of HCC by immunohistochemical study using the monoclonal anti-PIVKA-II antibody (MU-3). We examined the relationship between tissue PIVKA-II staining and serum PIVKA-II level, tumor histology and tumor size. PIVKA-II was mainly detected in the cytoplasm of the HCC cells. The positive rates of PIVKA-II were as follows: adenomatous hyperplasia (AH), 0% (0/9); well-differentiated HCC, 65% (15/23); moderately differentiated HCC, 85% (22/26); poorly differentiated HCC, 54% (7/13). The expression of tissue PIVKA-II staining in moderately differentiated HCC was significantly higher than in well- or poorly differentiated HCC, whereas the serum PIVKA-II level in poorly differentiated HCC was higher than well- or moderately differentiated HCC. There was no relationship between the expression of PIVKA-II in cancer tissues and serum levels of PIVKA-II. Immunohistochemical studies revealed that PIVKA-II was expressed even in small-sized or well-differentiated HCC cells, but expression was not detected in AH. It was concluded that PIVKA-II is a useful immunohistochemical marker, even in small-sized or well-differentiated HCC.


Transcriptomic analysis of submergence-tolerant and sensitive Brachypodium distachyon ecotypes reveals oxidative stress as a major tolerance factor.
When excessive amounts of water accumulate around roots and aerial parts of plants, submergence stress occurs. To find the integrated mechanisms of tolerance, we used ecotypes of the monocot model plant Brachypodium distachyon to screen for genetic material with contrasting submergence tolerance. For this purpose, we used a set of previously studied drought sensitive/tolerant ecotypes and the knowledge that drought tolerance is positively associated with submergence stress. We decided to contrast aerial tissue transcriptomes of the ecotype Bd21 14-day-old plants as sensitive and ecotype Bd2-3 as tolerant after 2 days of stress under a long-day photoperiod. Gene ontology and the grouping of transcripts indicated that tolerant Bd2-3 differentially down-regulated NITRATE REDUCTASE and ALTERNATIVE OXIDASE under stress and constitutively up-regulated HAEMOGLOBIN, when compared with the sensitive ecotype, Bd21. These results suggested the removal of nitric oxide, a gaseous phytohormone and concomitant reactive oxygen species as a relevant tolerance determinant. Other mechanisms more active in tolerant Bd2-3 were the pathogen response, glyoxylate and tricarboxylic acid cycle integration, and acetate metabolism. This data set could be employed to design further studies on the basic science of plant tolerance to submergence stress and its biotechnological application in the development of submergence-tolerant crops.


Effect of chitosan irrigant solutions on the release of bioactive proteins from root dentin.
To identify the effect of two chitosan solutions on the release of root dentin matrix proteins and to describe the chemical changes observed following conditioning with chelating agents. The release of dentin sialoprotein (DSP), transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-BB (PDGF-BB) with different chelating agents, including ethylenediaminetetraacetic acid (EDTA), chitosan solution (CS), and nanoparticulate chitosan (CSnp), was investigated. DSP was quantified using an enzyme-linked immunosorbent assay (ELISA). TGF-β1, VEGF, and PDGF-BB were quantified using a cytokine bead panel (CBA). Raman spectroscopy was performed to identify surface chemical changes. Statistical analysis was performed using Kruskal-Wallis test with Mann-Whitney-Wilcoxon rank-sum test (p < 0.05). TGF-β1, VEGF, and DSP solubilized in all irrigants tested. CSnp showed the highest concentration of DSP. PDGF-BB did not exceed the detection limits. Raman spectroscopy revealed a decrease in the phosphate and carbonate peaks, representing the chelating effect of EDTA, CS, and CSnp. Additionally, CSnp showed the greatest preservation of the amide I and III content. Proteins can be released from dentin via EDTA, CS, and CSnp conditioning. Raman spectroscopic revealed changes in the inorganic content of the root dentin after chelation. Furthermore, use of CSnp facilitated a preservation of the organic content. Chelation allows the release of proteins, justifying the use of chelating agents in regenerative endodontics. The chitosan-dentin matrix interaction also promotes the protection of the organic content as an additional benefit to its protein releasing effect.


A novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-PD-1 therapy.
In this study, we investigated the immune-modulating effects of a novel metronomic chemotherapy (MCT) featuring combined oral oxaliplatin (OXA) and pemetrexed (PMX) for colon cancer. OXA and PMX were ionically complexed with lysine derivative of deoxycholic acid (DCK), and incorporated into nanoemulsions or colloidal dispersions, yielding OXA/DCK-NE and PMX/DCK-OP, respectively, to improve their oral bioavailabilities. MCT was not associated with significant lymphotoxicity whereas the maximum tolerated dose (MTD) afforded systemic immunosuppression. MCT was associated with more immunogenic cell death and tumor cell MHC-class I expression than was MTD. MCT improved the tumor antigen presentation of dendritic cells and increased the number of functional T cells in the tumor. MCT also helped to enhance antigen-specific memory responses both locally and systemically. By combining MCT with anti-programmed cell death protein-1 (αPD-1) therapy, the tumor volume was suppressed by 97.85 ± 84.88% compared to the control, resulting in a 95% complete response rate. Upon re-challenge, all tumor-free mice rejected secondary tumors, indicating the induction of a tumor specific memory response. Thus, MCT using an OXA and PMX combination, together with αPD-1, successfully treated colon cancer by activating both innate and adaptive immune cells and elicited tumor-specific long-term immune memory while avoiding toxicity caused by MTD treatment.


Progesterone protects normative anxiety-like responding among ovariectomized female mice that conditionally express the HIV-1 regulatory protein, Tat, in the CNS.
Increased anxiety is co-morbid with human immunodeficiency virus (HIV) infection. Actions of the neurotoxic HIV-1 regulatory protein, Tat, may contribute to affective dysfunction. We hypothesized that Tat expression would increase anxiety-like behavior of female GT-tg bigenic mice that express HIV-1 Tat protein in the brain in a doxycycline-dependent manner. Furthermore, given reports that HIV-induced anxiety may occur at lower rates among women, and that the neurotoxic effects of Tat are ameliorated by sex steroids in vitro, we hypothesized that 17β-estradiol and/or progesterone would ameliorate Tat-induced anxiety-like effects. Among naturally-cycling proestrous and diestrous mice, Tat-induction via 7days of doxycycline treatment significantly increased anxiety-like responding in an open field, elevated plus maze and a marble-burying task, compared to treatment with saline. Proestrous mice demonstrated less anxiety-like behavior than diestrous mice in the open field and elevated plus maze, but these effects did not significantly interact with Tat-induction. Among ovariectomized mice, doxycycline-induced Tat protein significantly increased anxiety-like behavior in an elevated plus maze and a marble burying task compared to saline-treated mice, but not an open field (where anxiety-like responding was already maximal). Co-administration of progesterone (4mg/kg), but not 17β-estradiol (0.09mg/kg), with doxycycline significantly ameliorated anxiety-like responding in the elevated plus maze and marble burying tasks. When administered together, 17β-estradiol partially antagonized the protective effects of progesterone on Tat-induced anxiety-like behavior. These findings support evidence of steroid-protection over HIV-1 proteins, and extend them by demonstrating the protective capacity of progesterone on Tat-induced anxiety-like behavior of ovariectomized female mice.


Synthetic microvascular networks for quantitative analysis of particle adhesion.
We have developed a methodology to study particle adhesion in the microvascular environment using microfluidic, image-derived microvascular networks on a chip accompanied by Computational Fluid Dynamics (CFD) analysis of fluid flow and particle adhesion. Microfluidic networks, obtained from digitization of in vivo microvascular topology were prototyped using soft-lithography techniques to obtain semicircular cross sectional microvascular networks in polydimethylsiloxane (PDMS). Dye perfusion studies indicated the presence of well-perfused as well as stagnant regions in a given network. Furthermore, microparticle adhesion to antibody coated networks was found to be spatially non-uniform as well. These findings were broadly corroborated in the CFD analyses. Detailed information on shear rates and particle fluxes in the entire network, obtained from the CFD models, were used to show global adhesion trends to be qualitatively consistent with current knowledge obtained using flow chambers. However, in comparison with a flow chamber, this method represents and incorporates elements of size and complex morphology of the microvasculature. Particle adhesion was found to be significantly localized near the bifurcations in comparison with the straight sections over the entire network, an effect not observable with flow chambers. In addition, the microvascular network chips are resource effective by providing data on particle adhesion over physiologically relevant shear range from even a single experiment. The microfluidic microvascular networks developed in this study can be readily used to gain fundamental insights into the processes leading to particle adhesion in the microvasculature.


Regulation of vascular smooth muscle cell growth by endothelial-synthesized extracellular matrices.
Previous work has demonstrated that aortic endothelial cells (EC) produce a heparin-like inhibitor of smooth muscle cell (SMC) growth when both cell types were cultured on plastic. We have now tested the influence of the extracellular matrix on this EC-SMC interaction. Specifically, we examined: 1) the role of different substrates (plastic, fibronectin, monomeric, and fibrillar collagens I and III, and EC-derived matrices) on the growth rate and population density of SMC; 2) the heparin-sensitivity of SMC on these diverse substrates; and 3) the effect of these same substrates on EC ability to secrete heparin-like and polypeptide inhibitors of SMC growth. SMC demonstrated a sixfold difference in sensitivity to heparin when grown on different substrates, with the following rank order: EGTA matrix greater than collagens = plastic = fibronectin greater than deoxycholic acid (DOC) matrix. Maximally, we found a 10-fold difference in the potency of the inhibitory activity secreted by EC grown on different substrates, with the following order: plastic = EGTA matrix greater than fibronectin greater than collagens = DOC matrix. Treatment of the conditioned mediums with heparinase and trypsin indicated that 58% to 76% of the inhibitory activity was due to heparin-like species, and 24% to 42% was due to protein(s). When EC cultured on EGTA matrix are compared to those pleated on DOC matrix, the potency of the heparin-like and peptide inhibitory activities increased 8- and 17-fold, respectively. Hypothetically, one would predict a 60-fold change in the potency of the antiproliferative effect if the contributions of substrate to EC production of inhibitors and SMC sensitivity were additive.(ABSTRACT TRUNCATED AT 250 WORDS)


Prenatal ultrasound, magnetic resonance imaging and therapeutic options for fetal thoracic anomalies: a pictorial essay.
Congenital thoracic anomalies are uncommon malformations that require a precise diagnosis to guide parental counseling and possible prenatal treatment. Prenatal ultrasound (US) is the gold standard imaging modality to first detect and characterize these abnormalities and the best modality for follow-up. Fetal magnetic resonance imaging (MRI) is a complementary tool that provides multiplanar assessment and tissue characterization and can help estimate prognosis. Prenatal treatment is increasingly being used in fetuses with signs of distress and to potentially decrease morbidity and mortality. In this essay, the authors illustrate side-by-side US, MRI and therapeutic options for congenital thoracic anomalies in cases that presented to a tertiary pediatric hospital during the 7-year period 2014-2021. Entities included are congenital diaphragmatic hernia, congenital pulmonary airway malformation, bronchopulmonary sequestration, hybrid lesions, foregut duplications cysts and congenital lobar overinflation. Treatment options include maternal steroids, thoraco-amniotic shunt and fetal endotracheal occlusion. Recognition of typical findings in congenital thoracic anomalies is helpful to establish diagnosis, predict prognosis and plan perinatal treatment.


[Significance of biochemical examination of the bile in the early diagnosis of chronic diseases of the biliary tract].
Three groups of subjects were examined without complaints characteristic of involvement of the hepatobiliary system. In 11% of healthy persons disorders of the biochemical composition of bile were revealed, namely reduction of the level of bile acids and phospholipids, 23% changes in the ratio of bile acids and phospholipid fractions.


(2E)-3-(4-Fluoro-phen-yl)-1-[5-methyl-1-(4-methyl-phen-yl)-1H-1,2,3-triazol-4-yl]prop-2-en-1-one.
With respect to the triazole ring in the title compound, C19H16FN3O, the p-tolyl ring is inclined [dihedral angle = 51.79 (11)°], whereas the chalcone residue is almost coplanar [O-C-C-N and C-C-C-C torsion angles = -178.71 (19) and 178.42 (18)°, respectively]. The conformation about the C=C bond [1.328 (3) Å] is E, and the triazole methyl group and the carbonyl O atom are syn. In the crystal, centrosymmetrically related mol-ecules are connected by π-π inter-actions between the triazole and p-tolyl rings [centroid-centroid distance = 3.6599 (12) Å] and these are linked into a three-dimensional architecture by C-H⋯N and C-H⋯π inter-actions.


Effects of laryngoscopy and tracheal intubation on cerebral and systemic haemodynamics in children under different protocols of anaesthesia.
The effects of laryngoscopy and tracheal intubation on cerebral and systemic haemodynamics were studied in 30 children. The objective was to identify conditions in which the alterations of cerebral and systemic haemodynamics were minimal. The children were intubated after muscular relaxation and following 10 min of mechanical ventilation with end-tidal halothane concentrations of 1.5%, 2.0% and 2.5%, respectively. With 1.5%, 2.0% and 2.5% end-tidal halothane, the mean flow velocity increased by 26%, 19% and 5%, the mean blood pressure by 14%, 10% and 1%, and the heart rate by 26%, 8% and 5% respectively after intubation. Adverse effects of laryngoscopy and tracheal intubation on cerebral haemodynamics in children can be avoided by adequate anaesthetic protocols.