Purification and characterization of an antimicrobial histone H1-like protein and its gene from the testes of olive flounder, Paralichthys olivaceus.
An approximately 21 kDa antimicrobial protein was purified from an acidified testis extract of olive flounder, Paralichthys olivaceus, by ion-exchange and C(18) reversed-phase HPLC. A comparison of the N-terminal amino acid sequence with those of other known antimicrobial polypeptides revealed high homology between this antimicrobial protein and other histone H1 molecules; thus, it was designated flounder histone H1-like protein (fH1LP). fH1LP showed potent antimicrobial activity against Gram-positive bacteria, including Bacillus subtilis, Staphylococcus aureus, and Streptococcus iniae (minimal effective concentrations [MECs], 2.8-30.0 μg/ml), Gram-negative bacteria, including Aeromonas hydrophila, Escherichia coli D31, Vibrio parahaemolyticus (MECs, 1.4-12.0 μg/ml), and Candida albicans (MEC, 2.0 μg/ml). cDNA cloning and tissue distribution studies of fH1LP indicated that it is constitutively expressed in testis and ovary. The fH1LP expression level was significantly dependent on developmental stage, and decreased dramatically after hatching. However, lipopolysaccharide stimulation did not induce fH1LP mRNA in other immune organs, including the kidney and spleen. These results suggest that fH1LP plays an important role in innate immunity in fish during reproduction, including mating, fertilization, and hatching.


Gravitational syndrome and tensile properties of skin in the elderly.
To evaluate the influence of gravitational edema due to chronic venous insufficiency upon the tensile properties of skin. A total of 30 women aged 66-75 years participated in the study. Evaluations were made twice in the same subjects following the use or nonuse of daytime elastic compression. Mechanical properties of the skin were measured in the midportion of the legs using a computerized suction device. The consistency of skin which shows abnormal rheological characteristics at the site of gravitational edema was significantly modified by compression therapy. Both skin extensibility and hysteresis were increased after wearing tight stockings although the biologic elasticity remained unchanged. Noninvasive measurements of the tensile properties of the skin represent an objective assessment of the severity of leg edema and of its correction by compression therapy.


Liquid Chromatography-Mass Spectrometry Analysis of Cytosine Modifications.
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a widely used technique in the global analysis of epigenetic DNA modifications. The high-resolution chromatographic separation along with sensitive MS detection permits the identification and quantification of deoxyribonucleosides with precision and reliability. Although there have been tremendous advances in LC and MS instrumentation in recent years, sample preparation has not experienced a similar rate of development and is often a bottleneck to chemical analysis. Here we present a protocol for identification and quantification of cytosine modifications that combines a robust and efficient method to generate single nucleosides from genomic DNA samples followed by direct LC-MS/MS analysis.


Biomarkers of disseminated intravascular coagulation in pediatric intensive care unit in Thailand.
Disseminated intravascular coagulation (DIC) is a systemic activation of hemostatic system caused by several causes. Biomarkers including antithrombin (AT), protein C (PC), and thrombomodulin (TM) were reported as the additional markers for DIC in adults. This study aimed to determine the association between biomarkers among patients with overt DIC (ODIC) and nonovert DIC (NDIC) in children in PICU. We enrolled 103 subjects, aged 1 month-18 years, who were admitted to PICU at Chiang Mai University (CMU) Hospital >24 hours with underlying conditions predisposing to DIC were enrolled. Biomarkers were tested after 24 hours of admission. Subject who had NDIC on the 1st investigations would have other tests on days 3-5 of admission. The incidence of ODIC by the International Society on Thrombosis and Hemostasis (ISTH) DIC score was found 24%. The bleeding, thrombosis, and death were significantly higher in ODIC group (P < 0.05). Mean levels of AT and PC in ODIC group were significantly different from NDIC one (66.9% vs 79.9%, P < 0.001 and 46.1% vs 59.2%, P = 0.004, respectively) while mean level of TM was not different between two groups. Adding AT to DIC score was better than the original score for predict mortality [area under curve (AUC) = 0.662 vs AUC = 0.65] and bleeding (AUC = 0.751 vs AUC = 0.732). ODIC is prevalent among critically ill children. Adverse outcomes were more commonly found in children with ODIC. AT and PC levels after 24 hours of PICU admission seem to be the useful biomarkers for ODIC in PICU.


A sweeter future: Using protein language models for exploring sweeter brazzein homologs.
With growing concerns over the health impact of sugar, brazzein offers a viable alternative due to its sweetness, thermostability, and low risk profile. Here, we demonstrated the ability of protein language models to design new brazzein homologs with improved thermostability and potentially higher sweetness, resulting in new diverse optimized amino acid sequences that improve structural and functional features beyond what conventional methods could achieve. This innovative approach resulted in the identification of unexpected mutations, thereby generating new possibilities for protein engineering. To facilitate the characterization of the brazzein mutants, a simplified procedure was developed for expressing and analyzing related proteins. This process involved an efficient purification method using Lactococcus lactis (L. lactis), a generally recognized as safe (GRAS) bacterium, as well as taste receptor assays to evaluate sweetness. The study successfully demonstrated the potential of computational design in producing a more heat-resistant and potentially more palatable brazzein variant, V23.


Probing CP symmetry and weak phases with entangled double-strange baryons.
Though immensely successful, the standard model of particle physics does not offer any explanation as to why our Universe contains so much more matter than antimatter. A key to a dynamically generated matter-antimatter asymmetry is the existence of processes that violate the combined charge conjugation and parity (CP) symmetry1. As such, precision tests of CP symmetry may be used to search for physics beyond the standard model. However, hadrons decay through an interplay of strong and weak processes, quantified in terms of relative phases between the amplitudes. Although previous experiments constructed CP observables that depend on both strong and weak phases, we present an approach where sequential two-body decays of entangled multi-strange baryon-antibaryon pairs provide a separation between these phases. Our method, exploiting spin entanglement between the double-strange Ξ- baryon and its antiparticle2 [Formula: see text], has enabled a direct determination of the weak-phase difference, (ξP - ξS) = (1.2 ± 3.4 ± 0.8) × 10-2 rad. Furthermore, three independent CP observables can be constructed from our measured parameters. The precision in the estimated parameters for a given data sample size is several orders of magnitude greater than achieved with previous methods3. Finally, we provide an independent measurement of the recently debated Λ decay parameter αΛ (refs. 4,5). The [Formula: see text] asymmetry is in agreement with and compatible in precision to the most precise previous measurement4.


Edible flowers: Review of flower processing and extraction of bioactive compounds by novel technologies.
Edible flowers have a long history of consumption in the form of vegetable flowers, fruit flowers or aromatic flowers. Because of their colorful and flavorful nature, edible flowers are believed to contain various nutritional and bioactive components. Today, people are advocating to eat nutritious food and paying attention to healthy foods, flower foods have become a new fashion diet trend. Although edible flowers have great sensory attraction, they have not used in food yet as widely as fresh vegetables and fruits have. The extremely short shelf-life limits the commercial use of edible flowers. In order to find some novel processing technologies which can extend the shelf-life and ensure the commercial use of flowers, we summarized the data of more than 100 studies performed until now on edible flowers. This review concludes emerging technologies including modified atmosphere packaging, high hydrostatic pressure, irradiation and edible coating to keep flower fresh, drying technologies including microwave drying, freeze drying and hybrid drying to maintain the optimal state of flower materials, as well as different extraction methods to extract the bioactive compounds and the microencapsulation of these compounds.


Vitamin D supplementation and exercise for improving physical function, body composition and metabolic health in overweight or obese older adults with vitamin D deficiency: a pilot randomized, double-blind, placebo-controlled trial.
Vitamin D supplementation may have non-skeletal health benefits and enhance exercise responsiveness, particularly in those with low vitamin D levels. We determined whether, compared with placebo, vitamin D supplementation taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight and obese older adults with vitamin D deficiency. Fifty overweight or obese older adults (mean ± SD age: 60 ± 6 years; BMI 30.6 ± 5.7 kg/m2) with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 50 nmol/L) were recruited. Participants were randomly allocated to receive either vitamin D3 (4000 IU/day) or matching placebo for 24 weeks. Between weeks 12 and 24, all participants completed multi-modal exercise three days per week while continuing with vitamin D/placebo. Mean changes in physical function (primary outcome: gait speed), body composition and biochemical parameters at weeks 12 and 24 were compared between groups. Vitamin D supplementation, with or without exercise, had no effect on gait speed. From baseline to week 12, vitamin D supplementation increased serum 25(OH)D levels (placebo: 2.5 ± 14.7 nmol/L; treatment: 43.4 ± 18.4 nmol/L; P < 0.001) and reduced stair climb times (placebo: 0.3 ± 1.0 s; treatment: - 0.2 ± 1.0 s; P = 0.046). From 12 to 24 weeks, vitamin D supplementation combined with exercise decreased waist circumference (placebo: 1.3 ± 7.3 cm; treatment: - 3.0 ± 6.1 cm; P = 0.02) and waist-to-hip ratio (placebo: 0.01 ± 0.05; treatment: - 0.03 ± 0.05; P = 0.01) relative to placebo. Vitamin D supplementation, with or without exercise, had no effect on other physical function, body composition or metabolic health outcomes. Vitamin D supplementation had no effect on most physical function, body composition or metabolic health parameters when taken alone, or during exercise, in overweight or obese older adults with vitamin D deficiency. Vitamin D-related improvements in stair climb times and waist circumference suggest that future trials should explore the effects of vitamin D on muscle power, and its effects on body composition when combined with exercise, in populations with moderate or severe vitamin D deficiency.


Vitamin B12 deficiency as a potential cause of dementia.
There is a patient case with dementia and brain MRI massive abnormalities, probably in the course of vitamin B12 deficiency.


Evaluation of Health-related Quality of Life Improvement in Patients Undergoing Spine Versus Adult Reconstructive Surgery.
Retrospective analysis of outcomes in single-level spine and primary hip and knee arthroplasty patients. The aim of this study was to compare baseline and postoperative outcomes in patients undergoing spine surgery procedures with total hip arthroplasty (THA) and total knee arthroplasty (TKA) to further define outcomes in orthopedic surgery. Computer-adaptive Patient Reported Outcome Information System (PROMIS) allows for standardized assessment of the health-related quality of life across different disease states. Patients who underwent spine surgery (anterior cervical discectomy and fusion, cervical disc replacement, lumbar laminectomy, microscopic lumbar discectomy, transforaminal lumbar interbody fusion or adult reconstruction surgery [THA, TKA]) were grouped. Mean Charlson Comorbidity Index (CCI), Baseline (BL), and 6-month PROMIS scores of physical function, pain interference, and pain intensity were determined. Paired t tests compared differences in CCI, BL, 6 months, and change in PROMIS scores for spine and adult reconstruction procedures. A total of 304 spine surgery patients (age = 58.1 ± 15.6; 42.9% female) and 347 adult reconstruction patients (age = 62.9 ± 11.8; 54.1% Female) were compared. Spine surgery groups had more disability and pain at baseline than adult reconstruction patients according to physical function ([21.0, 22.2, 9.07, 12.6, 10.4] vs. [35.8, 35.0], respectively, P < 0.01), pain interference ([80.1, 74.1, 89.6, 92.5, 90.6] vs. [64.0, 63.9], respectively, P < 0.01), and pain intensity ([53.0, 53.1, 58.3, 58.5, 56.1] vs. [53.4, 53.8], respectively, P < 0.01). At 6 months, spine surgery patients remained more disabled and had more pain compared to adult reconstruction patients. Over the 6-month timespan, spine patients experienced greater improvements than adult reconstruction patients in terms of physical function ([+8.7, +22.2, +9.7, +12.9, +12.1] vs. [+5.3, +3.9], respectively, P < 0.01) and pain interference scores ([-15.4,-28.1, -14.7, -13.1, -12.3] vs. [-8.3, -6.0], respectively, P < 0.01). Spinal surgery patients had lower BL and 6-month PROMIS scores, but greater relative improvement in PROMIS scores compared to adult reconstruction patients. 3.


Relative Income and Subjective Well-being of Urban Residents in China.
The purposes of this study are to examine subjective well-being and to test its correlation with social reference and self-expectations of urban residents in China. Data are obtained from the 2015 Chinese General Social Survey, and we focus on urban residents (N=4,857). Because the dependent variable is a sequence variable, the ordered logit model is used for data analysis. We find that absolute income remains an important factor in determining people's subjective well-being. We also find that when relative income factors are included, the correlation between absolute income and subjective well-being is reduced. This suggests that the subjective well-being of urban residents is influenced not only by absolute income itself, but also - more importantly - by relative income based on social comparison and self-expectations. These findings have implications for the formulation of social policies to improve citizens' happiness.


Treating locally advanced lung cancer with a 1.5T MR-Linac - Effects of the magnetic field and irradiation geometry on conventionally fractionated and isotoxic dose-escalated radiotherapy.
This study investigates the feasibility and potential benefits of radiotherapy with a 1.5T MR-Linac for locally advanced non-small cell lung cancer (LA NSCLC) patients. Ten patients with LA NSCLC were retrospectively re-planned six times: three treatment plans were created according to a protocol for conventionally fractionated radiotherapy and three treatment plans following guidelines for isotoxic target dose escalation. In each case, two plans were designed for the MR-Linac, either with standard (∼7mm) or reduced (∼3mm) planning target volume (PTV) margins, while one conventional linac plan was created with standard margins. Treatment plan quality was evaluated using dose-volume metrics or by quantifying dose escalation potential. All generated treatment plans fulfilled their respective planning constraints. For conventionally fractionated treatments, MR-Linac plans with standard margins had slightly increased skin dose when compared to conventional linac plans. Using reduced margins alleviated this issue and decreased exposure of several other organs-at-risk (OAR). Reduced margins also enabled increased isotoxic target dose escalation. It is feasible to generate treatment plans for LA NSCLC patients on a 1.5T MR-Linac. Margin reduction, facilitated by an envisioned MRI-guided workflow, enables increased OAR sparing and isotoxic target dose escalation for the respective treatment approaches.


Capillary gas chromatography of hydroxylated bile acid stereoisomers of the allo and normal series.
Relative retention times and methylene unit (MU) values were determined for 56 bile acids of the allo (5 alpha, A/B-trans) and normal (5 beta, A/B-cis) series, which differ from one another in the number, position and configuration of the hydroxyl groups at positions C-3, C-6, C-7 and/or C-12. The bile acids were derivatized to their methyl ester O-trimethylsilyl ethers (Me-TMS) and methyl ester O-dimethylethylsilyl ethers (Me-DMES), and chromatographed on fused-silica capillary columns, chemically bonded with non-selective OV-1 and selective PEG-20M liquid phases. Of the four possible combinations of derivatives and columns examined, Me-DMES on OV-1 and Me-TMS on PEG-20M were most suitable. The differences in the MU values between the 5 alpha- and 5 beta-series, and between the Me-DMES and Me-TMS ether derivatives, are also summarized. These retention data would be helpful in the identification of closely related bile acid stereoisomers or for estimation of their structures. photolysis.


Unmedicated patients with schizophrenia in economically underdeveloped areas of China.
Untreated schizophrenia commonly leads to poor prognosis. The medication treatment rate of schizophrenia patients in economically underdeveloped areas of China has not been well-studied. This study aimed to examine the pattern of unmedicated schizophrenia patients in economically underdeveloped rural and urban areas of China. A total of 4240 schizophrenia patients in Lanzhou (1720 rural and 2520 urban patients) registered in the community mental-health service system in Lanzhou, Gansu province were included. Their socio-demographic and clinical characteristics including medication treatment status were collected and analyzed. The proportion of unmedicated schizophrenia patients was 22.5% (n = 953) in the whole sample, with 32.3% (556/1720) in rural and 15.8% (397/2520) in urban patients (X2=161.1, P < 0.001). Multiple logistic regression analyses revealed that unmedicated schizophrenia patients in rural area were more likely to be older (OR=1.02, 95%CI: 1.01-1.03), male (OR=1.35, 95%CI: 1.07-1.71), unmarried (OR=0.71, 95%CI: 0.55-0.91), and have lower educational level (OR=0.39, 95%CI: 0.24-0.65), longer illness duration (OR=1.01, 95%CI: 1.00-1.02) and less frequent admissions (OR=0.46, 95%CI: 0.38-0.54). In contrast, unmedicated patients in urban area were more likely to be older (OR=1.01, 95%CI: 1.00-1.02), unmarried (OR=0.77, 95%CI: 0.61-0.98), employed (OR=2.38, 95%CI: 1.87-3.04), and have lower educational level (OR=0.49, 95%CI: 0.37-0.65), better financial status (OR=0.60, 95%CI: 0.48-0.76) and less frequent admissions (OR=0.81, 95%CI: 0.75-0.87). The rate of unmedicated schizophrenia patients is high in economically underdeveloped areas of China, particularly in rural areas. Effective policies and measures should be implemented urgently to improve the treatment rate in this population.


Regulation of phosphoinositide hydrolysis in cultured astrocytes by sphingosine and psychosine.
The effects of sphingosine and psychosine on phosphoinositide hydrolysis in primary cultured astrocytes were determined. Exposure to sphingosine produced a dose-dependent stimulation of phosphoinositide hydrolysis requiring the presence of external Ca++ for optimal activity. The addition of 10 microM norepinephrine resulted in a stimulation additional to that with sphingosine. The alpha 1-antagonist prazosin completely inhibited norepinephrine-induced phosphoinositide hydrolysis but had no effect on that produced by sphingosine. Psychosine (108 microM), when co-incubated with sphingosine, produced complete inhibition of sphingosine-induced phosphoinositide hydrolysis at all doses of sphingosine tested (33-668 microM). Likewise, psychosine totally inhibited norepinephrine-induced phosphoinositide hydrolysis. The protein kinase C inhibitor staurosporine (1 microM) had no effect on sphingosine-induced phosphoinositide hydrolysis. These findings suggest that lysosphingolipids such as sphingosine and psychosine may play an important role in the regulation of phosphoinositide turnover in astrocytes by a mechanism dependent on extracellular Ca++ and independent of the alpha 1-adrenergic receptor and protein kinase C.


The pathogenesis of autoimmune diabetes mellitus.
There is increasing evidence that both DP and DR BB rats fail to clonally delete autoreactive T cells in the thymus that are important in the development of autoimmune IDDM. The DP BB rat also has a defect in its ability to generate a regulatory (RT6+) T-cell population that would prevent the onset of diabetes and, therefore, it becomes spontaneously diabetic. The DR rat develops autoreactive T cells, but does not express diabetes because of the concurrent development of a regulatory (RT6+) T-cell population. We suggest that in the BB rat, the initial immunological lesion is orchestrated by an APC in close proximity to pancreatic islet beta cells, and may be specifically directed to the beta cell itself. The release of cytokines in the vicinity of the beta cell destroys this highly susceptible target, causing the release of beta cell 'autoantigens'. These autoantigens, in turn, target autoreactive T cells to the beta cells, allowing a focal destructive process to spread throughout the pancreas. The ultimate destruction of the islets and the development of diabetes result from a cascading effect of this process, with the recruitment of other non-specific immune mediators. A similar process may also be initiated by APC within the thyroid of the rat, resulting in thyroiditis. The fact that the thyrocyte does not die is unexplained, but it could relate to the relative insensitivity of this cell type to various cytokines.


A polymorphism in the human cytotoxic T-lymphocyte antigen 4 ( CTLA4) gene (exon 1 +49) alters T-cell activation.
The cytotoxic T-lymphocyte antigen 4 (CTLA4) is an important modifier of T-cell activation with down-regulatory properties upon B7 engagement. An allelic polymorphism in exon 1 of the CTLA4 gene coding for the peptide leader sequence of CTLA4 was recently described. This polymorphism was detected in association with several autoimmune diseases. In this study, we investigated the functional impact of the CTLA4 exon 1 +49 A/G dimorphism on T-cell activation and cellular localization. We examined the T-cell response from healthy donors either homozygous for A or G at position +49 of the exon 1. Under suboptimal stimulation conditions we found a greater proliferative response of cells from donors homozygous for G at position +49. FACS analysis of CTLA4 expression revealed a reduced up-regulation of CTLA4 from G/G donors upon T-cell activation, if compared with wild-type cells. Intracellular CTLA4 distribution demonstrated qualitatively different staining patterns between the two genotypes as determined using confocal fluorescence microscopy. Our results suggest that the G allele at position +49 of exon 1 affects the CTLA4-driven down-regulation of T-cell activation and may be an important factor in the pathogenesis of autoimmune diseases.


Erratum: An advanced workflow for single-particle imaging with the limited data at an X-ray free-electron laser. Corrigendum.
[This corrects the article DOI: 10.1107/S2052252520012798.].


Association between HLA genotype and antiseizure medications (ASMs)-induced maculopapular eruption among epilepsy patients in Xinjiang, China.
To determine genetic associations between antiseizure medications (ASMs)-induced maculopapular eruption (MPE) and human leukocyte antigen (HLA) variants in Xinjiang, China. A total of 409 patients were enrolled in this study, including 36 subjects with ASMs-induced MPE (case group) and 373 ASMs-tolerant patients (control group). We detected the whole sequence of the HLA alleles in the 409 Uighur patients using next-generation sequencing (NGS). The carried rate of HLA alleles were compared between the case group, the control group, and the general Chinese population. The carried rate of HLA-A*03:01, HLA-B*07:02, HLA-C*01:02, and HLA-DRB1 *06:09 allele was significantly higher in the ASMs-MPE group when compared with both the ASMs-tolerant group (p = 0.000, odds ratio (OR) = 23.92, 95 % confidence interval (CI) = 3.96-74.84; p = 0.000, OR = 21.40, 95 % CI = 3.55-67.52; p = 0.030, OR = 4.69, 95 % CI = 0.90-61.73 and p = 0.000, OR = 18.94, 95 % CI = 3.15-60.58; respectively), and the general Chinese population (p = 0.000, OR = 21.34, 95 % CI = 3.31-38.98; p = 0.000, OR = 23.92, 95 % CI = 3.96-74.84; p = 0.019, OR = 5.53, 95 % CI = 0.14-19.86 and p = 0.000, OR = 21.67, 95 % CI = 3.68-11.73; respectively). Moreover, the carried rate of the HLA-B*4001 allele was significantly higher in the ASMs-tolerant group when compared with the ASMs-MPE group (p = 0.024, OR = 5.13, 95 % CI = 1.01-9.99). In this study, we identified for the first time that the carried rate of HLA-A*03:01, HLA-B*07:02, HLA-C*01:02, and HLA-DRB1 *06:09 allele was significantly higher in the ASMs-MPE group when compared with the ASMs-tolerant group.


Species-specific differences in response to anesthetics and other modulators by the K2P channel TRESK.
TRESK (TWIK-related spinal cord K+ channel) is the most recently characterized member of the tandem-pore domain potassium channel (K2P) family. Human TRESK is potently activated by halothane, isoflurane, sevoflurane, and desflurane, making it the most sensitive volatile anesthetic-activated K2P channel yet described. Herein, we compare the anesthetic sensitivity and pharmacologic modulation of rodent versions of TRESK to their human orthologue. Currents passed by mouse and rat TRESK were enhanced by isoflurane at clinical concentrations but with significantly lower efficacy than human TRESK. Unlike human TRESK, the rodent TRESKs are strongly inhibited by acidic extracellular pH in the physiologic range. Zinc inhibited currents passed by both rodent TRESK in the low micromolar range but was without effect on human TRESK. Enantiomers of isoflurane that have stereoselective anesthetic potency in vivo produced stereospecific enhancement of the rodent TRESKs in vitro. Amide local anesthetics inhibited the rodent TRESKs at almost 10-fold smaller concentrations than that which inhibit human TRESK. These results identified interspecies differences and similarities in the pharmacology of TRESK. Further characterization of TRESK expression patterns is needed to understand their role in anesthetic mechanisms. Mouse and rat TRESK (TWIK-related spinal cord K+ channel) have different pharmacologic responses compared with human TRESK. In particular, we found stereospecific differences in response to isoflurane by the rodent TRESKs but not by human TRESK. TRESK may be a target site for the mechanism of action of volatile anesthetics.


Relationships of quantitative structure-activity for normal aliphatic alcohols.
The relative toxicity of 14 normal aliphatic alcohols has been determined as 48-hr 50% population growth inhibition (log BR, biological response) of Tetrahymena pyriformis. A linear relationship was observed between log BR and the 1-octanol/water partition coefficient (log Kow). Comparison of log BR with 96-hr 50% mortality data for Pimephales promelas revealed excellent agreement between the two test systems. A relatively constant steady-state biophase toxicant concentration is calculated for each alcohol. Calculated chemical activity increased with an increase in hydrocarbon chain length. In addition, there was good agreement between chemical activity and the activity coefficient for narcosis.


Preparation and identification of dipeptidyl peptidase IV inhibitory peptides from quinoa protein.
The objective of this study was to investigate the dipeptidyl peptidase IV (DPP-IV) inhibitory properties of quinoa protein-derived peptides. After germination, quinoa protein was extracted and then hydrolyzed by different enzymes such as papain, Alcalase, Neutrase, and Flavourzyme and pepsin-trypsin digestion. Results showed that the quinoa protein hydrolysates (QPH) by pepsin-trypsin digestion displayed the highest DPP-IV inhibitory activity. When ultrafiltrated, the fraction of quinoa protein hydrolysate with molecular weight less than 1 kDa (QPH1) exhibited a superior DPP-IV inhibitory activity with IC50 of 3.40 ± 0.20 mg/mL in vitro and 2.20 ± 0.29 mg/mL in Caco-2 based in situ. Furthermore, the peptide sequences of QPH1 were identified by UPLC-MS/MS. Twenty quinoa-derived peptides were determined with in vitro DPP-IV inhibitory activities with IC50 values less than 500 μM. The peptides IPI, IPV, VAYPL and IPIN showed the highest in vitro DPP-IV inhibitory activities with IC50 of 5.25 ± 0.16, 26.15 ± 0.58, 42.93 ± 1.15, and 56.58 ± 3.36 μM, respectively. The in situ DPP-IV activities of Caco-2 cells were also attenuated by these four peptides with IC50 of 10.75 ± 0.87, 29.11 ± 1.79, 61.9 ± 4.23, and 92.59 ± 12.89 µM, respectively. Moreover, these four peptides were identified as competitive inhibitors of DPP-IV. Molecular docking showed that quinoa peptides IPI and IPV were predicted to form multiple hydrogen bonds, attractive charge, and hydrophobic interactions with the residues of active site of DPP-IV. This study confirms that quinoa protein is a good source for DPP-IV inhibitory peptides and has potential as ingredients in functional foods for the prevention or management of type 2 diabetes.


Ceramic-on-ceramic bearings total hip arthroplasty in young patients.
The results of ceramic-on-ceramic (CoC) total hip arthroplasty (THA) in younger patients were not univocal. This study aims to evaluate the results of CoC bearing THA in patients younger than 50 years. A total of 90 younger patients performed CoC THAs during March 2003 and May 2008 were included in this study. Hip function and activity were evaluated with Harris hip score and University of California Los Angeles activity score. We had discussed survival rates, radiological findings of component loosening or osteolysis, and ceramic-related complications in these patients. The mean Harris hip score increased from 46.3 ± 12.0 points (range, 28-70 points) before surgery to 92.5 ± 5.6 points (range, 78-100 points) at the final follow-up. The mean preoperative University of California Los Angeles activity score was 4.2 ± 1.1 points (range, 2-6 points), which improved to a mean of 7.2 ± 1.3 points (range, 4-10 points). At the time of the last follow-up, there was found to be 1 occurrence of hip dislocation, 1 squeaking, and 2 "sandwich" ceramic liners fractured during normal activity of daily living. No hips showed osteolysis or required revision for aseptic loosening. Kaplan-Meier survivorship with revision due to loosening or osteolysis was 100% and with revision due to ceramic fracture was 97.3% (95% confidence interval, 93.7%-100%) at a mean of 9.4 years. This study with the use of CoC bearings THAs in younger patients have shown promising results and higher rate of survivorship without evidence of osteolysis.


Whole dietary patterns to optimize cognitive function for military mission-readiness: a systematic review and recommendations for the field.
Optimizing cognitive performance, particularly during times of high stress, is a prerequisite to mission-readiness among military personnel. It has been of interest to determine whether such performance could be enhanced through diet. This systematic review assesses the quality of the evidence for whole dietary patterns across various outcomes related to cognitive function in healthy adult populations to develop research recommendations for the military. PubMed, CINAHL, Embase, PsycInfo, and the Cochrane Library were searched. Peer-reviewed randomized controlled trials published in the English language were eligible. Fifteen included trials were assessed for methodological quality, and descriptive data were extracted. Of the 6 acceptable-quality studies, 1 demonstrated statistically nonsignificant results, whereas the other 5 showed conflicting results across the cognitive outcomes assessed. Due to the heterogeneity across the included studies, no recommendations could be reached concerning whether certain whole dietary patterns have an effect on cognitive outcomes in healthy populations. Specific recommendations for future research are offered.


COVID-19 and the second exams fiasco across the UK: four nations trying to avoid immediate policy failure.
In 2021, the UK and devolved governments tried to avoid the school exams fiasco of 2020. Their immediate marker of success was to prevent a similar U-turn on their COVID-19 school exams replacement policies. They still cancelled the traditional exam format, and sought teacher assessments to determine their grades, but this time without using an algorithm to standardise the results. The outcomes produced some concerns about inequity, since the unequal exam results are similar to those experienced in 2020. However, we did not witness the same sense of acute political crisis. We explain these developments by explaining this year's 'windows of opportunity' overseen by four separate governments, in which the definition of the problem, feasibility of each solution, and motive of policymakers to select one, connects strongly to the previous U-turn. A policy solution that had been rejected during the first window became a lifeline during the second and a likely choice during the third. This action solved an immediate crisis despite exacerbating the problem that ministers had previously sought to avoid ('grade inflation'). It produced another year of stark education inequity, but also ensured that inequity went from part of an acute political crisis to its usual status as a chronic low-attention policy problem.


Liver adenomatosis: re-evaluation of aetiology and management.
Liver adenomatosis (LA) is a rare benign parenchymal liver disease with unknown aetiology. In recent reports, LA has been associated with hepatic steatosis, with potential implications for the management of this disease. The aim of this study was to determine prognosis and optimal management of patients with LA. Clinical presentation, diagnostic studies and management of patients with LA were analysed in our centre. Furthermore, a Medline search of all published case reports and series of LA patients was performed. Ninety-four patients with LA have been reported in the literature. Fifty-two per cent of females had a history of oral contraceptive use. Eighteen per cent of patients had steatosis in nontumoral tissue. In our own series, five of six patients had histologically confirmed steatosis. Forty-three per cent of patients presented with acute pain, of whom 46% had a haemorrhagical complication, in contrast to 2% of nonsymptomatic patients. Tumours <5 cm tended to increase in size during follow-up and only in four patients tumour regression was observed. Liver adenomatosis is a progressive, benign parenchymal disease mainly occurring in females. There is a potential link with hepatic steatosis with implications for the management of patients with LA. Noninvasive diagnosis is difficult because of the variety of tumoral and nontumoral components. Management should primarily be conservative.


A simplified concept for controlling oxygen mixtures in the anaesthetic machine--better, cheaper and more user-friendly?
Modern anaesthetic machines are equipped with several safety components to prevent delivery of hypoxic mixtures. However, such a technical development has increased the complexity of the equipment. We report a reconstructed anaesthetic machine in which a paramagnetic oxygen analyzer has provided the means to simplify the apparatus. The new machine is devoid of several components conventionally included to prevent hypoxic mixtures: oxygen failure protection device, reservoir O2 alarm, N2O/air selector, and proportioning system for oxygen/nitrous oxide delivery. These devices have been replaced by a simple safety system using a paramagnetic oxygen analyzer at the common gas outlet, which in a feed-back system cuts off the supply of nitrous oxide whenever the oxygen concentration falls below 25%. The simplified construction of the anaesthetic machine has important consequences for safety, cost and user-friendliness. Reducing the complexity of the construction also simplifies the pre-use checkout procedure, and an efficient 5-point check list is presented for the new machine.


Serogroups of beta-haemolytic streptococci isolated from clinical specimens in parts of eastern Nigeria.
From 470 patients, mainly of respiratory infection, attending University of Nigeria Teaching Hospital, Enugu, Nigeria 212 (45 per cent) strains of beta-haemolytic streptococci were isolated and 25 per cent of the isolates belonged to Group B Streptococcus. Percentage isolation of other groups was A(21.2), G(20.3), C(16.1), D(10.8) and F(5.2). Maximum (11.2 per cent) isolates were from age group of 5-17 years. All serogroups were sensitive to penicillin G and ampicillin despite the prevalent misuse of drugs in the state and the country at large.


Froth flotation beneficiation and physiochemical characterization of coal from Achibo-Sombo-Dabaso area, southwestern Ethiopia.
This study was carried out with one of the physiochemical techniques of coal sample beneficiation using froth flotation technique for upgrading the quality of Achibo-Sombo-Dabaso coal, southwestern Ethiopia. The investigations aimed to beneficiate high impure Ethiopian coal and to minimize its impurities present, so that it can replace the imported coal and the environmental pollution generated during combustion is reduced. The proximate and ultimate characterization studies show that the raw coal samples contain 11.81-20.27% moisture, 22.47-36.58% ash, 22.74-34.85% volatile matter, 23.85-38.31% fixed carbon, 1.22-1.44% nitrogen, 0.57-1.9% sulfur with 3243.59-5295.34 kcal/kg calorific value. Froth flotation experiments were carried out on the raw coal samples at varying parameters of collector dosages (0.0095 kg/ton, 0.0283 kg/ton, 0.0472 kg/ton, 0.0661 kg/ton and 0.085 kg/ton of diesel oil), frother dosages (0.0922 kg/ton, 0.1845 kg/ton, 0.2767 kg/ton, 0.3689 kg/ton and 0.4611 kg/ton of n-octanol) and particle size (500-250, 250-125, 125-63 μm). The experimental results for the treated coal samples are 8.12-14.02% moisture, 7.49-13.62% ash, 21.92-30.64% volatile matter, 44.47-55.87% fixed carbon, 0.52-0.92% nitrogen, 0.25-0.41% sulfur content with 5243.40-6531.46 kcal/kg of calorific value. The results of this study indicate that the treated coal samples are relative with high calorific value, fixed carbon and low ash content compared to the raw samples. The coal samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Scanning electron microscopy (SEM) to understand the flotation and size distribution of coal. Therefore, the froth flotation technique at parameters of collector dosages (0.0472 kg/ton of diesel oil), frother dosages (0.3689 kg/ton of n-octanol) and particle size (125-63 μm) is effective to increase the calorific value above 5000 kcal/kg and increment carbon content of Achibo-Sombo-Dabaso coal that suitable as an energy source in cement and steel industries.


Variations in Postpartum Opioid Prescribing Practices among Obstetrician-Gynecologists.
There have been many efforts to combat the United States opioid crisis that has been occurring for the past two decades, specifically with postpartum patients that often were prescribed opioids. Prior studies described how accounting for usage of inpatient opioids on the day prior to discharge had an impact on how much discharge opioids were prescribed on the day of discharge. These studies provided a guideline to use the inpatient opioid amount from the day before discharge to determine discharge opioid quantity and minimize how much was being prescribed. In July 2018, the American College of Obstetrics and Gynecologists (ACOG) published Committee Opinion 742, guidelines for obstetricians-gynecologists about post-partum pain management. Prescription pain medications (including opioids, if necessary) require a shared decision-making approach between the physician and patient to determine the medication type and quantity. This study aimed to determine if there were differences in prescribing practices based on the specific post-operative day that opioid prescriptions were written, and if there were differences in the prescribing practices for cesarean deliveries following the publication of ACOG Committee Opinion 742. This retrospective chart review included patients who had a live cesarean birth at one rural Midwest facility anytime between July 1, 2017 and February 28, 2021. This study excluded those with chorioamnionitis and those discharged after more than four days. Opioid amounts were converted to oral morphine milligram equivalents (MME) for comparison, and total MME was calculated for each prescription. Patients were stratified into two groups based on the day that their discharge opioid medication prescriptions were written (i.e., a day prior to discharge or the day of discharge). Patients were also stratified based on date of delivery, before or after the publication of ACOG Committee Opinion 742. Of 411 cesarean patients, 93.9% (n = 386) had opioids prescribed at discharge, 86% (n = 330) of whom received a prescription written on the day of discharge. There was no difference in the quantity of MMEs, doses per day, or dosage from discharge prescriptions between those written on the day of discharge and those written on a prior day. Patients whose deliveries occurred after the publication of ACOG Committee Opinion 742 (63.9%, n = 263) received discharge prescriptions with fewer average MMEs (159.53 ± 61.64) than those whose deliveries occurred before the publication (36%, n = 148; 187.35 ± 53.42; χ2 (1, N = 411) = 17.71; p < 0.001), and they were prescribed fewer doses per day. After cesarean sections, the specific post-operative day did not seem to impact the prescribing trends as there were no differences in MMEs, doses per day, or dosage between prescriptions that were written on the day of discharge and before the day of discharge. Patients whose deliveries occurred after the publication of ACOG Committee Opinion 742 received discharge prescriptions with fewer MMEs, fewer doses per day, and the same dosage than those whose deliveries occurred before the publication, reflecting the overall national trend of decreasing prescription opioids over these years.


Eukaryotic artificial ON-riboswitches that respond efficiently to mid-sized short peptides.
We chose two types of mid-sized Arg-rich peptides (Rev-pep and Tat-pep) as ligands and used their aptamers to construct efficient eukaryotic ON-riboswitches (ligand-dependently upregulating riboswitches). Due to the aptamers' high affinities, the best Rev-pep-responsive and Tat-pep-responsive riboswitches obtained showed much higher switching efficiencies at low ligand concentrations than small ligand-responsive ON-riboswitches in the same mechanism. In addition, despite the high sequence similarity of Rev-pep and Tat-pep, the two best riboswitches were almost insensitive to each other's peptide ligand. Considering the high responsiveness and specificity along with the versatility of the expression platform used and the applicability of Arg-rich peptides, this orthogonal pair of riboswitches would be widely useful eukaryotic gene regulators or biosensors.


S-adenosylmethionine-dependent methyltransferase inhibitor DZNep blocks transcription and translation of SARS-CoV-2 genome with a low tendency to select for drug-resistant viral variants.
We report the in vitro antiviral activity of DZNep (3-Deazaneplanocin A; an inhibitor of S-adenosylmethionine-dependent methyltransferase) against SARS-CoV-2, besides demonstrating its protective efficacy against lethal infection of infectious bronchitis virus (IBV, a member of the Coronaviridae family). DZNep treatment resulted in reduced synthesis of SARS-CoV-2 RNA and proteins without affecting other steps of viral life cycle. We demonstrated that deposition of N6-methyl adenosine (m6A) in SARS-CoV-2 RNA in the infected cells recruits heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), an RNA binding protein which serves as a m6A reader. DZNep inhibited the recruitment of hnRNPA1 at m6A-modified SARS-CoV-2 RNA which eventually suppressed the synthesis of the viral genome. In addition, m6A-marked RNA and hnRNPA1 interaction was also shown to regulate early translation to replication switch of SARS-CoV-2 genome. Furthermore, abrogation of methylation by DZNep also resulted in defective synthesis of the 5' cap of viral RNA, thereby resulting in its failure to interact with eIF4E (a cap-binding protein), eventually leading to a decreased synthesis of viral proteins. Most importantly, DZNep-resistant mutants could not be observed upon long-term sequential passage of SARS-CoV-2 in cell culture. In summary, we report the novel role of methylation in the life cycle of SARS-CoV-2 and propose that targeting the methylome using DZNep could be of significant therapeutic value against SARS-CoV-2 infection.


Flow cytometric analysis of DNA and cell proliferation in ovarian tumors.
DNA content in tumor cells from 50 patients with ovarian tumors was analysed by flow cytometry (FCM). Solid tissue samples were processed to obtain monodispersed cells. Staining for DNA analysis was achieved with ethidium bromide and mithramycin. Peripheral blood lymphocytes were used as reference diploid cell population. All benign ovarian tumors exhibited only diploid cells. DNA aneuploid cell lines were found 66.6% of serous carcinomas and in 80% of malignant granulosa cell tumors. The S-phase fraction of DNA diploid cells in benign ovarian tumors (S = 2.4 +/- 1.2%) was smaller than those of malignant tumors (S = 8.2 +/- 5.2%). DNA aneuploid cell populations in serous carcinomas display a higher S-phase fraction (S = 19.2 +/- 9.3%) than DNA diploid cells (S = 11.7 +/- 3.2%). No major differences were obtained between primary ovarian tumors and their metastases, as far as degree of aneuploidy and S-phase fraction are concerned. A high degree of correlation was established between the grade of differentiation of ovarian tumors and the DNA ploidy abnormalities.


Analysis of Chinese donors' return behavior.
It is important to understand donor return behavior. Converting first-time donors to become repeat donors is essential for maintaining an adequate blood supply. Characteristics of 241,552 whole blood (WB) donations from first-time and repeat donors who donated in 2008 at the five blood centers in China were compared. A subset of 54,394 WB donors who donated between January 1 and March 31, 2008, were analyzed for their return behavior in 2008 after the index donation using logistic regression. Of all donations, 64% were from first-time donors. Donors with self-reported previous donations tended to be male, older, and married; donated larger volume (≥ 300 mL); and were heavier in weight. Among donors who donated from January to March 2008, 14% returned for subsequent WB donations by the end of 2008. The number of previous donations and blood collection location were the two strongest predictors for making subsequent donations. Donors with one, two to three, and more than three previous donations were 3.7, 5.7, and 11.0 times more likely to return than first-time donors. Those who donated in a blood collection vehicle were four times more likely to return than those who donated at a blood center. Being female, younger, and of a lower education level (middle school or less) were positively associated with subsequent return blood donation during the follow-up period observed in this study. Most of the Chinese blood supply is from first-time donors. Strategies aimed at encouraging current donors to become repeat donors are needed.


Arrhythmias: Opening Pandora's Box -- incidental genetic findings.
A major goal of precision medicine is to improve disease prevention and therapy by using big data provided by genomic technology and electronic health records. In a new study, assessment of a patient population without a history of cardiac disease revealed that genetic variants putatively associated with a risk of sudden death were not linked with arrhythmia phenotypes.


The long noncoding RNA TINCR promotes self-renewal of human liver cancer stem cells through autophagy activation.
Hepatocellular carcinoma (HCC) is an extraordinarily heterogeneous tumor, which holds high recurrence and metastasis rates. Liver cancer stem cells (LCSCs) have been considered to be important influencing factors of these pathological properties, but the underlying mechanisms are poorly understood in HCC. Considerable evidences have shown that autophagy has an important role in cancer stemness. However, it is still unknown whether a long noncoding RNA (lncRNA) TINCR is involved in autophagy and self-renewal maintenance of HCC. In this study, TINCR was found to be highly expressed in HCC tissues and LCSCs. In vitro and in vivo assays for the first time showed that TINCR was required for LCSC self-renewal and tumorigenesis. Moreover, gene ontology analysis revealed the involvement of autophagy in the maintenance of TINCR-regulated stemness. Mechanically, TINCR was associated with polypyrimidine tract binding protein 1 (PTBP1) protein, which further promoted the transcription activity of autophagy related gene ATG5. In conclusion, we demonstrated that TINCR regulated LCSC self-renewal by autophagy activation through PTBP1/ATG5 regulatory pathway, offering a potential new target for HCC therapy.


Application of 3D reconstruction through CT to measure the abdominal cavity volume in the treatment of external abdominal hernia.
To evaluate 3D reconstruction through CT in the measurement of abdominal cavity volume. From January 1, 2019 to December 31, 2019, 61 patients diagnosed as external abdominal hernia were included in this prospective study. Multislice computed tomography (MSCT) was applied to patients scanning, and the images were transferred to post-processing workstation for further analysis. We measured the abdominal cavity volumes using volume rendering (VR) method and diameter rendering (DR) method, and the results were used to test whether there is a correlation between them. In addition, the time required for the measurement was recorded and analyzed. In this study, we found that there was no significant difference in the abdominal cavity volumes between these two groups (VR vs. DR = 7857.316 ± 2035.786 cm3 vs. 7967.268 ± 2925.792 cm3, P > 0.05). Besides, the correlation analysis between the measured values of VR method and DR method showed there was a significant positive correlation (r = 0.922, P < 0.01). The linear regression equation based on the scatter plot was established as follows: y = 0.6417x + 2745, R2 = 0.8504. Furthermore, this regression equation was simplified as follows: y = 0.64x + 2800, R2 = 0.8499. Meanwhile, the time required for measurement of VR was significantly longer than that of DR (VR vs. DR = 64.3 ± 7.1 min vs. 2.6 ± 0.6 min, P < 0.01). In conclusion, the DR method can quickly measure and calculate the abdominal cavity volume, and its accuracy can more suitable for clinical requirement.


Inhibition of botulinum neurotoxins interchain disulfide bond reduction prevents the peripheral neuroparalysis of botulism.
Botulinum neurotoxins (BoNTs) form a growing family of metalloproteases with a unique specificity either for VAMP, SNAP25 or syntaxin. The BoNTs are grouped in seven different serotypes indicated by letters from A to G. These neurotoxins enter the cytosol of nerve terminals via a 100 kDa chain which binds to the presynaptic membrane and assists the translocation of a 50 kDa metalloprotease chain. These two chains are linked by a single disulfide bridge which plays an essential role during the entry of the metalloprotease chain in the cytosol, but thereafter it has to be reduced to free the proteolytic activity. Its reduction is mediated by thioredoxin which is continuously regenerated by its reductase. Here we show that inhibitors of thioredoxin reductase or of thioredoxin prevent the specific proteolysis of VAMP by the four VAMP-specific BoNTs: type B, D, F and G. These compounds are effective not only in primary cultures of neurons, but also in preventing the in vivo mouse limb neuroparalysis. In addition, one of these inhibitors, Ebselen, largely protects mice from the death caused by a systemic injection. Together with recent results obtained with BoNTs specific for SNAP25 and syntaxin, the present data demonstrate the essential role of the thioredoxin-thioredoxin reductase system in reducing the interchain disulfide during the nerve intoxication mechanism of all serotypes. Therefore its inhibitors should be considered for a possible use to prevent botulism and for treating infant botulism.


Effects of some antidepressant drugs on the activity of glial cell enzymes in culture.
An oligodendrocyte-enriched culture was incubated with the antidepressant drugs, amitriptyline, desipramine, mianserin and citalopram, in a concentration of 3 X 10(-6) M for 24 h and 14 days. The activity of glycerol-3-phosphate dehydrogenase (G3PDH), lactate dehydrogenase (LDH), pyruvate carboxylase (PC) and the incorporation of [3H]thymidine was measured. An increase in both the incorporation of [3H]thymidine into DNA and the activities of G3PDH and PC was observed. However, LDH activity decreased after a 2-week incubation. The above results indicate that the antidepressant drugs change the metabolism of glial cells.


In utero myelomeningocele repair: The natural history of patients with incontinent pattern (sphincteric deficiency: leakage below 40 CMH20).
Since 2011 we have been following prospectively myelomeningocele patients treated in utero with particular interest to patients with sphincter weakness/deficiency. We investigated the changes of bladder pattern and upper urinary tract with time in children who underwent in utero repair and had low-pressure incontinence based on urodynamic evaluation (UE). From the 120 patients in our database, 117 had at least one UE. Of these, 30 were classified as incontinent when leaking at low pressure (<40 cmH20). We reviewed clinical evaluation, urinary tract ultrasound, voiding cystourethrography (VCUG), and other UE parameters at first and last evaluation. We found 30 cases (25.64%). Mean age at initial evaluation was 4.97 months followed by UE done initially at mean age of 5.73 months. Follow-up was 28.4 months. Febrile urinary tract infection has been found in four patients (13.3%), hydronephrosis in four patients, and bladder neck thickening in three (10%). The VCUG showed vesicoureteral reflux in three cases (3/27, 11.1%). A total of 90% of patients had detrusor overactivity with mean maximum detrusor pressure (33.37 cmH20). Only 16.67% of patients showed normal bladder capacity. From the 30 patients, 23 had at least two UE. We noticed a change of bladder pattern as follows: six patients became of high-risk pattern, five normal, and two with underactive bladder pattern. The average interval between the first and last UE was 25.5 months (median: 15 months). We concluded that 43.47% of patients with low DLPP have kept the incontinent pattern. If the initial LPP was below 30 cmH20, 70% remained with the incontinet pattern.


Effect of date palm pollen supplementation on female sexual function in non-menopausal women: A double blind randomized clinical trial.
Despite numerous experimental studies in the literature, there are few clinical trials regarding the effect of date palm pollen (DPP) supplementation on sexual function improvement. In the present study, we sought to evaluate the impact of DPP on female sexual function in Iranian non-menopausal women. Between October 2019 and December 2019, health centers in the city of Khalkhal, volunteers meeting the inclusion criteria were recruited in randomized clinical trials. Sixty-eight women were randomly stratified and assigned to one of the two study groups: placebo group (n = 35) and palm pollen group (n = 35), and received a starch or palm pollen capsule (300 mg per day), respectively, for 35 d. The Female Sexual Function Index (FSFI) instrument was used to assess female sexual function. After DPP supplementation, the increase in desire, lubrication, and the overall score, was statistically significant compared to the placebo group (P = 0.002, P = 0.000, and P = 0.042; respectively); Whilst there was no significant differences in the remaining domains (arousal: P = 0.763; orgasm: P = 0.370; satisfaction: P = 0.474; pain: P = 0.259). There was a statistically significant positive correlation between the coitus and preintervention levels of desire (r = 0.298, P = 0.038), arousal (r = 0.328, P = 0.021), lubrication (r = 0.361, P = 0.011), orgasm (r = 0.320, P = 0.025), satisfaction (r = 0.327, P = 0.022), and overall scores (r = 0.338, P = 0.018). This study suggests that DPP (300 mg supplementation for 35 d), given to non-menopausal women, could improve the lubrication and desire domains of FSFI.


Death and nonfatal reinfarction within the first 24 hours after presentation with an acute coronary syndrome: experience from GUSTO-IIb. Global Utilization of Strategies for Total Occlusion.
A large proportion of deaths among patients with myocardial infarction occurs within the first 24 hours after presentation. It is not clear whether this phenomenon is also true of patients without ST-segment elevation who may or may not have infarction at the time of presentation. Thrombin activity may also be greatest during the first 24 hours after plaque rupture. Accordingly, this study was designed to examine the pattern of early ischemic events among patients with acute coronary syndromes and to determine whether the direct thrombin inhibitor desirudin (r-hirudin) would be most effective during this period. Among the 11,142 patients enrolled in GUSTO-II, death or (re)infarction occurred within 24 hours in 210 patients (1.7%), representing 19% of the 1135 deaths that had occurred by 30 days. Death or (re)infarction occurred within 24 hours in 113 patients (2. 7%) with ST-segment elevation and in 97 patients without ST-segment elevation (1.2%, P <.001), representing 26% and 14% of the 30-day event rates, respectively, for the 2 enrollment strata. Among patients with ST-segment elevation, most of these events were deaths, whereas among patients without ST-segment elevation, most events were (re)infarctions. Death or (re)infarction by 24 hours occurred in 80 (1.3%) patients treated with desirudin and 130 (2.1%) patients treated with heparin (P =.01). This finding predominantly consisted of prevention of death among patients with ST-segment elevation and of (re)infarction among patients without ST-segment elevation. These findings have important implications for early triage of patients with acute coronary syndromes and for the development of new therapies directed at stabilizing the unstable atherosclerotic plaque.


Validation of the NASA-TLX Score in Ongoing Assessment of Mental Workload During a Laparoscopic Learning Curve in Bariatric Surgery.
Fatigue and mental workload are directly associated with high-complexity tasks. In general, difficult tasks produce a higher mental workload, leaving little opportunity to deal with new/unexpected events and increasing the likelihood of performance errors. The laparoscopic Roux-en-Y gastric bypass (LRYGB) learning curve is considered to be one of the most difficult to complete in laparoscopic surgery. We wished to validate the National Aeronautics and Space Administration Task Load Index (NASA-TLX) in LRYGB and identify factors that could provoke a higher mental workload for surgeons during the learning curve. A single surgeon was enrolled to undertake 70 consecutive LRYGB procedures with two internal surgeons mentoring the first 35 cases. Patients were consecutive and ranked from case 35 to case 105 according to the date of the surgical procedure ("case rank"). Self-ratings of satisfaction, performance, and fatigue were measured at the end of surgery using a validated NASA-TLX questionnaire. The procedure was recorded for later viewing by two external evaluators. General data for patients and surgical variables were collected prospectively. A moderate correlation between the NASA-TLX score, BMI, operative time, and volumes of blood drainage was observed. There was no correlation between the NASA-TLX score and duration of hospital stay or time of drain removal. BMI ≥50 kg/m(2), male sex, inexperienced first assistant, and type 2 diabetes mellitus were identified as independent predictive factors of a higher NASA-TLX score. The NASA-TLX is a valid tool to gauge mental workload in LRYGB.


Bovine babesiosis: An insight into the global perspective on the disease distribution by systematic review and meta-analysis.
Bovine babesiosis is continuing as a great threat to the livestock sector causing havoc production losses with significant morbidity and mortality. Being a tick-borne disease, the great complexity in the agent-host- vector relationship has severely hampered the sincere efforts towards the development of an effective vaccine against bovine babesiosis. In these circumstances, assessing the global scenario of disease prevalence is a prerequisite to strategize the available control measures. Keeping this in view, the objective of this study was to estimate the pooled prevalence of bovine babesiosis globally. The literature search was conducted to identify all relevant published articles reporting the prevalence of bovine babesiosis and a total of 163 studies were found eligible for final systematic review and meta-analysis. Meta-analysis was conducted using meta package of R software and summary estimates of the prevalence were calculated. Meta analysis of 81099 samples from 62 countires representing six continents revealed pooled global prevalence of bovine babesiosis as 29% (95% CI = 24%-34%) with estimated prevalence of active infection as 16% (95% CI = 13%-20%) and seroprevalence as 50% (95% CI = 45%-56%) using random effects model. Continent wise highest prevalence of bovine babesiosis in South America 64% (95% CI = 49%-77%) and lowest in Asia 19% (95% CI = 14%-25%). Highest prevalence was estimated with B. bigemina 22% (95% CI = 18%-27%) and least prevalence was recorded with B. divergens 12% (95% CI = 2%-46%). The pooled prevalence estimates generated in the study is revealing an increase in disease trend and the need for immediate planning of mitigation strategies paralleled with the development of early diagnostic methods to reduce the impact of disease throughout the world.


The extracellular domain of syndecan-2 regulates the interaction of HCT116 human colon carcinoma cells with fibronectin.
The cell surface heparan sulfate proteoglycan, syndecan-2, is known to play an important role in the tumorigenic activity of colon cancer cells, but the function of its extracellular domain is not yet clear. Cell spreading assays showed that HCT116 human colon cancer cells attached and spread better on fibronectin compared to the other tested extracellular matrixes (ECMs). Notably, syndecan-2 overexpression enhanced the spreading of HCT116 cells on fibronectin, and the opposite effects were observed when syndecan-2 expression was reduced. In addition, an oligomerization-defective syndecan-2 mutant failed to increase cell-ECM interactions and adhesion-related syndecan-2 functions, including migration. Furthermore, analyses using a microfabricated post array detector system revealed that syndecan-2, but not the oligomerization-defective mutant, enhanced the interaction affinity of HCT116 cells on fibronectin. Taken together, these results suggest that the extracellular domain of syndecan-2 regulates the interaction of HCT116 human colon carcinoma cells with fibronectin.


Do secondary conditions explain the relationship between depression and health care cost in women with physical disabilities?
To examine the influence of depression on health care utilization and costs among women with disabilities and to determine whether the severity of other secondary health conditions affects this association. A time series of 7 interviews over a 1-year period. Large, southern metropolitan area. Community-dwelling women (N=349) with a self-identified diagnosis of a physical disability. Not applicable. Primary disability, secondary health conditions (Health Conditions Checklist), depressive symptoms (Beck Depression Inventory-Second Edition), and health care utilization (based on the Health and Social Service Utilization Questionnaire and the Stanford Health Assessment Questionnaire). We estimated health care costs using standardized criteria and published average costs. Outpatient and emergency department health care utilization and overall costs were higher in women with depressive symptoms and increased with the frequency and severity of the symptoms. Depressive symptoms were highly correlated with the severity of secondary health conditions. Adjusting for demographics and primary disability, both the presence and severity of depressive symptoms were associated with significantly higher health care costs. However, secondary health condition severity explained the association between depressive symptoms and cost; it also substantially increased the variance in cost that was explained by the multivariate models. Secondary health conditions are significantly associated with depressive symptoms and higher health care costs, with secondary health conditions accounting for the association between depressive symptoms and costs. This association suggests that effective management of secondary health conditions may help reduce both depressive symptomatology and health care costs.


Targeting the apoptosis pathway to treat tumours of the paediatric nervous system.
New, more effective therapeutics are required for the treatment of paediatric cancers. Current treatment protocols of cytotoxic treatments including chemotherapy trigger cancer-cell death by engaging the apoptosis pathway, and chemotherapy efficacy is frequently impeded by apoptosis dysregulation. Apoptosis dysregulation, through genetic or epigenetic mechanisms, is a feature of many cancer types, and contributes to reduced treatment response, disease progression and ultimately treatment resistance. Novel approaches are required to overcome dysregulated apoptosis signalling, increase the efficacy of cancer treatment and improve patient outcomes. Here, we provide an insight into current knowledge of how the apoptosis pathway is dysregulated in paediatric nervous system tumours, with a focus on TRAIL receptors, the BCL-2 proteins and the IAP family, and highlight preclinical evidence demonstrating that pharmacological manipulation of the apoptosis pathway can restore apoptosis signalling and sensitise cancer cells to treatment. Finally, we discuss the potential clinical implications of these findings.


AXL Inhibits Proinflammatory Factors to Relieve Rheumatoid Arthritis Pain by Regulating the TLR4/NF-κB Signaling Pathway.
This study aims to explore the role and mechanism of AXL receptor tyrosine kinase (AXL) in relieving inflammatory pain caused by rheumatoid arthritis (RA). RA mouse model was constructed by collagen antibody induction. RT-qPCR and Western blot were used to detect the level of AXL in RA fibroblast-like synovial cells (RA-FLS) and joint synovium. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) were detected by ELISA. The inflammatory infiltration in joints was determined via HE staining. The mechanical abnormal pain and hyperalgesia were detected by the Von Frey microfilament test. The protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (3COX-2), toll-like receptor 4 (TLR4), p65, and phosphor (p)-p65 were detected by Western blotting. The expression of AXL in RA-FLS and RA mice was downregulated, while the expression of iNOS and COX-2 was upregulated. The levels of inflammatory cytokines IL-6, TNF-α, and NO were increased in RA-FLS and RA mice. RA mice presented inflammatory cell infiltration, bone and cartilage destruction, and joint space stenosis. AXL overexpression alleviated inflammatory cell infiltration, inflammatory cytokine secretion, and pathological injury in RA mice. Additionally, AXL overexpression inhibited the expression of TLR4 and p-p65. AXL inhibits inflammatory pain in RA mice by suppressing TLR4/NF-κB pathway.


Relationship between mutagenic potency in Salmonella typhimurium and chemical structure of amino- and nitro-substituted biphenyls.
All positional isomers of mononitro- and monoaminobiphenyls and those of dinitro-, diamino- and aminonitrobiphenyls, which have one substituent on each benzene ring, were assayed for mutagenicity in Salmonella typhimurium by the Ames method. The results suggest that the structural requirements favoring mutagenic activity are the presence of substituents at the 4-position and their absence at the 2'-position. The introduction of an amino group to the 3'- or 4'-position of 4-nitrobiphenyl or a nitro group to 3'- or 4'-position of 4-aminobiphenyl enhanced the mutagenicity. Among the mutagenic compounds, 4-nitro analogues were mutagenic in strains TA98 and TA100 in the absence of a microsomal metabolic activation system. Strain TA98NR was not reverted by the direct-acting mutagens, whereas strain TA98/1,8-DNP6 was as revertible as strain TA98; these results suggest that the direct-acting mutagenicity involves the reduction of the nitro group by bacterial nitroreductase but does not involve specific esterification enzymes.


Comprehensive cytogenetic evaluation of a mature ovarian teratoma case.
Mature ovarian teratomas are benign ovarian germ cell tumors that usually present with a normal karyotype. There are very few reports describing chromosomal abnormalities in these tumors, none of which are recurrent. In this study we report on a mature teratoma case with clonal chromosomal alterations which include monosomies of chromosomes 6, 14, 16, and 21; trisomies of chromosomes 14 and 21; and deletions of Xq, 5p, 16p, and 17p. Comparative genomic hybridization evaluation of the sample revealed a normal profile. These findings are discussed together with the cytogenetic reports on other cases of ovarian teratomas described in the literature.


Association between urinary 1-hydroxypyrene and genotoxic effects in coke oven workers.
To investigate whether current occupational exposure of coke oven workers to polycyclic aromatic hydrocarbons (PAHs) results in genotoxic effects measured in peripheral blood lymphocytes and whether these biomarkers are associated with the biomarkers of exposure. Blood and urine samples were collected immediately after a shift at the end of a working week from 50 coke oven workers and 50 control workers not exposed to PAHs. Methods included: (1) biomarkers of exposure: urinary 1-hydroxypyrene (HpU), urinary mutagenicity by the plate Salmonella test with strains TA98 and YG1024 after metabolic activation, expressed as mutagenic rate (MR98 and MR1024, respectively), urinary cotinine; and (2) biomarkers of biological effects in peripheral blood lymphocytes (PBL): sister chromatid exchanges (SCE/cell), cells of high frequency of SCE (% HFC), micronuclei (MN/1000 cells), chromosomal aberrations (CA/100 cells), and DNA damage by the Comet assay. Occupational exposure to PAH resulted in significantly increased levels of HpU and mutagenic effect of urine. Median values of these biomarkers in coke oven workers were: 9.0 micromol/mol creatinine for HpU, 2.7 for MR98, and 8.2 for MR1024, compared to the controls: HpU = 0.6 micromol/mol creatinine, MR98 = 1.2, and MR1024 = 5.5. Occupational exposure caused significant induction of SCE, HFC, and MN in coke oven workers: median SCE = 5.9, HFC = 12.0%, MN = 6.0 compared to the controls: 3.9, 5.0%, and 3.0, respectively. No effect of occupational exposure was found in relation to CA and DNA damage measured with the Comet assay. HpU concentration was positively associated with SCE and HFC. The concentration of urinary 1-hydroxypyrene corresponding to a 5% probability of increased SCE was 1.0 micromol/mol creatinine. The occupational exposure to PAHs resulted in measurable biological effects (SCE, HFC, MN). In coke oven workers an increased level of SCE was not observed below the level of 1.0 micromol HpU/mol creatinine.


Molecular cloning of the gene cluster for lariatin biosynthesis of Rhodococcus jostii K01-B0171.
The biosynthetic gene cluster for lariatins A and B, anti-mycobacterial peptide antibiotics with a unique "lasso" structure, was cloned from Gram-positive bacterium Rhodococcus jostii K01-B0171. Random transposition mutagenesis using IS1415 derivative was carried out to identify a chromosomal locus involved in lariatin biosynthesis and six independent lariatin non-producing variants were obtained. Arbitrary PCR revealed that one insertion was located near the region involved in lariatin biosynthesis. Using the lariatin gene as a probe, a genomic library of R. jostii K01-B0171 was screened by colony hybridization, and two clones were obtained. Sequence analysis of these clones revealed that the gene cluster for lariatin biosynthesis spanning about 4.5 kb consisted of five open reading frames (larA to larE). We proposed that the linear precursor LarA is processed by LarB, LarC, and LarD, and the mature lariatin is exported by LarE.


CT ring sign imitating tumour, disclosed as multiple sclerosis by MRI: a case report.
A 21 year old woman with subacute onset of moderate left hemiparesis showed on CT scanning a left parietal ring shaped enhancing lesion indicative of tumour or abscess, while MRI revealed bilateral white matter lesions highly suggestive of MS. In none of the few similar cases reported was MRI available and most patients underwent biopsy or operation. The few reports of a CT-ring sign in MS are reviewed and the value of MRI in avoiding operation is stressed.


Estimating road traffic mortality more accurately: use of the capture-recapture method in the West Azarbaijan province of Iran.
The study estimates the rate of fatal road traffic injuries (RTIs) by population and road-users group in one Iranian province. The capture - recapture method was employed, using both the death register and the forensic medicine register over one year. They recorded totals of 669 and 665 RTIs respectively, giving a non-overlapping number of 897 cases. An estimate of 1018 fatalities occurred, at rates of 34 per 100,000 of the population for all road users aggregated, 10 per 100,000 for pedestrians and 25 per 100,000 for other road users. Coverage was somewhat better for victims less than 15 years of age, and also for males. The method showed 121 under-reported cases in both sources; however, it can help Iranian policy-makers to produce a good estimation of fatal RTIs number each year, when following up current RTIs-prevention programmes. Yet, given that each registry operates separately, optimum coverage will only be obtained when both sources are integrated and work together.


Antisecretory medication is associated with decreased Helicobacter pylori detection in gastric marginal zone lymphoma.
Helicobacter pylori status influences the prognosis and management of gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), so accurate determination of H pylori status is of clinical importance. The low rate of histologic H pylori positivity among gastric MALT lymphoma cases at our institution prompted investigation for possible causes. A case series of 24 patients as having gastric MALT lymphoma (with no diffuse large B-cell component) in a tertiary care setting between 1997 and 2010 was identified, and clinical records were reviewed. Immunohistochemical staining for H pylori and BCL10 was performed. This study received institutional review board approval (protocol number M13-033). Thirty-nine percent of cases (9/23) were H pylori positive by histology, and 4 additional patients had positive serologic results; overall, 57% of cases (13/23) were positive for H pylori. Treatment with antisecretory medications was associated with a lower likelihood of histologic positivity (13% among treated patients vs 75% among untreated; P = .04). Nuclear localization of BCL10 was seen in 2 cases and was not associated with H pylori status. Antisecretory medications decrease the likelihood of histologic detection of H pylori in gastric MALT lymphoma cases. Incorporation of results of serologic or other testing is needed to ensure correct classification with respect to H pylori status.


Mutation of OsALDH7 causes a yellow-colored endosperm associated with accumulation of oryzamutaic acid A in rice.
Aldehyde dehydrogenase proteins consist of a superfamily and the family 7 (ALDH7) is a typical group with highly conserved proteins across species. It catalyzes oxidation of α-aminoadipic semialdehyde (AASA) in lysine degradation, participates in protection against hyperosmotic stress, and detoxifies aldehydes in human; however, its function in plants has been much less documented. Here we reported a mutant with yellow-colored endosperm in rice, and showed that the yellow endosperm was caused by mutation of OsALDH7. OsALDH7 is expressed in all tissues detected, with the highest level in mature seeds. We found that oryzamutaic acid A accumulated during late seed development and after a year-long storage in the colored endosperm, whereas it was undetectable in the wild type endosperm. Moreover, lysine degradation was enhanced in yeast over-expressing OsALDH7 and as a result, content of lysine, glutamate and saccharopine was changed, suggesting a role of OsALDH7 in lysine catabolism.


Estimation of HIV prevalence and burden in Nigeria: a Bayesian predictive modelling study.
The cost of population-based surveys is high and obtaining funding for a national population-based survey may take several years, with follow-up surveys taking up to five years. Survey-based prevalence estimates are prone to bias owing to survey non-participation, as not all individuals eligible to participate in a survey may be reached, and some of those who are contacted do not consent to HIV testing. This study describes how Bayesian statistical modeling may be used to estimate HIV prevalence at the state level in a reliable and timely manner. We analysed national HIV testing services (HTS) data for Nigeria from October 1, 2020, to September 30, 2021, to derive state-level HIV seropositivity rates. We used a Bayesian linear model with normal prior distribution and Markov Chain Monte Carlo approach to estimate HIV state-level prevalence for the 36 states +1 FCT in Nigeria. Our outcome variable was the HIV seropositivity rates and we adjusted for demographic, economic, biological, and societal covariates collected from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS), 2018 Nigeria Demographic and Health Survey (NDHS) and 2016-17 Multiple Indicator Cluster Surveys (MICS). The estimated population of 15-49 years olds in each state was multiplied by estimates from the estimated prevalence to generate state-level HIV burden. Our estimated national HIV prevalence was 2.1% (95% CI: 1.5-2.7%) among adults aged 15-49 years in Nigeria, which corresponds to approximately 2 million people living with HIV, compared to previous national HIV prevalence estimates of 1.4% from the 2018 NAIIS and UNAIDS estimation and projection package PLHIV estimation of 1.8 million in 2022. Our modelled HIV prevalence in Nigeria varies by state, with Benue (5.7%, 95% CI: 5.0-6.3) having the highest prevalence, followed by Rivers (5.2%, 95% CI: 4.6-5.8%), Akwa Ibom (3.5%, 95% CI: 2.9-4.1%), Edo (3.4%, 95% CI: 2.9-4.0%) and Taraba (3.0%, 95% CI: 2.6-3.7%) placing fourth and fifth, respectively. Jigawa had the lowest HIV prevalence (0.3%), which was consistent with prior estimates. This model provides a comprehensive and flexible use of evidence to estimate state-level HIV seroprevalence for Nigeria using program data and adjusting for explanatory variables. Thus, investment in program data for HIV surveillance will provide reliable estimates for HIV sub-national monitoring and improve planning and interventions for epidemiologic control. This article was made possible by the support of the American people through the United States Agency for International Development (USAID) under the U.S. President's Emergency Plan for AIDS Relief (PEPFAR).


COX-2 mediates tumor-stromal prolactin signaling to initiate tumorigenesis.
Tumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single-cell RNA sequencing in an orthotopic mouse prostate cancer model, we find up-regulation of prolactin receptor as cancer cells that have disseminated to the lungs expand into micrometastases. Secretion of the ligand prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E2 (PGE2). PGE2 treatment of fibroblasts activates the orphan nuclear receptor NR4A (Nur77), with prolactin as a major transcriptional target for the NR4A-retinoid X receptor (RXR) heterodimer. Ectopic expression of prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor celecoxib abrogates prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, prolactin, and prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine cross-talk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression.


Ubiquitin-Conjugating Enzyme 2S Enhances Viral Replication by Inhibiting Type I IFN Production through Recruiting USP15 to Deubiquitinate TBK1.
Type I interferon (IFN) plays an essential role in the host innate immune responses. Several ubiquitin-conjugating enzyme (E2) family members were reported to regulate type I IFN production and host antiviral immune responses. However, the molecular mechanisms are still not fully understood. Here, we report that UBE2S acts as a negative regulator in the type I IFN signaling pathway. Ectopic expression of UBE2S inhibits host antiviral immune responses and enhances viral replications, whereas deficiency of UBE2S enhances host antiviral immune responses and suppresses viral replications both in vitro and in vivo. Inhibition of type І IFN production by UBE2S is independent on its E2 and E3 enzymic activity. Mechanistically, UBE2S interacts with TBK1 and recruits ubiquitin-specific protease 15 (USP15) to remove Lys63 (K63)-linked polyubiquitin chains of TBK1. Our findings reveal a role of the UBE2S-USP15-TBK1 axis in the regulation of host antiviral innate immune responses.


Protein kinase D: an intracellular traffic regulator on the move.
Recent research has identified protein kinase D (PKD, also called PKCmu) as a serine/threonine kinase with potentially important roles in growth factor signaling as well as in stress-induced signaling. Moreover, PKD has emerged as an important regulator of plasma membrane enzymes and receptors, in some cases mediating cross-talk between different signaling systems. The recent discovery of two additional kinases belonging to the PKD family and the plethora of proteins that interact with PKD point to a multifaceted regulation and a multifunctional role for these enzymes, with functions in processes as diverse as cell proliferation, apoptosis, immune cell regulation, tumor cell invasion and regulation of Golgi vesicle fission.


Characteristics of Giant Nodular Melanomas in Special Locations: a Case Series and Review of the Literature.
Nodular melanoma (NM) is a rare subtype of melanoma, responsible for more than 40% of melanoma deaths, characterized by rapid growth and high metastatic potential. Only a few case studies concerning the dermoscopic presentations of giant nodular melanoma have been reported so far. The aim of the study was to assess dermoscopic features of giant nodular melanomas in special locations, along with their clinical and histopathologic aspects. Among 120 patients with histopathologically confirmed melanoma treated by the Skin Cancer and Melanoma Team between September 2020 and February 2021, we identified six patients with giant nodular melanoma in special locations. We retrospectively assessed the archived dermoscopic images to determine the dermoscopic features of these tumors. The group consisted of six cases of giant melanoma in special locations, including the scalp (4/6) and the heel (2/6). The giant tumors were large in size (at least 5 cm in diameter). The most common dermoscopic structures in polarized light included asymmetric distribution of dermoscopic structures, the presence of structureless, multicolored zones (showing three or more colors), and the presence of white perpendicular lines or small, pink globules. It seems that there are no significant differences in dermoscopy between small and giant melanomas; however, further studies should be conducted on a larger scale.


Antigen-Specific Activation of Blood Lymphocytes in Mice Immunized with Brucella abortus 19 BA.
We studied the expression of activation markers CD25 and CD69 by blood lymphocytes in white mice vaccinated with Brucella abortus 19 BA in antigen-specific tests in vitro. During incubation of blood lymphocytes with brucellosis polysaccharide-protein antigen, a statistically significant increase in the expression of CD25 by B cells and CD69 by T cells was observed; brucellin increased the expression of CD25 by B and T cells. Comparative analysis of the action of antigen preparations B. abortus showed that only brucellin has antigen-specific activity against CD19+CD25+ cells. The used method can be considered as a promising test for evaluation of the effectiveness of brucellosis immunoprophylaxis, which substantiates the need for further research.


Chronobiologic optimization of aging.
Chronobiologic facts, concepts and methods are relevant to gerontology and geriatrics. Circadian and other rhythms are prominent sources of predictable variation requiring a reassessment of the "normal range" at all ages. Changes in the characteristics (e.g., the amplitude) of these rhythms during aging emphasize the need for careful evaluation of time dependency in research and clinical practice. Manipulation of periodic environmental factors that synchronize circadian rhythms can affect lifespans in plants and animals, further supporting the suggestion of an interaction between rhythms and senescence.


Interruption of treatment with individual therapeutic drug classes in adults with multidrug-resistant HIV-1 infection.
Many antiretroviral-treated human immunodeficiency virus (HIV)-infected patients experience sustained immunologic and virologic benefit despite the presence of multidrug-resistant HIV. We hypothesized that the use of simplified regimens could maintain treatment benefit while preventing viral evolution and reducing drug-related toxicity and costs. We conducted a 48-week nonrandomized study of adults with multidrug-resistant HIV type 1 infection. Subjects interrupted protease inhibitor (PI) (n=18), reverse-transcriptase inhibitor (RTI) (n=6), or nonnucleoside RTI (NNRTI) (n=6) treatment. At study entry, subjects had a median reduction in HIV RNA levels of 1.2 log10 copies/mL relative to pretreatment levels. Interruption of PI treatment was associated with stable HIV RNA levels (mean change per week, +0.005 log10 copies/mL; P=.36). PI mutations waned and replicative capacity and HIV RNA levels increased after long-term observation. HIV RNA levels also remained stable in subjects interrupting NNRTI treatment. In contrast, all subjects who interrupted RTI treatment exhibited immediate increases in HIV RNA levels, and most exhibited a subsequent loss of the M184V mutation. These data indicate that nucleoside analogues often exert continued antiviral activity in the setting of drug-resistance mutations and that both nucleoside analogues and PIs can select for drug-resistance mutations that reduce viral fitness. These observations support the evaluation of treatment strategies aimed at maintaining the treatment benefit of therapy while reducing drug exposure.


Assessing the effectiveness of postacute care rehabilitation.
This commentary reviews a number of issues related to determining the effectiveness of postacute care including what it is (in terms of type and site of care), how to tease out the critical elements (what components of this multifaceted process are essential), the role of research designs (given the logistic difficulties of doing randomized trials, how can nonexperimental designs be used to the greatest advantage), how to assess the relation between treatment and outcomes, measurement issues (what, when, how), correcting for case mix, and potential payment schemes.


Specific adsorption of H-2-restricted cytotoxi T cells to macrophage monolayers.
These experiments tested whether Tc cells specific for foreign antigen (X) plus self H-2 adsorbed to macrophage monolayers displaying (a) X with allogeneic H-2; (B) self H-2 alone; (c) X plus self H-2. Specific adsorption occurred only in case (c), a result compatible with altered self and requiring further operational assumptions in dual recognition models.


The role of phospholipase D1 in liver fibrosis induced by dimethylnitrosamine in vivo.
Phospholipase D (PLD) has been proved to be involved in regulating function of fibroblasts and might play a role in mediating organic fibrosis. To investigate the role and mechanism of PLD on dimethylnitrosamine (DMN)-induced rat liver fibrosis. Fifty-five male Wistar rats were divided into normal control group, DMN model group, N-methylethanolamine (MEA) control group, and MEA-intervention group. We observed the effects of MEA, a PLD inhibitor on the development and progression of rat liver fibrosis by comparing the physical and biochemical indexes, tissue pathology, PLD activity, and typical markers and cytokines related to fibrosis in the four groups. Accompanied by the down-regulation of PLD1 expression, the MEA-intervention group had improved outcomes compared with the DMN model group in terms of spleen weight, spleen/weight index, serum and tissue biochemical indexes, tissue hydroxyproline, and tissue pathology. The MEA-intervention group had lower TIMP1, COL1A1, and higher MMPs expression level than the DMN model group. The activity of PLD and PLD1, α-SMA expression level in the MEA-intervention group was much lower than those in the DMN model group. There was no significant difference between the two groups in the expression level of TGF-β1 and MCP1. Meanwhile, there were no significant differences between normal control group and MEA control group in the parameters stated above. Phospholipase D1 may play an important role in the development and progression of rat liver fibrosis. Inhibition of PLD may become a new strategy to prevent or alleviate liver fibrosis.


Identifying prognostic factors for clinical outcomes and costs in four high-volume surgical treatments using routinely collected hospital data.
Identifying prognostic factors (PFs) is often costly and labor-intensive. Routinely collected hospital data provide opportunities to identify clinically relevant PFs and construct accurate prognostic models without additional data-collection costs. This multicenter (66 hospitals) study reports on associations various patient-level variables have with outcomes and costs. Outcomes were in-hospital mortality, intensive care unit (ICU) admission, length of stay, 30-day readmission, 30-day reintervention and in-hospital costs. Candidate PFs were age, sex, Elixhauser Comorbidity Score, prior hospitalizations, prior days spent in hospital, and socio-economic status. Included patients dealt with either colorectal carcinoma (CRC, n = 10,254), urinary bladder carcinoma (UBC, n = 17,385), acute percutaneous coronary intervention (aPCI, n = 25,818), or total knee arthroplasty (TKA, n = 39,214). Prior hospitalization significantly increased readmission risk in all treatments (OR between 2.15 and 25.50), whereas prior days spent in hospital decreased this risk (OR between 0.55 and 0.95). In CRC patients, women had lower risk of in-hospital mortality (OR 0.64), ICU admittance (OR 0.68) and 30-day reintervention (OR 0.70). Prior hospitalization was the strongest PF for higher costs across all treatments (31-64% costs increase/hospitalization). Prognostic model performance (c-statistic) ranged 0.67-0.92, with Brier scores below 0.08. R-squared ranged from 0.06-0.19 for LoS and 0.19-0.38 for costs. Identified PFs should be considered as building blocks for treatment-specific prognostic models and information for monitoring patients after surgery. Researchers and clinicians might benefit from gaining a better insight into the drivers behind (costs) prognosis.


Risk analysis of grade ≥ 2 radiation pneumonitis based on radiotherapy timeline in stage III/IV non-small cell lung cancer treated with volumetric modulated arc therapy: a retrospective study.
Radiotherapy is an important treatment for patients with stage III/IV non-small cell lung cancer (NSCLC), and due to its high incidence of radiation pneumonitis, it is essential to identify high-risk people as early as possible. The present work investigates the value of the application of different phase data throughout the radiotherapy process in analyzing risk of grade ≥ 2 radiation pneumonitis in stage III/IV NSCLC. Furthermore, the phase data fusion was gradually performed with the radiotherapy timeline to develop a risk assessment model. This study retrospectively collected data from 91 stage III/IV NSCLC cases treated with Volumetric modulated arc therapy (VMAT). Patient data were collected according to the radiotherapy timeline for four phases: clinical characteristics, radiomics features, radiation dosimetry parameters, and hematological indexes during treatment. Risk assessment models for single-phase and stepwise fusion phases were established according to logistic regression. In addition, a nomogram of the final fusion phase model and risk classification system was generated. Receiver operating characteristic (ROC), decision curve, and calibration curve analysis were conducted to internally validate the nomogram to analyze its discrimination. Smoking status, PTV and lung radiomics feature, lung and esophageal dosimetry parameters, and platelets at the third week of radiotherapy were independent risk factors for the four single-phase models. The ROC result analysis of the risk assessment models created by stepwise phase fusion were: (area under curve [AUC]: 0.67,95% confidence interval [CI]: 0.52-0.81), (AUC: 0.82,95%CI: 0.70-0.94), (AUC: 0.90,95%CI: 0.80-1.00), and (AUC:0.90,95%CI: 0.80-1.00), respectively. The nomogram based on the final fusion phase model was validated using calibration curve analysis and decision curve analysis, demonstrating good consistency and clinical utility. The nomogram-based risk classification system could correctly classify cases into three diverse risk groups: low-(ratio:3.6%; 0 < score < 135), intermediate-(ratio:30.7%, 135 < score < 160) and high-risk group (ratio:80.0%, score > 160). In our study, the risk assessment model makes it easy for physicians to assess the risk of grade ≥ 2 radiation pneumonitis at various phases in the radiotherapy process, and the risk classification system and nomogram identify the patient's risk level after completion of radiation therapy.


New briarane-type diterpenoids from gorgonian Ellisella dollfusi from the South China Sea.
Two new briarane-type diterpenoids, dollfusilin A (1) and dollfusilin B (2), along with five known briarane-type diterpenoids (3-7), were isolated from the gorgonian Ellisella dollfusi collected from the South China Sea. The structures of the two new compounds (1 and 2) were elucidated through a comprehensive analysis of spectroscopic data, especially 2D NMR. The bioactivities of the isolated compounds were evaluated using the zebrafish toxicity model.


Enterotoxigenic Bacteroides fragilis.
Bacteroides fragilis is a minor component of the microbial flora of the intestine but the most frequent disease--causing anaerobe. Virulence characteristics are its capsule, which induces abscess formation, and the production of fragilysin, a Zn-metalloprotease. This toxin's action is to hydrolyze the extracellular domain of E-cadherin, the effect of which is to disrupt intercellular adhesion and thus increase permeability of the epithelium, causing intracellular redistribution of actin with morphologic changes to the cells and release of beta-catenin, which translocates to the nucleus and ultimately increases cellular proliferation. Clinically, enterotoxigenic B. fragilis is linked to secretory diarrhea, particularly in children. Preliminary evidence suggests that enterotoxigenic B. fragilis may also be linked to inflammatory bowel disease and colon cancer.


Isolated fallopian tube torsion associated with hydrosalpinx in a 12-year-old girl: a case report.
Isolated fallopian tube torsion associated with hydrosalpinx is a rare condition in the pediatric population. We present this unusual clinical case study in a sexually inactive girl. a12-year-old Caucasian girl presented symptoms of acute abdominal pain. Pelvic ultrasound revealed a normal looking uterus and ovaries and next to left ovary a imaging compatible with hydrosalpinx. She was discharged 48 hours later after clinical monitoring with oral analgesia and normal blood workup. At 3 weeks, she was readmitted for acute abdominal pain. Leukocytosis with left shift and raised C-reactive protein were observed. Her clinical condition worsened, and complication of the preexisting hydrosalpinx was suspected. Exploratory laparoscopy confirmed torsion of the fallopian tube. Left salpingectomy was performed. Histopathologic study confirmed a fallopian tube with hemorrhagic infarct. Torsion of the fallopian tube must be considered in the event of acute abdominal pain. Early diagnosis and trying conservative management with a view to preserving fertility in this group of patients are essential.