Smart, degradable, and eco-friendly carboxymethyl cellulose-CaII hydrogel-like networks gated MIL-101(FeIII) nanoherbicides for paraquat delivery.
Nanopesticides have been selected as one of the top 10 chemical innovations for enhancing the efficacy and safety of agrochemicals. Herein, smart, degradable, and eco-friendly metal-organic framework MIL-101(FeIII) nanoherbicides coated with carboxymethyl cellulose-CaII (CMC-CaII) cross-linking hydrogel-like networks are synthesized via a simple strategy. The coating of the CMC-CaII hydrogel-like gatekeepers is oriented by the coordination unsaturated FeIII clusters on the surfaces of the MIL-101(FeIII) nanocarriers to form a dense film network to prevent paraquat (PQ) leakage. Based on the stimuli factors (acid/basic pH, GSH, phosphates, and EDTA) of physiological and natural environments of target plants, the nanoherbicides are combined with five stimuli-responsive properties to attain the various controlled release of packaged PQ by the disassembly of the gatekeepers and/or the degradation of the MOF skeleton structure. More importantly, based on the stimuli-responsive controlled release mechanisms, the eco-friendly nanocarriers are ultimately degraded against bioaccumulation in plants or soil. The coating of natural CMC could promote the spreading of PQ owing to improvement of wettability for aqueous droplets of nanoherbicides on hydrophobic foliage. The PQ trapped in nanocarriers can effectively prevent PQ degradation, which showed that cumulative degradation rate is ca. 2.6 times lower than that of technical PQ under UV irradiation. The prepared nanoherbicides loaded with PQ show good control efficacy against weeds by controlling the release of PQ; good safety on seed germination (germination rate 97.32-99.67 %), seedling emergence (emergence rate 95.53-99.67 %), and are beneficial for the growth of wheat seedling (increase rate of plant height 1.89-6.97 % and 0.54-5.67 % after 7 and 15 days of seedling emergence, respectively) in the greenhouse; good biosafety for honeybees (Apis mellifera L.), which shows that lethal rates were 2.04 and 2.55 times lower than technical PQ for incubation 24 and 48 h, respectively. The nanoherbicides have potential applications in the field for PQ green agriculture.


Nuclear magnetic resonance studies of hemoprotein. Proton hyperfine shifts and structural characterization of the different heme environments in methemoglobin and metmyoglobin.
The different features of the nature of heme iron-proximal binding in methemoglobin and metmyoglobin were investigated by high resolution proton nuclear magnetic resonance spectroscopy at 220 MHz. From the comparison of the hyperfine-shifted heme methyl resonances of various methemoglobin and metmyoglobin derivatives it was revealed that the metHb derivatives exhibit smaller hyperfine shifts than the corresponding metMb derivatives. This observation was interpreted in terms of the stronger interaction between proximal histidine and ferric heme iron in methemoglobin than in metmyoglobin. The spectral contributions from the alpha and beta subunits in methemoglobin in high spin state were successfully separated by the analysis of the temperature dependent heme methyl shifts of the methemoglobin azide complex which is in the high and low thermal spin equilibrium. It was shown that the beta heme methyl resonances have smaller hyperfine shifts than the alpha heme ones in ferric high spin state. This tendency in methemoglobin derivatives was also interpreted in terms of the stronger iron-histidine binding in the beta subunits than in the alpha subunits within the tetramer. From the comparisons between methemoglobin and metmyoglobin, and between the alpha and beta subunits in methemoglobin, the order of the strength of the iron-histidine bond interaction was deduced as follows: metmyoglobin less than alpha subunits in methemoglobin less than or equal to beta units in methemoglobin.


Mechanism of ESAT-6 membrane interaction and its roles in pathogenesis of Mycobacterium tuberculosis.
The 6-kDa early secreted antigenic target (ESAT-6; EsxA) of Mycobacterium tuberculosis was first identified as a potent T-cell antigen, and it is now recognized as a pore-forming toxin that is essential for virulence of M. tuberculosis. ESAT-6 is secreted through the ESX-1 secretion system (Type VII) of M. tuberculosis and has been implicated to mediate mycobacterial cytosolic translocation within the host macrophages by rupturing the phagosomal membranes. Recent studies have made significant progresses in understanding of the mechanism of ESAT-6 membrane interaction and its role in M. tuberculosis pathogenesis, but important questions still remain to be answered. Here, we summarize the current progress in study of ESAT-6 membrane interaction and its roles in pathogenesis and discuss some of the key remaining questions for future investigation.


Standardized system and App for continuous patient symptom logging in gastroduodenal disorders: Design, implementation, and validation.
Functional gastroduodenal disorders include functional dyspepsia, chronic nausea and vomiting syndromes, and gastroparesis. These disorders are common, but their overlapping symptomatology poses challenges to diagnosis, research, and therapy. This study aimed to introduce and validate a standardized patient symptom-logging system and App to aid in the accurate reporting of gastroduodenal symptoms for clinical and research applications. The system was implemented in an iOS App including pictographic symptom illustrations, and two validation studies were conducted. To assess convergent and concurrent validity, a diverse cohort with chronic gastroduodenal symptoms undertook App-based symptom logging for 4 h after a test meal. Individual and total post-prandial symptom scores were averaged and correlated against two previously validated instruments: PAGI-SYM (for convergent validity) and PAGI-QOL (for concurrent validity). To assess face and content validity, semi-structured qualitative interviews were conducted with patients. App-based symptom reporting demonstrated robust convergent validity with PAGI-SYM measures of nausea (rS =0.68), early satiation (rS =0.55), bloating (rS =0.48), heartburn (rS =0.47), upper gut pain (rS =0.40), and excessive fullness (rS =0.40); all p < 0.001 (n = 79). The total App-reported Gastric Symptom Burden Score correlated positively with PAGI-SYM (rS =0.56; convergent validity; p < 0.001), and negatively with PAGI-QOL (rS = -0.34; concurrent validity; p = 0.002). Interviews demonstrated that the pictograms had adequate face and content validity. The continuous patient symptom-logging App demonstrated robust convergent, concurrent, face, and content validity when used within a 4-h post-prandial test protocol. The App will enable standardized symptom reporting and is anticipated to provide utility in both research and clinical practice.


The role of flagellin F in Vibrio Parahaemolyticus-induced intestinal immunity and functional domain identification.
The marine pathogen Vibrio parahaemolyticus has caused huge economic losses to aquaculture. Flagellin is a key bacterial virulence factor that induces an inflammatory response via activation of Toll-like receptor 5 (TLR5) signaling. Herein, to explore the inflammatory activity of V. parahaemolyticus flagellins (flaA, flaB, flaC, flaD, flaE, and flaF), we investigated their ability to induce apoptosis in a fish cell line. All six flagellins induced severe apoptosis. Moreover, treatment with V. parahaemolyticus flagellins increased TLR5 and myeloid differentiation factor 88 (MyD88) expression and the production of TNF-α and IL-8 significantly. This indicated that flagellins might induce a TLR5-meditated immune response via an MyD88-dependent pathway. FlaF exhibited the strongest immunostimulatory effect; therefore, the interaction between TLR5 and flaF was screened using the yeast two-hybrid system. A significant interaction between the two proteins was observed, indicating that flaF binds directly to TLR5. Finally, the amino acids that participate in the TLR5-flaF interaction were identified using molecular simulation, which indicated three binding sites. These results deepen our understanding of the immunogenic properties of flagellins from V. parahaemolyticus, which could be used for vaccine development in the future.


Plasma 25-hydroxyvitamin D levels are favorably associated with β-cell function.
The association of hypovitaminosis D with type 2 diabetes is well recognized. Although hypovitaminosis D is associated with insulin resistance, there is much less information about its impact on β-cell function in humans. We enrolled 150 healthy, glucose-tolerant subjects for the assessment of β-cell function (acute insulin response) and insulin sensitivity index (ISI) using a hyperglycemic clamp. Adjusted β-cell function (ABCF) was defined as the product of acute insulin response and ISI. The relations of plasma 25-hydroxyvitamin D [25(OH)D] level with insulin sensitivity and ABCF were examined. Plasma 25(OH)D levels were positively associated with ABCF (P = 0.00004) and ISI (P < 0.00001). The associations remained significant after adjustment for age, sex, body mass index, physical activity, ethnicity, and season of study. Plasma 25(OH)D levels are positively association with both β-cell function and insulin sensitivity. Our observations suggest the roles of vitamin D deficiency in the dual defect of type 2 diabetes.


Gouty arthritis of the axial skeleton including the sacroiliac joints.
We treated a 62-year-old man with intermittent polyarthritis whose neck pain was prominent. Progressive deformities, limited neck motion, and the appearance of subcutaneous nodules prompted his admission to the hospital. The diagnosis of gout was established; the erosive and destructive changes in C6-7 were believed to be due to gout as well. Cervical spine involvement, although rare, can occur in gout.


Expecting dirt but saying dart: the creation of a blend memory.
During a naming task, time pressure and a manipulation of the proportion of related prime-target pairs were used to induce subjects to generate an expectation to the prime. On some trials, the presented target was orthographically and generally phonologically similar to the expected target. The expectancy manipulation was barely detectable in the priming data but was clearly evident on a final recognition test. In addition, the recognition data showed that the nearly simultaneous activation of an expectation and sensory information derived from the orthographically and phonologically similar target produced a false memory. It is argued that this represents a blend memory.


Using the Health Belief Model to assess COVID-19 perceptions and behaviours among a group of Egyptian adults: a cross-sectional study.
It is crucial to study the public's perceptions and behaviour during a pandemic as this will be the driving force for practicing recommended precautions. The current study aimed to identify perceptions of a group of Egyptian adults to COVID-19 using the Health Belief Model (HBM), to measure self-reported practice of preventive behaviours and to identify influencing factors. Cross sectional study was used, including Egyptian adults aged 18 + years. A structured anonymous online questionnaire was used including: a demographic section, the modified MERS- CoV Health Belief Model scale after addition of questions related to COVID-19 and questions on preventive behaviours to COVID-19. Of the 532 study participants, 28.6% were males, age ranges (18 to 74 years). There was a statistically significant positive correlation between total practice score and all COVID-19 Health Belief Model constructs total scores except for perceived barriers score showing negative correlation (P value < 0.05). Linear regression analysis showed that older age, male gender and living inside Cairo were associated with lower practice score (P value < 0.01). Increased perceived susceptibility, perceived benefits, cues to action and perceived self-efficacy scores were associated with higher practice score in the current study. Additionally, results revealed that social media and websites can play an important role in shaping risk perception in the community. Stressing risk perception and efficacy beliefs prevention message can drive people to practice preventive behaviors.


High-Throughput Plant Gene Expression Analysis by 384-Format Reverse Transcription-Quantitative PCR for Investigating Plant Iron Homeostasis.
Analysis of plant gene expression is important in determining iron (Fe) homeostasis gene functions during plant development or in response to biotic and abiotic factors. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) has many advantages. It is fast, inexpensive, accurate, and reproducible in any lab. Furthermore, RT-qPCR can be scaled up to study several genes of interest in many biological samples from any organism. We hereby provide a straightforward protocol on RT-qPCR analysis using a 384-well format for large-scale gene expression studies on Fe-regulated responses. The protocol highlights in detail, the steps ranging from choice and design of qPCR analysis, collection of plant material and RNA preparation, cDNA synthesis, set up of qPCR and run, thorough analysis of qPCR run data, and display of multiple gene expression data for convenient interpretation.


Partial nephrectomy is not associated with an overall survival advantage over radical nephrectomy in elderly patients with stage Ib-II renal masses: An analysis of the national cancer data base.
Partial nephrectomy (PN) is recommended for localized T1a (≤4 cm) renal masses and is preferred over radical nephrectomy (RN) for amenable T1b/T2 (>4 cm) tumors. The objective of the current study was to assess overall survival (OS) differences between PN and RN in patients with T1 and T2 renal cell carcinoma (RCC). The National Cancer Data Base was queried for patients with T1 and T2 RCC who underwent PN or RN from 2004 to 2014. Trends in surgery were evaluated using Cochran-Armitage tests. Differences in OS were assessed using adjusted Kaplan-Meier methods. The effects of procedure on OS were analyzed using propensity score-based, weighted Cox proportional hazards models. In total, 212,016 patients with T1 and T2 RCC who underwent either RN (59.7%) or PN (40.3%) were included. The use of PN rose from 2004 to 2014 (T1a: from 40.6% to 71.4%; T1b/T2: from 8.4% to 26.5%; P < .01). Adjusted 5-year OS was longer for patients who underwent PN in both subsets, although effect magnitude was reduced in the T1b/T2 cohort (T1a: 89.6% vs 85.1%; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.70-0.75; P < .01; T1b/T2: 82.5% vs 80.8%; HR, 0.88; 95% CI, 0.83-0.94; P = .01). The benefit of PN on OS diminished as age and time from diagnosis increased; no OS improvement was observed in patients age ≥75 years who had T1b/T2 tumors (HR, 0.89; 95% CI, 0.76-1.06). Receipt of PN is associated with improved OS in patients with T1a RCC. No procedure-related differences in OS were observed for patients age ≥75 years who had tumors measuring >4 cm. Decisions to undergo PN for T1b/T2 tumors should be based on individualized risk assessment.


Influence of Norm-Based Messages on College Students' Binge Drinking Intentions: Considering Norm Type, Regulatory Mode, and Level of Alcohol Consumption.
This study examined the influence of norm-based messages on U.S. college students' binge drinking intentions, focusing on norm type, locomotion and assessment regulatory modes, and level of alcohol consumption as possible moderators. Results of an online experiment (N = 519) revealed significant three-way interactions among regulatory mode (assessment/locomotion), level of alcohol consumption, and norm type (i.e., descriptive vs. injunctive norms) on binge drinking intentions. The relative persuasiveness of descriptive vs. injunctive norm-based messages was contingent upon an individual's locomotion/assessment regulatory mode and overall alcohol consumption level. Findings from this study extend research on social norms and regulatory mode and provide useful suggestions for the norm-based college drinking intervention.


Galanin-stimulated high-affinity GTPase activity in plasma membranes from RINm5F cells.
GTPase activity was studied in plasma membranes purified from the clonal beta-cell line RINm5F. GTPase activities were identified as two broad classes with high or low affinity for GTP. The low-affinity GTPase activity had a Km > 60 microM. In contrast, the high-affinity activity had a Km of 225 nM. Only the high-affinity activity was stimulated by galanin. The stimulated activity had a higher Km (448 nM) and Vmax (75 pmol P(i).min-1.mg-1 protein) compared with the basal. This does not necessarily reflect a complex mechanism of stimulation. Rather, it may reflect that basal activity most likely results from multiple GTPases, whereas the stimulated activity probably reflects one or two specific GTPases. Galanin stimulated the high-affinity GTPase, over the concentration range in which it inhibits stimulated insulin secretion, to a maximal rate 80% greater than the basal rate. The EC50 was 5 nM. Murine and porcine galanin had similar potencies and intrinsic activities on the GTPase. Treatment of the RINm5F cells with PTX before making membranes completely eliminated the stimulatory effect of galanin. Thus, galanin stimulates PTX-sensitive GTPase activity in RINm5F cell membranes in a manner consistent with receptor activation.


[Slipped capital femoral epiphysis].
Slipped capital femoral epiphysis (SCFE) is characterized by displacement of the capital femoral epiphysis from the metaphysis through the physis. The term is confusing, because the metaphysis moves upward and outward while the epiphysis remains in the acetabulum. The SCFE is considered stable when the child is able to walk with or without crutches, and it is considered unstable when the child cannot walk with or without crutches. Patients with SCFE present with pain in the groin, knee and limp. The current treatment of stable SCFE is in situ stabilization with a single screw.


Myoepithelial cells in needle aspirations of two cases of unusual breast lesions: an aid in differential diagnosis.
The observation of myoepithelial cells bordering abnormal epithelial cells in fine-needle aspiration smears of two unusual breast lesions helped to prevent misdiagnosis of these lesions as malignant. The presence of myoepithelial cells has been a well-established criterion for histologically benign lesions. Their presence or absence appears to be equally valuable in fine-needle aspiration smears of breast lesions.


Characterization of protein conjugates using capillary electrophoresis.
With the aim of generating antibodies, a calix[4]arene-crown-6 was coupled to bovine serum albumin. For that purpose, a complete procedure to optimize and characterize the coupling of hydrophobic haptens based on capillary electrophoresis (CE) was developed. We demonstrated the existence of a polynomial relationship between the electrophoretic mobility (mu(ep)) and the hapten density. This correlation was used not only to study the coupling reaction in terms of optimization and kinetics but also to determine the average coupling molar ratio of any given conjugate. An estimation of the heterogeneity of these conjugates by simulation of experimental peaks was also proposed.


Surgical treatment of lung cancer in patients with human immunodeficiency virus.
Since January 1986, more than 20 patients have been seen at the University of Miami/Jackson Memorial Medical Center and the Miami Veterans Administration Medical Center with concurrent human immunodeficiency virus infection and bronchogenic carcinoma. Four of these patients were treated surgically with curative intent. The histories, records, operative reports, and pathology reports of the 4 patients were reviewed. The 4 surgically treated patients had stage I T1 N0 M0 lung cancer. Three patients had T4 cell counts of less than 200/microL and were managed by lobectomy. These patients died 5, 3 1/2, and 5 months postoperatively. More recently, a fourth patient had a T4 cell count of 963/microL and was treated with wedge resection. He is currently alive 12 months postoperatively. It is concluded that surgically treated patients with lung cancer, human immunodeficiency virus infection, and T4 cell counts lower than 200/microL have high mortality and morbidity. Although it may be best to base surgical intervention on the stage of the patient's human immunodeficiency virus infection, further analysis is essential to determine which subgroup of human immunodeficiency virus-positive patients, if any, would benefit from surgical treatment of lung cancer.


Nephrotic range proteinuria with "minimal change glomerulopathy" in human renal allografts: report of four cases.
Four patients who received renal allografts developed nephrotic range proteinuria 2 to 16 months after renal transplantation. Twenty-four-hour urine protein excretion at the time of renal allograft biopsy ranged from 5.9 to 17.0 g/24 hours. The serum creatinine at the time of renal allograft biopsy ranged from 2.0 to 3.9 mg/dl (180 to 350 mumol/L). Biopsies of the allografts demonstrated minimal glomerular abnormalities by light microscopy, immunomicroscopy, and electron microscopy. Two biopsies exhibited severe interstitial fibrosis. These four cases illustrate the unusual finding of "minimal change glomerulopathy" in renal allograft recipients exhibiting nephrotic range proteinuria. All four patients progressed to dialysis 4, 36, 46, and 53 months after transplantation. Transplant nephrectomy was performed in three patients. One showed acute cortical necrosis. Two showed glomerular, vascular, and tubular-interstitial features of chronic rejection.


Coupled-column chromatography on immobilized protein phases for direct separation and determination of drug enantiomers in plasma.
Columns packed with immobilized alpha 1-acid glycoprotein and albumin were used in coupled-column chromatography to increase their utility for determining low concentrations of enantiomers in biological samples. The two enantiomers eluted from the protein columns were trapped and compressed on two separate columns, packed with hydrophobic stationary phase, and subsequently transferred to a fourth column for final separation. The overall effect was an increase in efficiency and selectivity. Examples are given of separations of the enatiomers of terbutaline, metoprolol, oxazepam and bupivacaine in plasma. For quantitative determination a single calibration can be used for both enantiomers.


Direct in vivo evidence of CD4+ T cell requirement for CTL response and memory via pMHC-I targeting and CD40L signaling.
CD4(+) T cell help contributes critically to DC-induced CD8(+) CTL immunity. However, precisely how these three cell populations interact and how CD4(+) T cell signals are delivered to CD8(+) T cells in vivo have been unclear. In this study, we developed a novel, two-step approach, wherein CD4(+) T cells and antigen-presenting DCs productively engaged one another in vivo in the absence of cognate CD8(+) T cells, after which, we selectively depleted the previously engaged CD4(+) T cells or DCs before allowing interactions of either population alone with naïve CD8(+) T cells. This protocol thus allows us to clearly document the importance of CD4(+) T-licensed DCs and DC-primed CD4(+) T cells in CTL immunity. Here, we provide direct in vivo evidence that primed CD4(+) T cells or licensed DCs can stimulate CTL response and memory, independent of DC-CD4(+) T cell clusters. Our results suggest that primed CD4(+) T cells with acquired pMHC-I from DCs represent crucial "immune intermediates" for rapid induction of CTL responses and for functional memory via CD40L signaling. Importantly, intravital, two-photon microscopy elegantly provide unequivocal in vivo evidence for direct CD4-CD8(+) T cell interactions via pMHC-I engagement. This study corroborates the coexistence of direct and indirect mechanisms of T cell help for a CTL response in noninflammatory situations. These data suggest a new "dynamic model of three-cell interactions" for CTL immunity derived from stimulation by dissociated, licensed DCs, primed CD4(+) T cells, and DC-CD4(+) T cell clusters and may have significant implications for autoimmunity and vaccine design.


Zinc application alleviates the adverse renal effects of arsenic stress in a protein quality control way in common carp.
The potential antagonistic mechanism between zinc (Zn) and arsenic (As) on renal toxicity was investigated in common carp. The results showed that by increased Zn efflux and retention (as reflected by zinc transporter 1 (ZnT-1), Zrt- and Irt- 1ike protein (ZIP) and metallothionein (MT) expression), Zn co-administration significantly recovered the antioxidant function (catalase, CAT) and the level of renal barrier function (Occludin, Claudins and Zonula Occludens) in comparison to As treatment. Interestingly, Zn co-administration with As resulted in carps undergoing reduction of heat shock response (HSPs), a low induction of autophagy flux (Beclin-1, microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (P62)) and decreased endoplasmic reticulum (ER) stress (activating transcription factor 6 (ATF-6), inositol requiring-1α (IRE1) and PKR-like ER kinase (PERK)) in the aspect of mRNA or protein levels. All these alleviated protein quality control processes induced by Zn under As stress was correlated with the no longer loosen tight connection, less swollen endoplasmic reticulum as well as reduced formation of autophagosomes and autophagic vesicles. Mechanically, post-transcriptional regulated protein quantities compromising phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway was demonstrated true causative forces inside the cell for Zn against As poisoning. In conclusion, we suggested the potential renal protective effect of Zn supplementation against As exposure by the modulation of protein quality control processes.


The Impact of Different Sources of Zinc, Manganese, and Copper on Broiler Performance and Excreta Output.
Commercial premixes provide trace minerals (TM) such as zinc (Zn), manganese (Mn), and copper (Cu) in excess of the requirements to maximize broiler performance. High inclusion levels of TM in broiler feed and their low absorption in the gastrointestinal tract leads to increased levels of TM in the excreta, resulting in the contamination of the environment. A 35-day broiler trial was conducted with 2880 one-day-old Cobb broiler males to test the effect of the supplementation of different sources of TM on growth performance, while evaluating levels in the excreta. Inorganic (ITM), organic (OTM), and hydroxy (HTM) sources of TM were tested against a positive control of current recommended levels of ITM. At 35 d, birds fed HTM were 55 g (p < 0.05) heavier than those fed ITM at the same inclusion level. In contrast, birds fed the control, OTM, and HTM showed no significant difference in body weight. Providing broilers with HTM significantly (p < 0.05) reduced Zn and Cu excretion at 35 d of when compared to those who were fed diets containing ITM or PC. Supplementing different sources of TM to broiler diets at levels below the recommendations showed no negative effect on broiler performance. The use of HTM significantly reduced TM excretion in broilers. The use of HTM in broiler diets can maintain broiler performance and reduce the negative impact on the environment.


Antibiotic resistome associated with influencing factors in industrial-scale organic waste aerobic composting plants.
This study investigated the fate of antibiotic resistance genes (ARGs) and bacterial evolution in six industrial-scale organic wastes aerobic composting plants and identified key factors driving ARGs dynamics. A total of 226 ARGs and 46 mobile genetic elements (MGEs), mainly resistant to aminoglycoside and MLSB, were detected by high-throughput qPCR. Briefly, aerobic composting showed good performance in reducing the diversity and abundance of ARGs, where the total absolute abundance was reduced by 88.34%-97.08% except for cattle manures. Rapid composting may lead to a rebound of ARGs due to long-term storage compared to traditional composting. Hub ARGs and bacterial genera were screened out by co-occurrence patterns. As the dominant phyla in composting, the main potential hosts of ARGs were Firmicutes, Bacteroidota and Proteobacteria. Structural equation model indicated that MGEs and heavy metals were key factors affecting ARGs dynamics. In addition, nutrients and bacterial α-diversity can indirectly influence ARGs by affecting MGEs.


'A normal delivery takes place at home': a qualitative study of the location of childbirth in rural Ethiopia.
To identify reasons why women who access health facilities and utilise maternal newborn and child health services at other times, do not necessarily deliver at health facilities. Forty-six semi-structured interviews were conducted with mothers who had recently delivered (n = 30) or were pregnant (n = 16). Thematic analysis of the interview data resulted in emerging trends that were critically addressed according to the research objective. Of the 30 delivered cases, 14 had given birth at a health facility, but only 3 of those had planned to do so. The remaining 11 had attended due to long or complicated labours. Five dominant themes influencing location of delivery were identified: perceptions of a normal delivery; motivations encouraging health facility delivery; deterrents preventing health facility deliveries; decision-making processes; and level of knowledge and health education. Understanding the socio-cultural determinants that influence the location of delivery has implications for service provision. Alongside timely health education and maximising the contact between women and healthcare professionals, these determinants should be actively incorporated into maternal newborn and child health policy and programming in ways that encourage the utilisation of health facilities, even for routine deliveries.


Arthroscopic reduction versus fluoroscopic reduction in the management of intra-articular distal radius fractures.
Although arthroscopy offers an unparalleled view of intra-articular pathology, its use in the treatment of intra-articular distal radius fractures remains controversial. This study was designed to compare functional and radiologic outcomes of arthroscopically assisted (AA) versus fluoroscopically assisted (FA) reduction and external fixation of distal radius fractures. Retrospective, case-matched comparison of 2 different procedures. Between January 1995 and December 1999, 15 patients with comminuted intra-articular distal radius fractures underwent AA external fixation and percutaneous pinning. Fifteen patients underwent external fixation and FA reduction and pinning. Patients in both groups were matched for fracture pattern and age. Follow-up evaluation consisted of an evaluation of grip strength and range of motion as well as radiographic evaluation of palmar tilt, radial shortening, stepoff, and degenerative changes. Health-related quality of life outcomes were assessed using the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Patients who underwent AA surgery had significantly improved supination compared with those who underwent FA surgery (88 degrees v 73 degrees; P =.02). AA reduction also resulted in improved wrist extension (mean, 77 degrees v 69 degrees; P =.01) and wrist flexion (mean, 78 degrees v 59 degrees; P =.02). Radial shortening, Knirk and Jupiter congruity grades, and DASH scores were similar for both groups. AA reduction and fixation of intra-articular distal radius fractures permits a more thorough inspection of the ulnar-sided components of the injury. At follow-up evaluation, patients who underwent AA procedures had a greater degree of supination, flexion, and extension than patients undergoing FA surgery. Level II prospective cohort study.


Evaluation of Anxiety and Depression in Women Undergoing Mastectomy in Greece.
To determine the levels of depression and anxiety in women undergoing mastectomy and to investigate the factors related to the onset of anxiety and depression on the eve of the surgery. This is a prospective observational study. The sample of the study consisted of 82 women with breast cancer who are going to undergo surgery. The assessment of patient anxiety and depression was done with the HADS anxiety and depression hospital scale. The study sample was 82 patients aged 56.8 ± 12.9 years. Most of them were married (68.3%), had children (87.5%), were Greek (93.6%), Orthodox Christians (97.4%), housewives (28%), and retired (23.2%). In total, 70 (85.4%) participants would be subjected to single mastectomy and 12 (14.6%) both of them. More than half of respondents (51.9%) smoked, while 32.7% consumed alcohol. 51.2% had pathological stress levels and 31.7% pathological levels of depression. Participants with abnormal levels of anxiety were significantly younger (p < 0.05), smoked at a significantly lower rate (p < 0.05), and made significantly fewer cigarettes per day (p < 0.05). Participants with abnormal levels of depression were significantly younger (p < 0.05), significantly more "other" (p < 0.05) and "other" (p < 0.05) and had a significantly higher educational level (p < 0.05). The factors found to affect participants stress levels were young age, reduced smoking rates, and the smallest number of cigarettes per day, while the factors found to affect participants' levels of depression were the young age, the other ethnicity except for Greek, the other religion except Christianity, and the highest educational level.


Glomerular galactose-deficient IgA1 expression analysis in pediatric patients with glomerular diseases.
Galactose-deficient IgA1 (Gd-IgA1) is important in the pathogenesis of IgA nephropathy (IgAN). A Gd-IgA1-specific monoclonal antibody (KM55) has revealed glomerular Gd-IgA1 deposition solely in patients with IgAN and IgA vasculitis with nephritis (IgAV-N). However, this specificity is controversial and has not been demonstrated in pediatric patients. Here, we conducted double-immunofluorescence staining of IgA and Gd-IgA1 in 60 pediatric patients with various glomerular diseases. We divided patients into four groups: (1) patients with IgAN and IgAV-N (n = 23); (2) patients with immunocomplex-mediated glomerulonephritis accompanied by IgA deposition, including lupus nephritis, membranoproliferative glomerulonephritis, and membranous nephropathy (n = 14); (3) patients with other glomerular diseases involving IgA deposition, including idiopathic nephrotic syndrome (INS), oligomeganephronia, Alport syndrome, dense deposit disease, and crescentic glomerulonephritis (n = 11); and (4) patients with IgA-negative diseases including INS, membranoproliferative glomerulonephritis, membranous nephropathy, oligomeganephronia, Alport syndrome, C3 glomerulonephritis, poststreptococcal acute glomerulonephritis, and hemolytic uremic syndrome (n = 12). KM55 staining revealed Gd-IgA1-positive findings in 23/23 patients in Group 1 and 13/14 patients in Group 2, but not in patients in Groups 3 or 4. Therefore, KM55 may detect incidental IgA deposition in pediatric patients. Gd-IgA1 may be involved in the pathogenesis of these immune-related diseases; alternatively, KM55 may recognize IgA-related immunocomplexes in a non-specific manner.


Investigation of the Interaction between N-Acetyl-l-Cysteine and Ovalbumin by Spectroscopic Studies, Molecular Docking Simulation, and Real-Time Quartz Crystal Microbalance with Dissipation.
This study investigated the interaction between N-acetyl-l-cysteine (NAC) and ovalbumin (OVA) using multispectroscopic technology, molecular docking, and quartz crystal microbalance with dissipation (QCM-D). Fluorescence intensity and UV absorption of OVA were decreased substantially upon the addition of NAC. The calculated Kq values were obtained at 298, 304, and 310 K for 13.48, 15.59, and 17.50 (× 1012 L mol-1), respectively, suggesting that the static quenching was dominated. Thermodynamic parameters such as ΔH (-150.58 kJ mol-1), ΔS (-433.51 J mol-1 K-1), and ΔG values (-21.39 kJ mol-1), combined with molecular docking and QCM-D data, showed that the interaction was spontaneous and van der Waals and hydrogen bonding were identified as the main driving forces. FTIR and CD results showed that the α-helix content of OVA increased from 2.8 to 22.9%, and the β-sheet decreased from 0.2 to 21.9% in the presence of 5 and 10 μM NAC, respectively, compared to the pure OVA, respectively.


Rhenium-catalyzed formation of indene frameworks via C-H bond activation: [3+2] annulation of aromatic aldimines and acetylenes.
A rhenium complex, [ReBr(CO)3(thf)]2, catalyzes the reaction of an aromatic aldimine with an acetylene to give an indene derivative in a quantitative yield. The reaction proceeds via C-H bond activation, insertion of the acetylene, intramolecular nucleophilic cyclization, and reductive elimination. In contrast to ruthenium and rhodium catalysts, which are usually employed in this type of reaction, the rhenium catalyst promotes the intramolecular nucleophilic cyclization of the alkenylmetal species generated by insertion of the acetylene.


Altered level of plasma exosomes in patients with Gaucher disease.
Mutations in the glucocerebrosidase gene (GBA) cause Gaucher disease (GD), the lysosomal storage disorder (LSD), and are the most common genetic risk factor of Parkinson's disease (PD). Lysosome functionality plays a critical role for secretion of extracellular vesicles (EVs) and their content. Here we compared EVs from the blood plasma of 8 GD patients and 8 controls in terms of amounts, size distribution, and composition of their protein cargo. EVs were isolated via sequential centrifugation and characterized by сryo-electron microscopy (cryo-EM), nanoparticle tracking analysis (NTA), and dynamic light scattering (DLS). The presence of exosomal markers HSP70 and tetrasponins were analyzed by Western blot and flow cytometry. Protein profiling was performed by mass-spectrometry (shotgun analysis). Here, for the first time we reported an increased size and altered morphology in exosomes derived from blood plasma of GD patients. An increased size of plasma exosomes from GD patients compared to controls was demonstrated by cryo-EM and DLS (р<0.0001, p < 0.001, respectively) and confirmed by mode size detected by NTA (p < 0.02). Cryo-EM demonstrated an increased number of double and multilayer vesicles in plasma EVs from GD patients. We found that the EVs were enriched with the surface exosomal markers (CD9, СD63, CD81) and an exosome-associated protein HSP70 in case of the patients with the disease. Proteomic profiling of exosomal proteins did not reveal any proteins associated with PD pathogenesis. Thus, we showed that lysosomal dysfunction in GD patients lead to a striking alteration of plasma exosomes in size and morphology.


Screening test for preeclampsia through assessment of uteroplacental blood flow and biochemical markers of oxidative stress and endothelial dysfunction.
This study was undertaken to evaluate whether screening through a uterine artery (UtA) Doppler and biochemical markers of oxidative stress and endothelial dysfunction predict preeclampsia. UtA Doppler was performed at 11 to 14 and 22 to 25 weeks on 1447 asymptomatic pregnant women. Oxidative stress, endothelial dysfunction, and antiangiogenic state were assessed in women who later developed preeclampsia and normotensive controls. There was a significantly increased of UtA pulsatility index (PI), plasma levels of soluble fms-like tyrosine kinase 1 (sFlt1), PAI-1/PAI-2 ratio, and F-2 isoprostane in women who subsequently developed preeclampsia compared with control pregnancies. Multivariate logistic regression showed that increased UtA PI performed at 23 weeks was the best predictor for preeclampsia. This study demonstrates early changes in markers of impaired placentation, antiangiogenic state, oxidative stress, and endothelial dysfunction suggesting that these derangements may play a role in the pathogenesis of preeclampsia. Our data point to UtA as the best test to predict preeclampsia at 23 weeks of gestation.


The determination of moments for extension of the wrist generated by muscles of the forearm.
In deciding on suitable tendon transfers to replace denervated muscle-tendon units, important considerations are the strength and effectiveness of possible substitutes. A method is presented by which the strength of the wrist extensor muscles and their moment arms can be determined. The method can be applied to other muscles at other joints. It involves the use of a force transducer which measures the combined forces of the three wrist extensors in an isometric contraction. This moment for wrist extension, measured in the living intact arm, is the same as the sum of the moments of the three wrist extensor muscles. The contribution of each muscle to the total moment is calculated from ratios that have been developed from a quantitative study of moment arms and muscle masses in sixteen cadaver limbs. It is suggested that the ratio of one moment arm to another is fairly constant from subject to subject, and that muscle masses also have sufficiently similar ratios to each other to serve as the basis for practical estimations by the surgeon. Thus the surgeon needs only one or two direct measurements of moments externally and only one or two skeletal measurements on any living subject to be able to estimate the effectiveness of a number of muscles on the basis of cadaver studies such as this, and to project the behavior of a muscle after it has been transferred to a position where it will have new moment arms.


Discerning static and causal interactions in genome-wide reverse engineering problems.
In the past years devising methods for discovering gene regulatory mechanisms at a genome-wide level has become a fundamental topic in the field of systems biology. The aim is to infer gene-gene interactions in an increasingly sophisticated and reliable way through the continuous improvement of reverse engineering algorithms exploiting microarray data. This work is inspired by the several studies suggesting that coexpression is mostly related to 'static' stable binding relationships, like belonging to the same protein complex, rather than other types of interactions more of a 'causal' and transient nature (e.g. transcription factor-binding site interactions). The aim of this work is to verify if direct or conditional network inference algorithms (e.g. Pearson correlation for the former, partial Pearson correlation for the latter) are indeed useful in discerning static from causal dependencies in artificial and real gene networks (derived from Escherichia coli and Saccharomyces cerevisiae). Even in the regime of weak inference power we have to work in, our analysis confirms the differences in the performances of the algorithms: direct methods are more robust in detecting stable interactions, conditional ones are better for causal interactions especially in presence of combinatorial transcriptional regulation. Supplementary data are available at Bioinformatics online.


Dispersion of argininosuccinate-synthetase-like human genes to multiple autosomes and the X chromosome.
DNA sequences closely homologous to argininosuccinate synthetase are present at ten or more distinct locations in the human genome, including sites on chromosomes 6, 9 and X. Argininosuccinate synthetase thus represents one of the most widely dispersed multigene families described to date, the first instance of a multigene family associated with an enzyme of intermediary metabolism and, perhaps most striking, the first instance of a multigene family with members on both autosomes and sex chromosomes.


Changing Public Tolerance for Same-Sex Sexual Behaviors in China, 2010-2017: A Decomposition Analysis.
Although the majority of the Chinese general public remains unaccepting of same-sex sexual behaviors, results from multiple waves of the Chinese General Social Survey have shown a substantial change in the public tolerance for same-sex sexual behaviors between 2010 and 2017. Using logistic regression models and decomposition analysis, the current study revealed that while changes in the changes in the demographic predictors (e.g., cohort succession and improved education) contributed to some of the attitudinal change, changes in the predictor coefficients explained most of the attitudinal change. Specifically, the Internet historically played a critical role in shaping pro-LGBTQ consciousness in China, but its effect has diminished over time. Socioeconomic factors such as education and household registration status (i.e., urban versus rural origin) have gained statistical significance and effect size in their prediction of public tolerance. Policy and advocacy implications of the findings are also discussed.


Court-ordered assessments and routine access to confidential health information: findings from a regional forensic mental health service.
Health Assessors undertaking court ordered assessments are granted access to material related to the alleged They do not have access to defendant's confidential health records. Defendant's consent must be obtained for their health information to be accessed. One hundred files of court ordered reports were audited, to see whether Health Assessors in a New Zealand regional forensic mental health service had obtained such consent. The results were categorised as follows: Category 1: Consent was provided and health record accessed, c (n = 76). Category 2: Consent was not provided and health information not accessed (n = 5) - included defendants deemed unfit to stand trial and unable to give informed consent (n = 2). Category 3: Consent was not provided but health information accessed (n = 19). Ethical and medico-legal implications of Health Assessors accessing defendant's confidential health records are discussed. Recommendations are made for improving services so that public trust in the integrity of confidential information can be maintained.


Clozapine and neutrophil response in patients of African descent: A six-month, multinational, prospective, open-label clinical trial.
Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil count (ANC). People of African descent have a lower normative ANC range than the White population, which is associated with a specific "ACKR1-null" ("Duffy null") CC genotype (SNP rs2814778) on the ACKR1 gene, termed benign ethnic neutropenia (BEN). The range of ANC variability and safety of clozapine have not been established in people with BEN or examined prospectively in people of African descent. We completed a multisite, 6-month, prospective, open-label clinical trial of clozapine treatment in people of African descent with schizophrenia spectrum disorders for whom clozapine was clinically indicated, with or without the ACKR1-null genotype. We examined clozapine safety and weekly ANC during clozapine treatment and evaluated ANC variability by ACKR1-null genotype, sex, study site, and clozapine dosing using repeated measures analysis of covariance. Genotype was assayed using TaqMan® technology. We enrolled 274 participants, of whom 227 (82.8 %) completed 6 months of clozapine treatment. There was one case of severe neutropenia (<500 cells/mm3) (0.36 %) over 1467.6 person-months of clozapine exposure. This participant recovered without sequelae after discontinuation of clozapine. Of the 249 participants with known genotypes, 199 (79.9 %) had the ACKR1-null genotype. Neutropenia (<1500 cells/mm3) occurred significantly more often in the ACKR1-null group (33 % [65/199]) than in those with the T allele (6 % (3/50); p < 0.001). Fourteen (5 %) patients discontinued due to adverse events. Rates of infection and fever were low and sialorrhea was the commonest side effect (N = 187, 68 %). To our knowledge, this is the largest prospective clozapine trial in people of African descent. Severe neutropenia was rare, despite the high prevalence (80 %) of the ACKR1-null genotype. Our findings suggest that clozapine can be used safely in Black patients including those with BEN.


The comparative effects of telmisartan and ramipril on P-wave dispersion in hypertensive patients: a randomized clinical study.
Prolongation of P-wave times and increase of P-wave dispersion (PWD) were shown to be independent predictors of atrial fibrillation (AF). Angiotensin II receptor blockers (AARBs) and angiotensin-converting enzyme inhibitors (ACEIs) have beneficial effects on atrial conduction times. However, there are not enough data about the comparative effects of those drugs on PWD. We aimed to compare the effects of telmisartan and ramipril on PWD after 6-month treatment in hypertensive patients. In all, 100 newly diagnosed hypertensive patients were enrolled in the study and were randomly assigned to two groups. Group 1 and Group 2 each consisted of 50 patients, taking daily doses of 80 mg telmisartan and 10 mg ramipril, respectively. Twelve-lead surface electrocardiograms (ECG) were recorded from all patients before and after 6-month drug therapy. The P-wave duration (Pdur) measurements were calculated from the 12-lead surface ECG. When pretreatment PWD and Pmaximum values were compared with post-treatment values, a statistically significant decrease was found in both groups after 6 months (Group 1 and 2; p < 0.001 for PWD and Pmaximum). P-wave dispersion and Pmaximum values after treatment in Group 1 were statistically significantly lower than those in Group 2 after the 6-month treatment period (p = 0.01 for PWD; p = 0.008 for Pmaximum). Telmisartan has a much greater lowering effect on PWD and Pmaximum values than ramipril. This finding may be important in the prevention of AF in hypertensive patients.


Geometric parameter analysis to predetermine optimal radiosurgery technique for the treatment of arteriovenous malformation.
To develop a method of predicting the values of dose distribution parameters of different radiosurgery techniques for treatment of arteriovenous malformation (AVM) based on internal geometric parameters. For each of 18 previously treated AVM patients, four treatment plans were created: circular collimator arcs, dynamic conformal arcs, fixed conformal fields, and intensity-modulated radiosurgery. An algorithm was developed to characterize the target and critical structure shape complexity and the position of the critical structures with respect to the target. Multiple regression was employed to establish the correlation between the internal geometric parameters and the dose distribution for different treatment techniques. The results from the model were applied to predict the dosimetric outcomes of different radiosurgery techniques and select the optimal radiosurgery technique for a number of AVM patients. Several internal geometric parameters showing statistically significant correlation (p < 0.05) with the treatment planning results for each technique were identified. The target volume and the average minimum distance between the target and the critical structures were the most effective predictors for normal tissue dose distribution. The structure overlap volume with the target and the mean distance between the target and the critical structure were the most effective predictors for critical structure dose distribution. The predicted values of dose distribution parameters of different radiosurgery techniques were in close agreement with the original data. A statistical model has been described that successfully predicts the values of dose distribution parameters of different radiosurgery techniques and may be used to predetermine the optimal technique on a patient-to-patient basis.


Prognostic significance of different molecular typing methods and immune status based on RNA sequencing in HR-positive and HER2-negative early-stage breast cancer.
This study was conducted to evaluate the prognostic significance of different molecular typing methods and immune status based on RNA sequencing (RNA-seq) in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HR + /HER2-) early-stage breast cancer and develop a modified immunohistochemistry (IHC)-based surrogate for intrinsic subtype analysis. The gene expression profiles of samples from 87 HR + /HER2- early-stage breast cancer patients were evaluated using the RNA-seq of Oncotype Dx recurrence score (RS), PAM50 risk of recurrence (ROR), and immune score. Intrinsic tumor subtypes were determined using both PAM50- and IHC-based detection of estrogen receptor, progesterone receptor, Ki-67, epidermal growth factor receptor, and cytokeratins 14 and 5/6. Prognostic variables were analyzed through Cox regression analysis of disease-free survival (DFS) and distant metastasis-free survival (DMFS). Survival analysis showed that ROR better predicted recurrence and distant metastasis compared to RS (for DFS: ROR, P = 0.000; RS, P = 0.027; for DMFS, ROR, P = 0.047; RS, P = 0.621). Patients with HR + /HER2- early-stage breast cancer was classified into the luminal A, luminal B, HER2-enriched, and basal-like subtypes by PAM50. Basal-like subgroups showed the shortest DFS and DMFS. A modified IHC-based surrogate for intrinsic subtype analysis improved the concordance with PAM50 from 66.7% to 73.6%, particularly for basal-like subtype identification. High level of TILs and high expression of immune genes predicted poor prognosis. Multi-factor Cox analysis showed that IHC-based basal-like markers were the only independent factors affecting DMFS. Prognosis is better evaluated by PAM50 ROR in early-stage HR + /HER2- breast cancer and significantly differs among intrinsic subtypes. The modified IHC-based subtype can improve the basal-like subtype identification of PAM50. High immunity status and IHC-based basal-like markers are negative prognostic factors.


Preventing type 2 diabetes.
The rapid and often relentless progression of type 2 diabetes suggests that high-risk patients should be provided with an equally aggressive strategy to protect their remaining beta-cell function and endogenous insulin secretion. Management of patients with prediabetes should incorporate both lifestyle and pharmacologic intervention. Although no specific recommendations are published for the management of prediabetes, one can assume that preservation of pancreatic beta-cell function, improvement in peripheral insulin resistance and pancreatic insulin secretion, reducing pancreatic alpha-cell secretion of glucagon, preventing long- and short-term diabetes-related complications, and assisting patients to loose weight are beneficial. Aggressive, timely, and physiologic management of prediabetes should be advocated.


Nonlinear viscoelasticty plays an essential role in the functional behavior of spinal ligaments.
Despite the significant role ligament viscoelasticity plays in functional spinal biomechanics, relatively few studies have been performed to develop constitutive models that explicitly characterize this complex behavior. Unfortunately, the application and interpretation of these previous models are limited due to the use of simplified (quasi-linear) viscoelastic formulations or characterization techniques that have been shown to affect the predictive accuracy of the fitted coefficients. In order to surmount these previous limitations, the current study presents the application of a novel fitting technique (applied to stress relaxation experiments) and nonlinear viscoelastic constitutive formulation to human cervical spine anterior longitudinal ligament (ALL), posterior longitudinal ligament (PLL) and ligamentum flavum (LF). The fitted coefficients were validated by quantifying the ability of the constitutive equation to predict an independent cyclic data set across multiple physiologic strain amplitudes and frequencies. The resulting validated constitutive formulation indicated that the strain-dependent viscoelastic behavior of the longitudinal ligaments (ALL and PLL) was dominated by both the short-term (t=0.1s) and the steady-state (as t→∞) behavior. Conversely, the LF exhibited consistent relaxation behavior across the investigated temporal spectrum. From these data, it can be hypothesized that the unique strain-dependent temporal behavior of these spinal ligaments may be a functional adaptation that minimizes muscular expenditure during quasi-static postures while maximizing structural stability of the spine during transient loading events.


An unusual case of double teeth with facial and lingual talon cusps.
Double teeth and talon cusps are rare developmental dental anomalies affecting both primary and permanent dentitions. Talon cusps normally occur on the palatal surface of permanent maxillary incisors, although double teeth are more common in the primary anterior dentition. This paper describes a rare case of fusion of the mandibular permanent incisors with labial and lingual talon cusps. An understanding of these dental anomalies and their associated problems are important to provide prophylactic measures, thereby preventing or minimizing possible complications.


Thromboelastography in Patients with Inflammatory Bowel Disease.
Patients with inflammatory bowel disease (IBD) frequently suffer from venous thromboembolic events, and the risk of thromboembolism increases along with disease activity. This study was conducted to discover novel thrombophilic markers using thromboelastography (TEG) and to evaluate the relation between the predisposing factors and the activity of disease in Chinese patients with Crohn's disease (CD) and ulcerative colitis (UC). Thirty-four patients with CD, 29 patients with UC, and 53 healthy volunteers were enrolled into this study. Blood levels of R, K, α Angle, G, maximal amplitude (MA), and LY30 with TEG were determined. Mean values of R, K, α Angle, G, and MA were significantly different in patients with CD and UC compared with the healthy individuals. Patients with active CD had different K, α Angle, G, and MA levels compared with patients in remission (P < 0.05, P < 0.001, P < 0.001, and P < 0.001). Levels of R, α Angle, G, and MA were also significantly different in active UC patients compared with those in remission (P < 0.01, P < 0.001, P < 0.001, and P < 0.001). Except for the G level in the CD group, differences in all TEG levels between healthy individuals and IBD patients in remission were not statistically significant. No statistical differences were observed in LY30 among patients with active phase, patients in remission, and the healthy individuals. Thrombophilic defects are common in Chinese patients with IBD, and TEG can be considered a new direction to anticoagulant thromboprophylaxis in IBD.


Case-matching analysis of head and neck squamous cell carcinoma in racial and ethnic minorities in the United States--possible role for human papillomavirus in survival disparities.
Several studies have documented disparities in head and neck cancer outcomes for black patients in the United States. Recent studies have found that differences in oropharyngeal tumor human papillomavirus (HPV) status may be a cause of this disparity. In all, 76,817 cases of head and neck squamous cell carcinoma (HNSCC) recorded in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program were analyzed. Racial/ethnic groups were studied, for disease-specific survival in both case-matched and nonmatched cohorts. Calculation of expected disparity magnitudes based on HPV status was performed using data reported in the literature. A disease-specific survival disparity was demonstrated for Hispanic patients. However, case matching eliminated this disparity. Conversely, the disparity for black patients persisted in matched cohorts. The oropharyngeal subsite was found to be the dominant contributor to this disparity. The survival disparity for Hispanic patients in SEER with HNSCC is explained by differences in presentation and treatment. Also, HPV tumor status is likely a key determinant of the disparity for black patients.


[Tumor heterogeneity and the mechanisms of natural resistance in the metastatic process].
Data from literature concerning differences in cell populations between the primary and metastatic tumours are generalized. Their properties are considered as dependent on heterogeneity of the cell composition, karyotype, cell surface peculiarities and oncogene expression. The problem of the dependence of the ability of tumours to metastasize on their interaction with macrophages and natural killer cells is under discussion.


Flow cytometric DNA analysis of malignant lymphomas with primary bone manifestation.
Malignant lymphomas with primary skeletal manifestation have received controversial evaluation with regard to histological classification and histogenesis. Recent histological and immunohistological studies on the rare bone lymphomas conducted by our team, have shown that they do not differ from primary nodal lymphomas with regard to the spectrum of histological subtypes. The present flow cytometric DNA analysis of paraffin-embedded material from 17 lymphomas documented in the Bone Tumor Registry of Westfalia yielded the following distribution pattern of DNA ploidy: among 12 non-Hodgkin's lymphomas (NHL) (according to the Kiel classification) there was only 1 case of low grade malignancy; this centroblastic-centrocytic lymphoma showed a unimodal diploid DNA histogram. Of 11 highly malignant NHL, 6 were DNA hyperdiploid. Among the 5 cases of Hodgkin's lymphoma, 4 were DNA diploid, (1 nodular sclerosing, 3 mixed types) and one DNA tetraploid (lymphocytic depletion type). Comparison with data from the literature reveals that even with regard to DNA ploidy, malignant lymphomas primarily manifesting in bone do not differ from those of exclusively nodal manifestation.


Identification of a Robust Five-Gene Risk Model in Prostate Cancer: A Robust Likelihood-Based Survival Analysis.
In this paper, we aimed to develop and validate a risk prediction method using independent prognosis genes selected robustly in prostate cancer. We considered 723 samples obtained from TCGA (the Cancer Genome Atlas), GSE46602, and GSE21032. Prostate cancer prognosis-related genes with P < 0.05 were selected using Univariable Cox regression analysis. We then built the lowest AIC (Akaike information criterion score) optimal gene model using the "Rbsurv" package in TCGA train set. The coefficients were obtained by Multivariable Cox regression analysis. We named the new prognosis method CMU5. The CMU5 risk score was verified in TCGA test set, GSE46602, and GSE21032. FAM72D, ARHGAP33, TACR2, PLEK2, and FA2H were identified as independent prognosis factors in prostate cancer patients. We built the computing model as follows: CMU5 risk score = 1.158∗FAM72D + 1.737∗ARHGAP33 - 0.737∗TACR2 - 0.651∗PLEK2 - 0.793∗FA2H. The AUC of DFS was 0.809 in the train set (274 samples), 0.710 in the test set (273 samples), and 0.768 in the complete set (547 samples). The benign prediction capacity of CMU5 was verified by GSE46602 (36 samples; AUC = 0.6039) and GSE21032 GPL5188 (140 samples; AUC = 0.7083). Using the cut-off point of 2.056, a significant difference was shown between high- and low-risk groups. A prognosis-related risk score formula named CMU5 was built and verified, providing reliable prediction of prostate cancer outcome. This signature might provide a basis for individualized treatment of prostate cancer.


Rational design of 4-((6-phenoxypyrimidin-4-yl)amino)-N-(4-(piperazin-1-yl)phenyl)-1H-pyrazole-3-carboxamide (LT-540-717) as orally bioavailable FLT3 inhibitor.
In recent years, fms-like tyrosine kinase 3 (FLT3) was confirmed as an exciting target for treatment of AML. However, resistance to FLT3 inhibitors caused by acquired point mutations in tyrosine kinase domain (TKD) have limited their sustained efficacious. Thus, there remains an unmet need to develop high-efficacy FLT3 inhibitors against both FLT3 internal tandem duplication (ITD) and FLT3 (TKD) mutations. Herein, we describe the discovery of compound LT-540-717 (32), a potent FLT3 inhibitor (IC50: 0.62 nM), starting from FN-1501. Compound 32 exhibited highly inhibitory activity against several acquired FLT3 mutations including FLT3 (ITD, D835V), FLT3 (ITD, F691L), FLT3 (D835Y) and FLT3 (D835V). Additionally, 32 displayed potent antiproliferative activity against FLT3-mutation driven BaF3 and AML cells. Oral administration of 32 (25 mg/kg, QD) significantly prohibited tumor growth (tumor-inhibition rate is 94.18%), and no obvious side effect was observed even when increasing dose to 50 mg/kg (tumor-inhibition rate is 93.98%). Furthermore, 32 showed an acceptable bioavailability (F = 33.3% in rat and 72.7% in beagles), a suitable half-life time (T1/2 = 3.5 h in rat and T1/2 = 11.1 h in beagles), and a satisfactory metabolic stability. In summary, these results show the therapeutic potential of 32 to become a new anti-AML drug, especially for AML harboring dual FLT3 (ITD, TKD) mutations.


Phasic coronary blood flow pattern during a continuous flow left ventricular assist support.
Continuous flow left ventricular assist devices (LVADs) have been introduced and tested as a bridge to heart transplantation, bridge to recovery, and destination therapy, and several studies have been conducted to assess the physiologic effects of continuous flow LVADs. However, the effect of reduced pulsatility on the phasic coronary blood flow pattern is unknown. The aim of this study was to investigate the phasic coronary blood flow patterns during continuous flow LVAD support. Phasic coronary blood flow patterns and hemodynamic data were analyzed using three flow probes placed around the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX), and the right coronary artery (RCA) in 16 pigs before and after initiating the LVAD support with or without creating LAD stenosis. The total coronary blood flow (TCBF, 112.8+/-31.4 mL/min) gradually decreased when the continuous flow LVAD support increased to 2.0 L/min (110.7+/-29.0 mL/min, P = 0.571), 2.5 L/min (103.7+/-26.1 mL/min, P = 0.079), and 3.0 L/min (101.5+/-27.2 mL/min, P = 0.027) because of decreases in LAD flow and LCX flow. LVAD support caused decrease in systolic and peak systolic LAD flow, LCX flow, and RCA flow, whereas diastolic RCA flow increased. In the presence of LAD stenosis, the TCBF (97.7+/-36.1 mL/min) decreased when the continuous flow LVAD support increased to 2.0 L/min (83.9+/-22.1 mL/min, P = 0.029), 2.5 L/min (83.2+/-25.2 mL/min, P = 0.012), and 3.0 L/min (87.6+/-23.4 mL/min, P = 0.005) because of decreases in LCX flow. Use of a continuous flow LVAD decreased TCBF, LAD flow, and LCX flow secondary to reduced systolic LAD flow and LCX flow, and decreased TCBF and LCX flow in the presence of LAD stenosis. These findings are potentially relevant to understanding the physiology of myocardial blood perfusion during continuous flow LVAD support especially in patients with coronary artery disease.


Making choices-how stochastic decisions determine disease progression.
In this issue of Genes & Development, Ginart and colleagues (pp. 567-578) study a mouse model for Russell-Silver syndrome (RSS) and show that similar cells within one individual can display distinct gene expression patterns because of epigenetic marks that are established stochastically during early development. Their results provide an excellent explanation for phenotypes seen in RSS and other imprinting disorders and especially help us understand how patients with similar or even identical genetic mutations can display distinct disease profiles.


Minimum alveolar concentration of halogenated volatile anaesthetics in left ventricular hypertrophy and congestive heart failure in rats.
Although many physiological and pathological conditions affect minimal alveolar concentration (MAC), there are no reliable data on the MAC for halogenated anaesthetics during left ventricular hypertrophy (LVH) and congestive heart failure (CHF). The aim of this experimental study was to determine the MAC values of halothane, isoflurane, and sevoflurane in rats, at early and later stages of cardiomyopathic hypertrophy. LVH was induced by ascending aortic stenosis in 3-4-week-old rats. LVH and CHF in each animal were assessed weekly by echocardiography. MAC of halothane, isoflurane, and sevoflurane was determined using the tail-clamp technique in spontaneously breathing rats from each group. Response vs no-response data were analysed using logistic regression analysis. Data are medians (95% confidence interval). The MAC of halothane [1.30% (1.26-1.34)], isoflurane [1.52% (1.48-1.57)], and sevoflurane [2.93% (2.78-3.07)] in rats with LVH was not different from sham-operated rats [respectively, 1.23% (1.20-1.26), 1.52% (1.47-1.56), and 2.90% (2.79-3.00)]. Conversely, the MAC of halothane [1.44 (1.39-1.50)] and isoflurane [1.74 (1.69-1.78)], but not sevoflurane [2.99 (2.93-3.06)], was significantly increased in rats with CHF. MAC values for halothane, isoflurane, and sevoflurane were unchanged in rats with pressure-induced overload LVH. Conversely, the MAC for halothane and isoflurane, but not sevoflurane, was significantly increased in rats with CHF.


Frequency-risk and duration-risk relations between occupational livestock contact and methicillin-resistant Staphylococcus aureus carriage among workers in Guangdong, China.
Increasing evidence indicates a strong association between occupational livestock contact and methicillin-resistant Staphylococcus aureus (MRSA) carriage. However, it remains unclear whether there are frequency-risk and duration-risk relations between occupational livestock contact and human MRSA carriage. A cross-sectional survey was conducted in Guangdong, China, using a multistage sampling method. Participants were interviewed and provided a nasal swab for S aureus analysis. All MRSA isolates were genotyped by multilocus sequence typing. The dose-response relation was examined using logistic regression models. Among the 1,860 participants, 1.4% of controls tested positive for MRSA (characterized as sequence type [ST] 59 and ST7), and 7% of workers with livestock contact tested positive for MRSA (characterized as ST9, ST59, and ST7). There was a 5.31 times increased risk of MRSA carriage corresponding to occupational livestock contact (odds ratio = 6.31; 95% confidence interval, 3.44-11.57) using no contact as reference. We found frequency and short-term duration of occupational livestock contact were associated with increased risk of MRSA carriage in a dose-response manner. These significant trends were observed consistently among workers with occupational pig contact. However, no long-term duration-risk increasing trend was observed for occupational livestock or pig contact. Our findings suggest that there may be dose-response relations between occupational livestock contact and human MRSA carriage. Nasal MRSA clonal complex 9 is not found in controls, but it is found in workers with livestock contact.


An ancient eye test--using the stars.
Vision testing in ancient times was as important as it is today. The predominant vision testing in some cultures was the recognition and identification of constellations and celestial bodies of the night sky. A common ancient naked eye test used the double star of the Big Dipper in the constellation Ursa Major or the Big Bear. The second star from the end of the handle of the Big Dipper is an optical double star. The ability to perceive this separation of these two stars, Mizar and Alcor, was considered a test of good vision and was called the "test" or presently the Arab Eye Test. This article is the first report of the correlation of this ancient eye test to the 20/20 line in the current Snellen visual acuity test. This article describes the astronomy, origin, history, and the practicality of this test and how it correlates with the present day Snellen visual acuity test.


Efficacy of microwave versus radiofrequency ablation for treatment of small hepatocellular carcinoma: experimental and clinical studies.
To prospectively compare microwave (MW) ablation using a modified internal cooled-shaft antenna with radiofrequency (RF) ablation in in vivo porcine liver and in patients with small hepatocellular carcinoma (sHCC). In an animal study, MW and RF ablations using a cooled-shaft antenna or internally cooled electrode were performed in in vivo porcine liver. Coagulation diameters of both ablations were compared. For clinical study, 42 patients with sHCC were treated with MW or RF ablation. Complete ablation (CA) and local tumour progression (LTP) were compared. MW ablation produced significantly larger ablation zones than RF ablation in both porcine liver and sHCC with an ablated volume of 33.3 ± 15.6 cm(3) vs. 18.9 ± 9.1 cm(3) and 109.3 ± 58.3 cm(3) vs. 48.7 ± 30.5 cm(3), respectively. The CA rate was 95.5 % (21/22) for MW ablation and 95.0 % (19/20) for RF ablation. In a 5.1-month follow-up, the LTP rate was 18.2 % (4/22) in the MW ablation group and 15.0 % (3/20) in the RF ablation group. MW ablation using a modified cooled-shaft antenna produces a larger ablation zone than RF ablation, with an efficacy similar to RF ablation in local tumour control. MW ablation is a safe and promising treatment of sHCC.


Effect of culture medium on propagation and phenotype of corneal stroma-derived stem cells.
The limbal area of the corneal stroma has been identified as a source of mesenchymal-like stem cells, which have potential for exploitation as a cell therapy. However, the optimal culture conditions are disputed and few direct media comparisons have been performed. In this report, we evaluated several media types to identify the optimal for inducing an in vitro stem cell phenotype. Primary human corneal stroma-derived stem cells (CSSCs) were extracted from corneoscleral rims. Culture in seven different media types was compared: Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum (FBS); M199 with 20% FBS; DMEM-F12 with 20% serum replacement, basic fibroblast growth factor and leukemia inhibitory factor (SCM); endothelial growth medium (EGM); semi-solid MethoCult; serum-free keratinocyte medium (K-SFM); and StemPro-34. Effects on proliferation, morphology, protein and messenger RNA expression were evaluated. All media supported proliferation of CSSCs with the exception of K-SFM and StemPro-34. Morphology differed between media: DMEM produced large cells, whereas EGM produced very small cells. Culture in M199 produced a typical mesenchymal stromal cell phenotype with high expression of CD105, CD90 and CD73 but not CD34. Culture in SCM produced a phenotype more reminiscent of a progenitor cell type with expression of CD34, ABCG2, SSEA-4 and PAX6. Culture medium can significantly influence CSSC phenotype. SCM produced a cell phenotype closest to that of a pluripotent stem cell, and we consider it to be the most appropriate for development as a clinical-grade medium for the production of CSSC phenotypes suitable for cell therapy.


Inhibition of NADH oxidase and lactate dehydrogenase of Mycoplasma gallisepticum by copper complexes of 2,2'-bipyridyl analogues.
In the presence of copper, 2,2'-bipyridyl analogues possess growth-inhibitory activity against Mycoplasma gallisepticum. Inhibition of the energy yielding metabolism plays a role in the mechanism of action. We showed that probably inhibition of lactate dehydrogenase and NADH oxidase is involved. Both enzymes were inhibited in vitro and in vivo by several copper 2,2'-bipyridyl complexes. A two-step mechanism of action is proposed, i.e. first a copper complex enters the cell, then after dissociation of the complex the enzymes are inhibited by free copper.


Proposal of optically tunable and reconfigurable multi-channel bandstop filter using sum-frequency generation in a PPLN waveguide.
A multi-wavelength bandstop filter is proposed and numerically demonstrated using the sum-frequency generation (SFG) process in a waveguide of periodically poled lithium niobate (PPLN). This proposed device achieves channels number reconfigurable, central filtering wavelength of each filtering channel independently tunable and extinction ratios (ERs) equalized via all-optical methods.


Reduction of low-density lipoprotein receptor-related protein (LRP1) in hippocampal neurons does not proportionately reduce, or otherwise alter, amyloid deposition in APPswe/PS1dE9 transgenic mice.
The low-density lipoprotein receptor-related protein (LRP1) and its family members have been implicated in the pathogenesis of Alzheimer's disease. Multiple susceptibility factors converge to metabolic pathways that involve LRP1, including modulation of the processing of amyloid precursor protein (APP) and the clearance of Aβ peptide. We used the Cre-lox system to lower LRP1 levels in hippocampal neurons of mice that develop Alzheimer-type amyloid by crosses between mice that express Cre recombinase under the transcriptional control of the GFAP promoter, mice that harbor loxp sites in the LRP1 gene, and the APPswe/PS1dE9 transgenic model. We compared amyloid plaque numbers in APPswe/PS1dE9 mice lacking LRP1 expression in hippocampus (n = 13) to mice with normal levels of LRP1 (n = 12). Student t-test was used to test whether there were significant differences in plaque numbers and amyloid levels between the groups. A regression model was used to fit two regression lines for these groups, and to compare the rates of Aβ accumulation. Immunohistochemical analyses demonstrated efficient elimination of LRP1 expression in the CA fields and dentate gyrus of the hippocampus. Within hippocampus, we observed no effect on the severity of amyloid deposition, the rate of Aβ40/42 accumulation, or the architecture of amyloid plaques when LRP1 levels were reduced. Expression of LRP1 by neurons in proximity to senile amyloid plaques does not appear to play a major role in modulating the formation of these proximal deposits or in the appearance of the associated neuritic pathology.


Antibiotic prophylaxis for radical abdominal hysterectomy.
Records of 35 patients with cervical cancer Stage IB operated with radical abdominal hysterectomy and pelvic lymphadenectomy were surveyed retrospectively for incidence of febrile morbidity and site-related infections. Febrile morbidity was observed in 6 patients (17%). No surgical site-related infections were observed. It is concluded that radical abdominal hysterectomy in our hospital does not carry any significant risk of postoperative site-related infections and that prophylactic antibiotics cannot be recommended.


Alexis Carrel: Jules Verne of cardiovascular surgery.
There is in every field one individual who stands apart as a great thinker, leader, or teacher. In the field of cardiovascular surgery, Alexis Carrel was each of these. Proof of this lies in the fact that daily, the modern cardiovascular surgeon is likely to use a concept or technique first developed by Carrel. During the 75th anniversary year of Carrel's receipt of the Nobel Prize, the life and work of this great innovator should be remembered.


Oral pectin/oligochitosan microspheres for colon-specific controlled release of quercetin to treat inflammatory bowel disease.
Inflammatory bowel disease (IBD) is a chronic, life quality-reducing disease with no cures available yet. To develop an effective medication suitable for long-term use is an urgent but unmet need. Quercetin (QT) is a natural dietary flavonoid with good safety and multifaceted pharmacological activities against inflammation. However, orally administrated quercetin yields unproductive outcomes for IBD treatment because of its poor solubility and extensive metabolism in the gastrointestinal tract. In this work, a colon-targeted QT delivery system (termed COS-CaP-QT) was developed, of which the pectin (PEC)/Ca2+ microspheres were prepared and then crosslinked by oligochitosan (COS). The drug release profile of COS-CaP-QT was pH-dependent and colon microenvironment-responsive, and COS-CaP-QT showed preferential distribution in the colon. The mechanism study showed that QT triggered the Notch pathway to regulate the proliferation of T helper 2 (Th2) cells and group 3 innate lymphoid cells (ILC3s) and the inflammatory microenvironment was remodeled. The in vivo therapeutic results revealed that COS-CaP-QT could relieve the colitis symptoms and maintain the colon length and intestinal barrier integrity.


Spectroscopic Characterisation of a Bio-Inspired Ni-Based Proton Reduction Catalyst Bearing a Pentadentate N2 S3 Ligand with Improved Photocatalytic Activity.
Inspired by the sulfur-rich environment found in active hydrogenase enzymes, a Ni-based proton reduction catalyst with pentadentate N2 S3 ligand was synthesised. When coupled with [Ru(bpy)3 ]2+ (bpy=2,2'-bipyridine) as photosensitiser and ascorbate as electron donor in a 1:1 mixture of dimethylacetamide and aqueous ascorbic acid/ascorbate buffer, the catalyst showed improved photocatalytic activity compared with a homologous counterpart bearing a tetradentate N2 S2 ligand. The mechanistic pathway of photoinduced hydrogen evolution was comprehensively analysed through optical transient absorption and time-resolved X-ray absorption spectroscopy, which revealed important electronic and structural changes in the catalytic system during photoirradiation. The NiII catalyst undergoes a photoinduced metal-centred reduction to form a NiI intermediate with distorted square-bipyramidal geometry. Further kinetic analyses revealed differences in charge-separation dynamics between the pentadentate and tetradentate forms.


NS3 protein of hepatitis C virus regulates cyclooxygenase-2 expression through multiple signaling pathways.
Hepatitis C virus (HCV) causes chronic hepatitis, which often results in the development of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. In this study, we demonstrated that the non-structural protein NS3 of HCV enhances cyclooxygenase-2 (COX-2) gene promoter activity, COX-2 mRNA expression, COX-2 protein production, and prostaglandin E2 (PGE2) release in HepG2 cells in a concentration-dependent fashion. We also showed that transcription factor NF-kappaB is required for the activation of COX-2 regulated by NS3. In addition, multiple signaling pathways are involved cooperatively in the expression of COX-2 activated by the viral protein in a calcium-independent manner, which requires signaling components including JNK, ERK, and PKD2. A thorough investigation of mechanism involved in the activation of COX-2 regulated by HCV would provide insights into our understanding the processes of liver inflammatory response and hepatocellular carcinoma development caused by the viral infection and also into the development of novel therapeutics against HCV infection.


Moving Toward Implementation of Person-Centered Care for Older Adults in Community-Based Medical and Social Service Settings: "You Only Get Things Done When Working in Concert with Clients".
Specialized, fragmented acute care is not aligned optimally to serve older adults. Person-centered care (PCC) has emerged as an evidence-based solution that involves enlisting patients as partners in treatment planning. Although several efforts have captured person-centered voices in outpatient care, more information is needed at the organizational and provider level to better understand the feasibility, challenges, and effect of PCC in community-based and social services settings. To assess themes and emerging trends, researchers conducted telephone interviews with leaders at nine organizations providing PCC for older adults. Questions were focused on the legacy of PCC services, whether and how PCC was connected to better quality care, and what tools were used for measuring PCC. Three themes on PCC for older adults emerged. (1) Each organization ascribed to a unique definition and operational structure for PCC. (2) Despite these differences, all organizations specified a strong commitment to PCC. Most noted financial resources and staffing as challenges and opportunities affecting feasibility. (3) Terms such as "patient-centered" care and other PCC synonyms may warrant greater clarification, because ideological differences set these classifications apart. Results from this analysis indicate the lack of a single, established definition for PCC. As interest in and support for PCC mounts, organizations in outpatient medical and community-based settings clearly have undertaken individual efforts to interpret what PCC is and how to provide it. Interview responses reflect this inconsistency, highlighting how staff and financing in particular can bolster or burden the PCC paradigm and what a consensus definition could do for the field.


[Analysis of factors associated with changes in the oral glucose tolerance test, regardless of the values of fasting glucose].
To identify factors associated with changes in oral glucose tolerance test (OGTT), regardless of fasting glucose (FG). 377 patients (53.8 ± 15.2 years, 77.7% women and BMI = 31.4 ± 5.9 kg/m²) with no history of diabetes mellitus(DM), underwent OGTT and compared according to the results: normal (NGT), impaired (IGT) and DM. 202 patients (53.6%) had altered glucose tolerance: 69 with DM (18.3%) and 133 with IGT (35.3%). In multivariate analysis, factors regardless of FG that were associated (P < 0.05) with changes in the OGTT were age (DM = 58.7 ± 12.9; IGT = 56.7 ± 14.3; NGT = 49.6 ± 15.6 years), hypertension (DM = 69.6%; IGT = 63.9%; NGT = 43.4%), FG (DM = 111.9 ± 9.2; IGT = 103.5 ± 10.3; NGT = 96.6 ± 11.1 mg/dL), HbA1C (DM = 6.1 ± 0.7%; IGT = 6.1 ± 0.5%; NGT = 5.8 ± 0.4%), triglycerides (DM = 179.3 ± 169.9; IGT = 154.2 ± 84.1; NGT = 129.1 ± 71.9 mg/dL), HDL-c (DM =44.7 ± 9.2; IGT = 47.5 ± 12.3; NGT = 50.6 ± 13.4 mg/dL) and uric acid in women (DM = 5.3 ± 1.5; IGT = 5.3 ± 1.3; NGT = 4.7 ± 1.3 mg/dL). Age, hypertension, elevated triglycerides, HbA1C, uric acid (in women) and low HDL-C are associated with changes in the OGTT patients with overweight / obesity, irrespective of FG.


Late onset ataxia phenotype in dentatorubro-pallidoluysian atrophy (DRPLA).
ABSTRACT We clinically and genetically studied three patients in a family with dentatorubro-pallidoluysian atrophy (DRPLA). The proband patient had 58/24 CAG repeat alleles of the DRPLA gene (normal < or = 34 repeats). Cerebellar ataxia first developed in the 6-7th decades and was the predominant feature for more than 10 years in all three, after which two of them manifested dementia and choreiform movements in the advanced stage. Atrophy of the cerebellum and brain stem an CT or MRI had suggested dominant spinocerebellar ataxia as a diagnosis in their ataxia-predominant stage, with a diagnosis of DRPLA being impossible based on the clinical findings alone. Our experience implies that DRPLA must be taken into account in the differential diagnosis of late onset ataxic disorders, since it can easily be overlooked.


Measuring the growth rate of UK dairy heifers to improve future productivity.
Sub-optimal heifer growth is associated with higher disease rates and reduced future performance and longevity in the dairy herd. This report describes a system for measuring heifer growth from birth to first calving that was used on commercial dairy farms in South West England, in order to gather benchmarking data to feed back to farmers. Weights (n = 8443) were collected from 20 farms. There was a marked variation in individual and herd mean growth rates. Overall, calves gained no weight in the first 8 days after birth and had a very low growth rate (median 0.12 kg/day) up to 30 days, a period when feed conversion efficiency is high and calves are vulnerable to disease. Heifers whose growth rate up to 180 days was low were significantly less likely to achieve target service weight (374 kg) by 420 days. Monitoring heifer growth during the rearing period enables farmers to improve heifer growth rates and so impact both the efficiency of heifer rearing and, potentially, the productivity and performance of the adult herd.


A conformational rationale for the wobble behaviour of the first base of the anticodon triplet in tRNA.
We present a conformational rationale for wobble behaviour of the first base in the anticodon triplet of tRNA and hence for the well-known degeneracy of the genetic code. The U-turn hydrogen bond plays an important role in the structure of the anticodon arm and particularly for the anticodon triplet to be in a geometry suitable for the process of recognition in the adaptor-mediated synthesis of proteins. This hydrogen bond in turn precludes a hydrogen bond between the first two sugars of the anticodon triplet, allowing the first base to wobble, while it facilitates one between the second and third sugars of the triplet, positioning these bases for the standard base-pairing with the codon. This neatly explains why there is a degeneracy in the code and why a RNA happens to be the adaptor for protein synthesis. Relevent conformational calculations are presented in support of the theory.


Update on the effect of estradiol in postmenopause women with Alzheimer's disease: a systematic review.
Estradiol (E2) has been used in the treatment of Alzheimer's disease (AD) for many years but with various responses. Evidence from clinical studies, randomized clinical trials (RCTs), and observational studies further underscores the importance of E2 in postmenopause women diagnosed with AD. The purpose of this article is to review all clinical trials to date focusing on the E2 in AD patients to explore the evidence regarding use of E2 in AD treatments. To achieve this objective, clinical studies regarding E2 levels in AD patients and RCTs assessing AD treatment in postmenopause women were identified through searches of MEDLINE, The Cochrane Library, EMBASE, Web of Science, Ovid, and Google Scholar. E2 has demonstrated good therapeutic effectiveness in AD patients, however, further larger scale, double-blind RCTs are required before a definitive conclusion can be reached and the results need to be compared with other drugs. This update reviews the newest clinical information regarding the role of E2 in postmenopause women with AD. To our knowledge, this is the only systematic review of this area.


Causes of low vision and blindness in south western Saudi Arabia. A hospital-based study.
The authors studied 1,681 consecutive patients who attended their ophthalmic outpatient clinics over a period of 12 months to determine the patients' visual acuity status and the causes of any visual loss. Using the World Health Organization criteria for definition of visual acuity status, 1004 (59.7%) patients had normal vision. Four hundred and thirty-one (25.6%) patients had low vision or visual impairment and 246 (14.6%) patients were blind. Twenty-eight (1.9%) patients had no light perception in both eyes. Cataract, both in isolation and co-existing with other ocular pathology, was the major cause of both low vision and blindness (58.5% and 81.7%, respectively). A concerted attack on cataract alone will markedly reduce blindness and low vision in this region.


A single step, centrifuge-free method to harvest bone marrow highly concentrated in mesenchymal stem cells: results of a pilot trial.
The aims of the present study were: (1) to characterize the bone-marrow aspirate (BMA) obtained with a centrifuge-free process, employing a dedicated aspiration device; (2) to test the in vitro efficacy of BMA in a model of cartilage inflammation; and (3) to report the preliminary clinical results in a small cohort of patients affected by knee OA. Ten patients (4 M, 6 W; mean age: 51.9 ± 9.2 yy) affected by mild to moderate unicompartmental knee OA (KL grade 2-3) were treated by intra-articular and subchondral injections of BMA obtained by a centrifuge-free process. To evaluate the effectiveness of the device in harvesting mesenchymal stem cells (MSCs), samples of the obtained BMA were tested by flow cytometry before and after subculture; BMA ability to counteract inflammation was also tested in an in vitro model of cartilage cell inflammation, evaluating the expression of MMP1, MMP3, TGFβ and TIMP-1 by real-time PCR. Patients were also evaluated up to two years' follow-up by using: VAS for pain, IKDC-subjective and KOOS scores. The laboratory analysis showed that BMSCs accounted for 0.011% of BMA cells, similar to what had been expected in native bone marrow. The paracrine activity of BMA was able to reduce in vitro the catabolic response of human chondrocyte, as shown by the decrease in metalloproteases concentration and increase in anti-inflammatory mediators. Moreover, the clinical evaluation showed significant improvements in all scores adopted, with stable results up to two years. The present data showed the effectiveness of the study device to harvest pure bone marrow with minimal peripheral blood contamination. The relevant content of MSCs resulted in the ability to counteract the catabolic cascade through a paracrine action. The clinical outcomes in patients affected by unicompartmental knee OA were encouraging in terms of pain reduction and functional improvement up to mid-term evaluation.


Transcriptomic and in vivo approaches introduced human iPSC-derived microvesicles for skin rejuvenation.
The skin undergoes the formation of fine lines and wrinkles through the aging process; also, burns, trauma, and other similar circumstances give rise to various forms of skin ulcers. Induced pluripotent stem cells (iPSCs) have become promising candidates for skin healing and rejuvenation due to not stimulating inflammatory responses, low probability of immune rejection, high metabolic activity, good large-scale production capacity and potentials for personalized medicine. iPSCs can secrete microvesicles (MVs) containing RNA and proteins responsible for the normal repairing process of the skin. This study aimed to evaluate the possibility, safety and effectiveness of applying iPSCs-derived MVs for skin tissue engineering and rejuvenation applications. The possibility was assessed using the evaluation of the mRNA content of iPSC-derived MVs and the behavior of fibroblasts after MV treatment. Investigating the effect of microvesicle on stemness potential of mesenchymal stem cells was performed for safety concerns. In vivo evaluation of MVs was done in order to investigate related immune response, re-epithelialization and blood vessel formation to measure effectiveness. Shedding MVs were round in shape distributed in the range from 100 to 1000 nm in diameter and positive for AQP3, COL2A, FGF2, ITGB, and SEPTIN4 mRNAs. After treating dermal fibroblasts with iPSC-derived MVs, the expressions of collagens Iα1 and III transcripts (as the main fibrous extracellular matrix (ECM) proteins) were upregulated. Meanwhile, the survival and proliferation of MV treated fibroblasts did not change significantly. Evaluation of stemness markers in MV treated MSCs showed negligible alteration. In line with in vitro results, histomorphometry and histopathology findings also confirmed the helpful effect of MVs in skin regeneration in the rat burn wound models. Conducting more investigations on hiPSCs-derived MVs may lead to produce more efficient and safer biopharmaceutics for skin regeneration in the pharmaceutical market.


The effects of luteinising hormone gene polymorphism on the outcomes of in vitro fertilisation and embryo transfer.
Trp8Arg polymorphism of the LH beta gene has decreased bioactivity in vivo and previous studies showed conflicting data on the effect of LH beta gene polymorphism on the IVF outcome. In this study, 591 IVF patients were recruited. Patients with the variant allele(s) were the carrier group. In GnRH antagonist cycles, the clinical pregnancy rate was significantly lower in the carrier group (18.9%) than in the noncarrier group (37.1%). In long GnRH agonist cycles, the clinical pregnancy rate was comparable between both groups. To clarify the effect of COH protocols, IVF outcomes in the GnRH antagonist and long GnRH agonist protocol groups in carriers were analysed. Among carriers, the clinical pregnancy rate was significantly lower in the GnRH antagonist protocol group (18.9%) than in the long GnRH agonist protocol group (45.2%). Single nucleotide polymorphism analysis may contribute to the individualisation of COH protocols for each patient in the future.Impact StatementWhat is already known on this subject? Trp8Arg polymorphism of the LH beta gene is known to have decreased bioactivity in vivo. Previous studies have demonstrated hypo-sensitivity in the patients with the variant LH beta protein, while other study showed similar carrier frequency between the poor and the normal response group.What the results of this study add? The variant LH beta gene was associated with a lower clinical pregnancy rate in GnRH antagonist cycles but not in long GnRH agonist cycles.What the implications are of these findings for clinical practice and/or further research? Single nucleotide polymorphism analysis may contribute to the individualisation of COH protocols for each patient in the future.


Spodiobacter cordis gen. nov. sp. nov., a member of the family Flavobacteriaceae isolated from patients with infective endocarditis.
Two gram-negative, catalase-negative, oxidase-positive strains (PAGU 1467T and PAGU 1468) isolated from patients with infective endocarditis were investigated to determine their taxonomic status. 16S rRNA gene sequence analysis indicated that the two strains were members of the Bergeyella-Chryseobacterium-Riemerella branch of the family Flavobacteriaceae. Strains PAGU 1467T and PAGU 1468 were highly related to each other (98.8% 16S rRNA gene sequence similarity). Phylogenetically closely-related species to PAGU 1467T comprised Bergeyella zoohelcum (95.0% 16S rRNA gene sequence similarity), Riemerella anatipestifer (94.3%) and Cloacibacterium normanense (94.3%). The major fatty acids of the two isolates were iso-C15:0 , iso-C17:0 3-OH and iso-C15:0 3-OH. The presence of C16:0 3-OH and iso-C15:0 2-OH allowed these isolates to be distinguished from B. zoohelcum. Menaquinone MK-6 was the only respiratory quinone in these organisms; this is a consistent characteristic of the family Flavobacteriaceae. The guanine-plus-cytosine content of the genomic DNA was 42.0%, which is higher than that of other close phylogenetic relatives. On the basis of their phenotypic properties and genetic distinctiveness, isolates PAGU 1467T and PAGU 1468 were classified within the novel genus Spodiobacter, as Spodiobacter cordis gen. nov., sp. nov., which is also the type species. The type strain of S. cordis is PAGU 1467T ( = CCUG 65564T = NBRC 109998T ).