Early Predictors of the Long-term Response to Therapy in Patients With Crohn Disease Derived From a Time-Intensity Curve Analysis After Microbubble Contrast Agent Injection.
The aim of this study was to identify early predictors of the long-term response to therapy in patients with Crohn disease (CD) from time-intensity curves obtained after microbubble injection. One hundred fifteen consecutive patients with a proven diagnosis of CD involving the terminal ileal loop who were scheduled to begin pharmacologic therapy with biologics (infliximab or adalimumab) were scanned after sulfur hexafluoride-filled microbubble injection before the beginning and at the end of the sixth week of treatment. The absolute value and percentage change of each semiquantitative kinetic parameter (peak enhancement, time to peak enhancement, rise time, mean transit time, wash-in and wash-out rates, area under the curve [AUC] for the whole time-intensity curve, AUC during wash-in, AUC during wash-out, and wash-in perfusion index) as measured on the terminal ileal tract and adjacent reactive mesenteric fat were calculated from time-intensity curves. Patients were followed for at least 24 months with redetermination of the Crohn Disease Activity Index and with at least 1 endoscopy within 18 weeks after the beginning of pharmacologic treatment. The absolute values and percentage changes of kinetic parameters were assessed as potential predictors of the therapeutic outcome by a logistic regression analysis. The study group included 66 male and 49 female patients (mean age ± SD, 45.76 ± 11 years). The pretreatment values and percentage changes of the peak enhancement, AUC, AUC during wash-in, and AUC during wash-out were found to be predictors (P < .05) of the long-term therapeutic outcome. The analysis of time-intensity curves obtained after microbubble contrast agent injection provides early predictors of the long-term therapeutic outcome in patients with CD.


Efforts Towards Repurposing of Antioxidant Drugs and Active Compounds for Multiple Sclerosis Control.
Multiple Sclerosis (MS) is a degenerative disorder of the central nervous system (CNS) with complicated etiology that has not been clearly analyzed until nowadays. Apart from anti-inflammatory, immune modulatory and symptomatic treatments, which are the main tools towards MS control, antioxidant molecules may be of interest. Oxidative stress is a key condition implicated in the disease progression. Reactive species production is associated with immune cell activation in the brain as well as in the periphery, accounting for demyelinating and axonal disruptive processes. This review refers to research articles, of the last decade. It describes biological evaluation of antioxidant drugs, and molecules with pharmaceutical interest, which are not designed for MS treatment, however they seem to have potency against MS. Their antioxidant effect is accompanied, in most of the cases, by anti-inflammatory, immune-modulatory and neuroprotective properties. Compounds with such characteristics are expected to be beneficial in the treatment of MS, alone or as complementary therapy, improving some clinical and mechanistic aspects of the disease. This review also summarizes some of the pathobiological characteristics of MS, as well as the role of oxidative stress and inflammation in the progression of neurodegeneration. It presents known drugs and bioactive compounds with antioxidant, and in many cases, pleiotropic activity that have been tested for their efficacy in MS progression or the experimentally induced MS. Antioxidants may offer reduction or prevention of the disease symptoms and progression. Thus, their results may, combined with already applied treatments, be beneficial for the development of new molecules or the repurposing of drugs and supplements that are used with other indication so far.


Isolation of plasma membrane fragments from cultured murine melanoma cells.
The various manipulations involved in the isolation of membrane fragments from culture fluids of murine melanoma cells were examined to discern their effect on membrane fragment structure. Ultracentrifugation and gel chromatography were compared using the presence of marker enzymes and the sensitivity to a non-ionic detergent (Triton X-100). Fractionation of media by gel chromatography resulted in only one major form of membrane particles, while ultracentrifugation, followed by resuspension, produced at least two major populations from the identical material. These results indicate that the optimal procedure for membrane fragment isolation is fractionation by an agarose-containing gel, followed by concentration using PEG 20,000.


Confidentiality--at any price?
Confidentiality is a well respected and integral part of medical and dental practice and not without good reason. So fundamental is it to medicine in all its aspects, and so entrenched in the attitudes of those of us in the health care field, that it is never questioned. All patients are individuals in their own right and treated as such in strict confidence.


Secretagogin Regulates Insulin Signaling by Direct Insulin Binding.
Secretagogin (SCGN) is a β-cell enriched, secretory/cytosolic Ca2+-binding protein with unknown secretory regulation and functions. Recent findings suggest that SCGN deficiency correlates with compromised insulin response and diabetes. However, the (patho)physiological SCGN-insulin nexus remains unexplored. We here report that SCGN is an insulin-interacting protein. The protein-protein interaction between SCGN and insulin regulates insulin stability and increases insulin potency in vitro and in vivo. Mutagenesis studies suggest an indispensable role for N-terminal domain of SCGN in modulating insulin stability and function. SCGN supplementation in diabetogenic-diet-fed mice preserves physiological insulin responsiveness while relieving obesity and cardiovascular risk. SCGN-insulin interaction mediated alleviation of hyperinsulinemia by increased insulin internalization, which translates to reduced body fat and hepatic lipid accumulation, emerges as a plausible mechanism for the preservation of insulin responsiveness. These findings establish SCGN as a functional insulin-binding protein (InsBP) with therapeutic potential against diabetes.


[In vitro adherence of bacteria to intraocular lenses of different materials].
To compare the in vitro adherence of different bacteria onto the surface of various intraocular lenses (IOLs). Electron microscopic and bacterial culture quantitative methods were used to study the adherence of Staphylococcus (S) epidermidis, Staphylococcus aureus and Pseudomonas (P) aeruginosa onto the surface of PMMA and other three foldable IOL materials (HEMA, ACRY, SI). S. Epidermidis: HEMA < ACRY < SI < PMMA; S. aureus: HEMA was the least and PMMA was the most, no significant difference between ACRY and SI IOLs; P. aeruginosa: HEMA was the least while no significant difference among PMMA, SI and ACRY IOLs (P > 0.05). The foldable IOLs have the potent ability to reduce the infectious endophthalmitis after surgery of extraction of cataract with IOL implantation.


Oxygen consumption and neonatal sleep states.
1. In thirty full-term infants in the first week of life, nursed in a constant volume, closed-circuit metabolism chamber in a neutral thermal environment (31.5-33.5 degrees C), measurements were made of oxygen consumption ( V(O2)) during periods of rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep.2. The mean V(O2) during REM sleep was 5.97 ml. kg(-1). min(-1). In NREM sleep the mean V(O2) was 5.72 ml. kg(-1). min(-1). This difference was significant (paired t test P < 0.05).3. When the direction of sleep state change was taken into account the difference in V(O2) between the two states was much less when REM sleep preceded NREM than when the change was in the opposite direction. In nineteen infants in whom the change was from REM to NREM the difference in V(O2) (6.18 and 6.03 ml. kg(-1). min(-1)) was not significant (P > 0.05). The mean difference when the sleep state change was from NREM to REM was significant (P < 0.01), the values being 5.54 and 5.81 ml. kg(-1). min(-1) respectively.4. In the NREM state, a gradual diminution of V(O2) with time was consistently found. This was not the case in REM sleep.5. In twelve infants studied in a cool environment (29 +/- 0.5 degrees C) V(O2) during REM sleep was 7.77, and during NREM sleep it was 6.58 ml. kg(-1). min(-1), (P < 0.001). Thus even the maximum difference found in a neutral thermal environment of 6.6% was significantly increased to 14.9% (P < 0.01) with mild thermal stress.6. No consistent changes in V(O2) with time were found in either REM or NREM sleep in twelve infants studied in a cool environment, in contrast to the findings in thermal neutrality


The bleeding severity index: validation and comparison to other methods for classifying bleeding complications of medical therapy.
Reports of bleeding complications of medical therapy should be based on valid methods of classification, but the reproducibility of existing methods has not been tested. Therefore, we prospectively studied three methods to classify the severity of bleeding: a purely subjective implicit method, a previously published explicit method using brief criteria, and the bleeding severity index, which is a new explicit method using detailed criteria about the amount, rate, and consequences of bleeding. Three physicians independently reviewed abstracts of 168 patients treated with anticoagulants. The proportion of cases classified as major bleeding varied widely when the implicit method was used (2, 14 and 39%), less when the old explicit method was used (28, 40 and 47%), and not at all when the new bleeding severity index was used (20, 20 and 20%). Intraobserver agreement was excellent for both explicit methods (kappa greater than or equal to 0.95). However, interobserver agreement was better for the bleeding severity index (kappa = 0.87) than for the old explicit method (kappa = 0.69) or the implicit method (kappa = 0.39). We conclude that the classification of bleeding complications of medical therapy depends on the method used. In comparison to older methods, the bleeding severity index is highly reproducible and should be tested more widely to determine whether it can be applied to the burgeoning clinical research in anticoagulation and thrombolysis.


Variation in Specialty Outpatient Care Patterns in the Medicare Population.
Multiple payment reform efforts are under way to improve the value of care delivered to Medicare beneficiaries, yet few directly address the interface between primary and specialty care. To describe regional variation in outpatient visits for individual specialties and the association between specialty physician-specific payments and patient-reported satisfaction with care and health status. Retrospective cross-sectional study. A 20 % random sample of Medicare fee-for-service beneficiaries in 2012. Regions were grouped into quartiles of specialist index, defined as the observed/expected regional likelihood of having an outpatient visit to a specialist, for ten common specialties, adjusting for age, sex, and race. Outcomes were per capita specialty-specific physician payments and Medicare Current Beneficiary Survey responses. The proportion of beneficiaries seeing a specialist varied the most for endocrinology and gastroenterology (3.7- and 3.9-fold difference between the highest and lowest quartiles, respectively) and least for orthopedics and urology (1.5- and 1.7-fold difference, respectively). Multiple analyses suggested that this variation was not explained by prevalence of disease. Average specialty-specific payments were strongly associated with the likelihood of visiting a specialist. Differences in per capita payments from lowest (Q1) to highest quartiles (Q4) were greatest for cardiology ($89, $135, $172, $251) and dermatology ($46, $64, $82, $124). Satisfaction with overall care (median [interquartile range] across specialties: Q1, 93.3 % [92.6-93.7 %]; Q4, 93.1 % [92.9-93.2 %]) and self-reported health status (Q1, 37.1 % [36.9-37.7 %]; Q4, 38.2 % [37.2-38.4 %]) was similar across quartiles. Satisfaction with access to specialty care was consistently lower in the lowest quartile of specialty index (Q1, 89.7 % [89.2-91.1 %]; Q4, 94.5 % [94.4-94.8 %]). Substantial regional variability in outpatient specialist visits is associated with greater payments with limited benefits in terms of patient-reported satisfaction with care or reported health status. Reducing outpatient physician visits may represent an important opportunity to improve the efficiency of care.


A health program's effect on neonatal mortality in eastern Kentucky.
We examined the impact of an innovative rural health program in central Appalachia on neonatal mortality by comparing improvements in the neonatal mortality rates of the serviced counties to those of the 13 control counties. Using data on all births and neonatal deaths in the study and control counties from 1970 to 1978 (tabulated by mother's county of residence), an expected neonatal mortality rate of each county was calculated by standardizing for the most important risk components: birth weight, sex, and birth multiplicity. An index of medical care effectiveness, the standardized mortality rate (SMR) for the study and control counties was computed by dividing the observed neonatal mortality rate by the expected rate. The SMRs of the study and control counties were then compared using a standard normal test statistic. The results indicated that the SMRs were significantly different in the control and study counties in the preintervention period 1970-1972. In subsequent years the SMRs converged, resulting in nearly equal rates for 1977-1978. The improvement in neonatal mortality in both areas may be due to their improved economic status rather than health care alone.


Palatal injection for removal of maxillary teeth: is it required? A systematic review.
There is a growing body of work examining whether a palatal injection is necessary for the extraction of maxillary teeth with contemporary local anaesthetics. The available literature was reviewed systematically by conducting a search of the PubMed, EMBASE, and Cochrane CENTRAL databases for trials examining outcomes of maxillary tooth extraction where buccal injection of local anaesthetic only was used for one or more test groups. The selected studies were reviewed for study type, sample size, quality, participant characteristics and methodology, outcome variables, and findings. Fifteen studies met the inclusion criteria. Six of the studies were randomized controlled trials. Four studies were controlled clinical trials that did not report randomization. Five were clinical trials that were not controlled and examined outcomes of one or more test groups. The pain of local anaesthetic injection(s) in the test group (buccal injection only) versus control group (buccal and palatal injection), number of cases requiring supplemental buccal or palatal injection in cases of unsuccessful local anaesthesia, and pain during the procedure were designated as primary outcomes. Pain on probing of the mucosa was designated as a secondary outcome. All nine controlled studies that assessed pain during the procedure found no statistically significant difference between the test and control groups.


Residual effects of 12 weeks of power-oriented resistance training plus high-intensity interval training on muscle dysfunction, systemic oxidative damage, and antioxidant capacity after 10 months of training cessation in older people with COPD.
This study aimed to assess the residual effects of a 12-week concurrent training program (power training + high-intensity interval training) in older adults with chronic obstructive pulmonary disease (COPD). A total of 21 older adults with COPD [intervention (INT), n = 8; control (CON), n = 13; 76.9 ± 6.8 years] were assessed at baseline and 10 months after the completion of the intervention by the short physical performance battery (SPPB), health-related quality of life (EQ-5D-5L), vastus lateralis muscle thickness (MT), peak pulmonary oxygen uptake (peak VO2 ) and peak work rate (Wpeak ), early and late isometric rate of force development (RFD), leg and chest press maximum muscle power (LPmax and CPmax ), and systemic oxidative damage and antioxidant capacity. Compared to baseline, after 10 months of detraining, the INT group presented increased SPPB (∆ = 1.0 point), health-related quality of life (∆ = 0.07 points), early RFD (∆ = 834 N∙s-1 ), LPmax (∆ = 62.2 W), and CPmax (∆ = 16.0 W) (all p < 0.05). In addition, a positive effect was noted in INT compared to CON regarding MT and Wpeak (both p < 0.05). No between-group differences were reported in peak VO2 , late RFD, systemic oxidative damage, and antioxidant capacity from baseline to 10 months after the completion of the intervention (all p > 0.05). Twelve weeks of concurrent training were enough to ensure improved physical function, health-related quality of life, early RFD and maximum muscle power and to preserve MT and Wpeak but not peak VO2 , late RFD, systemic oxidative damage and antioxidant capacity in the subsequent 10 months of detraining in older adults with COPD.


Short- and mid-term repeatability of macular pigment optical density measurements using spectral fundus reflectance.
Several methods have been proposed for measuring macular pigment optical density (MPOD). To date, none of the realized techniques can be considered as "gold standard". A key issue for the clinical applicability of a method is its repeatability. In this study, we investigated short- and mid-term repeatability of MPOD measurements using reflectometry. A total of 12 healthy young subjects were measured 5 times on 5 consecutive days. Repeatability over 6 months was investigated in patients with AMD. The data in AMD patients were taken from a recently published placebo controlled study investigating the effect of lutein supplementation on MPOD (n = 37; [1]). Four measurements over 6 months were used to calculate repeatability. Spectral fundus reflectance of the fovea was measured in a 2.3° detection field with a custom-built fundus reflectometer. Calculation of MPOD was based on a previously published fundus reflectance model. The coefficients of variation were 6.2 ± 2.4% and 8.0 ± 5.5% in the healthy and AMD group, respectively. Bland-Altman plots indicate that the difference between measurements at day 1 and day 5 in healthy subjects and day 1 and month 6 in AMD patients was small. The maximum deviation in MPOD in a healthy subject was 0.07 (22.6%), and 0.17 (51.5%) in a patient with AMD. Reflectometry provides adequate short-term and mid-term repeatability for measuring MPOD. Accordingly, the technique makes it possible to monitor MPOD in patients with AMD and to study the influence of supplementation in these subjects. In addition, the variability of the technique is small enough to allow for clinical trials with reasonable sample size.


Thermodynamics of the hydrolysis of sucrose.
A thermodynamic investigation of the hydrolysis of sucrose to fructose and glucose has been performed using microcalorimetry and high-pressure liquid chromatography. The calorimetric measurements were carried out over the temperature range 298-316 K and in sodium acetate buffer (0.1 M, pH 5.65). Enthalpy and heat capacity changes were obtained for the hydrolysis of aqueous sucrose (process A): sucrose(aq) + H2O(liq) = glucose(aq) + fructose (aq). The determination of the equilibrium constant required the use of a thermochemical cycle calculation involving the following processes: (B) glucose 1-phosphate2-(aq) = glucose 6-phosphate2-(aq); (C) sucrose(aq) + HPO4(2-)(aq) = glucose 1-phosphate2-(aq) + fructose(aq); and (D) glucose 6-phosphate2-(aq) + H2O(liq) = glucose(aq) + HPO4(2-)(aq). The equilibrium constants determined at 298.15 K for processes B and C are 17.1 +/- 1.0 and 32.4 +/- 3.0, respectively. Equilibrium data for process D was obtained from the literature, and in conjunction with the data for processes B and C, used to calculate a value of the equilibrium constant for the hydrolysis of aqueous sucrose. Thus, for process A, delta G0 = -26.53 +/- 0.30 kJ mol-1, K0 = (4.44 +/- 0.54) x 10(4), delta H0 = -14.93 +/- 0.16 kJ mol-1, delta So = 38.9 +/- 1.2 J mol-1 K-1, and delta CoP = 57 +/- 14 J mol-1 K-1 at 298.15 K. Additional thermochemical cycles that bear upon the accuracy of these results are examined.


Transcriptome analysis and SNP identification in SCC of horn in (Bos indicus) Indian cattle.
Single Nucleotide Polymorphisms (SNPs) have become the marker of choice for genome wide association studies. In order to provide the best genome coverage for the analysis of disease, production and performance traits, a large number of relatively evenly distributed SNPs are needed. The main objective of present work was to identify large numbers of gene-associated SNPs using high-throughput sequencing in squamous cell carcinoma of horn. RNA-seq analysis was conducted on 2 tissues viz. Horn Cancer (HC) and Horn Normal (HN) in Kankrej breed of cattle. A total of 909,362 reads with average read length of 405 bp for HC and 583,491 reads with average read length of 411 bp for HN were obtained. We found 9532 and 7065 SNPs as well as 1771 and 1172 Indels in HC and HN, respectively, from which, 7889 SNPs and 1736 Indels were uniquely present in HC, 5886 SNPs and 1146 Indels were uniquely present in HN and reported first time in Bos indicus, whereas the rest are already reported in Bos taurus dbSNP database. The gene-associated SNPs and Indels were high in upregulated genes of HC as compared to HN. Analysis of differentially expressed genes was identified, these genes are involved in regulation of cell proliferation, apoptosis, gene transcription, cell survival and metabolism through various metabolic pathways. The result of transcriptome expression profiling was validated using Real Time quantitative PCR in nine randomly selected genes. We identified numbers aberrant signaling pathways responsible for carcinogenesis in HC which are also commonly altered in squamous cell carcinoma (SCC) of lung in human being. We conclude that a large number of altered genes and dysfunction of multiple pathways are involved in the development of Horn Cancer. The present findings contribute to theoretical information for further screening of genes and identification of markers for early diagnosis of HC as well as SNPs identified in this report provide a much needed resource for genetic studies in B. indicus and shall contribute to the development of a high density SNP array. Validation and testing of these SNPs using SNP arrays will form the material basis for gene associated SNPs in HC.


Extraction technology, components analysis and anti-inflammatory activity in vitro of total flavonoids extract from Artemisia anomala S. Moore.
Artemisia anomala S. Moore exerts many pharmacological activities, including the removing of the blood stasis, relieving of the fever and analgesia, reducing the swelling and dampness. In this study, the extraction technology, chemical compositions and anti-inflammatory effect in vitro and mechanism of total flavonoids extract from Artemisia anomala S. Moore were studied. The optimal yield rate of total flavonoids extract was optimized by single factor experiments and response surface method, and the chemical constituents were analyzed by UPLC-QTOF-MS method; and the anti-inflammatory activity of the extract was evaluated with lipopolysaccharide induced RAW 264.7 cells. The highest extraction rate was 2.02% under these conditions of the concentration of ethanol 50%, the ultrasonic extraction time 30 min, and the ratio of solvent volume to material weight 20:1 (ml/g). In addition, the main components of total flavonoid extract were preliminarily identified and deduced based on mass spectrometry information and relevant literatures, and its stronger anti-inflammatory activity was demonstrated by reducing the phagocytosis, the content of nitric oxide and the level of related cytokines (tumor necrosis factor-α, interleukin-10, interleukin-6). Furthermore, it was further revealed that the anti-inflammatory effect of the extract was closely connected with the activation of TLR4-MyD88-NF-κB signalling pathway. This study indicated that the total flavonoids extract from Artemisia anomala S. Moore may be a better candidate anti-inflammatory natural medicine.


p53 and bcl-2 immunohistochemistry in preoperative biopsies as predictors of biochemical recurrence after radical prostatectomy.
To evaluate p53 and bcl-2 immunohistochemistry in preoperative biopsies and radical prostatectomy specimens, as predictors of biochemical recurrence. Preoperative biopsies from 73 men, and the radical prostatectomies from these men and from a further 47 men, were evaluated. The serum prostate specific antigen (PSA) level, Gleason score, pathological stage and margin involvement were recorded. The immunohistochemical expression of p53 and bcl-2 was studied on a representative area of tumour with the highest Gleason grade. The median follow-up was 53 months. During the follow-up 47 of the 120 patients had a biochemical recurrence. Capsular penetration was present in 63 (53%) and the surgical margins were positive in 47 (39%). The Gleason score was < 7 in 81 (68%) patients; p53 was positive in 40 (66%) of 61 biopsies and 84 (71%) of 118 prostatectomy specimens. Bcl-2 was positive in eight (13%) of 63 biopsies and 20 (17%) of 118 prostatectomies. On multivariate analysis the biopsy p53, Gleason score and serum PSA were significant predictors of recurrence. On multivariate analysis, capsular penetration, PSA and margin status at prostatectomy were significant predictors of recurrence. There was also a significant interaction between PSA and margin status. Although univariately significant, neither p53 nor bcl-2 featured in the final multivariate model. Biopsy p53 status significantly predicts recurrence after radical prostatectomy, but its low specificity and technical issues suggest that it will not be useful in the clinical setting. However, a patient with negative p53 on biopsy is likely to have a good prognosis on prolonged follow-up.


Sodium hypochlorite versus Formocresol in primary molars pulpotomies: a randomized clinical trial.
The aim of this randomised clinical trial was to compare the clinical and radiographic success rate of 5% sodium hypochlorite (NaOCl) and 20% Formocresol (FC) as a pulpotomy medicament in carious primary molars. Twenty-four children aged 4-8 years with at least 2 primary molars indicated for pulpotomy were included in this study. Eighty-two teeth received either 5% NaOCl or 20% FC using split mouth design, followed by restoration with IRM base/stainless steel crown (SSC). Clinical and radiographic evaluations were performed at 3, 6 and 12 months. NaOCl and FC groups demonstrated 100% clinical success at 3 months. At 6 months, NaOCl showed 95% and 87.5% clinical and radiographic success rate respectively, while FC showed 95% clinical and radiographic success rate. After 12 months, the clinical and radiographic success rates were 94.6% and 86.5% respectively for NaOCl, and 92.1% and 86.8% for FC. The results of this study showed the success rate for NaOCl pulpotomy to be comparable to those for FC pulpotomy.


Enlarged vestibular aqueduct and Mondini Malformation: audiological, clinical, radiologic and genetic features.
When referring to enlarged vestibular aqueduct (EVA) we should differentiate between nonsyndromic enlarged vestibular aqueduct (NSEVA) and Pendred Syndrome (PDS), a disease continuum associated with pathogenic sequence variants of Pendrin's Gene (SLC26A4) in about half of the cases. The study was aimed to analyse the clinical and audiological features of a monocentric cohort of Caucasian patients with NSEVA/PDS, their genetic assessment and morphological inner ear features. We retrospectively reviewed the audiologic, genetic and anamnestic data of 66 patients with NSEVA/PDS followed by our audiology service. SLC26A4 mutations was significantly correlated with the presence of PDS rather than NSEVA (p < 0.019), with the expression of inner ear malformations (p < 0.001) and with different severity of hearing loss (p = 0.001). Furthermore, patients with PDS showed significantly worse pure tone audiometry (PTA) than patients with NSEVA (p = 0.001). Anatomically normal ears presented significantly better PTA than ears associated with Mondini Malformation or isolated EVA (p < 0.001), but no statistically significative differences have been observed in PTA between patients with Mondini Malformation and isolated EVA. NSEVA/PDS must be investigated in all the congenital hearing loss, but also in progressive, late onset, stepwise forms. Even mixed or fluctuating hearing loss may constitute a sign of a NSEVA/PDS pathology. Our findings can confirm the important role of SLC26A4 mutations in determining the phenotype of isolated EVA/PDS, both for the type/degree of the malformation, the hearing impairment and the association with thyroid dysfunction.


Rituximab as a rescue treatment added on mycophenolate mofetil background therapy in progressive systemic sclerosis associated interstitial lung disease unresponsive to conventional immunosuppression.
To test whether the use of rituximab (RTX) is effective and safe as a rescue therapy add-on treatment to mycophenolate (MMF) in patients with progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) in whom conventional immunosuppressants (IS) have failed. Longitudinal retrospective observational study of a cohort of patients with SSc-ILD that started treatment with RTX due to ongoing lung function impairment despite treatment with glucocorticoids and IS (cyclophosphamide and/or MMF). All patients were treated with 2 or more cycles of RTX and evaluated for at least 12 months. Twenty-four patients were included. Before initiation of RTX the mean decline in%pFVC and %pDLCO during the previous 2 years (delta) was -12.9% and -12.5%, respectively. After 1 year of treatment with RTX, a significant improvement in %pFVC (∆+8.8% compared to baseline, 95% CI: -13.7 to -3.9; p = 0.001) and%pDLCO (∆+4.6%, 95% CI: -8.2 to -0.8; p = 0.018) was observed. In addition, there was a significant reduction in the median dose of prednisone and it could be suspended in 25% of patients. At 2 years of treatment, RTX had been discontinued in 9 patients (due to adverse events in 3 cases and inefficacy in 6). In the 15 patients (62.5%) that completed 24 months of therapy, the statistically significant amelioration in pulmonary function test parameters was maintained: ∆%pFVC: +11.1% (95% CI: -17.6 to -4.5; p = 0.003) and ∆%pDLCO: +8.7% (95% CI: -13.9 to -8.3; p = 0.003). Based on our results, RTX's use as an add-on treatment to MMF appears to be effective as a rescue therapy in patients with a more aggressive SSc-ILD phenotype.


Accreditation as a path to achieving universal quality health coverage.
As many low- and middle-income countries (LMICs) pursue health care reforms in order to achieve universal health coverage (UHC), development of national accreditation systems has become an increasingly common quality-enhancing strategy endorsed by payers, including Ministries of Health. This article describes the major considerations for health system leaders in developing and implementing a sustainable and successful national accreditation program, using the 20-year evolution of the Thai health care accreditation system as a model. The authors illustrate the interface between accreditation as a continuous quality improvement strategy, health insurance and other health financing schemes, and the overall goal of achieving universal health coverage.


Perioperative oral care can prevent surgical site infection after colorectal cancer surgery: A multicenter, retrospective study of 1,926 cases analyzed by propensity score matching.
Surgical site infection is a common postoperative complication of colorectal cancer surgery, and surgical site infection increases medical costs, prolongs hospitalization, and worsens long-term prognosis. Perioperative oral care has been reported to be effective in preventing postoperative pneumonia, although there are only a few reports on its effectiveness in preventing surgical site infection. This study aimed to determine the role of perioperative oral care in surgical site infection prevention after colorectal cancer surgery. In this study, 1,926 patients with colorectal cancer from 8 institutions were enrolled; 808 patients (oral care group) received perioperative oral care at the hospital's dental clinic, and 1,118 (control group) did not receive perioperative oral care. The data were matched by propensity score to reduce bias. Ultimately, a total of 1,480 patients were included in the analysis. The incidence of surgical site infection was significantly lower in the oral care group than in the control group (8.4% vs 15.7%, P < .001). Multivariate logistic regression analysis revealed 4 independent risk factors for surgical site infection: low albumin level, rectal cancer, blood loss, and lack of perioperative oral care. Lack of perioperative oral care had an odds ratio of 2.100 (95% confidence interval 1.510-2.930, P < .001). These results suggest that perioperative oral care can reduce the incidence of surgical site infection after colorectal cancer resection. Perioperative oral care may have an important role in the future perioperative management of colorectal cancer as a safe and effective method of surgical site infection prevention, although further validation in prospective studies is needed.


Potential applications of ficin in the production of traditional cheeses and protein hydrolysates.
Using proteolytic enzymes extracted from plant materials is a promising way to ensure the sustainability of the food industry. This is particularly true for the dairy industry, especially in cheesemaking and the production of different milk protein hydrolysates for special food applications, particularly nutrition for infants, older adults, and people with food allergies. Ficin, a cysteyl protease isolated from the latex of the fig tree (Ficus carica), is characterized by strong enzymatic activity and can be used for milk clotting and protein hydrolysis for application in different foods. In particular, it can be used for milk protein hydrolysis to produce ingredients with reduced or eliminated allergenicity and improved bioavailability. Ficin can also be used as an active and effective replacement for calf rennet in cheesemaking, such as in traditional Cacioricotta and Teleme cheeses. It can also be used to produce protein hydrolysates with low or no allergenicity for application in infant formula and geriatric nutrition. This work provides an overview of ficin, a plant-derived protease, with an emphasis on its potential application in the production of some traditional cheeses and milk protein hydrolysates for special food applications.


Reconstruction of a post-traumatic tibial defect of 10 cm in a 6 month old induced membrane by non-vascularised fibula autograft - A case report.
Reconstruction of post-traumatic large bone defect in tibia is a surgical challenge. Masquelet technique is a two stage procedure to achieve bone union. After cement spacer implantation in defect, optimal time for 2nd stage bone grafting is at 1 month. After 2 months, osteoinductive property of induced membrane is doubtful. We managed a post- traumatic tibial defect of 10 cm with cement spacer as 1st stage of Masquelet procedure. But 2nd stage was delayed for 6 months at which time osteoinductive property of induced membrane was doubtful. Osteopenia, pin track infection with stiff knee and ankle made 2nd stage surgery more challenging. We reconstructed 6 months old induced membrane with 12 cm non-vascularised fibula autograft in combination of cancellous autograft from iliac crest. The construct was fixed with locking compression plate on medial side. Patient achieved bone consolidation and successful union at 9 months with knee flexion of 100 degrees. This case demonstrated that induced membrane is able to preserve osteoinduction property even up to 6 months and with good structural support like fibula strut graft, successful reconstruction is possible in delayed 2nd stage of Masquelet technique.


Treatment-Related Adverse Events of Combination EGFR Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitor in EGFR-Mutant Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.
(1) Background: We performed a meta-analysis to examine whether combined epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) and immune checkpoint inhibitor (ICI) increases treatment-related adverse events (trAEs) in advanced non-small cell lung cancer (NSCLC). (2) Methods: Articles from MEDLINE, EMBASE, and Cochrane databases were searched. Proportions and odds ratios (ORs) of the pooled incidence of overall and organ-specific trAEs in combination EGFR-TKI and ICI were compared to TKI monotherapy. (3) Results: Eight studies fulfilled our selection criteria. Any-grade organ-specific trAEs were more common in combination EGFR-TKI and ICI than TKI monotherapy (skin: OR = 1.19, p = 0.012; gastrointestinal tract: OR = 1.04, p = 0.790; ILD: OR = 1.28, p = 0.001). Grade ≥ 3 trAEs were also more frequent in combination treatment (skin: OR = 1.13, p = 0.082; gastrointestinal tract: OR = 1.13, p = 0.076; ILD: OR = 1.16, p = 0.003). (4) Conclusions: A higher proportion of grade ≥3 skin and gastrointestinal trAEs and ILDs was observed in combination TKI and ICI compared to TKI alone. Caution has to be taken when interpreting the results owing to the small number of studies included in this meta-analysis.


Quantitative analysis of blend uniformity within a Three-Chamber feed frame using simultaneously Raman and Near-Infrared spectroscopy.
This study reports the use of Raman and Near-infrared (NIR) spectroscopy to simultaneously monitor the drug concentration in flowing powder blends within a three-chamber feed frame. The Raman probe was located at the top of the dosing chamber, while the NIR probe was located at the top of the filling chamber. The Raman and NIR spectra were continuously acquired while the powder blends flowed through the feed frame. Calibration models were developed with spectra from a total of five calibration blends ranging in caffeine concentration among 3.50 and 6.50% w/w. These models were optimized to predict three test set blends of 4.00, 5.00, and 6.00% w/w caffeine. The results showed a high predictive ability of the models based on root mean square error of predictions of 0.174 and 0.235% w/w for NIR and Raman spectroscopic models, respectively. Concentration profiles with higher variability were observed for the Raman spectroscopy predictions. An estimate of the mass analyzed by each spectrum showed that a NIR spectrum analyzes approximately 4.5 times the mass analyzed by a Raman spectrum; despite these differences in the mass analyzed, blend uniformity results are equivalent between techniques. Variographic analysis demonstrated that both techniques have significantly low sampling errors for the real-time monitoring process of drug concentration within the feed frame.


Anionic dye uptake via composite using chitosan-polyacrylamide hydrogel as matrix containing TiO2 nanoparticles; comprehensive adsorption studies.
In the present study, TiO2 nanoparticles dispersed in chitosan grafted polyacrylamide matrix (TiO2-PAM-CS) was synthesized using in situ technique, and applied for the uptake of Sirius yellow K-CF dye from aqueous solution. The synthesized nano-composite was characterized by FE-SEM, TEM, XRD and FT-IR analysis. The effect of significant parameters such as pH, dose, time and temperature in batch adsorption experiments were investigated. The adsorption process was pH dependent and the optimum value of pH was obtained 2 with 96.81% dye removal at 40 °C. The equilibrium data were compatible well with the Langmuir isotherm having qm value of 1000 mg/g. The Dubinin-Radushkevich (D-R) isotherm and thermodynamic studies prove that the adsorption is physical, endothermic and spontaneous. Kinetic study also verifies that pseudo second order kinetic model is the predominant model. The interactions between amin groups of polyacrylamide-chitosan (PAM-CS) composite in from of NH3+ and molecules of anionic dye via hydrogen bond formation (Dye-NH3+), also electrostatic interactions between Ti+4 available in PAM-CS composite and anionic dye (free energy of 1.66 kJ/mol calculated from D-R model) govern the adsorption mechanism. The reusability test showe that TiO2-PAM-CS composite can be renewed easily with HCl solution as an efficient adsorbent for practical wastewater treatment.


Genetic Diversity and Drug Resistance Mutations in HIV-1 from Untreated Patients in Niamey, Niger.
The objective of the study was to estimate the prevalence of transmitted resistance to antiretroviral of HIV-1 circulating in Niger. We collected plasmas from 96 drug-naive patients followed up in the main HIV/AIDS Care Center of Niamey, the capital city of Niger. After RNA extraction and retrotranscription to proviral DNA, nested PCR was performed to amplify PR (codons 1-99) and RT (codons 1-240) fragments for sequencing. Sequences were analysed for phylogeny, then for resistance-associated mutations according to IAS-USA and Stanford's lists of mutations. We characterized six HIV-1 genetic variants: CRF02-AG (56.3%), CRF30_0206 (15.6%), subtype G (15.6%), CRF06_cpx (9.4%), CRF11_cpx (2.1%), and CRF01_AE (1%). About 8.3% of HIV strains had at least 1 resistance mutation: 4 strains with at least 1 mutation to NRTI, 5 for NNRTI, and 1 for PI, respectiveley 4.2%, 5.2%, and 1.0%. These preliminary results gave enough information for the need of instauring HIV drug resistance national surveillance.


A comparison of different murine models for cytomegalovirus-induced sensorineural hearing loss.
To compare three different inoculation techniques for the development of cytomegalovirus (CMV)-induced sensorineural hearing loss (SNHL) in a mouse model. A prospective experimental animal study. BALB/c mice underwent inoculation using green fluorescent protein-expressing mouse cytomegalovirus (mCMV-GFP) via transtympanic (TT), intraperitoneal (IP), or intracranial (IC) routes. Control mice received an equal volume of saline. Hearing thresholds were measured using both distortion product otoacoustic emissions (DPOAE) and evoked auditory brainstem response studies (ABR). Cochleas were harvested for histological examination and cytocochleogram. No mice in the TT or IP groups showed significant hearing loss. All infected mice in the IC group showed significantly elevated ABR and DPOAE thresholds at 4 weeks of age. Ten mice (55%) had profound hearing loss (≥80 dB) at 4 weeks of age, while the other eight mice (45%) initially showed moderate hearing loss (≤20 dB), which progressed to profound hearing loss by 6 to 8 weeks. Asymmetric hearing loss was seen in 40% of the mice. Temporal bone histology showed diffuse loss of outer hair cells (OHC). Green fluorescent protein (GFP)-labeled virus was abundant in the spiral ganglion and adjacent to the scala tympani at the basal region of the cochlea at 7 days postinjection, and devoid of GFP labeling by 14 days postinfection. Intracerebral injection of mCMV preferentially causes mCMV-mediated hearing loss relative to IP or TT injections. These results are consistent with the hearing loss reported in human congenital infection and may have implications for understanding the pathophysiology of CMV-mediated labyrinthitis.


Layer structured α-Fe₂O₃ nanodisk/reduced graphene oxide composites as high-performance anode materials for lithium-ion batteries.
A composited anode material with combined layered α-Fe2O3 nanodisks and reduced graphene oxide was produced by an in situ hydrothermal method for lithium-ion batteries. As thin as about 5-nm-thickness α-Fe2O3 nanosheets, open channels, and face-to-face tight contact with reduced graphene oxide via oxygen bridges made the composite have a good cyclability and rate performance, especially at high charge/discharge rates.


Effects of a postural cueing for head and neck posture on lumbar lordosis angles in healthy young and older adults: a preliminary study.
Postural rehabilitation plays an important role in the treatment of non-specific low back pain. Although pelvic inclination has been widely used to improve lumbar lordosis, the effect of cervical anterior inclination on lumbar lordosis in young and older adults in sitting and standing posture is still unclear. This preliminary study was designed to examine the influence of changing the cervical anterior angle on the lumbar lordosis angle, through alterations of the head position under the natural sitting and standing conditions, aiming to provide a basis for establishing a new postural rehabilitation strategy. Thirty-six young (24.0 ± 2.2 years, 14 females and 22 males) and 38 older (68.4 ± 5.9 years, 36 females and 2 males) healthy adults participated in this study. The four spinal regional angles-cervical anterior angle, thoracic kyphosis angle, lumbar lordosis angle, and pelvic forward inclination angle, were measured in standing and relaxed sitting postures to determine the effects of a postural cueing for the head and neck posture, "inclining head backward and performing chin tuck," on lumbar lordosis angle. In the standing posture, the pelvic forward inclination angle in the older adult group was significantly smaller (P < 0.001, by ANOVA) than that in the young adult group and increased significantly (P < 0.001) in response to the postural cueing. In addition, the thoracic kyphosis angle in the standing (P = 0.001) and sitting (P = 0.003) positions was significantly reduced in response to the postural cueing. However, the lumbar lordosis angle in response to the postural cueing increased significantly in both the standing position (P < 0.001) and sitting position (P < 0.001). The results suggest that increasing the cervical anterior angle can increase the lumbar lordosis angle, and the cervical anterior inclination can be used as an alternative to pelvic forward inclination to improve the lumbar lordosis angle. Furthermore, the change in head and neck posture can reduce the thoracic kyphosis angle, making it possible to establish a new noninvasive body posture rehabilitation strategy.


Environmental and biological monitoring of chloroform in indoor swimming pools.
The presence of chloroform as the result of disinfection with sodium hypochlorite was demonstrated in the water and ambient air of indoor swimming pools. Environmental monitoring was performed in 12 indoor swimming pools in northern Italy and the level of human exposure was assessed. Biological monitoring performed by gas chromatography on human plasma and alveolar air samples evidenced that the uptake of chloroform in swimmers varies according to the intensity of the physical activity and age. The elimination of chloroform in alveolar air in one subject showed a very short half-life (from 20 to 27 min) and a complete clearance within 10 h after the end of exposure.


The role of the operating parameters of SBR systems on the SMP production and on membrane fouling reduction.
In this work, six identical laboratory SBRs treating simulated wastewater were operated in parallel studying the effect of three food-to-microorganisms ratio (F/M ratio; 0.20, 0.35 and 0.50 kg COD·kg MLSS-1·d-1), two hydraulic retention times (HRT; 24 and 16 h) and two values of number of cycles per day (3 and 6). Influence of these operational parameters on the SMPs production and reactor performance, were studied. Results indicated that the highest F/M ratio, HRT and cycles/day produced 72.7% more of SMP. In a second experimental series, biological process yielding the maximal and the minimal SMPs production were replicated and both mixed liquors (ML) and treated effluents were ultrafiltrated. The flux decay in the conditions of minimum and maximum SMPs production were 52% and 72%, when the SBRs effluents were ultrafiltrated while no significant differences in the ultrafiltration of ML were found. In terms of permeability recovery, this was lower for the case of the ML (73% and 49% of initial permeability recovered for effluent and ML ultrafiltration, respectively).


Continuous multi-element (Cu, Mn, Ni, Se) monitoring in saline and cell suspension using on-line microdialysis coupled with simultaneous electrothermal atomic absorption spectrometry.
We have developed a microdialysis sampling technique coupled on-line with simultaneous electrothermal atomic absorption spectrometry (SIMAAS) for the continuous monitoring of copper (Cu), manganese (Mn), nickel (Ni), and selenium (Se) in saline solutions and in cell suspensions. These trace elements are considered to be those associated most significantly with oxidative stress in biological systems. We employed ultrapure saline (0.9% NaCl) as the perfusate and, thus, the dialysate samples contained a high concentration of salt in the matrix. The use of modifiers [Pd coupled with Mg(NO3)2] prevented the target elements from undergoing evaporation at a pyrolysis temperature of 1200 degrees C, a process that effectively eliminated interference from NaCl. The excellent linearity, detection limits, and precision of the SIMAAS technique allowed the Cu, Mn, Ni, and Se concentrations to be determined in saline. For the on-line microdialysis-SIMAAS system, the ultrapure saline was perfused at a flow rate of 1 microL/min. The probe recoveries of Cu, Mn, Ni, and Se in saline were 57.9, 65.0, 65.5, and 67.9%, respectively. A standard saline solution was measured continuously by the on-line system to ensure long-term stability; each measurement fell within a range of two standard deviations. We determined the on-line spiked recoveries of Cu, Mn, Ni, and Se (101.3, 88.8, 91.3, and 98.5%, respectively) by adding a spiking standard into the stirred saline. The spiked recoveries (Cu, 37.5%; Mn, 3.8%; Ni, 71.1%; Se, 33.8%) were also determined through on-line spiking of a standard into the stirred cell suspension; these values demonstrate that Cu, Mn, and Se were depleted in the cell suspension, but Ni was not. The use of this on-line microdialysis-SIMAAS system permitted the in situ, dynamic, and continuous monitoring of Cu, Mn, Ni, and Se in cell suspensions at a temporal resolution of 20 min.


De novo resonance assignment of the transmembrane domain of LR11/SorLA in E. coli membranes.
Membrane proteins perform many important cellular functions. Historically, structural studies of these proteins have been conducted in detergent preparations and synthetic lipid bilayers. More recently, magic-angle-spinning (MAS) solid-state NMR has been employed to analyze membrane proteins in native membrane environments, but resonance assignments with this technique remain challenging due to limited spectral resolution and high resonance degeneracy. To tackle this issue, we combine reverse labeling of amino acids, frequency-selective dipolar dephasing, and NMR difference spectroscopy. These methods have resulted in nearly complete resonance assignments of the transmembrane domain of human LR11 (SorLA) protein in E. coli membranes. To reduce background signals from E. coli lipids and proteins and improve spectral sensitivity, we effectively utilize amylose affinity chromatography to prepare membrane vesicles when MBP is included as a fusion partner in the expression construct.


Traffic-related organic and inorganic air pollution and risk of development of childhood asthma: A meta-analysis.
The effect of early childhood exposure to traffic-related air pollution (TRAP) on the development of asthma remains unclear. The aim of this study was to clarify potential associations between TRAP (fine particulate matter, PM2.5; nitrogen dioxide, NO2; Benzene and total volatile organic pollutants, TVOCs) and childhood asthma by integrating the results from previous studies. Elsevier, LISTA (EBSCO) and Web of Science databases were searched for relevant studies. Adjusted odds ratio (OR) with corresponding 95% confidence interval (CI) for the association between traffic-related air pollutants and health effects were recovered from individual studies and summary effect estimates (meta-OR) were generated in Review Manager 5.3. Twenty-seven studies were included in the meta-analysis and the results showed that TRAP increased the risk of asthma among children: PM2.5 (meta-OR = 1.07, 95% CI:1.00-1.13), NO2 (meta-OR = 1.11, 95% CI:1.06-1.17), Benzene (meta-OR: 1.21, 95% CI:1.13-1.29) and TVOC (meta-OR:1.06, 95% CI: 1.03-1.10). Sensitivity analyses supported these findings. In addition, regional analysis showed that ORs of inorganic TRAP (PM2.5 and NO2) on the risk of childhood asthma were significantly higher in Asia than those in Europe and North America. Subsequent research should focus on the association between organic pollutants in TRAP and childhood asthma. Furthermore, the disentanglement between TRAP and other pollutant sources may be investigated in future studies.


Rigidity-Activity Relationships of bisQPC Scaffolds against Pathogenic Bacteria.
Biscationic quaternary phosphonium compounds (bisQPCs) represent a promising class of antimicrobials, displaying potent activity against both Gram-negative and Gram-positive bacteria. In this study, we explored the effects of structural rigidity on the antimicrobial activity of QPC structures bearing a two-carbon linker between phosphonium groups, testing against a panel of six bacteria, including multiple strains harboring known disinfectant resistance mechanisms. Using simple alkylation reactions, 21 novel compounds were prepared, although alkene isomerization as well as an alkyne reduction were observed during the respective syntheses. The resulting bisQPC compounds showed strong biological activity, but were hampered by diminished solubility of their iodide salts. One compound (P2P-10,10 I) showed single-digit micromolar activity against the entire panel of bacteria. Overall, intriguing biological activity was observed, with less rigid structures displaying better efficacy against Gram-negative strains and more rigid structures demonstrating slightly increased efficacy against S. aureus strains.


Cytotoxic effects of colicins E1-E5 and K on hamster fibroblasts.
As a further model of mammalian tissue cells, Chinese hamster fibroblasts of the stable line V79 were used to check the cytotoxic effects of colicins. The efficiency of plating of cells treated with colicins E1-E5 and with colicin K was followed. The V79 cells were, in general, poorly sensitive to colicins; only colicins E1, E3 and E5 lowered the number of colony-forming cells to some degree. Again, a different action of colicins E1 and K (which is the same in bacteria) was found in eukaryotic cells.


Early Shared Decision-Making for Older Adults with Traumatic Brain Injury: Using Time-Limited Trials and Understanding Their Limitations.
Older adults account for a disproportionate share of the morbidity and mortality after traumatic brain injury (TBI). Predicting functional and cognitive outcomes for individual older adults after TBI is challenging in the acute phase of injury. Given that neurologic recovery is possible and uncertain, life-sustaining therapy may be pursued initially, even if for some, there is a risk of survival to an undesired level of disability or dependence. Experts recommend early conversations about goals of care after TBI, but evidence-based guidelines for these discussions or for the optimal method for communicating prognosis are limited. The time-limited trial (TLT) model may be an effective strategy for managing prognostic uncertainty after TBI. TLTs can provide a framework for early management: specific treatments or procedures are used for a defined period of time while monitoring for an agreed-upon outcome. Outcome measures, including signs of worsening and improvement, are defined at the outset of the trial. In this Viewpoint article, we discuss the use of TLTs for older adults with TBI, their potential benefits, and current challenges to their application. Three main barriers limit the implementation of TLTs in these scenarios: inadequate models for prognostication; cognitive biases faced by clinicians and surrogate decision-makers, which may contribute to prognostic discordance; and ambiguity regarding appropriate endpoints for the TLT. Further study is needed to understand clinician behaviors and surrogate preferences for prognostic communication and how to optimally integrate TLTs into the care of older adults with TBI.


Social behaviours by Bacillus subtilis: quorum sensing, kin discrimination and beyond.
Here, we review the multiple mechanisms that the Gram-positive bacterium Bacillus subtilis uses to allow it to communicate between cells and establish community structures. The modes of action that are used are highly varied and include routes that sense pheromone levels during quorum sensing and control gene regulation, the intimate coupling of cells via nanotubes to share cytoplasmic contents, and long-range electrical signalling to couple metabolic processes both within and between biofilms. We explore the ability of B. subtilis to detect 'kin' (and 'cheater cells') by looking at the mechanisms used to potentially ensure beneficial sharing (or limit exploitation) of extracellular 'public goods'. Finally, reflecting on the array of methods that a single bacterium has at its disposal to ensure maximal benefit for its progeny, we highlight that a large future challenge will be integrating how these systems interact in mixed-species communities.


Evidence of increased cardiac parasympathetic drive in subjects meeting current physical activity recommendations.
Aerobic fitness seems to provide extra protection to the cardiovascular system beyond changing the traditional risk factors, a phenomenon referred to as the risk factor gap model. Aerobic fitness may possibly lead to improved autonomic regulation. The Task Force of the American Heart Association supports a national campaign to reach specific cardiovascular health goals considering various metrics, including recommended physical activity (PA) volumes. It may be clinically relevant to assess whether autonomic remodeling occurs in those who adhere to the PA recommendations. We studied 39 healthy subjects (22 males and 17 females), subdivided into two groups, according to whether they were meeting or not meeting PA recommendations (150 min/week of moderate aerobic activity, or 75 min/week of vigorous aerobic activity, or a combination of both). For each group, we evaluated aerobic capacity (VO2 Peak), body composition (Fat Mass) and autonomic nervous system profile, by way of mono and bivariate spectral analysis of cardiovascular beat by beat variability. Subjects following PA recommendations show higher RR period, higher RR variance, greater absolute power of the respiratory component of RR variability (HFRR) and higher index alpha (a measure of spontaneous baroreflex). Moreover, as expected, the group that was meeting or exceeding current PA recommendations had higher VO2 peak, less fat mass and greater weekly energy expenditure. Data show that subjects meeting current PA recommendations present a phenotype suggestive of enhanced parasympathetic drive to the SA node. This finding is compatible with the hypothesis that a more favorable autonomic profile is part of the mechanisms of the risk factor gap.


Extraskeletal paraarticular osteochondroma of the knee--a case report and tumor overview.
Extraskeletal paraarticular osteochondromas are rather unusual osteocartilaginous lesions that arise in the soft tissues adjacent to the joint with no bony or joint continuity. This diagnosis should be considered with the demonstration of a well-circumscribed extraskeletal mineralized mass without any direct continuity with adjacent bone or joint. However, as with other lesions, clinicoradiographic features with histological correlation clinch the diagnosis. Differentiation from other lesions, particularly synovial osteochondromatosis and chondrosarcoma is essential to avoid unnecessary aggressive surgical procedures as marginal excision is adequate for these lesions. We present here such an infrapatellar lesion and discuss criteria helpful in distinguishing these benign lesions from other morphological similar lesions.


Novel anatomical reconstruction of distal tibiofibular ligaments restores syndesmotic biomechanics.
To date, there is a paucity of literature on syndesmotic reconstruction techniques that restore both anatomic stability and physiologic syndesmotic biomechanics. In this cadaveric study, (1) a novel syndesmotic reconstruction surgical technique using autogenous peroneus brevis tendon was described and (2) the biomechanical properties of the reconstruction was investigated. Ten fresh-frozen lower extremities were used in this study. Reconstruction of the anterior and posterior, as well as the interosseous tibiofibular ligaments was performed with a halved peroneus brevis tendon. Biomechanics were assessed using foot external rotation torque and ankle dorsiflexion axial loading tests, which were performed in (a) intact, (b) cut, (c) anatomically reconstructed syndesmotic ligaments, and (d) 3.5 mm tricortical syndesmotic screw fixation. Medial-lateral and anterior-posterior displacements of the distal fibula were recorded during foot external rotation and fibular axial displacement was recorded during ankle axial loading. The fibula was displaced posteriorly and proximally with respect to the tibia in all specimens during external rotation and axial loading tests, respectively. Significant differences (p < 0.05) were found in distal fibular displacements between anatomically reconstructed ligaments and screw fixation. Tricortical syndesmotic screw fixation resulted in 59% of posterior fibular displacement when compared to intact ligaments. No significant differences (n.s.) in distal fibular displacement were demonstrated between intact ligaments and anatomically reconstructed ligaments. Anatomical reconstruction of the distal tibiofibular ligaments with the peroneus brevis tendon provides stability and recreates the biomechanical properties of an intact syndesmosis. This new surgical technique may be a viable alternative for the treatment of syndesmotic injuries. V.


Survival time of post and cores: A 16 year retrospective follow-up study.
The retrospective survival study (1995-2004) by Balkenhol et al. [1]. led to changes in the decision-making process for treatment with post and cores (special focus on the covering prosthetic restoration while deciding for treatment with post and cores, high primary friction at the try-in stage for conventional cementation, only indirect fabrication technique, no semi-precious alloy) in our clinic. The aim of this study was to examine the influence of these changes on the survival probability. In the observation period (2004-2020) 653 patients received in total 953 post and cores. The patient files were analysed due to the parameters: Type of covering prosthetic restoration, location, type of tooth, luting material, post and core material, bone attachment, therapist and cause of failure. According to the previous study the survival probability was assessed using Kaplan-Meyer analysis. Cox regression was used to assess the risk of failure and identify possible covariates. The average survival time of the post and cores was 10.9 years. The cumulative failure rate was 28.2%. A significant influence on the survival time (Kaplan-Meyer analysis) could be found for the parameters: Type of covering prosthetic restoration, location, type of tooth, post and core material and bone attachment. The multifactorial survival analysis (Cox regression) showed a significant influence of the age of the patient at the time of fitting the post, the type of covering prosthetic restoration and the bone attachment. The changes in the decision-making process did not lead to a better survival probability. The conclusions stated in the previous study were not strict enough. Treatments with post and cores should be critically scrutinized on the basis of covering prosthetic restoration and bone attachment. Post and cores under primary crown retained RPDs should be avoided because of the bad survival probability.


Preferential effect of lead exposure during lactation on non-essential fatty acids in maternal organs.
This study determined the effects of lead exposure during the lactational period on maternal organ FA compositions in rat dams that were fed either an n-3 adequate (n-3 Adq) or deficient (n-3 Def) diet prior to conception. On giving birth, dams were subdivided into four groups in a 2 x 2 design with n-3 FA supply and Pb exposure as the dependent variables. Pb acetate (0.2 wt%) was administered in the drinking water from the time they gave birth to weaning 3 wk later. Following weaning, the dams were decapitated, and the liver, plasma, kidney, brain, and retina analyzed for FA composition. The n-3 deficient diets markedly decreased the percentages of total n-3 FA, including docosahexaenoic acid (DHA), and increased total n-6 FA including both arachidonic (AA) and n-6 docosapentaenoic acids in all tissues (P < 0.05). The principal effects of Pb occurred in the liver and plasma, where 20-32% losses in total FA concentration concurrent with increased relative percentages of AA (P < 0.05) were observed. In kidney, the percentages of AA and DHA also increased after Pb exposure (P < 0.05) with lesser effects in the nervous system. There was a diet x Pb interaction for liver, plasma, and retinal 20-C n-6 PUFA (P < 0.05). Generally, shorter-chain saturated and monounsaturated FA concentrations were decreased after Pb exposure. An analysis of the changes in the tissue concentrations induced by Pb indicated that the increases in the percentages of PUFA likely reflected a preferential loss of non-EFA. The mechanisms by which Pb affects saturated and monounsaturated FA concentration are unknown.


Feasibility of T1 mapping with histogram analysis for the diagnosis and staging of liver fibrosis: Preclinical results.
To compare the diagnostic accuracy of parameters derived from the histogram analysis of precontrast, 10-min hepatobiliary phase (HBP) and 20-min HBP T1 maps for staging liver fibrosis (LF). LF was induced in New Zealand white rabbits by subcutaneous injections of carbon tetrachloride for 4-16 weeks (n = 120), and 20 rabbits injected with saline served as controls. Precontrast, 10-min and 20-min HBP modified Look-Locker inversion recovery (MOLLI) T1 mapping was performed. Histogram analysis of T1 maps was performed, and the mean, median, skewness, kurtosis, entropy, inhomogeneity and 10th/25th/75th/90th percentiles of T1native, T110min and T120min were derived. Quantitative histogram parameters were compared. For significant parameters, further receiver operating characteristic (ROC) analyses were performed to evaluate the potential diagnostic performance in differentiating LF stages. Finally, 17, 20, 21, 21 and 20 rabbits were included for the F0, F1, F2, F3, and F4 pathological grades of fibrosis, respectively. The mean/75th of T1native, entropy of T110min and entropy/mean/median/10th of T120min demonstrated a significant good correlation with the LF stage (|r| = 0.543-0.866, all P < 0.05). The 75th of T1native, entropy10min, and entropy20min were the three most reliable imaging markers in reflecting the stage of LF. The area under the ROC curve of entropy20min was larger than that of entropy10min (P < 0.05 for LF ≥ F2, ≥F3, and ≥ F4) and the 75th of T1native (P < 0.05 for LF ≥ F2 and ≥ F3) for staging LF. Magnetic resonance histogram analysis of T1 maps, particularly the entropy derived from 20-min HBP T1 mapping, is promising for predicting the LF stage.


Atopic profile of inner-city asthma with a comparative analysis on the cockroach-sensitive and ragweed-sensitive subgroups.
Inner-city asthma is well known for its high risk of mortality. To better understand urban asthma, we examined clinical characteristics and aeroallergen sensitivities of 592 of 680 consecutive urban Chicago residents with asthma. A total of 227 male and 453 female subjects who met the criteria for the study were registered. A comprehensive clinical evaluation was followed by allergy skin testing (prick and intradermal testing) with 10 groupings (5 indoor and 5 outdoor) of common aeroallergens. Serum total IgE and selective antigen-specific IgE levels, including cockroach-specific IgE, were routinely measured. A total of 592 (196 male and 396 female) subjects with an average age of 35 years were skin tested. The average duration of asthma was 12.6 years, and 31% of the population was receiving corticosteroids. Aeroallergen sensitivity was noted in 85%, and 94 subjects (15%) were nonallergic. House dust sensitivity (76%) was most prevalent, distantly followed by sensitivity to cockroach (48%), ragweed (45%), other weeds (42%), cat (40%), and dust mite (24%). The average number of aeroallergen sensitivities detected was 4 of 10 groupings of both indoor and outdoor allergens. Twenty percent of subjects were allergic to only indoor allergens, whereas 4% were allergic to outdoor allergens only. Serum IgE was 245 +/- 17.3 IU/ml (geometric mean+SEM), and 74% of 444 serum samples showed IgE antibody levels greater than or equal to 100 IU/ml. A cockroach-sensitive subgroup (283 subjects) had longer duration of asthma (p < 0.0001) and fewer additional aeroallergen sensitivities (p < 0.0001) than the ragweed-sensitive subgroup (264 subjects). The results indicate that a great majority (85%) of inner-city Chicago residents with asthma have atopic asthma, as demonstrated by highly elevated IgE levels and multiple aeroallergen sensitivities. Sensitivity to indoor allergens is more prevalent than sensitivity to outdoor allergens. The subjects with cockroach-sensitive asthma appear to be a distinctive subgroup characterized by chronicity and elevated serum IgE antibody levels with fewer aeroallergen skin test sensitivities.


Prostaglandin-mediated hypercalcemia in transitional cell carcinoma of the bladder.
A patient with known transitional cell carcinoma of the bladder and hypercalcemia was evaluated for urinary prostaglandin levels when no bone metastases or elevated parathormone levels could be demonstrated. Urinary levels of prostaglandin E metabolite were assessed in relation to serum and urinary calcium levels during treatment. The serum calcium levels decreased from the 13.0 mg. per cent range whenever the rpimary tumor was manipulated (transurethral resection) or when other treatments directed at the tumor were used (radiation therapy and chemotherapy). Serum and urinary calcium levels, and urinary prostaglandin E metabolite decreased when 3 gm. aspirin were given daily. These data suggest that the somewhat unusual hypercalcemia in our patient was caused by a prostaglandin-secreting transitional cell carcinoma. Prostaglandin-secreting tumors are reviewed herein.


Unusual molecular conformation in dissymmetric propylene-linker compounds containing pyrazolo[3,4-d]pyrimidine and phthalimide moieties.
The crystal structure of 4,6-bis(methylsulfanyl)-1-phthalimidopropyl-1H-pyrazolo[3,4-d]pyrimidine, C(18)H(17)N(5)O(2)S(2), (VI), reveals an unusual folded conformation due to an apparent intramolecular C-H.pi interaction between the 6-methylsulfanyl and phenyl groups. However, the closely related compound 6-methylsulfanyl-1-phthalimidopropyl-4-(pyrrolidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine, C(21)H(22)N(6)O(2)S, (VII), exhibits a fully extended structure, devoid of any intramolecular C-H.pi or pi-pi interactions. The crystal packing of both molecules involves intermolecular stacking interactions due to aromatic pi-pi interactions. In addition, (VI) exhibits intermolecular C-H.O hydrogen bonding and (VII) exhibits dimerization of the molecules through intermolecular C-H.N hydrogen bonding.


The contribution of ApoB and ApoA1 measurements to cardiovascular risk assessment.
LDL has been widely recognized as the major atherogenic lipoprotein and designated as the primary target for prevention of coronary heart disease (CHD); however, there is growing evidence that other triglyceride-rich lipoproteins, such as very low-density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) carry atherogenic potential as well. This led to the designation of non-HDL cholesterol (HDL-C) (LDL + IDL + VLDL) as a secondary target of treatment for hyperlipidaemia. As each one of LDL, IDL and VLDL particles carries only one apolipoprotein B-100 (ApoB-100) molecule, the total ApoB value represents the total number of potentially atherogenic lipoproteins, whereas non-HDL-C provides the cholesterol content of these same lipoproteins. Recent data from epidemiological, observational and interventional studies suggest that non-HDL-C, apolipoproteins ApoA1 and ApoB may improve CHD risk assessment by identifying more high-risk individuals than the usual lipid profile alone. However, the targets for the optimal treatment of dyslipidaemia remain a subject of considerable debate. Further studies are needed to determine whether ApoB and ApoA1 are superior to conventional lipid parameters as predictors of cardiovascular disease or therapeutic targets of hyperlipidaemias. In this review, we summarize the current opinions on the use of ApoA1 and ApoB values as estimates of cardiovascular risk or as treatment goals in patients undergoing treatment for hyperlipidaemia.


The brain of Lymnaea contains a family of FMRFamide-like peptides.
Authentic FMRFamide and two FMRFamide-related heptapeptides were purified from the central nervous system of the fresh water snail Lymnaea stagnalis. The sequences of the heptapeptides were determined as: Ser-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (SDPFLRFamide) and Gly-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (GDPFLRFamide) by modified Edman degradation and enzymatic digestion. Relatively high quantities of the deamidated and therefore non-immunoreactive analogs of these two peptides (SDPFLRF and GDPFLRF) were also found. SDPFLRFamide and GDPFLRFamide were synthesized and were found to be chromatographically and biologically indistinguishable from the natural peptides, confirming the sequences. The log dose-response curves for the chronotropic action of either synthetic peptide on the heart of Lymnaea was very similar to that of FMRFamide. These data indicate that Lymnaea contains a family of FMRFamide-like peptides.


Prenatal diagnosis of hypochondrogenesis using fetal MRI: a case report.
We describe the successful prenatal diagnosis of hypochondrogenesis by MRI. Fetal MR findings were the presence of a conspicuous cartilaginous structure in the basioccipital region, ill-defined ossification of the cervical vertebral bodies, hypoplastic thorax, retarded ossification of the pubic bones, and broad, short long bones. In contrast, fetal US revealed only the presence of short long bones. MRI accurately delineated the axial skeleton in this case and is an effective clinical tool for diagnosing skeletal dysplasias in utero.


β-d-Galacto-pyranosyl-(1→4)-2-amino-2-de-oxy-α-d-gluco-pyran-ose hydro-chloride monohydrate (lactosamine).
The title compound, C12H24NO10 +·Cl-·H2O, (I), crystallizes in the monoclinic space group P21 and exists as a monohydrate of a monosubstituted ammonium chloride salt, with the reducing carbohydrate portion existing exclusively as the α-pyran-ose tautomer. The glycosidic bond geometry in (I) is stabilized by an intra-molecular hydrogen bond and is close to that found in crystalline α-lactose. All heteroatoms except gluco-pyran-ose ring O4 participate in an extensive hydrogen-bonding network, which propagates in all directions in the crystal structure of (I).


Observations on the application of counterimmunoelectrophoresis for the seroepidemiology of human cysticercosis.
An immunoepidemiological survey for cysticercosis was carried out in an endemic focus of Irian Jaya by use of a counterimmunoelectrophoresis (CIEP) technique. All individuals with palpable subcutaneous cysticerci were serologically positive by this technique as were 77.3% of the individuals giving a history of epileptiform seizures and 22.5% with no clinical complaints. The possible application of CIEP for epidemiological surveillance is discussed.


Molecular characterization and expression analysis of B cell activating factor from rock bream (Oplegnathus fasciatus).
B cell activating factor (BAFF) is a member of the tumor necrosis factor (TNF) ligand family. BAFF has been shown to induce survival and proliferation of lymphocytes. We characterized the gene encoding BAFF (RbBAFF) in rock bream (Oplegnathus fasciatus), and attempted to determine its biological functions upon immune responses. In silico analysis of RbBAFF demonstrated the presence of common TNF ligand family features, including a TNF domain, a D-E loop, and three cysteine residues that are crucial for trimer formation. Amino acid sequence alignment confirmed that RbBAFF and its homologs were conserved at secondary and tertiary levels. Transcriptional analysis indicated that RbBAFF mRNAs were ubiquitously expressed in wide array of tissues. The higher levels of constitutive expression were observed in the kidney, head kidney and spleen, suggesting an important physiological relationship with lymphocytes. Under pathological conditions, RbBAFF mRNA levels were significantly elevated. The role of RbBAFF in lymphocyte survival and proliferation was confirmed by MTT assays and flow cytometry. Recombinant RbBAFF protein (10 μg/mL) was able to prolong the survival and/or enhance the proliferation of rock bream lymphocytes by approximately 30%. Transcription of IL-10 and NFκB-1 was significantly stimulated by RbBAFF. Our findings provide further information regarding fish BAFF gene and its role in adaptive immunity.


Health promotion and disease prevention beliefs and behaviors of dietetic practitioners.
Fifty-three percent of a random sample of 500 members of the Texas Dietetic Association responded to a survey designed to determine their personal health behavior, beliefs, and patient counseling practices related to health promotion and disease prevention. This article reports the responses of the 180 practitioners involved in direct patient care in order to depict the health promotion/disease prevention beliefs and behaviors of that particular group. Health habits (e.g., smoking, physical activity, and dietary patterns) of dietetic practitioners were better than those of the general female population. Personal health habits related to not smoking and to getting regular exercise were significantly associated with belief in the importance of that behavior for others. Although most of the dietetic practitioners indicated that the identified health behaviors were important to the health of the average person, only a few practitioners gave them routine attention in their practice. Respondents generally expressed a lack of confidence in their ability to educate clients about specified health behaviors, with the exception of weight control, high-fat diets, elevated blood pressure, and exercise patterns. The practitioners' confidence in their counseling skills was significantly correlated with intensity of counseling (p less than or equal to .001) and the likelihood of client compliance, except in the area of weight control. The majority of the dietitians strongly agreed that health promotion will be more important in the future.


Accurate prediction of NOx emissions from diesel engines considering in-cylinder ion current.
The main purpose of current study is accurate prediction of NOx emissions from diesel engines considering in-cylinder ion current. To reach this goal, a validated thermodynamic multi-zone model was used. A modified chemical kinetics mechanism of diesel fuel oxidation was used too. A chemical kinetics mechanism of NOX formation including 103 reactions was added to the main mechanism. A set of ions and ionic reactions was added to the developed chemical kinetics mechanism and finally a modified chemical kinetics mechanism with 445 reactions and 100 species was formed. The developed mechanism was coupled to the multi-zone model and a diesel engine was simulated. The importance of Zeldovich mechanism, prompt mechanism, N2O mechanism and NNH mechanism were investigated. The progress rates of reactions were calculated and important reactions were identified. The results show that the oxygenated ions, NO+, O+ and O2+, has more effects on NO production than other ions. The prompt mechanism plays an important role in predicting the ion current inside the chamber. Because this mechanism has reactions that can lead to CH production. The CH radicals produced by this mechanism can be employed by basic ionic reactions and lead to ion production. The results show that using NOx related ionic reactions results in accurate prediction of engine exhaust NOx.


Cadmium-manganese interaction in the rat's duodenum.
Five-week-old female albino rats were given different doses of cadmium chloride (0.002-5.0 mg) by gastric intubation daily for 3 or 7 days. Manganese-54 was used as marker to assess manganese transfer through and retention in the duodenal wall by the "everted gut sac" method. No significant differences were found in these parameters between rats receiving no cadmium and those receiving 0.002 mg cadmium daily, irrespective of the period of treatment. A daily dose of 0.02 mg cadmium decreased manganese transfer significantly but only in animals treated with cadmium for 3 days. Daily doses of 0.2 mg cadmium or higher always decreased manganese transfer and intestinal uptake significantly--an effect which was independent of whether the rats were killed on the 4th or on the 8th days of the experiment. On the whole, the effect of cadmium was much more intense in the 3-day-than in the 7-day-treated animals and it was more pronounced on manganese transfer than on its intestinal uptake.


Lymphocyte-Specific Protein-1 Suppresses Xenobiotic-Induced Constitutive Androstane Receptor and Subsequent Yes-Associated Protein-Activated Hepatocyte Proliferation.
Activation of constitutive androstane receptor (CAR) transcription factor by xenobiotics promotes hepatocellular proliferation, promotes hypertrophy without liver injury, and induces drug metabolism genes. Previous work demonstrated that lymphocyte-specific protein-1 (LSP1), an F-actin binding protein and gene involved in human hepatocellular carcinoma, suppresses hepatocellular proliferation after partial hepatectomy. The current study investigated the role of LSP1 in liver enlargement induced by chemical mitogens, a regenerative process independent of tissue loss. 1,4-Bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a direct CAR ligand and strong chemical mitogen, was administered to global Lsp1 knockout and hepatocyte-specific Lsp1 transgenic (TG) mice and measured cell proliferation, hypertrophy, and expression of CAR-dependent drug metabolism genes. TG livers displayed a significant decrease in Ki-67 labeling and liver/body weight ratios compared with wild type on day 2. Surprisingly, this was reversed by day 5, due to hepatocyte hypertrophy. There was no difference in CAR-regulated drug metabolism genes between wild type and TG. TG livers displayed increased Yes-associated protein (YAP) phosphorylation, decreased nuclear YAP, and direct interaction between LSP1 and YAP, suggesting LSP1 suppresses TCPOBOP-driven hepatocellular proliferation, but not hepatocyte volume, through YAP. Conversely, loss of LSP1 led to increased hepatocellular proliferation on days 2, 5, and 7. LSP1 selectively suppresses CAR-induced hepatocellular proliferation, but not drug metabolism, through the interaction of LSP1 with YAP, supporting the role of LSP1 as a selective growth suppressor.


Molecularly Imprinted Polymeric Sorbent for Targeted Dispersive Solid-Phase Microextraction of Fipronil from Milk Samples.
Fipronil, a phenyl pyrazole insecticide, is extensively used in agriculture to control insect infestation. It has the potential to assimilate into the food chain, leading to serious health concerns. We report molecularly imprinted polymer (MIP)-based dispersive solid-phase microextraction for the targeted determination of fipronil in milk samples. Designing such a sorbent is of paramount importance for measuring the accurate amount of fipronil for monitoring its permissible limit. Response surface methodology based on a central composite design following a face-centered approach was used to optimize experimental conditions. The maximum binding capacity of 47 mg g-1 was achieved at optimal parameters of time (18 min), temperature (42 °C), pH (7), and analyte concentration (120 mg L-1). Under these conditions, a high percentage recovery of 94.6 ± 1.90% (n = 9) and a low limit of detection (LOD) and limit of quantitation (LOQ) (5.64 × 10-6 and 1.71 × 10-5 μg mL-1, respectively) were obtained. The MIP was well characterized through a scanning electron microscope (SEM) as well as Brunauer-Emmett-Teller (BET), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA) methods. Adsorption kinetics of the MIP followed the pseudo-first-order model (R 2 0.99 and χ2 0.96), suggesting the MIP-analyte interaction to be a physiosorptive process, while adsorption isotherms followed the Freundlich model (R 2 0.99). The real sample analysis through high-performance liquid chromatography (HPLC) confirmed the selective determination of fipronil from milk samples.


Design of a rapid electrochemical biosensor based on MXene/Pt/C nanocomposite and DNA/RNA hybridization for the detection of COVID-19.
Since the rapid spread of the SARS-CoV-2 (2019), the need for early diagnostic techniques to control this pandemic has been highlighted. Diagnostic methods based on virus replication, such as RT-PCR, are exceedingly time-consuming and expensive. As a result, a rapid and accurate electrochemical test which is both available and cost-effective was designed in this study. MXene nanosheets (Ti3C2Tx) and carbon platinum (Pt/C) were employed to amplify the signal of this biosensor upon hybridization reaction of the DNA probe and the virus's specific oligonucleotide target in the RdRp gene region. By the differential pulse voltammetry (DPV) technique, the calibration curve was obtained for the target with varying concentrations ranging from 1 aM to 100 nM. Due to the increase in the concentration of the oligonucleotide target, the signal of DPV increased with a positive slope and a correlation coefficient of 0.9977. Therefore, at least a limit of detection (LOD) was obtained 0.4 aM. Furthermore, the specificity and sensitivity of the sensors were evaluated with 192 clinical samples with positive and negative RT-PCR tests, which revealed 100% accuracy and sensitivity, 97.87% specificity and limit of quantification (LOQ) of 60 copies/mL. Besides, various matrices such as saliva, nasopharyngeal swabs, and serum were assessed for detecting SARS-CoV-2 infection by the developed biosensor, indicating that this biosensor has the potential to be used for rapid Covid-19 test detection.


Structural diversity and biological role of the 5' untranslated regions of picornavirus.
The genomic arrangement of most picornavirus of the Picornaviridae family shares a similar monocistronic genomic pattern and a defining organizational feature. A defining feature of picornavirus is the presence of evolutionarily conserved and highly-structured RNA elements in untranslated regions (UTRs) at the genome' 5'and 3' ends, essential for viral replication and translation. Given the diversity and complexity of RNA structure and the limitations of molecular biology techniques, the functional characterization and biological significance of UTRs remain to be fully elucidated, especially for 5' UTR. Here, we summarize the current knowledge of the 5' UTR of picornavirus. This review focuses on the structural characterization and the biological function of the RNA secondary and tertiary structures in the 5' UTR of picornavirus. Understanding the role of the 5' UTR of picornavirus can provide a deep insight into the viral replication cycle and pathogenic mechanisms.


Bat parasites (Acari, Anoplura, Cestoda, Diptera, Hemiptera, Nematoda, Siphonaptera, Trematoda) in France (1762-2018): a literature review and contribution to a checklist.
This paper is a bibliographical survey of records of bat parasites in France (including Corsica) between 1762 and 2018. In total, 237 scientific publications were analysed. They show that bats are infected with a large diversity of endoparasites and ectoparasites. A total of 113 parasite taxa were identified from 27 host species; in addition, six bats were not identified to the species-level. The helminth fauna of bats comprises three species of Cestoda, 15 of Trematoda, and 13 of Nematoda. Acari parasites include 53 species (in addition to 22 invalid species). Finally, insect parasites comprise 13 species of Diptera (bat flies), 12 of Siphonaptera (fleas), 3 of Hemiptera (bugs), and 1 Anoplura species. Bat taxa reported with parasites were Barbastella barbastellus, Eptesicus serotinus, Hypsugo savii, Miniopterus schreibersii, Myotis bechsteinii, M. blythii, M. capaccinii, M. dasycneme, M. daubentonii, M. emarginatus, M. myotis, M. mystacinus, M. nattereri, M. punicus, Nyctalus lasiopterus, N. leisleri, N. noctula, Pipistrellus kuhlii, P. nathusii, P. pipistrellus, Plecotus auritus, P. austriacus, Rhinolophus euryale, R. ferrumequinum, R. hipposideros, R. mehelyi, Tadarida teniotis, Eptesicus sp., Myotis sp., Pipistrellus sp., Plecotus sp., Rhinolophus sp. and the species complex Pipistrellus pipistrellus/kuhlii/nathusii. As regards E. nilssonii, Vespertilio murinus (Particoloured Bat), M. alcathoe, M. escalerai, P. macrobullaris and P. pygmaeus, no records were found. These published field data originated from 72 of the 96 departments in metropolitan France. The most commonly cited were Ardèche, Ariège, Bouches-du-Rhône, Haute-Savoie, Maine-et-Loire, Moselle, Meurthe-et-Moselle, Pyrénées-Orientales, Sarthe, Haute-Corse and Corse-du-Sud.


Proteasome: a complex protease with a new fold and a distinct mechanism.
The structure of the proteasome from Thermoplasma acidophilum introduces threonine proteases as a fifth class of proteolytic enzymes, and offers insights into the catalytic activity of this complicated piece of molecular machinery with its 14 active sites.


The decoy SNARE Tomosyn sets tonic versus phasic release properties and is required for homeostatic synaptic plasticity.
Synaptic vesicle (SV) release probability (Pr) is a key presynaptic determinant of synaptic strength established by cell-intrinsic properties and further refined by plasticity. To characterize mechanisms that generate Pr heterogeneity between distinct neuronal populations, we examined glutamatergic tonic (Ib) and phasic (Is) motoneurons in Drosophila with stereotyped differences in Pr and synaptic plasticity. We found the decoy soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) Tomosyn is differentially expressed between these motoneuron subclasses and contributes to intrinsic differences in their synaptic output. Tomosyn expression enables tonic release in Ib motoneurons by reducing SNARE complex formation and suppressing Pr to generate decreased levels of SV fusion and enhanced resistance to synaptic fatigue. In contrast, phasic release dominates when Tomosyn expression is low, enabling high intrinsic Pr at Is terminals at the expense of sustained release and robust presynaptic potentiation. In addition, loss of Tomosyn disrupts the ability of tonic synapses to undergo presynaptic homeostatic potentiation.


Adrenocorticoids control 5-hydroxytryptamine metabolism in rat brain.
The influence of surgical adrenalectomy was examined on the biosynthetic capacity for 5-hydroxytryptamine of rat brain. The results demonstrate that adrenalectomy decreased tryptophan hydroxylase activity and its substrate tryptophan in the brain stem. A parallel change in the concentration of 5-hydroxytryptamine was seen in brain stem and striatal region of adrenalectomized rats. In contrast, the level of 5-hydroxyindoleacetic acid was significantly elevated in both of these brain regions. Replacement therapy with corticosterone (10 mg/kg i.p.) produced time-dependent increases in tryptophan, tryptophan hydroxylase and 5-hydroxytryptamine and decreases in 5-hydroxyindoleacetic acid levels. Alterations in these neurochemical parameters were more conspicuous in adrenalectomized rats receiving corticosterone for 7 days as compared to those given only for 3 days. Our data demonstrate that adrenocortical hormones regulate brain 5-hydroxytryptamine synthesis probably by enhancing both the levels of tryptophan and the activity of rate-limiting enzyme tryptophan hydroxylase. It is postulated that emotional instability seen during altered adrenocortical function might partly be associated with abnormal metabolism of central 5-hydroxytryptamine.


Ascaridia galli infection in a checkered keelback (Xenochrophis piscator) snake.
The checkered keelback is also known as Asiatic water snake and is common species of non-venomous snake known to occur in India. The present study report the occurrence of Ascaridia galli infection in a checkered keelback snake, which was found dead near Veterinary College hostel premises. The post-mortem examination of the snake revealed catarrhal exudate without ingesta in the stomach and showed gastric ulcerations with edema. Large numbers of round worms were packed in the lumen of small intestine with petechial haemorrhages and necrotic enteritis. The nematode parasites were recovered and processed for identification. Based on morphological characters, the worms were identified as A. galli and the intestinal contents of the snake showed A. galli eggs.


Can placebo or nocebo pills improve or impair cognition performance?
Although the placebo effect is well known to affect many behaviors, the effects on cognitive performance are less well investigated. In this study, the effects of a placebo and a nocebo manipulation on cognitive performance was investigated in healthy young participants in an unblinded between-subjects study. In addition, the participants were asked about their subjective experience in the placebo and nocebo condition. The data suggested that the placebo condition induced the feeling of being more attentive and more motivated and the nocebo condition induced a feeling of being less attentive and alert and that they performed less well than normal. However, no placebo or nocebo effects were found on the actual performance on word learning, working memory, Tower of London task, or spatial pattern separation. These findings further support the notion that placebo or nocebo effects are not likely to occur in young healthy volunteers. However, other studies suggest that placebo effects can be found in implicit memory tasks and in participants with memory problems. Further placebo/nocebo studies are indicated using different experimental designs and different populations in order to better understand the placebo effect on cognitive performance.


Prognostic value of the five-repetition sit-to-stand test for mortality in people with chronic obstructive pulmonary disease.
Prognostic studies suggest that some musculoskeletal and functional capacity tests are independently associated with mortality in chronic obstructive pulmonary disease (COPD), but comparing their prognostic value is difficult because of differences in the selected covariates for regression modelling in those studies. To assess the prognostic value of five musculoskeletal and functional capacity tests in predicting mortality risk in patients with COPD after adjusting for existing and confounding prognostic factors and to compare their ability to correctly discriminate the mortality of individual participants using the 6-min walk test (6MWT). We hypothesized that the examined tests have different prognostic value. Prospective and longitudinal study. A total of 137 patients with stable COPD (mean [SD] age 67 [8.33] years; 87% male) were recruited from a hospital in Spain during 2014 and followed for 5 years (2014-2019). No one refused and only one was lost to follow-up. The outcome measure was 5 year all-cause mortality. A total of 37 patients died within 5 years. All musculoskeletal tests were associated with 5 year all-cause mortality in Cox proportional-hazards regression models. However, only the five-repetition sit-to-stand test (5-STS) score was an independent prognostic factor (hazard ratio 1.04 per sec, 95% confidence interval 1.01-1.08) after adjusting for history of heart disease, number of previous severe exacerbations, and dyspnoea. This model explained 50.7% of the variance in mortality. This test exhibited similar discriminative ability as the 6MWT for 5 year mortality (area under the receiver operating characteristic curve: 0.741vs 0.722; p = 0.92), and a highly prognostic cut-off for discriminating (15.98 s). This cut-off had higher likelihood ratios (LRs) than the 6MWT cut-off (∼350 m), especially for negative LRs (1/LR-: 7.69vs 2.00). The 5-STS is an objective measure for predicting mortality in patients with COPD and has good discriminative ability, with a cut-off for discriminating survival slight better than the 6MWT. The prognostic value of the other tests remains to be confirmed.