Testing Regimen Research Articles

Efficacy of a long-term home parenteral nutrition regimen containing fish oil-derived n-3 polyunsaturated fatty acids: a single-centre, randomized, double blind study

BackgroundData on the use of lipid emulsions containing fish-oil (FO) derived n-3 polyunsaturated fatty acids (n-3 PUFAs) in addition to medium- and long-chain triglycerides (MCT/LCT) for long-term home parenteral nutrition (HPN) are limited. This study aimed to compare HPN regimens containing either MCT/LCT/FO-derived n-3 PUFAs (test group) or MCT/LCT (control group) with respect to efficacy and safety during 8 weeks of HPN using a non-inferiority trial design with change of body mass index (BMI) as primary endpoint.MethodsThis prospective, randomized, double-blind study was conducted at the Charité, Berlin, Germany, from 02/2008 until 01/2014. Adult patients (n = 42; aged 18 to 80 years) requiring HPN for at least 8 weeks were randomly assigned to the test or control group. Assessments included weight, height, physical examination (cardiovascular system, abdomen, respiratory tract, liver, spleen, kidney, urine tract, skin, mucous membrane, neurology, psyche, musculoskeletal system, lymph nodes), bio impedance analysis, calorimetry, blood samplings (haematology, biochemistry, fatty acid analysis) and quality of life questionnaire.ResultsBMI increased in both groups with 8 weeks of HPN (ΔBMI(test group) = 1.3 ± 1.1 kg/m2; ΔBMI(control group) = 0.6 ± 0.9 kg/m2) demonstrating non-inferiority of the test regimen regarding nutritional efficacy. Assessment of secondary efficacy endpoints revealed that after 8 weeks of HPN with the test regimen, the proportion of n-3 PUFAs in serum, platelet and red blood cell phospholipids significantly increased, while the proportion of n-6 PUFAs decreased. The fatty acid pattern in the control group remained mostly stable. No statistically significant differences were detected between groups regarding inflammatory markers or quality of life. Laboratory parameters reflecting the safety endpoints liver function, bone metabolism, renal function, metabolic activity, lipid metabolism, coagulation and haematology were stable in both groups and no group differences were detected regarding (serious) adverse events.ConclusionsThe HPN regimen prepared with MCT/LCT/FO-derived n-3 PUFAs was at least as efficient in maintaining or even improving nutritional status during HPN as the control MCT/LCT regimen. Administration of FO-derived n-3 PUFAs for 8 weeks altered the fatty acid pattern of serum, platelet and red blood cell phospholipids. Both regimens were safe and well tolerated.Trial registrationwww.clinicaltrials.gov, registration number: NCT00530738.

A real-time PCR regimen for testing environmental samples for Salmonella enterica subsp. enterica serovars of concern to the poultry industry, with special focus on Salmonella Enteritidis.

A real-time PCR (qPCR) regimen, using up to six genetic targets, was developed to rapidly detect Salmonella and in particular identify Salmonella Enteritidis. The test regimen was first evaluated using a reference culture collection of Salmonella to confirm the appropriateness of the selected targets, which included up to three genetic markers for discrimination of Salmonella Enteritidis from other Salmonella serovars commonly found in poultry facilities. The qPCR procedure was then compared with culture methods used to detect Salmonella using a collection of enrichment broths previously generated from 239 environmental samples collected from a large number of hatchery facilities across Canada over several years. The qPCR regimen facilitated specific detection of Salmonella Enteritidis, and on a sample basis, it showed excellent agreement with the culture methods. Moreover, in many cases, qPCR detected Salmonella earlier in the culture process than did the culture method. Application of this method will significantly shorten test times and allow more timely identification of infected poultry premises, thereby improving present programmes aimed at controlling Salmonella Enteritidis at the environmental source.

A multicenter study to evaluate automated platelet aggregometry on Sysmex CS‐series coagulation analyzers—preliminary findings

Background and ObjectivesInvestigations of platelet function by light transmission aggregometry (LTA) using a dedicated aggregometer is time consuming and labor intensive. This multicenter study evaluated an automated LTA method using a coagulation analyzer to establish reference ranges and ideal testing regimen. MethodsSysmex CS‐2x00 series analyzers were used to measure aggregation using a range of agonists and concentrations: ADP (1‐20 μM); arachidonic acid (0.5‐1.5 mM); collagen (1.25‐5 μg/mL); ristocetin (0.5‐1.5 g/L); epinephrine (5‐10 μM); TRAP (1‐20 μM); U46619 (1 μM); and saline. Maximum and final aggregation, disaggregation, slope, and acquisition time were compared for each. ResultsFor 42 normal subjects there was no significant difference in aggregation parameters for: 10 μM and 20 μm ADP; 2 and 2.5 μM ADP; 1 and 1.5 mM arachidonic acid; 2.5 and 5 μg/mL collagen; 1 and 1.25 μg/mL collagen; 1.25 and 1.5 g/L ristocetin; 5 and 10 μM epinephrine; 5 and 10 μM or 20 μM TRAP. Maximum aggregation was reached by 300 seconds with 20 and 10 μM ADP, 1 μM U46619, 1 and 1.25 μg/mL collagen, 1.5 g/L ristocetin and 5, 10, and 20 μM TRAP: all others agonists required 600s. ConclusionsA standard panel of agonists can be used on the Sysmex CS‐2x00 series analyzers: ADP (10, 5, 2.5, and 1.25 μM); 1 mM arachidonic acid; 1 μM U46619; 2.5 and 1.25 μg/mL collagen; 1.25 and 0.5 g/L ristocetin; 5 μM epinephrine; 5 and 10 μM TRAP; and saline. Aggregation should be observed for 600 seconds for all agonists except TRAP and U46619, which require 300 seconds. If further studies confirm these concentrations detect platelet disorders then Sysmex CS‐series analyzers could replace dedicated aggregometers, or perform LTA where it is currently not available.

Shifting epistemologies during instructional conversations about “good” argumentative writing in a high school English language arts classroom

A widespread instructional practice in the teaching of argumentative writing is the use of writing samples or models during instructional conversations about what counts as “good argumentative writing.” In this article, we focus on a set of lessons in a high school English language arts classroom in order to gain insight into how a teacher’s use of writing samples contributed not only to what counts as “good argumentative writing” in that classroom, but how her instructional conversations with a group of 11th grade students revealed a shift in her “argumentative epistemologies” for teaching literature-related argumentative writing. We examine simultaneously the impact of instructional conversations on the evolution of the socially constructed definitions of good argumentative writing and the teacher’s shifting argumentative epistemologies by tracing the teacher’s socially constructed definitions of good argumentative writing in the instructional conversations around argumentative writing samples as they evolve and change over time. The findings suggest that the interactional construction of “good argumentative writing” in instructional conversations was influenced by the broader instructional context (e.g., a testing regimen), by the teacher’s argumentative epistemologies for what counts as good writing, and by the conversational interaction of teachers and students in classroom lessons.

Surveillance Testing and Preventive Care After Fontan Operation: A Multi-Institutional Survey.

More children with single ventricle heart disease are surviving after Fontan surgery. This circulation has pervasive effects on multiple organ systems and has unique modes of failure. Many centers have created multidisciplinary programs to care for these patients. Our aim was to survey such programs to better understand current approaches to care. We hypothesized that significant variability in surveillance testing strategy would be present. Eleven academic institutions with established Fontan care programs performing a combined estimated 300 Fontan surgeries per year, with a total population of 1500-2000 Fontan patients, were surveyed using a REDCap survey regarding surveillance testing and basic practice philosophies. Fontan care programs were structured both as consultative services (64%) and as the primary clinical team (9%). Electrocardiograms (73%) and echocardiograms (64%) were most commonly obtained annually. Serum studies, including complete blood count (73%), complete metabolic panel (73%), and Brain-type natriuretic peptide (54%), were most commonly obtained annually. Hepatic testing consisted of liver ultrasound in most centers, obtained biennially (45%) or > every 2years (45%). Liver biopsy was not routinely recommended (54%). Neurodevelopmental outcomes were assessed at most institutions (54%), with a median frequency of every 3-4years. There is considerable variability in the surveillance testing regimen and management strategy after a Fontan procedure at surveyed programs. There is an urgent need for surveillance guidelines to reduce variability, define quality metrics, streamline collaborative practice, and prospective research to better understand the complex adaptations of the body to Fontan physiology.

Abstract 1689: Ovarian tumor-induced CISH expression is an immune checkpoint for NK cells

Abstract Background: Non-specificity of symptoms in early stages of ovarian cancer (OVCA), lack of an early detection test and inefficient chemotherapy regimens lead to frequent recurrence and high mortality rates. OVCA differs from other malignancies as it disseminates by diffusion in the peritoneal cavity. Local immune function is critical and NK cells provide a first line of defense against a developing tumor. Tumors escape NK cell recognition by cleaving off ligands (MICA/B) for NK cell receptors (NKG2D) from their surface. However, preventing the cleaving of ligands does not improve tumor recognition by NK cells to desired levels, suggesting the existence of an additional inhibitory mechanism. Cytokines, including IL-15, play important roles in the proliferation and activation of NK cells. Nevertheless, longstanding exposure to cytokines induces exhaustion of NK cells through expression of CISH (Cytokine-inducible SH2-containing protein). The goal of this study was to examine whether NK cells in ovarian tumors express CISH and whether CISH expression is associated with tumor progression. Materials and methods: This study was conducted in an exploratory design using normal ovaries from postmenopausal women (60-80 years old, n=10), malignant ovarian tumors at early and late stages (n=12 from each stage, 3 from each of 4 histological OVCA types). Localization of CISH-expressing NK cells and expression of GRP78, a marker of cellular stress, were examined by immunohistochemistry (IHC) using paraffin sections. Representative samples were used for immunoblotting (WB) and gene expression studies. Results: Intense staining for CISH was observed for NK cells with occasional staining of malignant cells. Compared with normal ovaries, the population of CISH-expressing NK cells was greater in OVCA at early stage and increased further at late stages. The population of CISH-expressing NK cells was higher in serous OVCA at early stage as compared to other histological types at early stages. However, significant differences were not observed in the population of CISH-expressing NK cells among different histological types of OVCA at late stages. Immunoblotting showed stronger bands at ~30kDa for CISH for malignant tumors at early and late stages. Expression of GRP78 was significantly greater in ovarian tumors as compared with normal ovaries and increased further in OVCA at late stages. These results suggest the presence of cellular stress in ovarian malignant tumors and in their microenvironment are conducive to express a marker of exhaustion (CISH) by NK cells, which may suppress their anti-tumor functions. Thus, CISH may be an immune checkpoint for NK cells. Conclusion: The results of this study suggest that ovarian tumor development and progression is associated with increased expression of CISH by malignant cells and NK cells. Tumor-induced CISH expression may be associated with decreased anti-tumor function of NK cells. Support: NIH CA187309 Citation Format: Amy K. Stasik, Aparna Yellapa, Pincas Bitterman, Sameer Sharma, Sanjib Basu, Animesh Barua. Ovarian tumor-induced CISH expression is an immune checkpoint for NK cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1689.

Comparison Study for Physical Quality Performance and Body composition Between Elite-Normal Junior Swimmers

The aim of the study was to assess the Body composition and fitness between elite and normal junior swimmers. Methods The data was collected from randomly selected (100 mal) sport healthy swimmers in Egypt in 2019.The variables consist of 22 items during three testes Swimming, Fitness and Physiological and Anthropometrical testes. Control value for each parameter was calculated as an average value mean and standard deviation ±SD. The level used for accepting significance was *P < 0.05 and **P<0.001 Results The relative changes were calculated for each subject, an individual mean value and skewness between elite swimmers and normal swimmers for all parameters. it was a different significant for elite swimmers in most of parameters vital capacity between elite and normal junior Swimmers for elite Swimmers (P=5.07) with a Correlation for 100 m freestyle (0.4608-**), in Body Mass(P=2.82) with a Correlation (0.5726-**), in Pull up (P=1.46), with a Correlation (0.232-*).vertical jump(P=2.86**) with a Correlation (0.2675-*). available test of 4×50m /10 sec (P=5.57**) with a Correlation (0.4583**).400m Run (P=3.71**)with a Correlation (0.3275**).10:20 Swim sprint (P=3.10**)with a Correlation (0.4061**).25:50 Swim sprint (P=7.78**)with a Correlation for 100 m freestyle (0.6045**). Grab/Track Start 15 m(P=2.41*) with a Correlation (0.3222**). Core Flexibility (P=4.12**) with a Correlation (0.4343-**). Core Flexibility (P=4.12**) with a Correlation (0.4343-**). Flexibility front Foot (P=2.74**) and Agility(P=2.15*) for the elite junior swimmers. Discussion. in Total and Specific Contribution Ratio: first Sprint (S), second Lead Body Mass (LBM), Third Reaction time (RT), fourth Core Flexibility (CF), fifth vital capacity (VC), sixth Shoulder Flexibility (SF).in a correlation for the 100 m freestyle time record. Conclusions. Common assessments of Body composition and specific physical fitness in elite swimmers explain more variance in competition performance than Normal swimmers, as well as for 100 m events. These findings highlight the need to empirically assess testing regimens and suggest new tests in physical fitness and Anthropometrical characteristics

The relationship between talent identification testing parameters and performance in elite junior swimmers

ObjectivesIn elite age-group swimming it is unclear to what degree common assessments of anthropometric, jump performance and front-crawl critical speed (CS) correlate with competition performance. DesignCross-sectional field study. MethodsForty eight elite national-level junior swimmers (22 males, age 16.5±1.2 y, 26 females, age 15.5±1.1 y; mean±SD) completed anthropometry tests, loaded and unloaded countermovement jumps and a series of front-crawl time-trials to determine CS and supra-CS distance capacity (D’). Years from peak height velocity (PHV) predicted from anthropometric data was used as a maturity indicator. Race performances within 3 months of testing were standardised to compare across distances and strokes. Multiple linear regression models were formulated using these data. ResultsLoaded jump height, mass, D’, PHV and humerus breadth best predicted 100m performance in males (R2Adj=0.88, p<0.001), while loaded jump height, chest depth and sitting height predicted female 100m performances (R2Adj=0.74, p=0.002). Loaded and unloaded jump height, mass, CS and PHV (R2Adj=0.73, p=0.003) and CS and chest depth (R2Adj=0.33, p=0.03) predicted 200m performance in males and females respectively. ConclusionsCommon assessments of power and aerobic capacity in elite junior swimmers explain more variance in competition performance for male than female swimmers, as well as for 100m rather than 200m events. These findings highlight the need to empirically assess testing regimens and suggest new tests in this population may be required.

Preclinical tools for the evaluation of tuberculosis treatment regimens for children.

Tuberculosis (TB) treatment regimens have been extrapolated from adults to children. However, pediatric disease merits different treatment strategies to avoid under- or over-treatment. While animal models have been pivotal in identifying effective regimens for adult disease, pediatric TB is heterogeneous and cannot be represented by a single preclinical model. Infants and young children most commonly have disseminated disease or tuberculous meningitis (TBM), school-aged children have paucibacillary disease, and adolescents have adult-like cavitary lung disease. Models simulating these forms of pediatric TB have been developed, but their utility in assessing treatment regimens is in the early stages. Disseminated, intracellular disease can be partly reproduced by an in vitro pharmacodynamic system, TBM by a pediatric rabbit model of TBM, paucibacillary TB by the balbC mouse model, and cavitary disease by a rabbit model and a C3HeB/FeJ mouse model of pulmonary TB. Although there is no one-size-fits-all preclinical 'pediatric TB model', these models can be employed to study drug distribution to the sites of disease and, coupled with translational modeling, used to help select and optimize regimens for testing in children. Use of these models may accelerate the development of regimens for rare or hard-to-treat TB, namely drug-resistant TB and TBM.

S89. EEG reactivity for prognosis in patients after cardiac arrest

Introduction EEG reactivity testing is often suggested to have prognostic value in patients after cardiac arrest. EEG reactivity testing regimens, however, vary and definitions for reactivity are poorly described (Admiraal et al., Eur J Neurol. 2016). We investigate the prognostic value of standardized EEG reactivity testing in a cohort of patients after cardiac arrest. Methods This is a multicenter prospective observational study. We aim to enroll and monitor 160 patients, using continuous (c) EEG, from Results Up till now a total of 141 patients are enrolled; inclusion is expected to be complete in January 2018. In an interim analysis of 80 patients an intra–class correlation coefficient of 0.78 is found for scoring an EEG as ‘reactive’. Of these 80 patients, 39 (49%) have a good outcome. Mean age is 59 (±15) years in the good outcome group and 61 (±14) years in the poor outcome group. Time to return of spontaneous circulation is shorter in the good outcome group, 15 (±12) min versus 25 (±12) min in respectively good and poor outcome groups. Conclusion We conduct a dedicated prospective trial to determine the prognostic value of EEG reactivity and place this modality in the context of other known prognostic markers. An interim analysis showed a good correlation between raters when scoring EEG reactivity and a representative distribution of patient characteristics. Final results on the prognostic value of EEG reactivity will be presented at the conference.

Experimental determination of the effects of boundary reflection on the angular resolution of microphone arrays

The Rayleigh criterion has long been considered the standard criterion for angular resolution of imaging systems, including microphone arrays. However, advanced beamforming methods have been developed in the past 20 years that have dramatically improved the angular resolution of microphone array systems. In this investigation, the angular resolution performance of three scaled microphone arrays and one alternative array geometry were tested with both approximately free-field and reflective boundary conditions. All of the arrays were subjected to a thorough regimen of testing with broadband acoustic sources. Beamforming analysis was performed with the Delay-and-Sum, TIDY, DAMAS, DAMAS2, and CLEAN-SC algorithms. The Delay-and-Sum algorithm is shown to offer the lowest angular resolution performance because it does not separate the acoustic source map from the point spread function of the array. The DAMAS algorithm offers the greatest angular resolution because it numerically deconvolutes the acoustic source map from the point spread function. However, deconvolution-based algorithms (DAMAS and DAMAS2) were the most negatively affected by boundary reflection effects. The logarithmic spiral array is shown to offer versatile performance across a wide range of frequencies, while an alternative quasi-periodic array yields results that are highly frequency-dependent. It is demonstrated that this is because of gaps in the source-to-element differences coverage, and the gaps in coverage correspond to half-wavelengths of frequency bands with significantly lower angular resolution performance.

Short-course Regimen for Subsequent Treatment of Pulmonary Tuberculosis: A Prospective, Randomized, Controlled Multicenter Clinical Trial in China

PurposeWe designed a prospective, multicenter, randomized, controlled study to assess a 5-month regimen compared with the standard regimen on previously treated patients with pulmonary tuberculosis (TB). MethodsWe enrolled 917 sputum smear–positive patients undergoing additional treatment in 27 major tuberculosis hospitals in China. Patients were randomly assigned to a test group (n = 626)treated with a 5-month regimen of moxifloxacin, pasiniazid, rifabutin, ethambutol, and pyrazinamide or a reference group (n = 291) treated with an 8-month regimen of isoniazid, rifampicin, and streptomycin. All patients with a favorable response were followed up for 5 years after the end of treatment. FindingsOf the study patients, 61 in the test group and 19 in the reference group had multidrug-resistant (MDR) TB. The treatment success rate in the study group was 74.12%, which was significantly higher than the 67.70% in the reference group (P = 0.04), whereas the treatment success rate of patients with MDR-TB was not significantly different between the test and reference groups (70.5% vs 63.1%, P =0.79). The adverse effects rates in the test and reference groups were 7.4% and 3.1%, respectively (P = .01). The difference in the TB recurrence rates between the group arm (9.6%) and the reference group (21.8%) was statistically significant (P < 0.001). ImplicationsThe moxifloxacin, pasiniazid, rifabutin, ethambutol, and pyrazinamide test regimen yielded higher success and lower recurrence rates than the currently recommended isoniazid, rifampicin, and streptomycin regimen, but the rate of adverse effects was higher. ClinicalTrials.gov identifier: NCT02331823.

Johne’s disease: a successful eradication programme in a dairy goat herd

This retrospective analysis and report describes the successful eradication and posteradication surveillance programme for Johne’s disease (Mycobacterium avium subspecies paratuberculosis (MAP)) in a closed herd of dairy goats. In 1994,...

Analytical Methods for Quantification of Vitamin D and Implications for Research and Clinical Practice.

A plethora of contradictory research surrounds vitamin D and its influence on health and disease. This may, in part, result from analytical difficulties with regard to measuring vitamin D metabolites in serum. Indeed, variation exists between analytical techniques and assays used for the determination of serum 25-hydroxyvitamin D. Research studies into the effects of vitamin D on clinical endpoints rely heavily on the accurate assessment of vitamin D status. This has important implications, as findings from vitamin D-related studies to date may potentially have been hampered by the quantification techniques used. Likewise, healthcare professionals are increasingly incorporating vitamin D testing and supplementation regimens into their practice, and measurement errors may be also confounding the clinical decisions. Importantly, the Vitamin D Standardisation Programme is an initiative that aims to standardise the measurement of vitamin D metabolites. Such a programme is anticipated to eliminate the inaccuracies surrounding vitamin D quantification.

Drug Utilization Pattern of Ciprofloxacin, Meropenem and Amikacin in Tertiary Care Hospital in Pakistan

Drug utilization pattern is premeditated to evaluate appropriateness of drug usage. The current study was performed in a multifaceted tertiary care setting in qualitative and cross sectional manner between January to June 2016. In the present study, the proportion and rate of antibacterial prescribing was found to be comparable to other studies conducted in the recent past. The standard integer of remedial moieties per encounter was also found to be elevated when compared to the analogous investigations carried out in various regions of the world at secondary and tertiary care levels. Patient medical charts were retrieved and retrospectively analyzed to extract relevant data. Demographic variables, gender, age, hospital stay, residing ward were taken into consideration. Whereas other variables for ciprofloxacin, meropenem and amikacin were studied with respect to initial/final diagnoses, administered dose, duration of treatment, dosing interval, frequency of administration, microbial culture/sensitivity test and multiple therapeutic regimen. Outcome measures composed of clinical outcome with respect to therapeutic success or failure. An approximation range of 48-59 % of one additional antibiotic and 30-36 % with two or more drugs was found to be for ciprofloxacin, meropenem and amikacin in selected patient’s cohort during their hospitalization period. Prophylactic, empiric and specific use of ciprofloxacin, meropenem and amikacin were in order of 17-39, 12-22 and 30-43 %. Study results highlighted the need for educational intercessions, development of robust and standard utilization guidelines for antibiotics, which could help overcome irrational practice.

Association of Immunotherapy With Durable Survival as Defined by Value Frameworks for Cancer Care

Modern immuno-oncology agents have generated great excitement because of their potential to provide durable survival for some patients. However, there is concern regarding the cost of cancer care, and multiple frameworks have been developed to assess value. The American Society of Clinical Oncology (ASCO) framework awards bonus points if substantial durable survival is demonstrated. To assess whether modern immuno-oncology agents reach defined efficacy thresholds in value frameworks. In this analysis, all US Food and Drug Administration (FDA) approvals for immuno-oncology agents between March 2011 and August 2017 were reviewed. Data required for the ASCO framework were collected, specifically improvement in proportion of patients alive with the test regimen and survival rate with standard treatment. Awarding of bonus points for durable survival based on the ASCO criteria. Twenty-three metastatic indications for 6 immuno-oncology agents (ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, and durvalumab) were approved by the FDA from March 2011 to August 2017. Ten (43%) of the approvals were based on survival end points, while 13 (57%) were based on response rates. Only 3 drug indications fulfilled the threshold defined for the survival rate of patients receiving standard care (minimum 20%). Nine indications achieved the required level of improvement in proportion to patients alive in the test regimen compared with the standard (above 50%). There was overlap between these 2 criteria for 3 drug indications, allowing them to gain the durable survival bonus points awarded by the ASCO framework. Durable survival and response rates of modern immuno-oncology agents are rarely recognized as significant by current oncology value frameworks. This may be due to insufficient demonstration of efficacy of such agents or inappropriately calibrated value frameworks.

Effects of array scaling and advanced beamforming algorithms on the angular resolution of microphone array systems

Several advanced beamforming methods have been developed in the past 20 years that have dramatically improved the angular resolution of microphone array systems. Meanwhile, the Rayleigh criterion has long been considered the standard criterion for angular resolution of such systems. In this investigation four microphone arrays were constructed as scaled models of a fifth microphone array. All of the arrays were subjected to a thorough regimen of testing with both broadband and narrowband sources. Using conventional beamforming, the angular resolution of each scaled array was determined as a function of frequency and compared to the Rayleigh criterion. The analysis was repeated with the advanced TIDY, DAMAS, DAMAS2, and CLEAN-SC beamforming algorithms so that the effects of array scaling and advanced beamforming can be determined as a function of frequency and compared to conventional beamforming.

Risk of Superinfection in Peri-implantitis After Systemic Broad Spectrum Antibiotics.

Peri-implant disease has developed over the last few years as a complication that is often difficult to resolve. The disease process is mainly attributed to bacterial infection. Proposed combined therapies use broad-spectrum antibiotics to halt its progression. A major associated risk is the undetected development of superinfections that are difficult to eradicate. A group of healthy individuals with advanced peri-implantitis (PI) were referred for evaluation due to severe, rapidly progressive bone loss. Previous nonsurgical and empiric antibiotic therapy had been rendered. Culture and polymerase chain reaction-based identification were performed for PI lesions, healthy implants, and saliva. Clinical and radiographic examinations revealed peri-implant bleeding on probing, deep pockets, and severe radiographic bone loss with absence of lamina dura. A number of superinfecting agents were identified, such as Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Candida albicans, and Epstein-Barr virus (EBV). EBV is significantly more prevalent at peri-implantitis sites than at healthy implants and in saliva. Specific systemic antimicrobial therapy and nonsurgical or surgical debridement may eradicate some opportunistic pathogens, but follow-up tests should be performed to identify potential emerging pathogenic microbiota, such as C albicans and enteric rods, at peri-implant sites. Antifungal and antiviral therapy may be needed. Due to the extent and severity of tissue loss, some implants were removed. Peri-implant superinfections are a major risk associated with broad-spectrum antibiotics in immunocompetent individuals. Lack of follow-up and antibiotic susceptibility testing and indiscriminate empiric treatment regimens may lead to ongoing microbial challenge that exacerbates and maintains the disease progression. Personalized periodontal supportive therapy could prevent risks by sustaining a healthy microbial ecologic balance, reducing specific pathogen proportions, maintaining optimal plaque control, and detecting early signs of inflammation.

Development of a phosphorylated Momordica charantia protein system for inhibiting susceptible dose-dependent C. albicans to available antimycotics: An allosteric regulation of protein

A regulatory Momordica charantia protein system was constructed allosterically by in vitro protein phosphorylation, in an attempt to evaluate antimycological pluripotency against dose-dependent susceptibilities in C. albicans. Fungal strain lineages susceptible to ketoconazole, econazole, miconazole, 5-flucytosine, nystatin and amphotericin B were prepared in laboratory, followed by identification via antifungal susceptibility testing. Protein phosphorylation was carried out in reactions with 5′-adenylic, guanidylic, cytidylic and uridylic acids and cyclic adenosine triphosphate, through catalysis of cyclin-dependent kinase 1, protein kinase A and protein kinase C respectively. Biochemical analysis of enzymatic reactions indicated the apparent Michaelis-Menten constants and maximal velocity values of 16.57–91.97mM and 55.56–208.33μM·min−1, together with an approximate 1:1 reactant stoichiometric ratio. Three major protein phosphorylation sites were theoretically predicted at Thr255, Thr102 and Thr24 by a KinasePhos tool. Additionally, circular dichroism spectroscopy demonstrated that upon phosphorylation, protein folding structures were decreased in random coil, β6-sheet and α1-helix partial regions. McFarland equivalence standard testing yielded the concentration-dependent inhibition patterns, while fungus was grown in Sabouraud's dextrose agar. The minimal inhibitory concentrations of 0.16–0.51μM (at 50% response) were obtained for free protein and phosphorylated counterparts. With respect to the 3-cycling susceptibility testing regimen, individuals of total protein forms were administrated in-turn at 0.14μM/cycle. Relative inhibition ratios were retained to 66.13–81.04% of initial ones regarding the ketoconazole-susceptible C. albicans growth. An inhibitory protein system, with an advantage of decreasing antifungal susceptibilities to diverse antimycotics, was proposed because of regulatory pluripotency whereas little contribution to susceptibility in itself.

Effects on the QT Interval of a Gatifloxacin-Containing Regimen versus Standard Treatment of Pulmonary Tuberculosis.

ABSTRACTThe effects on ventricular repolarization—recorded on the electrocardiogram (ECG) as lengthening of the QT interval—of acute tuberculosis and those of standard and alternative antituberculosis regimens are underdocumented. A correction factor (QTc) is introduced to make the QT independent of the heart rate, translating into the slope of the regression line between QT and heart rate being close to zero. ECGs were performed predosing and 1 to 5 h postdosing (month 1, month 2, and end of treatment) around drugs' peak concentration time in tuberculosis patients treated with either the standard 6-month treatment (rifampin and isoniazid for 6 months and pyrazinamide and ethambutol for 2 months; “control”) or a test regimen with gatifloxacin, rifampin, and isoniazid given for 4 months (pyrazinamide for the first 2 months) as part of the OFLOTUB study, a randomized controlled trial conducted in five African countries. Drug levels were measured at steady state (month 1) in a subset of patients. We compared treatment effects on the QTc and modeled the effect of individual drugs' maximum concentrations of drug in serum (Cmax) on the Fridericia-corrected QT interval. A total of 1,686 patients were eligible for the correction factor analysis of QT at baseline (mean age, 30.7 years; 27% female). Median heart rate decreased from 96/min at baseline to 71/min at end of treatment, and body temperature decreased from 37.2 to 36.5°C. Pretreatment, the nonlinear model estimated the best correction factor at 0.4081 in between Bazett's (0.5) and Fridericia's (0.33) corrections. On treatment, Fridericia (QTcF) was the best correction factor. A total of 1,602 patients contributed to the analysis of QTcF by treatment arm. The peak QTcF value during follow-up was >480 ms for 21 patients (7 and 14 in the test and control arms, respectively) and >500 ms for 9 patients (5 and 4, respectively), corresponding to a risk difference of −0.9% (95% confidence interval [CI], −2.0% to 2.3%; P = 0.12) and 0.1% (95% CI, −0.6% to 0.9%; P = 0.75), respectively, between the test and control arms. One hundred six (6.6%) patients had a peak measurement change from baseline of >60 ms (adjusted between-arm difference, 0.8%; 95% CI, −1.4% to 3.1%; P = 0.47). No evidence was found of an association between Cmax of the antituberculosis drugs 1 month into treatment and the length of QTcF. Neither a standard 6-month nor a 4-month gatifloxacin-based regimen appears to carry a sizable risk of QT prolongation in patients with newly diagnosed pulmonary tuberculosis. This is to date the largest data set studying the effects of antituberculosis regimens on the QT, both for the standard regimen and for a fluoroquinolone-containing regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT00216385.)