Enhancing type 2 diabetes treatment through digital plans of care - a randomized controlled trial: evaluation of change in patient reported outcome measures.

BACKGROUND: We investigated how a personalized care-planning software and linked mobile-app may aid people to self-manage their type 2 diabetes (T2D) more effectively. RESEARCH DESIGN AND METHODS: People with T2D and glycated hemoglobin (HbA1c) greater than 58 mmol/mol (7.5%) were randomized to either an intervention group receiving a personalized care plan, or the control group receiving usual care. Quality of life (QoL) was measured for both groups using validated questionnaires and one-on-one interviews with a subset of 12 participants from each group. RESULTS: QoL for the active treatment group increased, by their EQ -5D-5 L score increasing on average by 0.046, whereas it decreased for the control group on average by 0.009. The EQ Visual Analogue Score (VAS) of the intervention group also increased by 8.2%, whereas the control group had a reduction in EQ VAS score of 2.8% (p = 0.008 for difference). CONCLUSION: In this prospective RCT, the findings point to how the provision of personalized care plans can result in an improvement in individuals' self-rated QoL. This may lead to longer term health benefits.

Nicardipine or Nitroprusside for Postoperative Blood Pressure Control in Infants After Surgery for Congenital Heart Disease: Single-Center Retrospective Noninferiority and Cost Analysis, 2016-2020.

OBJECTIVES: Postoperative hypertension frequently occurs after surgery for congenital heart disease. Given safety concerns when using calcium channel blockers in infants along with the cost and side-effect profile of nitroprusside, we retrospectively assessed our experience of using nicardipine and nitroprusside for postoperative blood pressure control in infants who underwent surgery for congenital heart disease. We also investigated the cost difference between the medications. DESIGN: This study was a single-center retrospective, pre-post chart review of patients who had surgery for congenital heart disease between 2016 and 2020. The primary aim was a noninferiority comparison of achievement of blood pressure goal at 1-hour post-initiation of an antihypertensive agent. Secondary comparisons included achievement of blood pressure goal at 2 hours after medication initiation, Vasoactive-Inotropic Score (VIS), and blood transfusion, crystalloid volume, and calcium needs. SETTING: Academic quaternary-care center. PATIENTS: Infants under 1 year old who required treatment for hypertension with nitroprusside (n = 71) or nicardipine (n = 52) within 24 hours of surgery for congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We failed to identify any difference in proportion of patients that achieved blood pressure control at 1-hour after medication initiation (nitroprusside 52% vs. nicardipine 54%; p = 0.86), with nicardipine noninferior to nitroprusside within a 15% margin. Of patients who did not achieve control at 1-hour post-medication initiation, receiving nicardipine was associated with blood pressure control at 2 hours post-medication initiation (79% vs. 38%; p = 0.003). We also failed to identify an association between antihypertensive types and mean VIS scores, blood transfusion volumes, crystalloid volumes, and quantities of calcium administered. Index cost of using nitroprusside was 16 times higher than using nicardipine, primarily due to difference in wholesale cost. CONCLUSIONS: In our experience of achieving blood pressure control in infants after surgery for congenital heart disease (2016-2020), antihypertensive treatment with nicardipine was noninferior to nitroprusside. Furthermore, nicardipine use was significantly less expensive than nitroprusside. Our contemporary practice is therefore to use nicardipine in preference to nitroprusside.

Standard Amblyopia Therapy in Adults with Longstanding Amblyopia Improves Visual Acuity and Contrast Sensitivity.

Purpose: Perceptual learning or dichoptic training may result in improved acuity in adult amblyopes. However, for amblyopic children (<18 years), most clinicians recommend standard part-time patching. The purpose of this study was to determine if standard amblyopia therapy results in an enhancement in vision in the amblyopic eye of adults. Patients and Methods: Fifteen amblyopes (20/30 or worse) were recruited and nine (age (SD) 32.9 (16.31)) with anisometropia or anisometropia and strabismus (ie, combined mechanism amblyopia) completed the study. Previous therapy did not exclude subjects. The subjects received a comprehensive eye exam and wore their best correction for at least four weeks prior to baseline testing. The non-amblyopic eye was patched for 2 hours per day (Amblyopia iNET training for 30 minutes and near/distance activities for 1.5 hours). The subjects had a baseline amblyopia evaluation followed by one visit per week for 12 weeks. At 12 weeks, the treatment was tapered off over one month and the subjects had a final amblyopia evaluation at 24 weeks. Contrast sensitivity was measured at baseline and 12 weeks with the Quick CSF system. Results: The subjects had a significant improvement in visual acuity across the weeks (p < 0.001). At baseline, weeks 12 and 24, the average logMAR acuities (SE) were 0.55 (0.09), 0.41 (0.08), and 0.38 (0.09), respectively. Weeks 4 to 24 were significantly different (p < 0.001) from baseline. The average acuity improvement over the 24 weeks was 1.7 logMAR lines. There was a significant increase in the area under the log contrast sensitivity function (p = 0.002) and its estimated acuity (p = 0.036) from baseline to 12 weeks. Conclusion: Standard amblyopia treatment can result in an improvement in visual acuity and contrast sensitivity in adults with longstanding anisometropic or combined mechanism amblyopia even if they had prior therapy.

Study protocol for First Dental Steps Intervention: feasibility study of a health visitor led infant oral health improvement programme.

BACKGROUND: Dental caries in childhood is a burden on the daily lives of children and their families, and associated with poor oral health in adulthood. In England, dental caries is the most common reason for young children to be admitted to hospital. It is believed that most tooth extractions (due to decay) for children aged 10 years and under, could be avoided with improved prevention and early management. National public health policy recommendations in England include specific oral health initiatives to tackle tooth decay. One of these initiatives is delivered as part of the Healthy Child Programme and includes providing workforce training in oral health, integrating oral health advice into home visits, and the timely provision of fluoride toothpaste. This protocol seeks to assess the delivery of the First Dental Steps intervention and uncertainties related to the acceptability, recruitment, and retention of participants. METHODS: This study seeks to explore the feasibility and acceptability of the First Dental Steps intervention and research methods. First Dental Steps intervention will be delivered in local authority areas in South West England and includes oral health training for health visitors (or community nursery nurses) working with 0-5-year-olds and their families. Further, for vulnerable families, integrating oral health advice and the provision of an oral health pack (including a free flow cup, an age appropriate toothbrush, and 1450 ppm fluoride toothpaste) during a mandated check by a health visitor. In this study five local authority areas will receive the intervention. Interviews with parents receiving the intervention and health visitors delivering the intervention will be undertaken, along with a range of additional interviews with stakeholders from both intervention and comparison sites (four additional local authority areas). DISCUSSION: This protocol was written after the start of the COVID-19 pandemic, as a result, some of the original methods were adjusted specifically to account for disruptions caused by the pandemic. Results of this study will primarily provide evidence on the acceptability and feasibility of both the First Dental Steps intervention and the research methods from the perspective of both families and stakeholders.

Part Three: A Brief Primer of Non-Insulin Treatments for Type 2 Diabetes Mellitus in Older People.

Diabetes is a heterogeneous condition that manifests differently in each patient. Fortunately, there are multiple different medication classes that can be used to help patients achieve their treatment goals. Diabetes is highly prevalent in older people, including patients who have been living with the condition for many years and those who are newly diagnosed. It is essential for senior care pharmacists to evaluate patient-specific goals, compelling indications, and risks and benefits of treatment. When evaluating therapy appropriateness, pharmacists must take into consideration the impact of medication therapy beyond glucose-lowering effects, including the overall impact on cardiovascular, renal, heart failure, and weight-related outcomes.

An Innovative Approach to Remote Electronic Health Onboarding Record Education Amid a Global Pandemic.

The COVID-19 pandemic required social and physical distancing to reduce the spread of disease. The reduction in meeting sizes made it difficult to offer traditional in-person EHR training to new and transferring employees. This paper aims to share how one nurse educator team used an innovative approach to transition traditional EHR onboarding education to synchronous remote learning during the global pandemic. Participants in the remote learning course (n = 94) were compared with those who had previously completed the traditional course (n = 110). Postcourse evaluations for each group were comparable. Remote learning participants found the technology conducive to training and reported higher scores for locating and reviewing patient information than those in the traditional course. Providing remote EHR education is comparable with traditional classroom education. Remote learning provided a safe, effective way to onboard new staff during the pandemic.

Validity of 1% Hormonal Receptor Positivity Cutoff by the ASCO/College of American Pathologists Guidelines at the Georgia Cancer Center.

PURPOSE: Treatment of breast cancer (BC) with borderline or low (1%-9%) estrogen and progesterone expression remains controversial, with recent data disputing ASCO/College of American Pathologists 2010 guidelines that lowered the threshold of receptor positivity from 10% to 1%. The objective of this retrospective study was to validate these guidelines at the Georgia Cancer Center with a high percentage of Black race. METHODS: All female patients with invasive BC diagnosed between 2005 and 2010 at the Georgia Cancer Center were chart reviewed up to an 11-year follow-up with data cutoff at 2016. We used Cox regression to explore survival among three hormonal status (HS) groups (< 1%, 1%-9%, and ≥ 10%) adjusting for all known BC clinicopathologic variables. Fisher's exact test was used to evaluate response to endocrine therapy (ET). RESULTS: Among 431 patients with mean age 59 years, 24.75% had HS < 1%, 17.5% HS 1%-9%, and 57.75% HS ≥ 10%. Race was 43.75% Black and 54% White. Disease stages were early (I-IIIA) in 84.4% and advanced (IIIB-IV) in 15.56%. Mortality in HS < 1% was significantly higher than that in HS ≥ 10% (hazard ratio [HR]: 1.8; 95% CI, 1.07 to 3.02), whereas no significant mortality difference between HS 1%-9% and HS ≥ 10% (HR: 1.05; 95% CI, 0.48 to 2.30) was observed. ET was protective, and treated patients had higher predicted survival than untreated patients in the 1%-9% group (HR: 0.10; 95% CI, 0.01 to 0.85). There was no significant mortality difference between ET-treated HS 1%-9% and ≥ 10% groups. CONCLUSION: One percent cutoff predicted superior survival on treatment with ET compared with the other groups, and HS as low as 1%-9% was equiprognostic to HS ≥ 10%. Whether other factors such as lymphovascular invasion, grade, and other parameters change the behavior of the 1%-9% HS group remains to be explored.

The UroLift® System for lower urinary tract obstruction: patient selection for optimum clinical outcome.

INTRODUCTION: The minimally invasive UroLift® System procedure in moderate-to-severe benign prostate hyperplasia (BPH) refractory to medical treatment may be superior over other prostate procedures regarding its preserved sexual function post-operatively. We aimed to optimise patient selection criteria for the UroLift® System. MATERIAL AND METHODS: Fifty-one men that underwent UroLift® System surgery were retrospectively reviewed over >24 months. We evaluated the efficacy and safety of UroLift® System, pre-operatively and at three, six, 12, and 24 months post-operatively, assessing the International Prostate Symptom Score (IPPS), urinary flow rates (Qmax), post void residual (PVR) bladder scan volumes and the International Index of Erectile Function (IIEF). Adverse events were assessed by Clavien-Dindo Classification. RESULTS: The 51 men undergoing UroLift® System had a success rate of 92.2% over 2 years, with improvements in Qmax, IPSS and PVR. IIEF was preserved in all cases. Adverse events were Clavien-Dindo grade 1, most commonly mild-to-severe dysuria (19.6%), and resolved spontaneously. Four patients failed to improve. CONCLUSION: Patient-related selection criteria to optimise the UroLift® System clinical outcomes include age, Qmax, PVR urine, median lobe, PSA levels, prostate volume, IPSS and IIEF scores. The UroLift® System is safe and effective in moderate-to-severe BPH refractory to pharmacological treatments and avoids retrograde ejaculation.

Combination of ZEN-3694 with CDK4/6 inhibitors reverses acquired resistance to CDK4/6 inhibitors in ER-positive breast cancer.

CDK4/6 inhibitors significantly prolong progression-free survival in patients with advanced hormone receptor-positive (HR+) HER2-negative breast cancer. Despite recent successes, patients acquire resistance, necessitating the development of additional novel therapeutic strategies. Bromodomain and extra-terminal domain (BET) proteins are key epigenetic regulators that interact with acetylated lysine (AcLys) residues of histones or transcription factors. BET proteins are directly involved in modulating estrogen receptor (ER) signaling and the cell cycle. Therefore, BET inhibitors can potentially offer new strategies in the treatment of advanced ER+ breast cancer. ZEN-3694 is an orally bioavailable small molecule BET inhibitor currently being evaluated in Phase 1/2 clinical trials (NCT03901469). To assess a potential combination strategy in a CDK4/6i resistant breast cancer population, we investigated the mechanism of action of ZEN-3694 combined with CDK4/6 inhibitors in the ER+ cell lines resistant to palbociclib or abemaciclib. Here, we describe that the combination of ZEN-3694 with CDK4/6i potently inhibits proliferation and induces apoptosis in CDK4/6i resistant cell lines. The resistance to both palbociclib and abemaciclib was associated with the strong upregulation of CDK6 and CCND1 protein levels, which was reversed by the ZEN-3694 treatment. Furthermore, RNAseq data and pathway analysis elucidated the combinatorial effects of ZEN-3694 with CDK4/6 inhibitors through significant downregulation of multiple pathways involved in cell cycle regulation, cellular growth, proliferation, apoptosis, inflammation, and cellular immune response. Our data indicate that ZEN-3694 has therapeutic potential in combination with CDK4/6 inhibitors in patients with advanced ER+ breast resistant to CDK4/6 inhibitors.

Predictive In Vitro-In Vivo Extrapolation for Time Dependent Inhibition of CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2D6 Using Pooled Human Hepatocytes, Human Liver Microsomes, and a Simple Mechanistic Static Model.

Inactivation of Cytochrome P450 (CYP450) enzymes can lead to significant increases in exposure of comedicants. The majority of reported in vitro to in vivo extrapolation (IVIVE) data have historically focused on CYP3A, leaving the assessment of other CYP isoforms insubstantial. To this end, the utility of human hepatocytes (HHEP) and human liver microsomes (HLM) to predict clinically relevant drug-drug interactions was investigated with a focus on CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2D6. Evaluation of IVIVE for CYP2B6 was limited to only weak inhibition. A search of the University of Washington Drug-Drug Interaction Database was conducted to identify a clinically relevant weak, moderate, and strong inhibitor for selective substrates of CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2D6, resulting in 18 inhibitors for in vitro characterization against 119 clinical interaction studies. Pooled human hepatocytes and HLM were preincubated with increasing concentrations of inhibitors for designated timepoints. Time dependent inhibition was detected in HLM for four moderate/strong inhibitors, suggesting that some optimization of incubation conditions (i.e., lower protein concentrations) is needed to capture weak inhibition. Clinical risk assessment was conducted by incorporating the in vitro derived kinetic parameters maximal rate of enzyme inactivation (min-1) (kinact) and concentration of inhibitor resulting in 50% of the maximum enzyme inactivation (KI) into static equations recommended by regulatory authorities. Significant overprediction was observed when applying the basic models recommended by regulatory agencies. Mechanistic static models, which consider the fraction of metabolism through the impacted enzyme, using the unbound hepatic inlet concentration lead to the best overall prediction accuracy with 92% and 85% of data from HHEPs and HLM, respectively, within twofold of the observed value. SIGNIFICANCE STATEMENT: Coupling time-dependent inactivation parameters derived from pooled human hepatocytes and human liver microsomes (HLM) with a mechanistic static model provides an easy and quantitatively accurate means to determine clinical drug-drug interaction risk from in vitro data. Optimization is needed to evaluate time-dependent inhibition (TDI) for weak and moderate inhibitors using HLM. Recommendations are made with respect to input parameters for in vitro to in vivo extrapolation (IVIVE) of TDI with non-CYP3A enzymes using available data from HLM and human hepatocytes.

A new prognostic model for predicting 30-day mortality in acute oncology patients.

INTRODUCTION: Acute oncology services (AOS) provide rapid review and expedited pathways for referral to specialist care for cancer patients. Blood tests may support AOS in providing estimates of prognosis. We aimed to develop and validate a prognostic model of 30-day mortality based on routine blood markers to inform an AOS decision to actively treat or palliate patients. METHODS AND MATERIALS: Using clinical data from 752 AOS referrals, multivariable logistic regression analysis was conducted to develop a 30-day mortality prognostic model. Internal validation and then internal-external cross-validation were used to examine overfitting and generalizability of the model's predictive performance. RESULTS: Urea, alkaline phosphatase, albumin and neutrophils were the strongest predictors of outcome. The model separated patients into distinct prognostic groups from the cross-validation (C Statistic: 0.70; 95% CI: 0.64-0.76). Admission year was included as a predictor in the model to improve the model calibration. CONCLUSION: The developed prediction model was able to classify patients into distinct prognostic risk groups, which is clinically useful for delivering an evidence-based AOS. Collation of data from other AOS centers would allow for the development of a more generalizable prognostic model.

Case Report: Focal Choroidal Excavation: Conversion from Conforming to Nonconforming in a Pregnant Female.

SIGNIFICANCE: Although rarely seen, clinicians should closely monitor patients, especially pregnant patients with focal choroidal excavation (FCE), as it can convert between subtypes and has been linked to pachychoroidal disease and potential for vision loss. PURPOSE: This study aimed to report a case of the conversion of conforming FCE to nonconforming FCE with spontaneous resolution in a pregnant female. CASE REPORT: A 35-year-old Indian woman presented with a slightly decreased vision in the right eye. The patient was 3 months pregnant at this visit. Her ocular history included stable conforming FCE in both eyes that was diagnosed 1 year earlier. Retinal pigmentary changes were noted in both eyes and consistent with previous examinations as being conforming FCEs in both eyes. Optical coherence tomography through the pigmented changes revealed FCE in the right eye with overlying serous fluid, with the left eye showing stable conforming FCE. She was diagnosed with a nonconforming FCE in the right eye secondary to her pregnancy. She was monitored with subsequent visits showing spontaneous resolution of the fluid and conversion back to a conforming FCE. CONCLUSIONS: This case highlights the conversion of a conforming FCE to a nonconforming FCE with spontaneous resolution in a pregnant female. Similarities are seen in terms of pathophysiology with central serous chorioretinopathy, a fellow pachychoroidal disease, which also has pregnancy as a risk factor. Risk factors in pregnant patients such as increased cortisol and increased ocular blood flow may play an important part in the pathophysiology of the conditions, as they both result in choroidal hyperpermeability. Frequent monitoring and follow-up times are suggested for the patients. Lifelong monitoring is also indicated, as reoccurrences have been reported. Further research is needed at this time to elucidate the exact etiology of FCE and conversions between conforming and nonconforming FCE.

Nocardia farcinica masquerading as intracerebral metastases in advanced metastatic prostatic cancer.

A 67-year-old man with metastatic prostate cancer and underlying asymptomatic pancytopenia presented with a 1-week history of general malaise, left leg weakness and facial numbness. Initial brain imaging demonstrated two rim-enhancing lesions felt to represent intracerebral metastasis. Following neurosurgical referral, a multidisciplinary meeting decision was made for best supportive care and dexamethasone was given. He developed multiple cutaneous lesions, which on incision and drainage revealed Nocardia farcinica Repeat brain imaging showed enlargement of the existing cavitating lesions and appearance of new lesions, now typical of cerebral abscesses. A diagnosis of disseminated nocardiosis with cutaneous and intracerebral infection was reached. He started taking empirical treatment with intravenous meropenem, co-trimoxazole and subsequent addition of amikacin, with little improvement. On further review of sensitivities, moxifloxacin was added. Following over 1 month of antimicrobial treatment, his neurological symptoms, cutaneous lesions and repeat MRI of the brain had improved.

Red cell differential width (RDW) as a predictor of survival outcomes with palliative and adjuvant chemotherapy for metastatic penile cancer.

PURPOSE: Red cell distribution width (RDW) measures red cells' size variability. Metastatic penile cancer displays poor chemotherapy response. As no validated prognostic predictor exists, we investigated whether RDW correlates independently with survival outcomes in metastatic penile cancer treated by chemotherapy. METHODS: Electronic chemotherapy files of patients with metastatic penile cancer (M1 or N3) from a large academic supra-regional centre were retrospectively analysed between 2005 and 2018. Patients were stratified into RDW > 13.9% and < 13.9%, as per published data on RDW in renal cell carcinoma. Survival time was calculated from the date of chemotherapy initiation until the date of death. RESULTS: 58 patients were analysed. The RDW-high group (n = 31) had a poorer survival than the RDW-low group (n = 27). Median overall survival (mOS) in all patients was 19.0 months (95% CI 13.1-24.9). mOS for RDW-high was 15.0 months (95% CI 10.1-19.9) and 37.0 months (95% CI 32.3-43.1) for RDW-low. Kaplan-Meier curves showed a clear disparity in survival (log rank p = 0.025). Cox proportional hazard ratio for death, corrected for T-stage, grade, age and deprivation score was 0.43 (p = 0.04). Sub-analysis of the M1 patients showed mOS in RDW-high of 17 m (95% CI 11.6-22.4) vs. NR; HR for death of 0.42. N3 patients' mOS in RDW-high cohort was 30 months (95% CI 4.5-55.9) vs. 13 months (95% CI 1.8-24.2) in RDW-low; HR for death was 0.30. CONCLUSION: RDW correlates independently with survival outcomes in metastatic penile cancer and may act as a potential predictor of survival outcomes for patients with metastatic penile cancer receiving chemotherapy.

Instrumenting Polyodon spathula (Paddlefish) Rostra in Flowing Water with Strain Gages and Accelerometers.

The prominent rostrum of the North American Paddlefish, supported by a lattice-like endoskeleton, is highly durable, making it an important candidate for bio-inspiration studies. Energy dissipation and load-bearing capacity of the structure from extreme physical force has been demonstrated superior to that of man-made systems, but response to continuous hydraulic forces is unknown and requires special instrumentation for in vivo testing on a live fish. A single supply strain gage amplifier circuit has been combined with a digital three-axis accelerometer, implemented in a printed circuit board (PCB), and integrated with the commercial-off-the-shelf Adafruit Feather M0 datalogger with a microSD card. The device is battery powered and enclosed in silicon before attachment around the rostrum with a silicon strap "watch band." As proof-of-concept, we tested the instrumentation on an amputated Paddlefish rostrum in a water-filled swim tunnel and successfully obtained interpretable data. Results indicate that this design could work on live swimming fish in future in vivo experiments.

Impact of Occlusal Intercuspal Angulation on the Quality of CAD/CAM Lithium Disilicate Crowns.

PURPOSE: Modification of intercuspal angulation (ICA) influences the amount of tooth structure removal, which may impact the retention and resistance form of the preparation. This study evaluated the impact of ICA on the marginal gap of CAD/CAM crowns and the influence that tooth structure removal, caused by variation of ICA, has on the resistance and retention form of the preparation. MATERIALS AND METHODS: Sixty ivorine molars were manufactured with various ICAs (100°, 110°, 120°, 140°, 160°, and 180°; 10 per group). The preparations were digitized using an intraoral scanner, and the crowns were designed using a design software. The designed crowns were then manufactured from lithium disilicate using a 3-axis milling machine, with the "detailed mode" selected for the manufacturing. The marginal gap of each crown was evaluated using a stereomicroscope at 20× magnification. Then, the marginal integrity and the resistance form of the preparation were assessed by tactile-visual evaluation, and they were given a categorical score. Crowns were then secured on their associated preparations using a temporary luting agent, and retention force was measured on a universal testing machine under tension with a 0.5 mm/min crosshead speed. Wilcoxon test followed by post-hoc tests (α = 0.05) were used to evaluate the impact of the ICA on the marginal gap and the retention form of the preparation. Fisher's exact test followed by post-hoc tests (α = 0.05) were used to assess the impact of the occlusal preparation design on the marginal integrity and the resistance form of the preparation. RESULTS: The marginal gap was significantly larger for ICA-180 preparations (72 µm), compared to the other groups (ICA-180 vs ICA-100, ICA-110, ICA-120, and ICA-160 p = 0.0001; ICA-180 vs. ICA-140 p = 0.0017). None of the crowns for ICA-180 preparations had clinically acceptable resistance form. Preparations with ICAs of 100°, 110°, and 120° had a significantly higher value of retention than the other groups (ICA-100 vs. ICA-120 p = 0.0119; ICA-100 vs. ICA-140, ICA-160, and ICA-180 p < 0.0001; ICA-110 vs. ICA-140, ICA-160, and ICA-180 p = 0.0001; ICA-120 vs. ICA-180 p = 0.0017). CONCLUSIONS: Crowns fabricated for preparations with various ICAs had clinically acceptable marginal adaptation. Variation in ICA impacts the loss of tooth structure. This loss of tooth structure may influence the resistance and retention form of the preparation.

Microbiological profiles in clinical and subclinical cases of mastitis in milking Jafarabadi buffalo.

Mastitis is one of the important diseases affecting the dairy industry across the globe. Identification of bacterial pathogens associated with mastitis becomes essential in order to understand the etiology of disease which in turn will help to new strategies to control it. Microbial diversity analysis using pyrosequencing is widely studied for mastitis pathogens in dairy cows. However it is unexplored in case of buffalo. In the present study 16SrDNA gene pyrosequencing was used to characterize microbiota associated with clinical and subclinical mastitis in 28 Jafarabadi buffalo. The obtained sequencing data were analyzed by Quantitative Insights into Microbial Ecology (QIIME) and statistical analysis was done using Paleontological Statistics (PAST). Pyrosequencing produced 47.3 million base pairs reads. Phylogenetic profiles using ribosomal database revealed differences in abundance of Staphylococcus (25.95%, 10.09% and 0.03%), Enterococcus (10.80%, 8.72% and 0.36%), Escherichia (8.88%, 0.38% and 0.00%), Streptococcus (3.97%, 0.42% and 0.00%), Lactococcus (3.73%, 23.96% and 0.01%), and Ralstonia (0.54%, 12.72% and 0.00%), genera in clinical, subclinical and healthy samples, respectively. Different microbial profiles in clinical and subclinical mastitis in buffalo suggest the composition of bacteria in the milk is more diverse and complex hence single therapeutic regimes cannot be applied.