Assessment Of Clinical Parameters Research Articles

Assessing Chitinases and Neurofilament Light Chain as Biomarkers for Adult-Onset Leukodystrophies.

Leukodystrophies represent a large and complex group of inherited disorders affecting the white matter of the central nervous system. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare leukodystrophy which still needs the proper identification of diagnostic, prognostic, and monitoring biomarkers. The aim of this study was to determine the diagnostic and prognostic value of chitinases and neurofilament light chain as biomarkers for ALSP. A cross-sectional study was performed to analyze cerebrospinal fluid levels of chitinases (chitotriosidase and chitinase 3-like 2) and neurofilament light chain in five different groups: (i) normal health individuals; (ii) patients with definitive diagnosis of ALSP and genetic confirmation; (iii) asymptomatic patients with CSF1R variants; (iv) patients with other adult-onset leukodystrophies; and (v) patients with amyotrophic lateral sclerosis (external control group). Chitinase levels showed a statistical correlation with clinical assessment parameters in ALSP patients. Chitinase levels were also distinct between ALSP and the other leukodystrophies. Significant differences were noted in the levels of chitinases and neurofilament light chain comparing symptomatic (ALSP) and asymptomatic individuals with CSF1R variants. This study is the first to establish chitinases as a potential biomarker for ALSP and confirms neurofilament light chain as a good biomarker for primary microgliopathies.

Electromyography Analysis of the Masseter Muscle's Activity in the Management of Oral Submucous Fibrosis.

Introduction Oral submucous fibrosis (OSMF) is a persistent, collagen metabolic disorder distinguished by the presence of fibrosis of the connective tissue stroma in the oral mucosa with a higher malignant potential rate for oral cancer. This study aimed to analyze the utility of electromyography (EMG) as the prognostic assessment tool in the management of OSMF with conventional intralesional corticosteroid therapy. Materials and methods This study included 20 OSMF cases of age range 20 to 80 years without systemic comorbidities to assess pre-treatment and post-treatment changes with intralesional corticosteroid therapy as an intervention and to determine if it could be assessed using electromyographic study. Clinical and histopathological grading of OSMF was done. The five clinical parameters were evaluated for measuring treatment prognosis. Among them, mouth opening, tongue protrusion, and burning sensation assessments were quantitative parameters, and palpable fibrotic bands and mucosa colour were qualitative parameters. As OSMF involves changes in muscle plane in moderately advanced and advanced cases, EMG was used as an assessment tool for measuring muscle activity. Among the muscles of mastication, the masseterand temporalis were selected for evaluation. Twenty age and gender-matched healthy controls were required for this study as there are no standardized normal values for amplitude and onset of activity in muscle analysis. The EMG activity of the right and left temporalis and masseter muscles were recorded using surface electrodes and were correlated with five clinical assessment parameters. Results In the right masseter, the rest amplitude of 1.6010 µV of the OSMFwas statistically significant (p-value: 0.050) when compared with 4.1275 µV of the control. The clench amplitude of 133.370 µV of the OSMFwas statistically significant (p-value: 0.062) when compared with 94.310 µV of the control. In the left masseter, the rest amplitude of 1.6695 µV of the OSMFwas statistically significant (p-value 0.066) when compared with 2.5735 µV of the control. In the left masseter, the onset of muscle action of 62.670 ms of the OSMFwas statistically significant (p-value: 0.017) when compared with 131.835 ms of the control. The clench amplitude differences in the right masseter of 133.370 µV pre-treatment, and 102.775 µV post-treatment were statistically significant (p-value: 0.007). The clench amplitude in the left masseter of 102.535 µV pre-treatment, and 92.090 µV post-treatment were statistically significant (p-value: 0.036). The correlation was seen between tongue protrusion and rest amplitude in the right masseter in OSMF (r = 0.376, p-value: 0.023). Conclusion There was a correlation between tongue protrusion and rest amplitude in the right masseter muscle in OSMF patients before treatment. In the right and left masseter, during rest, the amplitude of the OSMF group was lesser than that of the control group. During clench, in the right masseter, the amplitude of the OSMF group was higher than that of the control group. During clench in the left masseter, the onset of muscle action was lesser in the OSMF group than in the control group. After treatment, there was a reduction in clench amplitude in OSMF patients from their pretreatment values signifying muscle relaxation and a better onset of muscle action.

Transferrin levels are associated with malnutrition markers in hemodialysis patients in KwaZulu-Natal, South Africa

Introduction Malnutrition is a global phenomenon and may be contributing to the increasing size of the hemodialysis (HD) population in South Africa and is affecting morbidity and clinical outcomes. Our study assessed whether transferrin could be a possible marker for malnutrition in the HD population. Methods Clinical parameters (including skinfold thickness and mid-upper arm circumference [MUAC]) and laboratory markers (including transferrin and hemoglobin) were measured during a six-month period in a sample of 59 HD patients. Results Linear regression analysis showed that MUAC (p = 0.027) as well as skinfold thickness (p = 0.021) had a significant association with transferrin levels within the HD participants. There was no significant association between transferrin levels or MUAC with hemoglobin levels (p = 0.075). Furthermore, the study found that decreased transferrin levels (< 2.15 g/dL to 3.80 g/dL) were closely related to malnutrition in the malnutrition distribution groups within the study, with 97.7% of HD participants being classified in one of the malnutrition groups. Conclusion Thus, transferrin levels are a valuable marker for malnutrition within the HD patient population and can be included along with clinical assessment parameters such as MUAC and skinfold thickness as primary indicators for malnutrition.

Effect of Antenatal Magnesium Sulfate Exposure on Patent Ductus Arteriosus in Premature Infants.

Magnesium sulfate (MgSO4) provides effective fetal neuroprotection. However, there is conflicting evidence regarding the association between antenatal MgSO4 exposure and patent ductus arteriosus (PDA). Thus, herein, we aimed to evaluate the association between antenatal MgSO4 exposure and PDA. Preterm infants born between 240/7 and 316/7 weeks of gestation were included in this retrospective study. Infants who died within the first 72 hours of life and those with significant congenital anomalies were excluded from the study. Echocardiographic and clinical assessment parameters were used to define PDA and hemodynamically significant PDA (hsPDA). Treatments were planned according to the standard protocols of the unit. The following data were collected from hospital medical records: perinatal characteristics, neonatal outcomes, detailed PDA follow-up findings, and maternal characteristics including MgSO4 exposure and doses. Of the 300 included infants, 98 (32.6%) were exposed to antenatal MgSO4. hsPDA rates were similar in the infants exposed and not exposed to antenatal MgSO4, when adjusted for antenatal steroid administration, gestational age, and birth weight (OR: 1.6, 95% CI: 0.849-3.118, p = 0.146). The rates of PDA ligation and open PDA at discharge were similar between the groups. A cumulative MgSO4 dose of >20 g was associated with an increased risk of hsPDA (crude OR: 2.476, 95% CI: 0.893-6.864, p = 0.076; adjusted OR: 3.829, 95% CI: 1.068-13.728, p = 0.039). However, the cumulative dose had no effect on the rates of PDA ligation or open PDA at discharge. Rates of prematurity-related morbidities and mortality were similar between the groups. Although antenatal MgSO4 exposure may increase the incidence of hsPDA, it may not affect the rates of PDA ligation or open PDA at discharge. Further studies are required to better evaluate the dose-dependent outcomes and identify the MgSO4 dose that not only provides neuroprotection but also has the lowest risk of adverse effects. · Antenatal exposure of MgSO4 may cause PDA.. · Antenatal MgSO4 exposure may not increase the rates of PDA ligation or open PDA at discharge.. · Further studies are required to better evaluate the dose-dependent outcomes and optimal MgSO4 dose..

Efficacy of Siddha Therapeutics on Mantha Sanni (Autism Spectrum Disorder) Among Pediatric Patients: An Interventional Non-randomized Open-Label Clinical Trial.

Autism Spectrum Disorder (ASD) refers to a collection of neurodevelopmental disorders that affect brain development and can lead to various psychological imbalances in caregivers of affected children. Siddha formulations have been shown to have a role beyond the physical body and play a significant role in managing Mantha sannior ASD. The objective of this study was to examine the impacts of Amukkara chooranam and Yegamooli thylam in the pediatric population diagnosed with ASD. This was a prospective, interventional, non-randomized, open clinical trial involving 30 patients who met the inclusion and exclusion criteria. Patients received Amukkara chooranamat a dose of 300 mg for ages 3-4 years, 500 mg for ages 5-7 years, and 1 gm for ages 8-12 years, twice a day with honey for 90 days, and Yegamooli thylam was administered using the Thuvalai external manipulation technique once a day for 90 days. Scoring by the Indian Scale for Assessment of Autism (ISAA) was documented at the end of the 0th day, 45th day, and 90th day. The scores were compared at each follow-up, and a statistically significant difference was found at the end of the 90th day of treatment with Amukkara chooranam and Yegamooli thylam (P < 0.05). The statistical analysis included calculating the mean and standard deviation of the clinical assessment, parameters both before and after the treatment were 37.66667 ±13.82485. The treatment with Amukkara chooranam and Yegamooli thylam resulted in a clinically significant improvement in clinical assessment parameters in children with ASD.

Effects of Scaling and Root Planing on Salivary Interleukine-6 Levels in Chronic Periodontitis Patients and Glycemic Controls.

Type 2 diabetes mellitus (DM) and periodontitis have a bidirectional relationship that is well documented in many reviews and epidemiological studies. Periodontitis has been referred to as the sixth complication of diabetes mellitus. Various studies showed improvement inInterleukin-6 levels as well as metabolic parameters after non-surgical periodontal therapy in chronic periodontitis patients with type 2 DM. Objective: To evaluate the effect of scaling and root planing (SRP) on salivary levels of IL-6 and assessment of clinical parameters in CP patients with and without T2DM. We included 50 CP patients with well-controlled T2DM (Group I), and 50 CP patients without T2DM as controls (Group II) with evident clinical inflammation, ≥ 5mm probing depth (PD) and a relative attachment level (RAL) of ≥ 5mm. Following a brief medical and dental history plaque index (PI), gingival index (GI), gingival bleeding index (BI), PD, and RAL were recorded, and an unstimulated saliva was collected.Following SRP therapy, the clinical parameters and IL-6 levels were measured after seven days, 14 days, and 30 days. Intragroup and intergroup comparisons were carried out using a paired t-test and an independent t-test. The statistical significance was set atP< 0.05. Data were analyzed using computer software, Statistical Package for Social Sciences (SPSS) v. 22.0 (IBM Corp., Armonk, NY). Intergroup comparisons of IL-6 levels at different intervals showed a significantly higher reduction in Group II than in Group I (p=0.000). While the mean difference in the GI scores from baseline to 30 days was significantly higher in Group I patients (p=0.000), the difference in the mean PI (p=0.004), mean BI (p=0.000), mean PD (p=0.000) and mean RAL scores (p=0.000) were significantly higher in Group II patients. This study indicates that scaling and root planing is effective in glycemic control and also has a role to play in the level of salivary IL-6 in periodontal healthand T2DM with chronic periodontitis. Elevated salivary IL-6 levels indicate periodontal inflammation which is further increased in T2DM patients. Hence, elevated IL-6 can be considered a marker of periodontal destruction.

Efficiency of therapeutic underwater ultrasound therapy in mild-to-moderate carpal tunnel syndrome: A randomized sham-controlled study.

This study aimed to evaluate the efficiency of therapeutic pulsed ultrasound (US) applied underwater in mild-to-moderate carpal tunnel syndrome (CTS). This randomized, placebo-controlled study included 75 patients (114 hands; 7 males, 68 females; mean age: 46.7±9.9 years; range, 24 to 64 years) diagnosed with CTS through clinical evaluation and electroneuromyography (ENMG) results between March 2012 and January 2013. Patients were randomized into three groups. Group 1 received underwater pulsed US, Group 2 received sham US, and Group 3 was the control group. All groups were given night splints. Patients were evaluated at baseline, at the end of treatment (two weeks), and 12 weeks after the treatment using clinical examination tests (Tinel, Phalen, and hand elevation test), hand grip strength, Visual Analog Scale (VAS) for pain, Pain Quality Assessment Scale (PQAS), and ENMG. In all groups, a significant improvement was detected in the clinical assessment parameters, including the pain VAS, PQAS scores, physical examination outcomes, and hand grip strength. The decrease in VAS score and PQAS was found to be superior in the pulsed US group at both two weeks after the treatment and at the 12th week after the treatment compared to the sham US and control groups (p<0.001). Improvement in ENMG parameters, such as median motor latency, median sensorial velocity, and median sensory latency, was observed only in the underwater pulsed US group (p<0.001). Therapeutic underwater pulsed US is an effective, safe, and easy-to-apply treatment option in the conservative treatment of mild-to-moderate CTS.

Dengue virus infection during window period of consecutive outbreaks in Nepal and assessment of clinical parameters

Nepal is an endemic country for dengue infection with rolling of every 3 year’s clear cyclic outbreaks with exponential growth since 2019 outbreak and the virus gearing towards the non-foci temperate hill regions. However, the information regarding circulating serotype and genotype is not frequent. This research discusses on the clinical features, diagnosis, epidemiology, circulating serotype and genotype among 61 dengue suspected cases from different hospitals of Nepal during the window period 2017–2018 between the two outbreaks of 2016 and 2019. E-gene sequences from PCR positive samples were subjected to phylogenetic analysis under time to most recent common ancestor tree using Markov Chain Monte Carlo (MCMC) and BEAST v2.5.1. Both evolution and genotypes were determined based on the phylogenetic tree. Serotyping by Real-time PCR and Nested PCR showed the co-circulation of all the 3 serotypes of dengue in the year 2017 and only DENV-2 in 2018. Genotype V for DENV-1 and Cosmopolitan Genotype IVa for DENV-2 were detected. The detected Genotype V of DENV-1 in Terai was found close to Indian genotype while Cosmopolitan IVa of DENV-2 found spreading to geographically safe hilly region (now gripped to 9 districts) was close to South-East Asia. The genetic drift of DENV-2 is probably due to climate change and rapid viral evolution which could be a representative model for high altitude shift of the infection. Further, the increased primary infection indicates dengue venturing to new populations. Platelets count together with Aspartate transaminase and Aalanine transaminase could serve as important clinical markers to support clinical diagnosis. The study will support future dengue virology and epidemiology in Nepal.

Severe COVID-19 pneumonia in an intensive care setting and comparisons with historic severe viral pneumonia due to other viruses.

PurposeSevere viral pneumonia is associated with significant morbidity and mortality. Recent COVID‐19 pandemic continues to impose significant health burden worldwide, and individual pandemic waves often lead to a large surge in the intensive care unit (ICU) admissions for respiratory support. Comparisons of severe SARS‐CoV‐2 pneumonia with other seasonal and nonseasonal severe viral infections are rarely studied in an intensive care setting.MethodsA retrospective cohort study comparing patients admitted to ICU with COVID‐19 between March and June 2020 and those with viral pneumonias between January and December 2019. We compared patient specific demographic variables, duration of illness, ICU organ supportive measures and outcomes between both groups.ResultsAnalysis of 93 COVID‐19 (Group 1) and 52 other viral pneumonia patients (Group 2) showed an increased proportion of obesity (42% vs. 23%, p = 0.02), non‐White ethnicities (41% vs. 6%, p < 0.001) and diabetes mellitus (30% vs. 13%, p = 0.03) in Group 1, with lower prevalence of chronic obstructive pulmonary disease (COPD)/asthma (16% vs. 34%, p = 0.02). In Group 1, the neutrophil to lymphocyte ratio was much lower (6.7 vs. 10, p = 0.006), and invasive mechanical ventilation (58% vs. 26%, p < 0.001) was more common. Length of ICU (8 vs. 4, p < 0.001) and hospital stay (22 vs. 11, p < 0.001) was prolonged in Group 1, with no significant difference in mortality. Influenza A and rhinovirus were the most common pathogens in Group 2 (26% each).ConclusionsKey differences were identified within demographics (obesity, ethnicity, age, ICU scores, comorbidities) and organ support. Despite these variations, there were no significant differences in mortality between both groups. Further studies with larger sample sizes would allow for further assessment of clinical parameters in these patients.

Lipidomic and Metabolomic Signature of Progression of Chronic Kidney Disease in Patients with Severe Obesity.

Severe obesity is a major risk for chronic kidney disease (CKD). Early detection and careful monitoring of renal function are critical for the prevention of CKD during obesity, since biopsies are not performed in patients with CKD and diagnosis is dependent on the assessment of clinical parameters. To explore whether distinct lipid and metabolic signatures in obesity may signify early stages of pathogenesis toward CKD, liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-high resolution accurate mass-mass spectrometry (GC-HRAM-MS) analyses were performed in the serum and the urine of severely obese patients with and without CKD. Moreover, the impact of bariatric surgery (BS) in lipid and metabolic signature was also studied, through LC-MS and GC-HRAM-MS analyses in the serum and urine of patients with severe obesity and CKD before and after undergoing BS. Regarding patients with severe obesity and CKD compared to severely obese patients without CKD, serum lipidome analysis revealed significant differences in lipid signature. Furthermore, serum metabolomics profile revealed significant changes in specific amino acids, with isoleucine and tyrosine, increased in CKD patients compared with patients without CKD. LC-MS and GC-HRAM-MS analysis in serum of patients with severe obesity and CKD after BS showed downregulation of levels of triglycerides (TGs) and diglycerides (DGs) as well as a decrease in branched-chain amino acid (BCAA), lysine, threonine, proline, and serine. In addition, BS removed most of the correlations in CKD patients against biochemical parameters related to kidney dysfunction. Concerning urine analysis, hippuric acid, valine and glutamine were significantly decreased in urine from CKD patients after surgery. Interestingly, bariatric surgery did not restore all the lipid species, some of them decreased, hence drawing attention to them as potential targets for early diagnosis or therapeutic intervention. Results obtained in this study would justify the use of comprehensive mass spectrometry-based lipidomics to measure other lipids aside from conventional lipid profiles and to validate possible early markers of risk of CKD in patients with severe obesity.

Next Evolutions in Particle Therapy: Helium Ion Treatment Planning, Delivery and Clinical Implications of Biological Modeling

This work aims to investigate the implication of relevant biological parameters in clinical treatment planning for the first helium ion beam therapy with active beam delivery.Patient plan optimization was performed using the first clinical TPS commissioned for Helium ion therapy with active beam delivery. Biological calculations are coupled to the modified microdosimetric kinetic model (mMKM) for considering bio-effect specific to each tumor and mixed radiation field spectra. Several plans for patients previously treated with proton beams were re-optimized with helium ions. Comparisons of the resulting biological dose distributions between the ions for the same fractionation scheme were conducted. Sensitivity studies were performed with these plans with respect to the chosen (α/β)x for changes in β (high or low in its clinical range) or on the fractionation scheme. Physical and biological quantities such as physical dose, LET and BED were also compared after computation with the secondary dose engine FRoG.During treatment plan optimization, all clinical constraints were reached with the helium ions. Overall, results indicate better CTV conformity and sparing of surrounding healthy tissue. Robustness analysis on 2mm/3% do not show any disadvantages in setup/SPR inaccuracies of helium ions compared to protons. Investigation on the sensitivity studies suggest clinically relevant levels of RBE-related uncertainties with selected (α/β)x, thus calling for compromise between fractionation scheme and RBE sensitivity in treatment design. All plans were dosimetrically verified in water and found to be within clinical tolerances.Prior to the first patient treatment using helium ions with active beam scanning delivery, assessment of clinical parameters and feasibility of patient planning using the mMKM was successfully performed.

EVALUATION OF EFFICACY OF DEMINERALIZED FREEZE DRIED BONE ALLOGRAFT WITH AND WITHOUT PLATELET-RICH FIBRIN IN THE TREATMENT OF INTRABONY DEFECTS BY CONE BEAM COMPUTED TOMOGRAPHY: A CLINICAL AND RADIOGRAPHIC STUDY

Background: Eventhough the combination of DFDBA (demineralized freeze dried bone allograft) with PRF (platelet-rich fibrin) has been attempted in periodontal practice with significant results, assessment of the intrabony defect and defect bone fill largely done with two-dimensional imaging modalities. Three dimentional analysis of the intrabony defect and defect bone fill has not been attempted with cone beam computer tomography (CBCT). The present study evaluated the efficacy of DFDBA with and without PRF in the treatment ofintrabony defects by CBCT. Methods: 60 defects in systemically healthy patients ranging from 18 to 50 years of age will be included in the study.30 defects were treated with PRF+DFDBA and 30 defects were treated with DFDBA alone. The study will include the assessment of clinical parameters involving probing depth (PD), relative attachment level(RAL), full mouth bleeding scores(FMBS),plaque index and gingival index from baseline to 3 , 6, 9 months. Hard tissue changes will be assessed radiographically by evaluating defect fill and defect resolution by CBCT at baseline&amp; 9 months. Results: The results of the present study are statistically significant in both groups in terms of clinical and radiographical parameters (P &lt; 0.001). In inter-group comparison, there was a statistically significant greater PD reduction and attachment gain while there was not significant reduction in terms of PI, GI, FMBS, defect fill and defect resolution in DFDBA+ PRF group. Conclusion: DFDBA along with PRF failed to provide additional value in terms of defect fill and defect resolution over DFDBA alone.

Septaly Oriented Mild Aortic Regurgitant Jets Negatively Influence Left Ventricular Blood Flow-Insights From 4D Flow MRI Animal Study.

Objectives: Paravalvular leakage (PVL) and eccentric aortic regurgitation remain a major clinical concern in patients receiving transcatheter aortic valve replacement (TAVR), and regurgitant volume remains the main readout parameter in clinical assessment. In this work we investigate the effect of jet origin and trajectory of mild aortic regurgitation on left ventricular hemodynamics in a porcine model.Methods: A pig model of mild aortic regurgitation/PVL was established by transcatheter piercing and dilating the non-coronary (NCC) or right coronary cusp (RCC) of the aortic valve close to the valve annulus. The interaction between regurgitant blood and LV hemodynamics was assessed by 4D flow cardiovascular MRI.Results: Six RCC, six NCC, and two control animals were included in the study and with one dropout in the NCC group, the success rate of model creation was 93%. Regurgitant jets originating from NCC were directed along the ventricular side of the anterior mitral leaflet and integrated well into the diastolic vortex forming in the left ventricular outflow tract. However, jets from the RCC were orientated along the septum colliding with flow within the vortex, and progressing down to the apex. As a consequence, the presence as well as the area of the vortex was reduced at the site of impact compared to the NCC group. Impairment of vortex formation was localized to the area of impact and not the entire vortex ring. Blood from the NCC jet was largely ejected during the following systole, whereas ejection of large portion of RCC blood was protracted.Conclusions: Even for mild regurgitation, origin and trajectory of the regurgitant jet does cause a different effect on LV hemodynamics. Septaly oriented jets originating from RCC collide with the diastolic vortex, reduce its size, and reach the apical region of the left ventricle where blood resides extendedly. Hence, RCC jets display hemodynamic features which may have a potential negative impact on the long-term burden to the heart.

Influence of Different Lactation Stages on Circadian Rhythmicity of Metabolic Biomarkers in Dairy Cows: A Pilot Study.

Simple SummaryCircadian rhythms are present in most species and play an important role in their metabolism. Metabolic biomarkers, which are commonly used to assess the health status, are also affected by those rhythms. In this study, we investigate the influence of lactation and time on four metabolic biomarkers in dairy cows. Our findings provide new insights into the physiology of circadian rhythms in dairy cows, which enables novel metabolic monitoring approaches.Currently, subclinical metabolic imbalances at the individual cow and herd level are detected by measuring biomarkers in single blood samples. However, diurnal variations have not been fully described yet but need to be considered when sampling for a robust ad consistent analysis. The study describes the influence of lactation phases on circadian rhythms and diurnal variations for non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), total bilirubin (tBIL) and aspartate aminotransferase (AST) in dairy cows. In an observational pilot study, we used 16 clinically healthy Simmental dairy cows subdivided in four different lactation stages (dry-off, fresh, high and late lactating). Every cow was monitored for 24 h, with blood sampling and assessment of clinical parameters every 2 h. Time and lactation stage influence the concentration of the biomarkers NEFA, BHB and tBIL in serum. Further, circadian rhythmicity was found in high lactating cows for NEFA peaking at 5:39 am and BHB peaking at 4:20 pm. We suggest blood sampling for single-point measurements within three hours after the first feeding until two hours after the last feeding of the day. The results provide a new insight into the physiology of circadian rhythms in dairy cows and enable improved metabolic monitoring.

Dose-Finding in the Development of an LPS-Induced Model of Synovitis in Sheep.

Models of transient synovitis that can be controlled with antiinflammatory and analgesic drugs have been used to study pain amelioration. To this end, we aimed to determine the dose of intraarticularly administered E. coli LPS that induced signs of synovitis without systemic signs in clinically healthy male castrated sheep (n = 14). In phase 1, a single dose of LPS (0.5, 1.0, 1.5, or 2.0 ng in a total volume of 0.5 mL) was administered into the right stifle joint. In phase 2, a dose of LPS (1.0 or 2.0 μg) in 0.3 mL was administered to 4 naïve sheep. In phase 3, 4 sheep from phase 1 were inoculated after a 60 d washout period with either 0.5 or 1.0 μg of LPS. During the first 48 h after LPS administration, the following were performed: assessment of clinical parameters; scoring for lameness, pain on limb flexion, and local swelling; and ultrasonography of the joints were performed. The doses tested during phase 1 produced subtle signs. During phase 2, mild to moderate lameness with no evidence of systemic signs occurred at both doses. In phase 3, clinical responses were similar between the 0.5- and 1-μg doses. Signs of swelling were not observed at any time. Therefore, we consider the 0.5-μg to be the most appropriate for this model, because it was the lowest dose tested capable of causing lameness without signs of systemic inflammation in all animals.

Effect of Locally Delivered Melatonin as an Adjunct to Nonsurgical Therapy on GCF Antioxidant Capacity and MMP-9 in Stage II Periodontitis Patients: A Randomized Controlled Clinical Trial.

Objectives Periodontitis is characterized by inflammatory destruction of periodontal tissue, loss of attachment, and bone resorption. The increase in reactive oxygen species (ROS) is responsible for the oxidative damage occurring in periodontal tissues. Melatonin has important immunomodulatory, anti-inflammatory, and powerful antioxidant functions. The current study was carried out to evaluate the effect of topical melatonin gel as an adjunct to nonsurgical periodontal therapy. Methods This split-mouth randomized controlled clinical trial was performed on 24 patients with grade II periodontitis. Two sites in each patient were randomly assigned; test sites were treated by nonsurgical therapy followed by intrapocket application of 5% melatonin gel. Control sites were treated by nonsurgical therapy followed by intrapocket application of placebo gel. Both the melatonin and placebo gel were applied weekly once for four weeks. Assessment of clinical parameters (PD and CAL) was done at baseline and 3 months after therapy. Total antioxidative capacity (TAC) and matrix metalloproteinase-9 (MMP-9) levels in GCF were also evaluated utilizing commercially available enzyme-linked immunosorbent assay kits (ELISA) at baseline and 3 months after therapy. Results Treatment with topical melatonin was associated with a reduction in periodontal inflammation reflected as an improvement in the clinical periodontal parameters. Melatonin-treated sites showed a more statistically significant percent reduction in PD and more statistically significant percent gain in CAL than the control site. Additionally, a significant increase in TAC and a significant decrease in MMP-9 levels in GCF were found in melatonin-treated sites in comparison to control sites. Conclusions The adjunctive use of topical melatonin gel with nonsurgical periodontal therapy has potent anti-inflammatory and antioxidant activity in the treatment of grade II periodontitis patients.

Partial resection of the infrapatellar fat pad during anterior cruciate ligament reconstruction has no effect on clinical outcomes including anterior knee pain.

Anterior knee pain (AKP) is a major complication that occurs after anterior cruciate ligament reconstruction (ACLR), even when hamstring tendon (HT) grafts are used. Damage to the infrapatellar fat pad (IPFP) during arthroscopy can cause AKP. The purpose of this study was to evaluate the influence of IPFP preservation on clinical outcomes, including AKP, in patients who underwent ACLR with HT autografts using the inside-out technique. Forty-two patients who underwent primary ACLR with HT autografts were prospectively assessed for 2years after surgery. They were randomly selected to undergo treatment with as much intercondylar IPFP preservation as possible or with intercondylar IPFP resection to confirm the ACL origin on the femoral and tibial sides, especially the femoral footprint in deep flexion of the knee joint. The total IPFP volume was calculated using sagittal MR images before and 6months after surgery. The patients completed a subjective knee score questionnaire and were assessed for patellar tendon tenderness and pain with the half-squat test or single-leg hop test at 6months and 2years postoperatively. There were no differences in the patient characteristics, including age, sex, BMI, time from injury to surgery, and meniscus tear. The difference in the total size of the IPFP preserved was significant (P = 0.004). However, there were no significant differences in the subjective knee scores. Moreover, there were no differences in the clinical assessment parameters between the IPFP preservation and resection groups. The size of the IPFP decreased more in the resection group than in the preservation group at 6months after surgery. However, partial IPFP resection, which was used to better visualize the origin of the ACL, had no effect on the clinical outcomes, including AKP. Level II.

Composition of Immune Subpopulations Influence Multiple Myeloma Disease Progression

Immune dysfunction is an important feature of multiple myeloma (MM). Characterization of lymphocytic infiltrates, comparing precursor, early &amp; later disease stages, indicate that the anti-myeloma immune response evolves in conjunction with the progression of disease, while distinctive patterns identified in the infiltrating immune population have prognostic relevance (Pessoa de Magalhaes, Vidriales et al. 2013, Paiva, Mateos et al. 2016).The primary objective of this project is to characterize the marrow-infiltrating lymphocytic and myeloid populations to identify specific patterns of immune dysregulation &amp; a biomarker signature that will guide predictions of efficacy of different immunotherapeutic modalities.(Willenbacher et al. 2016, Kini Bailur, Mehta et al. 2017). Patient samples are identified for inclusion based on clinical assessment parameters: detection of a monoclonal gammopathy, the presence or absence of end-organ damage indicative of active/symptomatic MM, and &lt;2 prior lines of therapy. 15 Healthy donor samples were acquired from volunteers with no evidence of hematologic malignancy. Disease status was categorized as precursor MGUS stage, newly diagnosed untreated MM (NDMM), pre-transplant MM (PreT-MM) and 90 days post-transplant MM (D90-MM).Infiltrating leukocyte populations are isolated from 20ml of fresh bone marrow aspirates and analyzed by multi-parameter flow cytometry. Lymphocytes are analyzed for subset composition, memory/effector maturation &amp; exhaustion.The myeloid component analyzes the monocytic and granulocytic myeloid-derived suppressor cells, M1/M2 macrophages, dendritic cells and neutrophils. To date, 38 samples for lymphoid and 56 for the myeloid panel have been analyzed. All calculations and data analysis are performed in the industry standard bioinformatics platform, FlowJo v10.6.Dimensionality reduction is run for visualization of high parameter data using the t-distributed stochastic neighbor embedding (tSNE) algorithm. X-shift unsupervised clustering is employed to identify populations in an unbiased manner. Unsupervised clusters are compared and contrasted relative to known biomarkers of interest within the ClusterExplorer platform and batched across tSNE space in contrast to: subjects, conditions &amp; manually defined gating. The immunologic parameters are compared to histologic, molecular and genetic features of disease as detailed by the biopsy report &amp; to the extended longitudinal clinical course of the patient (disease progression &amp; response to therapy). Classical flow analysis of the myeloid panel clearly reveals significant changes occurring in the G-MDSC population with disease progression. tSNE-based unsupervised analysis show increases in CD4 T effector cells in NDMM patients, but the differences in the CD4 memory compartment in MGUS suggest that these variations in T cells may originate during premalignancy. The expression of CD95 on CD4 cells is downregulated with disease progression. In addition to changes in T cells, we observe changes in innate cells- NDMM samples show an increase in a CD194+NK cell population which may represent a transitional population expanded during pathological tumor growth. With recent studies suggesting that innate cells could be targets for immune-modulatory drugs, this opens a new avenue. Taken together, this data illustrates complex alterations in the immune landscape from a premalignant to malignant stage, implicating that engaging the immune system early in the evolution of clinical MM may improve the potential of durable remissions. Kini Bailur, J., et al. (2017). "Changes in bone marrow innate lymphoid cell subsets in monoclonal gammopathy: target for IMiD therapy." Blood Adv1(25): 2343-2347. Paiva, B., et al. (2016). "Immune status of high-risk smoldering multiple myeloma patients and its therapeutic modulation under LenDex: a longitudinal analysis." Blood127(9): 1151-1162. Pessoa de Magalhaes, R. J., et al. (2013). "Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry." Haematologica98(1): 79-86. Willenbacher, W., et al. (2016). "Bone marrow microenvironmental CD4 + and CD8 + lymphocyte infiltration patterns define overall- and progression free survival in standard risk multiple myeloma--an analysis from the Austrian Myeloma Registry." Leuk Lymphoma57(6): 1478-1481. Disclosures Shain: AbbVie: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees. Brayer:Janssen: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau.

Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery.

Neisseria meningitidis (meningococcus) is a narrow-host-range microorganism, globally recognized as the leading cause of bacterial meningitis. Meningococcus is a transient colonizer of human nasopharynx of approximately 10% of healthy subject. In particular circumstances, it acquires an invasive ability to penetrate the mucosal barrier and invades the bloodstream causing septicaemia. In the latest case, fulminating sepsis could arise even without the consequent development of meningitis. Conversely, bacteria could poorly multiply in the bloodstream, cross the blood brain barrier, reach the central nervous system, leading to fulminant meningitis. The murine models of bacterial meningitis represent a useful tool to investigate the host-pathogen interactions and to analyze the pathogenetic mechanisms responsible for this lethal disease. Although, several experimental model systems have been evaluated over the last decades, none of these were able to reproduce the characteristic pathological events of meningococcal disease. In this experimental protocol, we describe a detailed procedure for the induction of meningococcal meningitis in a mouse model based on the intracisternal inoculation of bacteria. The peculiar signs of human meningitis were recorded in the murine host through the assessment of clinical parameters (e.g., temperature, body weight), evaluation of survival rate, microbiological analysis and histological examination of brain injury. When using intracisternal (i.cist.) inoculum, meningococci complete delivery directly into cisterna magna, leading to a very efficient meningococcal replication in the brain tissue. A 1,000-fold increase of viable count of bacteria is observed in about 18 h. Moreover, meningococci are also found in the spleen, and liver of infected mice, suggesting that the liver may represent a target organ for meningococcal replication.

Efficacy of Mifepristone versus GNRH Analogue in the Treatment of Uterine Leiomyoma- A Comparative Study

Background: Uterine fibroids also called as uterine leiomyoma is the most common benign tumor of the uterus. Most women develop one or more uterine leiomyoma during their reproductive years. Hence; we assessed the efficacy of Mifepristone 25mg versus Inj.Leuprolide acetate 3.75mg in reducing size of uterine myoma. Subjects and Methods: The study was planned for detecting difference of 15 percent in the outcome variables between the two groups and Standard deviation of 156.00, with 90% statistical power and 5% level of significance, the sample size was calculated to be 70 for the study. The study subjects were randomly assigned into 2 groups of 35 patients each. Group 1: Patients treated with Tablet Mifepristone 25mg once daily for 3 months; Group 2: Patients treated with Inj. Leuprolide acetate depot preparation 3.75mg IM once a month for 3 months. Demographic data, history, clinical examination, details of drug prescription, laboratory investigations and imaging reports were recorded in the study proforma. Various clinical assessment parameters were assessed. Results: After three months of treatment, there was a marked relief with significant decrease in visual analog scale score in both the groups (p <0.001). 21 patients (60%) in group 1 and 25 patients (71%) in group 2 presented with mild anemia at the beginning of the study. After three months of treatment, there was a significant (p <0.001) rise in the hemoglobin and hematocrit values in both the groups. There was an increase in mean hemoglobin level by 2.9gm/dl in mifepristone group and 3gm/dl in leuprolide group. Conclusion: Treatment with either mifepristone or leuprolide acetate in uterine leiomyoma is safe and causes significant but temporary reductions in uterine size and myoma related symptoms.