Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

In vitro antibacterial activity of antibiotics and plant essential oils against Escherichia coli MTCC443 supported through the molecular docking and pharmacokinetics study.

Most of the Escherichia coli turned into serious pathogens or developed antibiotic resistance, mainly due to their ability to show different phenotypic traits. In order to overcome the resistance to these antibiotics, the use of essential oils (EOs) is of great significance against highly pathogenic microorganisms. This study has been made to compare the in vitro antibacterial activity and further validated the same through the molecular docking study of 13 antibiotics such as ciprofloxacin, chloramphenicol, erythromycin, ampicillin, cefotaxime, rifampicin, kanamycin, vancomycin, streptomycin, penicillin, nalidixic acid, trimethoprim, and polymyxin, and 10 EOs such as garlic, tulsi, neem, clove, thyme, peppermint, coriander, tea, lavender, and eucalyptus against the target protein (DNA gyrase) of E. coli MTCC443. E. coli Microbial Type Culture Collection 443 was found to be highly sensitive to ciprofloxacin (zone of inhibition [ZOI], 2.5 cm ±0.1) and chloramphenicol (ZOI, 1.8 cm ±0.1), whereas garlic oil (ZOI, 5.5 cm ±0.1) and coriander oil (ZOI, 4.4 cm ±0.1) were found comparatively most effective. Further, the in silico investigation observed the same; ciprofloxacin (binding affinity: -7.2 kcal/mol) and chloramphenicol (binding affinity: -6.6 kcal/mol). Penicillin (binding affinity: -4.2 kcal/mol) and polymyxin (binding affinity: -0.3 kcal/mol) were found to be least effective against the tested microbe, whereas vancomycin (binding affinity: +0.8 kcal/mol) had no effect on it. Garlic (binding affinity: -7.8 kcal/mol), coriander (binding affinity: -6.8 kcal/mol), peppermint (binding affinity: -6.2 kcal/mol), and neem (binding affinity: -6.2 kcal/mol) oil exhibited the potent antibacterial activity against E. coli MTCC443, whereas thyme (binding affinity: -6.1 kcal/mol), tea tree (binding affinity: -4.9 kcal/mol), and tulsi (binding affinity: -3.8 kcal/mol) oil were observed moderately effective. Eucalyptus (binding affinity: -2.9 kcal/mol) and lavender (binding affinity: -2.8 kcal/mol) oil were found to be the least effective among all the oils tested. The pharmacokinetics and networking were performed to the pharmacology of the potential compounds.

Influence of Chairside Simulated Adjustment (Finishing and Polishing) Protocol and Chlorhexidine Mouthwash Immersion on Color Stability and Translucency of 2 and 3 Preshaded Multilayered Monolithic Zirconia.

BACKGROUND Preshaded monolithic zirconia (MLZ) is reported to have high translucency. This study aimed to assess the effect of chlorhexidine gluconate (ChG) mouthwash on color and translucency parameter (TP) of 2 different preshaded MLZ dental ceramics after clinical adjustment. MATERIAL AND METHODS Two MLZ disk-shaped specimens [NPM (Nacera Pearl Multi-Shade) (n=72) and CZM (Ceramill Zolid FX Multilayer)] (n=72) were simulated for clinical adjustment, finished, and polished using 2 adjustment kits [recommended kit, third-party kit: Diasynt Plus and SUN (n=12 each)] and later immersed in ChG mouthwash (Avohex) for 2 weeks. Difference in color (ΔE) and TP (Y) were calculated using the CIELab formula after measuring the coordinates (Lab) with a colorimeter. Individual changes in color and TP were assessed on the Clinical acceptance (perceptible) threshold (CAT/CPT) and Translucency perception threshold (TPT), respectively. Differences between the 2 ceramics were assessed using one-way ANOVA and post hoc tests, with all differences considered significant at P<0.05. RESULTS NPM and CZM differed in color at baseline despite having the same Vita shade combination. Between the 2 preshaded MLZ ceramics, NPM showed significant changes in color when adjusted with a third-party kit. Chlorhexidine produced changes in color and TP that were designated as clinically perceptible (ΔE=1.0 to 3.3) on the CAT/CPT and TPT scales, irrespective of the adjustment kit used. ChG produced the least or no changes in glazed MLZ specimens. CONCLUSIONS ChG mouthwash, whenever prescribed for preshaded MLZ restoration, should be adjusted prior to final glazing to avoid clinical adjustments that adversely affects color and translucency of the restoration.

Outcome of buttress plate-nail construct used for reconstruction of broken lateral wall in intertrochanteric fractures.

PURPOSE: Intramedullary implants are well accepted fixation of all types of intertrochanteric (IT) fractures, both stable and unstable types. Intramedullary nails have an ability to effectively support the posteromedial part, but fail to buttress the broken lateral wall requiring lateral augmentation. The aim of this study was to evaluate the outcome of proximal femoral nail augmented with trochanteric buttress plate for broken lateral wall with IT fractures, which was fixed to the femur through hip screw and anti-rotation screw nail. METHODS: Of 30 patients, 20 had Jensen-Evan type III and 10 had type V fractures. Patients with IT fracture of broken lateral wall and aged more than 18 years, in whom satisfactory reduction was achieved by closed methods, were included in the study. Patients with pathologic or open fractures, polytrauma, prior hip surgery, non-ambulatory prior to surgery, and those who refused to participate were excluded. The operative time, blood loss, radiation exposure, quality of reduction, functional outcome, and union time were evaluated. All data were coded and recorded in Microsoft Excel spread sheet program. SPSS 20.0 was used for data analysis and normality of the continuous data was checked using Kolmogorv Smirnov test. RESULTS: The mean age of patients in the study was 60.3 years. The mean duration of surgery (min), mean intra-operative blood loss (mL) and mean number of exposures were 91.86 ± 12.8 (range 70 - 122), 144.8 ± 3.6 (range 116 - 208), and 56.6 (range 38 - 112), respectively. The mean union time was 11.6 weeks and the mean Harris hip score was 94.1. CONCLUSION: Lateral trochanteric wall in IT fractures is significantly important, and needs to be reconstructed adequately. Nail-plate construct of trochanteric buttress plate fixed with hip screw and anti-rotation screw of proximal femoral nail can be successfully used to augment, fix or buttress the lateral trochanteric wall giving excellent to good results of early union and reduction.

Effect of Effervescent Denture Cleansers on 3D Surface Roughness of Conventional Heat Polymerized, Subtractively, and Additively Manufactured Denture Base Resins: An In Vitro Study.

PURPOSE: To compare the change in surface roughness of denture bases fabricated using three different techniques (additive manufacturing, subtractive manufacturing, and conventional heat-polymerizing) when immersed in two commonly available denture cleansers. MATERIALS AND METHODS: One hundred and seventeen disc-shaped denture base specimens (39/group), were fabricated by subtractive manufacturing (Wieland), additive manufacturing (NextDent Denture 3D+), and conventional heat-polymerizing (Meliodent) techniques, following the manufacturers' instructions. Specimens were randomly divided into 3 groups and immersed in two effervescent denture cleansing solutions and distilled water to simulate 180 days of denture cleansing. A 3D optical noncontact surface profilometer was used to record the surface roughness of the tested denture base materials before and after immersion. Two-way ANOVA, followed by Bonferroni post hoc test, was used to assess the effects of denture cleansers on surface roughness of tested denture base resins. RESULTS: When immersed in Fixodent and Fittydent effervescent denture cleansing solutions, the highest change in absolute surface roughness (∆Sa, in µm) was observed in additively manufactured denture base material (0.181 ±0.018 and 0.079 ±0.008), followed by heat-polymerized denture base material (0.149 ±0.012 and 0.059 ± 0.011), while subtractively manufactured denture base material showed the least change (0.110 ±0.026 and 0.038 ±0.007), respectively. There was a difference in the extent of change in surface roughness between the denture cleansers. The change in surface roughness was much higher with the Fixodent denture cleanser as compared to the Fittydent denture cleanser. CONCLUSION: Subtractively manufactured denture base resin displayed the lowest change while additively manufactured denture base resin displayed the highest change in surface roughness in both denture cleansers, but the extent of change in surface roughness was variable.

Accuracy Comparison between Robot-Assisted Dental Implant Placement and Static/Dynamic Computer-Assisted Implant Surgery: A Systematic Review and Meta-Analysis of In Vitro Studies.

Background and Objectives: The present systematic review and meta-analysis undertake a comparison of studies that examine the accuracy of robot-assisted dental implant placement in relation to static computer-assisted implant surgery (SCAIS), dynamic computer-assisted implant surgery (DCAIS), and freehand procedures. This study aims to provide a comprehensive understanding of the precision of robot-assisted dental implant placement and its comparative efficacy in relation to other placement techniques. Methods: The guidelines recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were used to organize and compose this review. Four electronic databases (PubMed, Web of Science, Scopus, and Cochrane) were systematically searched for pertinent articles. Articles were selected following the inclusion and exclusion criteria. Qualitative and quantitative analyses of the selected articles were performed. Results: The initial electronic search resulted in 1087 hits. Based on the inclusion and exclusion criteria, five articles were selected for qualitative analysis, out of which three were considered for quantitative analysis. Three parameters were considered for accuracy evaluation (angular, coronal, and apical deviation). The mean angular deviation was -1.22 degrees (95% CI, -1.06--1.39), the mean coronal deviation was -0.15 mm (95% CI, -0.24--0.07), and the mean apical deviation was -0.19 mm (95% CI, -0.27--0.10). Conclusions: The robotic implant system was found to have significantly lower angular deviations and insignificantly lower coronal and apical deviations compared to DCAIS. Within the limitations of this review, it can be concluded that robot-assisted implant placement in resin models permits higher accuracy compared to DCAIS and SCAIS systems. However, due to the limited number of comparative studies with high heterogeneity, the findings of this review should be interpreted with caution. Further research is necessary to confirm the clinical application of robotics in implant surgery.

Adverse Events during Intrahospital Transport of Critically Ill Patients: A Multicenter, Prospective, Observational Study (I-TOUCH Study).

Background: Critically ill patients are frequently transported to various locations within the hospital for diagnostic and therapeutic purposes, which increases the risk of adverse events (AEs). This multicenter prospective observational study was undertaken to determine the incidence of AEs related to intrahospital transport, their severity, and their effects on patient outcomes. Patients and methods: We included consecutive unstable critically ill patients requiring intrahospital transport, across 15 Indian tertiary care centers over 5 months (October 11, 2022-February 20, 2023). Apart from the demographics and severity of illness, data related to transport itself, such as indications and destination, incidence of AEs, their category and treatment required, and patient outcomes, were recorded in a standard form. Results: Eight hundred and ninety-three patients were transported on 1065 occasions out of the intensive care unit (ICU). The mean (SD) acute physiology and chronic health evaluation II score of the patients was 15.38 (±7.35). One hundred and two AEs occurred, wherein cardiovascular instability was the most common occurrence (31, 30.4%). Two patients had cardiac arrest immediately after transport. Acute physiology and chronic health evaluation II [odds ratio (OR): 1.02, 95% confidence interval (CI) - 1.00-1.05, p = 0.04], emergent transport (OR: 5.11, 95% CI - 3.32-7.88, p = 0.00), and team composition (OR: 5.34, 95% CI - 1.63-17.5, p = 0.00) during transport were found to be independent predictors of AEs. Conclusion: We found a high incidence of AEs during intrahospital transport of critically ill patients. These events were more common during emergent transports and when the patients were transported by doctors. Transport by itself was not related to ICU mortality. We feel that stabilization of the patients before transport and adherence to a standardized protocol may help in minimizing the AEs, thereby enhancing patient safety. How to cite this article: Zirpe KG, Tiwari AM, Kulkarni AP, Govil D, Dixit SB, Munjal M, et al. Adverse Events during Intrahospital Transport of Critically Ill Patients: A Multicenter, Prospective, Observational Study (I-TOUCH Study). Indian J Crit Care Med 2023;27(9):635-641.

Continuous ambulatory peritoneal dialysis catheter insertion by open technique: 20-year experience from a single center.

Introduction: Continuous ambulatory peritoneal dialysis (CAPD) catheter placement is a part of renal replacement therapy. We describe our 20-year experience in using the open technique and assess its safety, efficacy, and outcome in the treatment of end-stage renal disease patients. Methods: In a retrospective study, we analyzed data of all patients who had a CAPD catheter placed using our open dissection technique using local anesthesia over the previous 20 years, with minimum 1 year of follow-up. Intraoperative data, postoperative data, and complications were noted. Results: A total of 1410 cases were included in the study. The mean duration of follow-up was 72 ± 18 months (range 12-120 months). The mean operative time was 19 ± 7.5 min and mean hospital stay was 3 ± 1 days. No major intraoperative complications were noted. We observed a peritonitis rate of 0.49 episodes/patient/year. The most common reason for permanent catheter removal was refractory peritonitis in 21%, followed by flow failure in 7%, and ultrafiltration failure in 6.5%. The death-censored technical survival rate was 94.3%, 83.2%, 75.9%, 69.2%, and 60.6% patients at 1 year, 2 years, 3 years, 4 years, and 5 years, respectively. Conclusions: The open dissection method of peritoneal dialysis catheter insertion using local anesthesia at well-experienced center is a simple, painless, and uncomplicated procedure with excellent outcomes. Optimal exposure, judicious use of energy source, and using appropriate technique provide good technical success rate with lesser complications.

A huge staghorn renal stone: Is there still a need for open surgery to protect against further damage to the kidney? A case report.

INTRODUCTION: Staghorn calculi (SC) occupy the renal pelvis and calyces and are common in females linked to repeated urinary tract infections (UTIs). Judicious surgery planning reduces the chance of further damage to the kidney due to renal SCs. Open stone surgery (OSS) is one of the various operative techniques to remove such huge stones with one operative intervention and protect the kidney from ongoing functional damage. CASE REPORT: A 47-year-old male patient presented with right-sided renal colic pain, and on further investigations, he was diagnosed with a large renal stone responsible for substantial renal function impairment on the same side. The SC measured 8 × 4 cm with another stone in the lower calyx. thinner parenchyma, and only 16% relative function. Therefore, open surgery was selected over less invasive approaches because multiple lithotripsy (ESWL) sittings may have been required in less invasive options. DISCUSSION: SCs, which can be complete or partial, often result in renal impairment. Hence, it is crucial to implement a proactive therapeutic approach that includes a thorough evaluation of the stone's size and position, the patient's choice, and institutional capacity. Complete elimination of SCs is preferred to maintain maximal renal function. Based on clinical, technical, and socioeconomic considerations, open pyelolithotomy or OSS was chosen over percutaneous nephrolithotomy for SC removal in the discussed case. CONCLUSION: The ability to remove large stones in a single intervention with open pyelolithotomy has been very effective due to its distinctive clinical presentation and pathological abnormalities.

Can urodynamic diagnosis of dysfunctional voiding/external sphincter nonrelaxation be made on two-channel pressure-flow study without video-urodynamics, electromyography, or urethral pressure profilometry? Plateau detrusor pattern in perspective.

AIMS: urodynamic diagnosis of dysfunctional voiding/external-sphincter nonrelaxation (DV/EUSD) needs assistance of specialized testing namely urethral pressure profilometry (UPP), electromyography (EMG), and/or videofluoroscopy (VUDS). We aimed to find a predictive model based on standard pressure-flow study without need for specialized testing. MATERIAL AND METHODS: In this retrospective study (2017-2021), clinical and urodynamic data of adult men and women presenting with voiding dysfunction was collected. Mandatory inclusion criteria were availability of all-(1) findings of clinical examination and neurological status, (2) a valid filling cystometry and pressure-flow study (with active detrusor contraction), (3) a final clinic-urodynamic diagnosis. Voiding cystourethrography (VCUG) was performed to confirm the location of obstruction. RESULTS: Data of 218 participants (178♂, 40♀) was eligible. Plateau detrusor contraction pattern was observed in 89.0% of men and 86% of women with DV/EUSD; whereas only 7.5% men and no women with other obstructions demonstrated this pattern. Forward likelihood Logistic regression analysis revealed presence of plateau pattern, lower bladder outlet obstruction index (BOOI), and smaller difference between Pdetmax and PdetQmax highly predictive of presence of DV/EUSD in men as per the following equation-Y = -9.900 + (0.085 × BOOI) + (0.123 × pdetmax - pdetQmax) + (4.061 × detrusor pattern). A kattan-type nomogram was constructed based on the above equation. In women, presence of plateau pattern alone was highly predictive of DV/EUSD. CONCLUSION: Diagnosis of DV/EUSD can be accurately predicted using parameters of three-channel urodynamics (plateau pattern, BOOI, Pdetmax-pdetQmax) minimizing need for specialized testing.

Does augmentation of intramedullary nails by a buttress plate effectively restore lateral wall integrity in intertrochanteric fractures.

BACKGROUND: Recent studies have proved the importance of intact lateral trochanteric wall, thus buttressing/fixing the broken lateral trochanteric wall irrespective of the implant, is likely to improve the alignment and outcome. We compared the outcome of lateral wall buttressing by trochanteric buttress plate (TBP) supplemented to proximal femoral nailing versus proximal femoral nailing alone in patients of broken lateral wall intertrochanteric fractures. MATERIAL AND METHOD: Sixty patients of intertrochanteric factures (IT) of femur with broken lateral wall were randomized into group A or B and were treated with either proximal femoral nail (PFN) alone or proximal femoral nail augmented with trochanteric buttress plate (PFN + TBP), respectively. The TBP plate used was primarily fixed to proximal femur via 8 mm hip screw and 6.4 mm antirotation screw of the PFN. Operative time, blood loss, radiation exposure, quality of reduction, functional outcome, union time, and complications were compared. RESULT: The mean age was 60.03 + 7.60 (range 42 to 70 years), with male to female ratio of 4:1 and left to right ratio of approximately 1:1. The mean follow up in the series was 16.2 months (range 13 to 36 months). Mean duration of surgery, mean intra-operative blood loss, and mean number of exposures in group A (PFN alone) were 64.88 + 12.24 min (48 to 88), 93 + 1.18 ml (60 to 120), and 32.13 (24 to 46) and in group B (PFN with TBP plate) were 91.86 + 12.78 min (70 to 122 min), 144.8 + 3.6 ml (116 to 208 ml), and 56.6 (38 to 112), respectively. Twenty-five patients and 28 patients in groups A and B respectively achieved score of 4 Chang quality reduction. Mean union time was 13.4 weeks in group A whereas in group B was 11.6 weeks. Mean HHS score in group A was 87.86 with 90% patients in comparison to 94.13 and 97% cases having excellent to good results in group B. In group A, 24 patients, while 29 patients in group B, had excellent to good results. Four patients had hip pain, four had impingement of screws, two had screw migration, three had Z/reverse effect, and four patients had shortening of more than 1 cm in group A. In group B, only one patient had impingement and none of the patient had hip pain, infection, implant failure, Z effect, or shortening. CONCLUSION: The lateral trochanteric wall in IT fractures is significantly important, and when the lateral wall is broken, it can lead to poor results. TBP plate which is applied laterally on femur along with nail and fixing the plate with hip screw and antirotational screw provides faster union, early weight bearing, better reduction, and so better hip functions. TBP can be used successfully to augment, fix, or buttress the lateral trochanteric wall giving excellent to good results but at the cost of surgical time, blood loss, and radiation exposure.

Efficacy of Various Implant Abutment Screw Access Channel Sealing Materials in Preventing Microleakage: A Systematic Review.

The aim of this systematic review is to evaluate the effectiveness of different materials used for sealing dental implant abutment screw access channel (ASAC), in preventing microleakage. As per the searched indexed English literature, this study is the first review of its kind. Indexed English literature published up to February 20, 2021 was systematically searched on relevant electronic databases. The recommendations specified by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) were applied for constructing framework, and reporting the current review. The focused PICO (Participant, Intervention, Comparison, Outcome) question was: "Which material (C) is more effective in sealing (I) implant ASAC (P) in terms of causing minimal microbial leakage (O)". Quality of articles was assessed with modified CONSORT scale for in vitro studies. Five in vitro studies were selected for qualitative analysis after final stage screening. Modified CONSORT scale suggested that out of the 5 selected studies, 1 each was of low and high quality, whereas 3 studies were of moderate quality. Included studies had contrasting results related to the efficacy these materials as sealants in ASAC. Sealing capacity against microleakage should be considered as one of the important criteria while selecting the material to fill implant ASAC. Definitive conclusions asserting superiority of a single material over others are difficult to draw, due to nonhomogeneity in study design of the included papers. More studies should be conducted in the near future to investigate the efficacy of various combination of materials in preventing microleakage.

Effect of cigarette smoke on color stability and surface roughness of different soft denture lining materials. An in vitro study.

PURPOSE: To evaluate the effect of cigarette smoke on the surface roughness and color stability of three different soft denture liners. METHODS: Three commonly used commercially available, chair-side, long-term vinyl polysiloxane soft denture liners were used for this study [Sofreliner Tough (S) Soft, Silagum Comfort Soft Relining, and GC Reline Soft\. Thirty disk-shaped specimens of each material, with a diameter of 25 mm and thickness of 2 mm, were fabricated. Initial color and surface roughness readings were recorded. The specimens of each group were randomly divided into two groups (n= 15): the control group (C) and the study group (S). The control group specimens were stored in distilled water and the study group samples were exposed to cigarette smoke in a custom-made smoking chamber. Final color and surface roughness readings were recorded. A single operator performed all the measurements. The differences in color and surface roughness were calculated. Statistical analysis was performed using two-way ANOVA, post-hoc Tukey test, and paired t-test. For all the analyses, a P< 0.05 was regarded as statistically significant. RESULTS: After exposure to smoke, all groups showed a significantly perceptible color change (ΔE > 3.7). The greatest color change was seen in the Silagum group (ΔE= 8.94 ± 0.42), followed by the Sofreliner group (ΔE= 7.85 ± 0.47), with the least change in the GC reline group (ΔE= 3.87 ± 0.46). The mean color change after smoke exposure showed a statistically significant difference among all three study groups. The highest change in surface roughness was observed in the Silagum group (ΔR= 0.687 ± 0.14) followed by the GC reline group (ΔR= 0.265 ± 0.12), with the least change in the Sofreliner group (ΔR= 0.238 ± 0.06). There was a statistically significant difference between each group before and after exposure to smoke. Exposure to cigarette smoke caused significant changes in the color and surface roughness of all three soft denture liners tested in this study. The extent of these changes varied for each material. CLINICAL SIGNIFICANCE: Proper selection of soft denture liners is essential to avoid premature replacement, due to esthetic and hygiene reasons in cigarette smokers.

Submental flap: Game changer in oral cancer reconstruction-A study of 1169 cases.

BACKGROUND: Free-flap reconstructions (FFRs) are the standard-of-care following resections for oral cancer. This study assessed an alternative, the pedicled submental flap (SF) for its versatility, oncological outcomes, and comparative operative time and cost. METHODS: This was a longitudinal prospective study of 1169 patients of oral cancer reconstructed with the SF. Oncological outcomes in terms of recurrence rate and disease-free survival (DFS), were analyzed in 730 cases with a minimum of 18 months follow-up. Surgical time and cost were compared between 20 SFs and 14 FFRs performed consecutively. RESULTS: SF was used to reconstruct defects in the cheek (29.2%), mandible (41.6%), tongue (26.3%) and palate (2.7%) with a 94% flap survival. N+ at level 1 did not adversely affect the recurrence rate as compared with N+ at levels other than level 1 (27.52% vs 29.81%). SFs took a shorter time (186 minutes vs 474 minutes) and cost significantly less than FFRs (P < .0001). CONCLUSIONS: SF can reconstruct various oral defects, is sturdy, and esthetically and functionally satisfactory. The procedure time is much shorter than for FFR and costs considerably less. With careful case selection and meticulous clearance, SF reconstruction is oncologically safe even in N+ neck.

Comparative Cerebroprotective Potential of d- and l-Carnosine Following Ischemic Stroke in Mice.

l-carnosine is an attractive therapeutic agent for acute ischemic stroke based on its robust preclinical cerebroprotective properties and wide therapeutic time window. However, large doses are needed for efficacy because carnosine is rapidly degraded in serum by carnosinases. The need for large doses could be particularly problematic when translating to human studies, as humans have much higher levels of serum carnosinases. We hypothesized that d-carnosine, which is not a substrate for carnosinases, may have a better pharmacological profile and may be more efficacious at lower doses than l-carnosine. To test our hypothesis, we explored the comparative pharmacokinetics and neuroprotective properties of d- and L-carnosine in acute ischaemic stroke in mice. We initially investigated the pharmacokinetics of d- and L-carnosine in serum and brain after intravenous (IV) injection in mice. We then investigated the comparative efficacy of d- and l-carnosine in a mouse model of transient focal cerebral ischemia followed by in vitro testing against excitotoxicity and free radical generation using primary neuronal cultures. The pharmacokinetics of d- and l-carnosine were similar in serum and brain after IV injection in mice. Both d- and l-carnosine exhibited similar efficacy against mouse focal cerebral ischemia. In vitro studies in neurons showed protection against excitotoxicity and the accumulation of free radicals. d- and l-carnosine exhibit similar pharmacokinetics and have similar efficacy against experimental stroke in mice. Since humans have far higher levels of carnosinases, d-carnosine may have more favorable pharmacokinetics in future human studies.

Assessment of Undercuts Relative to Abutment Teeth and Edentulous Area: A Retrospective Cross-sectional Study.

AIM: Undercuts on abutment teeth (AT) should be identified and quantified to establish the exact location of the active tip of the retentive arm of the direct retainer. The aim of this study was to locate and evaluate tissue and tooth undercut areas in various Kennedy's classes and to assess the correlation, if any, between Kennedy's classes and the location and depth of undercuts. MATERIALS AND METHODS: One hundred and seven patients' casts, with designated AT and edentulous areas (EAs), were surveyed. The undercuts on AT and EAs were measured using undercut gauges. Statistical analysis was performed. RESULTS: The median depth of the undercut was maximum on distal the surface of mandibular AT in a Kennedy's class III edentulous situation. No significant difference was found between the amount of tissue undercuts measured on the EA in each of the Kennedy's classes in the maxillary and mandibular arches. CONCLUSION: No significant difference was found between the amounts of undercut measured on AT and the EA in each of the Kennedy's classes in the maxillary and mandibular arches. No correlation was found between Kennedy's classes and the location and depth of undercuts. CLINICAL SIGNIFICANCE: The results of our study reinforce that the diagnosis and selection of ideal abutments should be stressed while planning for a removable dental prosthesis (RDP). In the majority of the cases, the anticipated design of the direct retainer can be applied, though one cannot overlook the need for proper diagnosis and survey.

High-resolution metabolic mapping of gliomas via patch-based super-resolution magnetic resonance spectroscopic imaging at 7T.

OBJECTIVES: To demonstrate the feasibility of 7 T magnetic resonance spectroscopic imaging (MRSI), combined with patch-based super-resolution (PBSR) reconstruction, for high-resolution multi-metabolite mapping of gliomas. MATERIALS AND METHODS: Ten patients with WHO grade II, III and IV gliomas (6/4, male/female; 45 ±â€¯9 years old) were prospectively measured between 2014 and 2018 on a 7 T whole-body MR imager after routine 3 T magnetic resonance imaging (MRI) and positron emission tomography (PET). Free induction decay MRSI with a 64 × 64-matrix and a nominal voxel size of 3.4 × 3.4 × 8 mm³ was acquired in six minutes, along with standard T1/T2-weighted MRI. Metabolic maps were obtained via spectral LCmodel processing and reconstructed to 0.9 × 0.9 × 8 mm³ resolutions via PBSR. RESULTS: Metabolite maps obtained from combined 7 T MRSI and PBSR resolved the density of metabolic activity in the gliomas in unprecedented detail. Particularly in the more heterogeneous cases (e.g. post resection), metabolite maps enabled the identification of complex metabolic activities, which were in topographic agreement with PET enhancement. CONCLUSIONS: PBSR-MRSI combines the benefits of ultra-high-field MR systems, cutting-edge MRSI, and advanced postprocessing to allow millimetric resolution molecular imaging of glioma tissue beyond standard methods. An ideal example is the accurate imaging of glutamine, which is a prime target of modern therapeutic approaches, made possible due to the higher spectral resolution of 7 T systems.

Relationship between Retinal Thickness Profiles and Visual Outcomes in Young Adults Born Extremely Preterm: The EPICure@19 Study.

PURPOSE: To quantify inner and outer retinal layer thicknesses and understand their relevance to visual function among young adults born extremely preterm (EP). DESIGN: Prospective observational study with 19 years of follow-up. PARTICIPANTS: A total of 354 eyes (226 eyes of former EP infants and 128 age-matched full-term control eyes) from 177 young adults were evaluated. Among EP participants, 50% of eyes (112/226) were not previously diagnosed with neonatal retinopathy of prematurity (ROP), 38% of eyes (84) had ROP not deemed to require treatment in the neonatal period, and 13% of eyes (30) had neonatal cryotherapy or laser ablation for ROP. METHODS: Subjects underwent eye examinations including best-corrected visual acuity (BCVA) and Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) macular spectral-domain (SD) OCT imaging. Retinal layers were auto-segmented and thickness profiles were computed at the fovea by the instrument software. MAIN OUTCOME MEASURES: Correlation between retinal sublayer thickness and BCVA. RESULTS: Compared with control eyes, the inner and outer retinal layers of EP eyes were significantly thicker and BCVA was significantly reduced. Retinal layer thicknesses and BCVA were similar for untreated EP eyes and those without neonatal ROP. In contrast, treated eyes had increased inner and outer retinal layer thickness and decreased vision. Inner retinal layer thickness was moderately correlated with worse BCVA (r = 0.30, P < 0.001), but outer retinal layer thickness was not (r = -0.01, P = 0.80). Multivariate regression indicated ganglion cell layer thickness was a significant independent predictor of BCVA. CONCLUSIONS: Extremely premature birth influences maturation of the fovea and visual outcomes into early adult life. Increased ganglion cell layer thickness was associated with worse BCVA. Eyes requiring neonatal treatment for ROP had associated worse BCVA at the age of 19 years.

Animal models of multiple sclerosis: From rodents to zebrafish.

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disease of the central nervous system. Animal models of MS have been critical for elucidating MS pathological mechanisms and how they may be targeted for therapeutic intervention. Here we review the most commonly used animal models of MS. Although these animal models cannot fully replicate the MS disease course, a number of models have been developed to recapitulate certain stages. Experimental autoimmune encephalomyelitis (EAE) has been used to explore neuroinflammatory mechanisms and toxin-induced demyelinating models to further our understanding of oligodendrocyte biology, demyelination and remyelination. Zebrafish models of MS are emerging as a useful research tool to validate potential therapeutic candidates due to their rapid development and amenability to genetic manipulation.

Native ureteroureterostomy in renal allograft recipient surgery: A single-center 5-year experience.

INTRODUCTION: In renal transplant, surgeons use a myriad of ureteral anastomotic techniques. Although ureteroneocystostomy (UNC) using Lich-Gregoir extravesical anastomosis is used most commonly, ureteroureterostomy with native ureter has its own importance in certain situations. MATERIALS AND METHODS: We retrospectively reviewed records of patients who underwent renal transplantation at our center from March 2011 to February 2016. Records of patients who underwent ureteroureterostomy with the native ureter were reviewed for the indications and complications of the procedure. RESULTS: Of 1050 renal transplants during the study period, 32 patients underwent native ureteroureterostomy. Among these 32 patients, 20 patients were planned preoperatively for native ureteroureterostomy (elective), and intraoperative decision was made in 12 patients (emergency). On follow-up, only one patient had ureteral obstruction due to kink just distal to ureteroureterostomy and was managed by double-J stenting. Other patients had an expected postoperative course. CONCLUSION: In our experience, ureteroureterostomy with native ureter is technically and functionally good option for ureteric reimplantation in kidney transplant patients. It can be used selectively for elective and emergency situations where UNC is not possible. Hence, the kidney transplant surgeon should be well versed with both techniques.