Improvement of chronic HCV infection-related depression, anxiety, and neurocognitive performance in persons achieving SVR-12: A real-world cohort study.

Chronic hepatitis C virus (HCV) infection is associated with neuropsychiatric changes. Also, patients with cirrhosis may develop overt or minimal hepatic encephalopathy. Sustained virological response (SVR) with direct-acting antiviral agents (DAAs) may improve the neuropsychiatric manifestations and quality of life (QoL). Consecutive patients (with and without cirrhosis, all genders and aged 18-65 years) with hepatitis C were assessed at enrolment and at 12 weeks after therapy completion for mood (Beck's Depression Inventory [BDI]), anxiety (generalized anxiety disorder [GAD-7]), QoL (SF-36 ver.2) and computer-based tests for number connection (NCT), visual memory, Stroop test and reaction times. We recruited 385 viraemic chronic HCV patients (76.1% male, 21.0% cirrhotic, mean age 39.4 ± 14.2 years, 59.3% genotype 3, mean HCV RNA load 5.8 log). Overall SVR-12 rates were 90.6%, with cure rates 87.6% and 91.4% in patients with and without cirrhosis, respectively. Patients who achieved SVR-12 had mean percentage reduction in BDI (11.3%, p = .000), GAD (8.6%, p = .001) and Stroop test (58.4%, p = .001), with improved NCT (1.7%, p = .001), visual memory (13.7%, p = .001) and digit span (23.8%, p = .002). On multivariate logistic regression, adherence (OR, 17.5 [95% CI 2.80-110.50], p = .000), high ALT (OR 1.02 [95% CI 1.00-1.05]), and BDI score (OR 1.73 [95% CI 1.42-3.26] p = .039) predicted cure. SVR-12 was associated with improved visual memory ≥5.5 (AUC-0.708; sensitivity 62.5%, specificity 63%, p = .000) and % correct Stroop test responses >26.6% (AUC-0.918, sensitivity 94.4% specificity 80.4%, p = .000). In conclusion, given the cumulative evidence of the safety of DAAs and efficacy of improving cognitive and neuropsychological and quality-of-life outcomes irrespective of age and gender, as shown in our study, future recommendations should focus on integrated universal HCV care to enable HCV elimination.

Comparative Evaluation of Implant Stability, Insertion Torque, and Implant Macrogeometry in Different Bone Densities Using Resonance Frequency Analysis.

AIM AND OBJECTIVE: Evaluation and comparison of insertion torque (IT) and the implant stability of two different implant macrogeometry in different bone densities using resonance frequency analysis. MATERIALS AND METHODS: A total of 48 implants (with two implant types having regular and novel macrogeometry) were classified into 4 groups with 12 samples in each group. Group A regular implant without surface treatment, group B regular implant with surface treating, group C novel implant deprived of surface treating, and group D was new dental implant with surface treatment were used. Implant stability quotient (ISQ), implant IT, removal torque (RT) percentage, and torque reduction percentage were calculated. RESULTS: The mean ± SD ISQ value of bone 1 in group A was 56.7 ± 3.2, in group B was 58.6 ± 2.4, in group C was 57.1 ± 3.5, and in group D was 59.3 ± 2.9. In bone 2, the value was 57.8 ± 1.4, 59.5 ± 1.5, 58.2 ± 2.6, and 59.5 ± 2.4 among A, B, C, and D groups correspondingly. In bone 3, it was 59.4 ± 2.4, 60.3 ± 2.3, 60.4 ± 2.8, and 62.7 ± 2.5 among A, B, C, and D groups correspondingly. In bone 4, it was 67.2 ± 3.4, 69.5 ± 2.7, 68.7 ± 2.4, and 69.4 ± 2.3 among A, B, C, and D groups correspondingly. There was a substantial difference in IT and nonsignificant difference in RT in different groups. CONCLUSION: There was a low IT value with new implant macrogeometry as compared to regular implant macrogeometry. There was absence of association between IT and implant stability. CLINICAL SIGNIFICANCE: Calculation of torque insertion score helps in implant placement. Higher bone density scores produce a higher option of decreasing the initial torque. Low IT of new implant types is useful to reduce failure.

Decentralized care with generic direct-acting antivirals in the management of chronic hepatitis C in a public health care setting.

BACKGROUND & AIMS: The prevalence of anti-hepatitis C virus antibody in Punjab, India is 3.6%, with 728,000 people estimated to have viremic chronic hepatitis C (CHC). The Mukh-Mantri Punjab Hepatitis C Relief Fund, launched on 18th June 2016, provides no-cost generic direct-acting antivirals (DAAs) with sofosbuvir + ledipasvir ±â€¯ribavirin or sofosbuvir + daclatasvir ±â€¯ribavirin with the goal of eliminating CHC from Punjab. We assessed the safety and efficacy of decentralized treatment of CHC in a public health care setting. METHODS: Primary care providers from 3 university and 22 district hospitals were trained to provide algorithm-based DAA treatment and supervised by telehealth clinics conducted fortnightly. The diagnosis of cirrhosis was based on clinical and radiological evidence, including aspartate aminotransferase-to-platelet ratio index (APRI ≥2.0) and FIB-4 score (>3.25), or on liver stiffness measurement ≥12.5 kPa on Fibroscan®. RESULTS: We enrolled 48,088 individuals with CHC (63.8% male; mean age 42.1 years; 80.5% rural; 14.8% compensated cirrhosis; 69.9% genotype [GT] 3) between 18th June 2016 to 31st July 2018. While 36,250 (75.4%) patients completed treatment, 5,497 (11.4%) had treatment interruptions and 6,341 (13.2%) patients are currently ongoing treatment. Sustained virological response at 12 weeks after treatment completion (SVR12) was achieved in 91.6% of patients per protocol, 67.6% in intention-to-treat (ITT) analysis, where all interruptions were treated as failures, and 91.2% in a modified ITT analysis where all patients with successful SVR12 in the interruptions arm were included as cured. SVR12 rates in patients with and without cirrhosis and GT3 versus non-GT3 were comparable. The SVR12 rate was 84.4% in patients who had treatment interruptions. CONCLUSION: Decentralized care of patients with CHC using generic all-oral DAA regimens is safe and effective regardless of genotype or presence of cirrhosis. ClinicalTrials.gov number: NCT01110447. LAY SUMMARY: We assessed the safety and efficacy of public health care using no-cost all-oral generic direct-acting antiviral drugs against hepatitis C in the state of Punjab, India. The goal is elimination of chronic hepatitis C (CHC) by 2030 and involves primary care providers at 25 sites in the state. We enrolled 48,088 individuals (63.8% male; mean age 42.1 years; 80.5% rural; 14.8% compensated cirrhotic; 69.9% genotype 3) between 18th June 2016 to 31st July 2018. Cure was achieved in 91.6% of patients, demonstrating that decentralized care of CHC with generic all-oral regimens is safe and effective.

Direct-acting antiviral Therapy Is Safe and Effective in Pediatric Chronic Hepatitis C: The Public Health Perspective.

OBJECTIVES: We assessed the efficacy of decentralized public health services and safety of direct-acting antiviral agents (DAAs) in the treatment of pediatric chronic hepatitis C (CHC) in the Mukh-Mantri Punjab Hepatitis C Relief Fund, a public-health initiative for prevention and control of CHC in Punjab, India. METHODS: Consecutive children with CHC [age ≥12 to <18 years; both treatment-naïve (TN) and treatment-experienced (TE)] were enrolled. Genotyping was not recommended for non-cirrhotic patients and were treated with sofosbuvir (SOF)+ daclatasvir (DCV) for 12 weeks, while genotyping was recommended for patients with cirrhosis. Patients with cirrhosis and genotype (G2) were treated with SOF+DCV+ribavirin (RBV) for 12 weeks, G3 with SOF+DCV+RBV for 24 weeks and G1, 4, 5, and 6 patients were treated with SOF+ledipasvir (LDV)+RBV for 12 weeks. Treatment duration was increased to 24 weeks if RBV was not tolerated. RESULTS: In the first 16 months (June 18, 2016-October 31, 2017), 88 children (mean age 15.8 years; 69.3.3% boys, 72.3% rural) were enrolled. The mean baseline hepatitis C virus RNA log10 IU/mL was 6.0 (range 4.2-7.5 log10 IU/mL), 65.5% with G3, and 2 (2.5%) with cirrhosis. Of 57 with completed treatment, sustained virological response (SVR) 12 was achieved in 56 (98.2%). Unsafe medical practices (55.5%), IV drug abuse (11.1%), and prior surgery (2.7%) were risk-factors for transmission (n = 36). Comparable results were noted in G3 (SVR at 12 weeks [SVR12], 94.3%) versus non-G3 (SVR12, 100%; P = 0.073). No serious adverse effects like anemia and decompensation were reported. CONCLUSIONS: The study demonstrates that the decentralized algorithm-based public-health program can ensure high efficacy (SVR12, 98.2%) and low-cost DAA-based treatment of pediatric patients with CHC.

Comparative Analysis of Local Anesthetic Techniques for Pain Management in Pediatric Dental Procedures: A Randomized Clinical Trial.

Objective: The present study aims to conduct a comparative analysis of different local anesthetic techniques for pain management in pediatric dental procedures. Goal is to evaluate and compare the efficacy and safety of various local anesthetic methods to identify the most effective approach in reducing pain and discomfort during dental treatments in children. Methods: A prospective, randomized clinical trial was conducted with 60 pediatric patients (aged 3 to 10 years) undergoing dental procedures in a single dental clinic. The participants were randomly assigned into three groups: Group A received conventional infiltration anesthesia (lidocaine 2% with epinephrine 1:100,000), Group B received topical anesthesia followed by the same infiltration anesthesia, and Group C received intraosseous anesthesia using articaine 4% with epinephrine 1:100,000. The patients' demographic data, treatment details, and pre-procedure anxiety levels were recorded. Results: The study demonstrated that all three local anesthetic techniques effectively managed pain during pediatric dental procedures. However, Group C, which received intraosseous anesthesia, showed significantly lower pain scores (mean ± standard deviation) compared to Group A and Group B: 1.5 ± 0.6, 2.3 ± 0.8, and 2.1 ± 0.7, respectively (P < 0.05). Additionally, Group C exhibited a shorter onset of anesthesia compared to Group A and Group B, with mean onset times of 1.8 ± 0.4, 3.2 ± 0.6, and 2.9 ± 0.5 minutes, respectively (P < 0.001). No significant differences in adverse events or post-procedure complications among the groups. Conclusion: Intraosseous anesthesia (articaine 4% with epinephrine 1:100,000) was found most effective local anesthetic technique for pain management during pediatric dental procedures.

Antiplasmodial peptaibols act through membrane directed mechanisms.

Our previous study identified 52 antiplasmodial peptaibols isolated from fungi. To understand their antiplasmodial mechanism of action, we conducted phenotypic assays, assessed the in vitro evolution of resistance, and performed a transcriptome analysis of the most potent peptaibol, HZ NPDG-I. HZ NPDG-I and 2 additional peptaibols were compared for their killing action and stage dependency, each showing a loss of digestive vacuole (DV) content via ultrastructural analysis. HZ NPDG-I demonstrated a stepwise increase in DV pH, impaired DV membrane permeability, and the ability to form ion channels upon reconstitution in planar membranes. This compound showed no signs of cross resistance to targets of current clinical candidates, and 3 independent lines evolved to resist HZ NPDG-I acquired nonsynonymous changes in the P. falciparum multidrug resistance transporter, pfmdr1. Conditional knockdown of PfMDR1 showed varying effects to other peptaibol analogs, suggesting differing sensitivity.

A 6-year retrospective review of psychiatric emergency service utilization by school-age children.

To explore utilization patterns and associated clinical factors of school-age children who present to a psychiatric emergency department. This was a 6-year retrospective chart review study of children 5-12 years of age who presented to a psychiatric emergency service from July 2012 to June 2018 (n = 1654 patients). Demographic variables, clinical diagnoses, lifetime adverse events (physical abuse, sexual abuse, and bullying), and history of self-harm were documented for each visit. We performed a chi square analysis to identify association between demographic and clinical features with key outcomes. Increased service utilization as defined by inpatient psychiatric admission, recurrent visits, or increased length of stay were found in patients who were adopted, presented with suicidal ideation or self-harm behaviors, had a history of abuse, and had a diagnosis of depression or autism. Trends over the course of the study indicated a significantly increased percentage of patients presenting with suicidal ideation, bullying, and self-harm behaviors. The data add to the limited literature regarding school-age children with a psychiatric emergency. Increased emergency service utilization for certain subgroups of children and trends over the course of the study underscore the need for enhanced treatment options for individuals with certain demographic or clinical features, and increased outpatient, intermediate, and inpatient treatment options, as well as preventative care.

Simultaneous transcatheter dual valve replacement (mitral and tricuspid valves): a case report.

Background: Structural valve dysfunction in bioprosthetic heart valves necessitates redo replacement procedure that are associated with high mortality and morbidity. The transcatheter valve-in-valve (VIV) approach has emerged as a preferred option for patients requiring redo procedures due to structural valve degeneration. We report from India the first case of the simultaneous transcatheter dual VIV implantation (mitral valve and tricuspid valves) in a high-surgical-risk patient. Case summary: A 57-year-old female was presented with a history of rheumatic heart disease, post-mitral valve as well as tricuspid valve replacement (perimount 33 mm) 11 years back. Bioprosthetic heart valve was chosen probably due to limited life expectancy and compliance issues with monitoring of international normalised ratio (INR). She now presented with progressive dyspnoea, oedema, and palpitations (New York Heart Association Class III) for the last 6 months. The patient was scheduled for transcatheter dual valve replacement simultaneously. The procedure was successful with a favourable outcome, short hospital stays, and early recovery. Discussion: This is the first case of simultaneous transcatheter dual valve replacement reported from India, which is fluoroscopically guided and supported by TEE. It is a valuable and considerable option for patients with failing bioprosthesis valves who are at increased peri-operative risk.

An Evaluation of Malaria Surveillance System in Punjab, India, 2020.

Background: India accounted for 6% of global burden of malaria with 95% population residing in malaria endemic areas. However, Punjab is in the malaria elimination phase with annual parasite incidence (API) <1/1000 population. Objectives: We evaluated malaria surveillance system in Punjab using CDC's updated guidelines for evaluating public health surveillance systems to provide recommendations for strengthening the existing system and to overcome the challenges in the path of malaria free Punjab. Methods: We chose two districts of Punjab, Amritsar (lowest API) and Mansa (highest API), interviewed stakeholders, and performed a retrospective desk review. We evaluated the overall usefulness of the system and assessed seven attributes at state, district, health facility, and village level during July-August 2020. Results: In Punjab, there was progressive decline in the malaria cases from 2,955 cases in 2009 to 1,140 in 2019 and no malaria deaths since 2011. Regarding various attributes, overall score for flexibility was good (85.9%); average for simplicity (77%), acceptability (74%), data quality (74%), and timeliness (70%); and poor for representativeness (59%) and stability (57%). Conclusions: Malaria surveillance system was useful in analyzing the trends of morbidity and mortality and for generating data to drive policy decisions. To improve stability, representativeness, and acceptability, surveillance staff should not be engaged in supplemental work, and reports from private sector must be ensured. Supportive supervision and regular trainings should be carried out regarding reporting formats, guidelines, and timely epidemiological investigations to improve timeliness, data quality, and simplicity.

Data on ultrasound therapy as an adjuvant pain control method among Indian TMDS patients.

It is of interest to evaluate the efficacy of ultrasound therapy as an adjuvant pain control modality in dysfunctions of the temporomandibular joint. The study comprised 20 patients with TMJ issues who had received a clinical diagnosis of temporomandibular disorders (TMDS). These patients underwent independent VAS evaluations for the intensity of pain, opening and closing of the mouth, and soreness of the muscles of mastication, including the masseter muscle, medial pterygoid muscle, lateral pterygoid muscle, and temporalis muscle, as well as additional auxiliary muscles. The chosen patients received ultrasonic treatment. The mean value of mouth opening before therapy was 39.51cm, with SD values of 7.61 cm. The mean value of mouth opening after therapy was 42.91 cm with SD values of 6.08.The findings were statistically significant, with a p-valueof0.021. The mean value of VAS in the TMJ area before therapy was 8.41 with SD values of 2.11.There was a reduction in the mean values of VAS after therapy, which was 3.11 with SD values of 1.12. The findings were significant statistically, with a p-value equal to 0.001. Thus, ultrasonographic therapy for temporomandibular joint pain demonstrated a considerable improvement in pain reduction and mouth opening. It is possible to view this therapy as the adjuvant methodology to control pain in disorders of TMJ.

Intra-articular platelet-rich plasma injection versus hydrocortisone with local anesthetic injections for temporo mandibular disorders.

Disorders of temporomandibular joint (TMDs) are characterised by a variety of symptoms, including discomfort in the orofacial region, muscle tenderness, restricted jaw motion and noise at the joint. Additional neurological symptoms such as headaches, vertigo, heaviness, and altered vision may also coexist with TMDs. Because prostaglandin production is a critical mediator of inflammatory reaction and is inhibited by corticosteroids, they have anti-inflammatory effects. Platelet rich plasma popularly considered as PRP is a concentration of platelets and related growth factors that may have therapeutic effects by attracting, promoting, and differentiating cells as well as redesigning tissue. 64 joints totaling 40 individuals with temporomandibular joint problems were split into two categories (Category A and Category B). PRP was applied to category A's (36 joints of 20 patients) joints, while Group B's joints received hydrocortisone combined with local anaesthetic (28 joints of 20 patients). Patients were evaluated for tenderness, , maximum inter incisal opening (MIO) and clicking sound at TMJ prior to and following treatment at intervals of one week, one month and 6 months of the first week and third month. When there was comparison of outcomes in study participants receiving injections of platelet rich plasma and study participants receiving injections of hydrocortisone with local anesthetic then it was found that although both type of study participants got reduction in pain, increased opening of mouth and reduction in clicking sound however the difference between two groups was not significant statistically. There was no statistically significant difference between injections of platelet rich plasma and hydrocortisone with local anesthetic solution regarding outcomes in disorders of temporomandibular joint, however the results were slightly better in study participants receiving platelet rich plasma injections. This study demonstrated that while treating patients with TMJ issues, local anaesthesia combined with hydrocortisone as well as intra-articular injection of PRP help in reduction in pain, increase mouth opening, and minimize joint sound. Additionally, it was discovered that intra-articular injection of PRP was more successful in treating patients in this trial than local anaesthetic combined with hydrocortisone.

Posterior corneal elevation after LASIK with three flap techniques as measured by Pentacam.

PURPOSE: To evaluate and compare posterior corneal changes using elevation data obtained from Pentacam (Oculus Optikgeräte GmbH) Scheimpflug imaging in eyes undergoing LASIK with three different modes of flap creation: IntraLase femtosecond laser FS60 (Abbott Medical Optics) (femtosecond group), Amadeus (Ziemer Group AG) mechanical microkeratome (keratome group), or flap formation using 20% alcohol laser epithelial keratomileusis (LASEK) (LASEK group). METHODS: Ninety myopic patients (90 eyes) undergoing refractive surgery were recruited. The change in posterior corneal elevation at 21 predetermined points in the central 5-mm area was measured using exported elevation data from the Pentacam before LASIK and 18 months postoperative and was compared among and within three modes of flap creation. RESULTS: Mean change in posterior elevation in the central 5-mm area was 5.13±4.16 µm for the femtosecond group, 5.78±4.42 µm for the keratome group, and 6.68±4.72 µm for the LASEK group and was similar among groups (P=.59). Change in posterior elevation before and after LASIK was not significant within any group (P=.342, P=.232, and P=.321 for the femtosecond, keratome, and LASEK groups, respectively). Preoperative spherical equivalent, central corneal thickness, ablation depth, and estimated residual bed thickness did not correlate with change in posterior corneal elevation for the femtosecond, keratome, or LASEK groups (P>.05). CONCLUSIONS: Using Pentacam elevation data, there were no significant changes in posterior corneal elevation following LASIK among or within the three methods of flap creation. At 18 months after LASIK, the posterior corneal surface is not displaced anteriorly significantly and is equally stable using these three surgical techniques.

Asymptomatic Incidental Pyogenic Hepatic Abscess in an Obese Adult.

A 35-year-old obese female patient presented to the emergency department (ED) endorsing symptoms of generalized weakness, dyspnea, and myalgia. Vitals on admission revealed hypotension, tachycardia, and a low-grade fever. Physical examination was unremarkable and was negative for any upper right quadrant tenderness or jaundice. Laboratory results revealed an elevated leukocytosis with a predominantly elevated neutrophil count, an elevated lactate dehydrogenase, aminotransferases, and an elevated anion gap. Sepsis protocol was initiated. Blood cultures revealed Group F Streptococcus. A chest x-ray for localization of the primary infection source was significant for an incidental hypodense liver mass. A follow-up magnetic resonance imaging (MRI) without contrast revealed a left hepatic multiloculated enhancing lesion prompting the diagnosis of beta-hemolytic Group F Streptococcus pyogenic hepatic abscess (PHA). This unusual case seeks to inform that an obese patient (i.e., immunocompromised) with systemic signs (e.g., fever, hypotension, tachycardia) should warrant careful monitoring as well as the inclusion of pyogenic liver abscess in the differential workup as our patient's PHA was found incidentally on a chest x-ray. Appropriate management via sonographic guided drainage was initiated and systemic antibiotics were administered in both inpatient and outpatient settings, resulting in complete resolution of the hepatic abscess over the course of a month.

Transient Receptor Potential Canonical Channels in Health and Disease: A 2020 Update.

This 2020 Special Issue "TRPC channels" of Cells was dedicated to commemorating the 25th anniversary of discovery of the Transient Receptor Potential Canonical (TRPC) channel subfamily [...].

Outcomes of Real-World Integrated HCV Microelimination for People Who Inject Drugs: An expansion of the Punjab Model.

BACKGROUND: The prevalence of chronic hepatitis C (CHC) in People Who Inject Drugs (PWID) is 8-10% as compared to 3·6% in the general population in Punjab, India. We assessed the real-world efficacy and safety of free-of-charge generic direct-acting antivirals (DAAs), sofosbuvir with an NS5A inhibitor (ledipasvir, daclatasvir or velpatasvir)±ribavirin in the microelimination of CHC in PWID in a public health setting. METHODS: An integrated care team at 25 sites provided algorithm based DAAs treatment to PWID supervised by telemedicine clinics between 18th June 2016 and 31st July 2019. The primary endpoint was sustained virological response at 12 weeks (SVR-12); the secondary endpoints were treatment completion, adherence, safety, and adverse events. ClinicalTrials.gov number: NCT01110447. FINDINGS: We enrolled 3477 PWID (87·2% men; mean age 33·6±12·5 years; 83·8% rural; 6·8% compensated cirrhosis). While 2280 (65·5%) patients completed treatment, 1978 patients completed 12 weeks of follow up for SVR-12. SVR-12 was achieved in 91·1% of patients per protocol, 49.5% as per intention to treat (ITT) and 90·1% in a modified ITT analysis. Of 546 (15·7%) patients with treatment interruptions, 99 (19·7%) could be traced to test for SVR-12 with a cure rate of 77·8%. There were no major adverse events or consequent treatment discontinuation. INTERPRETATION: Integrated care of PWID with CHC with DAAs is safe and effective. Measures for reducing treatment interruptions will further improve outcomes. FUNDING: The Government of the state of Punjab, India under the Mukh Mantri Punjab Hepatitis C Relief Fund (MMPHCRF) project, funds the project.

Surveillance-based estimation of the malaria disease burden in a low endemic state of Punjab, India, targeted for malaria elimination.

BACKGROUND: The state of Punjab in India qualifies for malaria elimination because the number of cases reported through routine surveillance is in decline. However, surveillance system prevalence mainly provides malaria trends. Therefore, a prospective epidemiological study was designed to estimate the malaria burden in the state. METHODS: District-wise annual parasite incidence (API) was used for identification of three strata, representing high, moderate and low API zones. A total of 0.9 million people from nine districts was under malaria surveillance for 1 y. The weighted estimates of API for the three regions was calculated and combined to give an estimate of API for the total population of the state. RESULTS: Based upon the primary data generated, malaria cases from high, moderate and low malaria-endemic areas were estimated to be 3727, 904 and 106, respectively. Further, the total number of malaria cases in the state was estimated to be 4737 (95% CI 4006 to 5469) cases per annum. CONCLUSION: Actual burden of malaria in the state of Punjab, India, is about seven to eight times higher than that reported by routine surveillance activities. However, the state still qualifies for malaria elimination but needs vigorous efforts to strengthen the active surveillance and reporting system along with implementation of effective control strategies to achieve malaria elimination.

Analysis of the evolutionary forces in an immunodominant CD8 epitope in hepatitis C virus at a population level.

Failure of the adaptive immune response to control infection with the hepatitis C virus (HCV) can result from mutational escape in targeted T-cell epitopes. Recent studies suggest that T-cell immune pressure is an important factor in the evolution of the nonstructural proteins in HCV. The aim of this study was to characterize the forces that contribute to viral evolution in an HLA-A*01-restricted epitope in HCV NS3. This epitope represents a potentially attractive target for vaccination strategies since it is conserved across all genotypes. In our cohort of subjects with chronic HCV infection (genotype 1b or 3a), it is a frequently recognized CD8 epitope in HLA-A*01-positive subjects. Viral sequence data reveal that an escape variant is the dominant residue in both genotypes. The predominant Y1444F substitution seemingly impairs binding to the HLA-A*01 molecule, which may have an important impact on the ability to prime a functional CD8 response upon infection. Interestingly, a case of evolution toward the prototype sequence was observed during chronic infection, possibly because the helicase activity of the protein containing the Y1444F substitution is reduced compared to the prototype sequence. Comparison of HCV sequences from Asia and Europe suggests that the frequency of the HLA-A*01 allele in a population may influence the frequency of the escape variant in circulating strains. These data suggest a complex interaction of multiple forces shaping the evolution of HCV in which immune pressure both within the individual and also at the population level in addition to functional constraints are important contributing factors.

Correlation of nuclear cataract lens density using Scheimpflug images with Lens Opacities Classification System III and visual function.

PURPOSE: To calculate the average lens density (ALD) and nuclear lens density (NLD) using Scheimpflug images and to determine their correlation with logarithmic minimal angle resolution (logMAR) best-corrected visual acuity (BCVA), contrast sensitivity (CS), and lens grading based on the Lens Opacities Classification System (LOCS) III. DESIGN: Cross-sectional observational study. PARTICIPANTS: One hundred ten patients with age-related nuclear cataract. METHODS: The logMAR BCVA was recorded using Early Treatment Diabetic Retinopathy Study charts and photopic contrast-sensitivity using CSV-1000LV (Vector Vision, Greeneville, OH). Fifty Scheimpflug images (Pentacam, Oculus, Germany) covering 360 degrees of the lens were obtained for 1 eye of each patient after dilation. All Scheimpflug images were exported to ImageJ software (NIH, Bethesda, MD) for analysis wherein the ALD and NLD (using a mask applied to the lens nuclear area) were calculated in pixel-intensity units. Repeatability was determined using coefficient of variation (CoV) and intraclass correlation coefficient (ICC). Lens opacity on slit-lamp images was graded using LOCS III for nuclear opalescence (NO) and nuclear color (NC). MAIN OUTCOME MEASURES: We evaluated ALD and NLD on Scheimpflug images and their correlation with NO and NC LOCS III grading, BCVA, and photopic CS. RESULTS: The ICC for ALD and NLD were 0.983 and 0.99, respectively; the CoV were 3.92+/-1.76% and 2.57+/-0.74%, respectively. The ALD correlated with NO (r = .774; P<0.001), NC (r = .732; P<0.001), BCVA (r = 0.696; P<0.001), and CS at 3 cycles per degree CPD (P = 0.011), 6, 12, and 18 CPD (P<0.001). The NLD correlated with NO (r = .859; P<0.001), NC (r = .81; P<0.001), BCVA (r = .760; P<0.001), CS at 3 CPD (P = 0.002), 6, 12, and 18 CPD (P<0.001). The NLD had a significantly stronger correlation with BCVA (P<0.05), NO (P<0.01), NC (P<0.01), and CS at 6 CPD (P<0.01) and 12 CPD (P<0.005) compared with ALD. CONCLUSIONS: Repeatable 360 degrees lens density measurements were obtained using Scheimpflug imaging. A stronger correlation was observed between NLD and LOCS III grading, BCVA, and photopic CS than with ALD. The NLD is an objective and repeatable method for assessment of lens density, which could be helpful in longitudinal studies monitoring nuclear cataracts.

Maxillary Osteomyelitis in a Patient with Pansinusitis and Recently Diagnosed Focal Segmental Glomerulosclerosis.

Given the rarity of osteomyelitis of the maxilla, a confirmed diagnosis requires extensive investigation into the possible underlying causes of the disease. The most common causes of osteomyelitis of the jaw are periodontal infections and sinusitis with contiguous seeding and infection of the bone. Even in those affected by these potential causes, an immunocompromised state is usually present for an extensive infection to occur. Early recognition is key for ensuring appropriate treatment and avoidance of life-threatening complications. We report a case of maxillary osteomyelitis in a patient with no clear predisposing risk factors, a history of recurrent pansinusitis, and recently diagnosed focal segmental glomerulosclerosis. Cultures of the bone revealed multiple bacterial and fungal organisms. He was treated with surgical debridement, teeth extraction, and a prolonged course of antifungals and antibiotics.