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Michael J Ang,1 Jeanne A Darbinian,2 Eliza N Hoskins,3 Douglas S Holsclaw,3 Sudha Sudesh,3 Naveen S Chandra3 1Department of Ophthalmology, California Pacific Medical Center, San Francisco, CA, USA; 2Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA; 3Department of Ophthalmology, The Permanente Medical Group, Oakland, CA, USACorrespondence: Naveen S Chandra, The Permanente Medical Group, 320 Lennon Lane, Walnut Creek, CA, 94598, 94598, Tel +1 925-906-2550, Fax +1 925-906-2332, Email Naveen.Chandra@kp.orgPurpose: To determine the occurrence of early post-operative complications following FDA-approved epithelium-off corneal cross-linking in the United States.Materials and Methods: This multicenter, retrospective cohort study identified patients who underwent epithelium-off (epi-off) corneal cross-linking (CXL) for keratoconus and post-refractive keratectasia within the Kaiser Permanente Northern California healthcare system between 2016 and 2018. Post-operative complications including delayed epithelial healing, infection, and loss of visual acuity were recorded.Results: The study included 878 eyes of 654 patients. The mean age was 27± 9.4 years (range 7– 71). Five hundred ninety-nine patients (91.6%) had keratoconus while 55 had post-refractive corneal ectasia (8.4%). Forty-seven eyes had prolonged follow-up because of the occurrence of complications in the early post-operative period. The respective rates of delayed epithelial healing, and keratitis were 3.9% (95% CI 2.7– 5.3%), and 1.5% (95% CI 0.8– 2.5%). Four approaches for management of delayed epithelial healing were compared; epithelium healing duration was the longest in the repeat bandage contact lens (BCL) group (23.8 days) and the shortest in the antibiotic ointment group (14.3 days), with statistically significant differences (p < 0.05) in the healing time between these 2 groups.Conclusion: The concern for early clinical complications after epi-off CXL often leads to delayed CXL intervention and further keratoconus progression with increased economic burdens. A large retrospective review of 878 eyes found that FDA-approved epi-off CXL protocol appears to be safe with low occurrence rates of early post-operative complications. The recommended management for delayed epithelial healing is using antibiotic ophthalmic ointment.Keywords: keratoconus, epithelium-off, corneal cross-linking, CXL, post-operative complications, epithelial healing

Purpose: To compare the effectiveness and safety of a single injection of subconjunctival triamcinolone acetonide (TA) with that of postoperative topical prednisolone acetate (PA) with and without nonsteroidal anti-inflammatory drugs (NSAIDs) for cataract surgery prophylaxis., Design: Retrospective, comparative effectiveness cohort study., Participants: Patients at Kaiser Permanente Northern California from 2018 through 2021., Intervention: Exposure groups included topical PA with or without NSAID and subconjunctival injection of TA (Kenalog; Bristol-Myers-Squibb) 10 mg/ml or 40 mg/ml in a low dose (1.0-3.0 mg) or high dose (3.1-5.0 mg)., Main Outcome Measures: The adjusted odds ratio (OR) and 95% confidence interval (CI) for the association of postoperative macular edema (ME) and iritis diagnoses 15 to 120 days after surgery (effectiveness measures) and a glaucoma-related event (safety measure) between 15 days and 1 year after surgery., Results: Of 69 832 eligible patient-eyes, postoperative ME, iritis, and a glaucoma-related event occurred on average in 1.3%, 0.8%, and 3.4% of eyes in the topical groups and 0.8%, 0.5%, and 2.8% of eyes in the injection groups, respectively. In multivariable analysis, compared with the PA reference group, the PA plus NSAID group had a lower OR of ME (OR, 0.88; 95% CI, 0.74-1.04; P = 0.135). and all injection groups had even lower odds, with the high-dose TA 10-mg/ml group reaching statistical significance (OR, 0.64; 95% CI, 0.43-0.97; P = 0.033). A trend of lower odds of a postoperative iritis diagnosis was noted in the high-strength (40 mg/ml) groups. For postoperative glaucoma-related events, compared with PA, the TA 10-mg/ml low-dose group showed lower odds (OR, 0.69; 95% CI, 0.55-0.86; P = 0.001), the TA 10-mg/ml high-dose group showed similar odds (OR, 0.90; 95% CI, 0.70-1.15; P = 0.40), and the TA 40-mg/ml low-dose and high-dose groups showed higher odds of an event occurring (OR, 1.46 [95% CI, 0.98-2.18; P = 0.062] and OR, 2.14 [95% CI, 1.36-3.37; P = 0.001], respectively)., Conclusions: The TA 10-mg/ml high-dose (4 mg) group was associated with a lower risk of postoperative ME and a similar risk of glaucoma-related events compared with the topical groups., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The host immune responses play a pivotal role in the establishment of long-term memory responses, which effectively aids in infection clearance. However, the prevailing anti-tuberculosis therapy, while aiming to combat tuberculosis (TB), also debilitates innate and adaptive immune components of the host. In this study, we explored how the front-line anti-TB drugs impact the host immune cells by modulating multiple signaling pathways and subsequently leading to disease relapse. Administration of these drugs led to a reduction in innate immune activation and also the cytokines required to trigger protective T cell responses. Moreover, these drugs led to activation-induced cell death in the mycobacterial-specific T cell leading to a reduced killing capacity. Furthermore, these drugs stalled the T cell differentiation into memory subsets by modulating the activation of STAT3, STAT4, FOXO1, and NFκB transcription factors and hampering the Th1 and Th17-mediated long-term host protective memory responses. These findings suggest the urgent need to augment directly observed treatment, short-course (DOTS) therapy with immunomodulatory agents to mitigate the adverse effects linked to the treatment.IMPORTANCEAs a central component of TB eradication initiatives, directly observed treatment, short-course (DOTS) therapy imparts immune-dampening effects during the course of treatment. This approach undermines the host immune system by delaying the activation process and lowering the immune response. In our investigation, we have unveiled the impact of DOTS on specific immune cell populations. Notably, the signaling pathways involving STAT3 and STAT4 critical for memory responses and NFκβ associated with pro-inflammation were substantially declined due to the therapy. Consequently, these drugs exhibit limited effectiveness in preventing recurrence of the disease. These observations highlight the imperative integration of immunomodulators to manage TB infection., Competing Interests: The authors declare no conflict of interest.

Introduction/aims: Although therapeutic electrical stimulation (TES) of injured peripheral nerve promotes axon regeneration and functional recovery, clinical applications of this therapy are limited to the intraoperative timeframe. Implantable, thin-film wireless nerve stimulators offer a potential solution to this problem by enabling delivery of electrical stimuli to an injured nerve over a period of several days post-surgery. The aim of this study was to determine the optimal time course of stimulation for maximizing functional recovery in a rat sciatic nerve isograft repair model., Methods: Adult male Lewis rats underwent thin-film wireless nerve stimulator implantation following sciatic nerve transection and 40 mm nerve isograft repair. Immediately after surgery, animals began a daily regimen of TES for up to 12 consecutive days. Functional recovery was assessed by compound muscle action potential (CMAP), evoked muscle force, wet muscle mass, and axon counting., Results: Serial CMAP measurements increased in amplitude over the course of the study, yet no significant difference between cohorts for serial or terminal CMAPs was observed. Axon counts and wet muscle mass measurements were greatest in the 6-day stimulation group, which correlated with a significant increase in evoked muscle force for the 6-day stimulation group at the terminal time point., Discussion: Six daily sessions of TES were found to be most effective for augmenting functional recovery compared to other time courses of stimulation. Future studies should incorporate additional subjects and track axonal sprouting or measure neurotrophin levels during the therapeutic window to further elucidate the mechanisms behind, and ideal amount of, TES., (© 2022 Wiley Periodicals LLC.)

Ocular drug delivery is a significantly challenging task due to the presence of various anatomical and physiological barriers in the eye. Naturally available polysaccharides, when used as drug vehicles provide increased retention time, bioavailability, and penetration due to their unique mucoadhesive and charge-possessing nature. This review discusses the polysaccharide-based drug delivery system for the eye. Polysaccharides like alginic acid, cellulose derivatives, chitosan, pectin, xanthan gum, gellan gum, and hyaluronic acid are reviewed in this report. Additionally, emphasis is given to some of the recently investigated polymers such as sugarcane bagasse cellulose, a polysaccharide extracted from the seeds of Manilkara zapota, and Tremella fuciformis polysaccharide as drug vehicles for effective ocular drug delivery. This review also provides insight on clinical status and FDA-approved polysaccharides for ophthalmic delivery of therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Rodent behavioral models with an electrophysiological component may require the joint operation of hardware from Med Associates, Inc. (St. Albans, VT) and Tucker-Davis Technologies (TDT; Alachua, FL). Although these manufacturers do produce supplemental hardware for interfacing with each other, investing in such hardware may be untenable for research groups with limited funds who wish to use equipment already in their possession., New Method: We designed a printed circuit board (PCB) in KiCad and had it fabricated by Advanced Circuits (Aurora, CO), with components sourced from Digi-Key (Thief River Falls, MN). The PCB provided 8 channels of bidirectional communication for the transmission of signals between Med Associates' SG-716B SmartCtrl connection panel and TDT's RZ5D base station. This setup enabled the coordinated operation of programs running separately on each set of hardware., Results: The custom-built PCB facilitated the joint operation of Med Associates and TDT hardware in a go/no-go detection task involving rats with electrical implants in their sciatic nerves., Comparison With Existing Methods: Conventional methods for interfacing Med Associates and Tucker-Davis Technologies rely on the purchase of pre-built hardware whose costs can add up to thousands of dollars. The present method offers a viable alternative that is easily implemented and considerably less expensive (below $200)., Conclusion: The present approach provides an inexpensive yet effective alternative to far more costly interfacing solutions offered by Med Associates and Tucker-Davis Technologies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Intuitive control of conventional prostheses is hampered by their inability to provide the real-time tactile and proprioceptive feedback of natural sensory pathways. The macro-sieve electrode (MSE) is a candidate interface to amputees' truncated peripheral nerves for introducing sensory feedback from external sensors to facilitate prosthetic control. Its unique geometry enables selective control of the complete nerve cross-section by current steering. Unlike previously studied interfaces that target intact nerve, the MSE's implantation requires transection and subsequent regeneration of the target nerve. Therefore, a key determinant of the MSE's suitability for this task is whether it can elicit sensory percepts at low current levels in the face of altered morphology and caliber distribution inherent to axon regeneration. The present in vivo study describes a combined rat sciatic nerve and behavioral model developed to answer this question. Approach: Rats learned a go/no-go detection task using auditory stimuli and then underwent surgery to implant the MSE in the sciatic nerve. After healing, they were trained with monopolar electrical stimuli with one multi-channel and eight single-channel stimulus configurations. Psychometric curves derived by the method of constant stimuli (MCS) were used to calculate 50% detection thresholds and associated psychometric slopes. Thresholds and slopes were calculated at two time points 3 weeks apart. Main Results: For the multi-channel stimulus configuration, the average current required for stimulus detection was 19.37 μA (3.87 nC) per channel. Single-channel thresholds for leads located near the nerve's center were, on average, half those of leads located near the periphery (54.92 μA vs. 110.71 μA, or 10.98 nC vs. 22.14 nC). Longitudinally, 3 of 5 leads' thresholds decreased or remained stable over the 3-week span. The remaining two leads' thresholds increased by 70-74%, possibly due to scarring or device failure. Significance: This work represents an important first step in establishing the MSE's viability as a sensory feedback interface. It further lays the groundwork for future experiments that will extend this model to the study of other devices, stimulus parameters, and task paradigms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chandra, McCarron, Yan, Ruiz, Sallinger, Birenbaum, Burton, Green, Moran, Ray and MacEwan.)

Antibiotic resistance has emerged as a threat to global health, food security, and development today. Antibiotic resistance can occur naturally but mainly due to misuse or overuse of antibiotics, which results in recalcitrant infections and Antimicrobial Resistance (AMR) among bacterial pathogens. These mainly include the MDR strains (multi-drug resistant) of ESKAPE ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter species). These bacterial pathogens have the potential to "escape" antibiotics and other traditional therapies. These bacterial pathogens are responsible for the major cases of Hospital-Acquired Infections (HAI) globally. ESKAPE Pathogens have been placed in the list of 12 bacteria by World Health Organisation (WHO), against which development of new antibiotics is vital. It not only results in prolonged hospital stays but also higher medical costs and higher mortality. Therefore, new antimicrobials need to be developed to battle the rapidly evolving pathogens. Plants are known to synthesize an array of secondary metabolites referred as phytochemicals that have disease prevention properties. Potential efficacy and minimum to no side effects are the key advantages of plant-derived products, making them suitable choices for medical treatments. Hence, this review attempts to highlight and discuss the application of plant-derived compounds and extracts against ESKAPE Pathogens., (© 2021 Published by Elsevier Ltd.)

Background: Supraglottic airway devices are used for anesthesia in elective surgical procedures circumventing the need for intubation. We investigated the efficacy and safety of Baska ® mask in comparison to an I-Gel ® device., Methods: In this cross-sectional, observational study, we randomized 100 female patients (age 18-45 years, American Society of Anaesthesiologists grade I or II) undergoing elective short gynecological procedures into two groups, to receive ventilation with either Baska mask ® (group 1, n = 50) or an I-Gel ® device (group 2, n = 50). We excluded patients with obesity, short neck, and known systemic and upper airway disorders. The primary outcome was the oropharyngeal airway seal pressure, and the secondary outcomes were the ease of insertion and the complication rate. The results were analyzed using Mann-Whitney U -test and Fisher's exact test, and correlation analysis was done by Spearman's correlation test., Results: A total of 56 patients underwent dilatation and curettage, whereas the remaining had hysteroscopy in the study. The airway seal pressure achieved was higher with Baska ® mask than I-Gel ® device (35.8 ± 10.3 and 26.9 ± 7.5 of cm H 2 O, respectively; P < 0.0001). The ease of insertion ( P < 0.0001) was better in group 1 and the complication rates were similar in both the groups ( P > 0.05)., Conclusion: Baska ® mask offers a superior airway seal pressure with minimum complications in comparison to an I-Gel ® device. Further studies with a large number of patients in different surgical settings are required to confirm our findings., Competing Interests: There are no conflicts of interest.

The mortality statistics of the medical patients at our tertiary care hospitals are sparse and lacking. We studied the mortality characteristics of the patients admitted to medical wards and intensive care unit at two hospitals based on the available fatal documents. Our objectives include analysis of the cause of death, duration of stay and presence of sepsis. The deceased (103 males, 47 females) had a mean age of 64.6 ± 15.5 yrs and mean duration of stay 7.1 ± 12.3 days. Infections and sepsis syndrome (33%), respiratory (17%), neurological (15%) and cardiovascular disorders (10%) were the top four causes of the mortality. Comorbid ailments were present in 71% of the deceased and the ventilator was used in 39% of them prior to the death. Age of the patients did not show any correlation with the duration of hospital stay ( P  = 0.8322). Infections and sepsis syndrome are the major reasons of death in medical patients. Mortality audit helps in identifying the prevalent causes of death in the hospital.

Inositol hexa phosphoric acid (IP6) or Phytic acid, a natural antioxidant of some leguminous plants, known to act as a protective agent for seed storage in plants by suppressing iron catalyzed oxidative process. Following the same mechanism, we have tested the effect of IP6 on iron overloaded in vitro oxidative stress, and studied it's in vivo hepatoprotective ability in iron-dextran (injection)-induced iron overloaded liver injury in mice (intraperitoneal). Our results showed that IP6 had in vitro iron chelation (IC 50 38.4μg/ml) activity, with the inhibition of iron-induced lipid peroxidation (IC 50 552μg/ml), and deoxyribose sugar degrading hydroxyl radicals (IC 50 448.6μg/ml). Oral administration of IP6 (0-200mg/kg) revealed significant decrease in biochemical markers such as serum iron, total iron binding, serum ferritin and serum enzymes. Histopathology of liver stained with hematoxylin-eosin and Prussian blue showed reduced hepatocellular necrosis, ballooning and inflammation, indicating the restoration of normal cellular integrity. Interestingly, the IP6 was found to down-regulate the mRNA expression of tumor necrosis factor (TNF)-α, Interleukin (IL)-1β, and IL-6 in iron overloaded liver tissues. Thus, we provide an insight that IP6, a natural food component, can serve as an iron chelator against iron overload diseases like Thalassemia, and also as a dietary hepatoprotective supplement., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The present study aimed at the molecular characterization of pathogenic and non pathogenic F. oxysporum f. sp. lycopersici strains isolated from tomato. The causal agent isolated from symptomatic plants and soil samples was identified based on morphological and molecular analyses. Pathogenicity testing of 69 strains on five susceptible tomato varieties showed 45% of the strains were highly virulent and 30% were moderately virulent. Molecular analysis based on the fingerprints obtained through ISSR indicated the presence of wide genetic diversity among the strains. Phylogenetic analysis based on ITS sequences showed the presence of at least four evolutionary lineages of the pathogen. The clustering of F. oxysporum with non pathogenic isolates and with the members of other formae speciales indicated polyphyletic origin of F. oxysporum f. sp. lycopersici. Further analysis revealed intraspecies variability and nucleotide insertions or deletions in the ITS region among the strains in the study and the observed variations were found to be clade specific. The high genetic diversity in the pathogen population demands for development of effective resistance breeding programs in tomato. Among the pathogenic strains tested, toxigenic strains harbored the Fum1 gene clearly indicating that the strains infecting tomato crops have the potential to produce Fumonisin.

Background: Natural product-inspired synthesis is a key incorporation in modern diversity-oriented synthesis to yield biologically novel scaffold. Inspired by β-carboline fused system, we have designed molecules with multi ring fused scaffold by modifying the tricyclic pyrido[3,4- b]indole ring with imidazo[1,2- a]isoquinoline., Methods: A highly convergent approach with new C-N and C-C bond formation to synthesize multiring fused complex scaffold imidazo[1,2- a]isoquinolinies as fluorophores. N-nucleophile-induced ring transformation of 2 H-pyran-2-one followed by in situ cis-stilbene-type oxidative photocyclization yielded new C-C bond formation without additional oxidant. The cytotoxicity, effective concentrations, and the mode of action of the synthesized analogs were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT),, plaque reduction, time of addition, and reverse transcriptase Polymerase Chain Reaction (PCR)., Results: Novel imidazo[1,2- a]isoquinoline analogs were prepared, and the results revealed that trans isomer of cyclopropyl analog (EC 50 35 and 37.5 µg/ml) and trans isomer of citric acid salt of phenyl analog (EC 50 38.2 and 39.8 µg/ml) possess significant anti-Herpes Simplex Virus (HSV) activity with selectivity index of >10. The kinetic study demonstrated that both the analogs inhibited HSV-1F and HSV-2G at 2-4 h postinfection. Finally, western blot and reverse transcriptase PCR assays revealed that both the analogs suppressed viral immediate early transcription., Conclusion: Novel imidazo[1,2- a]isoquinoline analogs were synthesized from pyranone with appropriate amines. Two compounds showed better antiviral profile on HSV-infected Vero cells, compared to the standard drug acyclovir (ACV). Overall, we discovered a promising scaffold to develop a nonnucleoside lead targeting the viral immediate early transcription for the management of HSV infections.

Two new megophthalmine species of leafhoppers, Igerna kolasibensis sp. nov. and I. shillongensis sp. nov., are described from India, Mizoram and Meghalaya, respectively. Detailed morphological descriptions, illustrations and photographs are provided. An updated key to the species and taxonomic notes on the genus are provided.

India is an endemic zone for hepatitis E virus (HEV), which is associated with both epidemic and sporadic infections. In West Bengal, only two hepatitis E outbreaks have been studied to date. However, sporadic cases of HEV infection also occur during inter-epidemic periods. The aim of this hospital-based study was to detect the prevalence of HEV infection in patients with acute sporadic hepatitis in West Bengal, India. Blood samples and clinical information were collected from 285 patients of both sexes and different ages with acute viral hepatitis (AVH) at Calcutta Medical College, Kolkata, a tertiary-care centre. Samples were tested for hepatitis B virus (HBV) surface antigen, anti-hepatitis C virus antibodies, anti-hepatitis A virus IgM and anti-HEV antibodies (IgM and IgG) by ELISA. Only those patients with AVH who were in their first week of illness and negative for all hepatotropic viral antibodies were tested for HEV RNA by reverse transcriptase nested PCR. HEV was identified as the most common cause of AVH (41.8% of patients), followed by HBV (21.4%), hepatitis A virus (17.2%) and hepatitis C virus (4.6%). Co-infections with more than one virus were found in 22 patients, with HBV-HEV the most common co-infection (3.8%). Only 14.7% of patients had no viral marker. To the best of our knowledge, this is the first documented epidemiological study of acute sporadic hepatitis with HEV in the state of West Bengal, India, indicating that this state is an endemic zone for HEV infection., (© 2014 The Authors.)

Background: Initial research has shown a negative correlation between the severity of periodontal disease and tissue inhibitor of matrix metalloproteinases (TIMPs) concentrations in gingival crevicular fluid (GCF). However, there are no enough reports to correlate the TIMP-1 concentrations in GCF in periodontal health, disease and after treatment. Hence, the present study aim is to estimate the levels of TIMP-1 in GCF in periodontal health, disease and to evaluate the effect of periodontal therapy on TIMP-1 concentrations in GCF., Materials and Methods: Periodontal examination and collection of GCF by extracrevicular method was performed in 25 subjects selected randomly and categorized into three groups. Group I (Healthy, n = 10), Group II (chronic periodontitis (CP), n = 15) and Group III (After treatment group, n = 15). Scaling and root planning was performed and GCF was collected after 8 weeks of treatment. TIMP-1 levels were estimated in GCF samples by using enzyme linked immunosorbent assay., Results: TIMPs-1 was detected in all samples. Highest mean TIMP-1 concentrations in GCF were obtained for Group I, whereas the lowest concentrations were seen in Group II. This suggests that TIMP-1 levels in GCF decreases proportionally with the progression of periodontal disease and increases after treatment., Conclusion: There is a substantial decrease in the concentrations of TIMP-1 in CP patients than in healthy and after treatment individuals. Since TIMP-1 levels in GCF are negatively correlated with periodontal disease, TIMP-1 may be considered as a biomarker in periodontal disease progression. However, controlled, longitudinal studies are needed to confirm this possibility.

Aim: To evaluate the applicability of the Tanaka and Johnston (1974) and Moyers (1988) methods in predicting the size of permanent canines and premolars in Chennai school children., Materials and Methods: 470 sets (127 female and 343 male) of cast models were included in the sample. Mesio-distal (m-d) widths of all teeth from left to right first molars were measured and compared with the predicted values derived from Tanaka and Johnston and Moyers methods., Results: There was significant bilateral symmetry and sexual dimorphism in teeth sizes seen in both the sexes. Sum of the m-d diameter of permanent mandibular incisors can be used reliably to predict the sum of m-d diameters of unerupted canines and premolars., Conclusions: Tanaka and Johnston's method cannot accurately predict the m-d widths. Moyers' prediction tables can be used to estimate the m-d widths of unerupted canines and premolars closer to 50% probability level.

Aim: To evaluate the in vitro antimicrobial activity of aqueous and methanol extracts of Odina wodier bark (OWB), a folk medicine, against representative bacteria, fungi and herpes simplex virus (HSV) associated with skin infections., Methods and Results: The OWB extract(s) was found to inhibit the isolates of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Klebsiella pneumonia, Escherichia coli at an MIC of 256-5000 μg ml(-1) and Candida albicans at and above 4000 μg ml(-1) by agar and broth dilution assays. The growth curve of Staph. aureus revealed the highest activity within 2-6 h of methanol extract (ME) exposure. Interestingly, the MTT and plaque reduction assay showed that the extracts can inhibit HSV-1 and HSV-2 at EC50 of 22·4 and 28·8 μg ml(-1) , with Selectivity index of 11·7-15. While the time kinetic and binding assays demonstrated that the ME at 50 μg ml(-1) prevents viral attachment into Vero cells. Phytochemical and HPLC analysis of ME revealed the presence of flavonoids, phytosterols, saponins and tannins including the pseudotannin chlorogenic acid., Conclusion: The traditional use of OWB for the management of skin infections has scientific basis., Significance and Impact of the Study: This study demonstrated the antimicrobial potential of OWB on selected isolates of bacteria, fungi and HSV, associated with skin infections., (© 2013 The Society for Applied Microbiology.)

Herpes genitalis, caused by HSV-2, is an incurable genital ulcerative disease transmitted by sexual intercourse. The virus establishes life-long latency in sacral root ganglia and reported to have synergistic relationship with HIV-1 transmission. Till date no effective vaccine is available, while the existing therapy frequently yielded drug resistance, toxicity and treatment failure. Thus, there is a pressing need for non-nucleotide antiviral agent from traditional source. Based on ethnomedicinal use we have isolated a compound 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole (HM) from the traditional herb Ophiorrhiza nicobarica Balkr, and evaluated its efficacy on isolates of HSV-2 in vitro and in vivo. The cytotoxicity (CC50), effective concentrations (EC50) and the mode of action of HM was determined by MTT, plaque reduction, time-of-addition, immunofluorescence (IFA), Western blot, qRT-PCR, EMSA, supershift and co-immunoprecipitation assays; while the in vivo toxicity and efficacy was evaluated in BALB/c mice. The results revealed that HM possesses significant anti-HSV-2 activity with EC50 of 1.1-2.8 µg/ml, and selectivity index of >20. The time kinetics and IFA demonstrated that HM dose dependently inhibited 50-99% of HSV-2 infection at 1.5-5.0 µg/ml at 2-4 h post-infection. Further, HM was unable to inhibit viral attachment or penetration and had no synergistic interaction with acyclovir. Moreover, Western blot and qRT-PCR assays demonstrated that HM suppressed viral IE gene expression, while the EMSA and co-immunoprecipitation studies showed that HM interfered with the recruitment of LSD-1 by HCF-1. The in vivo studies revealed that HM at its virucidal concentration was nontoxic and reduced virus yield in the brain of HSV-2 infected mice in a concentration dependent manner, compared to vaginal tissues. Thus, our results suggest that HM can serve as a prototype to develop non-nucleotide antiviral lead targeting the viral IE transcription for the management of HSV-2 infections.

Objective: Alteration in thyroid hormones are seen in critically ill patients admitted to intensive care units. Our objective was to study the thyroid hormone profile, prolactin and, glycosylated hemoglobin (HbA1c) at admission and analyze their correlation with mortality., Materials and Methods: In this single centre, prospective, observational study, 100 consecutive patients (52M; 48F) admitted to medical ICU irrespective of diagnosis were included. Patients with previous thyroid disorders and drugs affecting thyroid function were excluded. All participants underwent complete physical examination and a single fasting blood sample obtained at admission was analyzed for total triiodothyronine (T3), total thyroxine (T4), thyroid stimulating hormone (TSH), HbA1c, and prolactin. The patients were divided into two groups: Group 1 - survivors (discharged from the hospital) and Group 2 - nonsurvivors (patients succumbed to their illness inside the hospital). The data were analyzed by appropriate statistical methods and a P-value of <0.05 was considered significant., Results: The mean age of the participants was 58.7 ± 16.9 years and the mean duration of ICU stay was 3.3 ± 3.1 days. A total of 64 patients survived, whereas remaining 36 succumbed to their illness. The baseline demographic profile was comparable between survivors and nonsurvivors. Nonsurvivors had low T3 when compared with survivors (49.1 ± 32.7 vs. 66.2 ± 30.1, P = 0.0044). There was no significant difference observed between survivors and nonsurvivors with respect to T4, TSH, HbA1c, and prolactin., Conclusion: Our study showed that low T3 is an important marker of mortality in critically ill patients. Admission HbA1c, prolactin, T4, and TSH did not vary between survivors and nonsurvivors.

Background & Objectives: Hepatitis E virus (HEV) causes acute viral hepatitis. Majority of the documented studies on hepatitis E have been focused on the incidence of this disease in northern and south central India. Limited data are available on HEV infection among acute sporadic hepatitis cases in north western India. The present study was undertaken to investigate the contribution of hepatitis E virus infection in sporadic hepatitis cases in Rajasthan and neighbouring States., Methods: Seven hundred and thirty six patients suspected to have viral hepatitis were screened for the hepatotropic viral markers, hepatitis A, B, C and E by using commercial enzyme immunoassay kits with a high sensitivity and specificity. The acute nature of HEV infection was also confirmed by the detection of HEV RNA by nested RT-PCR., Results: Hepatitis E was found to be the major cause of acute sporadic viral hepatitis (49.7%) in this region of India. Mixed infections of HEV-HAV (1.2%), HEV-HBV (6.1%), and HEV-HCV (1.7%) were also detected. No viral marker was detected in 32 per cent cases., Interpretation & Conclusion: HEV was found as the major aetiological agent of acute sporadic viral hepatitis in Rajasthan (north western India). It is important to screen primarily for all the common enterically and parenterally transmitted hepatotropic viral markers in acute sporadic viral hepatitis. There is a need to do additional serological and molecular tests to identify the aetiological agent in the cases of acute hepatitis.

Purpose: The objective of this study was to report 2 cases of interface fungal keratitis in 2 separate patients following Descemet stripping automated endothelial keratoplasty (DSAEK) with tissue harvested from the same donor., Design: This was a retrospective simultaneous interinstitutional hosptial-based case reports., Methods: Two patients with corneal infections following DSAEK were identified from 2 individual practices. Both patients had undergone DSAEK from the same donor. Preoperative and postoperative eye examination included visual acuity, anterior and posterior segment evaluations, and clinical follow-up course from the time of surgery. Methods of medical therapy and surgical intervention are additionally discussed., Results: The 2 patients presented in our series present with interface fungal keratitis postoperatively in the face of the original source coming from a single donor (patient 1: 7 days postoperatively and patient 2: 7 weeks postoperatively). As medical treatment failed in both cases, surgery was undertaken in both cases (therapeutic penetrating keratoplasty). With prompt recognition as well as medical and surgical treatment, patient 1 achieved best corrected visual acuity of 20/30 at 6 months postoperatively, and patient 2 had best corrected visual acuity of 20/80 at 10 months postoperatively., Conclusions: Fungal keratitis following DSAEK occurs in a sequestered space and therefore represents a treatment challenge with potentially devastating outcome. We recommend an aggressive surgical approach with early removal of the donor button and irrigation with intracameral antifungal agents.

Genotyping and subtyping are important to understand epidemiology of the hepatitis E virus so as to improve control measures to prevent transmission of virus in the community. Hence, the aim of the current study was to identify the prevalent HEV genotypes in Rajasthan in acute sporadic hepatitis E cases with varying degree of liver failure. We studied hepatitis E virus (HEV) isolates from hospitalized patients in Rajasthan, western India. In a total of seventeen HEV sequences, six acute viral hepatitis, seven acute liver failure, and 4 acute- on-chronic cases were analyzed. Subtypes 1a and 1c of HEV are prevalent in Northwest India.

Recent developments in genomics have opened up for newer opportunities to study the diversity and classification of fungi. The genus Fusarium contains many plant pathogens that attack diverse agricultural crops. Fusarium spp. are not only pathogenic to plants but are also known as toxin producers that negatively affect animal and human health. The identification of Fusarium species still remains one of the most critical issues in fungal taxonomy, given that the number of species recognized in the genus has been constantly changing in the last century due to the different taxonomic systems. This review focuses of various molecular-based techniques employed to study the diversity of Fusarium species causing diseases in major food crops. An introduction of fusarial diseases and their mycotoxins and molecular-marker-based methods for detection introduce the concept of marker application. Various well-known molecular techniques such as random amplified polymorphic DNA, amplification fragment length polymorphism, etc. to more modern ones such as DNA microarrays, DNA barcoding, and pyrosequencing and their application form the core of the review. Target regions in the genome which can be potential candidates for generation of probes and their use in phylogeny of Fusarium spp. are also presented. The concluding part emphasizes the value of molecular markers for assessing genetic variability and reveals that molecular tools are indispensable for providing information not only of one Fusarium species but on whole fungal community. This will be of extreme value for diagnosticians and researchers concerned with fungal biology, ecology, and genetics.

Background: There is paucity of data regarding duration of fecal excretion and viremia on sequential samples from individual patients and its correlation with serum transaminases and antibody responses in patients with acute hepatitis E. This prospective study was undertaken at a tertiary care center in Northern India over 15 months. Only those patients of sporadic acute hepatitis E who were in their first week of illness and followed up weekly for liver function tests, IgM anti HEV antibody and HEV RNA in sera and stool were included. HEV RNA was done by RT - nPCR using two pairs of primers from RdRp region of ORF 1 of the HEV genome., Results: Over a period of 15 months 60 patients met the inclusion criterion and were enrolled for the final analysis. The mean age of the patients was 29.2 ± 8.92 years, there were 39 males. The positivity of IgM anti HEV was 80% at diagnosis and 18.3% at 7th week, HEV RNA 85% at diagnosis and 6.6% at 7th week and fecal RNA 70% at the time of diagnosis and 20% at 4th week. The maximum duration of viremia detected was 42 days and fecal viral shedding was 28 days after the onset of illness., Conclusion: Present study reported HEV RNA positivity in sera after normalization of transaminases. Fecal shedding was not seen beyond normalization of transaminases. However, viremia lasted beyond normalization of transaminases suggesting that liver injury is independent of viral replication.

Purpose: To evaluate the efficacy and safety of placement of Intacs in subjects with keratoconus., Design: Retrospective, nonrandomized comparative trial., Intervention: Intrastromal corneal ring segment implantation., Participants: Seventy-four eyes of 50 subjects (41 male and 9 female) were evaluated. The mean age of subjects in the study was 35 years, ranging from 20 to 73 years. Twenty-six subjects underwent single-eye treatment, and 24 subjects had both eyes treated., Methods: A modified Intacs procedure was performed on subjects with keratoconus. Pachymetry was measured at the incision site, and the incision was made at 66% of the corneal thickness. A thicker ring segment was typically placed inferiorly, and a thinner segment was placed superiorly on the basis of a refractive nomogram., Main Outcome Measures: Differences between preoperative and postoperative uncorrected visual acuity, best spectacle-corrected acuity, and spherical equivalent. Changes in irregular astigmatism were evaluated with the inferior-superior value from comeotopographic maps, and differences in refractive cylinder groups were studied., Results: Preoperative mean best-corrected logarithm of the minimum angle of resolution (LogMAR) visual acuity was 0.41 (20/50 - 1) (standard deviation [SD], +/-0.48), which improved to a postoperative mean of 0.24 (20/32 - 2) (SD, +/-0.31) (two lines of improvement). Preoperative mean uncorrected LogMAR visual acuity was 1.05 (20/200 - 2 1) (SD, +/-0.48), which improved to a mean of 0.61 (20/80-) (SD, +/-0.52) (four lines of improvement) at postoperative follow-up. Preoperative mean best-corrected LogMAR acuity in the corneal scarring group was 0.96 (20/200 + 2) (SD, +/-0.72), which improved to a mean of 0.54 (SD, +/-0.43) (20/63 - 2) (five lines of improvement). Uncorrected mean LogMAR acuity in the eyes with corneal scarring was 1.42 (20/400 - 4) (SD, +/-0.27), which improved to a mean of 1.03 (20/200 - 1) (SD, +/-73) (three lines of improvement). The mean spherical equivalent before surgery was -3.89 diopters (D) (SD, +/-5.16), which was reduced to a mean of -1.46 D (+/-4.11) at the postoperative follow-up., Conclusions: Asymmetric Intacs implantation can improve both uncorrected and best spectacle-corrected visual acuity and can reduce irregular astigmatism in corneas with and without corneal scarring.

Purpose: To describe a cluster of Mycobacterium chelonae keratitis cases involving patients who underwent laser in-situ keratomileusis (LASIK) at a single refractive surgery center., Design: Descriptive case series of four patients and cohort study to identify disease associations., Methods: Examination schedules, diagnostic tests, and therapy were based on best medical judgment. Isolates from three patients were compared by pulsed-field gel electrophoresis. Epidemiologic studies were performed to identify the source of infection., Results: Seven of eight eyes developed M. chelonae keratitis following bilateral simultaneous LASIK. Each patient was thought to have diffuse lamellar keratitis initially, but all seven eyes were noted to have opacities suggestive of infectious keratitis by 13 to 21 days after surgery. All eyes had undergone hyperopic LASIK over four days in April 2001 by one surgeon in a community-based refractive surgery center. A cohort study of all patients undergoing LASIK at the same center in April 2001 revealed that M. chelonae keratitis occurred only in persons undergoing correction of hyperopia (seven of 14 eyes vs. none of 217 eyes undergoing myopic LASIK, P <.001). The only difference identified between procedures was use of masks created from a soft contact lens in hyperopic LASIK. Three isolates (three patients) were indistinguishable by pulsed-field gel electrophoresis. Eyes were treated with a combination of antimicrobial agents, including topical azithromycin in three patients, with resolution of infection in all eyes over 6 to 14 weeks. The source of infection was not identified on environmental cultures., Conclusion: Postoperative nontuberculous mycobacterial keratitis can occur in an epidemic fashion following LASIK. Topical amikacin, azithromycin, clarithromycin, ciprofloxacin, or a combination of these agents, appears to be effective treatment for these infections.

The Sensory Organization Test (SOT) of dynamic posturography, a functional test of balance, has a low sensitivity for compensated unilateral peripheral vestibular lesions. Tilting the head 45 degrees laterally during SOT [i.e. lateral heat tilt (LHT) SOT] may better detect such lesions. Normal subjects and vestibular clinic patients were studied using SOT and LHT SOT. Caloric, rotational chair, and oculomotor testing were also performed for patients, in either a double-blind or non-double-blind manner. The results for both patient groups were similar and thus were collapsed. Normative LHT SOT performance ranges were established to be slightly lower than corresponding SOT scores, for subjects aged 20-59 years. Subjects in older age groups performed with similar equilibrium scores in both SOT and LHT SOT. Normal subjects aged 20-59 and 60-69 years performed similarly, whereas those aged 70-79 performed significantly worse. Sensitivity of LHT SOT to unilateral peripheral vestibular lesions was poor (24%). Specificity of LHT SOT from patients having balance-system weakness was 90%. The results of this study indicate that LHT posturography does not facilitate significant discrimination of patients with compensated unilateral peripheral weakness from those without such lesions.