Emergence of slip-ideal-slip behavior in tip-links serve as force filters of sound in hearing.

Tip-links in the inner ear convey force from sound and trigger mechanotransduction. Here, we present evidence that tip-links (collectively as heterotetrameric complexes of cadherins) function as force filters during mechanotransduction. Our force-clamp experiments reveal that the tip-link complexes show slip-ideal-slip bond dynamics. At low forces, the lifetime of the tip-link complex drops monotonically, indicating slip-bond dynamics. The ideal bond, rare in nature, is seen in an intermediate force regime where the survival of the complex remains constant over a wide range. At large forces, tip-links follow a slip bond and dissociate entirely to cut-off force transmission. In contrast, the individual tip-links (heterodimers) display slip-catch-slip bonds to the applied forces. While with a phenotypic mutant, we showed the importance of the slip-catch-slip bonds in uninterrupted hearing, our coarse-grained Langevin dynamics simulations demonstrated that the slip-ideal-slip bonds emerge as a collective feature from the slip-catch-slip bonds of individual tip-links.

Development of Consensus Recommendations on the Management of Vitiligo and the Role of Decapeptide in Vitiligo by the Delphi Method.

Background: Treatment of vitiligo is still a challenge in dermatology. Literature is sparse on the definitive clinical role of basic fibroblast growth factor (bFGF) in vitiligo patients. Aims: We decided to generate a consensus in an attempt to answer some critical questions related to the management of vitiligo and the role of bFGF. Materials and Methods: A Delphi method among 21 experts across India was conducted. A consensus (agreement was 75% or greater) was taken on 27 statements on the prevalence, epidemiology, and treatment of vitiligo and the role of bFGF in the management of vitiligo. The consensus process was completed after two rounds. Results: Topical corticosteroid therapy is the first-line therapy for vitiligo; however, its adverse effects are widely known, especially in sensitive areas. Topical calcineurin inhibitors are preferred in stable vitiligo of the face, neck, genitals, or intertriginous regions as an alternative to topical corticosteroids. Topical bFGF is a relatively newer therapy with a promising role in stable vitiligo. bFGF is safe and effective in inducing repigmentation of vitiligo lesions. Combination therapy of bFGF with other topical therapies, phototherapy, and surgical procedures can be beneficial in patients of vitiligo. Conclusion: This consensus would complement the currently available literature on bFGF and help the practitioner to recognize the unmet need in the treatment of vitiligo.

Design, synthesis and evaluation of 2-aryl quinoline derivatives against 12R-lipoxygenase (12R-LOX): Discovery of first inhibitor of 12R-LOX.

The 12R-lipoxygenase (12R-LOX), a (non-heme) iron-containing metalloenzyme belonging to the lipoxygenase (LOX) family catalyzes the conversion of arachidonic acid (AA) to its key metabolites. Studies suggested that 12R-LOX plays a critical role in immune modulation for the maintenance of skin homeostasis and therefore can be considered as a potential drug target for psoriasis and other skin related inflammatory diseases. However, unlike 12-LOX (or 12S-LOX) the enzyme 12R-LOX did not receive much attention till date. In our effort, the 2-aryl quinoline derivatives were designed, synthesized and evaluated for the identification of potential inhibitors of 12R-hLOX. The merit of selection of 2-aryl quinolines was assessed by in silico docking studies of a representative compound (4a) using the homology model of 12R-LOX. Indeed, in addition to participating in H-bonding with THR628 and LEU635 the molecule formed a hydrophobic interaction with VAL631. The desired 2-aryl quinolines were synthesized either via the Claisen-Schmidt condensation followed by one-pot reduction-cyclization or via the AlCl3 induced heteroarylation or via the O-alkylation approach in good to high (82-95%) yield. When screened against human 12R-LOX (12R-hLOX) in vitro four compounds (e.g. 4a, 4d, 4e and 7b) showed encouraging (>45%) inhibition at 100 µM among which 7b and 4a emerged as the initial hits. Both the compounds showed selectivity towards 12R-hLOX over 12S-hLOX, 15-hLOX and 15-hLOXB and concentration dependent inhibition of 12R-hLOX with IC50 = 12.48 ± 2.06 and 28.25 ± 1.63 µM, respectively. The selectivity of 4a and 7b towards 12R-LOX over 12S-LOX was rationalized with the help of molecular dynamics simulations. The SAR (Structure-Activity Relationship) within the present series of compounds suggested the need of a o-hydroxyl group on the C-2 phenyl ring for the activity. The compound 4a and 7b (at 10 and 20 µM) reduced the hyper-proliferative state and colony forming potential of IMQ-induced psoriatic keratinocytes in a concentration dependent manner. Further, both compounds decreased the protein levels of Ki67 and the mRNA expression of IL-17A in the IMQ-induced psoriatic-like keratinocytes. Notably, 4a but not 7b inhibited the production of IL-6 and TNF-α in the keratinocyte cells. In the preliminary toxicity studies (i.e. teratogenicity, hepatotoxicity and heart rate assays) in zebrafish both the compounds showed low safety (<30 µM) margin. Overall, being the first identified inhibitors of 12R-LOX both 4a and 7b deserve further investigations.

Longitudinal Course of Adverse Events With Esketamine Nasal Spray: A Post Hoc Analysis of Pooled Data From Phase 3 Trials in Patients With Treatment-Resistant Depression.

Objective: To describe the tolerability of esketamine nasal spray based on the adverse event profile observed during treatment sessions occurring early and later over the course of treatment.Methods: In 2 long-term, phase 3 studies (NCT02493868, October 1, 2015-February 16, 2018; NCT02497287, September 30, 2015-October 28, 2017), patients with treatment-resistant major depressive disorder (per DSM-5) and nonresponse to ≥ 2 oral antidepressants received esketamine nasal spray (56 or 84 mg) twice weekly during a 4-week induction phase, weekly for weeks 5-8, and weekly or every 2 weeks thereafter as maintenance treatment, in conjunction with a new oral antidepressant. A post hoc analysis using descriptive statistics evaluated occurrence (incidence, frequency, severity) and recurrence (incidence and severity) of events of specific interest.Results: In patients treated with esketamine nasal spray plus a newly initiated oral antidepressant (n = 928), spontaneously reported adverse events of dizziness, nausea, sedation, vertigo, and increased blood pressure were more likely to recur after the first week of treatment if they occurred more frequently (twice > once > none) during the first week. The same pattern was observed when these events were assessed by structured instruments. Incidences of dizziness, dissociation, increased blood pressure, nausea, vertigo, and sedation were highest in week 1 of treatment (20.6%, 16.7%, 4.3%, 14.0%, 12.1%, and 3.8%, respectively) and decreased thereafter. Initial occurrences and subsequent recurrences of events were mostly mild or moderate in severity.Conclusions: Adverse events during treatment with esketamine nasal spray plus an oral antidepressant generally become less frequent with ongoing treatment, and the majority are mild or moderate in severity.Trial Registration: ClinicalTrials.gov identifiers: NCT02493868; NCT02497287.

Oral Mucormycosis: An Inevitable Complication of COVID-19.

Individuals who have shown recovery from coronavirus disease (COVID-19) are increasingly getting diagnosed with Mucormycosis or "Black fungus." It is a difficult condition to diagnose as it has symptoms that are common among a variety of diseases. Hence, it is important to identify the presenting signs and understand the underlying pathogenesis of COVID-19 associated Mucormycosis. The incidence of these mycotic infections has shown a substantial increase in current times owing to an increase in the prevalence of immunocompromised subjects, human immunodeficiency virus (HIV) infection, and acquired immunodeficiency syndrome (AIDS). Any suspected case of mucormycosis requires rapid diagnosis and management due to its rapid progression as well as the destructive course of infection. This article reviews the taxonomy, pathogenesis, and clinical signs along with laboratory investigations that may play a vital role in the timely diagnosis of this condition as it is mostly fatal.

Hybrid Conferences in the Post-COVID-19 Era: Time Yet for a Paradigm Shift for Medical Associations.

Since the first COVID-19 lockdown in India was declared, all scientific conferences and related activities have been conducted in online formats (1). The ACS(I) [Association of Cutaneous Surgeons (India)] conducted its Annual National Conference called ACSICON-2021 for over 1150 delegates in mid-2021 in a hybrid mode. ACS(I) was one of the first organizations to embrace the hybrid conferencing strategy in the post-COVID-19 era in India. However, while meeting feedback and testimonials are typically gathered, there is very little public data documenting conference attendees' viewpoints. The goal of this research study was to look at the viewpoints of medical conference attendees (such as physicians and medical professionals) on hybrid conferencing as a future trend, the danger of infectivity and transmissibility of COVID-19 during and after the event, the effectiveness of stringent safety protocols and vaccination in preventing the disease and thereby assess the feasibility of hybrid conference as the most convenient mode of learning interaction in the current COVID-19 era and also Post COVID-19 era. Materials and Methods: The physical attendees were surveyed post-ACSICON 2021 conference online, using a mixed-methods technique. Attendees were given a 16-point questionnaire using Google Forms that covered subjects including the COVID-19 preventive procedure, immunization status, infection rates during and after the conference, and overall satisfaction with the hybrid conference. A total of 231 people were sent the survey questionnaire. Results: Only 0.4% (n = 1) of the participants reported being infected by COVID-19 virus after the conference. 86% (n = 198) of the respondents also felt that all the necessary precautions were taken during the ACSICON 2021conference. Most of the respondents (82%, n = 189) rated the hybrid conference interaction to be more satisfying than an online conference. An overwhelming majority of the respondents (92%, n = 209) found hybrid conferences to be a safer option than regular conference. Conclusion: The COVID-19 pandemic's scope has forced a paradigm change in medical practice and research (1). ACSICON 2021 is an example of how, with careful organization, strict implementation of meticulous preventive procedures, and strict adherence to the COVID-19 protocol, medical conferences may be held without danger of infection and its transmission. Given the pace with which vaccinations are being administered, a new reality in which technology and live networking intersect via hybrid conferences will result in a more engaging and adaptable medical conference experience. In the long run, this can bring about a significant shift in the conduct of scientific meetings to best suit delegates' needs and conveniences.

A Major Shell Protein of 1,2-Propanediol Utilization Microcompartment Conserves the Activity of Its Signature Enzyme at Higher Temperatures.

A classic example of an all-protein natural nano-bioreactor, the bacterial microcompartment is a prokaryotic organelle that confines enzymes in a small volume enveloped by an outer protein shell. These protein compartments metabolize specific organic molecules, allowing bacteria to survive in restricted nutrient environments. In this work, 1,2-propanediol utilization microcompartment (PduMCP) was used as a model to study the effect of molecular confinement on the stability and catalytic activity of native enzymes in the microcompartment. A combination of enzyme assays, spectroscopic techniques, binding assays, and computational analysis were used to evaluate the impact of the major shell protein PduBB' on the stability and activity of PduMCP's signature enzyme, dioldehydratase PduCDE. While free PduCDE shows ∼45 % reduction in its optimum activity (activity at 37 °C) when exposed to a temperature of 45 °C, it retains similar activity up to 50 °C when encapsulated within PduMCP. PduBB', a major component of the outer shell of PduMCP, preserves the catalytic efficiency of PduCDE under thermal stress and prevents temperature-induced unfolding and aggregation of PduCDE in vitro. We observed that while both PduB and PduB' interact with the enzyme with micromolar affinity, only the PduBB' combination influences its activity and stability, highlighting the importance of the unique PduBB' combination in the functioning of PduMCP.

Reliability of cheiloscopy and dermatoglyphics in hypertension and diabetes. A comparative study.

Background: Both dermatoglyphic and cheiloscopic patterns are genetically determined. These patterns are known to be associated with type II diabetes or diabetes mellitus and hypertension which are also considered to have genetic influence due to their familial occurrence. Hence, the aim of this study was to compare reliability of both cheiloscopy and dermatoglyphics with hypertension and type II diabetes. Materials and Methods: This was a prospective study conducted on 300 study participants. Both cheiloscopic and dermatoglyphic patterns were recorded using validated techniques. Obtained patterns were analyzed and assessed for statistical analysis using the SPSS version 21.0 statistical software. The Chi-square test was used for analyzing the obtained data. Results: In the present study, no statistical correlation was obtained between either dermatoglyphic or cheiloscopic patterns and type II diabetes or hypertension. Conclusion: The present study showed that cheiloscopy or dermatoglyphics cannot be used as a predictive tool for assessing a subject's risk of developing type II diabetes or hypertension. These are contradictory findings, thus emphasizing more research in this area so that these noninvasive techniques can be used as predictive tools for developing essential hypertension or type II diabetes.

Résumé Contexte: Les modèles dermatoglyphiques et cheiloscopiques sont génétiquement déterminés. Ces modèles sont connus pour être associés au diabète de type II ou au diabète sucré et à l'hypertension qui sont également considérés comme ayant une influence génétique en raison de leur occurrence familiale.Par conséquent, le but de cette étude était de comparer la fiabilité de la cheiloscopie et des dermatoglyphes avec l'hypertension et le diabète de type II. Matériaux et méthodes: Il s'agissait d'une étude prospective menée auprès de 300 participants à l'étude.Les modèles cheiloscopiques et dermatoglyphiques ont été enregistrés utilisant des techniques validées.Les modèles obtenus ont été analysés et évalués pour analyse statistique à l'aide du logiciel statistique SPSS version 21.0.Le test Chi-square a été utilisé pour analyser les données obtenues. Résultats: Dans la présente étude, aucune corrélation statistique n'a été obtenue entre les modèles dermatoglyphiques ou cheiloscopiques et le diabète ou l'hypertension de type II. Conclusion: La présente étude a montré que la chéiloscopie ou les dermatoglyphes ne peuvent pas être utilisés comme outil prédictif pour évaluer le risque de développer le diabète ou l'hypertension de type II d'un sujet.Ce sont des résultats contradictoires, mettant ainsi l'accent sur plus de recherche dans ce domaine afin que ces techniques non invasives puissent être utilisées comme outils prédictifs pour développer l'hypertension essentielle ou le diabète de type II. Mots clés: Dermatoglyphes, hypertension, empreintes de lèvres, diabète de type II.

Clinical patterns of congenital ocular anomalies in the pediatric age group (0 to 5 years) and its association with various demographic parameters.

PURPOSE: Congenital ocular anomalies are rare but important cause of childhood blindness. This study aimed to observe the clinical patterns of congenital ocular anomalies in the pediatric age group (0 to 5 years) and its association with various demographic parameters. METHODS: Hospital-based cross-sectional study done on all pediatric patients in the 0-to-5-year age group presenting with congenital ocular anomalies to the Ophthalmology department of a tertiary care hospital in Eastern India between October 2018 and October 2020. Thorough clinical history was obtained, and comprehensive ocular examination was done in each case. RESULTS: A total of 5686 patients in the 0 to 5 years age group attended the eye OPD during the study period. Congenital ocular anomalies were seen in 140 patients. The prevalence of ocular anomalies was 2.46%. Average age of patients was 3.32 ± 1.42 years. There were 74 (52.9%) males and 66 (47.1%) females. Unilateral and bilateral involvement was seen in 100 (71.45%) and 40 (28.6%) cases, respectively. Antenatal period was uneventful in 92.14% cases. Decreased vision was the most common presentation (40%). Congenital nasolacrimal duct obstruction was the most common anomaly seen in 29 (20.71%) cases followed by congenital cataract in 21 (15%) cases. CONCLUSION: Few of the congenital ocular anomalies can be prevented by increasing community awareness. Findings of the study can act as a reference guide for clinicians and health professionals for counseling and health planning.

Fe(III)-catalyzed regioselective and faster synthesis of isocoumarins with 3-oxoalkyl moiety at C-4: Identification of new inhibitors of PDE4.

In search of potent and new anti-inflammatory agents, we explored a new class of isocoumarin derivatives possessing the 3-oxoalkyl moiety at C-4 position. These compounds were synthesized via the FeCl3 catalyzed construction of isocoumarin ring. The methodology involved coupling of 2-alkynyl benzamides with alkyl vinyl ketone and proceeded via a regioselective cyclization to give the desired compound as a result of formation of CO and CC bonds. A large number of isocoumarins were synthesized and assessed against PDE4B in vitro. While isocoumarins containing an aminosulfonyl moiety attached to the C-3 aryl ring showed encouraging inhibition of PDE4B, some of the derivatives devoid of aminosulfonyl moiety also showed considerable inhibition. According to the SAR analysis the C6H4NHSO2R2-m moiety at C-3 position of the isocoumarin ring was favorable when the R2 was chosen as an aryl or 2-thienyl group whereas the presence of F or OMe substituent at C-7 of the isocoumarin ring was found to be beneficial. The compound 5f with IC50 values 0.125 ± 0.032 and 0.43 ± 0.013 µM against PDE4B and 4D, respectively was identified as an initial hit. It showed in silico interaction with the PHE678 residue in the CR3 region of PDE4B and relatively less number of interactions with PDE4D. Besides showing the PDE4 selectivity over other PDEs and TNF-α inhibition in vitro the compound 5f at an intraperitoneal dose of 30 mg/kg demonstrated the protective effects against the development of arthritis and potent immunomodulatory activity in adjuvant induced arthritic (AIA) rats. Furthermore, no significant adverse effects were observed for this compound when evaluated in a systematic toxicity (e.g. teratogenicity, hepatotoxicity and cardiotoxicity) studies in zebrafish at various concentrations. Collectively, being a new, potent, moderately selective and safe inhibitor of PDE4B the isocoumarin 5f can be progressed into further pharmacological studies.

Treatment Effect With Paliperidone Palmitate Compared With Oral Antipsychotics in Black/African American Patients With Schizophrenia and a History of Criminal Justice System Involvement: A Post Hoc Analysis of the PRIDE Study.

OBJECTIVE: To examine the efficacy and safety of paliperidone palmitate once-monthly (PP1M) versus oral antipsychotics (OAPs) in Black/African American patients with schizophrenia and a history of criminal justice system involvement. METHODS: This was a post hoc analysis of a 15-month prospective, randomized, open-label, parallel-group, multicenter US study conducted from May 2010 to December 2013 that examined a subpopulation of Black/African American patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria). The primary objective was to compare time to first treatment failure in patients treated with PP1M versus OAPs. Secondary objectives were to compare time to first institutionalization (psychiatric hospitalization or arrest/incarceration) and mean number of treatment failure events and institutionalizations over 15 months in PP1M-treated and OAP-treated patients. RESULTS: The intention-to-treat population included 275 Black/African American patients (PP1M, n = 145; OAPs, n = 130). Median time to first treatment failure was not reached for PP1M-treated patients and was 270 days for OAP-treated patients; hazard ratio (HR) was 1.39 (95% CI, 0.97-1.99; P = .075). Median time to first institutionalization was not reached for PP1M-treated patients and was 304 days for OAP-treated patients; HR was 1.49 (95% CI, 1.01-2.19; P = .043). Mean numbers of treatment failure events and institutionalizations were lower with PP1M than OAPs. The safety profile of PP1M was consistent with that of previous PP1M studies. CONCLUSIONS: In a Black/African American subpopulation of patients with schizophrenia and prior criminal justice system involvement, PP1M reduced the number of treatment failures, thereby reducing the number of psychiatric hospitalizations and/or arrests/incarcerations compared with daily OAPs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01157351.

Simultaneous Estimation of Apremilast and Betamethasone Dipropionate in Microsponge-Based Topical Formulation using a Stability Indicating RP-HPLC Method: A Quality-by-Design Approach.

A stability-indicating reverse phase high-performance liquid chromatography method was developed and validated for simultaneous quantification of apremilast (APL) and betamethasone dipropionate (BD) in bulk as well as drug loaded microsponges. Various mobile phase systems were screened to check the system suitability followed by force degradation analysis to determine APL and BD stability under varying stress conditions. A central composite design model was used to optimize the column temperature and flow rate using Design Expert® (9.0.1). One factor at a time approach with five independent factors were used to validate the robustness of the method. Finally, APL and BD were precisely and accurately quantified from drug loaded microsponges using the validated method. A favorable separation of APL and BD was obtained on a Phenomenex® Luna C18 column using a mixture of 50 mM phosphate buffer containing 0.1% triethylamine (pH 6.1) and acetonitrile (60:40%v/v) as mobile phase. Both the drugs were found to be stable when exposed to stressors such as heat-, light-, alkali-, acid- and peroxide-induced degradation. The calibration curves were found to be linear with appreciable limit of detection and limit of quantification. Recovery and percentage relative standard deviation of peak areas for APL and BD were found to be < 2.0% and 99-100% in bulk drug solution and <2.0% and 99-103% in microsponge formulation, respectively. Statistical analysis using analysis of variance indicated that the model was significant (P < 0.001). Hence, the developed method can be effectively used to quantify APL and BD, both in bulk as well as microsponge formulations.

The medicolegal importance of establishing human identity by using dactyloscopy and rugoscopy: A comparative study.

BACKGROUND: Palatal rugae are irregular and asymmetric mesenchymal ridges that extend in a lateral direction away from the incisive papilla and mid-palatine raphe. Their unique characteristics and environmental stableness justify their inclusion in forensic investigations. Dermatoglyphics or fingerprint patterns are epidermal ridges, which are genetically controlled and are specific to an individual. Hence they are used as a forensic tool. OBJECTIVES: The study aimed to assess the reliability of Rugoscopic and Dermatoglyphic patterns for gender identification. MATERIALS AND METHODS: A total of 200 subjects were recruited in this prospective study. All subjects were between the age range of 18 and 55 years. The subjects were categorized into 100 males and 100 females. Fingerprint dermatoglyphic patterns were recorded using stamp pad, ink, and A4 size white sheets. A subject's fingers were pressed onto the stamped ink pad and lightly pressed over a sheet of paper. Obtained patterns were coded and analyzed as per Galton's criteria into arch, loop, and whorl patterns. Palatal rugae patterns were obtained by making alginate impression material and impression trays. Obtained casts were analyzed for rugae pattern analysis using Kapali's classification. An unpaired t test was used as a statistical tool. RESULTS: On analyzing dermatoglyphic patterns, the arch pattern was most common among male subjects, whereas loop pattern was found to be most common among females. On rugoscopic pattern analysis, Straight pattern was most frequent among males, whereas the circular pattern was common among females. CONCLUSION: A statistically significant difference was noted between gender and rugoscopic patterns (P = 0.02) and dermatoglyphic patterns (P = 0.03).

Coexistence of hyperparathyroidism and peripheral giant cell granuloma of the jaw: A rare case report.

Peripheral giant cell granuloma (PGCG) known as "giant cell epulis" is a benign, reactive exophytic gingival lesion that accounts for less than 10% of all gingival lesions. PGCG affects females more than males with middle age predilection. Till now the etiology of PGCG remains unclear but various factors that can cause PGCG include poor oral hygiene, food impaction, following an extraction, dry mouth, hormonal disturbance, and hyperparathyroidism. The reported recurrence rate of the lesion is 5.0%-70.6%. The present case report describes the rare case of PGCG with primary hyperparathyroidism in a male patient with a history of swelling in the mandibular anterior region.

Probe into a multi-protein prokaryotic organelle using thermal scanning assay reveals distinct properties of the core and the shell.

BACKGROUND: Bacterial microcompartments represent the only reported category of prokaryotic organelles that are capable of functioning as independent bioreactors. In this organelle, a biochemical pathway with all the enzyme machinery is encapsulated within an all protein shell. The shell proteins and the enzymes have distinct structural features. It is hypothesized that flat shell proteins align sideways to form extended sheets and, the globular enzymes fill up the central core of the organelle. METHODS: Using differential scanning fluorimetry, we explored the structure and functional alteration of Pdu BMC, involving tertiary or quaternary structures. RESULTS: Our findings exhibit that these intact BMCs as a whole behave similar to a globular protein with a rich hydrophobic core, which is exposed upon thermal insult. The encapsulated enzymes itself have a strong hydrophobic core, which is in line with the hydrophobic-collapse model of protein folding. The shell proteins, on the other hand, do not have a strong hydrophobic core and show a significant portion of exposed hydrophobic patches. CONCLUSION: We show for the first time the thermal unfolding profile of the BMC domain proteins and the unique exposure of hydrophobic patches in them might be required for anchoring the enzymes leading to better packaging of the micro-compartments. GENERAL SIGNIFICANCE: These observations indicate that the genesis of these unique bacterial organelles is driven by the hydrophobic interactions between the shell and the enzymes. Insights from this work will aid in the genetic and biochemical engineering of thermostable efficient enzymatic biomaterials.

Update on psoriasis: A review.

Psoriasis is a disease characterized by the presence of papules and plaques over the surface of skin with variable morphology, distribution and severity. The lesions of psoriasis are distinct from these other entities and are classically very well circumscribed, circular, red papules or plaques with a grey or silvery-white, dry scale. In addition, the lesions are typically distributed symmetrically on the scalp, elbows, knees, lumbosacral area, and in the body folds. The oral manifestations of psoriasis may involve the oral mucosa or the tongue. The dorsal surface of the tongue shows characteristic red patches surrounded with a yellow white border. The relationship between eye lesions and psoriasis are the current findings in the literature. The ocular complications along with the several extracutaneous manifestations are common complications seen in psoriasis. The pathogenesis of exact relationship between these two is still controversial. Immunological studies have shown a positive relationship between T helper cells and uveitis. Various signs and symptoms of ocular psoriasis may be overlooked. Thus, a complete understanding of ophthalmic involvement is important to the comprehensive care of patients with psoriasis. Almost any part of the body can be affected in psoriasis, but the ophthalmic complications of psoriasis usually remain clinically subtle. This review highlights the various manifestations of psoriasis with their clinical sign and symptoms.

Assessment of diagnostic accuracy of a direct digital radiographic-CMOS image with four types of filtered images for the detection of occlusal caries.

BACKGROUND: Digital imaging has the potential to improve diagnostic accuracy and make quantitative diagnoses. In the recent decades, software for radiographic analysis has been investigated and developed for the detection of lesions and the quantitative assessment of the depth of a caries lesion. In addition, the accuracy of diagnosis may also be enhanced by programs that filter the images. These programs can adjust the brightness and contrast, determine the gray level, invert the shades of gray, and apply pseudocolors. Few studies compared different types of digital images in the diagnosis of changes in the tooth crown. AIM: The main aim of this study was to assess the the diagnostic accuracy of a direct digital radiography (DDR)-CMOS image with four types of filtered images for the detection of occlusal caries. MATERIALS AND METHODS: Fifty randomly selected patients' teeth were clinically examined and digitally radiographed. Radiographed images are converted into four filter images with the help of software. Filtered images were then selected for inter- and intraobserver examination and the result was subjected to statistical analysis. CONCLUSION: DDR-CMOS and negative image were found to be more useful in diagnosing occlusal caries.

Functional protein shells fabricated from the self-assembling protein sheets of prokaryotic organelles.

Fabricating protein compartments from protein units is challenging and limited by the use of external stimuli and crosslinkers. Here we explore the fabrication of all-protein compartments using self-assembled proteins of prokaryotic organelles. These proteins have intrinsic interacting domains which are ionic in nature, and spontaneously self-assemble into sheets when over-expressed. Using a one-step approach, we maneuvered the formation of the protein shells from the sheets without any external stimuli or crosslinker. The spontaneous self-assembly of the native protein sheets into protein shells not only preserves the native functional properties of the protein but also enhances their thermal stability compared to the sheets. We further demonstrate that these compartments can encapsulate macromolecular enzymes and, more interestingly, permit the free exchange of small molecules and substrates through their intrinsic conduit channels. The porous nature of the shell housing active enzymes and allowing movement of small molecules makes them suitable as active bioreactors. Furthermore, to extend the tunability of these protein-compartments with respect to stability, enzyme-encapsulation, and permeability, we fabricated three different compartments using three different sheet proteins, PduA/B/B' and compared their properties. Interestingly we find that all three protein shells show similar behaviour with respect to an encapsulated diol-dehydratase enzyme and vitamin B12, which are native to the Pdu BMC system. Furthermore, for the non-native enzyme CytC, the small molecule R6G dye, doxorubicin, NR and curcumin they behave diversely. Insights from this analysis will allow us to design and develop sheet protein based synthetic active bioreactors requiring meticulous, compartmentalization in process optimization.

Broken force dispersal network in tip-links by the mutations at the Ca2+-binding residues induces hearing-loss.

Tip-link as force-sensor in hearing conveys the mechanical force originating from sound to ion-channels while maintaining the integrity of the entire sensory assembly in the inner ear. This delicate balance between structure and function of tip-links is regulated by Ca2+-ions present in endolymph. Mutations at the Ca2+-binding sites of tip-links often lead to congenital deafness, sometimes syndromic defects impairing vision along with hearing. Although such mutations are already identified, it is still not clear how the mutants alter the structure-function properties of the force-sensors associated with diseases. With an aim to decipher the differences in force-conveying properties of the force-sensors in molecular details, we identified the conformational variability of mutant and wild-type tip-links at the single-molecule level using FRET at the endolymphatic Ca2+ concentrations and subsequently measured the force-responsive behavior using single-molecule force spectroscopy with an Atomic Force Microscope (AFM). AFM allowed us to mimic the high and wide range of force ramps (103-106 pN s-1) as experienced in the inner ear. We performed in silico network analysis to learn that alterations in the conformations of the mutants interrupt the natural force-propagation paths through the sensors and make the mutant tip-links vulnerable to input forces from sound stimuli. We also demonstrated that a Ca2+ rich environment can restore the force-response of the mutant tip-links which may eventually facilitate the designing of better therapeutic strategies to the hearing loss.

Force-activated catalytic pathway accelerates bacterial adhesion against flow.

Mechanical cues often influence the factors affecting the transition states of catalytic reactions and alter the activation pathway. However, tracking the real-time dynamics of such activation pathways is limited. Using single-molecule trapping of reaction intermediates, we developed a method that enabled us to perform one reaction at one site and simultaneously study the real-time dynamics of the catalytic pathway. Using this, we showed single-molecule calligraphy at nanometer resolution and deciphered the mechanism of the sortase A enzymatic reaction that, counter-intuitively, accelerates bacterial adhesion under shear tension. Our method captured a force-induced dissociation of the enzyme-substrate bond that accelerates the forward reaction 100×, proposing a new mechano-activated catalytic pathway. In corroboration, our molecular dynamics simulations in the presence of force identified a force-induced conformational switch in the enzyme that accelerates proton transfer between CYS184 (acceptor) and HIS120 (donor) catalytic dyads by reducing the inter-residue distances. Overall, the present study opens up the possibility of studying the influence of factors affecting transition states in real time and paves the way for the rational design of enzymes with enhanced efficiency.