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Introduction: Understanding of molecular model of oral carcinogenesis has carried cancer chemotherapy far forward from conventional drug therapies. Small molecule inhibitors have gained acceptance as it has fewer adverse effects and also provide targeted drug therapy. The association of HSP 70 (Heat Shock Protein 70) and BCL 2 (B-cell lymphoma 2) proteins with oral precancer and cancer is already established. However, the complex interaction between these two proteins and how they affect each other's expression is still not understood completely. In our study, we aimed to correlate the expression of HSP 70 and BCL 2 with different histopathological grades of oral precancer and cancer tissue samples using tissue immunohistochemistry. Materials and Methods: Tissue samples were taken from a total of 250 patients (100 OPMDs and 150 OSCCs) and subjected to immunohistochemistry using anti-human mouse monoclonal antibodies to HSP70 and BCL2. Immunostaining was done, and the immunostaining intensity distribution (IID) index was calculated. Results and Discussion: Immunoreactivity scores for both HSP 70 and BCL 2 correlated with different grades of dysplasia. However, only HSP 70 had a statistically significant association (p = 0.066). We also found that HSP 70 showed an inverse correlation, with higher expression majorly seen in well-differentiated OSCCs. Conclusion: Our study unveiled the HSP 70-BCL 2 interaction and provides insights about how this might affect drug designing and help overcome therapeutic lags. However, further studies are needed to provide a comprehensive review of such interactions among various small molecules.
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Visualization is a complex-integrated procedure of the eyes and brain that allows to see this colorful world. Hypothyroidism-associated ophthalmopathy (HAO), often known as dry eyes, swelling around the eyes, blurred vision, glaucoma, and cataracts, are some eye-related issues caused by hypothyroidism. Yet there is no permanent cure for hypothyroidism; taking medicine throughout life is the only solution to keep its harmful effects under control. This study used intermittent fasting (IF) and vitamin E (Vit.E) supplementation to prevent hypothyroidism-associated ophthalmopathy. This study hypothesized that intermittent fasting-like diet regimens and vitamin supplementation should reduce the propagation of HAO by its antioxidant potential. In the present study, experimental animals are divided into five groups: normal, hypothyroidism control, dual, Vit. E, and IF. Hypothyroidism is generated in the experimental groups by taking propylthiouracil (PTU) for 24 days while also taking IF and Vit. E supplements. The hypothyroid-induced experimental animals demonstrated an increase in IOP and lipid peroxidation while thyroid hormone levels depicted a massive decline which is a clear denotation of the effects of the thyroid on eyes and lifestyle. Ancient Ayurveda inspires these proposed therapies and has successfully reduced all the damage to the thyroid gland and the eye.
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Hypothyroidism , Vitamin E , Animals , Vitamin E/pharmacology , Vitamin E/therapeutic use , Intermittent Fasting , Oxidative Stress , Hypothyroidism/drug therapy , Dietary SupplementsABSTRACT
River water quality management is a tedious job as it comprises multiple variables. The River Yamuna, Delhi's urban reach, is highly contaminated with very low or zero freshwater flow during the non-monsoon periods. The river quality has been appraised for pre- and post-monsoon periods of 10 years of data collected from the Delhi Pollution Control Council (DPCC). A sharp declination of dissolved oxygen and acceleration of BOD have been observed after the outfalling of drain 1. The wastewater treatment plants data for 2020-2022 have been analyzed, and the removal efficiencies of BOD and COD were found between 65 and 94%. The BIOFORE technology has shown maximum removal efficiencies, around 94% and 89% for BOD and COD, respectively. The level of treatment has been evaluated by developing a water quality model with the existing QUAL2kw framework. Twelve strategies have been generated for four levels of treatment and three different flow conditions. The severely polluted reach of Yamuna has low self-purification capacity; flow augmentation has little effect on the existing load. Hence, the level of treatment required to increase. After the introduction of outfalling drain D13-D16, a sag of DO has been observed; to improve the DO concentration, external aeration is suggested before wastewater disposal into the river. The study is a novel effort to manage the river quality by developing scenarios, including the level of treatments and flow augmentation, and keeping up the desired DO concentration assigned for this river reach.
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Water Purification , Water Quality , Environmental Monitoring , Rivers , Wastewater , IndiaABSTRACT
This paper aims to assess the requirement of load reductions and flow augmentation to enhance the assimilation yield of the Yamuna River, Delhi. The framework QUAL2kw was used to predict river quality. The model was calibrated and confirmed in critical flow conditions of pre-monsoon periods. Three strategies were established for varying pollutant loads. The DO concentration was predicted with changing BOD and COD loads. The 16 outfalling drains were considered pollutant sources between the 22 km stretch of the river. Four cases with 41 scenarios were studied with varying flow augmentation upstream and varying load. It has been observed that with 80 cumecs of upstream flow, the reach can assimilate 31.33 tonnes per day of BOD and 142.85 tonnes per day of COD load, maintaining the desired level of DO (≥4 mg/L) and BOD (≤3 mg/L) throughout the reach.
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Environmental Pollutants , Water Pollutants, Chemical , Water Quality , Rivers , Water Pollutants, Chemical/analysis , India , Environmental MonitoringABSTRACT
Background: Maxillofacial trauma in polytrauma settings is often associated with multiple injuries both trivial and life threatening, and their timely detection is the mainstay of definitive trauma management for preventing mortality and morbidity. Emergency management of all the patients reporting to our maxillofacial unit is either done by our center or they have been managed at the peripheral health care facility and relatively stable patient is referred to us. Anecdotally, we found inadequacies in transport methods, diagnosis, and detection of associated injuries in the patients referred to us from the peripheral health care facility. To substantiate our finding, this observational study has been planned. Objective: To identify, diagnose, and document missed injuries associated with the maxillofacial trauma. Materials and Methods: All the trauma patients referred to the maxillofacial unit directly from the peripheral health care facility during the period of October 2017 to March 2019 were included in this study. Results: We observed a total of 270 patients having both pure maxillofacial trauma and patients having documented other injuries associated with maxillofacial injuries. In our maxillofacial unit, functioning as a secondary screen, head to toe clinical examination was performed to document any previously missed out injuries. Missed injuries diagnosed by us included spinal injuries, temporal bone fractures, fractures of the styloid process, and even head injury. Conclusion: Frequent reassessment of trauma patients at all levels of trauma care and training health care personnel particularly those at peripheral health care facility and those involved in prehospital care are pivotal in managing the trauma patients in most efficient manner.
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A TiO2-guanine nanocomposite (TG NC)-based electrochemical biosensor was immobilized with hemagglutinin (HA) gene specific probe with 5' NH2 group on screen-printed gold electrode (probe(ss)DNA-TG-SPGE). The modified biosensor was examined for H1N1 swine flu virus. TG NCs along with precursors were characterized spectroscopically and morphologically by employing several approaches. Electrochemical investigations were performed with the help of cyclic voltammetric (CV) and electrochemical impedance spectroscopy (EIS) in 0.1 M phosphate buffer saline (PBS; pH 7.4) with 1 µM methylene blue (MB) redox indicator. For better detection of single-stranded virus DNA, the modified electrode was optimized at various concentrations, pH, and scan rates. The modified biosensor showed high sensitivity (40.32 µA/ng.cm2), low LOD (0.00024 ng/6 µL), and broad linear range 0.0002-20 ng/6µL with coefficient of determination of R2=0.9981 for H1N1 virus detection. The HA gene-modified biosensor presented decent stability and specificity against different infectious pathogens including H3N2 virus and human DNA with negative response. Furthermore, the modified biosensor also responded well for real sample target DNA detection with a recovery of >96%. The simply designed HA gene-modified biosensor transduces decreased current response towards target-specific (ss)DNA binding and could be used as a rapid detection tool for H1N1 swine flu virus diagnosis.
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Influenza A Virus, H1N1 Subtype , Influenza A virus , Humans , Animals , Swine , Influenza A Virus, H3N2 Subtype , Influenza A Virus, H1N1 Subtype/genetics , DNA, Single-Stranded , GuanineABSTRACT
BACKGROUND: Viral therapies developed for cancer treatment have classically prioritized direct oncolytic effects over their immune activating properties. However, recent clinical insights have challenged this longstanding prioritization and have shifted the focus to more immune-based mechanisms. Through the potential utilization of novel, inherently immune-stimulating, oncotropic viruses there is a therapeutic opportunity to improve anti-tumor outcomes through virus-mediated immune activation. PV001-DV is an attenuated strain of Dengue virus (DEN-1 #45AZ5) with a favorable clinical safety profile that also maintains the potent immune stimulatory properties characterstic of Dengue virus infection. METHODS: In this study, we utilized in vitro tumor killing and immune multiplex assays to examine the anti-tumor effects of PV001-DV as a potential novel cancer immunotherapy. RESULTS: In vitro assays demonstrated that PV001-DV possesses the ability to directly kill human melanoma cells lines as well as patient melanoma tissue ex vivo. Importantly, further work demonstrated that, when patient peripheral blood mononuclear cells (PBMCs) were exposed to PV001-DV, a substantial induction in the production of apoptotic factors and immunostimulatory cytokines was detected. When tumor cells were cultured with the resulting soluble mediators from these PBMCs, rapid cell death of melanoma and breast cancer cell lines was observed. These soluble mediators also increased dengue virus binding ligands and immune checkpoint receptor, PD-L1 expression. CONCLUSIONS: The direct in vitro tumor-killing and immune-mediated tumor cytotoxicity facilitated by PV001-DV contributes support of its upcoming clinical evaluation in patients with advanced melanoma who have failed prior therapy.
Subject(s)
Dengue Virus , Dengue , Melanoma , Oncolytic Virotherapy , Oncolytic Viruses , Humans , Dengue Virus/physiology , Leukocytes, Mononuclear , Melanoma/therapy , MCF-7 Cells , Immunity , Cell Death , Oncolytic Virotherapy/methodsABSTRACT
The aim of this study is to present a case of facial asymmetry secondary to unilateral long-standing temporomandibular joint (TMJ) ankylosis managed by a staged treatment protocol. Treatment for facial asymmetry secondary to unilateral TMJ ankylosis can have varied approaches followed by different workers according to their experiences. This predistraction arthroplasty versus prearthroplastic distraction debate has been at the center stage in literature for quite some time. Hereby, we present a case followed by the latter approach along with double-sliding genioplasty to correct chin asymmetry. A 25-year-old male patient with a history of facial trauma 15 years ago reported a complaint of inability to open mouth and gradually developing facial asymmetry. The patient was thoroughly evaluated using radiographs and cephalometric analysis to establish the diagnosis of TMJ ankylosis with facial asymmetry and suspected sleep apnea. The patient was treated according to our institutional protocol of prearthroplastic asymmetry correction followed by ankylosis release along with double-sliding genioplasty to correct residual deformity at a later date. Correction of facial asymmetry before ankylosis release provides a more evidence-based approach as supported by the current literature. Plus, any residual deformity can be rectified using orthomorphic procedures such as genioplasty. Since there is an ongoing debate in the current literature about sequencing in the treatment of facial asymmetry cases, the presented case adds to the argument that the approach followed herein provides for more favorable outcome.
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Background: The use of dental implants has become a very predictive method of rehabilitation for patients with partial or complete edentulism. It is more challenging to treat the posterior quadrants of the maxillary ridges using dental implants due to their anatomical and physiological characteristics. So to overcome the limitations of other techniques, short implants were introduced recently as a new approach to simplify implant placement in compromised alveolar bone and to prevent possible damage to vital structures. Purpose: This study aims to compare the clinical outcomes of dental implants placed using the osteotomized sinus floor elevation (OSFE) technique side engaging the bony floor of the maxillary sinus (bicortical anchorage) on one side and the conventional technique by split mouth on the other side. Materials and Method: This study included 15 patients. Study participants had dental implants placed on both sides of the mouth at the same time, so one side was implanted according to the test method, while the other side used the control method. Randomization determined which side would be implanted. Conclusion: The OSFE technique provides greater stability to the implant via bicortical anchorage than conventional techniques, which only provide unicortical anchorage.
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A series of polypyrrole doped TiO2-SiO2 nanohybrids (Ppy/TS NHs) were synthesized thru in-situ oxidation polymerization by varying weight ratio of pyrrole. The structural analysis of NHs were characterized by X-ray Diffraction (XRD) spectra, UV-visible (UV-Vis) spectra and X-ray Photoelectron spectra (XPS) confirmed synthesis of nanomaterials. Surface and morphological study done by adopting, Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), Transmittance Electron Microscopy (TEM) and Brunauer-Emmett-Teller (BET) analysis confirmed the homogenous distribution, nano range size formation and mesoporous nature of nanohybrids. Further, electrochemical behavior of synthesized NHs investigated by adopting Electrochemical Impedance Spectroscopy (EIS) showed good kinetic behaviour and electron transport tendency. The nanohybrids and precursors were examined for photocatalytic degradation of methylene blue (MB) dye and revealed enhanced degradation tendency for the NHs series photocatalysts. It was found that variation of pyrrole (0.1 to 0.3 g) to TS nanocomposites (TS Nc) increased the photocatalytic potential of TS Nc. The maximum photodegradation efficacy was found to be 90.48% in 120 min for Ppy/TS0.2 NHs under direct solar light. Additionally, Ppy/TS0.2 NHs performed appreciably towards antibacterial studies against some Gram-positive and Gram-negative deleterious bacteria, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Shigella flexneri microbes.
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Introduction: Conservation agriculture is a sustainable system of farming that safeguard and conserves natural resources besides enhancing crop production. The biological properties of soil are the most sensitive indicator to assess the short term impact of management practices such as tillage and residue incorporation. Methods: Nine treatments of tillage and residue management practices [Reduced till direct seeded rice-zero till barley (RTDSR-ZTB); RTDSR-ZTB-green gram residue (Gg); Zero till direct seeded rice-zero till barley-zero till green gram (ZTDSR-ZTB-ZTGg); RTDSR-ZTB + rice residue at 4 t ha 1 (RTDSR-ZTBRR4); RTDSR-ZTBRR6; un-puddled transplanted rice (UPTR)-ZTB-Gg; UPTR-ZTBRR4; UPTR-ZTBRR6, and puddled transplanted rice (PTR)-RTB] executed under fixed plot for five years on crop productivity and soil biological properties under rice-barley production system. Results: The shifting in either RTDSR or ZTDSR resulted in yield penalty in rice compared to PTR. The PTR recorded highest pooled grain yield of 3.61 ha-1. The rice grain yield reduced about 10.6% under DSR as compared to PTR. The ZTB along with residue treatments exhibited significantly higher grain yield over ZTB, and the RTDSR-ZTBRR6 registered highest pooled grain yield of barley. The system productivity (12.45 t ha-1) and sustainable yield index (0.87) were highest under UPTR-ZTBRR6. Biological parameters including microbial biomass carbon, soil respiration, microbial enzymes (Alkaline phosphatase, nitrate reductase and peroxidase), fluorescein diacetate hydrolysis, ergosterol, glomalin related soil proteins, microbial population (bacteria, fungi and actinobacteria) were found to be significantly (p < 0.05) effected by different nutrient management practices. Based on the PCA analysis, Fluorescein diacetate hydrolysis, microbial biomass carbon, soil respiration, nitrate reductase and fungi population were the important soil biological parameters indicating soil quality and productivity in present experiment. The results concluded that UPTR-ZTBRR6 was a more suitable practice for maintaining system productivity and soil biological health. Discussion: The understanding of the impact of different tillage and residue management practices on productivity, soil biological properties and soil quality index under rice-barley cropping system will help in determining the combination of best conservation agriculture practices for improved soil quality and sustainable production.
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Background: Although early maladaptive schemas (EMSs) have been suggested as potential vulnerability markers for alcohol dependence (AD), there is less emphasis on addressing these schemas in substance abuse treatment programs. We thus aimed to examine the change in schemas in response to cognitive therapy in individuals with AD. Methods: In this an open-label randomized controlled study, individuals with alcohol dependence syndrome (ADS, n = 84) were randomized to the intervention group (n = 45), which received six cognitive therapy sessions combined with treatment as usual (TAU), or the control group (n = 39), which was on TAU only. Participants were assessed on the measures of EMSs, alcohol use severity, and perceived stress at baseline and posttreatment. Results: The intervention group showed significant improvement in 5 out of 18 EMSs, that is, emotional deprivation, defectiveness, self-sacrifice, unrelenting standard, and negativity, compared to the control group, at the end of the treatment. There was a significant between-group effect for perceived stress but not for alcohol use severity. Conclusion: EMSs can be changed with cognitive therapy in individuals with AD and could be a crucial area to address in treatment programs. Further studies with long-term follow-up are warranted. The trial was registered with the Clinical Trials Registry-India (CTRI/2015/12/006441) on December 17, 2015.
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An amperometric non-enzymatic glucose sensing based on polyvinylpyrrolidone and titanium dioxide nanocomposites (PVP-TiO2 NCs) fabricated over stainless-steel (SS) electrode was experimented. The electrode was fabricated of PVP-TiO2 NCs onto SS surface through drop casting coating. The NCs and the electrode were analyzed using Fourier transform infrared (FTIR) and UV-visible (UV-Vis) spectroscopy, X-ray diffraction spectra (XRD), X-ray photoelectron spectra (XPS), particle analyzer, scanning electron microscopy (SEM), EDS and transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET) analysis for surface. For electrochemical investigation, cyclic voltammetry, electrochemical impedance spectra, including Nyquist plots and Bode plots, and chronoamperometry were adopted. PVP-TiO2/SS-modified electrode manifested high sensitivity of 360.13 µA/mM.cm2, lower detection limit of 756.8 µM and 0 to 13 mM linear range with regression coefficient of R2 = 0.992. The electrode exhibited high stability with good anti-interference tendency against fructose, uric acid, ascorbic acid and sucrose. The modified electrode also performed well in real sample glucose detection. Further, PVP-TiO2 NCs performed appreciably toward antibacterial studies against some Gram-positive and Gram-negative deleterious bacteria, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Shigella flexneri microbes.
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Nanocomposites , Povidone , Titanium/chemistry , Anti-Bacterial Agents/pharmacology , Nanocomposites/chemistry , Glucose , X-Ray DiffractionABSTRACT
Purpose: The behavior of trigeminocardiac reflex (TCR) is limited to few case reports only in maxillofacial surgery, especially for temporomandibular joint (TMJ) ankylosis cases. The present study aims to find out the incidence of bradycardia due to TCR during intraoperative forceful mouth opening in TMJ ankylosis patients. Materials and Methods: A prospective, unicentric observational study was conducted selecting those patients who were planned for osteoarthrectomy with interpositional gap arthroplasty under general anesthesia. Sixty cases of TMJ ankylosis were randomly selected from December 2018 to-03-2020. Predictor variables were patient age, gender, and type of ankylosis, and outcome variables were pulse rate, mean arterial blood pressure (MABP), and oxygen saturation level (SPO2). Data were recorded at baseline and during intraoperative mouth opening via heister jaw stretcher. A Chi-square test was used for testing the association between variables. P values were considered statistically significant at <0.05. Results: The sample size of 60 subjects has been divided into two age groups (10-19) years and (20-40) years. The mean standard deviation age of the patients was 18.32 ± 6.81 years. About 63.3% were male. Out of 60 cases, 14 patients developed bradycardia. The frequency of bradycardia was found 23.3%. According to logistic regression analysis, age and type of ankylosis were the significant predictors of bradycardia. Conclusion: We conclude that bradycardia due to TCR in TMJ ankylosis patients is not an uncommon entity. Incidences are more prevalent in the age group of 10-19 years and type IV bony ankylosis. Male had a high incidence of bradycardia though P value was nonsignificant.
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Introduction: Blunt trauma to the orbital rim is a frequent cause of both orbital fractures and damage to the surrounding facial bones and soft tissues. The inception of endoscopy and minimal invasive intervention has revolutionized the surgical treatment of blow out fracture of orbital walls. Thus, the present study was conducted to compare the outcome of conventional open reduction approach with endoscopic approach for orbital floor repair. Materials and method: The study included 10 patients with clinical and radiographic evidence of orbital floor fracture, divided randomly into two groups: Group I-operated using endoscopic approach; and Group II- operated using conventional external approach. All the patients were evaluated clinically preoperatively, immediate post-operative and after 1 month for Diplopia, Extrinsic ocular motility, Enophthalmos and Hypoglobus. Results: The study consisted of 40% females and 60% males, with mean age of Endoscopic and Conventional group being 27.20 ± 6.14 years and 27.60 ± 7.23 years respectively. In relation to diplopia, an insignificant difference was observed statistically. The mean change in enophthalmos and hypoglobus in endoscopic and conventional group showed a significant difference statistically (p < 0.001). Unrestricted ocular motility was present only in one case of each group and significantly increased to 5 cases in both the groups (p = 0.048). The mean duration of surgery in endoscopic and conventional group showed a significant difference statistically. Conclusion: Diplopia, hypoglobus and Enophthalmos correction was better achieved in endoscopic group as compared to conventional group. But duration of surgery was more in endoscopic group as compared to conventional group.
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Oral squamous cell carcinoma (OSCC) is a major form of oral malignant tumors (oral cancer) with less than 50% five year survival rate. Its pathogenesis involves dysregulation in apoptosis. Early dysregulation at molecular level could not be correlated with clinical presentations because of complex interactions at molecular levels. HSP70 (Heat shock Protein 70) and BCL2 (B cell lymphoma 2) are known molecular players in oncogenesis. However, their interaction is not known till date. Expression analyses of BCL2 and HSP70 was done through Enzyme Linked Immunosorbent Assay (ELISA) and Bioinformatic tools using blood samples from 41 OSCC, 35 Oral Potentially Premalignant Disorders (OPMD) and 4 controls in BCL2 study and 48 OSCC and 32 OPMD cases in HSP70 study. Bioinformatic software showed experimentally determined interaction value of 0.32 amongst the two, predicting similarity in molecular functions or pathways between the two, which was confirmed by ELISA. Our data showed that first HSP70 boosts BCL2 while in later stages of oncogenesis BCL2 consumes HSP70. Both molecules interact at several steps by complementing and supplementing each other. Because of this complex interaction various anti BCL2 therapies have not achieved desired results till date.
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Background: Dysfunctional basic cognitions have been suggested as potential vulnerability markers for alcohol dependence (AD). Although there is a growing body of research on the role of distal cognitive vulnerability factors such as early maladaptive schema in the development of AD, little is known about the role of proximal cognitive factors such as cognitive distortions, dysfunctional attitude, and negative automatic thoughts. Methods: This comparative cross-sectional study aimed to examine dysfunctional cognitions in individuals with AD (n = 84) in comparison with healthy individuals (n = 60). The dysfunctional cognitions were assessed on the Young Schema Questionnaire third version of Short Form, Cognitive Distortion Scale, Dysfunctional Attitude Scale-Form A, and Automatic Thought Questionnaire. Multivariate analysis of covariance was conducted to analyze the group differences in dysfunctional cognitions. Results: After controlling for the group difference in employment status, 12 of 18 schemas were more prevalent in individuals with AD than in healthy individuals. Individuals with AD also scored higher on seven of 10 cognitive distortions, as well as in terms of dysfunctional attitude and negative automatic thoughts. Conclusion: Dysfunctional cognition may play a significant role in developing AD. The findings may enhance our understanding of the nature and severity of dysfunctional cognitions in the development of AD. The information may further assist the clinicians in implementing adequate intervention strategies to manage dysfunctional cognitions in individuals with AD.
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Objectives: To compare and evaluate the modified tragus edge approach (MTEA) with retromandibular approach for surgical access to mid-level or low-level mandibular condylar fractures. Materials and Methods: This study comprised of 22 patients with mid-level or low-level condylar fracture. Patients with clinical and radiological evidence of mid-level or low-level condylar fracture are included only in this study. Patients were randomly divided into two groups: group A includes 11 patients, in which modified tragus edge approach was used, and group B includes 11 patients treated with retromandibular approach. Patients were evaluated clinically after first week, second week, fourth week, third month, and sixth month radiographically. Results: The mean age of the study subjects in group A was 32.45 ± 8.98 years, while in group B, the mean age was 26.91 ± 5.79 years. Post-operatively, no significant difference was seen in relation to pain, occlusal relationship, mouth opening, and deviation of jaw during opening and closing movements. In terms of post-operative complication, only significant difference found between two groups is post-operative scar visibility, which is higher in retromandibular incision group as compared to MTEA. Conclusion: Thus, we can conclude that MTEA provides ease of operation as a good exposure of mandibular mid- or low-level condylar fracture as retromandibular approach but with less visibility of post-operative scar as compared to retromandibular approach.
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Government programs supporting self help groups (SHGs) generally target women on the assumption that doing so enhances women's decision-making. The empirical evidence, however, is mixed. We advance and test one explanation: the loan amounts offered by most SHGs may be too small to impact women. Our analysis is based on SHGs developed under India's National Rural Livelihoods Mission, a program that supported both small loans from internal savings and larger loans through Community Investment Funds (CIFs). Exploiting variation in their phasing and amount, we document a large effect of CIFs on women's decision-making and on intra-household allocations.
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Plasmepsin V (Plm V) is an essential aspartic protease required for survival of the malaria parasite, Plasmodium falciparum (Pf). Plm V is required for cleaving the PEXEL motifs of many Pf proteins and its inhibition leads to a knockout effect, indicating its suitability as potential drug target. To decipher new inhibitors of PfPlm V, molecular docking of four HIV-1 protease inhibitors active against PfPlmV was performed on Glide module of Schrödinger suite that supported saquinavir as a lead drug, and therefore, selected as a control. Saquinavir contains an important hydroxyethylamine (HEA) pharmacophore, which was utilized as backbone coupled with piperazine scaffold to build new library of compounds. Newly designed HEA compounds were screened virtually against Plm V. Molecular docking led to a few hits (1 and 3) with higher docking score over the control drug. Notably, compound 1 showed the highest docking score (-11.90 kcal/mol) and XP Gscore (-11.948 kcal/mol). The Prime MMGBSA binding free energy for compound 1 (-60.88 kcal/mol) and 3 (-50.96 kcal/mol) was higher than saquinavir (-37.51 kcal/mol). The binding free energy for the last frame of molecular dynamic simulation supported compound 1 (-92.88 kcal/mol) as potent inhibitor of PfPlm V over saquinavir (-72.77 kcal/mol), and thus, deserves experimental validations in culture and subsequently in animal models.Communicated by Ramaswamy H. Sarma.