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Precision in personalized medicine is a crucial subject that needs comprehensive discussion and scientific validation. Traditional healthcare approaches like the Ayurvedic Sciences are often contextually linked with personalized medicine. However, it is unfortunate that this knowledge concerning Ayurveda and personalized medicine is restricted to applying systems biology techniques to 'prakriti' the phenotypic expression and characterization detailed in the literature. There are other significant constructs besides prakruti that interest an Ayurvedic physician, which accounts for crafting precision in evidence-based medicinal practices. There is this influential model of Ayurvedic healthcare practice wherein the physician maps specific personalized characters in addition to prakruti to deduce the host responses to endogenous and exposome conditions. Subsequently, tailored protocols are administered that bring about holistic, personalized outcomes. The review aimed to determine the effective methods for integrating Systems Biology, Ayurvedic Sciences, and Personalized Medicine (precision medicinebased). Ayurveda adopts a holistic approach, considering multiple variables and their interconnections, while the modern reductionist approach focuses on understanding complex details of smaller parts through rigorous experimentation. Despite seeming extremes, ongoing research on lifestyle, gut health, and spiritual well-being highlights the evolving intersection between traditional Ayurvedic practices and modern science. The current focus is on developing the fundamental concept of Ayurveda Biology by incorporating Systems Biology techniques. Challenges in this integration include understanding diverse data types, bridging interdisciplinary knowledge gaps, and addressing technological limitations and ethical concerns. Overcoming these challenges will require interdisciplinary collaboration, innovative methodologies, substantial investment in technology, and cultural sensitivity to preserve Ayurveda's core principles while leveraging modern scientific advancements. The focus of discussions and debates on such collaborations should be breakthrough clinical models, such as chronic inflammation, which can be objectively related to specific stages of disease manifestations described in Ayurveda. Validating patient characteristics with systems biology approaches, particularly in shared pathologies like chronic inflammation, is crucial for bringing prediction and precision to personalized medicine.

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Introduction: Contemporary incisions used to access the frontozygomatic (FZ) sutures are the lateral brow and upper blepharoplasty incisions which are associated with specific limitations and complications. The authors describe the use of sub-brow incision as an alternate approach for exposure of the FZ region. Methods: This is a prospective cohort study involving patients requiring surgical management of zygomatico maxillary complex (ZMC) fractures with fixation at FZ suture alone or along with fixation at infra-orbital rim and/or zygomaticomaxillary buttress. A sub-brow incision was used to expose the fracture and fixation was done with a 4-hole miniplate. The parameters evaluated were specific to the FZ region (sub-brow incision), namely surgical access, bleeding, fracture exposure time, post-operative scar, and pain. Each patient was reviewed on 1st, 5th, 7th, 10th, 30th, and 90th day. Results: The study sample included eight male patients. The mean age was 30 years. The sub-brow incision demonstrated favorable postoperative outcomes; adequate exposure was achieved in all 8 patients. The scar formation was found to be higher on the 7th day and the least scar formation was seen by the third month. The mean pain score was found to be high on first post-operative day and the least pain was seen by the 10th day. The mean score of surgical field bleeding was found to be 1.75 which signified mild bleeding according to Fromme's scale. The mean time taken for adequate exposure of the fracture was 6.62 min. All the assessment parameters were statistically significant (P value <0.01). Conclusion: Sub-brow incision is an effective approach for ORIF of zygomatic fractures at FZ suture. The technique is quick, simple, and associated with minimal complications.

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The objective of this study was to assess the efficacy of calcitonin spray on bone healing following open reduction internal fixation (ORIF) of mandibular fractures. Fourteen patients were subdivided into a study group and a control group. A standardized surgical protocol for ORIF was followed. Postoperatively, salmon calcitonin nasal spray was administered to only the study group. The outcome parameters assessed were serum osteocalcin, pain, and radiographic bone healing. Serum osteocalcin was assessed pre- and postoperatively. Postoperative pain was documented using a visual analogue scale (VAS) on the 7th, 14th, 23rd, and 30th days. An orthopantomogram was used to score fracture healing at four time intervals, as follows: 1 - absence of callus; 2 - presence of minimal callus; 3 - considerable callus; and 4 - complete fusion of fracture. Pain scores were lower for the study group, with no pain from the fifth day, while the control group produced a mean score for day 5 of 2.43 ± 0.98 (p = 0.001). Mean postoperative serum osteocalcin levels were higher for the study group (67.82 ± 8.89) compared with the control group (57.69 ± 6.22; p = 0.029). Bone healing at 12 weeks postoperatively was level 4 for 28.6% of patients in the study group and level 3 for 71.4%. In comparison, 85.7% in the control group demonstrated level 3 healing, while 14.3% remained at level 2 (p = 0.462). Within the limitations of the study, it can be concluded that intranasal salmon calcitonin spray reduces postoperative pain and facilitates fracture healing, although its economic efficiency is still to be proven.

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BACKGROUND: We report patient characteristics, treatment pattern and one-year clinical outcome of nonvalvular atrial fibrillation (NVAF) from Kerala, India. This cohort forms part of Kerala Atrial Fibrillation (KERALA-AF) registry which is an ongoing large prospective study. METHODS: KERALA-AF registry collected data of adults with previously or newly diagnosed atrial fibrillation (AF) during April 2016 to April 2017. A total of 3421 patients were recruited from 53 hospitals across Kerala state. We analysed one-year follow-up outcome of 2507 patients with NVAF. RESULTS: Mean age at recruitment was 67.2 years (range 18-98) and 54.8% were males. Main co-morbidities were hypertension (61.2%), hyperlipidaemia (46.2%) and diabetes mellitus (37.2%). Major co-existing diseases were chronic kidney disease (42.1%), coronary artery disease (41.6%), and chronic heart failure (26.4%). Mean CHA2DS2-VASc score was 3.18 (SD ± 1.7) and HAS-BLED score, 1.84 (SD ± 1.3). At baseline, use of oral anticoagulants (OAC) was 38.6% and antiplatelets 32.7%. On one-month follow-up use of OAC increased to 65.8% and antiplatelets to 48.3%. One-year all-cause mortality was 16.48 and hospitalization 20.65 per 100 person years. The main causes of death were cardiovascular (75.0%), stroke (13.1%) and others (11.9%). The major causes of hospitalizations were acute coronary syndrome (35.0%), followed by arrhythmia (29.5%) and heart failure (8.4%). CONCLUSIONS: Despite high risk profile of patients in this registry, use of OAC was suboptimal, whereas antiplatelets were used in nearly half of patients. A relatively high rate of annual mortality and hospitalization was observed in patients with NVAF in Kerala AF Registry.

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Polyphenols have been suggested as potential therapeutic agents for the treatment of amyloidogenic diseases. In this work, we evaluate quercetin-rich onion extract for its ability to inhibit tau fibrillization. Considering the presence of polyphenols in multiple glycosidic and aglycosidic forms, a nanobiocatalyst-mediated approach has been used to extract quercetin from onion skins. The nanobiocatalysts facilitate greater release of quercetin compared to the use of free enzymes. Atomic force microscopy and fluorescence microscopy show that quercetin possesses a novel inhibitory character on tau-fibril aggregation. In contrast, quercetin-diglucoside does not have an inhibitory effect. Molecular Dynamics simulations reveal conformational changes in tau protein upon interaction with quercetin due to specific hydrogen bonding and hydrophobic interactions. The resulting conformational stability of tau monomer reduces propensity of the protein to aggregate. The ability of quercetin to inhibit tau fibrillization expands the paradigm for application of bioactive polyphenols.

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BACKGROUND: Carbamylation is a non-enzymatic post-translational modification (PTM), which involves the covalent modification of N-terminus of protein or ε-amino group of Lys. The role of carbamylation in several age-related disorders is well documented, however, the relationship between carbamylation and neurodegenerative disorders including Alzheimer's disease remains uncharted. METHODS: In the present study, using aggregation-prone tau-core hexapeptide fragments 306VQIVYK311 (PHF6) and 275VQIINK280 (PHF6*) as models, we have elucidated the effect of carbamylation on aggregation kinetics and the changes occurring in the 3-dimensional architecture of fibrils using biophysical assays and molecular dynamics simulations. RESULTS: We found that carbamylation aids in amyloid formation and can convert the unstructured off-pathway aggregates into robust amyloids, which were toxic to cells. Electron microscopy images and molecular dynamics simulations of PHF6 fibrils showed that carbamylated peptides can form excess hydrogen bonds and modulate the pitch length and twist of peptides fibrils. We have also compared N-terminal carbamylation to acetylation and further extended our finding to full length tau that exhibits aggregation upon carbamylation even in the absence of any external inducer. CONCLUSION: Our in vitro and in silico results together suggest that carbamylation can modulate the aggregation pathway of the amyloidegenic sequences and cause structural changes in fibril assemblies. GENERAL SIGNIFICANCE: Carbamylation acts as a switch, which triggers the aggregation in short amyloidogenic peptide fragments and modulate the structural changes in resulting amyloid fibrils.

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OBJECTIVE: To study the prognostic value of soluble Suppression of Tumorigenicity-2 (sST2) in heart failure patients with reduced ejection fraction (HFrEF). METHODS: In this prospective, observational, multicenter study, patients with heart failure (HF) and left ventricular ejection fraction (LVEF) <50% were included. Clinical evaluation and serum levels of sST2 were estimated at five time points during follow up. Study endpoint was the relationship of baseline and serial sST2 concentration in the blood to the composite endpoints of cardiac death and re-hospitalization for worsening of HF during one year follow up period. RESULTS: A total of 141 patients were enrolled. The mean age was 60±10.4years. At baseline evaluation, 49.6% patients were in New York Heart Association (NYHA) class III and 36.2% in class IV. Adverse events were observed in 57 patients (40.4%); 25 (17.7%) were re-hospitalized due to worsening of HF and 32 (22.7%) died due to cardiac causes. The median value of baseline sST2 was 46.36ng/ml (IQR 31.30-78.38). sST2 concentration at baseline was significantly higher among patients with adverse events in comparison to patients without adverse events (p=<0.001). Receiver operating characteristic curve (ROC) for baseline sST2 concentration identified 49ng/ml as optimal cut-off value to predict cardiac death and re-hospitalization, with a sensitivity and specificity of 72% and 75%, respectively. CONCLUSION: In patients with HFrEF, sST2 concentration at baseline as well as on serial testing was significantly correlated with cardiac death and re-hospitalization for worsening of HF.

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BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder which is characterized by the deposits of intra-cellular tau protein and extra-cellular amyloid-ß (Aß) peptides in the human brain. Understanding the mechanism of protein aggregation and finding compounds that are capable of inhibiting its aggregation is considered to be highly important for disease therapy. METHODS: We used an in vitro High-Throughput Screening for the identification of potent inhibitors of tau aggregation using a proxy model; a highly aggregation-prone hexapeptide fragment 306VQIVYK311 derived from tau. Using ThS fluorescence assay we screened a library of 2401 FDA approved, bio-active and natural compounds in attempt to find molecules which can efficiently modulate tau aggregation. RESULTS: Among the screened compounds, palmatine chloride (PC) alkaloid was able to dramatically reduce the aggregation propensity of PHF6 at sub-molar concentrations. PC was also able to disassemble preformed aggregates of PHF6 and reduce the amyloid content in a dose-dependent manner. Insights obtained from MD simulation showed that PC interacted with the key residues of PHF6 responsible for ß-sheet formation, which could likely be the mechanism of inhibition and disassembly. Furthermore, PC could effectively inhibit the aggregation of full-length tau and disassemble preformed aggregates. CONCLUSIONS: We found that PC possesses "dual functionality" towards PHF6 and full-length tau, i.e. inhibit their aggregation and disassemble pre-formed fibrils. GENERAL SIGNIFICANCE: The "dual functionality" of PC is valuable as a disease modifying strategy for AD, and other tauopathies, by inhibiting their progress and reducing the effect of fibrils already present in the brain.

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Intra-cellular tau protein tangles and extra-cellular ß-amyloid plaques are hallmarks of Alzheimer's disease (AD), characterized by the conversion of natively unfolded monomeric protein/peptide into misfolded ß-sheet rich aggregates. Therefore, inhibiting the aggregation cascade or disassembling the pre-formed aggregates becomes a pivotal event in disease treatment. In the present study, we show that Naphthoquinone-Tryptophan hybrids, i.e., NQTrp and Cl-NQTrp significantly disrupted the pre-formed fibrillar aggregates of Tau-derived PHF6 (VQIVYK) peptide and full-length tau protein in vitro, in a dose-dependent manner as evident from ThS assay, CD spectroscopy, and TEM. Molecular dynamics simulation of PHF6 oligomers and fibrils with the Naphthoquinone-Tryptophan hybrids provides a possible structure-function based mechanism-of-action, highlighting the role of hydrophobic interaction and hydrogen bond formation during fibril disassembly. These findings signify the effectiveness of NQTrp and Cl-NQTrp in disassembling fibrillar aggregates and may help in designing novel hybrid molecules for AD treatment.

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PURPOSE: This study aimed at assessing the change in salivary opiorphin levels before and after administration of local anesthesia, with the use of three different local anesthetic agents, and different anaesthetic techniques. METHODS: The investigators implemented a randomized controlled clinical study in 144 patients who required tooth extraction after administration of local anaesthesia. A total of 288 samples were collected in sterile containers before and after administration of local anesthetics. The salivary samples were centrifuged and salivary opiorphin levels were estimated using ELISA testing and spectrophotometric analysis. Statistical analysis was done using one way ANOVA and unpaired t test. RESULTS: There was a mean decrease in salivary opiorphin levels after administration of local anesthesia. There was no significant difference in the change in salivary opiorphin levels across different anesthetic techniques and different drug subgroups. CONCLUSION: The present study did not show much association between various local anesthetic agents and techniques and change in salivary opiorphin levels. The role of opiorphin as a biomarker for pain control and its effect on various pain control methods including local anesthesia must be evaluated in detail. Institutional review board number SRMDC/IRB/2014/MDS/No. 405.

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Abnormal neck posture while working is a crucial factor that predisposes to incidence of musculoskeletal disorders amongst oral and maxillofacial surgeons. The related spectrum of clinical symptoms may range from severe pain in the lower and upper back, neck and TMJ to neurological deficits of the hand and wrist. These posture-related problems may be prevented by use of reflected vision that ensures a balanced neck posture during surgical procedures.

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Tau is an intrinsically disordered protein responsible for maintaining the structure and stability of axonal microtubules. However, in certain disease conditions including Alzheimer's disease, tau protein may undergo biochemical and structural changes to form intracellular aggregates. Since tau is a proline- and arginine-rich eukaryotic protein, heterologous expression in Escherichia coli often results in poor yield and has been a major technical challenge. In the current work, we have improved the expressed yield of tau by overcoming codon bias problem and established a simplified protocol for efficient extraction. The reported method has two distinct features: (i) enhanced tau expression (upto eightfold) by supplementing deficient tRNAs that aid in rapid translation and (ii) direct boiling of expressed E. coli cells to extract tau with no separate cell lysis step. We further demonstrate that tau extracted by the direct boiling method is similar to tau purified by size-exclusion chromatography exhibiting similar structural and biophysical characteristics including aggregation propensity. Since morphologies and in vitro toxicity of fibrillar tau aggregates were also similar, tau extracted by the one-step direct boiling method can be used for tau aggregation assays without any additional purification.

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PURPOSE: The aim of this radiomorphometric study was to analyze the association between the mandibular gonial angle and the risk of mandibular angle fracture. MATERIALS AND METHODS: A retrospective analysis of medical records and radiographs of patients treated for mandibular fractures was performed. The exposure studied was the presence of a high gonial angle and the outcome was fracture of the mandibular angle. The mandibular gonial angle and mandibular height at the angle were measured using Facad software (Ilexis AB, Linköping, Sweden). Data obtained were analyzed using SPSS 16 (IBM Corp, Armonk, NY). RESULTS: The study sample was comprised of 210 mandibular fractures (70 mandibular angle fractures and 140 non-angle fractures). The mean gonial angle in patients with mandibular angle fractures was 126.8 ± 7.9°, which was 4.5° larger than in patients with other mandibular fractures (P = .0001). Patients with a high gonial angle were 11.77 times more likely to sustain an angle fracture than those with normal or low gonial angles (adjusted odds ratio = 11.77; 95% confidence interval, 3.65-37.94; P < .001). There also was a statistically significant decrease in mandibular height at the angle in patients with a high gonial angle (P = .0001). CONCLUSION: This study shows that people with a high gonial angle are at an increased risk for angle fracture and presents the related clinical implications.

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PURPOSE: To assess the influence of topical ozone administration on patient comfort after third molar surgery. MATERIALS AND METHODS: A single-blinded randomized controlled clinical trial was designed involving patients who required removal of bilateral impacted mandibular third molars. The predictor variable was the postoperative medication used after third molar surgery. Using the split-mouth design, the study group received topical ozone without postoperative systemic antibiotics, whereas the control group did not receive ozone but only systemic antibiotics. The 2 groups were prescribed analgesics for 2 days. The assessing surgeon was blinded to treatment assignment. The primary outcome variables were postoperative mouth opening, pain, and swelling. The secondary outcome variable was the number of analgesic doses required by each group on postoperative days 3 to 5. Data analysis involved descriptive statistics, paired t tests, and 2-way analysis of variance with repeated measures (P < .05). SPSS 20.0 was used for data analysis. RESULTS: The study sample included 33 patients (n = 33 in each group). The study group showed statistically relevant decreases in postoperative pain, swelling, and trismus. Further, the number of analgesics required was smaller than in the control group. No adverse effects of ozone gel were observed in any patient. CONCLUSION: Ozone gel was found to be an effective topical agent that considerably improves patient comfort postoperatively and can be considered a substitute of postoperative systemic antibiotics.

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We report few-cycle THz pulses emission from a novel organic crystal 2,6-diaminopyridinium-4-nitrophenolate-4-nitrophenol (DAP+NP-NP). The observed amplitude of the THz electric field from a DAP+NP-NP crystal is comparable with that from a ZnTe single crystal under the same optical pumping conditions. Both the waveform and spectra of the THz radiation from DAP+NP-NP are similar to those from ZnTe. We conclude that a high quality DAP+NP-NP crystal would be a high potential candidate in THz generation and applications.

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The wide applicability of silver nanoparticles in medicine and pharmaceutical industries leads to its over exploitation and thus contaminating our environment. Majority of these nanoscale dimension particles finally accumulates in fresh water and marine ecosystem. As the nanoparticles behave entirely different from its corresponding bulk material, a better understanding of their environmental impacts in aquatic ecosystems is inevitable. The study was focused on a comparative stress physiology analysis of chemically synthesized silver nanoparticles and biogenic silver nanoparticles. Half maximal inhibitory concentration of biologically synthesized and chemically synthesized nanoparticles was found out (30µg/mL and 20µg/mL respectively). The Heat Shock Protein (HSP70) secretion was analysed in the fresh water fish Oreochromis niloticus after exposing to different concentrations of biologically and chemically synthesized silver nanoparticles along with the silver in its ionic form. The intense immune-histochemical staining of fish tissues (muscle, kidney and liver) analyzed proportionately reflected the stress created. The colour intensity was directly proportional to the stress created or the stress protein released. High level of HSP70 expression was observed in all of the fish tissues exposed to silver ions and chemically synthesized silver nanoparticles, when compared to that of biologically synthesized. The results revealed the significance of comparatively safe and less toxic biogenic nanoparticles compared to the chemically synthesized.

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In this work, the vibrational spectral analysis is carried out by using Raman and infrared spectroscopy in the range 4000-400 cm(-1) and 4000-50 cm(-1) respectively for N,N-Diphenyl Formamide (DPF) molecule. The optimized molecular structures, vibrational frequencies and corresponding vibrational assignments, nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-VIS) spectra of the title molecule are evaluated using density functional theory (DFT) with standard B3LYP/6-31G(d,p) basis set. The harmonic vibrational frequencies are calculated and the scaled values have been compared with experimental FT-IR and FT-Raman spectra. The observed and calculated frequencies are found to be in good agreement. The stability of the molecule arising from hyper conjugative interactions and the charge delocalization has been analyzed using natural bond (NBO) analysis. The possible electronic transitions are determined by HOMO-LUMO orbital shapes and their energies. Thermodynamic properties (heat capacity, entropy and enthalpy) and the first hyperpolarizability of the title compound are calculated. The Mulliken charges and electric dipole moment of the molecule are computed using DFT calculations. The (1)H and (13)C nuclear magnetic resonance (NMR) chemical shift of the molecules are calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results.

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In this work, the vibrational characteristics of 2-Benzylpyridine have been investigated. The structure of the molecule has been optimized and the structural characteristics of the molecule have been determined by density functional theory B3LYP method with 6-31G(d,p) basis set. The infrared and Raman spectra have been simulated from calculated intensities. Both the experimental and theoretical vibrational data confirms the presence of functional groups in the title compound. The (1)H and (13)C NMR spectra were recorded and (1)H and (13)C nuclear magnetic resonance chemical shifts of the molecule were calculated using the gauge independent atomic orbital method. UV-Visible spectrum of the title compound was recorded in the region 190-1100 nm and the electronic properties HOMO and LUMO energies were calculated by CIS approach. Nonlinear optical and thermodynamic properties were interpreted. All the calculated results were compared with the available experimental data of the title molecule.

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Maltol (3-hydroxy-2-methyl-4pyrone) is widely known as metal ions chelator with many practical applications in catalysis, medicine and food chemistry. The FTIR and FT-Raman spectra of maltol have been recorded in the region 4000-400 and 4000-50 cm(-1), respectively. The conformational analysis, optimized geometry, frequency and intensity of the vibrational bands of maltol were obtained by the density functional theory (DFT) with complete relaxation in the potential energy surface using 6-31G* basis set. The observed and the calculated frequencies are found to be in good agreement. The (1)H and (13)C NMR spectra have been recorded and (1)H and (13)C nuclear magnetic resonance chemical shifts of the molecule were also calculated using the gauge independent atomic orbital (GIAO) method and their respective linear correlations were obtained. The electronic properties HOMO and LUMO energies were measured. Thermodynamic properties (heat capacity, entropy and enthalpy) of the title compound were calculated. The Mulliken charges, the values of electric dipole moment (µ) of the molecule were computed using DFT calculations. The first order hyperpolarizability (ßo) and related properties (ß, αo and Δα) of both are calculated using B3LYP/6-31G* method on the finite-field approach. The calculated first hyperpolarizability shows that the molecules are an attractive molecule for future applications in non-linear optics. The intramolecular contacts have been interpreted using Natural Bond Orbital (NBO).

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Organic 2,5-dichloroanilinium picrate crystal was grown by using slow evaporation solution technique. The lattice parameter was estimated by powder X-ray diffraction. The absence of absorption at around Nd:YAG fundamental wavelength was confirmed by ultraviolet-visible absorption study. The vibrational analyses confirm the various functional groups present in the grown crystal. The NMR study confirms the presence of chemical environment of hydrogen in the title crystal. The thermogravimetric (TG), differential thermal analysis (DTA) and differential scanning calorimetry (DSC) traces reveals the thermal stability of the compound. The second harmonic generation (SHG) of the crystal was confirmed by Kurtz Perry powder technique. The theoretical studies such as first-order hyperpolarizability (ß), molecular orbitals, electronic excitation and electrostatic potential (ESP) were performed using Gaussian 03W software at HF/6-31G (d) level.

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