Nanoarchitectonics for synergistic activity of multimetallic nanohybrids as a possible approach for antimicrobial resistance (AMR).

The global threat posed by antimicrobial resistance (AMR) to public health is an immensurable problem. The effectiveness of treating infections would be more at risk in the absence of effective antimicrobials. Researchers have shown an amplified interest in alternatives, such as developing advanced metallic nanohybrids as new therapeutic candidates for antibiotics due to their promising effectiveness against resistant microorganisms. In recent decades, the antimicrobial activity of monometallic nanoparticles has received extensive study and solid proof, providing new opportunities for developing multimetallic nanohybrid antimicrobials. Advanced metallic nanohybrids are an emerging remedy for a number of issues that develop in the field of medicine. Advanced metallic nanohybrids have shown a promising ability to combat resistant microorganisms due to their overall synergistic activity. Formulating advanced multimetallic nanohybrids falling under the umbrella of the growing field of nanoarchitectonics, which extends beyond nanotechnology. The underlying theory of nanoarchitectonics involves utilizing nanoscale units that follow the concepts of nanotechnology to architect nanomaterials. This review focuses on a comprehensive description of antimicrobial mechanisms of metallic nanohybrids and their enabling future insights on the research directions of developing the nanoarchitectonics of advanced multimetallic nanohybrids as novel antibiotics through their synergistic activity.

Green Synthesised TiO2 Nanoparticles-Mediated Terenna asiatica: Evaluation of Their Role in Reducing Oxidative Stress, Inflammation and Human Breast Cancer Proliferation.

Oxidative stress and chronic inflammation interplay with the pathogenesis of cancer. Breast cancer in women is the burning issue of this century, despite chemotherapy and magnetic therapy. The management of secondary complications triggered by post-chemotherapy poses a great challenge. Thus, identifying target-specific drugs with anticancer potential without secondary complications is a challenging task for the scientific community. It is possible that green technology has been employed in a greater way in order to fabricate nanoparticles by amalgamating plants with medicinal potential with metal oxide nanoparticles that impart high therapeutic properties with the least toxicity. Thus, the present study describes the synthesis of Titanium dioxide nanoparticles (TiO2 NPs) using aqueous Terenna asiatica fruit extract, with its antioxidant, anti-inflammatory and anticancer properties. The characterisation of TiO2 NPs was carried out using a powdered X-ray diffractometer (XRD), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray diffraction (EDX), high-resolution transmission electron microscopy (HR-TEM), dynamic light scattering (DLS), and zeta-potential. TiO2 NPs showed their antioxidant property by scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals in a dose-dependent manner with an IC50 value of 80.21 µg/µL. To ascertain the observed antioxidant potential of TiO2 NPs, red blood cells (RBC) were used as an in vitro model system. Interestingly, TiO2 NPs significantly ameliorated all the stress parameters, such as lipid peroxidation (LPO), protein carbonyl content (PCC), total thiol (TT), superoxide dismutase (SOD), and catalase (CAT) in sodium nitrite (NaNO2)-induced oxidative stress, in RBC. Furthermore, TiO2 NPs inhibited RBC membrane lysis and the denaturation of both egg and bovine serum albumin, significantly in a dose-dependent manner, suggesting its anti-inflammatory property. Interestingly, TiO2 NPs were found to kill the MCF-7 cells as a significant decrease in cell viability of the MCF-7 cell lines was observed. The percentage of growth inhibition of the MCF-7 cells was compared to that of untreated cells at various doses (12.5, 25, 50, 100, and 200 µg/mL). The IC50 value of TiO2 NPs was found to be (120 µg/mL). Furthermore, the Annexin V/PI staining test was carried out to confirm apoptosis. The assay indicated apoptosis in cancer cells after 24 h of exposure to TiO2 NPs (120 µg/mL). The untreated cells showed no significant apoptosis in comparison with the standard drug doxorubicin. In conclusion, TiO2 NPs potentially ameliorate NaNO2-induced oxidative stress in RBC, inflammation and MCF-7 cells proliferation.

Ten years survival results of randomized study comparing weekly vs. triweekly cisplatin with concurrent radiation in locally advanced carcinoma cervix.

Background: The current standard of treatment for locally advanced cervical cancer is concurrent chemo-radiation with improved overall survival (OS) by 6% with manageable toxicities. The cisplatin 40 mg/m2 given weekly is the widely practiced regimen for 4-6 cycles concurrently with irradiation. Materials and methods: Two hundred and twelve patients with histologically proven squamous cell carcinoma of cervix with stages IIB to IIIB were enrolled between 2007-2011. External beam radiation dose of 45 Gy in 25 fractions was delivered over 5 weeks. Brachytherapy was delivered by manual afterloading cesium-137 (Cs137) low dose brachytherapy (LDR) using modified Fletcher suit intracavitary applicators to a total dose of 30 Gy to Point A or interstitial template to dose of 21 Gy/3 fractions with remote afterloading iridium-192 (Ir192) high dose brachytherapy (HDR). Patients were randomized to arm A receiving 40 mg/m2 of concurrent cisplatin weekly and arm B receiving 100 mg/m2 of concurrent cisplatin triweekly. Results: One hundred and nine patients were randomized to weekly cisplatin and one hundred and three patients to triweekly cisplatin at the end of recruitment. At ten years, the OS was higher in the weekly arm (79.8%) compared to triweekly arm (70.9%). Disease free survival (DFS) was almost equal (76.1% and 73.8%) in the weekly and three-weekly arms. There is definite significance in overall DFS with patients receiving the cumulative cisplatin doses of more than 250 mg (p = 0.028). The patients with more than 45 years of age had better overall survival (OS) (79%) with statistical significance 31 (p = 0.020). Conclusion: Both cisplatin based triweekly and weekly concurrent chemotherapy are equally effective in terms of OS and DFS.

Effect of Biofunctional Green Synthesized MgO-Nanoparticles on Oxidative-Stress-Induced Tissue Damage and Thrombosis.

The present study describes the green biofunctional synthesis of magnesium oxide (MgO) nanoparticles using the aqueous Tarenna asiatica fruit extract. The characterization of Tarenna asiatica fruit extract MgO nanoparticles (TAFEMgO NPs) was achieved by X-ray powder diffraction, UV-Vis spectroscopy, FTIR, TEM, SEM, and energy-dispersive X-ray diffraction. TAFEMgO NPs scavenged the DPPH free radicals with an IC50 value of 55.95 µg/µL, and it was highly significant compared to the standard. To authenticate the observed antioxidant potential of TAFEMgO NPs, oxidative stress was induced in red blood cells (RBC) using sodium nitrite (NaNO2). Interestingly, TAFEMgO NPs ameliorated the RBC damage from oxidative stress by significantly restoring the stress parameters, such as the protein carbonyl content (PCC), lipid peroxidation (LPO), total thiol (TT), super-oxide dismutase (SOD), and catalase (CAT). Furthermore, oxidative stress was induced in-vivo in Sprague Dawley female rats using diclofenac (DFC). TAFEMgO NPs normalized the stress parameters in-vivo and minimized the oxidative damage in tissues. Most importantly, TAFEMgO NPs restored the function and architecture of the damaged livers, kidneys, and small intestines by regulating biochemical parameters. TAFEMgO NPs exhibited an anticoagulant effect by increasing the clotting time from 193 s in the control to 885 s in the platelet rich plasma. TAFEMgO NPs prolonged the formation of the clot process in the activated partial thromboplastin time and the prothrombin time, suggest the effective involvement in both intrinsic and extrinsic clotting pathways of the blood coagulation cascade. TAFEMgO NPs inhibited adenosine di-phosphate (ADP)-induced platelet aggregation. TAFEMgO NPs did not show hemolytic, hemorrhagic, and edema-inducing properties at the tested concentration of 100 mg/kgbody weight, suggesting its non-toxic property. In conclusion, TAFEMgO NPs mitigates the sodium nitrite (NaNO2)- and diclofenac (DFC)-induced stress due to oxidative damage in both in vitro and in vivo experimental models.

Long-term Outcomes of Intensive Inpatient Care for Severe, Resistant Obsessive-Compulsive Disorder: Résultats à long terme de soins intensifs à des patients hospitalisés pour un trouble obsessionnel-compulsif grave et résistant.

OBJECTIVE: A substantial proportion of severely ill patients with obsessive-compulsive disorder (OCD) do not respond to serotonin reuptake inhibitors (SRIs) and are unable to practice cognitive behavioral therapy (CBT) on an out-patient basis. We report the short-term (at discharge) and long-term (up to 2 years) outcome of a multimodal inpatient treatment program that included therapist-assisted intensive CBT with adjunctive pharmacotherapy for severely ill OCD patients who are often resistant to SRIs and are either unresponsive or unable to practice outpatient CBT. METHODS: A total of 420 patients, admitted between January 2012 and December 2017 were eligible for the analysis. They were evaluated using the Mini International Neuropsychiatric Interview, the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the Clinical Global Impression (CGI) scale. All patients received 4 to 5 therapist-assisted CBT sessions per week along with standard pharmacotherapy. Naturalistic follow-up information at 3, 6, 12, and 24 months were recorded. RESULTS: At baseline, patients were mostly severely ill (YBOCS = 29.9 ± 4.5) and nonresponsive to ≥2 SRIs (83%). Mean duration of inpatient stay was 42.7 ± 25.3 days. At discharge, there was a significant decline in the mean YBOCS score (29.9 ± 4.5 vs. 18.1 ± 7.7, P < .001, Cohen's d = 1.64); 211/420 (50%) were responders (≥35% YBOCS reduction and CGI-I≤2) and an additional 86/420 (21%) were partial responders (25% to 35% YBOCS reduction and CGI-I≤3). Using latent class growth modeling of the follow-up data, 4 distinct classes were identified, which include "remitters" (14.5%), "responders" (36.5%), "minimal responders" (34.7%), and "nonresponders" (14.6%). Shorter duration of illness, better insight, and lesser contamination/washing symptoms predicted better response in both short- and long-term follow-up. CONCLUSION: Intensive, inpatient-based care for OCD may be an effective option for patients with severe OCD and should be considered routinely in those who do not respond with outpatient treatment.

Examining the initial usability, acceptability and feasibility of a digital mental health intervention for college students in India.

Generalised anxiety disorder (GAD) is prevalent among college students in India; however, barriers like stigma, treatment accessibility and cost prevent engagement in treatment. Web- and mobile-based, or digital, mental health interventions have been proposed as a potential solution to increasing treatment access. With the ultimate goal of developing an engaging digital mental health intervention for university students in India, the current study sought to understand students' reactions to a culturally and digitally adapted evidence-based cognitive behavioural therapy (CBT) for GAD intervention. Specifically, through theatre testing and focus groups with a non-clinical sample of 15 college students in India, the present study examined initial usability, acceptability and feasibility of the "Mana Maali Digital Anxiety Program." Secondary objectives comprised identifying students' perceived barriers to using the program and eliciting recommendations. Results indicated high usability, with the average usability rating ranking in the top 10% of general usability scores. Participants offered actionable changes to improve usability and perceived acceptability among peers struggling with mental health issues. Findings highlight the benefits of offering digital resources that circumvent barriers associated with accessing traditional services. Results build on existing evidence that digital interventions can be a viable means of delivering mental healthcare to large, defined populations.

The Effect of Nutritive and Non-Nutritive Sweeteners on the Growth, Adhesion, and Biofilm Formation of Candida albicans and Candida tropicalis.

OBJECTIVE: To determine the effect of glucose, sucrose, and saccharin on growth, adhesion, and biofilm formation of Candida albicans and Candida tropicalis. MATERIALS AND METHODS: The growth rates of mono-cultures of planktonic C. albicans and C. tropicalis and 1:1 mixed co-cultures were determined in yeast nitrogen broth supplemented with 5% (30 mM) and 10% (60 mM) glucose, sucrose, and saccharin, using optical density measurements at 2-h intervals over a 14-h period. Adhesion and biofilm growth were performed and the growth quantified using a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The biofilm architecture was visualized using scanning electron microscopy. One- and two-way analysis of variance (ANOVA) was performed to analyse the differences among multiple means. RESULTS: The highest planktonic growth was noted in 5% glucose after 14 h (p < 0.05). No significant planktonic growth was observed in either concentration of saccharin. Both the concentrations of glucose and sucrose elicited significantly increased adhesion from MTT activity of 0.017 to >0.019 in mono- as well as co-cultures (p < 0.05), whilst the lower concentration of saccharin significantly dampened the adhesion. Maximal biofilm growth was observed in both species with the lower concentration of sucrose (5%), although a similar concentration of saccharin abrogated biofilm development: the highest MTT value (>0.35) was obtained for glucose and the lowest (>0.15) for saccharin. CONCLUSION: In this study, glucose and sucrose accelerated the growth, adhesion, and biofilm formation of Candida species. However, the non-nutritive sweetener saccharin appeared to dampen, and in some instances suppress, these virulent attributes of Candida.

Culture media profoundly affect Candida albicans and Candida tropicalis growth, adhesion and biofilm development.

As there are sparse data on the impact of growth media on the phenomenon of biofilm development for Candida we evaluated the efficacy of three culture media on growth, adhesion and biofilm formation of two pathogenic yeasts, Candida albicans and Candida tropicalis. The planktonic phase yeast growth, either as monocultures or mixed cultures, in sabouraud dextrose broth (SDB), yeast nitrogen base (YNB), and RPMI 1640 was compared, and adhesion as well as biofilm formation were monitored using MTT and crystal violet (CV) assays and scanning electron microscopy. Planktonic cells of C. albicans, C. tropicalis and their 1:1 co-culture showed maximal growth in SDB. C. albicans/C. tropicalis adhesion was significantly facilitated in RPMI 1640 although the YNB elicited the maximum growth for C. tropicalis. Similarly, the biofilm growth was uniformly higher for both species in RPMI 1640, and C. tropicalis was the slower biofilm former in all three media. Scanning electron microscopy images tended to confirm the results of MTT and CV assay. Taken together, our data indicate that researchers should pay heed to the choice of laboratory culture media when comparing relative planktonic/biofilm growth of Candida. There is also a need for standardisation of biofilm development media so as to facilitate cross comparisons between laboratories.

Candida infection in oral leukoplakia: an unperceived public health problem.

OBJECTIVES: The study aimed to determine the proportion, known risk factors and etiology for Candida infection in leukoplakia lesions among patients with oral leukoplakia attending the Oral and Maxillofacial Clinic at a Tertiary Care Hospital in Sri Lanka. MATERIALS AND METHODS: Eighty clinically suspected oral leukoplakia patients were included. Two oral swabs each, from leukoplakia patients: one swab from the lesion and the other one from the contralateral unaffected corresponding area (as a control) were collected. Direct microscopy and culture followed by colony count and phenotypic identification were performed to identify pathogenic Candida species. RESULTS: Candida infection was seen in 47% of patients with oral leukoplakia. Candida albicans (94.7%) was the most common Candida species followed by Candida tropicalis (5.3%). Majority of Candida-infected lesions were seen in the buccal mucosa region. Alteration of taste (p = 0.021), having other oral lesions (p = 0.008), angular cheilitis (p = 0.024) and periodontitis (p = 0.041) showed a significant association with Candida-associated leukoplakia. Increasing age showed a significant tendency for Candida infection (p = 0.020). Smoking (p = 0.026) and betel-quid chewing (p = 0.006) were also found to be significantly associated, although alcohol consumption alone did not show a significant association. Oral leukoplakia patients who had all three habits: alcohol consumption, smoking and betel-quid chewing had a significant association with Candida infection (p = 0.004). CONCLUSIONS: Patients who had a combination of risk factors: smoking, betel-quid chewing and alcohol consumption were seen to have a significant association with Candida infection. Further betel-quid chewing alone and smoking singly was also significantly associated with Candida infection in oral leukoplakia.

Crystal structure of ATP-binding subunit of an ABC transporter from Geobacillus kaustophilus.

The ATP binding cassette (ABC) transporters, represent one of the largest superfamilies of primary transporters, which are very essential for various biological functions. The crystal structure of ATP-binding subunit of an ABC transporter from Geobacillus kaustophilus has been determined at 1.77 Å resolution. The crystal structure revealed that the protomer has two thick arms, (arm I and II), which resemble 'L' shape. The ATP-binding pocket is located close to the end of arm I. ATP molecule is docked into the active site of the protein. The dimeric crystal structure of ATP-binding subunit of ABC transporter from G. kaustophilus has been compared with the previously reported crystal structure of ATP-binding subunit of ABC transporter from Salmonella typhimurium.

Dentigerous Cysts of Maxillofacial Region- Clinical, Radiographic and Biochemical Analysis.

BACKGROUND: Dentigerous cyst is the second most common type of odontogenic cysts that encloses the crown of an unerupted tooth by expansion of its follicle due to the collection of cystic fluid. In view of the capability of these lesions attaining a marked size if not diagnosed early and treated properly, the present study was done based on the clinical and radiographic presentation of the dentigerous cyst in addition to the analysis of the cystic contents. OBJECTIVE: The present study reported 14 cases of dentigerous cysts (DC) with their incidence and relative distribution of the maxillofacial region along with the clinical and radiographic features and biochemical analysis of cystic fluid. METHOD: The study was conducted at Sri Govind Tricentenary Dental College, Hospital and Research Institute, Gurgaon, Haryana for a period of one year and six months. A detailed case history and thorough clinical examination was done for the patients who were provisionally found to have odontogenic cysts. Necessary radiographs, aspiration of the cystic fluid and incisional biopsy were performed to the 14 patients who were provisionally diagnosed with dentigerous cysts (DC) after obtaining the informed consent and the cystic fluid was subjected to biochemical analysis. RESULTS: Majority of the affected patients with DC were in their second decade and showed more predilection for mandible with a male predominance. The area of predilection was third molar region in the mandible and it is the canine region in maxilla. All the cases were associated with impacted teeth and majority showed expansion of the buccal/labial cortical plate. The various biochemical variables (total protein content, albumin, globulin and albumin: globulin ratio) were also assessed in the present study. CONCLUSION: The awareness of protean features of DC evident through this study is essential for the general as well as specialty practitioners for the accurate diagnosis and proper treatment planning of these non cancerous but potentially destructive lesions and also opens new avenues for further research.

Crystal structure studies of NADP+ dependent isocitrate dehydrogenase from Thermus thermophilus exhibiting a novel terminal domain.

NADP(+) dependent isocitrate dehydrogenase (IDH) is an enzyme catalyzing oxidative decarboxylation of isocitrate into oxalosuccinate (intermediate) and finally the product α-ketoglutarate. The crystal structure of Thermus thermophilus isocitrate dehydrogenase (TtIDH) ternary complex with citrate and cofactor NADP(+) was determined using X-ray diffraction method to a resolution of 1.80 Å. The overall fold of this protein was resolved into large domain, small domain and a clasp domain. The monomeric structure reveals a novel terminal domain involved in dimerization, very unique and novel domain when compared to other IDH's. And, small domain and clasp domain showing significant differences when compared to other IDH's of the same sub-family. The structure of TtIDH reveals the absence of helix at the clasp domain, which is mainly involved in oligomerization in other IDH's. Also, helices/beta sheets are absent in the small domain, when compared to other IDH's of the same sub family. The overall TtIDH structure exhibits closed conformation with catalytic triad residues, Tyr144-Asp248-Lys191 are conserved. Oligomerization of the protein is quantized using interface area and subunit-subunit interactions between protomers. Overall, the TtIDH structure with novel terminal domain may be categorized as a first structure of subfamily of type IV.

Crystal structures of type IIIH NAD-dependent D-3-phosphoglycerate dehydrogenase from two thermophiles.

In the L-Serine biosynthesis, D-3-phosphoglycerate dehydrogenase (PGDH) catalyzes the inter-conversion of D-3-phosphoglycerate to phosphohydroxypyruvate. PGDH belongs to 2-hydroxyacid dehydrogenases family. We have determined the crystal structures of PGDH from Sulfolobus tokodaii (StPGDH) and Pyrococcus horikoshii (PhPGDH) using X-ray diffraction to resolution of 1.77Å and 1.95Å, respectively. The PGDH protomer from both species exhibits identical structures, consisting of substrate binding domain and nucleotide binding domain. The residues and water molecules interacting with the NAD are identified. The catalytic triad residues Glu-His-Arg are highly conserved. The residues involved in the dimer interface and the structural features responsible for thermostability are evaluated. Overall, structures of PGDHs with two domains and histidine at the active site are categorized as type IIIH and such PGDHs structures having this type are reported for the first time.

Temporal patterns of change in panic disorder during cognitive behaviour therapy: an Indian study.

BACKGROUND: CBT has been proven to be effective in the treatment of panic disorder; however, attempts to study the process of change are limited. AIM: The study evaluated the temporal patterns of change in the panic symptoms, cognitions, behaviours, and anxiety sensitivity in subjects with panic disorder being treated with CBT. METHOD: Thirty subjects with panic disorder were allocated to two groups: Cognitive Behaviour Therapy (CBT, n = 15) and Behaviour Therapy (BT, n = 15). Assessments were carried out weekly for five consecutive weeks using the Semi-Structured Interview Schedule, the Anxiety Sensitivity Index, the Agoraphobic Cognitions Questionnaire, and the Texas Panic Attack Record Form. The CBT group received comprehensive CBT and the BT group received psycho-education and Applied Relaxation. RESULTS: Following intervention the change was continuous and gradual on all the variables in the CBT group and the scores reduced to a functional range after 4-5 weeks of therapy. Such a change was not evident in the BT group. Significant change was evident in cognitive domains following the introduction of the exposure and cognitive restructuring within the CBT group. Both cognitive and behavioural techniques contributed to the overall change. CONCLUSION: CBT had an impact on the cognitive domains and significant changes were evident corresponding to the addition of cognitive restructuring and exposure techniques in the 3rd to 5th week. Both cognitive and behavioural components are therefore crucial for overall improvement to occur.

2-(3,4-Di-meth-oxy-phen-yl)-4-(thio-phen-2-yl)-2,3-di-hydro-1,5-benzo-thia-zepine.

In the title compound, C21H19NO2S2, the seven-membered thia-zepine ring adopts a slightly distorted twist boat conformation. The dihedral angle between the benzene rings is 67.4 (2)°. The mean plane of the thio-phene ring is twisted by 59.3 (2) and 87.7 (2)° from the mean planes of the benezene rings. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds generate R 2 (2)(20) loops.

4-(Thio-phen-2-yl)-2-[4-(tri-fluoro-meth-yl)phen-yl]-2,3-di-hydro-1,5-benzo-thia-zepine.

In the title compound, C20H14F3NS2, the seven-membered thia-zepine ring adopts a slightly distorted twist-boat conformation. The mean plane of the five-membered thio-phene ring fused to the thia-zepine ring is twisted by 32.3 (3) and 55.6 (4)° from the benzene and phenyl rings, respectively. In the crystal, inversion dimers linked by pairs of weak C-H⋯N inter-actions are observed.

Potential antifungal applications of heterometallic silica nanohybrids: A synergistic activity.

An estimated 1.7 million fatalities and 150 million cases worldwide are attributed to fungal infections annually, that are in rise due to immunocompromised patient population. The challenges posed by traditional treatments can be addressed with the help of nanotechnology advancements. In this study, Co, Cu, and Ag-were doped into silica nanoparticles. Then the synthesized monometallic silica nanohybrids were combined to formulate heterometallic silica nanohybrids, characterized structurally and morphologically, compared, and evaluated for antifungal activity based on their individual and synergistic activity. The antifungal assays were conducted by using ATCC cultures of Candida albicans and QC samples of Trichophyton rubrum, Microsporum gypseum, and Aspergillus niger. The MIC (ranging from 49.00 to 1560.00 µg/mL), MFC (ranging from 197.00 to 3125.00 µg/mL), IC50 values (ranging from 31.10 to 400.80 µg/mL), and FICI of nanohybrids were determined and compared. Moreover, well diffusion assay was performed. ABTS assay and DPPH assay were conducted to investigate the radical scavenging activity (RSA) of nanohybrids. SEM analysis clearly evidenced the structural deformations of each fungal cells and spores due to the treatment with trimetallic nanohybrid. According to the results, the trimetallic silica nanohybrids exhibited the most powerful synergistic RSA and the most effective antifungal activity, compared to the bimetallic silica nanohybrids.

Formulation and Development of a Herbal Antifungal Gel Containing Origanum vulgare and Syzygium aromaticum Essential Oils Against Oral Candida albicans.

Background Oral candidiasis is the most prevalent oral fungal infection, and existing antifungal agents have side effects such as drug intolerance, resistance, and toxicity. Herbal essential oils are emerging as an alternative therapeutic approach for treating fungal infections. Origanum vulgare (O. vulgare), commonly known as oregano, and Syzygium aromaticum (S. aromaticum), commonly known as clove, are known to have antifungal properties and are effective against fluconazole-resistant strains. A combination of essential oils has a synergistic effect and aids in achieving effective antifungal activity at sufficiently low concentrations, which could lead to reduced side effects and resistance. Aim of the study This study aimed to formulate and develop an herbal antifungal gel containing O. vulgare and S. aromaticum and evaluate its synergistic antifungal efficacy against oral Candida albicans (C. albicans). Methodology Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) determinations of O. vulgare and S. aromaticum essential oils were performed individually and in combination to assess the antifungal activity against C. albicans. Based on the obtained MIC and MFC of essential oils in combination, an herbal antifungal gel was formulated. Further, to determine the biocompatible nature of the gel, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed. Results We found that a combination of O. vulgare and S. aromaticum essential oils showed antifungal activity at a lesser concentration, with a MIC of 0.19 µl/ml and MFC of 0.39 µl/ml when compared to their individual concentrations. Based on our results, an antifungal herbal gel comprising a concentration of 0.6 µl/ml of both essential oils was developed to achieve synergistic antifungal activity against oral C. albicans. The MTT assay of the herbal gel did not show any cytotoxicity. Conclusion The novel herbal antifungal gel containing O. vulgare and S. aromaticum is biocompatible in nature and provides an alternative therapeutic approach for treating oral candidiasis.

Behavioural and psychological management of somatic symptom disorders: an overview.

The number of patients who seek help at primary and secondary care for somatic symptoms which cannot be explained by any known medical condition is enormous. It has been proposed to rename 'somatoform disorders' in DSM-IV as 'somatic symptom disorders' in DSM-5. This is supposed to include disorders such as somatization disorder, hypochondriasis, undifferentiated somatoform disorder, pain disorder and factitious disorder. The reason for the renaming and grouping is that all these disorders involve presentation of physical symptoms and/or concern about medical illness. In the literature, there is considerable variation adopted with respect to diagnosis and in the approaches adopted for intervention. However, the common feature of these disorders is the chronicity, social dysfunction, occupational difficulties and the increased healthcare use and high level of dissatisfaction for both the clinician and the patient. A number of behavioural and psychological interventions for somatic symptoms have been carried out at primary, secondary and tertiary care settings and recently there have been more attempts to involve the primary care physicians in the psychological interventions. This review aims at giving an overview of the components of the behavioural and other psychological interventions available for addressing medically unexplained somatic symptoms and to present their efficacy.

3-Methyl-1,5-diphenyl-4,5-dihydro-1H-pyrazole.

In the title compound, C16H16N2, the dihydro-pyrazole ring adopts a shallow envelope conformation, with the C atom bearing the phenyl group displaced by 0.298 (2) Šfrom the other atoms (r.m.s. deviation = 0.015 Å). The dihedral angles between the four near coplanar atoms of the central ring and the N- and C-bonded phenyl groups are 13.49 (13) and 82.22 (16)°, respectively.