Network pharmacology and molecular docking analysis on potential molecular targets and mechanism of action of BRAF inhibitors for application in wound healing.

Topical application of BRAF inhibitors has been shown to accelerate wound healing in murine models, which can be extrapolated into clinical applications. The aim of the study was to identify suitable pharmacological targets of BRAF inhibitors and elucidate their mechanisms of action for therapeutic applicability in wound healing, by employing bioinformatics tools including network pharmacology and molecular docking. The potential targets for BRAF inhibitors were obtained from SwissTargetPrediction, DrugBank, CTD, Therapeutic Target Database, and Binding Database. Targets of wound healing were obtained using online databases DisGeNET and OMIM (Online Mendelian Inheritance in Man). Common targets were found by using the online GeneVenn tool. Common targets were then imported to STRING to construct interaction networks. Topological parameters were assessed using Cytoscape and core targets were identified. FunRich was employed to uncover the signaling pathways, cellular components, molecular functions, and biological processes in which the core targets participate. Finally, molecular docking was performed using MOE software. Key targets for the therapeutic application of BRAF inhibitors for wound healing are peroxisome proliferator-activated receptor γ, matrix metalloproteinase 9, AKT serine/threonine kinase 1, mammalian target of rapamycin, and Ki-ras2 Kirsten rat sarcoma viral oncogene homolog. The most potent BRAF inhibitors that can be exploited for their paradoxical activity for wound healing applications are Encorafenib and Dabrafenib. By using network pharmacology and molecular docking, it can be predicted that the paradoxical activity of BRAF inhibitors can be used for their potential application in wound healing.

Role of Cytokines in Chemotherapy-related Cognitive Impairment of Breast Cancer Patients: A Systematic Review.

BACKGROUND: Cognitive impairment is one of the most common problems experienced by patients receiving chemotherapy, and evidence suggests that cytokines might play an important role. Various studies were conducted to evaluate the role of cytokines in chemotherapy-related cognitive impairment (CRCI). However, the association between CRCI due to cytokines is not well-established. Thus, this systematic review aims to assess the role of cytokines in CRCI in breast cancer patients. METHODS: This systematic review was conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) guidelines. An intense literature search was carried out for inclusion criteria in major databases, including PubMed and Clinicaltrials.gov, in August 2021. Studies assessing cognitive parameters through objective and subjective assessment in breast cancer patients receiving chemotherapy were included. RESULTS: A total of 4052 studies were identified, and 15 studies were included in this systematic review. We found that IL-6, IL-1ß, and TNF-α were associated with varying degrees of cognitive impairment in breast cancer patients receiving chemotherapy. CONCLUSION: This systematic review showed a correlation between various cytokines and chemotherapy- associated cognitive decline in breast cancer patients.

Cognitive impairment and elevated peripheral cytokines in breast cancer patients receiving chemotherapy.

BACKGROUND: Anthracyclines-based regimen (5-fluorouracil, doxorubicin, and cyclophosphamide (FAC); cyclophosphamide, epirubicin, and 5-fluorouracil [CEF]) and non-anthracycline based regimens (cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]) are widely used as neoadjuvant chemotherapy for breast cancer patients. OBJECTIVE: The present study was conducted to observe the effects of FAC, CEF, and CMF regimen on cognition and circulatory proinflammatory cytokines (interleukin 6 [IL-6] and interleukin 1ß [IL-1ß]) for the duration of three cycles of chemotherapy in breast cancer patients. METHODS: Eighty newly diagnosed HER-2 negative breast cancer patients were enrolled and divided into 3 groups as FAC- (n = 27), CEF- (n = 26), and CMF- (n = 27) receiving patients. Serum IL-6 and IL-1ß levels were measured by using enzyme-linked immunosorbent assay (ELISA), and cognition was assessed using the Mini-Mental State examination (MMSE) questionnaire. RESULTS: Anthracycline-based regimen was found to increase the levels of IL-6, IL-1ß, and decreased MMSE scores compared with CMF regimen (p < 0.05). CONCLUSION: Anthracycline-based regimen caused comparatively higher peripheral inflammation, which could be the reason for more decline in cognition in anthracycline-receiving patients than non-anthracycline group.

ANTECEDENTES: Regime baseado em antraciclinas (5-fluorouracil, doxorrubicina e ciclofosfamida [FAC]; ciclofosfamida, epirrubicina e 5-fluorouracil [CEF]) e regimes não baseados em antraciclina (ciclofosfamida, metotrexato e 5-fluorouracil (CMF]) são amplamente utilizados como quimioterapia neoadjuvante para pacientes com câncer de mama. OBJETIVO: O presente estudo foi realizado para observar os efeitos do regime FAC, CEF e CMF na cognição e citocinas pró-inflamatórias circulatórias (interleucina 6 [IL-6] e interleucina 1ß [IL-1ß]) durante três ciclos de quimioterapia em pacientes com câncer de mama. MéTODOS: Oitenta pacientes recém-diagnosticadas com câncer de mama HER-2 negativo foram recrutadas e divididas em 3 grupos de pacientes que receberam FAC (n = 27), CEF (n = 26) ou CMF (n = 27). Os níveis séricos de IL-6 e IL-1ß foram medidos por enzyme-linked immunosorbent assay (ELISA) e a cognição foi avaliada por meio do questionário Mini-Mental State Examination (MMSE). RESULTADOS: O regime baseado em antraciclinas aumentou os níveis de IL-6, IL-1ß e diminuiu os escores do MMSE em comparação com o regime CMF (p < 0,05). CONCLUSãO: O regime baseado em antraciclinas causou inflamação periférica comparativamente mais alta, o que pode ser a razão para maior declínio na cognição em pacientes que receberam antraciclinas do que no grupo que não recebeu antraciclina.

Cognitive impairment and elevated peripheral cytokines in breast cancer patients receiving chemotherapy / Comprometimento cognitivo e citocinas periféricas elevadas em pacientes com câncer de mama recebendo quimioterapia

Abstract Background Anthracyclines-based regimen (5-fluorouracil, doxorubicin, and cyclophosphamide (FAC); cyclophosphamide, epirubicin, and 5-fluorouracil [CEF]) and non-anthracycline based regimens (cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]) are widely used as neoadjuvant chemotherapy for breast cancer patients. Objective The present study was conducted to observe the effects of FAC, CEF, and CMF regimen on cognition and circulatory proinflammatory cytokines (interleukin 6 [IL-6] and interleukin 1β [IL-1β]) for the duration of three cycles of chemotherapy in breast cancer patients. Methods Eighty newly diagnosed HER-2 negative breast cancer patients were enrolled and divided into 3 groups as FAC- (n= 27), CEF- (n= 26), and CMF- (n= 27) receiving patients. Serum IL-6 and IL-1β levels were measured by using enzyme-linked immunosorbent assay (ELISA), and cognition was assessed using the Mini-Mental State examination (MMSE) questionnaire. Results Anthracycline-based regimen was found to increase the levels of IL-6, IL-1β, and decreased MMSE scores compared with CMF regimen (p< 0.05). Conclusion Anthracycline-based regimen caused comparatively higher peripheral inflammation, which could be the reason for more decline in cognition in anthracycline-receiving patients than non-anthracycline group.

Resumo Antecedentes Regime baseado em antraciclinas (5-fluorouracil, doxorrubicina e ciclofosfamida [FAC]; ciclofosfamida, epirrubicina e 5-fluorouracil [CEF]) e regimes não baseados em antraciclina (ciclofosfamida, metotrexato e 5-fluorouracil (CMF]) são amplamente utilizados como quimioterapia neoadjuvante para pacientes com câncer de mama. Objetivo O presente estudo foi realizado para observar os efeitos do regime FAC, CEF e CMF na cognição e citocinas pró-inflamatórias circulatórias (interleucina 6 [IL-6] e interleucina 1β [IL-1β]) durante três ciclos de quimioterapia em pacientes com câncer de mama. Métodos Oitenta pacientes recém-diagnosticadas com câncer de mama HER-2 negativo foram recrutadas e divididas em 3 grupos de pacientes que receberam FAC (n= 27), CEF (n= 26) ou CMF (n= 27). Os níveis séricos de IL-6 e IL-1β foram medidos por enzyme-linked immunosorbent assay (ELISA) e a cognição foi avaliada por meio do questionário Mini-Mental State Examination (MMSE). Resultados O regime baseado em antraciclinas aumentou os níveis de IL-6, IL-1β e diminuiu os escores do MMSE em comparação com o regime CMF (p< 0,05). Conclusão O regime baseado em antraciclinas causou inflamação periférica comparativamente mais alta, o que pode ser a razão para maior declínio na cognição em pacientes que receberam antraciclinas do que no grupo que não recebeu antraciclina.

Cross-sectional observational analysis of the genetic referral practices across pediatric ophthalmology outpatient departments in an urban setting.

Purpose: To analyze the genetic referral practices of pediatric ophthalmologists in an urban setting. Methods: (1) The first limb of the study: cross-sectional, observational study among children visiting the outpatient department of pediatric ophthalmology across five centers in Mumbai. All pediatric patients were screened separately by pediatric ophthalmologists and a clinical geneticist for their ophthalmic and systemic complaints. Children were marked for referral to genetics (RTG) by both the specialists based on identification of distinctive features (red flag) and were requested to meet a local geneticist. (2a) Twenty-three months later, patients who had been marked for RTG were contacted telephonically to follow-up if they had met the geneticist. (2b) Additionally, the last 20 proformas from each center were checked retrospectively to note the RTG marked by the ophthalmologist alone. Results: (1) In the first aspect of the study, 126 patients (male: female = 1.2:1) were included. Forty-nine (38.3%) patients were referred for genetic evaluation, of which three (6.1%), 31 (63.26%), and 15 (30.6%) cases were referred by the ophthalmologist alone, geneticist alone, and by both the specialists, respectively. Glaucoma (100%), nystagmus (86%), and leukocoria (83%) were the most prominent ocular diagnoses in cases referred for genetic evaluation. Facial dysmorphism (55.1%) and neurodevelopmental delays (51%) were among the most common systemic red flags found in patients referred to genetics. (2a) Twenty-three months later, on contacting the 49 patients marked for RTG, only one family had met the geneticist. (2b) Retrospective evaluation of 100 proformas: only three patients were marked for RTG by ophthalmologist alone. Conclusion: This study found that the genetic referrals by pediatric ophthalmologist were far lesser than those by geneticist. The study highlights an area of knowledge gap among pediatric ophthalmologists, prompting a need for heightened awareness in this area.

Efficacy and safety of nelarabine in patients with relapsed or refractory T-cell acute lymphoblastic leukemia: a systematic review and meta-analysis.

Nelarabine is approved for the treatment of relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) patients who relapse following at least two different chemotherapy regimens. Previous studies have evaluated the efficacy and safety of nelarabine with chemotherapy in the treatment of R/R T-ALL. However, the results are inconsistent. This review aimed to summarize findings on efficacy and safety data in R/R T-ALL patients administered with the drug nelarabine. The present review conducted a comprehensive search of MEDLINE (via PubMed), WHO Clinical Trial Registry, Clinical Trials.gov, and Cochrane Central Register of Controlled Trials until 15 January 2022. Thirteen studies fulfilled the eligibility criteria with a total of 2508 patients. The efficacy of nelarabine was studied in terms of complete remission (CR) and partial remission (PR). Included studies reported overall random-effects pooled prevalence of CR and PR were 37.2 (95% CI: 22.8, 51.5) and 10.2 (95% CI: 4.9, 15.5), respectively. Most common adverse events associated with nelarabine were neutropenia, thrombocytopenia, fatigue, infections, and reversible peripheral neuropathy. Nelarabine is being used as salvage therapy as a bridge to hematopoietic stem cell transplantation and the findings of this meta-analysis indicate that it is an effective and safe treatment to be used in addition to the first-line treatment for R/R T-ALL.

Uveitis, glaucoma, and cataract with mevalonate kinase deficiency.

We report 7 years of follow-up data on ocular findings in a 2-month-old boy who presented with early-onset bilateral granulomatous panuveitis with subsequent development of secondary glaucoma and total cataract, along with multisystem involvement. He was diagnosed with mevalonate kinase deficiency (MKD), with a homozygous missense variant in exon-6 of the mevalonate kinase (MVK) gene on chromosome-12 that resulted in the substitution of aspartic acid for asparagine at codon 205 (p.Asn205Asp). Despite being managed with topical/systemic steroids and immunosuppression therapy with methotrexate and a short course of adalimumab, the patient continued to develop recurrent episodes of uveitis along with multisystem manifestations. The occurrence of early-onset uveitis is rare, as is the diagnosis of MKD.

Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice.

Epilepsy is a complex neurological disorder, characterized by frequent electrical activity in brain regions. Inflammation and apoptosis cascade activation are serious neurological sequelae during seizures. Fisetin (3, 3',4',7-tetrahydroxyflavone), a flavonoid molecule, is considered for its effective anti-inflammatory and anti-apoptotic properties. This study investigated the neuroprotective effect of fisetin on experimental epilepsy. For acute studies, increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizure tests were performed to evaluate the antiseizure activity of fisetin. For the chronic study, the kindling model was established by the administration of PTZ in subconvulsive dose (25 mg/kg, i.p.). Mice were treated with fisetin (5, 10, and 20 mg/kg, p.o.) to study its probable antiseizure mechanism. The kindled mice were evaluated for seizure scores. Their hippocampus and cortex were assessed for neuronal damage, inflammation, and apoptosis. Histological alterations were observed in the hippocampus of the experimental mice. Levels of high mobility group box 1 (HMGB1), Toll-like receptor-4 (TLR-4), interleukin-1 receptor 1 (IL-1R1), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed in the hippocampus and cortex by ELISA. The immunoreactivity and mRNA expressions of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), cytochrome C, and caspase-3 were quantified by immunohistochemical analysis and real-time PCR. Phosphorylation ELISA was performed to evaluate AkT/mTOR (mammalian target of rapamycin) activation in the hippocampus and cortex of the kindled mice. The results showed that fisetin administration increased the seizure threshold current (STC) in the ICES test. In PTZ-induced seizures, fisetin administration increased the latency for myoclonic jerks (MJs) and generalized seizures (GSs). In the PTZ-induced kindling model, fisetin administration dose-dependently suppressed the development of kindling and the associated neuronal damage in the experimental mice. Further, fisetin administration ameliorated kindling-induced neuroinflammation as evident from decreased levels of HMGB1, TLR-4, IL-1R1, IL-1ß, IL-6, and TNF-α in the hippocampus and cortex of the kindled mice. Also, the immunoreactivity and mRNA expressions of inflammatory molecules, NF-κB, and COX-2 were decreased with fisetin administration in the kindled animals. Decreased phosphorylation of the AkT/mTOR pathway was reported with fisetin administration in the hippocampus and cortex of the kindled mice. The immunoreactivity and mRNA expressions of apoptotic molecules, cytochrome C, and caspase-3 were attenuated upon fisetin administration. The findings suggest that fisetin shows a neuroprotective effect by suppressing the release of inflammatory and apoptosis molecules and attenuating histological alterations during experimental epilepsy.

Impact of cardiovascular diseases on severity of COVID-19 patients: A systematic review.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) cases are increasing rapidly worldwide. Similar to Middle East respiratory syndrome where cardiovascular diseases were present in nearly 30% of cases, the increased presence of cardiovascular comorbidities remains true for COVID-19 as well. The mechanism of this association remains unclear at this time. Therefore, we reviewed the available literature and tried to find the probable association between cardiovascular disease with disease severity and mortality in COVID-19 patients. METHODS: We searched Medline (via PubMed) and Cochrane Central Register of Controlled Trials for articles published until Sept 5, 2020. Nineteen articles were included involving 6,872 COVID-19 patients. RESULTS: The random-effect meta-analysis showed that cardiovascular disease was significantly associated with severity and mortality for COVID-19: odds ratio (OR) 2.89, 95% confidence interval (CI) 1.98-4.21 for severity and OR 3.00, 95% CI 1.67-5.39 for mortality, respectively. Risk of COVID-19 severity was higher in patients having diabetes, hypertension, chronic obstructive pulmonary disease, malignancy, cerebrovascular disease and chronic kidney disease. Similarly, patients with diabetes, hypertension, chronic liver disease, cerebrovascular disease and chronic kidney disease were at higher risk of mortality. CONCLUSION: Our findings showed that cardiovascular disease has a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid cardiovascular disease are urgently needed to understand the extent of these concerning comorbidities.

Embelin ameliorates cognitive dysfunction and progression of kindling in pentylenetetrazol-induced kindling in mice by attenuating brain inflammation.

OBJECTIVE: This study was conducted to evaluate the effect of embelin (EMB) on various epileptic models and related brain inflammation. METHODS: Male Swiss albino mice were administered EMB (5, 10, and 20 mg/kg/p.o.) in acute and chronic study for 7 days and 35 days, respectively. Acute study included increasing current electroshock (ICES) and pentylenetetrazol (PTZ)-induced seizure test. Step-down latency (SDL) and forced swim test (FST) were performed to evaluate cognitive functions and depression-like behavior, respectively. Chronic study included PTZ-induced kindling. Levels of inflammatory biomarkers, namely interleukin-1 beta (IL-1ß), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were estimated in the hippocampus and cortex of the kindled brains by ELISA technique. Further, neurotransmitters (NTs), namely gamma aminobutyric acid (GABA), glutamate, and dopamine, were estimated by using validated liquid chromatography-mass spectrometry (LC-MS) method followed by ultra-high-performance liquid chromatography (UHPLC). RESULTS: Embelin (EMB) treatment increased the seizure threshold to hind limb extension (HLE) in the ICES test and decreased the seizure scores in the kindling experiment. Significantly low levels of IL-1ß, IL-1Ra, IL-6, and TNF-α were observed in the hippocampus of PTZ + EMB (10 and 20 mg/kg)-treated groups compared with PTZ+ vehicle-treated group. Significantly lower levels of IL-1Ra, IL-6, and TNF-α compared with PTZ+ vehicle-treated group were observed in the cortex of PTZ + EMB (10 and 20 mg/kg)-treated groups, while IL-1ß levels were found to be significantly lower only in the cortex of PTZ + EMB (20 mg/kg)-treated group. Increased levels of dopamine and GABA and decreased levels of glutamate in both hippocampus and cortex were observed in EMB + PTZ-treated groups compared with vehicle + PTZ-treated group. Latency of step down was found to be increased and immobility time in FST was decreased in EMB + PTZ groups compared with vehicle + PTZ group. CONCLUSION: Embelin suppressed epileptogenesis in the kindled mice via neurochemical modulation of neurotransmitters and inhibiting the inflammatory pathway. Further, EMB was also observed to be protecting the kindled animals from cognition and depression-like behavior.

Biofabricated platinum nanoparticles: therapeutic evaluation as a potential nanodrug against breast cancer cells and drug-resistant bacteria.

Use of plant extracts for the synthesis of various metal nanoparticles has gained much importance recently because it is a simple, less hazardous, conservative and cost-effective method. In this research work, platinum nanoparticles were synthesized by treating platinum ions with the leaf extract of Psidium guajava and their structural properties were studied using various characterization techniques. The formation of platinum nanoparticles was confirmed by the disappearance of the absorbance peak at 261 nm in UV-visible spectra. The results of gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared spectroscopy (FT-IR) analysis showed functional moieties responsible for bio-reduction of metal ions and stabilization of platinum nanoparticles. The use of dynamic light scattering (DLS) imaging techniques confirmed the formation of stable monodispersed platinum nanoparticles showing a zeta potential of -23.4 mV. The morphological examination using high resolution transmission electron microscopy (HR-TEM) and Scanning electron microscopy (SEM) confirmed the formation of spherical platinum nanoparticles with an average diameter of 113.2 nm. X-ray powder diffraction (XRD) techniques showed the crystalline nature of biosynthesized platinum nanoparticles with a face-centered cubic structure. The results of energy-dispersive X-ray spectroscopy (EDAX) showed 100% platinum content by weight confirming the purity of the sample. The cytotoxic effect of biosynthesized platinum nanoparticles assessed in a breast cancer (MCF-7) cell-line by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, revealed an IC50 of 167.2 µg ml-1. The results of a wound healing assay showed that treatment with platinum nanoparticles induced an anti-migratory effect on MCF-7 cells. In the cell cycle phase distribution, treatment with platinum nanoparticles inhibited cell proliferation as determined by flow cytometry with PI staining. Significant cell cycle arrest was detected at the G0/G1 phase with a notable decrease in the distribution of cells in the S and G2/M phases. The anti-bacterial activity of bio-synthesized platinum nanoparticles was evaluated against four pathogenic bacteria i.e. B. cereus (Gram positive), P. aeruginosa (Gram negative), K. pneumonia (Gram negative) and E. coli (Gram negative). The biosynthesized platinum nanoparticles were found to show dose-dependent inhibition against pathogenic bacteria with a significant effect on Gram-negative bacteria compared to Gram-positive bacteria. This synergistic blend of green and simplistic synthesis coupled with anti-proliferative and anti-bacterial properties makes these biogenic nanoparticles suitable in nanomedicine.

Risk Factors for Hematopoietic Stem Cell Transplantation-Associated Bone Loss.

Hematopoietic stem cell transplantation (HSCT), including bone marrow transplantation, is the treatment of choice for many hematologic diseases, including hematologic malignancies and different types of anemia. The use of HSCT is increasing annually, mainly because advanced research that has been conducted in this area has exponentially expanded the indications for HSCT and significantly improved transplantation techniques and supportive care practices. Collectively, these improvements have led to an increase in the overall survival of HSCT patients. However, as post-HSCT survival is increasing, awareness of the potential late complications of HSCT is also growing. Unpredictable bone loss is one of the major post-HSCT complications that can cause significant morbidity and impair the quality of life of survivors. Although the exact mechanism of post-HSCT bone loss is not yet known, previous studies have suggested that numerous factors, including destructive preparative regimens (eg, high-dose chemotherapy, total body irradiation), treatment-related complications (eg, graft-versus-host disease), endocrine abnormalities (eg, diabetes mellitus, thyroid dysfunction, adrenal insufficiency), lack of physical activity, and the underlying disease itself are responsible for HSCT-associated bone loss. Sufficient data have been collected to suggest that post-HSCT bone loss can be prevented and treated using the same preventive and treatment modalities as used for the general population. Various guidelines have been formulated to help keep a check on HSCT recipients' deteriorating bone health.

Increased serum interleukin-9 and interleukin-1β are associated with depression in type 2 diabetes patients / Interleucina-9 e interleucina-1β séricas aumentadas estão associadas à depressão em pacientes com diabetes tipo 2

ABSTRACT Background: Co-morbid diabetes and depression are prevalent chronic conditions negatively affecting quality of life (QoL). Inflammation has been considered as an integral mechanism in patients with both diabetes and depression. Objective: The aim of the present study was to investigate depression and its association with interleukins (IL)-1β and IL-9 in type 2 diabetic patients (T2DM) and controls. The QoL in diabetic patient was also assessed. Methods: Eighty subjects were included, distributed among three groups: Group 1 - Healthy controls; Group 2 - T2DM patients without depression; Group 3 - T2DM patients with depression. Depression and QoL were assessed using Patient Health Questionnaire (PHQ-9) and The Audit of Diabetes-Dependent QoL (ADDQoL), respectively. IL-1β and IL-9 were measured in serum samples of all the patients using ELISA kit. Results: The PHQ score in the Group 3 was significantly higher as compared to Group 1. The ADDQoL scores in the Group 3 were significantly higher as compared to Group 2. Levels of IL-9 and IL-1β were elevated in Group 3, as compared to the other groups. Conclusion: This study showed positive association between depression and IL-1β, IL-9 in T2DM patients. Additionally, the diabetic patients have poorer quality of life, which is further worsened by the presence of depression. Thus, routine assessment for the presence of depression is suggested in T2DM patients.

RESUMO Introdução: O diabetes e a depressão comórbidas são condições crônicas prevalentes que afetam negativamente a qualidade de vida (QdV). A inflamação tem sido considerada como um mecanismo integral em pacientes com diabetes e depressão. Objetivo: Investigar a depressão e sua associação com interleucinas (IL)-1β e IL-9 em pacientes diabéticos tipo 2 (DM2) e controles. A QdV em diabéticos também foi avaliada. Métodos: Foram incluídos 80 indivíduos, divididos em três grupos: Grupo 1 - controles saudáveis; Grupo 2 - pacientes com DM2 sem depressão; Grupo 3 - pacientes com DM2 com depressão. A depressão e a QdV foram avaliadas usando o Questionário de Saúde do Paciente (Patient Health Questionnaire - PHQ-9) e a auditoria de QdV dependente de diabetes (Audit of Diabetes-Dependent Quality of Life - ADDQoL), respectivamente. IL-1β e IL-9 foram medidas em amostras de soro de todos os pacientes utilizando kit de ELISA. Resultados: O escore do PHQ no grupo 3 foi significativamente maior em comparação ao grupo 1. Os escores de ADDQoL no grupo 3 foram significativamente maiores em comparação ao grupo 2. Os níveis de IL-9 e IL-1β foram elevados no grupo 3, como em comparação com os outros grupos. Conclusão: Este estudo mostrou associação positiva entre depressão e IL-1β, IL-9 em pacientes com DM2. Além disso, os pacientes diabéticos têm pior QdV, o que é ainda piorado pela presença de depressão. Assim, a avaliação rotineira da presença de depressão é sugerida em pacientes com DM2.

Invasive Fungal Infections in Patients with Acute Myeloid Leukemia Undergoing Intensive Chemotherapy.

Patients with hematological malignancies are severely immunocompromised and are at high risk of invasive fungal infection (IFI), particularly those undergoing remission-induction chemotherapy for acute myeloid leukemia (AML). IFIs are a major cause of morbidity and mortality in such patients. We planned to study the incidence of IFI in patients with AML undergoing intensive chemotherapy and receiving antifungal prophylaxis. We retrospectively reviewed consecutive 46 patients with non-M3 AML, who received induction chemotherapy and systemic antifungal prophylaxis. None of the patients had IFI at the time of initiation of the chemotherapy. Patients were monitored for the occurrence of IFI using high-resolution computerized tomography of the chest or para-nasal sinus and test for galactomannan antigen on serum or broncho-alveolar lavage and were followed up for 90 days. Of the 46 patients on intensive chemotherapies, 41, 4 and 1 patients were started on posaconazole, amphotericin B and voriconazole prophylaxis, respectively. The occurrence of possible and probable IFI was observed in 16 and 4 patients respectively, in which 19 patients were on posaconazole and 1 patient was on amphotericin-B prophylaxis. Overall mortality in the study population was 11 (23.9%). Four out of 20 patients died with IFI but none of the death was attributable to IFI. IFI still remains a significant cause of morbidity and mortality in patients with AML despite universal use of antifungal prophylaxis. With effective pharmacotherapy, the mortality due to IFI is preventable. Appropriate antifungal prophylaxis strategy still needs to be developed through larger and prospective studies.

Management of dental trauma in a child with Xeroderma Pigmentosa.

Xeroderma Pigmentosa is a rare dermatological autosomal recessive disorder that manifests itself early in life as severe sunburn usually after a short exposure to sunlight. The prime characteristic features include photosensitivity, hyperpigmentation and ichthyosis in sun exposed areas, and an increase in the risk of basocellular and squamous cell carcinomas and melanomas of the skin and eyes. The case report highlights the preventive treatment options along with all necessary precautions that should be taken to protect the patient from any iatrogenic inadvertent exposures that may be deleterious to his present state. The purpose of the report is also to discuss the important role of dental professionals when dealing with debilitating medical conditions.

To compare the effectiveness of different mouthrinses on Streptococcus mutans count in caries active children.

INTRODUCTION: Streptococcus mutans is the prime microbe responsible for caries. Mouthwashes represent an effective means for decreasing their count. To ascertain this, three commercially available mouthrinses were evaluated for their antimicrobial activity. MATERIALS AND METHOD: Chlorhexidine, Sodium fluoride and Herbal mouth rinse were evaluated for their efficacy against S. mutans in 60 children aged 6-12 years old. Plain water acted as the control group. RESULTS: The values obtained were subjected to statistical analysis. ANOVA test, student-t test and paired t-test were used for evaluation. Chlorhexidine and fluoride showed statistically significant reduction in S. mutans count as compared to herbal rinse. CONCLUSION: All the mouthrinses used in the present study have shown a definite decline in S. mutans count.

Obturator Nerve Block in Transurethral Resection of Bladder Tumor: A Comparative Study by two Techniques.

CONTEXT: Sparing of obturator nerve is a common problem encountered during transurethral resection of bladder tumor (TURBT) under spinal anesthesia. AIMS: To evaluate and compare obturator nerve block (ONB) by two different techniques during TURBT. SETTINGS AND DESIGN: This is prospective observational study. SUBJECTS AND METHODS: Forty adult male patients from the American Society of Anesthesiologists Class I-IV planned to undergo TURBT under spinal anesthesia were divided into two groups of twenty each. In one group, ONB was performed with nerve locator. In other group, transvesical nerve block was performed with a cystoscope. The primary endpoints of this study were the occurrence of adductor reflex, ability to resect the tumor, and number of surgical interruptions. A number of transfusions required and bladder perforation were the secondary endpoints. RESULTS: There was statistically significant difference between the groups for resection without adductor jerk, resection with a minimal jerk, and unresectable with high-intensity adductor jerk. Bleeding was observed in both groups and one bladder perforation was encountered. CONCLUSIONS: We conclude that ONB, when administered along with spinal anesthesia for TURBT, is extremely safe and effective method of anesthesia to overcome adductor contraction. ONB with nerve locator appears to be more effective method compared to the transvesical nerve block.

A Rare Case of Pyogenic Granuloma with a Natal Tooth.

Natal teeth are teeth present in the oral cavity at the time of birth. It is extremely rare to find natal teeth in association with pathological conditions of the oral cavity. Pyogenic granuloma is a type of inflammatory hyperplasia that appears as an over exuberant connective tissue response to a stimulus or injury, in the present case the injurious agent is the natal tooth. The parents of the eight day old male infant brought the child with a natal tooth associated with a soft tissue lesion growing from the gum pad. A provisional diagnosis of pyogenic granuloma was made on behalf of the clinical findings which were confirmed by histopathology. The natal tooth was extracted and the lesion was surgically excised. Complete healing of the gumpad took place after excision of the lesion and extraction of the natal tooth and the child was able to feed normally within a week. The purpose of this case report is that Pediatric Dentist should be aware of this rare unusual clinical presentation and plan for an appropriate treatment modality in order to avoid any future complications.

Early manifestation of mild cognitive impairment in B-cell non-Hodgkin's lymphoma patients receiving CHOP and rituximab-CHOP chemotherapy.

Existing evidence suggests that pro-inflammatory cytokines increases during chemotherapy which plays an intermediary role in Chemotherapy related cognitive impairment (CRCI) and thyroid dysregulation. Previous studies suggest that thyroid hormones are essential for neuronal development and neurotransmitter release. CHOP regimen has been the backbone of Non-Hodgkin's lymphoma (NHL) treatment from a decade but rituximab addition to CHOP (R-CHOP) has improved cure rates. However, their adverse event profile on behavior is not well studied on patients. In this study total 68 NHL patients were enrolled and divided equally in 2 groups as CHOP receiving (n = 34) and R-CHOP receiving (n = 34). Effects of R-CHOP and CHOP regimen on thyroid function, pro-inflammatory cytokines and cognitive function were determined at four time points that was from one day before 1st (TP0), 2nd (TP1), 3rd (TP2) and 4th (TP3) cycle of chemotherapy. Results indicated significant increase in levels of pro-inflammatory cytokines after each time point from TP0 to TP3of chemotherapy. Thyroid hormone levels i.e. T3, T4 were found significantly decreased and TSH was increased after each time point of both groups. MMSE score was found significantly decreased after each cycle of both groups. However, an inverse association was found between IL-1ß levels with TSH by applying correlation coefficient. Cognitive function was decreased in patients with decreased T3 and T4 levels and increased TSH. To conclude, patients receiving R-CHOP regimen were found to have more increased IL-6 and IL-1ß with more cognitive decline and thyroid abnormality as comparison to CHOP receiving patients.

Clinical evaluation of post-operative analgesia comparing suprascapular nerve block and interscalene brachial plexus block in patients undergoing shoulder arthroscopic surgery.

BACKGROUND: Shoulder arthroscopic surgeries have a high incidence of severe post-operative pain significant enough to interfere with recovery and rehabilitation. A regional anaesthetic technique combined with general anaesthesia reduces intra-operative requirements of anaesthesia and provides a better post-operative pain relief. As the commonly employed technique of interscalene brachial plexus block (ISB) is associated with potential serious complications, suprascapular nerve block (SSB) can be used as a safer alternative. METHODS AND MATERIAL: In this prospective study, 60 ASA 1 or 2 adult patients undergoing shoulder arthroscopic surgery were randomised into two groups - ISB and SSB. In group ISB, ISB with 20 ml of 0.5% bupivacaine mixed with 75 µg clonidine was given. In the SSB group SSB was given with 15 ml of 0.5% bupivacaine with 75 µg clonidine. Pain was assessed using visual analogue scale and verbal pain scale scores and time to first rescue analgesia was noted. We used Student's t test and Chi-square/Fisher Exact test and used a statistical software to compare data. RESULTS: In the present study, the mean duration of analgesia was 2.53 ± 2.26 h in SSB group compared to 7.23 ± 6.83 h in group ISB (p value < 0.05). Overall rescue analgesic requirements were higher in SSB group compared to ISB group (63.3% versus 40.0%) but this was statistically not significant (p value > 0.05). CONCLUSION: Both interscalene and SSB can be used to provide intra-operative and post-operative analgesia in patients undergoing shoulder arthroscopy.