Genetic alterations in Wnt family of genes and their putative association with head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the most frequent type of head and neck cancer that usually arises from the mucosal surfaces of several organs including nasal cavity, paranasal sinuses, oral cavity, tongue, pharynx, and larynx. The Wnt signaling pathway is a crucial mechanism for cellular maintenance and development. It regulates cell cycle progression, apoptosis, proliferation, migration, and differentiation. Dysregulation of this pathway correlates with oncogenesis in various tissues including breast, colon, pancreatic as well as head and neck cancers. The present study aims to assess the gene alterations in the Wnt family of genes so as to derive an association with HNSCC. Computational approaches have been utilized for the identification of gene alterations in the Wnt family of genes. Several databases such as cBioportal, STRING, and UALCAN were used for the purpose. The frequency of alteration was high in case of Wnt family member 11 (5%). Gene amplification, deep deletions, missense and truncating mutations were observed in HNSCC patients. There was a marked difference in the gene expression profile of WNT11 between grades as well as normal samples. The survival probability measured using the Kaplan-Meier curve also presented with a significant difference among male and female subjects experiencing a low/medium level expression. The female patients showed less survival probability when compared to the male subjects. This provides the prognostic significance of the WNT11 gene in HNSCC. Taken together, the present study provides clues on the possible association of WNT11 gene alterations with HNSCC, which has to be further validated using experimental approaches.

Genetic alterations in Wnt family of genes and their putative association with head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the most frequent type of head and neck cancer that usually arises from the mucosal surfaces of several organs including nasal cavity, paranasal sinuses, oral cavity, tongue, pharynx, and larynx. The Wnt signaling pathway is a crucial mechanism for cellular maintenance and development. It regulates cell cycle progression, apoptosis, proliferation, migration, and differentiation. Dysregulation of this pathway correlates with oncogenesis in various tissues including breast, colon, pancreatic as well as head and neck cancers. The present study aims to assess the gene alterations in the Wnt family of genes so as to derive an association with HNSCC. Computational approaches have been utilized for the identification of gene alterations in the Wnt family of genes. Several databases such as cBioportal, STRING, and UALCAN were used for the purpose. The frequency of alteration was high in case of Wnt family member 11 (5%). Gene amplification, deep deletions, missense and truncating mutations were observed in HNSCC patients. There was a marked difference in the gene expression profile of WNT11 between grades as well as normal samples. The survival probability measured using the Kaplan-Meier curve also presented with a significant difference among male and female subjects experiencing a low/medium level expression. The female patients showed less survival probability when compared to the male subjects. This provides the prognostic significance of the WNT11 gene in HNSCC. Taken together, the present study provides clues on the possible association of WNT11 gene alterations with HNSCC, which has to be further validated using experimental approaches.

Targeting the Secreted Aspartic Proteinase (SAP-1) Associated with Virulence in C. albicans by C. cassia Bio-compounds: A Computational Approach

Evaluation of the drug ligand interactions between the C. cassia bio-compounds with the SAP-1 in C. albicans to explore the inhibitory medicinal potential of C. cassia bio-compounds by a computational approach is performed in the present investigation. Antimicrobial assay was done using agar well diffusion method with the crude aqueous and ethanolic extracts of the dried barks of C. cassia against C. albicans. 2D & 3D structures of the active bio-compounds of C. cassia were optimized and the 3D structure of SAP-1 was retrieved from the PDB data bank. In-silico inhibitory potential of the selected C. cassia biocompounds against SAP-1 was done by Auto Dock 2.0 and was visualized with Accelrys discovery studio visualizing tool with the assessment of the molecular properties of the ligands against SAP-1 by molinspiration calculations and further assessment for their drug likeliness. In-vitro analysis showed a promising anti-fungal activity of C. cassia extracts against C. albicans. Cinnamoyl E-acetate and Eugenyl acetate seem to possess promising inhibitory effect to target SAP-1 with a least binding energy of –5.33 and -5.21 Kcal/mol with four hydrogen bonds respectively. Molinspiration assessments showed zero violations for all the C. cassia compounds with the TPSA scores of <140 Å towards the best oral bioavailability. The findings of the study emphasize that cinnamaldehyde, cinnamoyal acetate and eugenol from C. cassia seem to possess a promising inhibitory effect against SAP-1 of C. albicans suggesting the medicinal value of the spice against SAP-1

Frequency of Chromosomally Encoded gyrA and parC Genetic Determinants of Fluoroquinolone Resistance in A. baumannii

Fluoroquinolones are administered as routine drugs of choice for treating complicated urinary tract infections caused by multidrug resistant Acinetobacter baumannii strains. It is now a world-wide issue that gyr and par induced quinolone resistance as one of the major drug resistance mechanisms. This investigation is thus aimed to assess the prevalence of quinolone resistance and to characterize the gyrA and parC producing strains of A. baumannii. Genomic DNA from 50 fluoroquinolone resistant A. baumannii were screened for gyrA and parC by PCR for the genetic relatedness with fluoroquinolone resistance, with sequencing of the representative strains. All the strains were positive for gyrA(100%) and 82% (n=41)for parC. Presence of parC was observed in 56.09% (n=23) ciprofloxacin resistant A. baumannii with 43.90% (n=18) in levofloxacin resistant A baumannii. The findings of the present study showed the prevalence of fluoroquinolone resistance among A. baumannii in urinary tract infections and the frequency of gyrA and parC in inducing the resistance

Frequency of Adhesive Virulence Factor fimH among the Clinical Isolates of Acinetobacter baumannii in India

The objective of the study was to detect the presence of fimH geneamong the drug resistanst strains of Acinetobacter baumannii.fimH gene was found to be associated with a catch bond mechanism which led to better evolution of biofilm formation. Since there are not many studies done with this gene it would be a timely investigation and this study mainly aims in molecular characterizationof fimHgene among clinical isolates of A.baumannii. Semi quantitative bio adherent assay was done by the multidrug resistant strains of A.baumannii to find the formation of biofilm. The DNA was extracted with the help of kit and PCR was performed for amplification. Pearson correlation analysis was done to find the existing correlation between the fimHgene and MDR strains of A.baumanniiwith significant p-value of (<0.05). From the screened 73 genomes of MDR A.baumannii 6.8% showed positive amplicons for the fimH gene which were related to biofilm and porin formation (Fig. 1). Correlation of its existence was high in beta lactamase (100%), cephems (100%), folate (100%) resistant strains, followed by aminoglycosides (80%), carbapenems (60%) and fluoroquinolones (60%) and efflux pumps (20%). In Spite of various measures undertaken to prevent the disease, the prevalence of the pathogen is multiplying. The current study recorded the presence of fimHgene (6.8%) among the clinical isolates of A.baumannii. This gene can be used as a target to develop new drugs and vaccines to combat the menace of A.baumannii infection

Deciphering the Genetic Aberrations in DNA Damage Response Genes and Their Possible Association with HNSCC

Head and neck squamous cell carcinoma (HNSCC) includes carcinomas in the oral cavity, pharynx and larynx. It is considered as the sixth most common form of cancer in the world. Severalstudies have confirmed that smoking and alcohol consumption are the major risk factors for HNSCC. DNA damage response genes play an important role in the maintenance of the genome. Defects in cell cycle checkpoint and DNA repair mechanisms, such asmutation or abnormalities, may lead to the wide spectrum of human diseases. The present study employs databases and computational tools to identify the genetic abnormalities associated with DNA damage related genes which might have a direct or indirect association with HNSCC. The demographic details of HNSCC patients was obtained from The Cancer Gene Atlas (TCGA, Firehose Legacy) dataset hosted by the cBioportal database. The oncoprint data analysis revealed the highest frequency of gene alteration in the ATR gene (15%), followed by ATM, BRCA2and CHEK2(5%). Other genes showed less than 5% alteration. The gene expression profile of ATRgene revealed its differential expression pattern in different grades of tumor relative to normal samples. The survival curve analysis using Kaplan-Meier method revealed that a high level expression of the ATR gene leads to poor survival rate in the female HNSCC patients when compared to males. Thus the present study has identified gross and single nucleotide variants in the ATRgene which could have a putative role in the development of tumor. Further experimental research is required to confirm this association

Effect of Two Different Mouth Rinses on S. mutans Counts in Subjects Undergoing Orthodontic Treatment – A Pilot Study

The study is thus aimed to assess and compare the efficacy of Herbostra oil pulling mouthwash with Chlorhexidinemouthwash in reducing plaque accumulation around orthodontic brackets. A total of 20 patients were considered in this study randomly assigned into Group I (experimental group -Herbostra oil pulling mouthwash) and Group II (reference group-0.2% Chlorhexidine mouthwash). The plaque index scores were recorded in each individual at baseline (pre) and after 3 weeks (post).Dental plaque samples were collected around the orthodontic brackets at the cervical region of maxillary upper molars and lower incisors bycotton swabbing method and evaluated for the presence of microflora. Paired sample t-test for Streptococcus mutanscount showed that statistically significant difference only within the group II (p=0.000) (Chlorhexidine group) and there was no significantdifference within the group I (p=0.103) (Herbostra group). Paired sample t-test for plaque index score shows statistically significant difference within the groups (0.000).Independent t test showed statistically significant difference in the levels ofStreptococcus mutanscount after 3 weeks between the two groups (p=0.000) with the mean values of (2.230±0.5056), (1.080±0.3458) in group I and group II respectively. From this study we concluded that, even though there was a reduction in plaque scores and S. mutanscount with Herbostra oil pulling mouthwash but it was not as effective as Chlorhexidine mouth rinse

Genetic Aberrations in Caspase Family of Genes and Their Possible Association with HNSCC

The cell suicide pathway of apoptosis is a necessary event in the life of multicellular organisms. It is involved in many biological processes ranging from development to the immune response. Over expression of interleukin-1β-converting enzyme (later renamed caspase-1) was shown to be sufficient to induce apoptosis in mammalian cells. The present study aims to assess the gene alterations in the Caspase family of cytochromes so as to derive an association with HNSCC. Earlier eleven genes were found in the human genome to encode 11 human caspases, caspase-1 to caspase-10 and caspase-14, which is now populated to 13, whereas 10 genes were found in the mouse genome to encode 10 murine caspases including caspase-1, 2, 3, 6, 7, 8, 9, 11, 12 and 14 Caspases share a number of features distinguishable from other proteases. The analysis follows an observational study design, employing several computational tools to identify and predict the possible outcomes of gene alterations identified in HNSCC patients. cBioportal server was used to identify the gene alterations which was further analyzed using tools such as PROVEAN, I-Mutant and gnomAD. Several reported polymorphic variants were also identified. The pathogenicity and protein stability of gene alterations documented in the present study were identified at standard biological conditions. Further experimental studies would provide concrete evidence on the association of the observed genetic abnormalities with HNSCC especially in individuals exposed to habitual carcinogens

A preliminary study on the screening of emerging drug resistance among the caries pathogens isolated from carious dentine.

Background: Dental caries being the commonest unmet public health problem indicates its need to urge the dentists to overcome this problem globally. Caries exhibit in different types and is found to be associated with co-aggregation property of microbial flora with other oral hygienic factors. In spite of the surgical removals, excavations and administration of antimicrobials for carious dentine, there seems to be repeated infection and chronic prevalence of caries. A complete understanding of microbial etiology and prevention of emerging drug-resistant strains will aid in the eradication of this chronic dentine problem condition from the oral cavity. Aim: This study is aimed to isolate the predominant bacterial pathogens associated with caries and to screen for the emergence of drug resistance among the isolated caries pathogens. Materials and Methods: Carious dentine specimens were collected from 75 endodontic patients and the samples were processed microbiologically to isolate the caries pathogens. Identification of the strains was done by standard biochemical characterization studies. Statistical analysis of the isolates was done by Pearson Chi-square test and Fisher's exact test. The predominant isolates were subjected to antimicrobial sensitivity test using Kirby Bauer's method. The results were recorded and analyzed for drug resistance. Results: Carious dentine samples yielded a high percentage of Lactobacillus sp., and Candida albicans from different type of caries. Among the study population, dentinal caries was the most predominant type affecting most males with other associated risk factors. Nearly 47.3% of the isolated Lactobacillus sp. and 55.5% of the yeast C. albicans were screened to show resistance against the antimicrobials used for the study. Conclusion: This study concludes by stating that Lactobacillus sp., and C. albicans are mostly involved in the caries etiology and show resistance to the commonest antimicrobial agent. This implicates the need for periodical antimicrobial susceptibility examination of the caries pathogens that will aid to prevent the emergence of resistance property among the dentinal pathogenic organisms.

Neuromuscular junctional disorders.

Neuromuscular junctional disorders (NMJ) in children are distinct entity. They may be acquired or hereditary. They pose problem in diagnosis because of the higher occurrence of sero negative Myasthenia Gravis (MG) cases in children. The identity of MusK antibody positivity in a good percentage of sero negative cases further adds to problems in diagnosis. The Congenital Myasthenic Syndrome (CMS) which are rare disorders of hereditary neuromuscular transmission (NMT) has to be differentiated because immunotherapy has no benefit in this group. Molecular genetic studies of these diseases helps to identify specific type of CMS which is important as other drugs like Fluoxetine, Quinidine are found to be effective in some. In infancy, all can manifest as floppy infant syndrome. The important key to diagnosis is by detailed electrophysiological studies including repetitive nerve stimulation at slow and high rates and its response to anticholinesterases and estimation of Acetyl choline receptor antibodies. Other causes of neuromuscular transmission defects viz. snake venom poisoning and that due to drugs are discussed.

Invasive aspergillosis producing painful ophthalmoplegia.

Painful ophthalmoplegia is caused by the lesions of orbital apex and anterior cavernous sinus. Cavernous sinus syndrome can be produced by intracranial invasive aspergillosis. A case of painful ophthalmoplegia due to invasive aspergillosis caused by Aspergillus niger in a diabetic patient is presented.

Plasmapheresis in childhood acute disseminated encephalomyelitis.

Accepted modes of therapy in acute disseminated encephalomyelitis include intravenous methylprednisolone, intravenous immunoglobulin or a combination of both. Effectiveness of plasmapheresis has been demonstrated by many case reports. We used plasmapheresis to treat steroid non-responsive acute disseminated encephalomyelitis in two children. There was complete clinical and radiological recovery in both the cases.

Anterior inferior cerebellar artery infarct with unilateral deafness.

We report the case of a young man with anterior inferior cerebellar artery infarct causing unilateral deafness. Clinical features and audiometry suggested cochlear localization for deafness. MRI brain showed an infarct in the right AICA territory with involvement of pons. Involvement of the internal auditory artery explains the cochlear deafness.

Pyridoxine-dependent seizures: a review.

Pyridoxine-dependent seizure is a rare autosomal recessive disorder that usually presents with neonatal intractable seizures. This syndrome results from an inborn abnormality of the enzyme glutamic acid decarboxylase, which results in reduced pyridazine-dependent synthesis of the inhibitory neurotransmitter gamma amino butyric acid. The full range of symptomatology is unknown; but can be associated with autism, breath holding and severe mental retardation, bilious vomiting, transient visual agnosia, severe articulatory apraxia motor dyspraxia, microcephaly and intrauterine seizures. Parenteral pyridine injection test is a highly effective and reproducible test in confirming the diagnosis. Pyridoxine should be administered as a diagnostic test in all cases of convulsive disorders of infancy in which no other diagnosis is evident. Epileptic seizure discharges subside within 2-6 minutes after the intravenous injection of 50-100 mg of pyridaoxine. Once the diagnosis is confirmed, maintenance therapy should be continued indefinitely and doses increased with age or intercurrent illnesses. The maintenance dose of Bg needed is still not clear. There is a relatively wide range for the daily B6 dose necessary to control the seizure i.e., 10-200 mg/day.

Primary antiphospholipid antibody syndrome presenting as venous infarct and deep vein thrombosis.

We report the case of a young lady with primary antiphospholipid antibody syndrome, who had two spontaneous abortions and cerebral venous thrombosis and subsequently deep vein thrombosis of the leg veins. Three classes of antiphospholipid antibodies (IgG, IgM, IgA) were elevated. There was no clinical or laboratory evidence for other autoimmune or systemic illnesses. We are presenting the case due to the rarity of the same.

A case of hemeplegic migraine with leptomeningeal angiomatosis.

A 43 year old man with thirty years history of recurrent hemiplegic migraine, consistently occurring on one side (left sided paresthesia and weakness of less than forty five minutes followed by right sided headache) and lately increasing to once in three days was investigated. CT head and carotid angiogram showed gyral calcification with prominent medullary and subependymal veins confirming the diagnosis of leptomeningeal angiomatosis. Management and followup is discussed.

Social factors and psychopathology in epilepsy.

One hundred and six epilepsy patients were assessed over a period of 6 months for psychiatric morbidity, social support, stressful life events in previous year and disability. 45 patients (42.45%) had a psychiatric diagnosis. Organic depressive disorder headed the list (16.98%) followed by mild cognitive disorder (11.32%) and tobacco dependence (8.49%). There was no significant difference in the mean age, sex, mean education, age at onset of epilepsy, duration of epilepsy, psychiatric diagnosis, mean scores on social support scale, presumptive stressful life event scale and disability assessment schedule between different types of epilepsy. The difference in mean scores of presumptive stressful life events scale and disability assessment schedule between epileptics with and without psychiatric diagnosis was not statistically significant.

Seizures in hyperglycemic patients.

AIM OF STUDY: To study the pattern of seizures in hyperglycemic patients and its correlation with serum osmolality, blood sugar and serum sodium. MATERIALS AND METHODS: (Study period June 1999-June 2000) Forty patients who presented with first time seizures and who were detected to be diabetic were included in the study. All patients had detailed history, clinical examination blood sugar, BUN, serum electrolytes, serum osmolality, serum calcium estimation. EEG and CT head scan was also done. The seizures were classified as per ILAE classification (1981). The study group was further divided into Group A--those with normal CT (n 24) and Group B-- those showing infarcts in CT scan (n 16). The control group (n 40) were matched for age and had first occurrence of seizures and CT showed infarct and were euglycemic. All the investigations were done for the control group as well. Statistical analysis was done using ANOVA. RESULTS: None of the patient had diabetic ketoacidosis. Patients in study group had statistically significant incidence of (1) Focal seizures with or without generalisation (100%); (2) Visual hallucination (25%); (3) Epilepsia partialis continua (20%). Comparing the subgroups (A and B) complex partial seizures and visual hallucination was significant at 5% level in the group A (NKH with normal CT). Ninety percent in the study group had increased serum osmolality (Vs 22.5% in the control group). Duration (eight days Vs 1) and frequency (15 per day vs 1.45) were positively correlated with RBS > S.osmolality > S.sodium. CONCLUSION: 1. Long duration and frequent focal motor seizures with or without secondary generalisation occurs in NKH which at times may be the first manifestation of DM. 2. Complex partial seizures, visual hallucination and epilepsia partialis continua are more common in NKH patients than in euglycemic patients. 3. There is positive correlation of blood sugar, S.osmolality and S.sodium with frequency and duration of seizures. RBS > S.osmolality > S.Na. 4. Correction of hyperglycemia is the main stay of management of seizures. 5. Movement induced seizures which is specific for NKH is a rarity.