Effect of valproic acid on histone deacetylase expression in oral cancer (Review).

Oral squamous cell carcinoma (OSCC) is a frequent human malignancy that demonstrates a range of genetic and epigenetic alterations. Histone deacetylases (HDACs) are key epigenetic regulators of cell-cycle progression, differentiation and apoptosis and their dysregulation is implicated in cancer development. HDACs are promising targets for anticancer therapy through the utilisation of HDAC inhibitors (HDACis). OSCC cells have been shown to have low levels of histone acetylation, suggesting that HDACis may produce beneficial effects in patients with OSCC. Valproic acid (VPA) is a class I and IIa HDACi and, therefore, may be useful in anticancer therapy. VPA has been reported as a chemo-preventive epigenetic agent in individuals with high-risk oral dysplasia (OD) and thus associated with a reduced risk of HNSCC. It is hypothesised that HDAC inhibition by VPA triggers a change in the expression levels of different HDAC family gene-members. The present review summarises the current literature on HDAC expression changes in response to VPA in oral cancer patients and in vitro studies in an effort to better understand the potential epigenetic impact of VPA treatment. The present review outlined the need for exploring supportive evidence of the chemo-preventive role played by VPA-based epigenetic modification in treating oral pre-cancerous lesions and, thus, providing a novel tolerable chemotherapeutic strategy for patients with oral cancer.

Harnessing intra-varietal variation for agro-morphological and nutritional traits in a popular rice landrace for sustainable food security in tropical islands.

Introduction: Rice crop meets the calorie and nutritional requirements of a larger segment of the global population. Here, we report the occurrence of intra-varietal variation in a popular rice landrace C14-8 traditionally grown under the geographical isolation of the Andaman Islands. Methods: Based on grain husk color, four groups were formed, wherein the extent of intra-varietal variation was studied by employing 22 agro-morphological and biochemical traits. Results: Among the traits studied, flavonoid and anthocyanin contents and grain yield exhibited a wider spectrum of variability due to more coefficients of variation (>25%). The first five principal components (PCs) of principal components analysis explained a significant proportion of the variation (91%) and the first two PCs explained 63.3% of the total variation, with PC1 and PC2 explaining 35.44 and 27.91%, respectively. A total of 50 highly variable SSR (HvSSR) markers spanning over 12 chromosomes produced 314 alleles, which ranged from 1 to 15 alleles per marker, with an average of 6.28. Of the 314 alleles, 64 alleles were found to be rare among the C14-8 selections. While 62% of HvSSR markers exhibited polymorphism among the C14-8 population, chromosomes 2, 7, 9, and 11 harbored the most polymorphic loci. The group clustering of the selections through HvSSR markers conformed to the grouping based on grain husk coloration. Discussion: Our studies on the existence and pertinence of intra-varietal variations are expected to be of significance in the realms of evolutionary biology and sustainable food and nutritional security under the changing climate.

Perception of Leprosy Patients towards the Disease in a Tertiary Care Hospital of High Prevalent District in West Bengal, India: A Qualitative Study.

Background: Leprosy is a disease having tremendous social implications due to ostracization. Despite continuous efforts made so far to eliminate leprosy, stigma/misbeliefs/adverse attitude toward leprosy still prevails among common people. Community perceptions and attitudes towards leprosy patients are critical and unique indicator of how society stereotypes leprosy. Aims: The qualitative study was conducted to explore the perceptions of leprosy patients towards leprosy. Materials and Methods: Two focused group discussions (FGDs) with 19 newly-diagnosed leprosy patients who can speak vernacular were conducted with help of a predetermined FGD-guide between April and June 2019 in the dermatology out-patient department of the tertiary-care center. Both FGD sessions were recorded, transcribed, and translated into English. These verbatims were thematically analyzed and emerging themes were identified with illustrative quotations. Free list and pile sort data obtained were analyzed by Visual Anthropac version 1.0 software for Smith's salience value Cognitive mapping with two-dimensional scaling and hierarchical cluster analysis. Results: Small size of wound, not giving importance, failure to realize, bad luck and scared of being isolated etc., were the most common reported perceptions. Overall, five themes emerged after pile sorting, namely ignorance about the disease, stigma and economic burden, positive perception after diagnosis, treatment-related suggestions, and myths and frequently asked questions. Conclusion: The study concludes that more IEC campaigns are required to abolish the stigma; and ASHA workers/front-line workers can play a pivotal role. The program (NLEP) can also utilize the role of satisfied cured-patient as peer-educator to improve the attitude of society towards this disease.

Treatment response and long-term outcomes in biliary ascariasis: A prospective study.

BACKGROUND AND STUDY AIMS: Anti-helminthic therapy and endoscopic worm extraction had variable success rates in biliary ascariasis. Recurrent biliary events after worm clearance are common. We aimed to evaluate the outcomes of management in biliary ascariasis and find out the incidence and risk factors for the development of recurrent biliary events. PATIENTS AND METHODS: Consecutive patients with biliary ascariasis detected on abdominal ultrasound (AUS), were selected. Initial conservative treatment with oral Albendazole (400 mg) and analgesics was started in all. Successful therapy was defined as symptomatic resolution, and AUS confirmed biliary clearance after three weeks. ERCP (Endoscopic retrograde cholangiopancreatography) was performed in patients with failed conservative management. The patients were prospectively followed up for a minimum period of 1 year. RESULTS: Among 98 patients with biliary ascariasis, 23 (23.5%) responded to medical management alone. A presentation with obstructive jaundice (p = 0.04) and cholangitis (p = 0.007) was significantly associated with failure to medical management. Sixty-five (86.7%) among 75 patients had successful biliary clearance with ERCP. During a median follow up of 16 months, 24 (24.5%) patients had recurrent biliary events. Lower socioeconomic status (OR = 0.78, p = 0.023) and longer follow-up (OR = 1.16, p = 0.001) were independent risk factors for recurrent biliary events. CONCLUSION: Early ERCP among high-risk patients and proper hygiene are the keys to successful management in biliary ascariasis.

Endonasal surgery in the coronavirus era - Birmingham experience.

BACKGROUND: The World Health Organization declared coronavirus disease 2019 a pandemic on 11th March 2020. There is concern regarding performing endonasal surgical procedures because of a high viral load in the nasopharynx. This paper describes our experience in conducting emergency and urgent endonasal operations during the peak of the coronavirus disease 2019 pandemic in the UK. OBJECTIVES: To show the outcome of endonasal surgery during the peak of the coronavirus disease 2019 pandemic and to assess the post-operative rate of nosocomial coronavirus disease 2019 infection. METHODS: A retrospective cohort study was conducted of all patients who underwent high priority endoscopic nasal surgery or anterior skull base surgery between 23rd March and 15th June 2020 at University Hospitals Birmingham NHS Trust. RESULTS: Twenty-four patients underwent endonasal surgery during the study period, 12 were males and 12 were females. There was no coronavirus-related morbidity in any patient. CONCLUSION: This observational study found that it is possible to safely undertake urgent endonasal surgery; the nosocomial risk of coronavirus disease 2019 can be mitigated with appropriate peri-operative precautions.

Tracing the genetic root of Trinket cattle: an endangered cattle population of a small isolated island of Nicobar group of islands.

Trinket cattle are the inhabitant of a small island called Trinket, which is one of the picturesque islands of Andaman. This herd is thought to be of Danish leftover during their dynasty in Nicobar archipelago. When the island was abandoned by foreign invaders, indigenes utilized the animals for the purpose of meat. As a result, the cattle became semi-feral in nature. After the Great Sumatra earthquake and tsunami of Indian Ocean in 2004, Trinket island was left abandoned by indigenes and the cattle became totally feral in nature. To trace the genetic root of the cattle, this study has been undertaken based on the sequence information of the mitochondrial D-loop and cytochrome b gene. The genomic DNA was extracted from the blood samples of the Trinket cattle and was used for amplification of mitochondrial markers, and the sequence information was generated by Sanger sequencing. The analysis of sequence information revealed that the Trinket cattle belongs to Bos indicus (I) haplotype, sub-haplotype I2. The presence of I2 sub-haplotype in Trinket cattle may be due to the expansion of this I2 haplotype towards Southeast Asian countries. This is a novel input for the formulation of breeding strategy towards conservation of eco-friendly sustainable livestock in the isolated island ecosystem.

Prevalence of ticks (Acari: Ixodidae) and Theileria annulata infection of cattle in Gezira State, Sudan.

This study was conducted in Gezira State, central Sudan during January, May and August 2014 to determine species of ticks infesting cattle and prevalence of Theileria annulata infection and antibodies. A total of 200 head of cattle were sampled for ticks, blood smears, lymph node biopsy smears and sera from five study areas. Zebu (Butana and Kenana) and cross-bred (Zebu X Friesian) cattle of both sexes were sampled. Cattle age groups were younger than one year, one year to younger than four years and four years and older. Coat colour of cattle was recorded. The results revealed that cattle were infested with Rhipicephalus evertsi evertsi (n = 562, 51.6%), Hyalomma anatolicum (n = 289, 26.5%), H. rufipes (n = 70, 6.4%), R. sanguineus sanguineus (n = 59, 5.4%), R. decoloratus (n = 39, 3.6%), Amblyomma lepidum (n = 35, 3.2%), H. impeltatum (n = 26, 2.4%) and H. dromedarii (n = 9, 0.8%). Out of 200 blood and biopsy smears, 33 (16.5%) showed piroplasms for Theileria spp., while 29 (14.5%) were positive for Theileria spp. schizonts. Seropositivity for T. annulata using indirect fluorescent antibody (IFA) test was 94 (47%). It is concluded that there are three genera of hard ticks and eight species in Gezira State and tropical theileriosis is endemic in the state. These findings are the first records in Gezira State, Central Sudan and it is highly recommended to consider the endemicity of tropical theileriosis particularly in cattle upgrading programmes.

Overexpression of HURP mRNA in head and neck carcinoma and association with in vitro response to vinorelbine.

HURP gene encodes the hepatoma upregulated protein (HURP), a microtubule associated protein regulating mitotic spindle dynamics, which promotes chromosomal congression and alignment during mitosis, with a potential role in tumorigenesis. In the present study, HURP mRNA expression was investigated by reverse transcription-quantitative PCR in oropharyngeal squamous cell carcinoma (OPSCC). Primary OPSCC tumors from 107 patients and 48 adjacent normal tissues, as well as 12 respiratory tract cancer cell lines (9 head and neck squamous cell carcinoma, 2 lung cancer and 1 normal bronchial) were utilised in the present study. mRNA expression levels of HURP were higher in malignant OPSCC tissues compared with in normal mucosa (P<1×10-5) and significantly associated with sex and smoking status (P<0.0001). Vinorelbine in vitro toxicity at half-maximal inhibitory concentration (IC50) was measured in the 11 cancer cell lines using an MTT assay. Sensitivity to vinorelbine was significantly correlated with HURP expression (r=0.636; P=0.035). The data indicated that HURP overexpression is frequent in OPSCC tissues and associated with smoking. The correlation between HURP mRNA expression and vinorelbine in vitro response suggests that HURP is a potential modulator of vinorelbine response; therefore, it should be explored for its possible predictive value for the efficiency of vinorelbine treatment in this type of cancer.

The use of modified Silastic nasal splints as frontal sinus stents: a technical note.

BACKGROUND: Endoscopic frontal sinus surgery is frequently complicated by post-operative stenosis and obstruction of the frontal sinus outflow tract, resulting in recurrent disease. Frontal sinus stents may help prevent re-occlusion of the frontal neo-ostia. OBJECTIVE: This paper presents a simple and cost-effective approach to frontal sinus stenting using modified Silastic nasal splints. RESULTS AND CONCLUSION: The current technique provides an effective, reliable and inexpensive method for achieving post-operative frontal sinus outflow tract patency.

Effectiveness and safety of autologous platelet-rich plasma therapy with total contact casting versus total contact casting alone in treatment of trophic ulcer in leprosy: An observer-blind, randomized controlled trial.

BACKGROUND: Trophic ulcers secondary to leprosy pose a great stigma to patients and remain a challenge to the treating dermatologists. Platelet-rich plasma (PRP) introduces growth factors directly into the wound and aids in rapid healing. The role of PRP in the treatment of trophic ulcers in leprosy patients has not yet been established by randomized controlled trials. AIMS: To study the effectiveness and safety of autologous PRP therapy with total contact casting versus total contact casting alone in the treatment of trophic ulcers in leprosy. METHODS: In an observer-blind, randomized (1:1) controlled study, 118 patients were enrolled. PRP was prepared by the manual double-spin method (1600 rpm for 10 min followed by 4000 rpm for 10 min). After wound bed preparation, activated PRP was injected intra- and perilesionally, and platelet-poor plasma gel was applied over the ulcer bed. Occlusive dressings and total contact casting were then applied in Group A, and only total contact casting was applied in Group B. The same procedure was repeated every 2 weeks for 8 weeks. RESULTS: In all, 56 patients were analyzable in Group A and 52 in Group B. The surface area of the ulcer decreased significantly from first follow-up onward in both the groups (P < 0.001 in both the groups). Intergroup comparison showed that the reduction in the surface area of the ulcer was significantly more in Group A than in Group B from the first follow-up onward (P = 0.038) and the difference was maintained till the fifth follow-up (P < 0.001). At the end of the study, 91.10 ± 9.65% ulcer surface area reduction had occurred in Group A, whereas it was 79.77 ± 17.91% in Group B (P < 0.001). Trophic ulcers healed completely more often in paucibacillary leprosy patients (P < 0.001) and in those with a lower initial surface area of the ulcer (P < 0.001). LIMITATION: Short duration of treatment (8 weeks). CONCLUSION: PRP combined with total contact casting accelerates the healing of trophic ulcers of leprosy and is more effective than total contact casting alone. Complete remission is more likely to occur when the duration and surface area of ulcer are less and in the paucibacillary spectrum.

Mitogenome analysis of Indian isolate of Rhipicephalus microplus clade A sensu (): A first report from Maritime South-East Asia.

This communication reports a comprehensive profile of mitogenome analysis of Rhipicephalus microplus, isolated and identified from Andaman and Nicobar islands, a part of Maritime South East Asia. Complete mitogenome of Indian isolate of R. microplus (MK234703) was 14,903 bp. Mitochondrial (mt.) genome had 13 protein coding genes (PCGs), 22 tRNAs, two ribosomal subunits and two control regions. All PCGs were located on the H-strand except nad1, nad5, nad4 and nad4L. All start codons were ATN codon and abbreviated stop codons were seen in cox-2-3, nad-5 and cytb. A purine rich tick-box motif has been identified. A tandem repeat unit (TTTATT), described as a region alike to nad1 was identified in 130 bp insertion in between nad1 and tRNA-Glu and in nad1 sequence. Presence of two control regions (CRs) proved that, two CRs have evolved in concert rather than independently. Strong biasness towards A and T in Indian isolate of R. microplus is a typical feature for most of the arthropods. Subtracted values of dn and ds suggested that, there was least effect of nt. sequence of cox1 gene when Indian isolate was compared with other isolates of Rhipicephalus. On the basis of phylogenetic analysis, species of the genus Rhipicephalus could be clustered in three groups; ticks of the genera belonging to sub-family Rhipicephalinae could be grouped in a single cluster. Finally, cox1 sequence of MK234703 indicated that the isolate belonged to clade A sensu Burger et al., 2014 which has not been reported earlier from India.

Patulous Eustachian tube obliteration using endovascular coils: a novel technique.

BACKGROUND: Patulous Eustachian tube is a distressing condition characterised by chronic patency of the Eustachian tube and its failure to close. Patients typically present with symptoms of autophony and aural fullness. In patients requiring surgical intervention, a variety of different procedures have been demonstrated (both transtympanic and endonasal), with limited success. Evidence of the effectiveness of a number of surgical interventions is limited to small case series only. OBJECTIVE: This paper describes a novel treatment for patulous Eustachian tube using a 3 mm VortX Diamond endovascular coil.Case reportA transnasal endoscopic approach was adopted, with cannulation of the Eustachian tube orifice using a Relieva sinus guide suction tube from a balloon sinuplasty set. The coil was deployed 1.5 cm deep into the Eustachian tube. Post-operative imaging was used to confirm correct positioning. Regular follow up was arranged. The patient reported complete resolution of her symptoms. CONCLUSION: The technique has so far proved highly effective and minimally invasive. It will be employed in more patients to fully establish its effectiveness in treating patulous Eustachian tube.

AURKA mRNA expression is an independent predictor of poor prognosis in patients with non-small cell lung cancer.

Deregulation of mitotic spindle genes has been reported to contribute to the development and progression of malignant tumours. The aim of the present study was to explore the association between the expression profiles of Aurora kinases (AURKA, AURKB and AURKC), cytoskeleton-associated protein 5 (CKAP5), discs large-associated protein 5 (DLGAP5), kinesin-like protein 11 (KIF11), microtubule nucleation factor (TPX2), monopolar spindle 1 kinase (TTK), and ß-tubulins (TUBB) and (TUBB3) genes and clinicopathological characteristics in human non-small cell lung carcinoma (NSCLC). Reverse transcription-quantitative polymerase chain reaction-based RNA gene expression profiles of 132 NSCLC and 44 adjacent wild-type tissues were generated, and Cox's proportional hazard regression was used to examine associations. With the exception of AURKC, all genes exhibited increased expression in NSCLC tissues. Of the 10 genes examined, only AURKA was significantly associated with prognosis in NSCLC. Multivariate Cox's regression analysis demonstrated that AURKA mRNA expression [hazard ratio (HR), 1.81; 95% confidence interval (CI), 1.16-2.84; P=0.009], age (HR, 1.03; 95% CI, 1.00-1.06; P=0.020), pathological tumour stage 2 (HR, 2.43; 95% CI, 1.16-5.10; P=0.019) and involvement of distal nodes (pathological node stage 2) (HR, 3.14; 95% CI, 1.24-7.99; P=0.016) were independent predictors of poor prognosis in patients with NSCLC. Poor prognosis of patients with increased AURKA expression suggests that those patients may benefit from surrogate therapy with AURKA inhibitors.

Recurrent head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Recurrent cancers present some of the most challenging management issues in head and neck surgical and oncological practice. This is rendered even more complex by the poor evidence base to support management options, the substantial implications that treatments can have on the function and quality of life, and the difficult decision-making considerations for supportive care alone. This paper provides consensus recommendations on the management of recurrent head and neck cancer. Recommendations • Consider baseline and serial scanning with computed tomography and/or magnetic resonance (CT and/or MR) to detect recurrence in high-risk patients. (R) • Patients with head and neck cancer recurrence being considered for active curative treatment should undergo assessment by positron emission tomography combined with computed tomography (PET-CT) scan. (R) • Patients with recurrence should be assessed systematically by a team experienced in the range of management options available for recurrence including surgical salvage, re-irradiation, chemotherapy and palliative care. (R) • Management of patients with laryngeal recurrence should include input from surgeons with experience in transoral surgery and partial laryngectomy for recurrence. (G) • Expertise in transoral surgery and partial laryngectomy for recurrence should be concentrated to a few surgeons within each multidisciplinary teams. (G) • Transoral or open partial laryngectomy should be offered as definitive treatment modality for highly-selected patients with recurrent laryngeal cancer. (R) • Patients with OPC recurrence should have p16 human papilloma virus status assessed. (R) • Patients with OPC recurrence should be considered for salvage surgical treatment by an experienced team, with reconstructive expertise input. (G) • Transoral surgery appears to be an effective alternative to open surgery for the management of OPC recurrence in carefully selected patients. (R) • Consider elective selective neck dissections in patients with recurrent primaries with N0 necks, especially in advanced cases. (R) • Selective neck dissection (with preservation of nodal levels, especially level V, that are not involved by disease) in patients with nodal (N+) recurrence appears to be as effective as modified or radical neck dissections. (R) • Use salivary bypass tubes following salvage laryngectomy. (R) • Use interposition muscle-only pectoralis major or free flap for suture line reinforcement if performing primary closure following salvage laryngectomy. (R) • Use inlaid pedicled or free flap to close wound if there is tension at the anastomosis following laryngectomy. (R) • Perform secondary puncture in post chemoradiotherapy laryngectomy patients. (R) • Triple therapy with platinum, cetuximab and 5-fluorouracil (5-FU) appears to provide the best outcomes for the management of patients with recurrence who have a good performance status and are fit to receive it. If not fit, then combinations of platinum and cetuximab or platinum and 5-FU may be considered. (R) • Patients with non-resectable recurrent disease should be offered the opportunity to participate in phases I-III clinical trials of new therapeutic agents. (R) • Chemo re-irradiation appears to improve locoregional control, and may have some benefit for overall survival, at the risk of considerable acute and late toxicity. Benefit must be weighed carefully against risks, and patients must be counselled appropriately. (R) • Target volumes should be kept tight and elective nodal irradiation should be avoided. (R) • Best supportive care should be offered routinely as part of the management package of all patients with recurrent cancer even in the case of those who are being treated curatively. (R).

Unabsorbed dura patch removed eight years after pituitary surgery.

The Codman ETHISORB Dura Patch is a synthetic, absorbable material whose absorption is complete within approximately 90 days. We report the first case of an unabsorbed Codman Dura patch, in which a patient was presented with nasal obstruction and epistaxis 8 years after pituitary surgery for Cushing's disease.

Three-Dimensional Hand-to-Gland Combat: The Future of Endoscopic Surgery?

Objective To compare two dimensional (2D), three-dimensional (3D) non-high-definition (HD), and 3D HD endoscopic surgical techniques. Methods We describe our initial operative experience with a novel 3D HD endoscopic endonasal approach involving a pituitary adenoma resection, provide a case series, and review the current literature. This is the first case in Europe using the new 3D HD endoscope. Results Although research evidence remains limited, there are no significant negative perioperative or postoperative outcomes when compared with 2D endoscopic techniques. In our experience the narrow operating corridors of endoscopic surgery cannot be addressed with 3D endoscopic techniques. The new 3D HD endoscope creates imaging quality similar to conventional 2D HD systems. Conclusion Three-dimensional endoscopic endonasal techniques provide an exciting new avenue, effectively addressing potential depth perception difficulties with current 2D systems.

Pharmacokinetic analysis and tissue distribution of andrographolide in rat by a validated LC-MS/MS method.

CONTEXT: Andrographis paniculata (Burm.f.) Nees (Acanthaceae) is widely used in tribal medicine in India and some other countries for multiple clinical applications. It contains andrographolide (AG) (diterpenoid lactone), a major phytomarker which probably accounts for its medicinal properties. OBJECTIVE: This study investigates the site-specific distribution of AG in different tissues of rats and its pharmacokinetic parameter evaluation by using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. MATERIALS AND METHODS: A simple and sensitive LC-MS/MS method has been developed and validated to quantify the presence of AG in plasma and various tissues of rat following oral administration of A. paniculata extract and AG in a dose of 133.33 and 100 mg/kg/day, respectively, for four weeks. RESULTS: The present study showed that the highest concentration of AG was in kidney (156.12 ng/g) followed by liver, spleen and brain while almost same concentration was found in heart and lung. The apparent C(max), T(max), elimination half-life and total exposure (AUC(0-α)) were 115.81 ng/ml, 0.75, 2.45 and 278.44 ngh/ml, respectively. CONCLUSION: This was an attempt to determine the presence of AG (a known biomarker) in tissues such as kidney, heart, lungs, brain and plasma of rats using a validated LC-MS/MS method. Furthermore, the observed reduced concentration in plasma and various tissues from 1 to 8 h might be attributed to relatively rapid elimination or distribution of AG from the central compartment.