MobiTangibles: Enabling Physical Manipulation Experiences of Virtual Precision Hand-Held Tools' Miniature Control in VR.

Realistic simulation for miniature control interactions, typically identified by precise and confined motions, commonly found in precision hand-held tools, like calipers, powered engravers, retractable knives, etc., are beneficial for skill training associated with these kinds of tools in virtual reality (VR) environments. However, existing approaches aiming to simulate hand-held tools' miniature control manipulation experiences in VR entail prototyping complexity and require expertise, posing challenges for novice users and individuals with limited resources. Addressing this challenge, we introduce MobiTangibles-proxies for precision hand-held tools' miniature control interactions utilizing smartphone-based magnetic field sensing. MobiTangibles passively replicate fundamental miniature control experiences associated with hand-held tools, such as single-axis translation and rotation, enabling quick and easy use for diverse VR scenarios without requiring extensive technical knowledge. We conducted a comprehensive technical evaluation to validate the functionality of MobiTangibles across diverse settings, including evaluations for electromagnetic interference within indoor environments. In a user-centric evaluation involving 15 participants across bare hands, VR controllers, and MobiTangibles conditions, we further assessed the quality of miniaturized manipulation experiences in VR. Our findings indicate that MobiTangibles outperformed conventional methods in realism and fatigue, receiving positive feedback.

Shoulder Dysfunction and Quality of Life Following Modified Radical and Selective Neck Dissection: A Prospective Comparative Study.

Head and neck cancers are fairly common in India due to the widespread consumption of tobacco and neck dissection is a major component in the surgical management. The objective of this study is to analyze the effect of MRND and SND on shoulder function and quality of life in patients of head and neck cancer. Our study is a prospective comparative study on 65 head and neck cancer patients divided into 2 groups-33 in group A (MRND group) and 32 in group B (SND group). Clinical evaluation of shoulder function was done pre-operatively, 1 week, 1 month, 3 month and 6 month post-operatively using arm abduction scores (AAS) and shoulder pain and disability index (SPADI). Nerve-conduction study (NCS) was done pre-operatively and 3 months post-operatively for assessment of SAN. Neck dissection quality of life questionnaire (NDQOL) was used as a quality-of-life measure. A total of 65 neck dissections were included in the analysis (33 in group A and 32 in group B) out of which 53 were males and 12 were females. The mean AAS on the 6th post-operative month in group A was significantly lower than that of group B (p = 0.01). The mean SPADI scores on the 6th post-operative month was significantly worse in group A than group B (p value 0.01). On NCS, a significant decrease in amplitude was seen in group A (p = 0.02) and a significant increase in latency was noted in group B (p = 0.005). Quality of life score on 6th post-operative month showed no significant difference between both the groups (p > 0.05). Level V dissection in MRND is associated with higher incidence and greater severity of shoulder dysfunction. AAS and SPADI score are useful tools in post operative follow up of shoulder dysfunction. NCS helps in the detection of neuropathy and to determine its severity. Early rehabilitation promotes long term recovery.

Parapharyngeal Nodal Metastasis in Papillary Thyroid Carcinoma: Catching Early.

Background: Metastasis to parapharyngeal space in papillary carcinoma of the thyroid is rare and often missed in routine clinical and radiological investigations. Although contrast CT /MRI can be done to locate the parapharyngeal lesion, the diagnosis of metastasis mostly deepened upon aspiration cytology, which is a challenge in difficult anatomical locations. Here, we have emphasized the management dilemma of parapharyngeal metastasis in papillary carcinoma of the thyroid. Case Report: A 30-year-old female presented with multiple right-side neck swelling for two months. Ultrasonography of right thyroid showed TIRAD V and left thyroid showed TIRAD II. Aspiration cytology of the right thyroid showed Bethesda III and aspiration cytology revealed thyroid follicles. Due to the diagnostic ambiguity, contrast-enhanced CT scan was advised. It revealed a hypervascular lymph node in the parapharyngeal space besides multiple right cervical lymph nodes and later changed the treatment plan. Conclusion: - Metastasis to parapharyngeal space in Papillary carcinoma of the thyroid is rare and often missed on routine evaluation. Contrast-enhanced CT/MRI can be added as a primary investigation in challenging cases of suspicious malignancy of the thyroid.

Cochlear Implantation in a Case of Relapsing Polychondritis With Profound Hearing Loss and Labyrinthine Ossification.

Relapsing polychondritis is an autoimmune disorder causing inflammation of cartilaginous structures, sensory epithelium, and cardiovascular system. Hearing loss is a rare and dreadful complication of this pathology. We report a case of relapsing polychondritis in a 38-year-old female who developed gradually progressive bilateral profound hearing loss. She did not have any improvement with medical management. Cochlear implantation was performed to rehabilitate her hearing. As the scala tympani was obliterated, a scala vestibuli insertion was performed. A complete insertion was possible with a compressed electrode, and she had good evoked compound action potential scores. Her categories of auditory performance scores were 6 at the end of one year. Patients with relapsing polychondritis can progress to profound hearing loss in rare cases and should be carefully followed up to identify early labyrinthine ossification. A scala vestibuli insertion can be performed with good outcomes in cases with ossification involving scala tympani. The surgeon should be ready for a middle-turn cochleostomy or a drill-out procedure in patients with advanced ossification.

The Mizoroki-Heck reaction between in situ generated alkenes and aryl halides: cross-coupling route to substituted olefins.

This review covers palladium-catalyzed typical Mizoroki-Heck cross-coupling reactions of aryl halides with in situ generated alkenes, by following a typical Heck coupling mechanism to form substituted olefins unlike direct cross-coupling of alkenes with aryl halides in Heck olefination. These reactions solve the issue of alkenes undergoing polymerization at high temperatures and increase reaction efficiency by reducing the reaction time and purification steps.

Exclusive Endoscopic Approach in the Management of Sinonasal Inverted Papilloma.

Background: With the advancement in endoscopic endonasal surgeries, there has been a change in the surgical approach from the traditional open surgeries to the more conservative endoscopic endonasal approach for the management of sinonasal inverted papilloma. In the present study, we have shared our experience of endoscopic excision inverted papilloma involving the paranasal sinuses in a tertiary care hospital. Materials and methods: It is a retrospective case series of 28 patients who underwent endoscopic excision of inverted papilloma of paranasal sinus in a tertiary care hospital from April 2017 to October 2020. The medical records were retrospectively analyzed for the clinical, radiological, pathological, intraoperative and postoperative findings and later compared among the surgical approaches. Results: Of the total of 28 patients with inverted papilloma (3; Krouse 2 and 25; Krouse 3), 11(21.4%) patients were operated through endoscopic modified Denker, 8(39.3%) patients with endoscopic medial maxillectomy and 6(21.4%) patients with endoscopic sinus surgery. Patients who underwent modified endoscopic approach had lesser complications compared to the standard endoscopic procedures. Conclusion: Endoscopic excision of the sinonasal inverted papilloma can be a valid alternative to the open surgical approach, enabling complete clearance of the disease with a minimal complication rate. A large population with a long-term follow-up may be needed for a better understanding of the results. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03332-6.

Outcomes in Managing Vascular Tinnitus: Institutional Experience and Review of 6-Year Literature.

To evaluate the outcomes in patients of vascular tinnitus managed at our institute. The clinical data of all patients diagnosed with pulsatile tinnitus from January 2014 to April 2022 and managed at AIIMS, Bhubaneswar, was retrospectively reviewed. The diagnosis, treatment and outcomes were analyzed. A 6-year literature review was performed from March 2015 to April 2021. Our series discusses managing eleven cases of vascular tinnitus with varied aetiology and their outcomes. Out of the eleven cases, eight patients underwent surgical or radiological intervention, and seven had complete resolution of symptoms. Of the eleven patients, three had partial resolution. The 6-year literature review revealed sigmoid and transverse sinus as the most common causative anatomical sites for pulsatile tinnitus. Amongst those who received an intervention, 83.56% of the patients had complete resolution of symptoms. Vascular tinnitus can be cured if the exact vessel causing it is localized. Clinical suspicion is based on the character of tinnitus and patient history. A careful evaluation of the head and neck sites for any vascular anomaly that can cause pulsatile tinnitus must be done. Radiology demonstrates treatable causes of it. It delineates the aberrant anatomical variations that can lead to this disturbing aetiology. Treatable causes are best addressed, and pathology should be taken care of. A multidisciplinary team comprising ENT surgeons, audiologists and interventional radiologists must identify and treat the pathology.

To evaluate the efficacy of topical anti-fungal therapy in postoperative cases of COVID Associated Mucormycosis (CAM): A single-blinded randomized control trial.

PURPOSE: To compare the efficacy of 0.1 % w/w Liposomal Amphotericin-B gel with 10 % w/w Povidone-Iodine and saline nasal douching in preventing revision surgery in patients with CAM. STUDY DESIGN: Multi-arm, parallel randomized control trial. STUDY SETTING: The trial was conducted in the Department of ENT, All India Institute of Medical Sciences (AIIMS) Bhubaneswar. METHODS: Participants: Microbiologically and histologically proven cases of mucormycosis who underwent surgical debridement were included in the study. INTERVENTIONS: Postoperatively, patients were randomized into three groups based on the type of topical intervention received, in the form of Lipid-based Amphotericin B gel, povidone­iodine ointment or saline nasal douching. OUTCOME: Requirement of revision surgery in postoperative cases of CAM. RANDOMIZATION: Participants were allotted to one of the three arms by block randomization. BLINDING: Single-blinded trial. RESULTS: Numbers randomized: 15 participants were randomized to each group. Recruitment: Completed recruiting. Numbers analyzed: 15 participants were analyzed in each group. OUTCOMES: Control arm's risk of revision surgery was 4.50 (95 % CI: 1.16-17.44) times than Lipid-based Amphotericin B gel arm and 1.50 (95 % CI: 0.71-3.16) times that of the Povidone- Iodine arm. The difference was statistically significant (p = 0.02) for Amphotericin but not for Povidone-Iodine. CONCLUSIONS: Topical Amphotericin-B gel application in the postoperative cavity can decrease the need for revision surgery and help in early recovery. TRIAL REGISTRATION: CTRI/2021/10/037257. Clinical Trials Registry of India.

Noscapine-Amino Acid Conjugates Suppress the Progression of Cancer Cells.

Lung cancer is the leading cause of cancer deaths globally; 1 in 16 people are diagnosed with lung cancer in their lifetime. Microtubules, a critical cytoskeletal assembly, have an essential role in cell division. Interference with the microtubule assembly leads to genetic instability during mitosis and cancer cell death. Currently, available antimitotic drugs such as vincas and taxanes are limited due to side effects such as alopecia, myelosuppression, and drug resistance. Noscapine, an opium alkaloid, is a tubulin-binding agent and can alter the microtubule assembly, causing cancer cell death. Amino acids are fundamental building blocks for protein synthesis, making them essential for the biosynthesis of cancer cells. However, the ability of amino acids in drug transportation has yet to be exploited in developing noscapine analogues as a potential drug candidate for cancer. Hence, in the present study, we have explored the ninth position of noscapine by introducing a hydroxymethylene group using the Blanc reaction and further coupled it with a series of amino acids to construct five target conjugates in good yields. The synthesized amino acid conjugate molecules were biologically evaluated against the A549 lung cancer cell line, among which the noscapine-tryptophan conjugate showed IC50 = 32 µM, as compared to noscapine alone (IC50 = 73 µM). Morphological changes in cancer cells, cell cycle arrest in the G1 phase, and ethidium bromide/acridine orange staining indicated promising anticancer properties. Molecular docking confirmed strong binding to tubulin, with a score of -41.47 kJ/mol with all 3D coordinates and significant involvement of molecular forces, including the hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations demonstrated a stable binding of noscapine-tryptophan conjugate for a prolonged time (100 ns) with the involvement of free energy through the reaction coordinates analyses, solving the bioavailability of parent noscapine to the body.

Fabrication of Superparamagnetic Bimetallic Magnesium Nanoferrite Using Green Polyol: Characterization and Anticancer Analysis in Vitro on Lung Cancer Cell Line A549.

Magnetic bimetallic nanoparticles find many industrial and clinical applications in the field of water treatment, antibacterial and anticancer activities. Therefore, the current article reports green synthesis using oleo-polyol as a surface modifier and synthesis agent for bimetallic magnetic magnesium ferrite nanoparticles. The role of hydroxyl functionality of castor oil (a natural polyol) on the enhancement of structural, morphological, magnetic, and particle size properties has also been discussed. These properties were characterized using FTIR, XRD spectroscopy, SEM, AFM, and TEM microscopy, Brunauer-Emmett-Teller (BET), and vibrating sample magnetometer (VSM) techniques. The effect of calcination temperatures (600-900 °C) on particle size (23-40 nm to 500-600 nm), crystallite sizes (73.15-292.67 nm), and saturation magnetization (20.87, 23.07, 32.39, and 33.13 emu g-1) was analyzed. The influence of calcined temperatures on the anticancer activity of these nanoparticles has also been investigated in vitro using lung cancer cells (A549). Their biocompatibility, cytotoxicity, flow cytometry, and statistical analysis against lung cancer cells (A549) have been discussed. The green synthesis of magnesium nanoferrite particles using natural polyol and their application as anticancer agents against lung cancer cells (A549) have not been reported previously. They have exhibited far superior IC50 values and anticancer activity as compared to other reported metal oxides and magnesium oxide nanoparticles.

Use of gold nanoparticle-silibinin conjugates: A novel approach against lung cancer cells.

Lung cancer presents one of the most challenging carcinomas with meager 5-year survival rates (less than 20%), high metastasis and high recurrence due to chemo- and radio- resistance. An alternative or complementation to existing prognosis modalities is the use of phytochemicals such as silibinin, which targets essential cytokines, angiogenic factors and transcription factors for a profound anti-tumor effect. However, the problems of low solubility in an aqueous physiological environment, poor penetration, high metabolism and rapid systemic clearance limit the therapeutic use of silibinin. Conjugation of gold nanoparticles (GNPs) with silibinin may overcome the above challenges along with distinct advantages of biocompatibility, optical properties for monitoring and causation of cytotoxicity in cancer cells. The current study thus aims to develop silibinin conjugated gold nanoparticles (Sb-GNPs) with pH responsive release in the cancer microenvironment, optimizing several parameters for its higher activity and further evaluate the nanoplatform for their efficacy in inducing cell death in vitro against A549 lung cancer cells. GNPs was synthesized using trisodium citrate dihydrate as the reducing agent and further used for the conjugation of silibinin. The synthesized GNPs were found to be monodispersed and spherical in shape. The silibinin was successfully conjugated with gold nanoparticles and long-term stability of GNPs and Sb-GNPs nanoconjugates in suspension phase was confirmed by FTIR and DLS. Anticancer properties of Sb-GNPs were confirmed by different assay using MTT, Trypan blue dye exclusion assay and cell cycle analysis assay. After conjugation of silibinin with GNPs, the efficacy of silibinin increased 4-5 times in killing the cancer cells. This is the first report on using silibinin gold nanoconjugate system for lung cancer therapy with promising future applications.

Land use change and carbon emissions of a transformation to timber cities.

Using engineered wood for construction has been discussed for climate change mitigation. It remains unclear where and in which way the additional demand for wooden construction material shall be fulfilled. Here we assess the global and regional impacts of increased demand for engineered wood on land use and associated CO2 emissions until 2100 using an open-source land system model. We show that if 90% of the new urban population would be housed in newly built urban mid-rise buildings with wooden constructions, 106 Gt of additional CO2 could be saved by 2100. Forest plantations would need to expand by up to 149 Mha by 2100 and harvests from unprotected natural forests would increase. Our results indicate that expansion of timber plantations for wooden buildings is possible without major repercussions on agricultural production. Strong governance and careful planning are required to ensure a sustainable transition to timber cities even if frontier forests and biodiversity hotspots are protected.

Efficacy of endoscopic repair for CSF otorrhoea in children with recurrent meningitis due to incomplete partition type 1.

OBJECTIVE: To review the efficacy of endoscopic management with or without cochlear implantation in a pediatric population presenting with recurrent meningitis due to inner ear incomplete partition type 1 (IP-1). MATERIALS AND METHODS: A multicentric report of 6 patients with a history of recurrent meningitis due to IP-1 was done. Radiological evaluation was performed to confirm the diagnosis. Transcanal endoscopic repair of the defect was performed in 3 cases, 2 cases underwent endoscope-assisted repair followed by cochlear implantation in the contralateral ear later, and 1 patient underwent endoscopic repair along with simultaneous cochlear implantation. RESULTS: Radiology confirmed the diagnosis and identified the site of the leak. A leak was detected in all cases from the stapes footplate. Two patients with unilateral deformity had a CSF-filled cyst protruding through a defect in the stapes footplate, and the rest of the four had a high flow CSF leak from the footplate. Five patients who underwent repair have had no further episodes of meningitis. One patient who received simultaneous implantation and repair developed postoperative meningitis managed successfully with antibiotics. CONCLUSION: Hearing loss due to inner ear deformity can be easily missed as a cause for recurrent meningitis, especially if unilateral. A high index of suspicion, audiological screening and radiology are essential to clinch the diagnosis. In such cases, a pure endoscopic or endoscopic assisted transcanal approach to repair CSF otorrhoea is an effective alternative to more radical procedures like subtotal petrosectomy with obliteration. In patients with bilateral profound hearing loss, simultaneous cochlear implantation and repair of the defect can be performed successfully.

Reconstruction of Subtotal Defect of the Lower Lip: Combined Use of Karapandzic and Nasolabial Flap.

Subtotal reconstruction of the lower lip after excision of the tumor is always a challenge for surgeons. It is because of the difficulty in  regaining the function of the lip, including the oral competency and restoring the aesthetic subunit. A 46-year-old patient presented with an ulceroproliferative growth involving 70% of the lower lip, including the right commissure. After the confirmation to be a malignancy, patient underwent excision of the tumour and reconstruction of the lower lip using the left Karapandzic flap and right nasolabial flap. The patient was on regular follow-up in the postoperative period to assess the surgical outcomes. The combined use of Karapandzic flap and the nasolabial flap can be reliably used for subtotal reconstruction of the lower lip in advanced oral cavity malignancy, involving one of the commissures. Later can ensure good postoperative results in terms of aesthetic and functional lip reconstruction without any significant intraoperative or postoperative complications.

Tracheostomy in the COVID19 Patients: Our Experience in 12 Cases.

The incidence of tracheostomy has been significantly increased with the increase of patients admitted to the intensive care units. Looking into the literature, there have been various protocols proposed in the past for tracheostomy in COVID 19 patients. In the present case series, we have presented our experience of surgical tracheostomy in COVID 19 patients. It is a retrospective case series consisting of 12 COVID 19 patients who underwent tracheostomy from April 2020 to October 2020. We have discussed the tracheostomy in COVID 19 patients with references to their respective indication, location, the procedure, postoperative care and clinical outcomes. Of 12 patients, 6 were operated in the COVID ICU and 6 were operated in the COVID OT. The average duration of the intubation was 4 days (range 3-7 days). The average period of weaning was found to be 65 h (range 48 h 80 h). Of 4 patients associated with comorbidities, two had died 48 h after the surgery. The Primary indication of the tracheostomy can be made flexible based on the infrastructure of the hospital to accommodate increased patient load in a developing country like India. The location and surgical approach does not significantly affect the clinical outcomes of tracheostomy, and it can be safely performed in ICU/OT with adequate ventilation. Irrespective of the COVID status of the patients, Personal Protective Equipment (PPE) can ensure adequate protection to the health care personals preventing the spread of infection.

Predisposing factors of rhino-orbital-cerebral mucormycosis in patients with COVID 19 infection.

The predisposing factors of invasive fungal disease in COVID 19 infection are still debatable because of the limited human understanding of the virus with the current literature. In this study, we have tried to correlate the various predisposing factors influencing the clinical profile and treatment outcomes in patients with covid associated mucormycosis (CAM). It is a retrospective analysis of cases of CAM during the second wave of COVID 19 infection, which was managed in the department of Otorhinolaryngology from Dec 1, 2020, to June 10, 2021. The detailed clinical, radiological and management of patients with CAM were collected, recorded, evaluated and correlated with the predisposing factors. Of the total, 46 patients, 44(95.65%) were diabetic and 41 patients had a previous history of steroid intake. When clinical parameters were compared between blood sugar < 200 mg/dl and > 200 mg/dl, the old and newly diagnosed diabetes mellitus in patients with CAM, there was no significant differences in any of the above clinical parameters (p > 0.05), except the hospital stay (p = 0,004). Steroid intake in patients with coexisting DM associated with CAM is considered the most important factor for the development of the CAM. There was are no significant difference in any of the clinical/treatment outcomes in patients with CAM with respect to the initial blood sugar, except for the hospital stay. A large sample size with a long-term follow-up period may be needed for a better understanding of common predisposing factors for the development of CAM.

Management of Covid Associated Mucormycosis of Mandible: A Mountain Beneath a Molehill-A Lesson Learnt.

The opportunistic infection of post-Covid associated mucormycosis has been reported globally; however, it has reached alarming proportions in India. Mucormycosis of the mandibular region is rare, and only a few cases have been reported to date. Covid associated mucormycosis has not been reported in the literature before, and we are the first to report them. We report two patients who presented with tooth loosening with pus discharge a few weeks following recovery from Covid infection. After tooth extraction adjacent necrotic bony specimen was sent for calcofluor potassium hydroxide mount, which was found positive for broad pauciseptate hyphae. Although CT scan imaging demonstrated the involvement of a mandible segment, we found a much more extensive involvement in both cases during resection. There was intramedullary spread of the mucormycosis throughout the inferior alveolar canal, with pus discharge and foul odor. The management of covid associated mandibular mucormycosis consists of surgical debridement with antifungal therapy and control of the underlying disease. It became challenging because the radiological extent of the disease was different from the definite clinical extension of the lesion found during surgery. The authors recommend surgeons adopt a flexible approach during surgery to plan resection depending on the clinical judgment and not rely entirely on CT scans. And the reconstruction of the mandible will follow as per the extent of excision.

Silver Nanoparticles Synthesized Using Carica papaya Leaf Extract (AgNPs-PLE) Causes Cell Cycle Arrest and Apoptosis in Human Prostate (DU145) Cancer Cells.

Treatment of cancer has been limited by the poor efficacy and toxicity profiles of available drugs. There is a growing demand to develop alternative approaches to combat cancer such as use of nano-formulation-based drugs. Here, we report biosynthesis and characterization of silver nanoparticles (AgNPs) with papaya leaf extract (PLE) and its anti-cancer properties against different human cancer cells. Purified nanoparticles were characterized by standard techniques, such as TEM, STM, SEM, EDS, XRD, and FTIR. Furthermore, cytotoxic activity of AgNPs-PLE was carried out against different human cancer cells and non-tumorigenic human keratinocytes cells. AgNPs-PLE when compared with AgNPs-citric acid or PLE showed better efficacy against cancer cells and was also relatively less toxic to normal cells. Treatment of DU145 cells with AgNPs-PLE (0.5-5.0 µg/ml) for 24-48 h lowered total cell number by 24-36% (P < 0.05). Inhibition of cell growth was linked with arrest of cell cycle at G2/M phase at 24 h, while G1 and G2/M phase arrests at 48 h. ROS production was observed at earlier time points in presence of AgNPs-PLE, suggesting its role behind apoptosis in DU145 cells. Induction of apoptosis (57%) was revealed by AO/EB staining in DU145 cells along with induction of Bax, cleaved caspase-3, and cleaved PARP proteins. G1-S phase cell cycle check point marker, cyclin D1 was down-regulated along with an increase in cip1/p21 and kip1/p27 tumor suppressor proteins by AgNPs-PLE. These findings suggest the anti-cancer properties of AgNPs-PLE.

The ongoing nutrition transition thwarts long-term targets for food security, public health and environmental protection.

The nutrition transition transforms food systems globally and shapes public health and environmental change. Here we provide a global forward-looking assessment of a continued nutrition transition and its interlinked symptoms in respect to food consumption. These symptoms range from underweight and unbalanced diets to obesity, food waste and environmental pressure. We find that by 2050, 45% (39-52%) of the world population will be overweight and 16% (13-20%) obese, compared to 29% and 9% in 2010 respectively. The prevalence of underweight approximately halves but absolute numbers stagnate at 0.4-0.7 billion. Aligned, dietary composition shifts towards animal-source foods and empty calories, while the consumption of vegetables, fruits and nuts increases insufficiently. Population growth, ageing, increasing body mass and more wasteful consumption patterns are jointly pushing global food demand from 30 to 45 (43-47) Exajoules. Our comprehensive open dataset and model provides the interfaces necessary for integrated studies of global health, food systems, and environmental change. Achieving zero hunger, healthy diets, and a food demand compatible with environmental boundaries necessitates a coordinated redirection of the nutrition transition. Reducing household waste, animal-source foods, and overweight could synergistically address multiple symptoms at once, while eliminating underweight would not substantially increase food demand.

Flavonoids inhibit chronically exposed arsenic-induced proliferation and malignant transformation of HaCaT cells.

BACKGROUND: Apart from exposure to UV-radiation, studies show relationship between skin cancer and chronic ingestion of arsenic through drinking water. Chemopreventive strategies could help in reducing the toxic effects of arsenic and arsenic-induced skin cancer. METHODS: Cytotoxicity of arsenic on human skin keratinocytes HaCaT cells was evaluated using MTT and trypan blue assays. Arsenic-induced malignant transformant HaCaT cells were selected through soft agar colony assay. Cell cycle progression was analyzed through FACS. The expressions of genes modulated by arsenic were studied through RT-PCR. RESULTS: The lower concentrations (0.1-0.5 µmol/L) of arsenic were non-toxic and transformed HaCaT cells on chronic exposure, and also enhanced the cell proliferation. Silibinin and fisetin reduced the arsenic-induced cell proliferation and malignant transformation. A slight increase in G2-M phase cell population was also observed. The anti-proliferation effects of flavonoids on HaCaT transformants were further enhanced when combined with gamma radiation. Chronic and acute exposure to arsenic modulated the expression of transformation-associated genes including Bcl-2A1, IGFL-1, Rab31, and TNC in HaCaT cells. CONCLUSIONS: Chronic exposure to lower arsenic concentrations caused malignant transformation of skin keratinocytes and that effect was attenuated by flavonoids silibinin and fisetin. Thus, chemoprevention could reduce arsenic-caused detrimental effects on skin cells.