Reconstructive Options for Basal Cell Carcinoma Defects in the Head and Neck Region: An Institutional Experience.

Basal cell carcinoma (BCC) is the most common skin cancer with more than 80% occurring on the face occurring mainly due to exposure to ultraviolet rays in the elderly due to cumulative exposure of the UV rays during their lifetime. Though various treatment modalities are available for the treatment of basal cell carcinomas, wide local excision is the standard line of management. However, reconstruction of facial BCC poses a challenge to the reconstructive surgeon. Over a 4-year-old period from 2017 to 2021, a total of 30 patients of head and neck basal cell carcinoma were surgically excised in our institution. We have explored all modes of reconstruction from small to large BCC defects in terms of cosmesis, form and function. Four patients underwent primary closure, 8 patients underwent skin grafting, 13 patients underwent closure by local and advancement flaps and 5 patients with large defects underwent free flap reconstruction. No flap loss was reported. None reported any functional deficit. To achieve adequate aesthetic surgical outcomes after reconstruction, knowledge of facial aesthetic regions is of utmost importance. The size and location of the defect and the presence of vital structures adjacent to the defect should be assessed to determine the kind of reconstruction that should be carried out without adversely affecting adjacent structures. For greater patient satisfaction, the method of reconstruction should be tailor made, where donor tissue resembles native tissue with good contour and texture match, suture line scars are camouflaged, and complications are nil.

Trafficking and/or division: Distinct roles of nucleoporins based on their location within the nuclear pore complex.

The nuclear pore complex (NPC) facilitates the trafficking of proteins and RNA between the nucleus and cytoplasm. The role of nucleoporins (Nups) in transport in the context of the NPC is well established, yet their function in tRNA export has not been fully explored. We selected several nucleoporins from different parts of the NPC to investigate their potential role in tRNA trafficking in Trypanosoma brucei. We show that while all of the nucleoporins studied are essential for cell viability, only TbNup62 and TbNup53a function in tRNA export. In contrast to homologs in yeast TbNup144 and TbNup158, which are part of the inner and outer ring of the NPC, have no role in nuclear tRNA trafficking. Instead, TbNup144 plays a critical role in nuclear division, highlighting the role of nucleoporins beyond nucleocytoplasmic transport. These results suggest that the location of nucleoporins within the NPC is crucial to maintaining various cellular processes.

Dynamic queuosine changes in tRNA couple nutrient levels to codon choice in Trypanosoma brucei.

Every type of nucleic acid in cells undergoes programmed chemical post-transcriptional modification. Generally, modification enzymes use substrates derived from intracellular metabolism, one exception is queuine (q)/queuosine (Q), which eukaryotes obtain from their environment; made by bacteria and ultimately taken into eukaryotic cells via currently unknown transport systems. Here, we use a combination of molecular, cell biology and biophysical approaches to show that in Trypanosoma brucei tRNA Q levels change dynamically in response to concentration variations of a sub-set of amino acids in the growth media. Most significant were variations in tyrosine, which at low levels lead to increased Q content for all the natural tRNAs substrates of tRNA-guanine transglycosylase (TGT). Such increase results from longer nuclear dwell time aided by retrograde transport following cytoplasmic splicing. In turn high tyrosine levels lead to rapid decrease in Q content. Importantly, the dynamic changes in Q content of tRNAs have negligible effects on global translation or growth rate but, at least, in the case of tRNATyr it affected codon choice. These observations have implications for the occurrence of other tunable modifications important for 'normal' growth, while connecting the intracellular localization of modification enzymes, metabolites and tRNAs to codon selection and implicitly translational output.

Preferential import of queuosine-modified tRNAs into Trypanosoma brucei mitochondrion is critical for organellar protein synthesis.

Transfer RNAs (tRNAs) are key players in protein synthesis. To be fully active, tRNAs undergo extensive post-transcriptional modifications, including queuosine (Q), a hypermodified 7-deaza-guanosine present in the anticodon of several tRNAs in bacteria and eukarya. Here, molecular and biochemical approaches revealed that in the protozoan parasite Trypanosoma brucei, Q-containing tRNAs have a preference for the U-ending codons for asparagine, aspartate, tyrosine and histidine, analogous to what has been described in other systems. However, since a lack of tRNA genes in T. brucei mitochondria makes it essential to import a complete set from the cytoplasm, we surprisingly found that Q-modified tRNAs are preferentially imported over their unmodified counterparts. In turn, their absence from mitochondria has a pronounced effect on organellar translation and affects function. Although Q modification in T. brucei is globally important for codon selection, it is more so for mitochondrial protein synthesis. These results provide a unique example of the combined regulatory effect of codon usage and wobble modifications on protein synthesis; all driven by tRNA intracellular transport dynamics.

Prevalence and distribution of maxillofacial trauma in tertiary care centers before/ after motorcycle helmet use law in Sullia, India-A retrospective study.

BACKGROUND/AIMS: In India, motorcycles are commonly involved in accidents and traffic rules negligence, most of which include some type of maxillofacial trauma. In September 2019, the rules for motorcycle and helmet use were modified to compulsory use in the state of Karnataka. The aim of this study was to assess the impact of mandatory helmet use on maxillofacial fractures and injuries in Sullia Taluk, Karnataka. MATERIALS AND METHODS: The study was based on the information obtained from clinical records in the K.V.G Dental College and the K.V.G Medical College from February 2019 to February 2020. The inclusion criteria were subjects who met with two-wheeler accidents with complete case records and radiological investigations. RESULTS: A total of 78 individuals reported with maxillofacial trauma from February 2019 to February 2020. The mean age was 31 ± 14 years. There were 74 (94%) males and 4 (6%) females. Forty-nine cases reported before the mandatory helmet use rule and 29 cases reported after the helmet use rule. There was a 36.3% decrease in the incidence of maxillofacial trauma, 23.5% decrease in fractures, and an 89% reduction in the number of victims who underwent open reduction and internal fixation during the post-law period. CONCLUSION: There was a significant reduction in the incidence and severity of maxillofacial trauma after the implementation of the helmet rule.

The general mRNA exporters Mex67 and Mtr2 play distinct roles in nuclear export of tRNAs in Trypanosoma brucei.

Transfer RNAs (tRNAs) are central players in protein synthesis, which in Eukarya need to be delivered from the nucleus to the cytoplasm by specific transport receptors, most of which belong to the evolutionarily conserved beta-importin family. Based on the available literature, we identified two candidates, Xpo-t and Xpo-5 for tRNA export in Trypanosoma brucei. However, down-regulation of expression of these genes did not disrupt the export of tRNAs to the cytoplasm. In search of alternative pathways, we tested the mRNA export complex Mex67-Mtr2, for a role in tRNA nuclear export, as described previously in yeast. Down-regulation of either exporter affected the subcellular distribution of tRNAs. However, contrary to yeast, TbMex67 and TbMtr2 accumulated different subsets of tRNAs in the nucleus. While TbMtr2 perturbed the export of all the tRNAs tested, silencing of TbMex67, led to the nuclear accumulation of tRNAs that are typically modified with queuosine. In turn, inhibition of tRNA nuclear export also affected the levels of queuosine modification in tRNAs. Taken together, the results presented demonstrate the dynamic nature of tRNA trafficking in T. brucei and its potential impact not only on the availability of tRNAs for protein synthesis but also on their modification status.

Evaluation of the efficacy and safety of Capsule Longvida® Optimized Curcumin (solid lipid curcumin particles) in knee osteoarthritis: a pilot clinical study.

Purpose: Osteoarthritis is the single most common cause of disability in older adults with an estimated 10% to 15% prevalence in individuals above 60 years. The contemporary medications include nonsteroidal anti-inflammatory drugs acetaminophen, cyclooxygenase-2 inhibitors, and surgical interventions. In view of safety issues regarding their longterm use, necessitating search for effective and safe alternatives, we evaluated Capsule Longvida® Optimized Curcumin prepared using solid lipid curcumin particles (SLCP) technology in patients with knee osteoarthritis. Patients and methods: Eligible patients fulfilling American College of Rheumatology Criteria were randomized to SLCP group (400 mg twice daily delivering 80 mg of curcumin per capsule) or Ibuprofen with placebo group (400 mg each once daily) for 90 days. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analog Scale (VAS) were used for clinical assessment of knee pain and function. Degree of knee flexion and swelling were also noted. Blood biochemistry included hemogram, blood urea, creatinine, Random blood sugar and inflammatory markers viz. PGE2, TNF α, IL6, IL1ß and LTB4 while urine examination included degenerative marker CTX II. The parametric data was analyzed using unpaired t test while non-parametric data was analyzed using Friedman's test or Mann Whitney t test as applicable. A level of p<0.05 was considered as statistically significant. Results: Out of 50 recruitments, 25 from the Ibuprofen group and 17 from the SLCP group completed the study with significant improvements in VAS and WOMAC scores indicating comparable efficacy of SLCP in alleviating pain with Ibuprofen. None of the markers displayed significant changes. Except one withdrawal in the study group due to rash and itching, the study drug was found safe. Conclusions: SLCP in a dose of 160 mg daily was found to be effective and safe in alleviating symptoms in patients suffering from knee osteoarthritis when administered for 90 days.

Evaluation of Prevalence and Morphology of Dimple among Population of Sullia Taluk.

BACKGROUND: Dimple is one of the special indentations in skin of the face, which is considered as a sign of beauty. Dimpleplasty/surgical creation of dimple is a cosmetic procedure done by surgeons. Determining accurate position of dimple to create maximum beauty is always challenging to surgeons. AIMS AND OBJECTIVES: This study aimed at evaluating the prevalence and morphology (position and size) of naturally occurring dimple among population of Sullia taluk. MATERIALS AND METHODS: In total, 1462 people were screened for the occurrence of natural dimples in face. Among them, 121 were found to have natural dimples. Prevalence of dimple, position of the dimple, and the variation in distance from the Khoo Boo-Chai's (KBC) point to the naturally occurring dimple was assessed. RESULTS: Among 121 patients with dimples, unilateral cheek dimples (72.88%) were more common than bilateral (27.11%). Ninety-one dimples (60.66%) were at KBC point and 59 dimples (39.33%) occurred anterior to KBC point at a mean distance of 9.86 mm. The mean size of dimple superoinferiorly on the right side was 8.29 mm and on the left side it was 8.96 mm. The mean size anteroposteriorly on the right side was 6.48 and on the left side it was 6.51 mm. CONCLUSION: The mean measurements in size and position of the dimple might help the surgeon in creating dimples resembling naturally occurring dimples.

Neonatal Screening for Prevalence of Hearing Impairment in Rural Areas.

Hearing is one of the most important sense organs for man. Hearing loss is often associated with delayed speech and language development in young children. Early identification and intervention improves the chance a child gets to lesser delays in development and improving the overall quality of life. To find out the prevalence of hearing loss in neonates in the rural taluka of Maval, Pune, Maharashtra, India. Prospective Non Randomized Clinical Study. The study was carried out between April 2012 and April 2015. A total of 8192 babies were screened across various centers around the Maval area. The babies who had some high risk factors were 1683 in number and babies who had no high risk factors i.e. well babies were 6509. In our study, the overall prevalence of hearing loss in neonates in Maval taluka of Maharashtra was found to be 3.54 per 1000 live births, in normal born neonates (well babies) was 1.689 per 1000 births, in high risk babies was 10.69 per 1000 high risk births. The prevalence of low birth weight neonates, hyperbilirubinemia neonates and neonates with craniofacial abnormalities developing hearing impairment was found to be 5.9, 3.56 and 1.18 per 1000 high risk births respectively. India is the second most populated country in the world with nearly a fifth of the world's population. There is a need for the universal neonatal screening for deafness for earlier detection of deafness and rehabilitation. Level of Evidence: Level IV.

Retrograde nuclear transport from the cytoplasm is required for tRNATyr maturation in T. brucei.

Retrograde transport of tRNAs from the cytoplasm to the nucleus was first described in Saccharomyces cerevisiae and most recently in mammalian systems. Although the function of retrograde transport is not completely clear, it plays a role in the cellular response to changes in nutrient availability. Under low nutrient conditions tRNAs are sent from the cytoplasm to nucleus and presumably remain in storage there until nutrient levels improve. However, in S. cerevisiae tRNA retrograde transport is constitutive and occurs even when nutrient levels are adequate. Constitutive transport is important, at least, for the proper maturation of tRNAPhe, which undergoes cytoplasmic splicing, but requires the action of a nuclear modification enzyme that only acts on a spliced tRNA. A lingering question in retrograde tRNA transport is whether it is relegated to S. cerevisiae and multicellular eukaryotes or alternatively, is a pathway with deeper evolutionary roots. In the early branching eukaryote Trypanosoma brucei, tRNA splicing, like in yeast, occurs in the cytoplasm. In the present report, we have used a combination of cell fractionation and molecular approaches that show the presence of significant amounts of spliced tRNATyr in the nucleus of T. brucei. Notably, the modification enzyme tRNA-guanine transglycosylase (TGT) localizes to the nucleus and, as shown here, is not able to add queuosine (Q) to an intron-containing tRNA. We suggest that retrograde transport is partly the result of the differential intracellular localization of the splicing machinery (cytoplasmic) and a modification enzyme, TGT (nuclear). These findings expand the evolutionary distribution of retrograde transport mechanisms to include early diverging eukaryotes, while highlighting its importance for queuosine biosynthesis.

Highly efficient Cs-based perovskite light-emitting diodes enabled by energy funnelling.

The incorporation of phenylethylammonium bromide (PEABr) into a fully inorganic CsPbBr3 perovskite framework led to the formation of mixed-dimensional perovskites, which enhanced the photoluminescence due to efficient energy funnelling and morphological improvements. With a PEABr : CsPbBr3 ratio of 0.8 : 1, PeLEDs with a current efficiency of 6.16 cd A-1 and an EQE value of 1.97% have been achieved.

Modulating Excitonic Recombination Effects through One-Step Synthesis of Perovskite Nanoparticles for Light-Emitting Diodes.

The primary advantages of halide perovskites for light-emitting diodes (LEDs) are solution processability, direct band gap, good charge-carrier diffusion lengths, low trap density, and reasonable carrier mobility. The luminescence in 3 D halide perovskite thin films originates from free electron-hole bimolecular recombination. However, the slow bimolecular recombination rate is a fundamental performance limitation. Perovskite nanoparticles could result in improved performance but processability and cumbersome synthetic procedures remain challenges. Herein, these constraints are overcome by tailoring the 3 D perovskite as a near monodisperse nanoparticle film prepared through a one-step in situ deposition method. Replacing methyl ammonium bromide (CH3 NH3 Br, MABr) partially by octyl ammonium bromide [CH3 (CH2 )7 NH3 Br, OABr] in defined mole ratios in the perovskite precursor proved crucial for the nanoparticle formation. Films consisting of the in situ formed nanoparticles displayed signatures associated with excitonic recombination, rather than that of bimolecular recombination associated with 3 D perovskites. This transition was accompanied by enhanced photoluminescence quantum yield (PLQY≈20.5 % vs. 3.40 %). Perovskite LEDs fabricated from the nanoparticle films exhibit a one order of magnitude improvement in current efficiency and doubling in luminance efficiency. The material processing systematics derived from this study provides the means to control perovskite morphologies through the selection and mixing of appropriate additives.

Wire-shaped perovskite solar cell based on TiO2 nanotubes.

In this work, a wire-shaped perovskite solar cell based on TiO2 nanotube (TNT) arrays is demonstrated for the first time by integrating a perovskite absorber on TNT-coated Ti wire. Anodization was adopted for the conformal growth of TNTs on Ti wire, together with the simultaneous formation of a compact TiO2 layer. A sequential step dipping process is employed to produce a uniform and compact perovskite layer on top of TNTs with conformal coverage as the efficient light absorber. Transparent carbon nanotube film is wrapped around Ti wire as the hole collector and counter electrode. The integrated perovskite solar cell wire by facile fabrication approaches shows a promising future in portable and wearable textile electronics.

Carbon nanotubes as an efficient hole collector for high voltage methylammonium lead bromide perovskite solar cells.

A high open circuit voltage (V(OC)) close to 1.4 V under AM 1.5, 100 mW cm(-2) conditions is achieved when carbon nanotubes (CNTs) are used as a hole conductor in methyl ammonium lead bromide (MAPbBr3) perovskite solar cells. Time-resolved photoluminescence and impedance spectroscopy investigations suggest that the observed high V(OC) is a result of the better charge extraction and lower recombination of the CNT hole conductor. Tandem solar cells with all perovskite absorbers are demonstrated with a MAPbBr3/CNT top cell and a MAPbI3 bottom cell, achieving a V(OC) of 2.24 V in series connection. The semitransparent and high voltage MAPbBr3/CNT solar cells show great potential for applications in solar cell windows, tandem solar cells and solar driven water splitting.

Laminated carbon nanotube networks for metal electrode-free efficient perovskite solar cells.

Organic-inorganic metal halide perovskite solar cells were fabricated by laminating films of a carbon nanotube (CNT) network onto a CH3NH3PbI3 substrate as a hole collector, bypassing the energy-consuming vacuum process of metal deposition. In the absence of an organic hole-transporting material and metal contact, CH3NH3PbI3 and CNTs formed a solar cell with an efficiency of up to 6.87%. The CH3NH3PbI3/CNTs solar cells were semitransparent and showed photovoltaic output with dual side illuminations due to the transparency of the CNT electrode. Adding spiro-OMeTAD to the CNT network forms a composite electrode that improved the efficiency to 9.90% due to the enhanced hole extraction and reduced recombination in solar cells. The interfacial charge transfer and transport in solar cells were investigated through photoluminescence and impedance measurements. The flexible and transparent CNT network film shows great potential for realizing flexible and semitransparent perovskite solar cells.

High efficiency solid-state sensitized solar cell-based on submicrometer rutile TiO2 nanorod and CH3NH3PbI3 perovskite sensitizer.

We report a highly efficient solar cell based on a submicrometer (~0.6 µm) rutile TiO2 nanorod sensitized with CH3NH3PbI3 perovskite nanodots. Rutile nanorods were grown hydrothermally and their lengths were varied through the control of the reaction time. Infiltration of spiro-MeOTAD hole transport material into the perovskite-sensitized nanorod films demonstrated photocurrent density of 15.6 mA/cm(2), voltage of 955 mV, and fill factor of 0.63, leading to a power conversion efficiency (PCE) of 9.4% under the simulated AM 1.5G one sun illumination. Photovoltaic performance was significantly dependent on the length of the nanorods, where both photocurrent and voltage decreased with increasing nanorod lengths. A continuous drop of voltage with increasing nanorod length correlated with charge generation efficiency rather than recombination kinetics with impedance spectroscopic characterization displaying similar recombination regardless of the nanorod length.

Effects of particle size and surface modification on cellular uptake and biodistribution of polymeric nanoparticles for drug delivery.

PURPOSE: To investigate the effects of the particle size and surface coating on the cellular uptake of the polymeric nanoparticles for drug delivery across the physiological drug barrier with emphasis on the gastrointestinal (GI) barrier for oral chemotherapy and the blood-brain barrier (BBB) for imaging and therapy of brain cancer. METHODS: Various sizes of commercial fluorescent polystyrene nanoparticles (PS NPs) (viz 20 50, 100, 200 and 500 nm) were modified with the d-α-tocopheryl polyethylene glycol 1,000 succinate (vitamin E TPGS or TPGS). The size, surface charge and surface morphology of PS NPs before and after TPGS modification were characterized. The Caco-2 and MDCK cells were employed as an in vitro model of the GI barrier for oral and the BBB for drug delivery into the central nerve system respectively. The distribution of fluorescent NPs after i.v. administration to rats was analyzed by the high performance liquid chromatography (HPLC). RESULTS: The in vitro investigation showed enhanced cellular uptake efficiency for PS NPs in both of Caco-2 and MDCK cells after TPGS surface coating. In vivo investigation showed that the particle size and surface coating are the two parameters which can dramatically influence the NPs biodistribution after intravenous administration. The TPGS coated NPs of smaller size (< 200 nm) can escape from recognition by the reticuloendothelial system (RES) and thus prolong the half-life of the NPs in the blood system. CONCLUSIONS: TPGS-coated PS NPs of 100 and 200 nm sizes have potential to deliver the drug across the GI barrier and the BBB.

Nanoclay gelation approach toward improved dye-sensitized solar cell efficiencies: an investigation of charge transport and shift in the TiO2 conduction band.

Nanoclay minerals play a promising role as additives in the liquid electrolyte to form a gel electrolyte for quasi-solid-state dye-sensitized solar cells, because of the high chemical stability, unique swelling capability, ion exchange capacity, and rheological properties of nanoclays. Here, we report the improved performance of a quasi-solid-state gel electrolyte that is made from a liquid electrolyte and synthetic nitrate-hydrotalcite nanoclay. Charge transport mechanisms in the gel electrolyte and nanoclay interactions with TiO(2)/electrolyte interface are discussed in detail. The electrochemical analysis reveals that the charge transport is solely based on physical diffusion at the ratio of [PMII]:[I(2)] = 10:1 (where PMII is 1-propyl-3-methylimidazolium iodide). The calculated physical diffusion coefficient shows that the diffusion of redox ions is not affected much by the viscosity of nanoclay gel. The addition of nitrate-hydrotalcite clay in the electrolyte has the effect of buffering the protonation process at the TiO(2)/electrolyte interface, resulting in an upward shift in the conduction band and a boost in open-circuit voltage (V(OC)). Higher V(OC) values with undiminished photocurrent is achieved with nitrate-hydrotalcite nanoclay gel electrolyte for organic as well as for inorganic dye (D35 and N719) systems. The efficiency for hydrotalcite clay gel electrolyte solar cells is increased by 10%, compared to that of the liquid electrolyte. The power conversion efficiency can reach 10.1% under 0.25 sun and 9.6% under full sun. This study demonstrates that nitrate-hydrotalcite nanoclay in the electrolyte not only solidifies the liquid electrolyte to prevent solvent leakage, but also facilitates the improvement in cell efficiency.

A selective co-sensitization approach to increase photon conversion efficiency and electron lifetime in dye-sensitized solar cells.

Ruthenium-based C106 and organic D131 sensitizers have been judicially chosen for co-sensitization due to their complementary absorption properties and different molecular sizes. Co-sensitization yields a higher light-harvesting efficiency as well as better dye coverage to passivate the surface of TiO(2). The co-sensitized devices C106 + D131 showed significant enhancement in the performance (η = 11.1%), which is a marked improvement over baseline devices sensitized with either D131 (η = 5.6%) or C106 (η = 9.5%). The improved performance of the co-sensitized cell is attributed to the combined enhancement in the short circuit current, open circuit voltage, and the fill-factor of the solar cells. J(sc) is improved because of the complementary absorption spectra and favorable energy level alignments of both dyes; whereas, V(oc) is improved because of the better surface coverage helping to reduce the recombination and increase the electron life time. The origins of these enhancements have been systematically studied through dye desorption, absorption spectroscopy, and intensity modulated photovoltage spectroscopy investigations.

Distinct spatial and molecular features of notch pathway assembly in regulatory T cells.

Variations in the spatial localization of signaling components and crosstalk among signaling cascades are mechanisms through which diversity in signaling networks is generated. The receptor Notch provides an example of regulation by spatial localization: In the canonical Notch signaling pathway, Notch is cleaved to produce the Notch intracellular domain (NICD, also known as NIC), which translocates to the nucleus to regulate gene expression. We describe a T cell receptor-dependent, non-nuclear distribution and function of the processed receptor Notch, which was associated with the improved survival of regulatory T cells (T(regs)) in vitro and in vivo and was compromised by T cell-specific deletion of Notch1. Unlike a nuclear-restricted mutant of NICD, mutant NICD that underwent nuclear export or was targeted to the plasma membrane protected Notch1(-/-) T(regs) from apoptosis induced by nutrient deprivation and oxidative stress. Notch signaling integrated with phosphatidylinositol 3-kinase signaling and mammalian target of rapamycin complex 2 (mTORC2) for this cell survival function. Biochemical and imaging approaches revealed a membrane-proximal complex containing NICD and the mTORC2 component Rictor, and this complex was stabilized by specific interactions with the Notch ligand Delta-like-1 and mediated the survival of T(regs). Together, our evidence for the spatial control of Notch and the crosstalk of Notch signaling with other pathways reveals coupling between the localization of Notch and diverse intracellular signaling pathways.