Tumor-related denervation pseudohypertrophy of the tongue: A clinical entity in disguise!

Isolated hypoglossal nerve palsy in the base of tongue carcinomas is seldom noticed. The clinical signs are subtle in early stageand can often be overlooked. There may be slight tongue deviation to the affected side, and the tongue feels soft and edematouson careful palpation. There may be associated enlargement of the affected side of the tongue known as “pseudo hypertrophy” dueto denervation of its motor supply. Contrast-enhanced magnetic resonance imaging is the gold standard of diagnosis which showsdiffuse fatty changes in the affected half of tongue with the preservation of architecture. Clinicians need to be aware of this clinicalentity to distinguish it from actual tumor invasion

Frozen Section Evaluation in Head and Neck Oncosurgery: An Initial Experience in a Tertiary Cancer Center

Objective: Frozen section evaluation is routinely used by oncosurgeons across specialties for rapid assessment of the presence of tumor in any tissue and its most common use is in surgical margins. Today, the use of intraoperative frozen-section evaluation of surgical margins is an accepted and frequent practice in head and neck oncology. This study aims to determine the efficacy and accuracy of frozen sections in head and neck cancer patients and compare the results with the respective paraffin sections and also to analyze the reasons for any disparity between them. Material and Method: A retrospective study was conducted to evaluate efficacy and accuracy of frozen section in head and neck cancer of 265 patients, treated at a tertiary cancer centre hospital between January 2013 to December 2014. Results: Out of 265 cases, it was found that 12.6% of these sections showed true positivity, 6.3% false positivity, 2.9% false negativity and 78.2% true negativity. The study also shows a sensitivity of 82.05% and specificity of 96.46%. Conclusion: Our study shows that intraoperative frozen section reports are specific and highly sensitive. We recommend a minimum of 3-4 sections, optimum cryostat temperature, good section thickness and quality staining for a good concordance rate

The impact of COVID-19 on pulmonary, neurological, and cardiac outcomes: evidence from a Mendelian randomization study

BackgroundLong COVID is a clinical entity characterized by persistent health problems or development of new diseases, without an alternative diagnosis, following SARS-CoV-2 infection that affects a significant proportion of individuals globally. It can manifest with a wide range of symptoms due to dysfunction of multiple organ systems including but not limited to cardiovascular, hematologic, neurological, gastrointestinal, and renal organs, revealed by observational studies. However, a causal association between the genetic predisposition to COVID-19 and many post-infective abnormalities in long COVID remain unclear.MethodsHere we employed Mendelian randomization (MR), a robust genetic epidemiological approach, to investigate the potential causal associations between genetic predisposition to COVID-19 and long COVID symptoms, namely pulmonary (pneumonia and airway infections including bronchitis, emphysema, asthma, and rhinitis), neurological (headache, depression, and Parkinson’s disease), cardiac (heart failure and chest pain) diseases, and chronic fatigue. Using two-sample MR, we leveraged genetic data from a large COVID-19 genome-wide association study and various disorder-specific datasets.ResultsThis analysis revealed that a genetic predisposition to COVID-19 was significantly causally linked to an increased risk of developing pneumonia, airway infections, headache, and heart failure. It also showed a strong positive correlation with chronic fatigue, a frequently observed symptom in long COVID patients. However, our findings on Parkinson’s disease, depression, and chest pain were inconclusive.ConclusionOverall, these findings provide valuable insights into the genetic underpinnings of long COVID and its diverse range of symptoms. Understanding these causal associations may aid in better management and treatment of long COVID patients, thereby alleviating the substantial burden it poses on global health and socioeconomic systems

Short-Term History Based Authentication Using Smartphone Sensors and Apps

Secrete-QA could be a security primarily based application. A security question is asked once the user fails to login or forgets his/her password and to reset the password. A security question could be a secondary authentication, but these queries is guessed simply by an admirer or exposed to a strangers who might recognize our personal info like friends, relations or those that will access our personal info through public on-line tools. We will build these security queries additional customized by using the privilege of accessing our Smartphone sensors and apps while not affecting the user’s privacy. Three types of questions are generated that is, Yes/No questions, Multiple Choice questions and WH questions. An android app is created for the frequent updating of the Smartphone data and questions are asked in the web part using this updated data.The questions are generated by considering the legacy apps, GPS, calendar, app details etc.These have the mostmemorability to the users and high robustness to attacks

Spatially-resolved soft materials for controlled release – hybrid hydrogels combining a robust photo-activated polymer gel with an interactive supramolecular gel

Hybrid hydrogels based on self-assembling low-molecular-weight gelator (LMWG) DBS-CONHNH2 (DBS = 1,3;2,4-dibenzylidene-D-sorbitol) and crosslinked polymer gelator (PG) PEGDM (poly(ethyleneglycol) dimethacrylate) are reported, and an active pharmaceutical ingredient (naproxen, NPX) is incorporated. The use of PEGDM as PG enhances the mechanical stiffness of the hybrid gel (G′ increases from 400 to 4500 Pa) – the LMWG enhances its stability to very high frequency. Use of DBS-CONHNH2 as LMWG enables interactions with NPX and hence allows pH-mediated NPX release – the PG network is largely orthogonal and only interferes to a limited extent. Use of photo-activated PEGDM as PG enables spatially-resolved photo-patterning of robust hybrid gel domains within a preformed LMWG network – the presence of the LMWG enhances the spatial resolution. The photo-patterned multi-domain gel retains pH-mediated NPX release properties and directionally releases NPX into a compartment of higher pH. The two components within these hybrid PG/LMWG hydrogels therefore act largely independently of one another, although they do modify each others properties in subtle ways. Hybrid hydrogels capable of spatially controlled unidirectional release have potential applications in tissue engineering and drug-delivery

Substituent interference on supramolecular assembly in urea gelators: synthesis, structure prediction and NMR

Eighteen N-aryl-N'-alkyl urea gelators were synthesised in order to understand the effect of head substituents on gelation performance. Minimum gelation concentration values obtained from gel formation studies were used to rank the compounds and revealed the remarkable performance of 4-methoxyphenyl urea gelator 15 in comparison to 4-nitrophenyl analogue 14, which could not be simply ascribed to substituent effects on the hydrogen bonding capabilities of the urea protons. Crystal structure prediction calculations indicated alternative low energy hydrogen bonding arrangements between the nitro group and urea protons in gelator 14, which were supported experimentally by NMR spectroscopy. As a consequence, it was possible to relate the observed differences to interference of the head substituents with the urea tape motif, disrupting the order of supramolecular packing. The combination of unbiased structure prediction calculations with NMR is proposed as a powerful approach to investigate the supramolecular arrangement in gel fibres and help understand the relationships between molecular structure and gel formation

Multi-component hybrid hydrogels – understanding the extent of orthogonal assembly and its impact on controlled release

This paper reports self-assembled multi-component hybrid hydrogels including a range of nanoscale systems and characterizes the extent to which each component maintains its own unique functionality, demonstrating that multi-functionality can be achieved by simply mixing carefully-chosen constituents. Specifically, the individual components are: (i) pH-activated low-molecular-weight gelator (LMWG) 1,3;2,4-dibenzylidenesorbitol-4′,4′′-dicarboxylic acid (DBS–COOH), (ii) thermally-activated polymer gelator (PG) agarose, (iii) anionic biopolymer heparin, and (iv) cationic self-assembled multivalent (SAMul) micelles capable of binding heparin. The LMWG still self-assembles in the presence of PG agarose, is slightly modified on the nanoscale by heparin, but is totally disrupted by the micelles. However, if the SAMul micelles are bound to heparin, DBS–COOH self-assembly is largely unaffected. The LMWG endows hybrid materials with pH-responsive behavior, while the PG provides mechanical robustness. The rate of heparin release can be controlled through network density and composition, with the LMWG and PG behaving differently in this regard, while the presence of the heparin binder completely inhibits heparin release through complexation. This study demonstrates that a multi-component approach can yield exquisite control over self-assembled materials. We reason that controlling orthogonality in such systems will underpin further development of controlled release systems with biomedical applications

Cationic supramolecular hydrogels for overcoming the skin barrier in drug delivery

A cationic bis-imidazolium-based amphiphile was used to form thermoreversible nanostructured supramolecular hydrogels incorporating neutral and cationic drugs for the topical treatment of rosacea. The concentration of the gelator and the type and concentration of the drug incorporated were found to be factors that strongly influenced the gelling temperature, gel-formation period, and overall stability and morphology. The incorporation of brimonidine tartrate resulted in the formation of the most homogeneous material of the three drugs explored, whereas the incorporation of betamethasone resulted in a gel with a completely different morphology comprising linked particles. NMR spectroscopy studies proved that these gels kept the drug not only at the interstitial space but also within the fibers. Due to the design of the gelator, drug release was up to 10 times faster and retention of the drug within the skin was up to 20 times more effective than that observed for commercial products. Experiments in vivo demonstrated the rapid efficacy of these gels in reducing erythema, especially in the case of the gel with brimonidine. The lack of coulombic attraction between the gelator–host and the guest–drug seemed particularly important in highly effective release, and the intermolecular interactions operating between them were found to lie at the root of the excellent properties of the materials for topical delivery and treatment of rosacea

Diffusion across a gel-gel interface-molecular-scale mobility of self-assembled 'solid-like' gel nanofibres in multi-component supramolecular organogels

This paper explores macroscopic-scale diffusion of the molecular-scale building blocks of two-component self-assembled organogel nanofibres using a diffusion cell in which two different gels are in contact with one another. Both components of the 'solid-like' nanofibres (lysine peptide dendron acids and amines) can diffuse through these gels and across a gel-gel interface, although diffusion is significantly slower than that of a non-interactive additive in the 'liquid-like' phase of the gel. Amine diffusion was probed by bringing similar gels with different amines into contact. Dendron acid diffusion was tested by bringing similar gels with enantiomeric dendrons into contact. Surprisingly, dendron and amine diffusion rates were similar, even though the peptide dendron is more intimately hydrogen bonded in the self-assembled nanofibres. It is proposed that thermal disassembly of the acid-amine complex delivers both components into the liquid-like phase, allowing them to diffuse via a decomplexation/recomplexation mechanism. This is a rare observation in which molecules assembled into solid-like gel nanofibres are mobile-in dynamic equilibrium with the liquid-like phase. Gel nanofibre diffusion and reorganisation are vital in understanding dynamic materials processes such as metastability, self-healing and adaptability

Economic evaluation of shortened, bedaquiline-containing treatment regimens for rifampicin-resistant tuberculosis (STREAM stage 2) : a within-trial analysis of a randomised controlled trial

Background: The STREAM stage 2 trial assessed two bedaquiline-containing regimens for rifampicin-resistant tuberculosis: a 9-month all-oral regimen and a 6-month regimen containing an injectable drug for the first 2 months. We did a within-trial economic evaluation of these regimens. Methods: STREAM stage 2 was an international, phase 3, non-inferiority randomised trial in which participants with rifampicin-resistant tuberculosis were randomly assigned (1:2:2:2) to the 2011 WHO regimen (terminated early), a 9-month injectable-containing regimen (control regimen), a 9-month all-oral regimen with bedaquiline (oral regimen), or a 6-month regimen with bedaquiline and an injectable for the first 2 months (6-month regimen). We prospectively collected direct and indirect costs and health-related quality of life data from trial participants until week 76 of follow-up. Cost-effectiveness of the oral and 6-month regimens versus control was estimated in four countries (oral regimen) and two countries (6-month regimen), using health-related quality of life for cost-utility analysis and trial efficacy for cost-effectiveness analysis. This trial is registered with ISRCTN, ISRCTN18148631. Findings: 300 participants were included in the economic analyses (Ethiopia, 61; India, 142; Moldova, 51; Uganda, 46). In the cost-utility analysis, the oral regimen was not cost-effective in Ethiopia, India, Moldova, and Uganda from either a provider or societal perspective. In Moldova, the oral regimen was dominant from a societal perspective. In the cost-effectiveness analysis, the oral regimen was likely to be cost-effective from a provider perspective at willingness-to-pay thresholds per additional favourable outcome of more than US$4500 in Ethiopia,$1900 in India, $3950 in Moldova, and$7900 in Uganda, and from a societal perspective at thresholds of more than $15 900 in Ethiopia,$3150 in India, and $4350 in Uganda, while in Moldova the oral regimen was dominant. In Ethiopia and India, the 6-month regimen would cost tuberculosis programmes and participants less than the control regimen and was highly likely to be cost-effective in both cost-utility analysis and cost-effectiveness analysis. Reducing the bedaquiline price from$1·81 to $1·00 per tablet made the oral regimen cost-effective in the provider-perspective cost-utility analysis in India and Moldova and dominate over the control regimen in the provider-perspective cost-effectiveness analysis in India. Interpretation: At current costs, the oral bedaquiline-containing regimen for rifampicin-resistant tuberculosis is unlikely to be cost-effective in many low-income and middle-income countries. The 6-month regimen represents a cost-effective alternative if injectable use for 2 months is acceptable. Funding: USAID and Janssen Research & Development