Magnetic-field-induced propulsion of jellyfish-inspired soft robotic swimmers.

The multifaceted appearance of soft robots in the form of swimmers, catheters, surgical devices, and drug-carrier vehicles in biomedical and microfluidic applications is ubiquitous today. Jellyfish-inspired soft robotic swimmers (jellyfishbots) have been fabricated and experimentally characterized by several researchers that reported their swimming kinematics and multimodal locomotion. However, the underlying physical mechanisms that govern magnetic-field-induced propulsion are not yet fully understood. Here, we use a robust and efficient computational framework to study the jellyfishbot swimming kinematics and the induced flow field dynamics through numerical simulation. We consider a two-dimensional model jellyfishbot that has flexible lappets, which are symmetric about the jellyfishbot center. These lappets exhibit flexural deformation when subjected to external magnetic fields to displace the surrounding fluid, thereby generating the thrust required for propulsion. We perform a parametric sweep to explore the jellyfishbot kinematic performance for different system parameters-structural, fluidic, and magnetic. In jellyfishbots, the soft magnetic composite elastomeric lappets exhibit temporal and spatial asymmetries when subjected to unsteady external magnetic fields. The average speed is observed to be dependent on both these asymmetries, quantified by the glide magnitude and the net area swept by the lappet tips per swimming cycle, respectively. We observe that a judicious choice of the applied magnetic field and remnant magnetization profile in the jellyfishbot lappets enhances both these asymmetries. Furthermore, the dependence of the jellyfishbot swimming speed upon the net area swept (spatial asymmetry) is twice as high as the dependence of speed on the glide ratio (temporal asymmetry). Finally, functional relationships between the swimming speed and different kinematic parameters and nondimensional numbers are developed. Our results provide guidelines for the design of improved jellyfish-inspired magnetic soft robotic swimmers.

Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial.

PURPOSE: Benefit from convalescent plasma therapy for coronavirus disease 2019 (COVID-19) has been inconsistent in randomized clinical trials (RCTs) involving critically ill patients. As COVID-19 patients are immunologically heterogeneous, we hypothesized that immunologically similar COVID-19 subphenotypes may differ in their treatment responses to convalescent plasma and explain inconsistent findings between RCTs . METHODS: We tested this hypothesis in a substudy involving 1239 patients, by measuring 26 biomarkers (cytokines, chemokines, endothelial biomarkers) within the randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP) that assigned 2097 critically ill COVID-19 patients to either high-titer convalescent plasma or usual care. Primary outcome was organ support free days at 21 days (OSFD-21) . RESULTS: Unsupervised analyses identified three subphenotypes/endotypes. In contrast to the more homogeneous subphenotype-2 (N = 128 patients, 10.3%; with elevated type i and type ii effector immune responses) and subphenotype-3 (N = 241, 19.5%; with exaggerated inflammation), the subphenotype-1 had variable biomarker patterns (N = 870 patients, 70.2%). Subphenotypes-2, and -3 had worse outcomes, and subphenotype-1 had better outcomes with convalescent plasma therapy compared with usual care (median (IQR). OSFD-21 in convalescent plasma vs usual care was 0 (- 1, 21) vs 10 (- 1, to 21) in subphenotype-2; 1.5 (- 1, 21) vs 12 (- 1, to 21) in suphenotype-3, and 0 (- 1, 21) vs 0 (- 1, to 21) in subphenotype-1 (test for between-subphenotype differences in treatment effects p = 0.008). CONCLUSIONS: We reported three COVID-19 subphenotypes, among critically ill adults, with differential treatment effects to ABO-compatible convalescent plasma therapy. Differences in subphenotype prevalence between RCT populations probably explain inconsistent results with COVID-19 immunotherapies.

Signaling pathways and their potential therapeutic utility in esophageal squamous cell carcinoma.

Esophageal cancer is a complex gastrointestinal malignancy with an extremely poor outcome. Approximately 80% of cases of this malignancy in Asian countries including India are of squamous cell origin, termed Esophageal Squamous Cell Carcinoma (ESCC).The five-year survival rate in ESCC patients is less than 20%. Neo-adjuvant chemo-radiotherapy (NACRT) followed by surgical resection remains the major therapeutic strategy for patients with operable ESCC. However, resistance to NACRT and local recurrence after initial treatment are the leading cause of dismal outcomes in these patients. Therefore, an alternative strategy to promote response to the therapy and reduce the post-operative disease recurrence is highly needed. At the molecular level, wide variations have been observed in tumor characteristics among different populations, nevertheless, several common molecular features have been identified which orchestrate disease progression and clinical outcome in the malignancy. Therefore, determination of candidate molecular pathways for targeted therapy remains the mainstream idea of focus in ESCC research. In this review, we have discussed the key signaling pathways associated with ESCC, i.e., Notch, Wnt, and Nrf2 pathways, and their crosstalk during disease progression. We further discuss the recent developments of novel agents to target these pathways in the context of targeted cancer therapy. In-depth research of the signaling pathways, gene signatures, and a combinatorial approach may help in discovering targeted therapy for ESCC.

A unique case of light chain (AL) amyloidosis masquerading as hypophosphatemic osteomalacia.

Light chain (AL) amyloidosis is the result of a clonal plasma cell disorder which causes organ damage by deposition of misfolded light chains. Kidney is a common site of amyloid deposition. Proteinuria, usually in nephrotic range and unexplained renal insufficiency are the main manifestations of renal injury. We report a unique case of renal involvement by AL amyloidosis masquerading as metabolic bone disease. 38 year old male patient presented with progressively increasing diffuse bony pains, low backache and proximal weakness of both lower limbs since two years. On investigation, he was detected to have hypophosphatemic osteomalacia due to renal phosphate loss which was fibroblast growth factor 23 (FGF23)- independent. He also had nephrotic range low molecular weight proteinuria. Renal biopsy to ascertain the aetiology revealed deposition of amyloid fibrils in the glomerular mesangium on electron microscopy. Its characterization by immunofluorescence (IF) was consistent with immunoglobulin light chain (AL) amyloidosis. In the absence of a demonstrable plasma cell clone on bone marrow biopsy, we made a diagnosis of monoclonal gammopathy of renal significance (MGRS). He was treated with chemotherapy following which there was symptomatic improvement and reduction in phosphaturia. This case describes a unique presentation of renal injury due to AL amyloidosis masquerading as hypophosphatemic osteomalacia. The aim of this report is to highlight that hypophosphatemia in adults is usually acquired and treatment of underlying etiology results in cure, unlike in children where genetic counseling and phosphate replacement is the mainstay of treatment.

Influence of nanocellulose on mechanics and morphology of polyvinyl alcohol xerogels.

Xerogels are porous networks of crosslinked polymers that are useful for biomedical applications such as drug delivery, scaffold engineering, tissue regeneration, cell culture and wound dressing. However, inferior mechanical properties curtail their applications to a considerable extent. Nanocellulose fibers and crystals are often added into the polymer matrix to improve their mechanical strength. Here, nanocellulose in the mass ratios of 7%, 13% and 18% are loaded into polyvinyl alcohol (PVA) matrix followed by thermo-morpho-mechanical characterization. With increase in nanocellulose content, thermal degradation occurs at a lower temperature. It is observed that addition of higher quantity of nanocellulose crystals leads to the formation of weak cellulose-rich regions causing xerogel rupture. This is predominantly observed for xerogel loaded with 18% nanocellulose crystals. Similarly, addition of higher quantity of nanocellulose fibers increase brittleness of the xerogels causing fracture. This is predominantly observed for xerogel loaded with 18% nanocellulose fibers. Creep strain and stress relaxation is observed to decrease with addition of nanocellulose loading owing to molecular chain restriction and polymer chain immobility.

p40 in metastatic pulmonary trophoblastic tumour: potential diagnostic pitfall on histopathology.

p40, one of the two isomers of p63, is nowadays widely used for diagnosis of squamous cell carcinoma, especially in subtyping non-small cell carcinoma on lung biopsies. We describe a case in which lung tumour was misdiagnosed as squamous cell carcinoma due to p40 immunopositivity. A 36-year-old lady presented with cough and left sided chest pain of 2 months duration. Chest imaging revealed a lesion in left lower lobe of the lung and biopsy was suggestive of squamous cell carcinoma. However, past history revealed amputation of great toe for non-healing discharging ulcer which on histopathology was diagnosed as choriocarcinoma. She also had a history of hysterectomy five years ago, details of which were not available. Post-amputation ß-hCG levels were high and she had been treated with multimodality chemotherapy for choriocarcinoma. She had good response to chemotherapy initially, however became resistant later on. Review of the lung biopsy in the light of the past history along with extensive literature review led to the final diagnosis of metastatic trophoblastic tumour to lung. Hence, awareness that p40 immunopositivity can be seen in trophoblastic tumours is essential to avoid misdiagnosis, especially in sites like the lung where squamous cell carcinoma is common.

Changes in Saliva Rheological Properties and Mucin Glycosylation in Dry Mouth.

Saliva is vital for the maintenance of normal oral physiology and mucosal health. The loss of salivary function can have far-reaching consequences, as observed with dry mouth, which is associated with increased orodental disease, speech impairment, dysphagia, and a significant negative effect on quality of life. The timely diagnosis of oral dryness is vital for the management of orodental disease and any associated often-undiagnosed systemic disease (e.g., Sjögren syndrome). Our aim was to investigate differences in mucin glycoproteins and saliva rheological properties between sufferers and nonsufferers of dry mouth in order to understand the relationship between saliva composition, rheological properties, and dryness perception and provide additional potential diagnostic markers. All patients exhibited objective and subjective oral dryness, irrespective of etiology. Over half of the patients (n = 20, 58.8%) had a saliva secretion rate above the gland dysfunction cutoff of 0.1 mL/min. Mucin (MUC5B and MUC7) concentrations were generally similar or higher in patients. Despite the abundance of these moisture-retaining proteins, patients exhibited reduced mucosal hydration (wetness) and significantly lower saliva spinnbarkeit (stringiness), suggesting a loss of the lubricating and retention/adhesion properties of saliva, which, at least partially, are associated with mucin glycoproteins. Over 90% of patients with dry mouth (DMPs) consistently had unstimulated whole mouth saliva (UWMS) spinnbarkeit below the proposed normal cutoff (10 mm). Further analysis of mucins revealed the reduced glycosylation of mucins in DMPs compared to healthy controls. Our data indicate that UWMS mucin concentrations are not reduced in dry mouth but that the mucin structure (glycosylation) is altered. UWMS from DMPs had reduced spinnbarkeit, the assessment of which, in conjunction with sialometry, could improve sensitivity for the diagnosis of dry mouth. Additionally, it may be useful to take into consideration the altered mucin glycosylation and saliva rheological properties when designing synthetic or purified mucins for saliva substitutes and dry mouth therapy.

Ichthyosis follicularis, atrichia, and photophobia syndrome associated with a new mutation in MBTPS2.

Ichthyosis follicularis, atrichia and photophobia (IFAP) syndrome (OMIM 308205) is a rare X-linked genetic disorder. Mutations in MBTPS2 underlie IFAP syndrome, with 19 different mutations reported to date. Keratosis follicularis spinulosa decalvans (KFSD) is an allelic disorder that results from a single recurrent mutation, p.Asn508Ser. We report a case from the UK of IFAP syndrome resulting from a new mutation, p.Asn508Thr, emphasizing the significant overlap between IFAP and KFSD at both the molecular and clinical levels. An area of alopecia on the scalp of the proband's mother was also noted, suggesting lyonization.

Olmsted syndrome in an Iranian boy with a new de novo mutation in TRPV3.

Olmsted syndrome (OS) is a rare congenital skin disorder characterized by palmoplantar keratoderma, periorificial hyperkeratotic lesions and alopecia. Constriction of digits, onychodystrophy and pruritus may also occur. Recently, pathogenic heterozygous mutations in TRPV3 were identified, with most cases showing de novo dominant inheritance. We present the clinical and molecular features of OS in a 10-year-old Iranian boy. He had mutilating palmoplantar keratoderma, periorificial keratotic plaques, diffuse alopecia and constriction bands (pseudoainhum), which led to autoamputation of two digits. TRPV3 was sequenced and a new de novo heterozygous missense mutation, c.2076G>C (p.Trp692Cys), was identified. This case illustrates the characteristic clinical features and complications that can present in OS, and further expands the molecular basis of this genodermatosis.

Clinical assessment of oral dryness: development of a scoring system related to salivary flow and mucosal wetness.

OBJECTIVE: The aim of this study was to develop a clinical oral dryness score (CODS) for routine use in assessment of xerostomia patients and determine its relationship with salivary flow rates and mucosal wetness. STUDY DESIGN: CODS was determined from 10 features of oral dryness, each scoring as 1 point for a total score of 0-10. CODS, salivary flow rates, and mucosal wetness were measured in 100 patients and 50 healthy control subjects. The reproducibility of CODS was 0.89-0.96 (intraclass correlation coefficient). RESULTS: The mean ± SD CODS in patients was 6.0 ± 1.6 compared with 1.0 ± 0.9 for control subjects (P < .001), and the highest mean value was in the primary Sjögren syndrome group. There was a general inverse relationship in patients between mean CODS and salivary flow rate (P < .01) and mean CODS and mucosal wetness (P < .01). CONCLUSIONS: The CODS was found to be useful, easy to use, and reliable for routine assessment of the severity of dry mouth.

Investigating the relationship between hyposalivation and mucosal wetness.

BACKGROUND: Mucosal wetness (MW) reflects the layer of residual saliva that covers the oral mucosal surfaces. OBJECTIVES: The aim of this study was to determine MW at different oral mucosa sites and to investigate the relationship between MW, unstimulated whole salivary flow rates (UWS) and Clinical Oral Dryness Score (CODS). METHOD: A total of 100 dry mouth patients and 50 healthy subjects participated in the study. MW was sampled with filter paper strips at four sites inside the mouth; anterior hard palate (AHP), buccal mucosa (BUC), anterior tongue (AT), lower lip (LL) and measured with a micro-moisture meter. Reproducibility was assessed by repeated sampling and diurnal variation was examined. RESULTS: Mucosal wetness in healthy subjects differed according to site and means±SD were; AHP (11± 11.7µm), BUC (32±14.8µm), AT (65±17.2µm), and LL (25 ±13.5µm). Dry mouth patients with reduced UWS showed increased CODS. MW at all four sites was significantly reduced (P<0.05) in dry mouth patients compared with the healthy subjects. Reproducibility of MW measurement using the intra-class correlation coefficient showed agreement at different visits within subject. MW of the AT showed a positive correlation with UWS (P<0.05). CONCLUSION: Mucosal wetness is a reliable measure of oral dryness and had a positive correlation with UWS.

Lycopene inhibits DNA synthesis in primary prostate epithelial cells in vitro and its administration is associated with a reduced prostate-specific antigen velocity in a phase II clinical study.

Interest in lycopene has focused primarily on its use in the chemoprevention of prostate cancer (CaP); there are few clinical trials involving men with established disease. In addition, most data examining its mechanism of action have been obtained from experiments using immortal cell lines. We report the inhibitory effect(s) of lycopene in primary prostate epithelial cell (PEC) cultures, and the results of a pilot phase II clinical study investigating whole-tomato lycopene supplementation on the behavior of established CaP, demonstrating a significant and maintained effect on prostate-specific antigen velocity over 1 year. These data reinforce the justification for a large, randomized, placebo-controlled study.

NOL7 is a nucleolar candidate tumor suppressor gene in cervical cancer that modulates the angiogenic phenotype.

Cervical cancer is associated with human papilloma virus infection. However, this infection is insufficient to induce transformation and progression. Loss of heterozygosity analyses suggest the presence of a tumor suppressor gene (TSG) on chromosome 6p21.3-p25. Here we report the cloning NOL7, its mapping to chromosome band 6p23, and localization of the protein to the nucleolus. Fluorescence in situ hybridization analysis demonstrated an allelic loss of an NOL7 in cultured tumor cells and human tumor samples. Transfection of NOL7 into cervical carcinoma cells inhibited their growth in mouse xenografts, confirming its in vivo tumor suppressor activity. The induction of tumor dormancy correlated with an angiogenic switch caused by a decreased production of vascular endothelial growth factor and an increase in the production of the angiogenesis inhibitor thrombospondin-1. These data suggest that NOL7 may function as a TSG in part by modulating the expression of the angiogenic phenotype.

Biomonitoring insecticide pollution using non-target soil microarthropods.

The scope of biomonitoring insecticide pollution in soil is discussed with the help of field and laboratory findings on the density, prey-predator ratio and fecundity of non-target microarthropod fauna. Field experiments were conducted in small plots with mustard, wheat and lady's finger crops and insecticides namely heptachlor 20EC (3.25 kg ai/ha = 16.25 lit/ha) and endosulfan 35EC (0.875 kg ai/ha = 2.5 lit/ha) applied at the seedling stages. Soil microarthropod population estimated at fortnightly intervals in the treated and untreated control plots revealed a general trend of adverse effect of the insecticides, prominently on the density and relative abundance of major prey groups like Collembola and Acari leading to notable decline in prey-predator ratio. Comparison of the percentage reductions of major taxonomic and trophic groups between pre-treatment and post-treatment intervals also demonstrated the ill effect of both heptachlor and endosulfan, notably on Collembola and the prey category. In the laboratory the survival success and fecundity of Cyphoderus javanus (Collembola) and Archegozetes longisetosus (Acari) were compared by exposing freshly emerged adults to sub-lethal concentrations of heptachlor and endosulfan for varying durations. The untreated control sets recorded high fecundity for both C. javanus and A. longisetosus, but chronic toxicity of the insecticides on adults confined to the treated soil resulted into very low fecundity. Even short duration exposure to heptachlor and endosulfan treated soil for 24 or 72 hours only was found to delay the egg-laying and decrease the fecundity of both the species. It is concluded that population responses and reproductive sensitivity in non-target soil microarthropods are potential eco-toxicological parameters for detecting pesticide pollution in soil and for ecological health assessment since the results are based on the bioactivity of toxicants.

An in vitro model of chlorhexidine-induced tooth staining.

BACKGROUND: Tooth staining is a common feature of chlorhexidine treatment for periodontal disease and there is a large variation between patients as to the degree of their tooth staining. Although the mechanism of tooth staining is uncertain, diet, smoking and oral hygiene appear probable factors. OBJECTIVES: This study investigated the role of saliva in chlorhexidine-induced tooth staining and used tea as the staining agent in an in vitro model with hydroxyapatite mimicking teeth. METHODS: Saliva has been used to create an acquired pellicle and in solution to mimic its effects in vivo. Using different combinations of tea, chlorhexidine and parotid saliva, substances binding to hydroxyapatite were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Using this system, tea, chlorhexidine and salivary proteins were clearly identifiable following staining by Coomassie Brilliant Blue. RESULTS: The results indicated that tea interacted with many salivary proteins, in particular proline-rich proteins and histatins. Chlorhexidine did not appear to complex with or precipitate salivary proteins nor prevent the formation of an acquired pellicle on the hydroxyapatite. In isolation, tea and chlorhexidine bound in small amounts to hydroxyapatite, but when added in combination, binding of both to hydroxyapatite was greatly increased. The acquired pellicle reduced chlorhexidine and tea binding, but conversely increased the binding of either tea or chlorhexidine alone to hydroxyapatite. CONCLUSION: In conclusion, salivary proteins play an important role in the staining process and the combination of tea and chlorhexidine appears to be a very potent staining factor.

Salivary proteins interact with dietary constituents to modulate tooth staining.

Dietary components rich in polyphenols-for example, tea and red wine-are thought to cause tooth staining. In the present study, hydroxyapatite was used as a model of enamel for study of the influence of salivary proteins on the binding of different polyphenols to hydroxyapatite in vitro. Neither salivary protein pellicles nor salivary proteins in solution significantly altered the binding of the small polyphenol epigallocatechin to hydroxyapatite. However, hydroxyapatite binding of anthocyanin, a small grape-skin-derived polyphenol, or the larger polyphenols of black tea was increased by the presence of salivary proteins, either as a pellicle or in solution. Proline-rich proteins were enriched from parotid saliva and found to increase binding of anthocyanin and black tea polyphenols to hydroxyapatite, while enriched histatins did not increase binding. It is concluded that some salivary proteins, including proline-rich protein, can mediate increased staining of enamel by red-wine- and black-tea-derived polyphenols.

Rural people and fine needle aspiration cytology (FNAC)--some findings in North Bengal Medical College, Darjeeling, West Bengal.

A hospital based interdepartmental collaborative study was carried out from 1st July to 30th September, 2000 on 269 rural people residing in six districts of the northern part of West Bengal and attending the Pathology Department in North Bengal Medical College for Fine Needle Aspiration Cytology (FNAC) after being referred from different clinical departments. The objectives of the study were to study some aspects of the outcomes of FNAC among rural people and to suggest for its wider application in rural community through Community Health Centre/Rural Hospital/Block Primary Health Centre. The results shows that Hindus (80.3%) are attending more in number than Muslims (14.13%), Christians (4.83%) and Buddhist (0.74%); 53.54% of the population are in 11-40 years age group. In benign conditions 76.95% are coming from up to 100 kms. of N.B.M.C; people in lower per capita income group of up to Rs.400/- per month are attending twice in number than those in the income groups of Rs.401/- and more per month. In malignancy however people do not think of distance or expenses due to seriousness of the diseases. In 14.5% cases FNAC remains inconclusive whereas in 85.5% cases it provides definite diagnoses.

Studies of solvation of ketocyanine dyes in homogeneous and heterogeneous media by UV/Vis spectroscopic method.

Solvation characteristics of ketocyanine dyes (I-VI) have been investigated in pure solvents and heterogeneous media by absorption and fluorescence studies. The dyes are good reporters of solvent polarity. In protic solvents they exist as equilibrium mixtures of bare and hydrogen-bonded form in the ground state (S0), the latter being the emitting species. In aprotic solvents of low polarity association of the S1 state of the dye takes place. In aqueous micellar media the dye resides at the micelle water interface. The binding constant for dye-micelle interaction has been determined. Fluorescence data in beta-cyclodextrine solution resemble that for that neutral micellar solution indicating that the interaction between the -OH group of the heterogeneous part (micelle/cyclodextrine cavity) and the carbonyl oxygen of the dye is important in both the cases.