Role of tungsten disulfide quantum dots in specific protein-protein interactions at air-water interface.

The intriguing network of antibody-antigen (Ab-Ag) interactions is highly governed by environmental perturbations and the nature of biomolecular interaction. Protein-protein interactions (PPIs) have potential applications in developing protein-adsorption-based sensors and nano-scale materials. Therefore, characterizing PPIs in the presence of a nanomaterial at the molecular level becomes imperative. The present work involves the investigation of antiferritin-ferritin (Ab-Ag) protein interactions under the influence of tungsten disulfide quantum dots (WS2 QDs). Isothermal calorimetry and contact angle measurements validated the strong influence of WS2 QDs on Ab-Ag interactions. The interfacial signatures of nano-bio-interactions were evaluated using sum frequency generation vibration spectroscopy (SFG-VS) at the air-water interface. Our SFG results reveal a variation in the tilt angle of methyl groups by ∼12° ± 2° for the Ab-Ag system in the presence of WS2 QDs. The results illustrated an enhanced ordering of water molecules in the presence of QDs, which underpins the active role of interfacial water molecules during nano-bio-interactions. We have also witnessed a differential impact of QDs on Ab-Ag by raising the concentration of the Ab-Ag combination, which showcased an increased inter-molecular interaction among the Ab and Ag molecules and a minimal influence on the methyl tilt angle. These findings suggest the formation of stronger and ordered Ab-Ag complexes upon introducing WS2 QDs in the aqueous medium and signify the potentiality of WS2 QDs relevant to protein-based sensing assays.

Behavioral Interventions Targeting Base of Tongue to Posterior Pharyngeal Wall Approximation: A Scoping Review.

Pharyngeal pressure generated by approximation of the base of tongue to the posterior pharyngeal wall (BOT-PPW approximation) is critical for efficient pharyngeal bolus passage and is a frequent goal of dysphagia management. This scoping review evaluated behavioral interventions available to improve BOT-PPW approximation. We searched MEDLINE, CINAHL, Ovid Emcare, Web of Science, SCOPUS, and ProQuest for studies that met the following criteria: (i) behavioral interventions targeting BOT-PPW approximation, which (ii) were assessed using BOT-PPW-specific outcome measures, and (iiia) performed over a period of time (Review Part 1) or (iiib) studied immediate effects (Review Part 2). Study quality was rated using the GRADE framework. Data were extracted and synthesized into dominant themes. Of the 150 studies originally identified, three examined long-term effects (two single cases studies of individuals with dysphagia, and a third study evaluating effortful swallowing in healthy individuals). BOT-PPW approximation only increased in the two single case studies. Twenty-one studies evaluating immediate effects were categorized as follows: (1) effortful swallowing, (2) Mendelsohn maneuver, (3) tongue-hold maneuver, (4) super supraglottic swallowing maneuver, and (5) non-swallowing exercises. Across all studies, varying levels of success in increasing BOT-PPW approximation were reported. Four of 21 immediate effects studies evaluated patients with demonstrated swallowing impairment, whereas 17 studies evaluated healthy adults. Quality assessment revealed low strength of the existing evidence base. The evidence base for rehabilitative interventions targeting BOT-PPW approximation is severely limited and translation is hindered by small sample sizes and methodological limitations. Further clinical research is warranted.

Elucidating the Molecular Structure of Hydrophobically Modified Polyethylenimine Nanoparticles and Its Potential Implications for DNA Binding.

The structural properties of the polyethylenimine (PEI) polymer are generally tuned and selectively modified to reinforce its potential in a broad spectrum of applied domains of medicine, healthcare, material design, sensing, and electronic optimization. The selective modification of the polymer brings about changes in its interfacial characteristics and behavior. The current work involves the synthesis of naphthalimide conjugated polyethylenimine organic nanoparticles (NPEI-ONPs). The interfacial molecular structure of NPEI-ONPs is explored in an aqueous medium at pH 7.4 using surface tensiometry and sum-frequency generation vibrational spectroscopy (SFG-VS). The hydrophobic functionalization rendered a concentration-dependent surface coverage of NPEI-ONPs, where the SFG-VS analysis exhibited the molecular rearrangement of its hydrophobic groups at the interface. The interaction of NPEI-ONPs with double-stranded DNA (dsDNA) is carried out to observe the relevance of the synthesized nanocomposites in the biomedical domain. The bulk-specific studies (i.e., thermal denaturation, viscometry, zeta (ζ) potential, and ATR-FTIR) reveal the condensation of dsDNA in the presence of NPEI-ONPs, making its structure more compact. The interface-sensitive SFG-VS showcased the impact of the dsDNA and NPEI-ONP interaction on the interfacial molecular behavior of NPEI-ONPs at the air-aqueous interface. Our results exhibit the potential of such hydrophobically functionalized ONPs as promising candidates for developing biomedical sealants, substrate coatings, and other biomedical domains.

Behavioral Interventions Targeting Insufficient Upper Esophageal Sphincter Opening During Swallowing: A Scoping Review.

The upper esophageal sphincter (UES) plays a central role in safe swallowing. Impaired UES opening is commonly observed in individuals presenting with impaired swallowing and various interventions are available aiming to improve bolus passage across the UES during swallowing. This scoping review addressed the following question: Which behavioral interventions are available to improve UES opening for deglutition? We searched MEDLINE, CINAHL, Ovid Emcare, Web of Science, SCOPUS and ProQuest for studies that met the following criteria: i. behavioral interventions targeting UES opening ii. performed over a period of time, which iii. were assessed using UES specific outcome measures. Study quality was assessed using the Joanna Briggs Institute and GRADE frameworks. Data were extracted and synthesized into dominant themes. Of the 357 studies originally identified, 15 met inclusion criteria and reported interventions that were grouped into four intervention types: (1) floor of mouth exercises that were sub-categorized into the Shaker exercise and other strengthening exercises, (2) Mendelsohn maneuver, (3) lingual exercises and (4) mixed exercise paradigms. Across the included studies, varying levels of success in improving various aspects of UES opening metrics were reported. Nine of 15 studies evaluated patients with demonstrated swallowing impairment, whereas six studies evaluated healthy adults. Quality assessment revealed significant variability in study quality, unclear reporting of participant training and treatment fidelity, as well as training dosage. The evidence base for the four behavioral intervention approaches targeting deglutitive UES opening is limited. The translation of existing evidence to clinical practice is hindered by small sample sizes and methodological limitations. Further research in this space is warranted.

Interfacial molecular structure of phosphazene-based polymer electrolyte at the air-aqueous interface using sum frequency generation vibrational spectroscopy.

The change induced in the physicochemical properties of polymer while hosting ions provides a platform for studying its potential applications in electrochemical devices, water treatment plants, and materials engineering science. The ability to host ions is limited in very few polymers, which lack a detailed molecular-level understanding for showcasing the polymer-ion linkage behavior at the interfacial region. In the present manuscript, we have employed sum frequency generation (SFG) vibrational spectroscopy to investigate the interfacial structure of a new class phosphazene-based methoxyethoxyethoxyphosphazene (MEEP) polymer in the presence of lithium chloride salt at the air-aqueous interface. The interfacial aspects of the molecular system collected through SFG spectral signatures reveal enhanced water ordering and relative hydrogen bonding strength at the air-aqueous interface. The careful observation of the study finds a synchronous contribution of van der Waals and electrostatic forces in facilitating changes in the interfacial water structure that are susceptible to MEEP concentration in the presence of ions. The observation indicates that dilute MEEP concentrations support the role of electrostatic interaction, leading to an ordered water structure in proximity to diffused ions at the interfacial region. Conversely, higher MEEP concentrations promote the dominance of van der Waals interactions at the air-aqueous interface. Our study highlights the establishment of polymer electrolyte (PE) characteristics mediated by intermolecular interactions, as observed through the spectral signatures witnessed at the air-aqueous interface. The investigation illustrates the polymer-ion linkage adsorption effects at the interfacial region, which explains the macroscopic changes observed from the cyclic voltammetry studies. The fundamental findings from our studies can be helpful in the design and fine-tuning of better PE systems that can offer improved hydrophobic membranes and interface stability for use in electrochemical-based power sources.

Probing the Bovine Hemoglobin Adsorption Process and its Influence on Interfacial Water Structure at the Air-Water Interface.

*These authors contributed equally to this work.The molecular-level insight of protein adsorption and its kinetics at interfaces is crucial because of its multifold role in diverse fundamental biological processes and applications. In the present study, the sum frequency generation (SFG) vibrational spectroscopy has been employed to demonstrate the adsorption process of bovine hemoglobin (BHb) protein molecules at the air-water interface at interfacial isoelectric point of the protein. It has been observed that surface coverage of BHb molecules significantly influences the arrangement of the protein molecules at the interface. The time-dependent SFG studies at two different frequencies in the fingerprint region elucidate the kinetics of protein denaturation process and its influence on the hydrogen-bonding network of interfacial water molecules at the air-water interface. The initial growth kinetics suggests the synchronized behavior of protein adsorption process with the structural changes in the interfacial water molecules. Interestingly, both the events carry similar characteristic time constants. However, the conformational changes in the protein structure due to the denaturation process stay for a long time, whereas the changes in water structure reconcile quickly. It is revealed that the protein denaturation process is followed by the advent of strongly hydrogen-bonded water molecules at the interface. In addition, we have also carried out the surface tension kinetics measurements to complement the findings of our SFG spectroscopic results.

Introduction of Structured Feedback to Medical Undergraduate Students in the First Professional.

CONTEXT: Feedback is integral in medical education as it improves learner's knowledge, skills, and professional competence, however it is not routinely practiced in medical colleges. Therefore, the present educational research project was designed in a need-based attempt to introduce and implement a program of structured feedback in the department of biochemistry in the first professional MBBS. AIM: The aim was to introduce and implement a program of structured feedback in biochemistry for 1st year medical undergraduates and to collect students' and faculty perceptions about its effectiveness. SETTINGS AND DESIGN: it was a prospective, nonrandomized, interventional study. METHODS: The study was conducted over 135 first professional undergraduates with six faculties. The feedback questionnaires to assess the perceptions of students and faculty on the feedback program were designed and peer-expert validated. An educational program for giving structured feedback was designed, peer-expert validated, and introduced and perceptions of students and faculty were collected using the feedback questionnaires. The collected data were analyzed in terms of percentages, medians, modes, and satisfaction index and represented in graphs. Transcripts were prepared for qualitative data, themes were identified, and a thematic map was prepared. RESULTS: Students (n = 135) perceived the feedback sessions to be helpful in making them aware about their learning gaps (70%) and facilitated the process of bridging the learning gaps (62%). Students strongly agreed that feedback has helped in better understanding of the topic (82%), better retention (69%), and acted as effective learning tool (68%). The faculty did not find the feedback sessions as extra burden in their routine schedule (83%). The main themes identified were "More interaction with teacher," "Increased motivation," "Student centric," "Less stressful," "Improved confidence," "Identification and bridging of learning gaps," "Improved efficacy to attempt questions," and "Improved learning." CONCLUSIONS: The feedback program was perceived satisfactory by both students and faculty agreeing upon more of such sessions and implementation in the curriculum in the near future.

Subclinical Hypothyroidism and Associated Cardiovascular Risk Factor in Perimenopausal Females.

BACKGROUND: Perimenopause refers to the period around menopause (40-55 years). This includes the period before menopause and the first year after menopause. Perimenopausal age is an important stage in a women's life. Many women are diagnosed with hypothyroidism at midlife. Hypothyroidism - both overt and subclinical are associated with increased risk of CVS diseases. Subclinical hypothyroidism is more important as this stage is usually ignored from treatment point of view and if early intervention is done in SCH worsening of metabolic derangement may be avoided. OBJECTIVES: The present study was aimed to know the prevalence of subclinical hypothyroidism and associated dyslipidemia in perimenopausal females. MATERIAL AND METHODS: In our retrospective study we took 100 perimenopausal females (40-55years) who were investigated for thyroid and lipid profile. Atherogenic indices like TC/HDL-c, LDL-c/HDL-c, TG/HDL-c ratios were calculated from the individual lipid profile parameters. The reference guidelines for lipid profile was according to NCEP ATP III. RESULT: Subclinical hypothyroidism was found to be present in 18% of perimenopausal females The mean TSH levels were found to be higher in SCH as compared to euthyroid females with a mean value of 7.56±3.54(µIU/ ml). Dyslipidemia was seen in patients with SCH. TSH levels were found to be positively correlated with total cholesterol. CONCLUSION: We conclude that subclinical hypothyroidism is present in 18% females of perimenopausal age group. Increased TSH levels are associated with hypertension, hypertriglyceridemia, and elevated TC/HDL-C ratio and non cholesterol HDL. In perimenopausal women the condition is usually underdiagnosed and ignored but subclinical hypothyroidism in these females should be screened and treated timely to decrease the risk of accelerated atherosclerosis and premature coronary artery disease in them.

Mean corpuscular volume/mean corpuscular hemoglobin values are not reliable predictors of the ß-thalassemia carrier status among healthy diverse populations of Himachal Pradesh, India.

BACKGROUND: Himachal Pradesh is a hill state in North India in the Western Himalayas. ß-thalassemia is a genetic disorder of hemoglobin inherited in an autosomal recessive manner that results in defective globin production leading to the early destruction of red blood cells. ß-thalassemia has long been neglected in Himachal Pradesh due to popular belief that it runs along "Lahore-Gujarat-Punjab" belt in India. Therefore, there is no ß-thalassemia testing facility currently in the state. METHODS: To estimate the prevalence of ß-thalassemia carriers, we calculated the sample size based on probability proportional to size self-weighing design. In each of 20 selected colleges, 111 students having an age of 18-25 were tested for high-performance liquid chromatography (HPLC) and complete blood count. Some were further tested for the mutations. We computed sensitivity, specificity, positive predictive value (PPV) and negative predictive value, and receiver operating characteristic curve for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) red cell parameters. RESULTS: Of the 2220 students, 57 were found to be ß-thalassemia carrier by HPLC. The overall prevalence rate was 2.6% which translates to probable 180,000 ß-thalassemia carriers in Himachal Pradesh. Six districts bordering highly endemic Punjab had a higher prevalence. Hemoglobin D-Punjab, Heterozygous-Iran Trait, and raised fetal hemoglobin were found. Thalassemia major and sickle cell disease were not found. Anemic status or MCV/MCH parameters were not found to be reliable predictors of thalassemia carrier status among the healthy populations of HP. The predominant mutation found was IVS 1-5 G > C. CONCLUSION: Popular ongoing strategy for screening with MCV and MCH has low-PPV and can miss upto 37% of true thalassemia carriers. HPLC is better strategy for screening carriers and reduces further spread of thalassemia.

Crizotinib and erlotinib inhibits growth of c-Met+/EGFRvIII+ primary human glioblastoma xenografts.

OBJECTIVES: Receptor tyrosine kinases (RTK), such as c-Met and epidermal growth factor receptor (EGFR), are implicated in the malignant progression of glioblastoma. Studies show that RTK systems can co-modulate distinct and overlapping oncogenic downstream signaling pathways. EGFRvIII, a constitutively activated EGFR deletion mutant variant, leads to increased tumor growth and diminishes the tumor growth response to HGF: c-Met pathway inhibitor therapy. Conversely, activation of the c-Met pathway diminishes the tumor growth response to EGFR pathway inhibitors. Previously we reported that EGFRvIII and c-Met pathway inhibitors synergize to inhibit tumor growth in isogenic GBM cell lines engineered to express EGFRvIII. More recently, studies suggest that despite targeting RTK signaling in glioblastoma multiforme, a subpopulation of stem-like tumor-propagating cells can persist to replenish the tumor cell population leading to tumor recurrence. PATIENTS AND METHODS: Mayo 39 and Mayo 59 xenograft lines were cultured and xenografts were maintained. Subcutaneous xenograft lines were serially passaged in nude mice to generate subcutaneous xenografts. Xenografts were implanted in 6-8 week old nude mice. Once tumors reached a substantial size (150 mm3), mice were randomly divided into 4 groups: 1) control vehicle, 2) Crizotinib (crizo), 3) Erlotinib (erlot), or 4) Crizotinib + Erlotinib, (n = 5 per group). RESULTS: Crizotinib (c-Met pathway inhibitor) and Erlotinib (EGFR pathway inhibitor) in combination significantly inhibited tumor growth, phospho-EGFRvIII, phospho-Met, phospho-AKT, phospho-MAPK, and neurosphere growth in Mayo 39 and Mayo 59 primary GBM subcutaneous xenografts. The expression of the stem cell markers Nestin, Musashi, Olig 2 and Sox2 were also significantly down-regulated by c-Met inhibition, but no additive down-regulation was seen by co-treatment with Erlotinib. CONCLUSIONS: These results are consistent with and corroborate our previous findings demonstrating that targeting these two parallel pathways with c-Met and EGFR inhibitor therapy provides substantial anti-tumor activity in glioblastoma models.