Implementation of surface mechanomyography as a novel approach for objective evaluation of phasic muscle stretch reflexes in people with type 2 diabetes.

INTRODUCTION: Diabetic peripheral neuropathy is the most common complication of diabetes producing metabolic disruptions in the peripheral nervous system. Alteration in the predictable nature of tendon reflexes is the most common indicator suggesting the possibility of diabetic neuropathy. Evaluation of tendon reflexes is a part of various clinical scoring systems that assess neuropathy. The conventional reflex grading scales are subjective, lack temporal data, and have high inter-rater variability. Hence, an indigenous quantification tool was developed to evaluate the tendon reflexes in order to assess diabetic peripheral neuropathy. MATERIALS AND METHODS: A cross-sectional study was carried out in 140 healthy volunteers and 140 patients with type 2 diabetes. The mean age of controls and diabetics (49.1 ± 8.9, 50.7 ± 7.5) years, weight (66.9 ± 9.4, 69.8 ± 11.5) kilograms and BMI (24.5 ± 3.8, 26.1 ± 4.7), respectively. All of them are subjected to evaluation of tendon reflexes using the reflex quantification tool comprised of surface mechanomyography and electrogoniometry that can provide various static and dynamic variables of tendon reflex. RESULTS: The dynamic variables such as reflex amplitude, muscle velocity and angular velocity were significantly low in diabetic patients (p: <0.001) whereas latency and duration (p: <0.001) were prolonged. Furthermore, no significant difference was observed in the application of tendon striking force (p: 0.934) among the participants. CONCLUSION: The current study demonstrates that the proposed reflex quantification tool provides several dynamic variables of patellar tendon reflex, which are significantly affected and altered in diabetic patients suggesting the involvement of peripheral neurons.

Kisspeptin stimulates sheep ovarian follicular development in vitro through homologous receptors.

The present study was conducted to elucidate (1) the influence of kisspeptin (KP) on the in vitro development of preantral follicles (PFs) and (2) evolution of KP receptor gene (KISS1R) expression during ovarian follicular development in sheep. Kisspeptin was supplemented (0-100 µg/ml) in the culture medium of PFs for 6 days. The cumulus-oocyte complexes (COCs) from cultured PFs were subsequently matured to metaphase II (MII) for an additional 24 h. The proportions of PFs exhibiting growth, antrum formation, average increase in diameter, and maturation of oocytes to MII stage were the indicators of follicular development in vitro. The expression of the kisspeptin receptor gene at each development stages of in vivo developed (preantral, early antral, antral, large antral and COCs from Graafian follicles) and in vitro cultured PFs supplemented with KP was assessed using a real-time polymerase chain reaction. The best development in all the parameters under study was elicited with 10 µg/ml of KP. Supplementation of KP (10 µg/ml) in a medium containing other growth factors (insulin-like growth factor-I) and hormones (growth hormone, thyroxine, follicle-stimulating hormone) resulted in better PF development. The KISS1R gene was expressed in follicular cells and oocytes at all the development stages of both in vivo developed and in vitro cultured follicles. Higher KISS1R gene expression was supported by culture medium containing KP along with other hormones and growth factors. Accordingly, it is suggested that one of the mechanisms through which KP and other growth factors and hormones influence the ovarian follicular development in mammals is through the upregulation of expression of the KP receptor gene.

Collective modes, relaxations, de Vries behavior and field influence in SmA and SmC*deVr phases of chiral liquid crystal dimer C-10Bms with siloxy spacer.

Investigations in chiral liquid crystal dimer with trisiloxy unit on spacer unit, viz. C-10Bms, are reported with respect to its resolved dipole moment. Occurrence of SmA and SmC*deVr LC phases was characterized by POM and DSC. Relatively enhanced thermal range of LC phases in dimer configuration was detailed. Tilt angle, hysteresis, polarization, collective modes and other low-frequency relaxations were investigated. Primary order parameter revealed validity of critical field model. Moderate tilt for viewing angle and electro-clinic response for switch speed in dimer were addressed. Hysteresis in SmC*deVr ensued storage capability for memories. Slightly higher activation energy Ea was attributed to siloxy chain on spacer. Goldstone and Soft modes were identified in SmC*deVr phase. Field influence on Goldstone mode was analyzed. Equivalence of thermal/Arrhenius and field activation energies was observed. Curie-Weiss law for SM revealed strong collective ferroelectric response. Temperature and field trends of dielectric relaxation parameters were addressed in terms of chiral center-based out-of-phase dipole moment. Figure of merit parameters in SmC*deVr estimated by dielectric loss revealed its relative performance far below the SmA-SmC*deVr phase transition.

Kisspeptin promotes follicular development through its effects on modulation of P450 aromatase expression and steroidogenesis in sheep ovarian follicles.

The present study was conducted to ascertain whether the role of kisspeptin in promoting in vitro development of preantral follicles was through the regulation of P450 aromatase gene expression and steroidogenesis in sheep. Accordingly, the cumulus cells and oocytes were collected from different development stages of preantral follicles grown in vivo and cultured in vitro in TCM199B (Group I), TCM199B + KP (10 µg/mL) (Group II) and Standard medium + KP (10 µg/mL). To measure the steroid (Estradiol-17ß; E2 and Progesterone; P4 ) synthesis through ELISA, spent culture medium was collected separately from the same in vitro groups. E2 synthesis in the spent medium collected from all the three groups showed an increasing trend from PFs' exposed to respective culture media for 3 min to 2-day culture stage but decreased thereafter till 6-day culture stage. This is followed by a sharp increase in E2 concentration in the spent medium collected after in vitro maturation. However, P4 synthesis in group III followed increased pattern as the development progressed from PFs' exposed to culture medium for 3 min to in vitro maturation stage. The steroid production was observed at all stages of in vitro development in altered supplemented conditions. The steroid synthesis in the spent medium was highest in the 6 day cultured PFs' in Standard medium + KP matured in vitro for 24 h. Therefore, supplementation of kisspeptin along with other growth factors promoted steroid production in cultured preantral follicles far better than in other media.

Effects of Therapeutic Calf Massage on Cardiac Autonomic Function in Healthy Volunteers-a Pilot Study.

Background: Calf massage is a therapeutic intervention that improves circulation and relieves us from pain & tightness. The calf massage also improves autonomic performance by modulating the vagal tone of the cardiovascular system. Therefore, the current study was intended to determine therapeutic calf massage on cardio autonomic activity in healthy subjects. Objective: To assess the immediate effect of a single 20-min session of calf massage on cardiac autonomic modulation through heart rate variability (HRV) measurement. Materials & Methods: In this study, 26 apparent healthy female participants aged between 18 and 25 years participated. Massage over the calf muscles on both legs for 20 min was performed, and resting cardiovascular parameters and HRV parameters were measured at baseline, immediately after the massage, and during the recovery periods (10 and 30 min after the massage). Data were analyzed using one-way ANOVA followed with post hoc analysis. Results: Immediately after the massage intervention, heart rate (HR), systolic (SBP), and diastolic (DBP) blood pressure were decreased (p < .01), and the reduction was persisted at 10 min and 30 min of the recovery period (p < .01). In HRV parameters, the root mean square of successive differences (RMSSD) and high-frequency normalized unit (HF n.u.) increased, and low frequency (LF n.u.) decreased after the massage, and at the 10 and 30 min of the recovery period. Conclusion: The present study reports suggest a significant reduction in heart rate and blood pressure after the massage therapy. A drop in sympathetic tone and raise in parasympathetic tone can also attribute to the therapeutic effect.

Efficacy of palonosetron in the management of postoperative nausea vomiting in oral and maxillofacial surgery.

Objective: The objective is to evaluate the efficacy of prophylactic single intravenous dose of palonosetron in the management of postoperative nausea and vomiting (PONV) following oral and maxillofacial surgical interventions performed through an intraoral approach under general anesthesia (GA). Materials and Methods: A prospective study was conducted on 100 subjects who underwent intraoral surgical procedures for the management of maxillofacial trauma, pathology, dentofacial anomalies, and deformities under GA. All subjects received a prophylactic single intravenous dose of 0.075 mg palonosetron along with premedication. Predisposing factors for PONV such as patient age, gender, Apfel risk score, history of motion sickness, smoking, type of procedure, and administration of postoperative opioids were taken into consideration. All the patients were monitored for PONV for the 1st 24 h postoperatively (PO). First, at an interval of 30 min for 1st 4 h and then at every 2 h interval for next 8 h followed by monitoring every 6 h interval till 24 h. Time and frequency of rescue medication were noted. Results: Seventy-nine percentage subjects did not have PONV. 15% subjects had a single episode of vomiting PO which could be attributed to multiple intra oral surgical sites performed as well as longer duration of exposure to anesthetic agents in addition to providing opioid analgesics for the management of postoperative pain. Only 6% subjects needed rescue antiemetic drug. Palonosetron did not show any significant changes in cardiac status and serum profile. Conclusion: Palonosetron is effective in the management of PONV for maxillofacial surgical procedures performed through an intraoral approach under GA.

Simulated experimental investigation of microplastic weathering in marine environment.

Microplastics act as a potential vector for a wide range of contaminants, which have emerged as a major environmental hazard in the modern world. Considering the seriousness of the problem, a simulated laboratory and field experiment were conducted to study the weathering of pristine microplastics following long-term exposure to natural background radiation and the marine environment after being disposed of in the open environment. For the study, polyethylene-originating (HDPE and LDPE) microplastics were chosen. The study revealed that radiation exposure causes surface roughness and cracks, leading to an increased surface area, which can invite a wide spectrum of pollutants to sorb on their surface. Furthermore, we report that the radiation-induced morphological changes favor microbial colonization on the microplastic surface when exposed to the marine environment. The growth of biofilms on the surface of microplastics reduces their hydrophobicity, which may attract a wide variety of polar contaminants. The study led to an interesting finding: that the HDPE microplastic surface is more conducive for biofilm growth in comparison to the LDPE surface.

Microplastics as vectors of radioiodine in the marine environment: A study on sorption and interaction mechanism.

Radioiodine is one of the long-lived fission products and also an important radionuclide released during nuclear accidents, which generates interest in its environmental fate. Its sorption has been studied in a wide range of materials, but no equivalent study exists for microplastics, an emerging environmental vector. Weathering and biofilm formation on microplastics can enhance radioiodine sorption. For the first time, we're reporting how radioiodine interacts with different types of polyethylene derived microplastics (pristine, irradiated, and biofilm developed microplastics). This study revealed that exposure to radiation and the marine environment significantly alters the physico-chemical properties of microplastics. In particular, in marine-exposed samples, a signature of biofilm development was detected. Speciation study indicates that iodine exists in the iodide form in the studied marine environment. The study revealed that, iodide ions attach to biofilm-developed microplastics via electrostatic, ion-dipole, pore filling, and van der Waals interactions. Pore filling, ion-dipole, and van der Waals interactions may cause iodide binding to irradiated microplastics, whereas pore-filling and van der Waals interactions cause iodide binding to pristine microplastics. The distribution coefficient (Kd) of iodine on microplastics is positively correlated with biofilm biomass, which signifies the role of biofilm in radioiodine uptake. The Kd indicates microplastics are potential iodide accumulators and could be a possible vector in the marine system.

Depletion Induced Demixing and Crystallization in Binary Colloids Subjected to an External Potential Barrier.

Depletion interaction plays an important role in determining the structural and dynamical properties of binary colloidal mixtures. We have investigated the effect of the attractive depletion interaction between an external potential barrier and larger species in the binary mixture on the phase behavior of a binary colloidal mixture using canonical-isokinetic ensemble molecular dynamics simulations. The demixing of the binary mixture due to this depletion interaction increases as the volume fraction increases, and a pure phase of larger particles forms in the region of the potential barrier. The local density of this pure phase is high enough that a face centered cubic crystalline domain is formed at this region. This crystalline phase diffuses perpendicular to the external potential barrier, indicating that moving crystals can be obtained in an equilibrium system. The temperature dependence of diffusivity of larger particles is non-Arrhenius and changes from sub-Arrhenius to super-Arrhenius as the volume fraction increases. This crossover from sub-Arrhenius to super-Arrhenius diffusion coincides with the crystalline formation near the potential barrier.

Influence of TCM 199B, α-MEM, Waymouth MB 752/1 culture media, VEGF, Estradiol-17ß, GDF-9 and FGF on in vitro development of preantral follicles in sheep.

A total of 2792 preantral follicles (PFs') isolated from 750 ovaries of sheep were cultured in four different experiments. The efficacy of three commercially available culture media viz., TCM 199B, α-MEM and Waymouth MB 752/1 on the growth of sheep PFs' was tested in experiment I. Among the three media TCM 199B supported better development of PFs' in culture. The remaining experiments established the best concentrations of vascular endothelial growth factor (VEGF), Estradiol-17ß (E2), GDF-9, Fibroblast growth factor (FGF) and their best combinations for the in-vitro development of PFs'. Inclusion of VEGF at 10 ng/mL, Estradiol-17ß at 5 ng/mL, GDF-9 at 10 ng/mL or FGF at 10 ng/mL individually in a standard medium (SM) (containing FSH, IGF-I, GH and T4) supported better nuclear maturation of the oocytes to MII stage. Different combinations of VEGF, Estradiol-17ß, GDF-9 and FGF supplemented in the SM promoted similar overall follicular growth. However, (a) SM + VEGF(10 ng/mL) + E2(5 ng/mL) supported higher increase in the diameter, (b) SM without any supplements induced antrum formation in greater proportion of follicles, and (c) SM + VEGF(10 ng/mL) + GDF 9(10 ng/mL) or SM + E2 (5 ng/mL) + FGF(10 ng/mL) supported high proportion of oocytes to reach MII stage. To conclude, TCM 199B appeared to be a better medium for development of sheep PFs'. VEGF, Estradiol-17 ß, GDF-9 and FGF have beneficial influence on the development of sheep PFs' when supplemented in TCM 199B.

PAMAM dendrimer as a talented multifunctional biomimetic nanocarrier for cancer diagnosis and therapy.

Poly(amidoamine) dendrimers (PAMAM) are novel polymeric highly branched architectures with well-defined nano-size, narrow polydispersity index and numerous active amine functional groups at the periphery. The highly attractive feature of modifiable multiple surface functionalities facilitates conjugation of various ligands for cancer targeting, imaging and therapy. As well as, solubilization, high drug encapsulation, inherent passive targeting ability will also contribute to the therapeutic success of dendrimers. Cancer researchers are very eager about the utility of PAMAM dendrimer as a drug carrier and non-viral gene vector. This review highlighted the potential of non-targeted and ligand targeted surface engineered PAMAM dendrimers for the delivery of anticancer drugs and gene therapeutics and briefly focus on the diagnostic imaging applications of PAMAM dendrimers.

Impaired pupillary light reflex indices in Orbital Apex Syndrome - A rare case report.

BACKGROUND: The clinical presentation of reduced pupillary responses in orbital apex syndrome is currently not well understood clinically. The pupillary light reflex (PLR) is determined using dynamic pupillometry. CASE DETAILS: A newly diagnosed 35-year-old diabetic female patient had ocular symptoms including orbital pain and ptosis, but no visual loss. Cranial nerve autonomic impairment was identified with dynamic pupillometry and compared with cardiac autonomic activity using heart rate variability (HRV). RESULTS: PLR showed that pupil size and response were severely affected, with a small resting pupil size, and minimal response to a bright white light flash was seen, due to decreased sympathetic activity. However, HRV showed normal cardiac sympathetic activity. CONCLUSION: These findings suggest that orbital apex syndrome may lead to changes in pupil size and response due to compression of sympathetic fibers at the apex of the orbit. Quantitative PLR measurements help to reveal relevant information on anatomical reflex pathways.

Pyrrolo[2,3-b]quinoxalines in attenuating cytokine storm in COVID-19: their sonochemical synthesis and in silico / in vitro assessment.

In view of the recent global pandemic caused by COVID-19 intense efforts have been devoted worldwide towards the development of an effective treatment for this disease. Recently, PDE4 inhibitors have been suggested to attenuate the cytokine storm in COVID-19 especially tumour necrosis factor alpha (TNF-α). In our effort we have explored the 2-substituted pyrrolo[2,3-b]quinoxalines for this purpose because of their potential inhibitory properties of PDE-4 / TNF-α. Moreover, several of these compounds appeared to be promising in silico when assessed for their binding affinities via docking into the N-terminal RNA-binding domain (NTD) of N-protein of SARS-CoV-2. A rapid and one-pot synthesis of this class of molecules was achieved via the Cu-catalyzed coupling-cyclization-desulfinylation of 3-alkynyl-2-chloroquinoxalines with t-butyl sulfinamide as the ammonia surrogate under ultrasound irradiation. Most of these compounds showed good to significant inhibition of TNF-α in vitro establishing a SAR (Structure Activity Relationship) within the series. One compound e.g. 3i was identified as a promising hit for which the desirable ADME and acceptable toxicity profile was predicted in silico.

Super-Arrhenius diffusion in a binary colloidal mixture at low volume fraction: an effect of depletion interaction due to an asymmetric barrier.

We report results from the molecular dynamics simulations of a binary colloidal mixture subjected to an external potential barrier along one of the spatial directions at low volume fraction, ϕ = 0.2. The variations in the asymmetry of the external potential barrier do not change the dynamics of the smaller particles, showing Arrhenius diffusion. However, the dynamics of the larger particles shows a crossover from sub-Arrhenius to super-Arrhenius diffusion with the asymmetry in the external potential at the low temperatures and low volume fraction. Super-Arrhenius diffusion is generally observed in the high density systems where the transient cages are present due to dense packing, e.g., supercooled liquids, jammed systems, diffusion through porous membranes, dynamics within the cellular environment, etc. This model can be applied to study the molecular transport across cell membranes, nano-, and micro-channels which are characterized by spatially asymmetric potentials.

Super-Arrhenius diffusion in a binary colloidalmixture at low volume fraction: An effect ofdepletion interaction.

We report results from the molecular dynamics simulations of a binary colloidal mixture subjected to an external potential barrier along one of the spatial directions at low volume fraction, $\phi=$ 0.2. The variations in the asymmetry of the external potential barrier do not change the dynamics of the smaller particles, showing Arrhenius diffusion. However, the dynamics of the larger particles shows a crossover from sub-Arrhenius to super-Arrhenius diffusion with the asymmetry in the external potential at the low temperatures and low volume fraction. Super-Arrhenius diffusion is generally observed in the high density systems where the transient cages are present due to dense packing, e.g., supercooled liquids, jammed systems, diffusion through porous membranes, dynamics within the cellular environment, etc. This model can be applied to study the molecular transport across cell membranes, nano-, and micro-channels which are characterised by spatially asymmetric potentials.

A stochastic model for dynamics of FtsZ filaments and the formation of Z -ring.

Understanding the mechanisms responsible for the formation and growth of FtsZ polymers and their subsequent formation of the Z -ring is important for gaining insight into the cell division in prokaryotic cells. In this work, we present a minimal stochastic model that qualitatively reproduces in vitro observations of polymerization, formation of dynamic contractile ring that is stable for a long time and depolymerization shown by FtsZ polymer filaments. In this stochastic model, we explore different mechanisms for ring breaking and hydrolysis. In addition to hydrolysis, which is known to regulate the dynamics of other tubulin polymers like microtubules, we find that the presence of the ring allows for an additional mechanism for regulating the dynamics of FtsZ polymers. Ring breaking dynamics in the presence of hydrolysis naturally induce rescue and catastrophe events in this model irrespective of the mechanism of hydrolysis.

Phase separation in a two-dimensional binary colloidal mixture by quorum sensing activity.

We present results from Langevin dynamics simulations of a glassy active-passive mixture of soft-repulsive binary colloidal disks. Activity on the smaller particles is applied according to the quorum sensing scheme, in which a smaller particle will be active for a persistence time if its local nearest neighbors are equal to or greater than a certain threshold value. We start with a passive glassy state of the system and apply activity to the smaller particles, which shows a nonmonotonous glassy character of the active particles with the persistence time of the active force, from its passive limit (zero activity). On the other hand, passive particles of the active-passive mixture phase separate at the intermediate persistence time of the active force, resulting in the hexatic-liquid and solid-liquid phases. Thus, our system shows three regimes as active glass, phase separation, and active liquid, as the persistence time increases from its smaller values. We show that the solidlike and hexatic phases consisting of passive large particles are stable due to the smaller momentum transfer from active to passive particles, compared to the higher persistence time where the positional and orientational ordering vanishes. Our model is relevant to active biological systems, where glassy dynamics is present, e.g., bacterial cytoplasm, biological tissues, dense quorum sensing bacteria, and synthetic smart amorphous glasses.

Using positron-emission tomography-computed tomography for predicting radiotherapy-induced tumor regression in carcinoma esophagus in an Indian population.

Carcinoma esophagus is a common malignancy of the Indian subcontinent. The role of positron-emission tomography-computed tomography (PET-CT) in the assessment of response to radiotherapy has been widely studied and accepted. However, its precise use as a predictive tool for actual histopathological response to radiotherapy needs further evaluation, especially in an Indian population. The aim of this study was to identify a quantum of metabolic response on PET-CT that can also predict for a good pathological response. Forty-four patients of carcinoma esophagus treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. All patients underwent a PET-CT before starting treatment as well as at 4-6 weeks after completion of radiotherapy. The percentage change in pre and posttreatment maximum standardized uptake value (SUVmax) value (ΔSUV%) of the primary tumor was correlated against histopathological tumor regression grade (TRG) as per the Mandard's system. Seventy-five percent of the patients with a significant metabolic response, i.e., a ΔSUV% of 60% or more, also had a good pathological response to treatment. Thus, by considering a ΔSUV% of 60%, we could predict for a good pathological response (TRG of 1 or 2) to chemoradiotherapy in our patient set with a sensitivity of 95.45% and a specificity of 72.72%.