Predictors of Unilateral Arm Lymphedema in Non-obese Locoregionally Advanced Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy, Modified Radical Mastectomy, and Postoperative Irradiation.

Objective: The most dreaded long-term complication of axillary lymph node dissection remains upper arm lymphedema. Our study has strategized the three most common identified causes of post treatment arm lymphedema, i.e., obesity, radiation, and neoadjuvant chemotherapy and tried to identify the histopathological and clinical or surgical factors which can predict arm lymphedema. Materials and Methods: This is a prospective observational study was conducted at a tertiary care referral centre in India, with strict inclusion criteria of BMI <30 kg/m2, age <75 years, presence of metastatic axillary node proven by FNAC, received anthracycline based neoadjuvant chemotherapy and postoperative nodal irradiation, and completed 24 months of regular follow-up. Results: Total of 70 patients were included in the study. The mean age of the patients was 50.3 years (±12.9). lymphovascular invasion, total number of lymph nodes removed from level III, total number of days drain was left in situ and maximum drain output were found to be significantly (p<0.05) associated with arm lymphedema. Conclusion: In patients undergoing modified radical mastectomy with level III dissection, and postoperative irradiation, the incidence of unilateral arm lymphedema is significantly influenced by several clinicopathological factors like the total number of lymph nodes removed in level III, higher maximal drain output, prolonged duration of drain placement and the presence of lymphovascular invasion.

Thermal evolution of a polymer-nanoparticle binary mixture.

We experimentally probe the microscopic variations in a model polymer-nanoparticle (NP) binary mixture (mixture of polybutadiene and clay nanoplatelets) across a thermal evolution path for which Tevolution > Tg(polymer). The evolution of the NP dispersion, NP crystallinity, polymer chain-NP interface, and nature of polymer chain-NP interaction are mapped for a spectrum of temperatures and NP concentrations constrained by experiments. Multiple pieces of evidence indicate that thermal evolution does not influence the nature of interparticle dispersion and is also independent of NP concentration in the binary mixture. However, the NP crystalline order significantly reduces across the thermal evolution path. Thermal evolution induces a transition of a sharp polymer chain-NP interface to a diffuse interfacial layer. In contrast, an already diffuse polymer-NP interface existing in the binary mixture due to particle crowding at high NP concentrations undergoes no significant change in its nature across the evolution path. At all particle concentrations, thermal evolution changes the dominant interaction from polymer chain-polymer chain to polymer chain-NP. These insights aid in explaining the molecular origins of unique and anomalous behaviors shown by polymer-nanoparticle binary mixtures while undergoing thermal evolution.

The development and acceptability of an educational and training intervention for recruiters to neonatal trials: the TRAIN project.

BACKGROUND: Suboptimal or slow recruitment affects 30-50% of trials. Education and training of trial recruiters has been identified as one strategy for potentially boosting recruitment to randomised controlled trials (hereafter referred to as trials). The Training tRial recruiters, An educational INtervention (TRAIN) project was established to develop and assess the acceptability of an education and training intervention for recruiters to neonatal trials. In this paper, we report the development and acceptability of TRAIN. METHODS: TRAIN involved three sequential phases, with each phase contributing information to the subsequent phase(s). These phases were 1) evidence synthesis (systematic review of the effectiveness of training interventions and a content analysis of the format, content, and delivery of identified interventions), 2) intervention development using a Partnership (co-design/co-creation) approach, and 3) intervention acceptability assessments with recruiters to neonatal trials. RESULTS: TRAIN, accompanied by a comprehensive intervention manual, has been designed for online or in-person delivery. TRAIN can be offered to recruiters before trial recruitment begins or as refresher sessions during a trial. The intervention consists of five core learning outcomes which are addressed across three core training units. These units are the trial protocol (Unit 1, 50 min, trial-specific), understanding randomisation (Unit 2, 5 min, trial-generic) and approaching and engaging with parents (Unit 3, 70 min, trial-generic). Eleven recruiters to neonatal trials registered to attend the acceptability assessment training workshops, although only four took part. All four positively valued the training Units and resources for increasing recruiter preparedness, knowledge, and confidence. More flexibility in how the training is facilitated, however, was noted (e.g., training divided across two workshops of shorter duration). Units 2 and 3 were considered beneficial to incorporate into Good Clinical Practice Training or as part of induction training for new staff joining neonatal units. CONCLUSION: TRAIN offers a comprehensive co-produced training and education intervention for recruiters to neonatal trials. TRAIN was deemed acceptable, with minor modification, to neonatal trial recruiters. The small number of recruiters taking part in the acceptability assessment is a limitation. Scale-up of TRAIN with formal piloting and testing for effectiveness in a large cluster randomised trial is required.

A comparative study of rectal volume variation in patients with prostate cancer: A tertiary care center study.

INTRODUCTION: Every day variations in rectal filling in prostate cancer radiotherapy can significantly alter the delivered dose distribution from what was intended. The goal of this study was to see if the time of treatment delivery affected the rectal filling. METHODS: This is a retrospective study which included 50 patients with localized prostate cancer treated with volumetric modulated arc therapy (VMAT) to the primary and regional lymph nodes. Cone Beam Computed Tomography (CBCT) image-sets were done for all patient's daily setup verification. The radiation therapist contoured the rectum on all CBCT image sets. The rectal volumes delineated on CBCT and the planning CT image sets were compared. The change in rectal volumes between morning and afternoon treatments were calculated and compared. RESULTS: A total of 1000 CBCT image sets were obtained on 50 patients in the morning and afternoon. The percentage variation of the CBCT rectal volumes over the planning CT scan was 16.57% in the AM group and 24.35% in the PM group. CONCLUSION: The percentage change in rectal volume was significantly lesser in AM group compared to PM group and therefore morning treatments may result in dose distribution that is close to the intended dose distribution. IMPLICATIONS FOR PRACTICE: In prostate cancer radiotherapy our study suggests that a simple technique of changing the time of treatment from afternoon to morning can help to reduce the rectal volume.

Comparative in vitro evaluation of remaining dentine thickness following instrumentation with hand and rotary endodontic files during pulpectomy in primary molars: a systematic review.

PURPOSE: The aim was to compare the remaining dentine thickness (RDT) following instrumentation with hand and rotary endodontic files during pulpectomy in primary molars. Research question was 'Is there any difference between the remaining dentine thickness following instrumentation with hand and rotary endodontic files during pulpectomy in primary molars?'. METHODS: Electronic Databases like MEDLINE PubMed, Cochrane Library, EBSCOhost, Google scholar and grey literature were searched between January 1, 2006 and August 31, 2022 for in vitro and ex vivo studies that compared hand and rotary endodontic instrumentation to evaluate the RDT in primary molars. Articles published in English or which could be translated into English were searched. Two reviewers independently selected studies, extracted data, assessed risk of bias using the Revised, validated version of MINORS criteria. RESULTS: Twelve studies were included in qualitative analysis. All included studies showed low risk of bias. Six studies showed more RDT with rotary instrumentation compared to manual instrumentation. Whereas, five studies showed variable results for RDT with manual and rotary instrumentation at different levels of root canals. One study showed no significant difference between manual and rotary instrumentation. In view of methodological heterogeneity of the findings, a meta-analysis was not conducted. CONCLUSION: High quality of evidence based on low risk of bias was found in all the included studies. Statistically, rotary instrumentation showed more RDT than manual instrumentation according to majority of studies. Despite the shortcomings of this systematic review, it is possible to infer that the use of rotary instrumentation provides more RDT and thus there is considerable conservation of tooth structure.

Role of free volumes and segmental dynamics on ion conductivity of PEO/LiTFSI solid polymer electrolytes filled with SiO2 nanoparticles: a positron annihilation and broadband dielectric spectroscopy study.

The limited ionic conductivity of polymer electrolytes is a major issue for their industrial application. Enhancement of ionic conductivity in the poly(ethylene oxide), PEO, based electrolyte has been achieved by loading passive nanofillers such as SiO2 nanoparticles (NPs). To investigate the role of modifications in free volume characteristics and the polymer chain dynamics induced by the loading of passive fillers on the ionic conductivity of the PEO based ternary electrolyte, a systematic investigation has been carried out using positron annihilation and broadband dielectric spectroscopy. As a result of interfacial interactions, the loading of SiO2 NPs alters the semi-crystalline morphology of PEO resulting in a higher crystallinity at lower loadings due to the surface confinement of PEO chains, and the formation of smaller PEO crystallites at higher loadings due to interparticle nanoconfinement. These modifications are accompanied by a decrease in free volume fraction at the lowest loading (0.5 wt%) followed by an increase at higher loadings (≥2.0 wt%). The Almond-West formalism considering two different universalities in different temperature and frequency ranges has been used to explain the ion-conduction process at different NP loadings. The Li ion conductivity is observed to be maximum for a 5.0 wt% loading of SiO2 NPs. The enhancement in ionic conductivity is observed to be directly correlated with the free volume characteristics and segmental dynamics of the PEO matrix, confirming their role in ion transport in polymer electrolytes.

Exogenous ß-cyclocitral treatment primes tomato plants against drought by inducing tolerance traits, independent of abscisic acid.

Drought is the most devastating stress for crops. Intensity and duration of drought determine the magnitude of plant damage; similarly, plant ability to counteract drought determines its tolerance capacity. Recent studies revealed that exogenous apocarotenoid treatment confers abiotic stress tolerance to plants. However, much less is known about the role of ß-cyclocitral (ßCC), the major apocarotenoid, in drought tolerance. Here, we demonstrate ßCC's role in improving plants' tolerance against drought stress. Tomato (Solanum lycopersicum L.) plants were independently treated with water and ßCC and grown under either water-limited or irrigated conditions. The ßCC-treated drought-exposed (BD) and ßCC-treated irrigated (BH) plants were analysed for the major drought tolerance associated traits; water-treated drought-exposed (CD) and water-treated irrigated plants (CH) were used as controls. On exposure to drought, unlike controls, ßCC-treated plants showed no wilting, higher RWC and stomatal conductance, unchanged ABA levels and stomatal closure. The BD plants had increased photosynthesis, chlorophyll content and enhanced root, but not shoot, growth. In addition, ßCC treatment enhanced proline accumulation and activity of SOD in both drought-exposed and well irrigated plants. Taken together, ßCC was identified as a potential candidate that improves tomato osmolyte accumulation and superoxide elimination, independent of ABA, and prepares the plant for upcoming drought stress. Our results suggest that ßCC can be used to prime crops against drought stress.

Ablation of atrioventricular-nodal-reentrant- tachycardia in a patient with left-sided superior vena cava and dilated coronary sinus.

Atrioventricular (AV)-nodal-reentrant-tachycardia is a rare association in a patient with persistent left-sided superior vena cava and dilated coronary sinus. There are a few inherent difficulties in ablation in this condition, viz., difficulty in localization of good site for ablation and difficulty in stabilization of the ablation catheter at the designated site, making it difficult to produce transmural lesions and increasing risk of producing AV block. We hereby present a case highlighting the difficulties and possible solutions for them.

Atrial tachycardia from an unusual site-Left atrial appendage tachycardia: Challenges in ablation.

Left atrial appendage (LAA) tachycardia are rarely encountered in clinical practice (2.1% of focal atrial tachycardia). Out of these, the ones arising from the distal part of LAA are difficult to ablate due to higher risk of LAA perforation and thromboembolism. We hereby present a patient with LAA tachycardia mapped to the tip of LAA with the help of the CARTO system and ablated. This case highlights the inherent challenges faced in such a scenario.

Lung nodules are reliably detectable on ultra-low-dose CT utilising model-based iterative reconstruction with radiation equivalent to plain radiography.

AIM: To determine if ultra-low-dose (ULD) computed tomography (CT) utilising model-based iterative reconstruction (MBIR) with radiation equivalent to plain radiography allows the detection of lung nodules. MATERIALS AND METHODS: Ninety-nine individuals undergoing surveillance of solid pulmonary nodules undertook a low-dose (LD) and ULD CT during the same sitting. Image pairs were read blinded, in random order, and independently by two experienced thoracic radiologists. With LD-CT as the reference standard, the number, size, and location of nodules was compared, and inter-rater agreement was established. RESULTS: There was very good inter-rater agreement with regards nodules ≥4mm for both the LD- (k=0.931) and ULD-CT (k=0.869). One hundred and ninety-nine nodules were reported on the LD-CT by both radiologists and 196 reported on the ULD-CT, with no nodules reported only on the ULD-CT. This gives a sensitivity of 98.5% and specificity of 100% for ULD-CT with MBIR. The effective dose of radiation was significantly different between the two scans (p<0.0001), 1.67 mSv for the LD-CT and 0.13 mSv for the ULD-CT. CONCLUSION: ULD-CT utilising MBIR and delivering radiation equivalent to plain radiography, allows detection of lung nodules with high sensitivity. The attendant 10-fold reduction in radiation may allow for dramatic reductions in cumulative radiation exposure.

A microfluidic platform for the characterisation of membrane active antimicrobials.

The spread of bacterial resistance against conventional antibiotics generates a great need for the discovery of novel antimicrobials. Polypeptide antibiotics constitute a promising class of antimicrobial agents that favour attack on bacterial membranes. However, efficient measurement platforms for evaluating their mechanisms of action in a systematic manner are lacking. Here we report an integrated lab-on-a-chip multilayer microfluidic platform to quantify the membranolytic efficacy of such antibiotics. The platform is a biomimetic vesicle-based screening assay, which generates giant unilamellar vesicles (GUVs) in physiologically relevant buffers on demand. Hundreds of these GUVs are individually immobilised downstream in physical traps connected to separate perfusion inlets that facilitate controlled antibiotic delivery. Antibiotic efficacy is expressed as a function of the time needed for an encapsulated dye to leak out of the GUVs as a result of antibiotic treatment. This proof-of-principle study probes the dose response of an archetypal polypeptide antibiotic cecropin B on GUVs mimicking bacterial membranes. The results of the study provide a foundation for engineering quantitative, high-throughput microfluidics devices for screening antibiotics.

Pharmacokinetics of isoniazid in Indian children with tuberculosis on daily treatment.

OBJECTIVE: To assess the pharmacokinetics of isoniazid (INH) at 10 mg/kg/day among Indian children. METHODS: INH levels were estimated using liquid chromatography-tandem mass spectroscopy in 35 children aged 1-15 years on daily anti-tuberculosis treatment. Blood samples were collected 0, 1, 2, 3, 6 and 24 h after INH administration. The maximum concentration (Cmax) and area under the curve (AUC0-24) were determined. The normal therapeutic range for Cmax is 3-5 µg/ml. An AUC of <10.52 µg•h/ml for INH is low. RESULTS: The mean Cmax was 8.3 ± 4.28 µg/ml and was attained in 1.22 ± 0.5 h, with a median time to Cmax (Tmax) of 1 h. The mean AUC for INH was 46.23 ± 34.82 µg•h/ml. Children aged 1-4.9 years, 5-10 years and >10 years had a mean Cmax of respectively 9.87 ± 5.75 µg/ml, 7.62 ± 3.37 µg/ml and 7.21 ± 2.50 µg/ml (P = 0.08) and a mean AUC of respectively 60.97 ± 49.90 µg•h/ml, 38.95 ± 22.28 µg•h/ml and 36.09 ± 13.56 µg•h/ml (P = 0.29). The mean Cmax in children taking fixed-drug combinations and individual drugs was respectively 9.07 ± 4.67 µg/ml and 7.43 ± 3.71 µg/ml (P = 0.26); the mean AUC was respectively 50.48 ± 38.38 µg•h/ml and 41.20 ± 30.52 µg•h/ml (P = 0.44). Two children had hepatitis. CONCLUSION: Most Indian children had higher than normal INH AUC and Cmax values. It is necessary to determine the ideal dose of INH in Indian children using the genotypic acetylator status of the patients and pharmacokinetic toxicity analysis.

Rare variants in Protein tyrosine phosphatase, receptor type A (PTPRA) in schizophrenia: Evidence from a family based study.

The contribution of both common and rare risk variants to the genetic architecture of schizophrenia (SZ) has been documented in genome-wide association studies, whole exome and whole genome sequencing approaches. As SZ is highly heritable and segregates in families, highly penetrant rare variants are more likely to be identified through analyses of multiply affected families. Further, much of the gene mapping studies in SZ have utilized individuals of Caucasian ancestry. Analysis of other ethnic groups may be informative. In this study, we aimed at identification of rare, penetrant risk variants utilizing whole exome sequencing (WES) in a three-generation Indian family with multiple members affected. Filtered data from WES, combined with in silico analyses revealed a novel heterozygous missense variant (NM_080841:c.1730C>G:p.T577R; exon18) in Protein tyrosine phosphatase, receptor type A (PTPRA 20p13). The variant was located in an evolutionarily conserved position and predicted to be damaging. Screening for variants in this gene in the WES data of an independent SZ cohort (n = 350) of matched ethnicity, identified five additional rare missense variants with MAF < 0.003, which were also predicted to be damaging. In conclusion, the rare missense variants in PTPRA identified in this study could confer risk for SZ. This has also derived support from concordant data from prior linkage and association, as well as animal studies which indicated a role for PTPRA in glutamate function.

Proposal for a Radiological Classification System for Carpo-Metacarpal Joint Dislocations with or without Fractures.

Introduction: Though complex injuries like CarpoMetacarpal (CMC) Joint dislocations represent only 1% of all hand injuries, they have disabling impact on the functional status of patient. There are no reports in the literature classifying disabling complex injuries like CMC joint dislocations presumably because of low incidence. We propose a new classification through retrospective analysis of patients, along with literature search. Materials and Methods: A new classification system has been proposed and designed at our clinical unit and applied to eight patients with CMC joint dislocations. All patients were treated with open reduction with Kirschner wire fixation. At follow-up all these patients were analysed for radiographic assessments and functional scores. Results: The proposed classification identifies three types of dislocations and an additional complex category to supplement any basic type. The direction of dislocation describes the types as Type A: Dorsal, Type B: Volar and Type C: Divergent. Among the eight patients in our study, we had two of Type A, two Type B, three Type B.1, one Type C. 1. These patients had average follow-up of 18 months. The quick DASH score improved from 75.76 at 6 weeks to 1.9 at 18 months. We also did intra-observer and inter-observer reliability which scored 1. Conclusion: Our proposal is a reproducible, simple, comprehensive and practical classification, easily remembered and communicated among colleagues. It is clinically relevant as it helps us in planning surgical management and prognostic evaluation.

Molecular dynamics, physical and thermal stability of neat amorphous amlodipine besylate and in binary mixture.

In this paper, a stable amorphous solid dispersion of an antihypertensive drug, amlodipine besylate (AMB) was prepared by entrapping it in a polymer matrix, polyvinyl pyrrollidone, in different weight ratios (AMB/PVP 05:95, 10:90, 20:80, 30:70). The glass forming ability of all binary dispersions were studied by means of differential scanning calorimetry and found good correlation between experimental Tg and Fox Flory's prediction. By considering the daily dosage limit of 5 mg, a weight ratio of 05:95 was further considered for the study. The structures of neat and binary of AMB were characterized by density functional theory, Fourier transform infrared spectroscopy, Fourier transform Raman spectroscopy and UV-visible spectroscopy. Further, detailed molecular dynamics of both pure and binary were investigated using broadband dielectric spectroscopy to judge the physical stability of the amorphous dispersions. Translation-rotation coupling of AMB possibly explains the dual conductivity and dipolar nature of the secondary relaxation in neat AMB. Thus, the binary dispersion of AMB with commercially acceptable weight ratio with strong glass forming behaviour and better shelf life was prepared and characterized for practical applications.

Type I Cryoglobulinemic Nephritis in a Patient of Monoclonal Gammopathy of Renal Significance.

Monoclonal gammopathy of renal significance is a recently described entity in which a small B-cell clone not meeting the criteria for the diagnosis of multiple myeloma produces renal disease usually through deposition of a secreted monoclonal immunoglobulin. Here, we describe a case of Type I cryoglobulinemic glomerulonephritis diagnosed on a kidney biopsy and caused by a monoclonal IgM produced by a small bone marrow clone. The patient made a complete renal recovery after chemotherapy to suppress the clone.

A simple model for transit dosimetry based on a water equivalent EPID.

PURPOSE: The aim of this study was to demonstrate a new model for implementing a transit dosimetry system as a means of in vivo dose verification with a water equivalent electronic portal imaging device (WE-EPID) and a conventional treatment planning system (TPS). METHOD AND MATERIALS: A standard amorphous silicon (a-Si) EPID was modified to a WE-EPID configuration by replacing the metal-plate/phosphor screen situated above the photodiode detector with a 3 cm thick water equivalent plastic x ray converter material. A clinical TPS was used to calculate dose to the WE-EPID in its conventional EPID position behind the phantom/patient. The "extended phantom" concept was used to facilitate dose calculation at the EPID position, which is outside the CT field of view (FOV). The CT images were manipulated from 512 × 512 into 1024 × 1024 and padded pixels were assigned the density of air before importing to the TPS. The virtual WE-EPID was added as an RT structure of water density at the EPID plane. The accuracy of TPS dose calculations at the EPID plane in transit geometry was first evaluated for different field sizes and thickness of object in the beam by comparison with the dose measured using a 2D ion chamber array (ICA) and the WE-EPID. Following basic dose response tests, clinical fields including direct single fields (open and wedged) and modulated fields (integrated or control point by control point doses for VMAT) were measured for 6 MV photons with varying of solid water thickness or an anthropomorphic phantom present in beam. The EPID images were corrected for dark signal and pixel sensitivity and converted to dose using a single dose calibration factor. The 2D dose evaluation was conducted using 3%/3 and 2%/2 mm gamma-index criteria. RESULTS: The measured dose-response with the ICA and WE-EPID for all basic dose-response tests agreed with TPS dose calculations to within 1.5%. The maximum difference in dose profiles for the largest measured field size of 25 × 25 cm2 was 2.5%. Gamma evaluation showed at least 94% (3%/3 mm criteria) and 90% (2%/2 mm) agreement in both integrated and control-point doses for all clinical fields acquired by the WE-EPID and ICA when compared with TPS-calculated portal dose images. CONCLUSION: A new approach to transit dose verification has been demonstrated utilizing a water equivalent EPID and a commercial TPS. The accuracy of dose calculations at the EPID plane using a commercial TPS beam model was experimentally confirmed. The model proposed in this study provides an accurate method to directly verify doses delivered during treatment without the additional uncertainties inherent in modelling the complex dose-response of standard EPIDs.

Molecular dynamics and the translational-rotational coupling of an ionically conducting glass-former: amlodipine besylate.

We studied the conductivity relaxation originating from a glass-former composed of cations and anions, and the relation to the structural α-relaxation at temperatures above and below the glass transition temperature. The material chosen was amorphous amlodipine besylate (AMB), which is also a pharmaceutical with a complex chemical structure. Measurements were made using differential scanning calorimetry (DSC), broadband dielectric spectroscopy (BDS) and X-ray diffraction, and the characterization was assisted using density functional theory (DFT). The X-ray diffraction pattern confirms the amorphous nature of vitrified AMB. Both the ionic and dipolar aspects of the dynamics of AMB were examined using these measurements and were used to probe the nature of the secondary conductivity and dipolar relaxations and their relation to the conductivity α-relaxation and the structural α-relaxation. The coupling model predictions and quantum mechanical simulations were used side by side to reveal the properties and nature of the secondary conductivity relaxation and the secondary dipolar relaxation. Remarkably, the two secondary relaxations have the same relaxation times, and are one and the same process performing dual roles in conductivity and dipolar relaxations. This is caused by the translation-rotation coupling of the AMB molecule. Thus, AMB has both conductivity α- and ß-relaxations, and application of the coupling model shows that these two relaxations are related in the same way as the structural α-relaxation and the Johari-Goldstein ß-relaxation are. This important result has an impact on the fundamental understanding of the dynamics of ionic conductivity.