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Despite ongoing screening efforts, colorectal cancer (CRC) remains a leading cause of death in Canada. The aim of this study was to better understand the experiences of Canadian CRC patients with their family practitioners (FPs) during and after their CRC diagnosis. Patient-reported data were collected through an online questionnaire to understand their CRC diagnosis experiences and identify potential gaps in care. Various factors contributing to challenges throughout a patient’s CRC diagnosis (e.g., delayed CRC diagnosis) were determined using descriptive, qualitative, and inferential analyses. These factors could be targeted to optimize CRC care. This study found that 40.6% of the 175 respondents were unaware of at least one of the following aspects of CRC prior to their diagnosis: early-age onset (EAO), symptoms, and screening procedures. While 84.6% had access to a family physician (FP) before their diagnosis, only 17.7% were diagnosed by FPs. Higher proportions of younger individuals experienced misdiagnoses and felt dismissed compared to older individuals. Only half felt fully informed about their diagnosis when it was explained to them by their FP, while 53.1% had their diagnosis explained in plain language. Transitioning towards patient-centred care would promote pre-diagnosis CRC awareness, address differences in management of CRC care (e.g., dismissal and support), and accommodate for age and health-literacy-related disparities, thereby improving CRC care pathways for patients. Future research should investigate FPs experiences in detecting CRC cases to develop educational resources and recommendations, enhancing early detection and improving patient outcomes (1).

The COVID-19 pandemic caused disruptions in colorectal cancer (CRC) care by interrupting CRC screening across Canada, posing problems for program participants, patients, and physicians and no clear understanding of how provincial healthcare systems would adapt in the face of another pandemic or shock to the system. A nationwide online survey targeted to members of the National Colorectal Cancer Screening Network (NCCSN) using the SurveyMonkey platform was conducted to gain insight into the impact of the pandemic on CRC screening from March 2020 to March 2022 across all thirteen Canadian jurisdictions. The survey included 25 multiple-choice and free-text questions. Both quantitative and qualitative methods were used to analyze the data using Microsoft Excel and NVivo software. Twenty-one provincial and territorial representatives participated in the survey conducted between 13 May 2022 and 27 October 2022. All jurisdictions (100%) reported decreased screenings, including fecal immunochemical testing (FIT) or Fecal Occult Blood testing (FOBT) procedures, and subsequent diagnostic colonoscopies. The average wait time for colonoscopies due to a positive FIT/FOBT was 76 days. To mitigate the backlog and initiate an effective intervention plan, representatives highlighted some key points, including the importance of prioritizing high-risk patients. Survey results concluded that the COVID-19 pandemic impacted CRC screening across Canada. This landscape assessment can help inform intervention measures and policy-related solutions to create greater resilience for CRC screening in provincial and territorial healthcare systems.

The models of the foot available in the literature are either two- or three-dimensional (3-D), representing a part of the foot without considering different segments of bones, cartilages, ligaments, and important muscles. Hence, there is a need to develop a 3-D model with sufficient details. In this paper, 3-D, two-arch model of the foot is developed, taking foot geometry from the X-rays of nondisabled controls and a Hansen's disease (HD) subject, and taking consideration bones, cartilages, ligaments, important muscle forces, and foot sole soft tissue. The stress analysis is carried out by finite element (FE) technique using NISA software for the foot models, simulating quasi-static walking phases of heel-strike, mid-stance, and push-off. The analysis shows that the highest stresses occur during push-off phase in the dorsal central part of the lateral and medical metatarsals, the dorsal junction of the calcaneus, and the cuboid and plantar central part of th elateral metatarsals in the foot. The stresses in push-off phase in critical tarsal bone regions, for the early stage of HD with muscle paralysis, increase by 25-50% as compared with the control fot model. The model calculated stress results at the plantar surfaces are of the same order of magnitude as the measured foor pressures (0.2-0.5MPa). The high stress concentration areas in the foot bones indicated above are of great importance, since it is found from clinical reports that in some subjects with pathogenic decrease in the mechanical strength of the bone from HD, these areas of bone are disintegrated. Therefore, this investigation could possibly provide an insight into the factors contributing to disintegration of tarsal bones in HD. [ABSTRACT FROM AUTHOR]

Despite rising melanoma incidence in recent decades, there is a trend towards overall decreased mortality, reflecting multiple factors including improved treatment options for metastatic disease. While local treatments are the mainstay for early-stage melanoma, metastatic disease necessitates systemic treatment, with oncolytic virotherapy emerging as a promising option. For this review, articles were retrieved from PubMed from 1964 through 2024. We conducted title, abstract and full-text screening in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify articles describing the use of coxsackievirus A21 (V937), either as monotherapy or as part of combination therapy for malignant melanoma. Fifteen articles met inclusion criteria, offering preclinical and clinical data on V937's efficacy in reducing tumour burden. In addition to reporting manageable safety profiles, clinical trial data examining intratumoral V937 combination therapy with pembrolizumab and ipilimumab also endorsed favourable objective response rates compared to immune checkpoint inhibitor monotherapy (47% vs. 38% and 21% vs. 10%, respectively). In contrast, intravenous V937 monotherapy failed to yield additional benefit in a cohort of patients with Stage IIIC/IV melanoma (n = 3) despite achieving detectable levels in tumour tissue (1 × 10 9 TCID 50 ). Although small subsets of patients experienced severe adverse effects and study design limitations imposed constraints on collected data, evidence for the efficacy of V937 remains encouraging. With few clinical trials evaluating V937 in melanoma, additional data is required before routine usage in standard treatment for metastatic lesions., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Various metal ions exist in nature and human beings and play limitless vital roles in both the atmosphere and biology. A fundamental and useful aspect is the qualitative and quantitative assessment of Zn(II) at concentration levels as low as parts per billion (ppb). Thus, the design and development of novel fluorescent turn-on receptors have gained significant interest because of their potential for use in live cell imaging to detect biologically relevant metal ions with high selectivity and sensitivity. The present research illustrates the design and synthesis of a novel fluorescent sensor [(1,3,5-triazine-2,4,6-triyl)tris(hydrazine-2-yl-1-ylidene)tris(methaneylylidene)]tris(2,4-di- tert -butylphenol) (THDBP) for the selective and sensitive probing of Zn(II). The sensor exhibited a fluorescence turn-on mechanism upon treatment with Zn(II) ions at λ emi. 503 nm in aq. acetonitrile. The formation of a 1 : 3 complex between THDBP and Zn(II) is confirmed from the Job plot and ESI-MS spectrum. The evaluated limit of detection (LOD) and association constant ( K a ) of the sensor THDBP for Zn(II) were found to be 1.03 × 10 -10 M and 2.33 × 10 8 M -1 , respectively. Further research demonstrates the practical application of the sensor for the detection of Zn(II) ions in live cells. The sensing ability of the sensor THDBP was also explored through inexpensive test strips and TLC sheets.

Glucagon-like-peptide-1 (GLP-1) agonists are an emerging class of medications used to manage type 2 diabetes mellitus (T2DM) and weight loss, with demonstrated efficacy in reducing hemoglobin A1c levels, body mass index, and adverse cardiovascular events. While previous studies have reviewed notable cutaneous adverse effects with other antidiabetic medications, little is known about GLP-1 agonist-induced cutaneous reactions. Nevertheless, rare but significant cutaneous adverse reactions have been reported, including but not limited to dermal hypersensitivity reactions, eosinophilic panniculitis, bullous pemphigoid, and morbilliform drug eruptions. As GLP-1 induced cutaneous reactions are diverse, diagnosis requires clinical suspicion, thorough history-taking, and supportive histopathological findings when available. Management involves cessation of the offending agent with a tailored regimen to address inflammatory and/or immunogenic etiologies as well as irritative symptoms. This review aims to consolidate available information from case reports and case series regarding rare skin-related adverse outcomes due to GLP-1 use, aiming to provide a comprehensive overview of the presentation, pathogenesis, and management for dermatologists and other clinicians., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Conflicts of interest None disclosed.

Competing Interests: Conflicts of interest None disclosed.

Nitrogen (N) is one of the primary macronutrients required for crop growth and yield. This nutrient is especially limiting wheat yields in the dry and low fertile agro-ecologies having low N in the root zone soil strata. Moreover, majority of farmers in India and South Asia are small to marginal with meagre capacity to invest in costly nitrogen fertilizers. Therefore, there is an immense need to identify lines that use nitrogen efficiently. A set of 50 diverse wheat genotypes consisting of indigenous germplasm lines (05), cultivars released for commercial cultivation (23) and selected elite lines from CIMMYT nurseries (22) were evaluated in an alpha-lattice design with two replications, a six-rowed plot of 2.5m length for 24 agro morphological, physiological and NUE related traits during two consecutive crop seasons in an N-depleted precision field under two different N levels of 50%-N50 (T1) and 100%-N100 (T2) of recommended N, i.e., 100 kg/ha. Analysis of variance revealed significant genetic variation among genotypes for all the traits studied. About 11.36% yield reduction was observed at reduced N levels. Significant correlations among NUE traits and yield component traits were observed which indicated pivotal role of N remobilization to the grain in enhancing yield levels. Among N-insensitive genotypes identified based on their yielding ability at low N levels, UASBW13356, UASBW13358, UASBW13354, UASBW13357 and KRL1-4 showed their inherent genotypic plasticity toward N application. The genotypes with more yield and high to moderate NUtE can be used as parents for the breeding of N efficient genotypes for marginal agro-ecologies. Low N tolerant genotypes identified from the current investigation may be further utilized in the identification of genomic regions responsible for NUE and its deployment in wheat breeding programs. The comprehensive data of 24 traits under different nitrogen levels for diverse genotypes from India and global sources (mainly CIMMYT) should be useful for supporting breeding for NUE and thus will be of great help for small and marginal farmers in India and South Asia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Biradar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cation and anion sensing is vital owing to their universal dispersion in ecosystems and biological functions. It has been shown that fluorescent receptors based on organic platforms are efficient for detecting a number of ions and have many advantages such as low cost, superior sensitivity and simplicity in installation. This study demonstrates the design and synthesis of a novel receptor ( E )-3-[(3,5-di- tert -butyl-2-hydroxybenzylidene)amino]-2-(pyren-1-yl)-2,3-dihydroquinazolin-4(1 H )-one (DTQ) for the rapid recognition of Zn(II) ions. DTQ exhibited a significant fluorometric "turn-on" characteristic towards Zn(II) at λ max 444 nm in aqueous acetonitrile by inhibiting the photo-induced electron transfer (PET) and -CN- process. The ESI-MS analysis and Job's plot experimental results confirmed stoichiometric 1 : 1 complex formation between DTQ and Zn(II). Fluorometric investigations revealed the detection limit and association constant of DTQ towards Zn(II), which were found to be 13.4 nM and 1.47 × 10 5 M -1 , respectively. DTQ was employed to sense Zn(II) on low-cost test strips. The present research findings imply that DTQ can function as an effective sensor for Zn(II).

Background/purpose: Vitiligo is a depigmenting disorder that affects up to 2% of the population. Due to the relatively high prevalence of this disease and its psychological impact on patients, decisions concerning treatment can be difficult. As patients increasingly seek health information online, the caliber of online health information (OHI) becomes crucial in patients' decisions regarding their care. We aimed to assess the quality and readability of OHI regarding phototherapy in the management of vitiligo., Methods: Similar to previously published studies assessing OHI, we used 5 medical search terms as a proxy for online searches made by patients. Results for each search term were assessed using an enhanced DISCERN analysis, Health On the Net code of conduct (HONcode) accreditation guidelines, and several readability indices. The DISCERN analysis is a validated questionnaire used to assess the quality of OHI, while HONcode accreditation is a marker of site reliability., Results: Of the 500 websites evaluated, 174 were HONcode-accredited (35%). Mean DISCERN scores for all websites were 58.9% and 51.7% for website reliability and treatment sections, respectively. Additionally, 0/130 websites analyzed for readability scored at the NIH-recommended sixth-grade reading level., Conclusion: These analyses shed light on the shortcomings of OHI regarding phototherapy treatment for vitiligo, which could exacerbate disparities for patients who are already at higher risk of worse health outcomes., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic mutation) syndrome is a novel autoinflammatory, late-onset, disorder first identified in 2020. It is caused by mutations in the UBA1 gene. The most prominent clinical features reported by VEXAS patients are cutaneous and haematological, having characteristic skin features reported as the initial presenting findings of the disease. VEXAS is a severe and treatment-resistant condition with high morbidity and mortality rates. Here, we examine all case reports and case series of VEXAS syndrome through March 2023 focusing on those presenting cutaneous manifestations. We discuss these manifestations and their reported treatment strategies. In many cases, it might be first suspected and diagnosed by dermatologists, highlighting their vital role in initiating timely multidisciplinary care., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mitral annular disjunction (MAD) is the atrial displacement of the mitral valve (MV) hinge point, especially along the posterior mitral leaflet, which leads to inhomogeneous blood flow into the left ventricle, causing chronic fibrotic changes, malignant arrhythmias, and even sudden cardiac arrest. Some studies suggest that MAD is a part of normal heart morphology; however, the origin is still controversial. MAD commonly occurs with MV prolapse and myxomatous degenerative MV disease. In almost 20% of cases, MAD can occur independently as well. The prevalence of MAD in normal hearts varies from 8.6% to 96%, depending on the imaging modality and the cutoff used to define MAD. Transthoracic echocardiography is often the initial screening test, but the low sensitivity of transthoracic echocardiography to identify MAD makes it easy to miss the diagnosis altogether. More advanced imaging, especially cardiac MRI, is the gold standard for diagnosing MAD and risk stratification. MAD is an independent predictor of malignant arrhythmia. Among patients with MAD, risk stratification is based on the age at diagnosis, previous syncopal attacks, premature ventricular contractions, papillary muscle fibrosis, and longitudinal disjunction distance. Most asymptomatic patients are managed conservatively; however, radiofrequency ablation should be considered in patients with high-risk or symptomatic MAD due to the risk of ventricular arrhythmias and sudden cardiac death., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

In the current scenario of increased pollution and releasing toxic gases by burning petroleum products, switching to natural gas is more promising for reducing CO 2 emissions and air pollutants. Hence, research on Liquefied Natural Gas and Compressed Natural Gas is gaining more value. However, natural gas primarily consists of CH 4 , which has less energy density than conventional fuels. Interestingly, since the C-H ratio of CH 4 gas is 1 : 4, it is easily combustible, gives less carbon footprint, and reduces unburnt hydrocarbon pollution. Hence, research on storing and transporting CH 4 has utmost importance, and porous materials are one of the suitable candidates for storing CH 4 . Herein we report the scalable synthesis of highly porous and crystalline covalent organic frameworks for storing CH 4 at room temperature and pressure. Two COFs, namely, Tp-Azo and Tp-Azo-BD(Me) 2 , synthesized in 1 kg at ∼45 g batch scale using a Planetary mixer, displayed a maximum BET surface area of around 3345 m 2 /g, and 2342 m 2 /g and CH 4 storage of 174.10 cc/cc and 151 cc/cc, respectively. A comparison of the CH 4 sorption of Tp-Azo and Tp-Azo-BD(Me) 2 COFs synthesized in different batches has a variation of only ±5 cc/cc and shows the consistency in bulk scale synthesis of COFs. The cyclic equilibrium CH 4 adsorption studies showed the COFs are stable with consistent CH 4 adsorption and desorption cycles. The present study is a step towards the scalable mechanochemical synthesis of COFs for gas storage applications., (© 2022 Wiley-VCH GmbH.)

In this contribution, we have designed and synthesized a novel carbazole-1,3,4-oxadiazole based bipolar fluorophore (E)-2-(4-(4-(9H-carbazol-9-yl)styryl)phenyl)-5-(4-(tertbutyl) phenyl)-1,3,4-oxadiazole (CBZ-OXA-IV). Wittig reaction is utilised for the synthesis of the designed bipolar target compound CBZ-OXA-IV. 1 H NMR, 13 C NMR, FT-IR and ESI-MS results confirmed the designed chemical structure of the fluorophore CBZ-OXA-IV. The photophysical properties have been investigated in detail using UV-Vis absorption, photoluminescence spectroscopy. Also, the photoluminescence studies on solid state samples (as thin films) were carried out. The CBZ-OXA-IV dye emits intense deep blue fluorescence with observed absorption and emission maxima occurring are at 353 nm and 470 nm, respectively. Fluorophore CBZ-OXA-IV has shown high Stokes shift of 7052 cm -1 . The experimentally measured optical band gap ([Formula: see text]) value is found to be 3.01 eV and the fluorescence quantum yields (Φ f ) is 0.40. The intramolecular charge transfer property of CBZ-OXA-IV dye was examined by using photophysical properties such as absorption, emission in different solvents of different varying polarities. In addition, Density Functional Theory computations are studied in detail including the MEP surface plots and natural bond orbital analysis. The electrochemical properties have been investigated in detail by using cyclic voltammetry measurements. Thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) measurement results display a high thermal stability with decomposition temperature (T d5% ) 387 °C and a large glass transition temperature (Tg) of 98 °C. The obtained results demonstrated that the novel bipolar fluorophore CBZ-OXA-IV could play an important role in organic optoelectronics and possibly can be utilized as bipolar transport materials for electroluminescence applications in optoelectronic devices/OLEDs., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the present work, an extensive QSAR (Quantitative Structure Activity Relationships) analysis of a series of peptide-type SARS-CoV main protease (MPro) inhibitors following the OECD guidelines has been accomplished. The analysis was aimed to identify salient and concealed structural features that govern the MPro inhibitory activity of peptide-type compounds. The QSAR analysis is based on a dataset of sixty-two peptide-type compounds which resulted in the generation of statistically robust and highly predictive multiple models. All the developed models were validated extensively and satisfy the threshold values for many statistical parameters (for e.g. R 2  ​= ​0.80-0.82, Q 2 loo  ​= ​0.74-0.77, Q 2 LMO  ​= ​0.66-0.67). The developed QSAR models identified number of sp 2 hybridized Oxygen atoms within seven bonds from aromatic Carbon atoms, the presence of Carbon and Nitrogen atoms at a topological distance of 3 and other interrelations of atom pairs as important pharmacophoric features. Hence, the present QSAR models have a good balance of Qualitative (Descriptive QSARs) and Quantitative (Predictive QSARs) approaches, therefore useful for future modifications of peptide-type compounds for anti- SARS-CoV activity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier B.V. All rights reserved.)

A quantitative structure-activity relationship (QSAR) model was built from a dataset of 54 peptide-type compounds as SARS-CoV inhibitors. The analysis was executed to identify prominent and hidden structural features that govern anti-SARS-CoV activity. The QSAR model was derived from the genetic algorithm-multi-linear regression (GA-MLR) methodology. This resulted in the generation of a statistically robust and highly predictive model. In addition, it satisfied the OECD principles for QSAR validation. The model was validated thoroughly and fulfilled the threshold values of a battery of statistical parameters (e.g. r 2  = 0.87, Q 2 loo  = 0.82). The derived model is successful in identifying many atom-pairs as important structural features that govern the anti-SARS-CoV activity of peptide-type compounds. The newly developed model has a good balance of descriptive and statistical approaches. Consequently, the present work is useful for future modifications of peptide-type compounds for SARS-CoV and SARS-CoV-2 activity.

Herein we report, the effect of solvents on absorption and fluorescence spectra of Alexa Fluor-350 labelled fluorescent dye examined both experimentally and computationally. The steady state absorption and fluorescence measurements are carried out in a series of solvents to explore their solvatochromism and to determine its dipole moments. To this end, different empirical solvatochromic models like Bilot-Kawaski, Lippert-Mataga, Bakhshiev, Kawaski-Chamma-Viallet and Reichardt models are assessed against Alexa Fluor 350 dye to determine the singlet excited and ground state dipole moments. Computational studies were carried out to optimize ground and excited geometries using density functional theory (DFT) and time dependent density functional theory (TD-DFT), respectively, in vacuum. Additionally, this study encompasses estimation of the electronic transition energies from the ground to first excited state of dye employing TD-DFT. Further, TD-DFT has been combined with integral equation formalism of the polarizable continuum model (IEF-PCM) to calculate various solute-solvent interaction potentials which are then compared with experimental values. The highest occupied molecular orbital energy (HOMO), lowest unoccupied molecular orbital energy (LUMO), the energy gap, chemical hardness (η), softness (σ), electronegativity (χ) and chemical potential (μ) were estimated. Mulliken atomic charge, natural population analysis (NPA) and molecular electrostatic potential (MEP) map are correlated using density functional theory. The experimentally obtained ground and excited state dipole moments are compared with the ones obtained from computational and the results are discussed. NBO analysis is carried out to investigate the intramolecular charge transfer interactions and stabilization energy within the studied molecule., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The type III secretion system (T3SS) is an essential virulence factor for Shigella flexneri , providing a conduit through which host-altering effectors are injected directly into a host cell to promote uptake. The type III secretion apparatus (T3SA) is composed of a basal body, external needle, and regulatory tip complex. The nascent needle is a polymer of MxiH capped by a pentamer of invasion plasmid antigen D (IpaD). Exposure to bile salts (e.g., deoxycholate) causes a conformational change in IpaD and promotes recruitment of IpaB to the needle tip. It has been proposed that IpaB senses contact with host cell membranes, recruiting IpaC and inducing full secretion of T3SS effectors. Although the steps of T3SA maturation and their external triggers have been identified, details of specific protein interactions and mechanisms have remained difficult to study because of the hydrophobic nature of the IpaB and IpaC translocator proteins. Here, we explored the ability for a series of soluble N-terminal IpaB peptides to interact with IpaD. We found that DOC is required for the interaction and that a region of IpaB between residues 11-27 is required for maximum binding, which was confirmed in vivo. Furthermore, intramolecular FRET measurements indicated that movement of the IpaD distal domain away from the protein core accompanied the binding of IpaB11-226. Together, these new findings provide important new insight into the interactions and potential mechanisms that define the maturation of the Shigella T3SA needle tip complex and provide a foundation for further studies probing T3SS activation.

Shigella flexneri uses its type III secretion system (T3SS) to promote invasion of human intestinal epithelial cells as the first step in causing shigellosis, a life-threatening form of dysentery. The Shigella type III secretion apparatus (T3SA) consists of a basal body that spans the bacterial envelope and an exposed needle that injects effector proteins into target cells. The nascent Shigella T3SA needle is topped with a pentamer of the needle tip protein invasion plasmid antigen D (IpaD). Bile salts trigger recruitment of the first hydrophobic translocator protein, IpaB, to the tip complex where it senses contact with a host membrane. In the bacterial cytoplasm, IpaB exists in a complex with its chaperone IpgC. Several structures of IpgC have been determined, and we recently reported the 2.1 Å crystal structure of the N-terminal domain (IpaB(74.224)) of IpaB. Like IpgC, the IpaB N-terminal domain exists as a homodimer in solution. We now report that when the two are mixed, these homodimers dissociate and form heterodimers having a nanomolar dissociation constant. This is consistent with the equivalent complexes copurified after they had been co-expressed in Escherichia coli. Fluorescence data presented here also indicate that the N-terminal domain of IpaB possesses two regions that appear to contribute additively to chaperone binding. It is also likely that the N-terminus of IpaB adopts an alternative conformation as a result of chaperone binding. The importance of these findings within the functional context of these proteins is discussed.

In this paper, a three-dimensional two-arch model of the foot is developed, taking foot geometry from X-rays of normal and diabetic subjects, which considered bones, cartilages, ligaments, important muscle forces and foot-sole soft-tissue. The stress analysis is carried out by a finite element technique using NISA software for the foot models simulating quasi-static walking phases of heel-strike, mid-stance and push-off. The analysis shows that the highest stresses occur during the push-off phase in the dorsal central part of the lateral and medial metatarsals and the dorsal junction of the calcaneus and cuboid. The vertical stresses, in the foot-sole soft-tissue at the foot-ground interface, for normal and diabetic neuropathic subjects, are the highest in the push-off phase and were in good agreement with the experimentally measured foot pressures. It is found that the foot-sole vertical stresses (at the foot-ground interface), in diabetic neuropathy, increase considerably in the heel region in the heel-strike phase and in the fore-foot regions in the push-off phase. The high stress concentration areas, in the plantar surfaces indicated above, are of great importance since it is found from clinical reports that in diabetic neuropathic patients these areas of the foot-sole are prone to ulcers. Thus, this investigation could possibly provide information on the areas of high stress concentration of the foot bones in the normal foot giving rise to arthritis when the mechanical strength decreases and possible high stress regions of foot bone giving rise to disintegration of tarsal bones in leprosy, as well as an insight into the factors contributing to plantar ulcers in diabetic neuropathy.

The purpose of the investigation reported in this paper is to determine theoretically the fluid dynamic field in models of common iliac arterial bifurcation and to identify the flow features which might influence the predominant occurrence of atherosclerotic lesions at such sites. This has been accomplished by numerically simulating fluid flow through 90 degrees symmetric bifurcations with branch-to-trunk area ratios of 0.8-1.414 and for Reynolds numbers ranging from 100 to 400. The analysis predicts flow reversal along the outer wall in models with area ratios over unity for high Reynolds number range, while no flow reversal occurred in models with area ratio below unity; a low shear zone along the outer wall and high shear stresses at the divider lip. Adverse pressure gradients are observed along the outer wall downstream of the corner point, the magnitudes increased with Reynolds number for a given branch to area ratio. Biological implication of the results is discussed with specific reference to the sites of atherosclerotic lesions found in man for these geometries.

A regulated left ventricular dynamics model is presented which involves interaction of the dynamics of the left ventricular and circulatory systems and their regulation by the central nervous system. On-line human parametric stimulation (parameter estimation) and consequential prognostic implications (based on parametric values) are demonstrated. Model responses to stimulated physiologic stresses help delineate tolerances of subjects. In order to have an estimate of the reliability of the model, the sensitivity of the model's responses to changes in the values of its intrinsic parameters is assessed. Also determined is the extent to which errors in measuring the pressure affect the calculated values of the model's responses to changes in the values of its intrinsic parameters is assessed. Also determined is the extent to which errors in measuring the pressure affect the calculated values of the model's simulation parameters and subsequently influence the values of other diagnostically useful variables (such as contractility, oxygen consumption rate, heart rate), when the model is used to determine the limiting physiological stress sustainable by the subject. A comparison of the model's composition with those of other similar cardio-circulatory models is included.