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In habitats where stressors are frequent or persistent, it can become increasingly difficult for wildlife to appropriately match their endocrine responses to these more challenging environments. The dynamic regulation of glucocorticoid (GC) hormones plays a crucial role in determining how well individuals cope with environmental changes. Amphibians exposed to agricultural stressors can dampen aspects of their GC profile (baseline, agitation, recovery, stress responsiveness, and negative feedback) to cope in these stressful environments, but this dampening can lead to reductions in an individual's reactive scope and a loss of endocrine flexibility. Organic agriculture could potentially limit some of these effects, however, little is known about how amphibians respond physiologically to organic agricultural environments. We compared GC profiles of Hyla versicolor tadpoles from three treatments: natural ponds (<5% agriculture within 500m), ponds near organic farms, and ponds near conventional farms. We hypothesized that tadpoles would cope with agricultural habitats by dampening stress responsiveness and exhibiting more efficient negative feedback and that the magnitude of these changes in response would differ based on agricultural method. We found that tadpoles from conventional and organic ponds were less likely to downregulate GCs via negative feedback after stressor exposure than tadpoles from natural ponds. For agricultural tadpoles that did downregulate GCs after the stressor, we found lower stress responsiveness and faster downregulation to baseline corticosterone than tadpoles from natural ponds. These results point to an accumulation of wear-and-tear, leading to an overall reduction in reactive scope and limited GC flexibility in our agricultural tadpoles. Regardless of agricultural method used, agricultural tadpoles exhibited the same patterns of GC response, indicating that current efforts to incentivize farmers to switch to organic farming methods may not be sufficient to address negative agricultural impacts on amphibians., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Amanda R. Bryant reports financial support was provided by Texas State University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Abstract: Waldman, HS, Bryant, AR, Parten, AL, Grozier, CD, and McAllister, MJ. Astaxanthin supplementation does not affect markers of muscle damage or inflammation after an exercise-induced muscle damage protocol in resistance-trained males. J Strength Cond Res 37(7): e413-e421, 2023-It is well documented that exercise-induced muscle damage (EIMD) decreases exercise performance by elevated inflammation and subjective discomfort. Due to its potent antioxidative properties, astaxanthin (AX) may serve as a potential dietary supplement strategy for mitigating delayed-onset muscle soreness (DOMS) and enhancing recovery and performance. This study aimed to investigate the effects of AX on markers of muscle damage, inflammation, DOMS, and anaerobic performance and substrate metabolism. Thirteen resistance-trained men (mean ± SD , age, 23.4 ± 2.1 years) completed a double-blind, counterbalanced, and crossover design with a 1-week washout period between 2, 4-week supplementation periods at 12 mg·d -1 of AX or placebo. After each supplementation period, subjects completed 2 trials, with trial 1 including a graded exercise test (GXT) and a 30-second Wingate and trial 2 including an EIMD protocol followed by the collection of fasting blood samples (pre-post) to measure creatine kinase, advanced oxidative protein products, C-reactive protein, interleukin-6, insulin, and cortisol. Astaxanthin supplementation had no statistical effects on markers of substrate metabolism during the GXT, Wingate variables, or markers of muscle damage, inflammation, or DOMS when compared with placebo (all p > 0.05). However, 4 weeks of AX supplementation did significantly lower oxygen consumption during the final stage of the GXT (12%, p = 0.02), as well as lowered systolic blood pressure (∼7%, p = 0.04), and significantly lowered baseline insulin values (∼24%, p = 0.05) when compared with placebo. Collectively, these data suggest that 4 weeks of AX supplementation at 12 mg·d -1 did not affect markers of muscle damage, inflammation, or DOMS after an EIMD protocol in a resistance-trained male cohort., (Copyright © 2022 National Strength and Conditioning Association.)

Abstract: Waldman, HS, Bryant, AR, Knight, SN, Killen, LG, Davis, BA, Robinson, MA, and O'Neal, EK. Assessment of metabolic flexibility by substrate oxidation responses and blood lactate in women expressing varying levels of aerobic fitness and body fat. J Strength Cond Res 37(3): 581-588, 2023-Collection of substrate oxidation responses during exercise is proposed as a noninvasive means for assessing metabolic flexibility in male subjects. However, because of hormonal and metabolic differences between sexes, this method may not be applicable to female subjects. This study assessed metabolic flexibility through indirect calorimetry across female subjects with different maximal oxidative capacities. Thirty-eight (18-45 years) eumenorrheic female subjects were stratified ( p < 0.05) based on V̇ o2 peak (mL·kg -1 ·min -1 ) into (1) endurance-trained (ET, n = 12, 42.6 ± 5.3), (2) recreationally active (RA, n = 13, 32.3 ± 1.6), or (3) overweight female subjects (OW, n = 13, 21.0 ± 4.0). Subjects completed the same 5-stage graded exercise test with intensities of 30, 45, 60, 75, and 90 W. Lactate [La - ], carbohydrate (CHOox), and fat (FATox) oxidation rates were assessed during the last min of each 5-minute stage. Subjects then cycled to exhaustion to determine V̇ o2 peak. Endurance-trained and RA female subjects expressed significantly ( p ≤ 0.05) higher absolute rates and rates scaled to fat-free mass of CHOox and FATox compared with OW female subjects during multiple stages. [La - ] failed to consistently differentiate the 3 groups with higher [La - ] for OW only found during stage 4; however, RER differed by 0.09 units or more at each stage for OW vs. ET. It seems that RER was more sensitive to cohort characteristics than [La - ] contrasting recent findings in male cohorts. In conclusion, indirect calorimetry is a practical and noninvasive method for assessing metabolic flexibility in eumenorrheic female subjects of varying aerobic fitness levels., (Copyright © 2022 National Strength and Conditioning Association.)

Betaine (BET) has shown to be effective in improving body composition and performance, although research in women is lacking. This study investigated the effects of BET supplementation on markers of metabolic flexibility, body composition, and anaerobic performance in college females. Twenty-three active subjects with 21.8 ± 3.0 years of age, 66.6 ± 8.8 kg body mass, 1.6 ± 0.1 m height, and 23.2 ± 5.3% body fat performed a graded exercise test on a cycle ergometer consisting of 4 incremental, 3 min stages for collection of fat and carbohydrate oxidation rates. Three 10 s sprint tests were then completed against a resistance of 7.5% of body mass, separated by 2.5 min of recovery. The study comprised 3 phases: (a) pre-supplementation, (b) randomization to supplement for 2-weeks with either 2.4 g/day BET or placebo (parallel design), and (c) post-supplementation. Repeated-measures analysis of variance were conducted to determine interactions or main effects. There were no group differences for substrate oxidation rates ( p  > 0.05). Although body composition improved pre-post for both groups ( p  < 0.05), only the BET group experienced a significant increase in fat free mass ( p  < 0.01; ∼3%). Further, only the BET group experienced improvements to performance such as a higher mean power output during the final sprint ( p  = 0.02; ∼3%) and a lower RPE during the final stage of the graded exercise test ( p  = 0.02). Results from this study suggest BET supplementation may improve body composition and some markers of performance during exercise in collegiate women.

Invasive fish predators are an important factor causing amphibian declines and may have direct and indirect effects on amphibian survival. For example, early non-lethal exposure to these stressors may reduce survival in later life stages, especially in biphasic species. In amphibians, the glucocorticoid hormone corticosterone is released by the hypothalamo-pituitary-interrenal axis (HPI), as an adaptive physiological response to environmental stressors. The corticosterone response (baseline and response to acute stressors) is highly flexible and context dependent, and this variation can allow individuals to alter their phenotype and behavior with environmental changes, ultimately increasing survival. We sampled larvae of the spring salamander ( Gyrinophilus porphyriticus ) from two streams that each contained predatory brook trout ( Slavelinus fontinalis ) in the lower reaches and no predatory brook trout in the upper reaches. We measured baseline and stress-induced corticosterone release rates of larvae from the lower and upper reaches using a non-invasive water-borne hormone assay. We hypothesized that corticosterone release rates would differ between larvae from fish-present reaches and larvae from fish-free reaches. We found that baseline and stressor-induced corticosterone release rates were downregulated in larvae from reaches with fish predators. These results indicate that individuals from reaches with predatory trout are responding to fish predators by downregulating corticosterone while maintaining an active HPI axis. This may allow larvae more time to grow before metamorphosing, while also allowing them to physiologically respond to novel stressors. However, prolonged downregulation of corticosterone release rates can impact growth in post-metamorphic individuals.

Abstract: Waldman, HS, Bryant, AR, Shepherd, BD, Egan, B, and McAllister, MJ. No effect of a ketone monoester on markers of stress and performance in a live-burn search and rescue in firefighters. J Strength Cond Res 36(3): 763-771, 2022-Firefighters experience a range of stressors that impair performance and elevate the risk for developing cardiometabolic diseases. β-Hydroxybutyrate (βHB) has been shown to mitigate markers of oxidative stress and inflammation and serve as an alternative fuel with implications to physical performance. On 2 occasions in a double-blind, counterbalanced, and crossover design, 14 professional firefighters performed a live-burn, search and rescue (S&R) 30 minutes after ingestion of a ketone monoester (KME; 0.5 g·kg-1) or a placebo (PLA). Dependent variables collected before and after the S&R included salivary markers of stress and inflammation (cortisol, α-amylase, interleukin-1 beta, uric acid), perceptual markers (profile of mood state [POMS]), gastrointestinal distress (GI), rating of perceived exertion [RPE]), time to completion, and capillary blood measurement of βHB and glucose. KME resulted in capillary βHB concentrations of approximately 2.1-3.2 mM throughout the protocol. Capillary glucose concentrations were lower for the KME compared with PLA (∼7%) (interaction effect, p < 0.001). Salivary markers of stress, GI, and time to complete the S&R (∼10 minutes) did not differ between trials, although KME ingestion resulted in significantly higher RPE after the live-burn S&R (KME,6 ± 1; PLA, 4 ± 1). However, POMS data showed the KME also lowered subjective states of nervousness (KME, 0.0 ± 0.0; PLA, 0.6 ± 0.8) and anxiety (KME, 0.0 ± 0.0; PLA, 0.6 ± 0.7) before the S&R (all p < 0.05; large effect sizes). Compared with PLA, ingestion of a KME by firefighters did not mitigate the rise in various markers of salivary stress or impact physical performance during a live-burn S&R. However, differences in RPE and POMS variables were observed, suggesting a possible cognitive role for βHB., (Copyright © 2022 National Strength and Conditioning Association.)

Despite ongoing therapeutic advances, multiple myeloma (MM) remains largely incurable, and outcomes in patients who develop resistance to immunomodulatory drugs or proteasome inhibitors remain grim. Allogeneic hematopoietic cell transplantation (alloHCT) is an alternative option that may offer potential for cure. Although rates of transplantation-related morbidity and mortality have decreased in recent years, weighing this approach's potential benefits against nontransplantation therapies demands a thoroughly informed pre-alloHCT assessment. Here we assess the impact of pre-alloHCT variables on important clinical outcomes in a large cohort of relapsed refractory MM (RRMM) CD34 + -selected alloHCT recipients. We included all patients with MM who underwent CD34 + -selected alloHCT at our center between June 2010 and December 2015. Patients were conditioned with busulfan (0.8 mg/kg × 10), melphalan (70 mg/m 2  × 2), and fludarabine (25 mg/m 2  × 5), followed by infusion of a CD34 + -selected peripheral blood stem cell graft, without post-alloHCT graft-versus-host disease (GVHD) prophylaxis. The 73-patient cohort had a median age of 55 years (range, 37 to 66 years). Overall survival (OS) and progression-free survival (PFS) rates were 70% and 53%, respectively, at 1 year (95% confidence interval [CI], 58% to 79% and 41% to 64%) and 50% and 30%, respectively, at 3 years (95% CI, 38% to 62% and 19% to 41%). The cumulative incidence of relapse was 25% at 1 year (95% CI, 15% to 35%) and 47% at 3 years (95% CI, 35% to 58%). Nonrelapse mortality at 1 year was 22% (95% CI, 13% to 32%). The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 7% at 100 days (95% CI, 3% to 14%), and that of any chronic GVHD (cGVHD) was 8% at 1 year (95% CI, 3% to 16%). International Staging System (ISS) stage II-III assessed before salvage therapy was associated with poorer 3-year OS (30% versus 54%; P = .037) and 3-year PFS (9% versus 33%; P = .013), and increased 3-year relapse incidence (72% versus 39%; P = .004). Older age and GVHD before 6 months (aGVHD grade II-IV or cGVHD of any grade) were also associated with poorer OS, and a greater number of pre-alloHCT lines of therapy was also associated with increased relapse incidence. Our findings reinforce that CD34 + -selected alloHCT can achieve prolonged disease control and long-term survival in high- risk, heavily treated refractory MM populations. We also identified numerous pre-alloHCT variables associated with OS, PFS, and relapse. Amongst these, presalvage ISS stage II-III was consistently associated with poorer survival and relapse outcomes. Given the lack of established alternate therapies for patients with RRMM, we advocate the identification of adverse pre-alloHCT variables to inform alloHCT decision making rather than to exclude patient cohorts from this potentially curative treatment option., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: Recent three-dimensional (3D) kinematic research has revealed foot abduction is the strongest predictor of standing functional and forced turnout postures. However, it is still unknown how the internal foot joints enable a large degree of foot abduction in turnout. The primary purpose of this study was to use a dance specific multi-segment foot model to determine the lower leg and foot contributions to turnout that female university-level ballets use to accentuate their turnout., Methods: Eighteen female dance students (mean age, 18.8 ± 1.6 years) volunteered for this study. Retro-reflective markers were attached to the dancers' dominant foot. Each dancer performed three repetitions of functional turnout, forced turnout and ten consecutive sautés in first position. Repeated measures ANOVA with Bonferroni adjustments for the multiple comparisons were used to determine the kinematic adjustments, hindfoot eversion, midfoot and forefoot abduction, navicular drop (i.e. lowering of the medial longitudinal arch) and first metatarsophalangeal joint abduction between natural double leg up-right posture and the first position conditions., Results: Hindfoot eversion (4.6°, p  < 0.001) and midfoot abduction (2.8°, p  < 0.001) significantly increased in functional turnout compared to the natural double leg up-right posture. Thirteen dancers demonstrated increased first metatarsophalangeal joint (MTPJ) abduction in forced turnout, however no statistically significant increase was found. Navicular drop during sautés in first position significantly increased by 11 mm ( p  < 0.001) compared to the natural double leg up-right posture., Conclusion: Our findings suggest dancers do pronate, via hindfoot eversion and midfoot abduction in both functional and forced turnout, however, no immediate association was found between forced turnout and first MTPJ abduction. Foot pronation does play a role in achieving turnout. Further prospective research on in situ measures of the lower limb in turnout and injury surveillance is required to improve our understanding of the normal and abnormal dance biomechanics., Competing Interests: Not applicable.This research was approved by the Edith Cowan University Human Research Ethics, reference: 12534 HOPPER. Informed written consent was obtained from each participant prior to the study.Consent was obtained to publish unidentifiable individual participant data.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Graft-versus-host (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). As donor T cells are recognized as key drivers of GVHD, some approaches to prevent GVHD have focused on T cell depletion of the allograft. In this review we summarize methods and outcomes of ex vivo T cell depleted (TCD) HCT with a focus on CD34+ selection. This platform is efficacious in preventing acute and chronic GVHD across a wide range of hematologic malignancies, and with the exception of chronic myeloid leukemia, is not associated with adverse relapse or survival outcomes compared to conventional GVHD prophylaxis platforms. In retrospective comparisons recipients of CD34+ selected HCT have higher rates of GVHD-free relapse-free survival (GRFS) than conventional HCT counterparts. Although CD34+ selected allografts require myeloablative and antithymocyte-globulin based conditioning to support engraftment, abrogation of calcineurin inhibitors and methotrexate in this approach reduces its toxicity such that it can be considered in select older and more comorbid patients who could benefit from ablative HCT. A trial comparing GVHD prophylaxis regimens (BMT CTN 1301, NCT02345850) has completed accrual and will be the first to compare CD34+ selected HCT with conventional HCT in a randomized prospective setting. Its findings have potential to establish CD34+ selected HCT as a new standard-of-care platform for GVHD prevention., Competing Interests: Conflicts of interest Dr Perales reports personal fees from Abbvie, Merck, Incyte, Novartis, Takeda, and Nektar Therapeutics. He serves on the DSMB for Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune. He has also received research support (clinical trials) from Incyte and Miltenyi Biotec. Dr. Bryant declares no conflicts of interest.

Background: Turnout in ballet is produced through summation of the joint structure characteristics and ranges of motion at the hip, knee, ankle, and foot. Contributions of the hip joint to functional turnout in dancers have received extensive examination, whereas little is known about contributions from the knee, ankle, and foot. The aim of this study was to explore the nonhip components of turnout to dancers' functional turnout in first position by assessing passive external tibiofemoral rotation and active measures of foot pronation, ie, navicular drop and Foot Posture Index., Methods: Nineteen female university-level dance students aged 16 to 19 years participated in this descriptive correlational study. External tibiofemoral rotation, navicular drop, Foot Posture Index, and functional turnout were measured for the participants' right and left legs., Results: Regression analyses revealed a weak relationship between passive external tibiofemoral rotation and functional turnout. Correlation analysis revealed a moderate negative relationship between passive tibiofemoral external rotation and the Foot Posture Index in functional turnout., Conclusions: These findings suggest that the lower leg does contribute to dancers' overall position of functional turnout. However, current methods are not useful in predicting a dancer's lower-leg contribution and alignment in functional turnout in first position.

Background: Controversy exists regarding the structural and functional causes of hallux limitus, including metatarsus primus elevatus, a long first metatarsal, first-ray hypermobility, the shape of the first metatarsal head, and the presence of hallux interphalangeus. Some articles have reported on the radiographic evaluation of these measurements in feet affected by hallux limitus, but no study has directly compared the affected and unaffected feet in patients with unilateral hallux limitus. This case-control pilot study aimed to establish whether any such differences exist., Methods: Dorsoplantar and lateral weightbearing radiographs of both feet in 30 patients with unilateral hallux limitus were assessed for grade of disease, lateral intermetatarsal angle, metatarsal protrusion distance, plantar gapping at the first metatarsocuneiform joint, metatarsal head shape, and hallux abductus interphalangeus angle. Data analysis was performed using a statistical software program., Results: Mean radiographic measurements for affected and unaffected feet demonstrated that metatarsus primus elevatus, a short first metatarsal, first-ray hypermobility, a flat metatarsal head shape, and hallux interphalangeus were prevalent in both feet. There was no statistically significant difference between feet for any of the radiographic parameters measured (Mann-Whitney U tests, independent-samples t tests, and Pearson χ(2) tests: P > .05)., Conclusions: No significant differences exist in the presence of the structural risk factors examined between affected and unaffected feet in patients with unilateral hallux limitus. The influence of other intrinsic factors, including footedness and family history, should be investigated further.

Background: In health research, investigators and funders are emphasizing the importance of collaboration between communities and academic institutions to achieve health equity. Although the principles underlying community-academic partnered research have been well-articulated, the processes by which partnerships integrate these principles when working across cultural differences are not as well described., Objectives: We present how Project GRACE (Growing, Reaching, Advocating for Change and Empowerment) integrated participatory research principles with the process of building individual and partnership capacity., Methods: We worked with Vigorous Interventions In Ongoing Natural Settings (VISIONS) Inc., a process consultant and training organization, to develop a capacity building model. We present the conceptual framework and multicultural process of change (MPOC) that was used to build individual and partnership capacity to address health disparities., Conclusions: The process and capacity building model provides a common language, approach, and toolset to understand differences and the dynamics of inequity. These tools can be used by other partnerships in the conduct of research to achieve health equity.

Purpose: We conducted a systematic review and meta-analysis of randomized and observational studies to evaluate the associations between QRS duration (QRSd) at baseline or in follow-up and outcomes with cardiac resynchronization therapy (CRT)., Methods: We searched online databases to December 2010 and included 6 randomized controlled trials (RCTs) and 38 observational studies. Outcomes included clinical/functional response, left ventricular (LV) remodeling, hospitalizations and mortality., Results: In RCTs, a benefit of CRT was evident only in patients with QRSd >150ms. In observational studies, those meeting either clinical or remodeling CRT response definitions had both wider pooled baseline QRSd and significantly more QRS narrowing with CRT than non-responders., Conclusions: RCTs demonstrate that benefit with CRT appears restricted to those with baseline QRSd wider than 150ms. Both wider baseline QRS and more QRS narrowing are associated with CRT response in observational studies. Electrocardiographic QRSd plays an important role in CRT patient selection and follow-up., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Emotion regulation is widely studied in many areas of psychology and the number of publications on emotion regulation has increased exponentially over the past few decades. Additionally, interest in the relationships between emotion dysregulation processes and psychopathology has drastically increased in recent years. The Emotion Regulation Questionnaire (ERQ) was developed to measure two specific constructs related to emotion control: reappraisal and suppression (Gross & John, 2003). In its initial validation study and subsequent analyses, the instrument was shown to possess sound psychometric properties, but, to date, inquiry regarding the measure's characteristics has been limited. Factor analytic examinations of commonly used instruments are recommended to validate the properties of a given measure and increase researchers understanding of the measured constructs. The current study examined the psychometric properties of the ERQ in a sample of 1,188 undergraduates through confirmatory factor analysis. Additionally, tests of measurement invariance were employed in order to examine potential structural differences based on gender and ethnicity. The current study supported the original structure of the measure with all demographic groups and exceptional fit was demonstrated. Additional normative data for gender and ethnic groups are included. Results support the use of the instrument in future research., (© 2011 Wiley Periodicals, Inc.)

A rapid, selective, and sensitive gradient HPLC method was developed for the analysis of dissolution samples of levothyroxine sodium tablets. Current USP methodology for levothyroxine (L-T(4)) was not adequate to resolve co-elutants from a variety of levothyroxine drug product formulations. The USP method for analyzing dissolution samples of the drug product has shown significant intra- and inter-day variability. The sources of method variability include chromatographic interferences introduced by the dissolution media and the formulation excipients. In the present work, chromatographic separation of levothyroxine was achieved on an Agilent 1100 Series HPLC with a Waters Nova-pak column (250 mm × 3.9 mm) using a 0.01 M phosphate buffer (pH 3.0)-methanol (55:45, v/v) in a gradient elution mobile phase at a flow rate of 1.0 mL/min and detection UV wavelength of 225 nm. The injection volume was 800 μL and the column temperature was maintained at 28°C. The method was validated according to USP Category I requirements. The validation characteristics included accuracy, precision, specificity, linearity, and analytical range. The standard curve was found to have a linear relationship (r(2)>0.99) over the analytical range of 0.08-0.8 μg/mL. Accuracy ranged from 90 to 110% for low quality control (QC) standards and 95 to 105% for medium and high QC standards. Precision was <2% at all QC levels. The method was found to be accurate, precise, selective, and linear for L-T(4) over the analytical range. The HPLC method was successfully applied to the analysis of dissolution samples of marketed levothyroxine sodium tablets., (Published by Elsevier B.V.)

Background: Hallux abducto valgus and hallux limitus are two commonly encountered foot deformities causing altered structure and function of the first metatarsophalangeal joint and subsequent compensatory mechanisms. This study was undertaken to determine the relationships between these two deformities and transverse plane position of the foot, or angle of gait, and several radiographic angular and linear parameters with established reliability., Methods: A convenience sample of 23 subjects with hallux abducto valgus, 22 subjects with hallux limitus, and 20 control subjects was used. Radiographic parameters were standardized weightbearing views and included lateral stressed dorsiflexion of the first metatarsophalangeal joint, composite, dorsoplantar, and lateral views. Angle of gait was obtained from powdered footprints recorded on paper. Two left and two right footprints identified on each trial were used to calculate angle of gait., Results: The findings of the study suggest that an association between angle of gait and the presence of hallux abducto valgus or hallux limitus does not exist. Possible explanations may relate to the large variability of normal angle of gait, the need to identify factors extrinsic to the foot capable of affecting transverse plane orientation of the foot, and the addition of information relating to symptoms., Conclusions: In this study, the presence of hallux abducto valgus or hallux limitus did not correspond to an association with a particular angle of gait. Length and elevation of the first metatarsal were associated in subjects with hallux abducto valgus and hallux limitus.

4',6-diamidino-2-phenylindole (DAPI), netropsin, and pentamidine are minor groove binders that have terminal -C(NH2)2+ groups. The hydration changes that accompany their binding to the minor groove of the (AATT)2 sequence have been studied using the osmotic stress technique with fluorescence spectroscopy. The affinity of DAPI for the binding site decreases with the increasing osmolality of the solution, resulting in acquisition of 35+/-1 waters upon binding. A competition fluorescence assay was utilized to measure the binding constants and hydration changes of the other two ligands, using the DNA-DAPI complex as the fluorescence reporter. Upon their association to the (AATT)2 binding site, netropsin and pentamidine acquire 26+/-3 and 34+/-2 additional waters of hydration, respectively. The hydration changes are discussed in the context of the terminal functional groups of the ligands and conformational changes in the DNA.

The gastrointestinal (GI) tract plays a central role in the pathogenesis of transmissible spongiform encephalopathies. These are human and animal diseases that include bovine spongiform encephalopathy, scrapie and Creutzfeldt-Jakob disease. They are uniformly fatal neurological diseases, which are characterized by ataxia and vacuolation in the central nervous system. Although they are known to be caused by the conversion of normal cellular prion protein to its infectious conformational isoform (PrPsc) the process by which this isoform is propagated and transported to the brain remains poorly understood. M cells, dendritic cells and possibly enteroendocrine cells are important in the movement of infectious prions across the GI epithelium. From there, PrPsc propagation requires B lymphocytes, dendritic cells and follicular dendritic cells of Peyer's patches. The early accumulation of the disease-causing agent in the plexuses of the enteric nervous system supports the contention that the autonomic nervous system is important in disease transmission. This is further supported by the presence of PrPsc in the ganglia of the parasympathetic and sympathetic nerves that innervate the GI tract. Additionally, the lymphoreticular system has been implicated as the route of transmission from the gut to the brain. Although normal cellular prion protein is found in the enteric nervous system, its role has not been characterized. Further research is required to understand how the cellular components of the gut wall interact to propagate and transmit infectious prions to develop potential therapies that may prevent the progression of transmissible spongiform encephalopathies.

We describe the effects of the Austin bunionectomy on plantar pressure distribution and radiographic measurements in the forefoot in 31 subjects (44 feet) with mild-to-moderate hallux valgus deformity and 36 control subjects (36 feet). Plantar pressure measurements before and 24 months after surgery showed peak pressure beneath the hallux reduced to normal values. Peak pressure measurements beneath the first, second, and third metatarsal heads in hallux valgus feet were relatively unchanged after surgery and remained higher than normal values. The operation produced significant decreases in mean preoperative radiographic measurements of hallux abductus, metatarsus primus varus, and first metatarsal protrusion distance in these patients to below-normal values.

The effects of the Youngswick osteotomy on plantar peak pressure distribution in the forefoot are presented for 17 patients (23 feet) with mild-to-moderate hallux limitus deformity and 23 control subjects (23 feet). During 2 years of follow-up, the operation produced a significant increase in the range of dorsiflexion of the first metatarsophalangeal joint in these patients, reaching near-normal values. Preoperative and postoperative measurements, using a pressure-distribution measurement system, show that peak pressure beneath the hallux and the first metatarsal head remained unchanged. However, peak pressure was significantly increased beneath the second metatarsal head and decreased beneath the fifth metatarsal head. These findings suggest that the foot functioned in a less inverted manner postoperatively. Compared with normal feet, hallux limitus feet demonstrated significantly higher peak pressure beneath the fourth metatarsal head preoperatively and postoperatively.