Accuracy of heart rate measured by military-grade wearable ECG monitor compared with reference and commercial monitors.

INTRODUCTION: Physiological monitoring of soldiers can indicate combat readiness and performance. Despite demonstrated use of wearable devices for HR monitoring, commercial options lack desired military features. A newly developed OMNI monitor includes desired features such as long-range secure data transmission. This study investigated the accuracy of the OMNI to measure HR via accuracy of R-R interval duration relative to research-grade ECG and commercial products. METHODS: 54 healthy individuals (male/female=37/17, age=22.2±3.6 years, height=173.0±9.1 cm, weight=70.1±11.2 kg) completed a submaximal exercise test while wearing a reference ECG (Biopac) and a randomly assigned chest-based monitor (OMNI, Polar H10, Equivital EQ-02, Zephyr Bioharness 3). All participants also wore two wrist-based photoplethysmography (PPG) devices, Garmin fenix 6 and Empatica E4. Bland-Altman analyses of agreement, concordance correlation coefficient (CCC) and root-mean-squared error (RMSE) were used to determine accuracy of the OMNI and commercial devices relative to Biopac. Additionally, a linear mixed-effects model evaluated the effects of device and exercise intensity on agreement. RESULTS: Chest-based devices showed superior agreement with Biopac for measuring R-R interval compared with wrist-based ones in terms of mean bias, CCC and RMSE, with OMNI demonstrating the best scores on all metrics. Linear mixed-effects model showed no significant main or interaction effects for the chest-based devices. However, significant effects were found for Garmin and Empatica devices (p<0.001) as well as the interaction effects between both Garmin and Empatica and exercise intensity (p<0.001). CONCLUSIONS: Chest-based ECG devices are preferred to wrist-based PPG devices due to superior HR accuracy over a range of exercise intensities, with the OMNI device demonstrating equal, if not superior, performance to other commercial ECG monitors. Additionally, wrist-based PPG devices are significantly affected by exercise intensity as they underestimate HR at low intensities and overestimate HR at high intensities.

Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy.

Immune-checkpoint blockade (ICB) has shown remarkable clinical success in boosting antitumor immunity. However, the breadth of its cellular targets and specific mode of action remain elusive. We find that tumor-infiltrating follicular regulatory T (TFR) cells are prevalent in tumor tissues of several cancer types. They are primarily located within tertiary lymphoid structures and exhibit superior suppressive capacity and in vivo persistence as compared with regulatory T cells, with which they share a clonal and developmental relationship. In syngeneic tumor models, anti-PD-1 treatment increases the number of tumor-infiltrating TFR cells. Both TFR cell deficiency and the depletion of TFR cells with anti-CTLA-4 before anti-PD-1 treatment improve tumor control in mice. Notably, in a cohort of 271 patients with melanoma, treatment with anti-CTLA-4 followed by anti-PD-1 at progression was associated with better a survival outcome than monotherapy with anti-PD-1 or anti-CTLA-4, anti-PD-1 followed by anti-CTLA-4 at progression or concomitant combination therapy.

Acute simultaneous bilateral avulsion fractures of the tibial tubercles in a 15-year-old male hurler: case report and literature review.

BACKGROUND: Avulsion fractures of the tibial tubercle are an unusual injury pattern generally occurring in the adolescent male during sporting activities. Bilateral simultaneous fractures are extremely rare. They are often associated with other underlying orthopaedic pathology. AIMS: We present a case of bilateral tibial tubercle avulsions occurring in a 15 year-old male hurler. We describe the management and necessary investigations required for this type of trauma and present a literature review on this rarely encountered injury. CONCLUSION: Although this type of atypical fracture pattern is associated with high energy trauma and other underlying pathology, we have shown that once treated, the patient can expect to make a prompt return to sporting activities with no significant long-term functional deficit.

Infant HIV infection despite "universal" antenatal testing.

We reviewed the antenatal HIV testing history, clinical presentation and outcome of 25 infants diagnosed with HIV between 1 January 2001 and 31 December 2005 in a tertiary referral hospital in London. Of the 25 cases, 21 had received antenatal care in the UK. Twelve mothers had not had an antenatal HIV test, four had tested positive antenatally, while five had had a negative HIV test on antenatal booking, implying seroconversion in pregnancy. When mothers had not been diagnosed antenatally, infants presented with severe infections, which were fatal in six cases. The majority (65%) of the children have long-term neurological sequelae. HIV seroconversion is an important cause of infant HIV in the UK.

T cell lymphoma in the lumbar spine of a domestic ferret (Mustela putorius furo).

A 22-month-old castrated male ferret developed acute pelvic limb paresis. Radiographs and computed tomography revealed a soft tissue mass with associated bony lysis of L5, and ultrasound-guided fine needle aspirates suggested that it was a lymphoma. Treatment with prednisone at immunosuppressive doses did not produce any detectable improvement in the ferret's clinical signs and it became moribund less than two weeks after they developed. A postmortem biopsy confirmed the presence of a lymphoma which had invaded the vertebral bone. No viruses were detected by cell culture, or electron microscopy.

Secondary nutritional hyperparathyroidism associated with vitamin D deficiency in two domestic skunks (Mephitis mephitis).

Two privately owned domestic skunks (Mephitis mephitis) developed clinical signs of hyperparathyroidism. Survey radiographs, complete blood counts and biochemical profiles, including the concentrations of ionised calcium, parathyroid hormone and 25-(OH)-vitamin D, established that they were deficient in vitamin D and had secondary nutritional hyperparathyroidism. They both responded to treatment, as well as to changes in their diet, and levels of exercise and exposure to sunlight.

Successful long-term treatment of hepatic carnitine palmitoyltransferase I deficiency and a novel mutation.

Individuals with carnitine palmitoyltransferase I (CPT-I) deficiency cannot metabolize long-chain fatty acids and can develop life-threatening hypoglycaemia. We present a boy with CPT-I deficiency maintained on a very low-fat diet with nighttime uncooked cornstarch feedings for 5(1/2) years with good success. He has had normal growth and no episodes of hypoglycaemia or adverse side-effects. We found that he was homozygous for a previously undescribed mutation, T314I, in the CPT1A protein.

Results of early excision and full-thickness grafting of deep palm burns in children.

The timing and method of treatment of deep palm and finger burns varies widely. Our protocol involves performing full-thickness skin grafts (FTSG) in nonhealing palm burns. We reviewed the functional and cosmetic results after FTSG to the palm. From August 1997 to April 1999, 11 patients (12 palms) underwent excision and FTSG within 2 weeks of injury. A panel of medical and nonmedical professionals evaluated follow-up pictures of the grafts at 1, 2 to 4, and beyond 4 months. Parameters used for evaluation were color match with the unburned skin (1 = no difference to 4 = large difference), graft thickness (1 = flat to 4 = markedly raised), overall appearance (1 = poor to 100 = excellent), and time to maturity. Hand function, as assessed by occupational therapy notes, was also recorded. All 12 grafted palms had a 100% take and healed with minimal scarring. Mean color match scores were 2.4 at 1 month, 1.8 at 2 to 4 months, and 1.6 beyond 4 months. On the graft thickness scale, grafts were given scores of 2.6, 2.2, and 1.9 during the same intervals. The overall appearance was 71 at 1 month, 81 at 2 to 4 months, and 85 beyond 4 months. All grafts except 1 were judged to be mature at 2 to 4 months follow-up. Full passive range of motion was attained in all grafted hands within the period of 2 to 4 months after operation. Early excision and FTSG of deep pediatric palm burns can be performed in the outpatient setting. The grafts have an acceptable color match, are minimally raised, and achieve excellent cosmetic result. The grafts mature within a few months after surgery to allow for rapid return to normal range of motion. FTSG should be considered as a first choice for deep palm burns.

Neurophysiologic predictors of treatment response to fluoxetine in major depression.

Treatment with antidepressants is marked by heterogeneity of response; predicting individual response to any given agent remains problematic. Neuroimaging studies suggest that response is accompanied by physiologic changes in cerebral energy utilization, but have not provided useful markers at pretreatment baseline. Using quantitative EEG (QEEG) techniques, we investigated pretreatment neurophysiologic features to identify responders and non-responders to fluoxetine. In a double-masked study, 24 adult subjects with current major depression of the unipolar type were studied over 8 weeks while receiving fluoxetine (20 mg QD) or placebo. Neurophysiology was assessed with QEEG cordance, a measure reflecting cerebral energy utilization. Response was determined with rating scales and clinical interview. Subjects were divided into discordant and concordant groups based upon the number of electrodes exhibiting discordance. The concordant group had a more robust response than the discordant group, judged by lower final Hamilton Depression (HAM-D) mean score (8.0+/-7.5 vs. 19.6+/-4.7, P = 0.01) and final Beck Depression Inventory (BDI) mean score (14.0+/-9.4 vs. 27.8+/-3.7, P = 0.015), and by faster reduction in symptoms (HAM-D: 14.0+/-5.0 vs. 23.8+/-4.1, P = 0.004 at 1 week). Groups did not differ on pretreatment clinical or historical features. Response to placebo was not predicted by this physiologic measure. We conclude that cordance distinguishes depressed adults who will respond to treatment with fluoxetine from those who will not. This measure detects a propensity to respond to fluoxetine and may indicate a more general responsiveness to antidepressants.

Dementia caregiver burden: a review of the literature and guidelines for assessment and intervention.

Alzheimer's disease (AD) and other dementias are common degenerative disorders in the elderly. Most AD patients are cared for at home by family members, usually elderly spouses. Although caregiving is associated with significant psychological and physical morbidity, there are wide individual differences among caregivers in how well they adapt to caregiving demands. In addition, recent data suggest that caregiver variables can be important determinants of AD patient institutionalization and that AD patients living with highly distressed caregivers may exhibit higher frequencies of behavioral problems and agitation than those living with less distressed caregivers. Predictors of caregiver outcome, predictors of institutionalization, and the effect of the caregiver on the course and symptomatology of dementia are described. A model of assessment and intervention for the physician, referral processes, and resources for the caregiver are presented.

Brain structure and function and the outcomes of treatment for depression.

BACKGROUND: Depressed patients have a variety of brain structural alterations, the most common being atrophy and deep white-matter lesions. Alterations in brain function also are common, particularly regional decreases in cerebral metabolism and perfusion. METHOD: We review here the evidence that alterations in brain structure and function may explain some of the heterogeneity in outcomes of depression. We also report initial results suggesting that measurement of brain structure and function may help to predict outcomes of treatment for depression. Brain structure was examined using three-dimensional reconstruction and volumetric analysis of magnetic resonance imaging (MRI) scans. Brain function was examined using quantitative electroencephalography (QEEG), performed at baseline and serially during the course of treatment. QEEG measures included coherence (a measure of synchronized activity between brain regions) and cordance (a measure strongly associated with regional cerebral perfusion). RESULTS: Depressed patients have been reported to have larger volumes of white-matter lesions than controls. We have found that some types of white-matter lesions are associated with lower coherence and that subjects with low coherence had significantly poorer outcomes of treatment for depression at 2-year follow-up. Depressed subjects had low cordance at baseline, which decreased further during the course of effective treatment. Subjects who did not improve had little or no change in cordance. Changes in cordance were detected prior to the onset of clinical response, with decreases seen as early as 48 hours after the initiation of treatment in subjects who showed eventual response. CONCLUSION: These preliminary results suggest that functional imaging using QEEG may be useful for assessing, and possibly predicting, outcomes of treatment for depression.

Is endothelium necessary for transmural pressure-induced contractions of bovine truncal lymphatics?

The purpose of this study was to investigate the role of the endothelium in regulating lymphatic contractile activity in bovine mesenteric truncal lymphatics. To test the effects of endothelial denudation on lymphatic pumping, bovine lymphatics were suspended in an organ bath preparation with the vessels cannulated at both inflow and outflow ends. By raising the heights of the Krebs reservoir and the outflow catheters appropriately, a transmural pressure could be applied to the vessels. The relationship between transmural pressure and fluid pumping is expressed as a bell-shaped curve with pumping increasing up to a peak pressure (between 8 and 12 cm H2O), and declining at pressures above this level. We compared pressure/flow curves in endothelium-intact and endothelium-denuded vessels. Chemical methods to remove the endothelium were attempted (collagenase and dispase) but were unsuccessful since they resulted in inhibition of all contractile activity including that induced with KCl. A technique using suture silk (3-O to 6-O) threaded into PE 50 or PE 20 polyethylene catheters with a loop at one end proved to be effective. By passing the catheter with its exposed loop of silk through the lymphatic ducts and imparting a twisting motion, we were able to remove the endothelium and preserve the smooth muscle responses to KCl. Transmission electron microscopy as well as silver staining techniques confirmed that all of the endothelium had been removed leaving the subendothelium and smooth muscle undamaged. We established that removal of the endothelium had no effect on lymphatic pumping. Pumping could not have occurred without the normal function of the one-way valves indicating that the denudation procedures did not damage these elements. Maximum flow rates and the transmural pressures that induced peak flows were similar in the two groups. We conclude that the pumping activity of bovine mesenteric truncal lymphatics in response to transmural pressure changes does not depend on an intact endothelium.

Suppression of fluid pumping in isolated bovine mesenteric lymphatics by interleukin-1: interaction with prostaglandin E2.

In addition to local physiological forces, the modulation of lymphatic pumping by chemical mediators may play an important role in the regulation of extravascular water in inflammation and shock. Since Interleukin-1 (IL-1) appears to be of major importance in the host's response to infection by mediating many inflammatory events, we thought it important to determine if this cytokine could affect the lymphatic circulation and in particular to ask whether IL-1 was capable of altering lymphatic pumping in response to changes in transmural pressure. Bovine lymphatic segments (6 to 8 cm in length) were cannulated at both ends and suspended in an organ bath preparation. The vessels were provided with Krebs solution from a reservoir. With no net driving pressure, a transmural pressure applied to the ducts elicited contractile activity and fluid pumping with increases in pumping up to 8 cm H2O and reductions in flow above this level of distension. Human recombinant IL-1 alpha (10(-7) to 10(-9) M) administered into the lumina of the vessels depressed pumping activity approximately 5-30% at transmural pressures between 2 and 16 cm H2O. With limited supplies, we could only assess the effects of human recombinant IL-1 beta at 10(-8) M. However, it was more potent than IL-1 alpha, inhibiting pumping at all transmural pressures with maximum suppression in the range of 70% at peak flows. The ability of IL-1 to induce prostaglandin synthesis may be one of its most important biologic functions. It is likely therefore that IL-1 and PGE2 are closely linked and are probably present together in inflammatory lesions. With this in mind, we investigated the effects of PGE2 alone and in combination with IL-1 alpha. PGE2 by itself reduced pumping at concentrations between 10(-6) and 10(-9) M. When mixed with IL-1 alpha (both agents at a final concentration of 10(-9) M), the mixture had a marked inhibitory effect on flow, reducing pumping 50 to 70% at peak flows. The effect of the mixture of IL-1 alpha and PGE2 compared with the two agents administered separately was greater than the predicted additive effect at transmural pressures above 6 cm H2O. At lower transmural pressures, however, the level of real inhibition was less than the predicted additive effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Characterization of a partly folded protein by NMR methods: studies on the molten globule state of guinea pig alpha-lactalbumin.

NMR spectroscopy has been used to investigate the structure of a partially folded state of a protein, the molten globule or A-state of alpha-lactalbumin. The 1H NMR spectrum of this species differs substantially from those of both the native and fully unfolded states, reflecting the intermediate level of order. The resolution in the spectrum is limited by the widespread overlap and substantial line widths of many of the resonances. Methods have therefore been developed that exploit the well-resolved spectrum of the native protein to probe indirectly the A-state. A number of resonances of the A-state have been found to be substantially shifted from their positions in the spectrum of the unfolded state and have been identified through magnetization transfer with the native state, under conditions where the two states are interconverting. The most strongly perturbed residues in the A-state were found to be among those that form a hydrophobic core to the native structure. A number of amides were found to be highly protected from solvent exchange in the A-state. These have been identified through pH-jump experiments, which label them in the spectrum of the native protein. They were found to occur mainly in segments that are helical in the native structure. These results enable a model of the A-state to be proposed in which significant conformational freedom exists but where specific elements of native-like structure are preserved.

Coagulation of sheep intestinal and prefemoral lymph.

We have determined the most suitable method for the automated analysis of the clotting parameters in sheep intestinal and prefemoral lymph as defined by the Activated Partial Thromboplastin Times (APTT; measure of intrinsic coagulation pathway) and the Prothrombin Times (PT; measure of extrinsic coagulation pathway). As opposed to optical density systems, the use of a Fibro-System Fibrometer was found to provide the most consistent assessment of coagulation with the endpoint being the time to fibrin strand formation. We measured APTT in sheep intestinal and prefemoral lymph of 59.78 +/- 7.69 seconds and 51.03 +/- 10.49 seconds respectively. These values were more prolonged than those obtained from sheep blood plasma but only in the case of intestinal lymph were the differences significant (p less than 0.025). Human blood APTT values were significantly less than both sheep blood (p less than 0.05) and sheep intestinal (p less than 0.001) and prefemoral lymph (p less than 0.01). PT values were found to be 21.56 +/- 1.14 seconds in intestinal and 22.00 +/- 1.88 seconds in prefemoral lymph. These values were also significantly greater than those obtained from sheep blood (both p less than 0.001). Human blood PTs were significantly less than both sheep blood (p less than 0.001) and intestinal and prefemoral lymph (both p less than 0.001). Measurement of APTT and PT values in intestinal lymph and PT determinations in prefemoral lymph were not affected by storage in the refrigerator or freezer. There was some indication that APTT values in prefemoral samples were susceptible to storage artifacts; however, the differences in coagulation times were not significant.

Noncompliance in an exercise rehabilitation program for men who have suffered a myocardial infarction.

A group of 163 men in the Hamilton, Ont. region who had suffered a myocardial infarction were enrolled in a rehabilitation program of physical activity. These men constituted one cohort of a multicentre collaborative study designed to determine the effects of regular exercise of differing intensity on morbidity and mortality over a 4-year period.The noncompliance rate was 43% for the men who could have participated for 1 year, 46% of whom were classified as noncompliers within 1 month of entry into the program. There was no difference in overall compliance between the men exercising at high intensity and those exercising at low intensity; lack of motivation or interest was the most common reason for their leaving the program. Those leaving the program early tended to have a type A behaviour pattern (they were aggressive, ambitious and competitive, with a chronic sense of time urgency), were inactive during their leisure time, had had at least two previous infarctions and smoked. These characteristics suggest that the men leaving the program early may have been those at greatest risk for a further myocardial infarction.