A case report of granulomatous lymphomatoid papulosis.

Lymphomatoid papulosis is a chronic CD30-positive cutaneous lymphoproliferative disorder that is characterized by recurring red-brown necrotic papules. It exhibits a wide spectrum of histopathologic findings and is often associated with cutaneous T-cell lymphomas. Six different histological subtypes have been classified by the WHO, but there is limited understanding regarding rare histopathologic variants. We describe a 51-year-old man who presented with recurring, necrotic papules for 6 years that progressed to involve the face, scalp, trunk, axilla, and scrotum. Histopathology demonstrated sarcoidal granulomas, along with a CD30-positive T cell infiltrate which demonstrated clonality by T cell receptor gamma gene rearrangement. A diagnosis of lymphomatoid papulosis associated with granulomas was established based on the clinical and histopathologic presentation. The clinical understanding of granulomatous lymphomatoid papulosis is limited in the available literature and more awareness of this histopathologic variant is required for accurate classification of this disorder.

Changes in Muscle Architecture, Explosive Ability, and Track and Field Throwing Performance Throughout a Competitive Season and After a Taper.

The purpose of this study was to examine the effects of an overreach and taper on measures of muscle architecture, jumping, and throwing performance in Division I collegiate throwers preparing for conference championships. Six collegiate track and field throwers (3 hammer, 2 discus, 1 javelin) trained for 12 weeks using a block-periodization model culminating with a 1-week overreach followed by a 3-week taper (ORT). Session rating of perceived exertion training load (RPETL) and strength training volume-load times bar displacement (VLd) were recorded weekly. Athletes were tested pre-ORT and post-ORT on measures of vastus lateralis architecture, unloaded and loaded squat and countermovement jump performance, underhand and overhead throwing performance, and competition throwing performance. There was a statistical reduction in weight training VLd/session (d = 1.21, p ≤ 0.05) and RPETL/session (d = 0.9, p ≤ 0.05) between the in-season and ORT training phases. Five of 6 athletes improved overhead throw and competition throwing performance after the ORT (d = 0.50, p ≤ 0.05). Vastus lateralis muscle thickness statistically increased after the in-season training phase (d = 0.28, p ≤ 0.05) but did not change after the ORT. Unloaded countermovement jump peak force and relative peak power improved significantly after the ORT (d = 0.59, p ≤ 0.05, d = 0.31, p ≤ 0.05, respectively). These findings demonstrate that an overreaching week followed by a 3-week taper is an effective means of improving explosive ability and throwing performance in collegiate track and field throwers despite the absence of detectable changes in muscle architecture.

Hepatitis E seroprevalence in recipients of renal transplants or haemodialysis in southwest England: a case-control study.

Locally acquired HEV infection is increasingly recognized in developed countries. Anti-HEV IgG seroprevalence has been shown to be high in haemodialysis patients in a number of previous studies, employing assays of uncertain sensitivity. The aim of this study was to investigate anti-HEV IgG seroprevalence in recipients of haemodialysis and renal transplants compared to a control group using a validated, highly sensitive assay. Eighty-eight patients with functioning renal transplants and 76 receiving chronic haemodialysis were tested for HEV RNA and anti-HEV IgG and IgM. Six hundred seventy controls were tested for anti-HEV IgG. Anti-HEV IgG was positive in 28/76 (36.8%) of haemodialysis and 16/88 (18.2%) of transplant patients. HEV RNA was not found in any patient. 126/670 (18.8%) of control subjects were anti-HEV IgG positive. After adjusting for age and sex, there was a significantly higher anti-HEV IgG seroprevalence amongst haemodialysis patients compared to controls (OR = 1.97, 95% CI = 1.16-3.31, P = 0.01) or transplant recipients (OR = 2.63, 95% CI = 1.18-6.07, P = 0.02). Patients with a functioning transplant showed no difference in anti-HEV IgG seroprevalence compared to controls. The duration of haemodialysis or receipt of blood products were not significant risk factors for HEV IgG positivity. Patients receiving haemodialysis have a higher seroprevalence of anti-HEV IgG than both age- and sex-matched controls and a cohort of renal transplant patients. None of the haemodialysis patients had evidence of chronic infection. The reason haemodialysis patients have a high seroprevalence remains uncertain and merits further study.

Screening for - and prevalence of - anxiety and depression in cardiac rehabilitation in the post-COVID era. An observational study.

BACKGROUND: Approximately 20-30% of patients with a cardiac disease suffer from anxiety and/or depression, leading to poor health outcomes. To identify this subgroup, clinical guidelines recommend screening for anxiety and depression in cardiac rehabilitation (CR). It is unknown how screening practice is delivered post-COVID. METHODS: This observational study used data from the National Audit of Cardiac Rehabilitation from April 2018-March 2022. Descriptive statistics were used to assess screening rates and prevalence, while a multivariate logistic regression model was performed to analyse determinants for screening for anxiety and depression among patients participating in cardiac rehabilitation. RESULTS: The population consisted of 245,705 patients, where 128,643 (52.4%) were screened and 117,062 (47.6%) were not. Patients attending CR during first year of COVID-19 were less likely to be screened. Patients with female gender, living alone, non-white ethnicity, living in the most deprived areas, current smoking, and physical inactivity were less likely to be screened, while patients who were revascularized, having an objective physical fitness test, and attending a certified CR center were more likely to be screened. For patients attending CR during COVID-19, the prevalence of anxiety and depression decreased significantly. For anxiety the prevalence dropped from 34.4% to 15.8%, for depression the prevalence dropped from 33.5% to 16.5%. CONCLUSION: CR service provision was negatively impacted during COVID-19, leading to much lower screening for anxiety and depression in the CR setting. Prevalence of anxiety and depression decreased during COVID-19 for this population, possibly because psychologically affected patients refrained from attending CR.

Systematic screening for anxiety and depression in cardiac rehabilitation - are we there yet?

BACKGROUND: Anxiety and depression are prevalent in 20% of patients with acute coronary syndrome (ACS) and associated with poor outcomes. Guidelines recommend screening for these conditions in cardiac rehabilitation (CR) however, clinical practice is inconsistent. Sparse knowledge exists on determinants for screening. METHODS: This observational study used data from the National Audit of Cardiac Rehabilitation from January 2016-December 2019. A multivariate logistic regression model was performed to analyze patient- and provider level determinants for screening for anxiety and depression among patients with ACS. RESULTS: The population consisted of 138,018 patients, where 82,507 (59.8%) were screened and 55,511 (40.2%) were not. Younger age, non-white ethnicity, living in areas of social deprivation, current smoking, body mass index>30, and physical activity<150 min per week were negatively correlated with patients being screened. Compared to patients having a percutaneous coronary intervention, patients undergoing coronary artery bypass grafting or medical treatment were less likely to be screened. History of anxiety, depression, osteoporosis, chronic back problems, and asthma were positively correlated with screening, while chronic obstructive pulmonary disease, diabetes, hypertension, and stroke were negatively correlated with screening. Regarding provider level, certification of CR centers was positively associated with screening, while looking over time data showed an incremental negative trend in screening from 2016 to 2019. CONCLUSION: We found both patient and provider level determinants of screening for anxiety and depression. Clinical practice is still inconsistent especially for high-risk groups. We recommend systematic screening to enable tailored interventions which in turn may mitigate inequity in health outcomes.

Growth rates for freshwater ferromanganese concretions indicate regional climate change in eastern Canada at the Northgrippian-Meghalayan boundary.

The existence of freshwater ferromanganese concretions has been known for decades, but we are not aware of a generally accepted explanation for their formation, and there has been little research into their potential use as records of Holocene climate and paleohydrology. A conceptual model is presented to describe the environmental and geochemical processes which result in the formation and growth of freshwater ferromanganese concretions. In order to evaluate their potential as historical geochemical records, a concretion from Magaguadavic Lake, New Brunswick, Canada is the focus of a detailed geochronological and geochemical investigation. The radiocarbon data provide a coherent growth curve and a maximum age for the concretion of 8448 ± 43 years, consistent with the establishment of Magaguadavic Lake as a stable post-glacial lacustrine system. The data suggest accretion rates of 1.5 and 3.4 mm per 1000 years during the Northgrippian and Meghalayan stages of the Holocene, respectively. The abrupt change in growth rate observed at the stage boundary may be an indicator of Holocene climate change. These features are consistent with inferences from previous research that warmer climate in the Northgrippian led to eutrophication in some lakes in eastern North America. The results confirm that freshwater Fe-Mn concretions may yield important information about past climatic and environmental conditions.

To b or not to b: the ongoing saga of peptide b ions.

Modern soft ionization techniques readily produce protonated or multiply protonated peptides. Collision-induced dissociation (CID) of these protonated species is often used as a method to obtain sequence information. In many cases fragmentation occurs at amide bonds. When the charge resides on the C-terminal fragment so-called y ions are produced which are known to be protonated amino acids or truncated peptides. When the charge resides on the N-terminal fragment so-called b ions are produced. Often the sequence of y and b ions are essential for peptide sequencing. The b ions have many possible structures, a knowledge of which is useful in this sequencing. The structures of b ions are reviewed in the following with particular emphasis on the variation of structure with the number of amino acid residues in the b ion and the effect of peptide side chain on b ion structure. The recent discovery of full cyclization of larger b ions results in challenges in peptide sequencing. This aspect is discussed in detail.

Efficient Algorithm for the Topological Characterization of Worm-like and Branched Micelle Structures from Simulations.

Many surfactant-based formulations are utilized in industry as they produce desirable viscoelastic properties at low concentrations. These properties are due to the presence of worm-like micelles (WLMs), and as a result, understanding the processes that lead to WLM formation is of significant interest. Various experimental techniques have been applied with some success to this problem but can encounter issues probing key microscopic characteristics or the specific regimes of interest. The complementary use of computer simulations could provide an alternate route to accessing their structural and dynamic behavior. However, few computational methods exist for measuring key characteristics of WLMs formed in particle simulations. Further, their mathematical formulations are challenged by WLMs with sharp curvature profiles or density fluctuations along the backbone. Here, we present a new topological algorithm for identifying and characterizing WLMs in particle simulations, which has desirable mathematical properties that address shortcomings in previous techniques. We apply the algorithm to the case of sodium dodecyl sulfate micelles to demonstrate how it can be used to construct a comprehensive topological characterization of the observed structures.

Sequence-scrambling fragmentation pathways of protonated peptides.

The gas-phase structures and fragmentation pathways of the N-terminal b and a fragments of YAGFL-NH(2), AGLFY-NH(2), GFLYA-NH(2), FLYAG-NH(2), and LYAGF-NH(2) were investigated using collision-induced dissociation (CID) and detailed molecular mechanics and density functional theory (DFT) calculations. Our combined experimental and theoretical approach allows probing of the scrambling and rearrangement reactions that take place in CID of b and a ions. It is shown that low-energy CID of the b(5) fragments of the above peptides produces nearly the same dissociation patterns. Furthermore, CID of protonated cyclo-(YAGFL) generates the same fragments with nearly identical ion abundances when similar experimental conditions are applied. This suggests that rapid cyclization of the primarily linear b(5) ions takes place and that the CID spectrum is indeed determined by the fragmentation behavior of the cyclic isomer. This can open up at various amide bonds, and its fragmentation behavior can be understood only by assuming a multitude of fragmenting linear structures. Our computational results fully support this cyclization-reopening mechanism by showing that protonated cyclo-(YAGFL) is energetically favored over the linear b(5) isomers. Furthermore, the cyclization-reopening transition structures are energetically less demanding than those of conventional bond-breaking reactions, allowing fast interconversion among the cyclic and linear isomers. This chemistry can lead in principle to complete loss of sequence information upon CID, as documented for the b(5) ion of FLYAG-NH(2). CID of the a(5) ions of the above peptides produces fragment ion distributions that can be explained by assuming b-type scrambling of their parent population and a --> a*-type rearrangement pathways ( Vachet , R. W. , Bishop , B. M. , Erickson , B. W. , and Glish , G. L. J. Am. Chem. Soc. 1997, 119, 5481 ). While a ions easily undergo cyclization, the resulting macrocycle predominantly reopens to regenerate the original linear structure. Computational data indicate that the a --> a*-type rearrangement pathways of the linear a isomers involve post-cleavage proton-bound dimer intermediates in which the fragments reassociate and the originally C-terminal fragment is transferred to the N-terminus.

Peptide sequence scrambling through cyclization of b(5) ions.

The CID mass spectra of the MH(+) ions and the b(5) ions derived therefrom have been determined for the hexapeptides YAAAAA, AYAAAA, AAYAAA, AAAYAA, and AAAAYA. The CID mass spectra for the b(5) ions derived from the five isomers are essentially identical and show abundant ion signals for nonsequence b ions. This result is consistent with cyclization of the b(5) ions to a cyclic pentapeptide before fragmentation; this cyclic peptide can open at various positions, leading to losses of amino acid residues that are not characteristic of the original amino acid sequence. These nonsequence b ions are also observed in the fragmentation of the MH(+) ions and increase substantially in importance with increasing collision energy. A comparison of the fragmentation of AAAYAA and Ac-AAAYAA indicates that N-acetylation eliminates the cyclization of b(5) ions and, thus, eliminates the nonsequence ions in the CID mass spectra of both b(5) and MH(+) ions.

A novel technique using a steerable guide catheter to successfully deliver an Amplatzer septal occluder to close an atrial septal defect.

Correct positioning of an Amplatzer ASD occluder can be difficult in vertical hearts or in those with diminutive or missing septal rims. In this report we describe the use of a steerable sheath to position the device in the plane of the ASD to achieve success.

Does the mode of delivery in Cardiac Rehabilitation determine the extent of psychosocial health outcomes?

BACKGROUND: Cardiac Rehabilitation (CR) is a multicomponent tailored intervention aiming to reduce lifestyle risk factors and promote health in patients post cardiovascular disease. CR is delivered either as supervised or facilitated self-delivered yet little evidence exists evaluating the association between mode of delivery and outcomes. METHODS: This observational study used data routinely collected from the National Audit of Cardiac Rehabilitation from April 2012-March 2016. The analysis compared the populations receiving supervised and facilitated self-delivered modes for differences in baseline demographics, four psychosocial health measures pre and post CR and changes in anxiety, depression and quality of life following the intervention. The analysis also modelled the relationship between mode and outcomes, accounting for covariates such as age, gender, duration and staffing. RESULTS: The study contained 120,927 patients (age 65, 26.5 female) with 82.2% supervised and 17.8% self-delivered. The analysis showed greater proportion of females, employed and older patients in the self-delivered group. Following CR, patients in both groups demonstrated positive changes which were of comparable size. The regression model showed no significant association between mode of delivery and outcome in all four psychosocial outcomes when accounting for covariates (p-value>0.0.5). CONCLUSIONS: Patients benefited from attending both modes of CR showing improved psychosocial health outcomes with 3-76% change from baseline. Over half of CR programmes in the UK do not provide self-delivered CR yet this mode is known to reach older patients, female and employed patients. Facilitated self-delivered CR should be offered and supported as a genuine option, alongside supervised CR, by clinical teams.

Does the mode of delivery in routine cardiac rehabilitation have an association with cardiovascular risk factor outcomes?

AIMS: Cardiac rehabilitation is one of the most cost-effective interventions for patients with cardiovascular disease. Worldwide supervised group-based cardiac rehabilitation is the dominant mode of delivery followed by facilitated self-managed (FSM), which is emerging as part of a cardiac rehabilitation menu. Modern research evidence, using trials and well-resourced interventions, suggests FSM is comparable to supervised rehabilitation in its outcomes for patients; however, this is yet to be established using routine clinical practice data. METHODS: Including 81,626 patients from routine clinical data in the National Audit of Cardiac Rehabilitation, this observational study investigated whether mode of delivery, supervised or FSM, was associated with similar cardiac rehabilitation outcomes. Hierarchical regression models included patient and service covariates such as age, gender, cardiac rehabilitation duration and programme staff type. RESULTS: The results showed 85% of the population received supervised cardiac rehabilitation. The FSM group were significantly older, female and predominantly in lower socioeconomic groups. The results showed that all patients on average benefit from cardiac rehabilitation, independently of mode of delivery, across all risk factors. Additional benefit of 13% and 11.4% increased likelihood of achieving the target state for physical activity and body mass index respectively when using FSM approaches. CONCLUSION: This is the first study to investigate traditional cardiovascular risk factors with cardiac rehabilitation mode of delivery using routine clinical data. Both modes of delivery were associated with comparable statistically significant positive outcomes. Despite having equivalent outcomes, FSM cardiac rehabilitation continues to be underutilised, with less than 20% of patients receiving this mode of delivery in the UK.

Intensive care unit physician-delivered point of care renal tract ultrasound in acute kidney injury is feasible.

Acute kidney injury is common in critically ill patients, with ultrasound recommended to exclude renal tract obstruction. Intensive care unit clinicians are skilled in acquiring and interpreting ultrasound examinations. Intensive Care Medicine Trainees wish to learn renal tract ultrasound. We sought to demonstrate that intensive care unit clinicians can competently perform renal tract ultrasound on critically ill patients. Thirty patients with acute kidney injury were scanned by two intensive care unit physicians using a standard intensive care unit ultrasound machine. The archived images were reviewed by a Radiologist for adequacy and diagnostic quality. In 28 of 30 patients both kidneys were identified. Adequate archived images of both kidneys each in two planes were possible in 23 of 30 patients. The commonest reason for failure was dressings and drains from abdominal surgery. Only one patient had hydronephrosis. Our results suggest that intensive care unit clinicians can provide focussed renal tract ultrasound. The low incidence of hydronephrosis has implications for delivering the Core Ultrasound in Intensive Care competencies.

Fragmentation of protonated dipeptides containing arginine. Effect of activation method.

The fragmentation reactions of the protonated dipeptides Gly-Arg and Arg-Gly have been studied using collision-induced dissociation (CID) in a quadrupole ion trap, by in-source CID in a single-quadrupole mass spectrometer and by CID in the quadrupole cell of a QqTOF mass spectrometer. In agreement with earlier quadrupole ion trap studies (Farrugia, J. M.; O'Hair, R. A. J., Int. J. Mass Spectrom., 2003, 222, 229), the CID mass spectra obtained with the ion trap for the MH(+) ions and major fragment ions are very similar for the two isomers indicating rearrangement to a common structure before fragmentation. In contrast, in-source CID of the MH(+) ions and QqTOF CID of the MH(+), [MH - NH(3)](+) and [MH <23 HN = C(NH(2))(2)](+) ions provide distinctly different spectra for the isomeric dipeptides, indicating that rearrangement to a common structure has not occurred to a significant extent under these conditions even near the threshold for fragmentation in the QqTOF instrument. Clearly, under normal operating conditions significantly different fragmentation behavior is observed in the ion trap and beam-type experiments. This different behavior probably can be attributed to the shorter observation times and concomitant higher excitation energies in the in-source and QqTOF experiments compared to the long observation times and lower excitation energies relevant to the ion trap experiments. Based largely on elemental compositions derived from accurate mass measurements in QqTOF studies fragmentation schemes are proposed for the MH(+), [MH - NH(3)](+), and [MH - (HN = C(NH(2))(2))](+) ions.

Relationship between employment and mental health outcomes following Cardiac Rehabilitation: an observational analysis from the National Audit of Cardiac Rehabilitation.

BACKGROUND: Employment status has been shown to impact mental health state and intervention outcomes, yet still to be studied in a Cardiac Rehabilitation (CR) population. This observational study investigated the relationship between employment status and mental health outcomes following Cardiac Rehabilitation (CR). METHODS: All patients with an eligible cardiovascular incident entered into the National Audit of Cardiac Rehabilitation (NACR) 1 January 2013-31st December 2015. Logistic regression comparing the association between employment status and normal mental health categories. RESULTS: A total of 24,242 CR patients with completed post CR assessments were included and had representative age and gender distribution (mean 65years, 73.2% male). At baseline the unemployed status had a lower proportion of patients in normal healthy categories than other groups (T-test and chi-squared p=<0.05). The regression analyses revealed no significant association between retired and employed groups and outcome. There was significant association between unemployed patients and all mental health outcomes except anxiety; all p values<0.05 and odds ratios between 0.525 and 0.772 showing less likelihood of achieving the normal healthy category. CONCLUSIONS: This is the first UK study, using routinely collected data, to investigate in coronary heart disease patients the impact of employment status on outcomes. The findings were that when weighted for baseline differences, unemployed patients mostly had poorer outcomes. Teams involved in CR delivery should take particular care when interpreting mental health baseline measures when setting CR goals, especially in relation to unemployed patients, and efforts should be made in providing more patient tailored interventions.

Proton Mobility in b2 Ion Formation and Fragmentation Reactions of Histidine-Containing Peptides.

A detailed energy-resolved study of the fragmentation reactions of protonated histidine-containing peptides and their b2 ions has been undertaken. Density functional theory calculations were utilized to predict how the fragmentation reactions occur so that we might discern why the mass spectra demonstrated particular energy dependencies. We compare our results to the current literature and to synthetic b2 ion standards. We show that the position of the His residue does affect the identity of the subsequent b2 ion (diketopiperazine versus oxazolone versus lactam) and that energy-resolved CID can distinguish these isomeric products based on their fragmentation energetics. The histidine side chain facilitates every major transformation except trans-cis isomerization of the first amide bond, a necessary prerequisite to diketopiperazine b2 ion formation. Despite this lack of catalyzation, trans-cis isomerization is predicted to be facile. Concomitantly, the subsequent amide bond cleavage reaction is rate-limiting.

Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea.

OBJECTIVES: Since B-type natriuretic peptide (BNP) is secreted by the left ventricle (LV) in response to volume elevated LV pressure, we sought to assess whether a rapid assay for BNP levels could differentiate cardiac from pulmonary causes of dyspnea. BACKGROUND: Differentiating congestive heart failure (CHF) from pulmonary causes of dyspnea is very important for patients presenting to the emergency department (ED) with acute dyspnea. METHODS: B-natriuretic peptide levels were obtained in 321 patients presenting to the ED with acute dyspnea. Physicians were blinded to BNP levels and asked to give their probability of the patient having CHF and their final diagnosis. Two independent cardiologists were blinded to BNP levels and asked to review the data and evaluate which patients presented with heart failure. Patients with right heart failure from cor pulmonale were classified as having CHF. RESULTS: Patients with CHF (n = 134) had BNP levels of 758.5 +/- 798 pg/ml, significantly higher than the group of patients with a final diagnosis of pulmonary disease (n = 85) whose BNP was 61 +/- 10 pg/ml. The area under the receiver operating curve, which plots sensitivity versus specificity for BNP levels in separating cardiac from pulmonary disease, was 0.96 (p < 0.001). A breakdown of patients with pulmonary disease revealed: chronic obstructive pulmonary disease (COPD): 54 +/- 71 pg/ml (n = 42); asthma: 27 +/- 40 pg/ml (n = 11); acute bronchitis: 44 +/- 112 pg/ml (n = 14); pneumonia: 55 +/- 76 pg/ml (n = 8); tuberculosis: 93 +/- 54 pg/ml (n = 2); lung cancer: 120 +/- 120 pg/ml (n = 4); and acute pulmonary embolism: 207 +/- 272 pg/ml (n = 3). In patients with a history of lung disease but whose current complaint of dyspnea was seen as due to CHF, BNP levels were 731 +/- 764 pg/ml (n = 54). The group with a history of CHF but with a current COPD diagnosis had a BNP of 47 +/- 23 pg/ml (n = 11). CONCLUSIONS: Rapid testing of BNP in the ED should help differentiate pulmonary from cardiac etiologies of dyspnea.